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Sample records for carcinogenesis studies final

  1. Studies of pancreatic carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    JI Yu-bin; PANG Lin-lin; YU Lei; YANG Hai-fan; LIU Guang-da; LI Hai-jiao

    2008-01-01

    Pancreatic carcinoma is the most common pancreatic neoplasm characterized by latentmorbidit, poor prognosis, high mortality rate and limited choice of treatment. Quite a lot studies focused on its pathogenesis, and showed molecular genetic alterations, which derived of genetic and environmental factors and played an important role in tumorigenesis. Recently, more and more findings laid particular emphasis on the changes of gene molecule and some were confirmed in vitro and in vivo. In this paper, we made a review and summarized the arked molecular changes and signalings of the four pathways to understand their functions in Pancreatic carcinoma. The most important changes concentrate on K-RAS, p16 INK4α, P53 and SMAD4 gene, secondly, the changes of pl4ARF, TGF-β, LKB1 /STK11, BRCA2 and growth factor Hedgehog and Notch path way and Telomere also play a important role in pancreatic carcinoma. The vast majority (83%) of pancreatic carcinomas had a distinctive genetic fingerprint, comprising activation of the K-ras oncogene and inactivation of the p 16 gene, generally also accompanied by alterations in the p53 gene (in 76 % of the tumors). The activation of K-ras appears nearly to be a prerequisite for the development of pancreatic carcinoma. Also, the binary alteration of K-ras and p16 is an extremely uncommon combination among other human tumor types. This particular genetic imprint of pancreatic carcinomas could have diagnostic utility in the evaluation of patients with metastatic adenocarcinoma of unknown primary origin. The evaluation of genetic alterations as they naturally occur in humantumors allows the formulation of hypotheses concerning the biological processes that involve human tumongenesis. A central tenet of tumori genesis, that positive selection is exerted upon those tumor cells that alterrate-limiting regulatory pathways, implies that mutation of one gene abrogates the need for inactivation of another gene in the same tumor suppressive pathway. It

  2. Study of chemical and radiation induced carcinogenesis

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    Chmura, A.

    1995-11-01

    The study of chemical and radiation induced carcinogenesis has up to now based many of its results on the detection of genetic aberrations using the fluorescent in situ hybridization (FISH) technique. FISH is time consuming and this tends to hinder its use for looking at large numbers of samples. We are currently developing new technological advances which will increase the speed, clarity and functionality of the FISH technique. These advances include multi-labeled probes, amplification techniques, and separation techniques.

  3. 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.

  4. What gastric cancer proteomic studies show about gastric carcinogenesis?

    Science.gov (United States)

    Leal, Mariana Ferreira; Wisnieski, Fernanda; de Oliveira Gigek, Carolina; do Santos, Leonardo Caires; Calcagno, Danielle Queiroz; Burbano, Rommel Rodriguez; Smith, Marilia Cardoso

    2016-08-01

    Gastric cancer is a complex, heterogeneous, and multistep disease. Over the past decades, several studies have aimed to determine the molecular factors that lead to gastric cancer development and progression. After completing the human genome sequencing, proteomic technologies have presented rapid progress. Differently from the relative static state of genome, the cell proteome is dynamic and changes in pathologic conditions. Proteomic approaches have been used to determine proteome profiles and identify differentially expressed proteins between groups of samples, such as neoplastic and nonneoplastic samples or between samples of different cancer subtypes or stages. Therefore, proteomic technologies are a useful tool toward improving the knowledge of gastric cancer molecular pathogenesis and the understanding of tumor heterogeneity. This review aimed to summarize the proteins or protein families that are frequently identified by using high-throughput screening methods and which thus may have a key role in gastric carcinogenesis. The increased knowledge of gastric carcinogenesis will clearly help in the development of new anticancer treatments. Although the studies are still in their infancy, the reviewed proteins may be useful for gastric cancer diagnosis, prognosis, and patient management.

  5. Death receptors and ligands in cervical carcinogenesis : an immunohistochemical study

    NARCIS (Netherlands)

    Reesink-Peters, N; Hougardy, B M T; van den Heuvel, F A J; Ten Hoor, K A; Hollema, H; Boezen, H M; de Vries, E G E; de Jong, S; van der Zee, A G J

    2005-01-01

    OBJECTIVE: Increasing imbalance between proliferation and apoptosis is important in cervical carcinogenesis. The death ligands FasL and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce apoptosis by binding to their cognate cell-surface death receptors Fas or death receptor (DR)

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

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

    2012-07-16

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

  7. Recent advances in the study of HPV-associated carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Liyan; Jin; Zhi-Xiang; Xu

    2015-01-01

    Human papillomaviruses(HPVs) cause virtually all cervical cancers, the second leading cause of death by cancer among women, as well as other anogenital cancers and a subset of head and neck cancers. Approximately half of women, who develop cervical cancer die from it. Despite the optimism that has accompanied the introduction of prophylactic vaccines to prevent some HPV infections, the relatively modest uptake of the vaccine, especially in the developing world, and the very high fraction of men and women who are already infected, means that HPV-associated disease will remain as a significant public health problem for decades. In this review, we summarize some recent findings on HPV-associated carcinogenesis, such as mi RNAs in HPV-associated cancers, implication of stem cells in the biology and therapy of HPV-positive cancers, HPV vaccines, targeted therapy of cervical cancer, and drug treatment for HPV-induced intraepithelial neoplasias.

  8. Colorectal carcinogenesis: Review of human and experimental animal studies

    Directory of Open Access Journals (Sweden)

    Tanaka Takuji

    2009-01-01

    Full Text Available This review gives a comprehensive overview of cancer development and links it to the current understanding of tumorigenesis and malignant progression in colorectal cancer. The focus is on human and murine colorectal carcinogenesis and the histogenesis of this malignant disorder. A summary of a model of colitis-associated colon tumorigenesis (an AOM/DSS model will also be presented. The earliest phases of colorectal oncogenesis occur in the normal mucosa, with a disorder of cell replication. The large majority of colorectal malignancies develop from an adenomatous polyp (adenoma. These can be defined as well-demarcated masses of epithelial dysplasia, with uncontrolled crypt cell proliferation. When neoplastic cells pass through the muscularis mucosa and infiltrate the submucosa, they are malignant. Carcinomas usually originate from pre-existing adenomas, but this does not imply that all polyps undergo malignant changes and does not exclude de novo oncogenesis. Besides adenomas, there are other types of pre-neoplasia, which include hyperplastic polyps, serrated adenomas, flat adenomas and dysplasia that occurs in the inflamed colon in associated with inflammatory bowel disease. Colorectal neoplasms cover a wide range of pre-malignant and malignant lesions, many of which can easily be removed during endoscopy if they are small. Colorectal neoplasms and/or pre-neoplasms can be prevented by interfering with the various steps of oncogenesis, which begins with uncontrolled epithelial cell replication, continues with the formation of adenomas and eventually evolves into malignancy. The knowledge described herein will help to reduce and prevent this malignancy, which is one of the most frequent neoplasms in some Western and developed countries.

  9. Effects of Porcine Pancreatic Enzymes on the Pancreas of Hamsters. Part 2: Carcinogenesis Studies

    OpenAIRE

    2012-01-01

    Context Our previous study suggested that porcine pancreatic extract in hamsters with peripheral insulin resistance, normalizes insulin output, islet size and pancreatic DNA synthetic rate. It also inhibited the growth of human pancreatic cancer cells in nude mice. Objective To examine the potential value of the porcine pancreatic extract in controlling pancreatic carcinogenesis in this model, the present experiment was performed. Design Hamsters were fed a high fat diet and four wee...

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

    Energy Technology Data Exchange (ETDEWEB)

    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. (ACR)

  11. 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

  12. Emdogain in carcinogenesis: a systematic review of in vitro studies.

    Science.gov (United States)

    Laaksonen, Matti; Sorsa, Timo; Salo, Tuula

    2010-03-01

    Emdogain is a commercial product of unknown composition and is clinically used to induce periodontal regeneration. This study aims to review current knowledge of the in vitro effects of Emdogain on oral tissues and, in particular, factors related to carcinoma. A systematic approach was used to review studies from the Embase and Pubmed databases; a total of 76 studies were included. These comprised in vitro studies of the cytokines in, or regulated by, Emdogain and assays designed to study the effects of EMD on human cells in oral tissues or malignant cells. Several studies have shown that EMD regulates the proliferation, migration, adhesion, gene expression, and cytokine production of (pre-)osteoblasts, periodontal fibroblasts, and gingival fibroblasts. However, the effects of EMD on malignant oral cells are not well understood. EMD seems to have broad regulatory effects on malignant cells and on several carcinoma-related factors. Evidence suggests that patients with premalignant or malignant mucosal lesions should not be treated with EMD.

  13. CLIC Final Focus Studies

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    Tomás, R; Schulte, Daniel; Zimmermann, Frank

    2006-01-01

    The CLIC final focus system has been designed based on the local compensation scheme proposed by P. Raimondi and A. Seryi. However, there exist important chromatic aberrations that deteriorate the performance of the system. This paper studies the optimization of the final focus based on the computation of the higher orders of the map using MAD-X and PTC. The use of octupole tail folding to reduce the size of the halo in the locations with aperture limitations is also discussed.

  14. The AOM/DSS murine model for the study of colon carcinogenesis: From pathways to diagnosis and therapy studies

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    Robertis, Mariangela De; Massi, Emanuela; Poeta, Maria Luana; Carotti, Simone; Morini, Sergio; Cecchetelli, Loredana; Signori, Emanuela; Fazio, Vito Michele

    2011-01-01

    Colorectal cancer (CRC) is a major health problem in industrialized countries. Although inflammation-linked carcinogenesis is a well accepted concept and is often observed within the gastrointestinal tract, the underlying mechanisms remain to be elucidated. Inflammation can indeed provide initiating and promoting stimuli and mediators, generating a tumour-prone microenvironment. Many murine models of sporadic and inflammation-related colon carcinogenesis have been developed in the last decade, including chemically induced CRC models, genetically engineered mouse models, and xenoplants. Among the chemically induced CRC models, the combination of a single hit of azoxymethane (AOM) with 1 week exposure to the inflammatory agent dextran sodium sulphate (DSS) in rodents has proven to dramatically shorten the latency time for induction of CRC and to rapidly recapitulate the aberrant crypt foci–adenoma–carcinoma sequence that occurs in human CRC. Because of its high reproducibility and potency, as well as the simple and affordable mode of application, the AOM/DSS has become an outstanding model for studying colon carcinogenesis and a powerful platform for chemopreventive intervention studies. In this article we highlight the histopathological and molecular features and describe the principal genetic and epigenetic alterations and inflammatory pathways involved in carcinogenesis in AOM/DSS–treated mice; we also present a general overview of recent experimental applications and preclinical testing of novel therapeutics in the AOM/DSS model. PMID:21483655

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

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    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.

  16. 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.

  17. Atomic Bomb Survivors Life-Span Study: Insufficient Statistical Power to Select Radiation Carcinogenesis Model.

    Science.gov (United States)

    Socol, Yehoshua; Dobrzyński, Ludwik

    2015-01-01

    The atomic bomb survivors life-span study (LSS) is often claimed to support the linear no-threshold hypothesis (LNTH) of radiation carcinogenesis. This paper shows that this claim is baseless. The LSS data are equally or better described by an s-shaped dependence on radiation exposure with a threshold of about 0.3 Sievert (Sv) and saturation level at about 1.5 Sv. A Monte-Carlo simulation of possible LSS outcomes demonstrates that, given the weak statistical power, LSS cannot provide support for LNTH. Even if the LNTH is used at low dose and dose rates, its estimation of excess cancer mortality should be communicated as 2.5% per Sv, i.e., an increase of cancer mortality from about 20% spontaneous mortality to about 22.5% per Sv, which is about half of the usually cited value. The impact of the "neutron discrepancy problem" - the apparent difference between the calculated and measured values of neutron flux in Hiroshima - was studied and found to be marginal. Major revision of the radiation risk assessment paradigm is required.

  18. Introduction and overview. Perinatal carcinogenesis: growing a node for epidemiology, risk management, and animal studies.

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    Anderson, Lucy M

    2004-09-01

    Perinatal carcinogenesis as a cross-disciplinary concern is the subject of this special issue of Toxicology and Applied Pharmacology, which consists of a total of eight reviews or commentaries in the areas of epidemiology, risk assessment, and animal models. Some of the conclusions from these articles, and the Questions and Answers section that follows most of them, are summarized here. There is adequate reason to suspect that perinatal exposures contribute to human cancer risk, both childhood cancers, and those appearing later in life. The latter type of risk may actually be quantitatively the more important, and involve a wide range of types of effects, but has received only limited attention. With regard to childhood cancers, fetal irradiation and diethylstilbestrol exposure are known etiological agents, and it is likely, but not yet certain, there are additional external causes of a portion of these. Some current focal points of interest here include nitroso compounds, DNA topoisomerase inhibitors, viruses, anti-AIDS drugs, and endocrine disruptors. Regulatory agencies must rely heavily on animal data for estimation of human risk due to perinatal exposures to chemicals, and the quantity and quality of these data presently available for this purpose are greatly limiting. Correctly designed conventional animal studies with suspect chemicals are still needed. Furthermore, genetically engineered mouse models for childhood cancers, especially medulloblastoma, have become available, and could be used for screening of candidate causative agents for this cancer type, and for better understanding of gene-environment interactions.

  19. Gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Ismail Gomceli; Baris Demiriz; Mesut Tez

    2012-01-01

    Gastric cancer is the second most common cancer worldwide and the second most common cause of cancer-related deaths.Despite complete resection of gastric cancer and lymph node dissection,as well as improvements in chemotherapy and radiotherapy,there are still 700 000 gastric cancer-related deaths per year worldwide and more than 80% of patients with advanced gastric cancer die of the disease or recurrent disease within 1 year after diagnosis.None of the treatment modalities we have been applying today can influence the overall survival rates:at present,the overall 5-year relative survival rate for gastric cancer is about 28%.Cellular metaplasia due to chronic inflammation,injury and repair are the most documented processes for neoplasia.It appears that chronic inflammation stimulates tumor development and plays a critical role in initiating,sustaining and advancing tumor growth.It is also evident that not all inflammation is tumorigenic.Additional mutations can be acquired,and this leads to the cancer cell gaining a further growth advantage and acquiring a more malignant phenotype.Intestinalization of gastric units,which is called "intestinal metaplasia";phenotypic antralization of fundic units,which is called "spasmolytic polypeptide-expressing metaplasia"; and the development directly from the stem/progenitor cell zone are three pathways that have been described for gastric carcinogenesis.Also,an important factor for the development of gastrointestinal cancers is peritumoral stroma.However,the initiating cellular event in gastric metaplasia is still controversial.Understanding gastric carcinogenesis and its precursor lesions has been under intense investigation,and our paper attempts to high-light recent progress in this field of cancer research.

  20. MYC and gastric adenocarcinoma carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Danielle Queiroz Calcagno; Mariana Ferreira Leal; Paulo Pimentel Assumpcao; Marilia de Arruda Cardoso Smith; Rommel Rodriguez Burbano

    2008-01-01

    MYC is an oncogene involved in cell cycle regulation, cell growth arrest, cell adhesion, metabolism, ribosome biogenesis, protein synthesis, and mitochondrial function. It has been described as a key element of several carcinogenesis processes in humans. Many studies have shown an association between MYC deregulation and gastric cancer. MYC deregulation is also seen in gastric preneoplastic lesions and thus it may have a role in early gastric carcinogenesis. Several studies have suggested that amplification is the main mechanism of MYC deregulation in gastric cancer. In the present review, we focus on the deregulation of the MYC oncogene in gastric adenocarcinoma carcinogenesis, including its association with Helicobacter pylori (H pylori) and clinical applications.

  1. Agribusiness Industry Study Final Report

    Science.gov (United States)

    2005-01-01

    Instituto Riograndense do Arroz, Rio Grande do Sul, Brazil Empresa Bunge Alimentos, Rio Grande do Sul, Brazil Universal Leaf Tobacos Ltda., Rio...become a networked web . A final note on the industry defined. This study focuses primarily on the portion of the agribusiness industry concerned

  2. Oxidants, antioxidants and carcinogenesis.

    Science.gov (United States)

    Ray, Gibanananda; Husain, Syed Akhtar

    2002-11-01

    Reactive oxygen metabolites (ROMs), such as superoxide anions (O2*-) hydrogen peroxide (H2O2), and hydroxyl radical (*OH), malondialdehyde (MDA) and nitric oxide (NO) are directly or indirectly involved in multistage process of carcinogenesis. They are mainly involved in DNA damage leading sometimes to mutations in tumour suppressor genes. They also act as initiator and/or promotor in carcinogenesis. Some of them are mutagenic in mammalian systems. O2*-, H2O2 and *OH are reported to be involved in higher frequencies of sister chromatid exchanges (SCEs) and chromosome breaks and gaps (CBGs). MDA, a bi-product of lipid peroxidation (LPO), is said to be involved in DNA adduct formations, which are believed to be responsible for carcinogenesis. NO, on the other hand, plays a duel role in cancer. At high concentration it kills tumour cells, but at low concentration it promotes tumour growth and metastasis. It causes DNA single and double strand breaks. The metabolites of NO such as peroxynitrite (OONO-) is a potent mutagen that can induce transversion mutations. NO can stimulate O2*-/H2O2/*OH-induced LPO. These deleterious actions of oxidants can be countered by antioxidant defence system in humans. There are first line defense antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). SOD converts O2*- to H2O2, which is further converted to H2O with the help of GPx and CAT. SOD inhibits *OH production. SOD also act as antipoliferative agent, anticarcinogens, and inhibitor at initiation and promotion/transformation stage in carcinogenesis. GPx is another antioxidative enzyme which catalyses to convert H2O2, to H2O. The most potent enzyme is CAT. GPx and CAT are important in the inactivation of many environmental mutagens. CAT is also found to reduce the SCE levels and chromosomal aberrations. Antioxidative vitamins such as vitamin A, E, and C have a number of biological activities such as immune stimulation, inhibition of

  3. Epigenetic alterations in gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    In-Seon CHOI; Tsung-Teh WU

    2005-01-01

    Gastric cancer is believed to result in part from the accumulation of multiple genetic alterations leading to oncogene overexpression and tumor suppressor loss. Epigenetic alterations as a distinct and crucial mechanism to silence a variety of methylated tissue-specific and imprinted genes, have been extensively studied in gastric carcinoma and play important roles in gastric carcinogenesis. This review will briefly discuss the basic aspects of DNA methylation and CpG island methylation, in particular the epigenetic alterations of certain critical genes implicated in gastric carcinogenesis and its relevance of clinical implications.

  4. Methylation in esophageal carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Da-Long Wu; Feng-Ying Sui; Xiao-Ming Jiang; Xiao-Hong Jiang

    2006-01-01

    Genetic abnormalities of proto-oncogenes and tumor suppressor genes have been demonstrated to be changes that are frequently involved in esophageal cancer pathogenesis. However, hypermethylation of CpG islands, an epigenetic event, is coming more and more into focus in carcinogenesis of the esophagus. Recent studies have proved that promoter hypermethylation of tumor suppressor genes is frequently observed in esophageal carcinomas and seems to play an important role in the pathogenesis of this tumor type. In this review, we will discuss current research on genes that are hypermethylated in human esophageal cancer and precancerous lesions of the esophagus. We will also discuss the potential use of hypermethylated genes as targets for detection, prognosis and treatment of esophageal cancer.

  5. NTP Toxicology and Carcinogenesis Studies of Propylene (CAS No. 115-07-1) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1985-11-01

    Propylene is used as a starting material in the production of polypropylene plastics and various other chemicals, including acrylonitrile, isopropyl alcohol, propylene oxide, butyraldehyde, cumene, dodecane, nonene, and allyl chloride. The major derivatives are polypropylene (25%), acrylonitrile (15%), isopropyl alcohol (10%), and propylene oxide (10%). It is also a valuable feed-stock chemical for the production of gasoline. Other miscellaneous applications include use as a starting material for polymerization reactions to form vinyl chloride copolymers and low-molecular-weight homopolymers that are used as additives in lubricating oils and in the manufacture of hydroquinone. The chemical is also used as an aerosol propellant or component. The major end uses of propylene are in the production of fabricated plastics (50%) and fibers (15%). Toxicology and carcinogenesis studies of propylene (greater than 99% pure) were conducted by exposing groups of 50 F344/N rats and 49 or 50 B6C3F1 mice of each sex to propylene in air by inhalation at concentrations of 5,000 or 10,000 ppm, 6 hours per day, 5 days per week, for 103 weeks. Other groups of 50 rats and 50 mice of each sex in chambers received air only on the same schedule and served as chamber controls. The highest concentration of propylene that was considered safe for these studies was 10,000 ppm because of the risk of explosion that can occur at higher concentrations. The survival of exposed and control rats and mice was comparable. Throughout most of the studies, mean body weights of exposed male and female rats were slightly lower (0%-5%) than those of the controls, but the decrements were not concentration related. After week 59 of the study, mean body weights of 10,000-ppm male mice were usually slightly lower (5%) than those of the controls, whereas those in other exposed groups of male and female mice were generally comparable with those of the controls. No compound-related adverse clinical signs were

  6. Study on a Natural Carcinogenesis-Resistant in the Course of Rat Glandular Stomach Carcinogenesis%MNNG所致大鼠腺胃癌形成过程中机体自然抗癌机制的研究

    Institute of Scientific and Technical Information of China (English)

    苏衍萍; 李玉林; 齐云飞; 马风梅; 张景华

    2001-01-01

    Objective To investigate the mechanism of a natural carcinogenesis-resistant. Methods In our experiment, Wistar rat stomach carcinogenesis (formation of aneuploid cells in the glandular stomach mucosa) was induced by MNNG 20mg/kg gavaged, once a day for 10 days. At the 25th week,the incidence of aneuploid cells in mucosal epithelium of gastric antrum was determined by flow cytometry (FCM). Changes of Gastrin cell, Somatostatin cell in Wistar rat glandular stomach were detected by ABC immunohistochemical method in the course of selenium preventing formation of aneuploid cells. Situation and quantitative analyses of the results were made by image analysis, and statistical analysis was made by SPSS ware. Results It was significantly increased in immunohistochemical activities of Wistar rat glandular stomach Gastrin cells, somatostatin cells and 5-hydroxytryptamine cells in the course of the rat stomach carcinogenesis(P<0.01,P<0.05). Conclusion This study reveals rat stomach carcinogenesis induced by MNNG might be introduced by endocrine cell of rat stomach. The mechanism of relationship needs to be further explored.%目的探讨机体的自然抗肿瘤作用。方法给断乳雄性Wistar大鼠MNNG灌胃,每天一次,连续10天,以诱导大鼠腺胃粘膜异倍体形成(大鼠腺胃癌模型形成)。第25周时,用流式细胞仪测定大鼠腺胃幽门粘膜异倍体形成的情况,用免疫组织化学ABC法观察了大鼠腺胃粘膜异倍体形成过程中,腺胃胃泌素细胞胃泌素细胞、生长抑素细胞、5-羟色胺细胞的免疫组织化学变化,并对以上结果进行定性、定位、定量分析以及统计学处理。结果在MNNG所致大鼠腺胃癌形成过程中其腺胃胃泌素细胞、生长抑素细胞、5-羟色胺细胞的免疫组织化学阳性强度均明显增强(P<0.01,P<0.05)。结论胃内分泌细胞可能介导了MNNG所致大鼠胃癌的发生和发展;有关机理尚待进一步探讨。

  7. Cytotoxic effect of methanol extract of Conyza bonariensis on DMBA-induced skin carcinogenesis: An in vivo study

    Directory of Open Access Journals (Sweden)

    Mohammad Saleem

    2015-06-01

    Full Text Available In the present study, we examined the cytotoxic effect of Conyza bonariensis (methanolic extract. The skin carcinogenesis was induced in two stages, first, applying tumor initiator, 7-12-dimethyl benz(aantheracene and thereafter applying croton oil, a tumor promotor in Swiss albino mice. The morphological alterations observed and measured during the induction of skin ulceration, included; cumulative number of papilloma, tumor yield and tumor burden. C. bonariensis extract (300 and 600 mg/kg/day was applied locally on mice skin for 16 weeks. The higher dose (600 mg/kg/day inhibited the tumor formation up to 40% and showed a significant decline in cumulative number of papilloma of continuous group. The results indicated that extract increased the reduced glutathione, superoxide dismutase and catalase, and decreased lipid peroxidation compared to carcinogen group. Histopathological changes showed papilomatosis and ulceration in carcinogen control group. HPLC analysis indicated the presence of flavonoid i.e. quercetin which may be responsible for the cytotoxic action of C. bonariensis methanol extract.

  8. Nanoscale intracellular mass-density alteration as a signature of the effect of alcohol on early carcinogenesis: A transmission electron microscopy (TEM) study

    CERN Document Server

    Ghimire, Hemendra M; Sahay, Peeyush; Almabadi, Huda; Tripathi, Vibha; Skalli, Omar; Rao, R K; Pradhan, Prabhakar

    2015-01-01

    Alcohol consumption interferes with the functioning of multiple organ systems, causing changes in the chemistry, physiology and pathology of tissues and cellular organelles. Although epigenetic modifications underlie the development of cancer, exposure to carcinogenic chemicals, such as alcohol, can also contribute to disease development. However, the effects of chronic alcoholism on normal or pre-carcinogenic cells/tissues in different organelles are not well understood. Therefore, we herein study the effect of alcohol consumption on colonic nucleus using control and azoxymethane (AOM) and dextran sulfate sodium (DSS) treated carcinogenic mice. Previous studies showed that progression of carcinogenesis is associated with increase in the degree of intranuclear nanoscale structural disorder. In the present work, we quantify the degree of nanostructural disorder as a measure of carcinogenesis. To accomplish this, transmission electron microscopy (TEM) imaging of respective colonic epithelial cell nuclei are use...

  9. NTP Toxicology and Carcinogenesis Studies of Trichloroethylene (CAS No. 79-01-6) in Four Strains of Rats (ACI, August, Marshall, Osborne-Mendel) (Gavage Studies).

    Science.gov (United States)

    1988-04-01

    Trichloroethylene is an industrial solvent used primarily for vapor degreasing and cold cleaning. It was selected for study because of its industrial use and for potential for human exposure. (An estimated 3.5 million workers are exposed to trichloroethylene.) In an earlier study trichloroethylene (stabilized with epichlorohydrin and 1,2-epoxybutane) administered by gavage caused hepatocellular carcinomas in male and female B6C3F1 mice. Trichloroethylene administration did not increase the incidence of tumors in male or female Osborne-Mendel rats. However, the survival of dosed rats was reduced, thereby compromising the sensitivity of the study to detect a carcinogenic effect. The studies described in this report were conducted to compare the sensitivities of four strains of rats (ACI, August, Marshall, and Osborne-Mendel) to diisopropylamine-stabilized trichloroethylene. The results of the present studies demonstrate that long-term administration of trichloroethylene produces nephrotoxicity in four strains of rats and that the susceptibilities of these strains to the nephrotoxic effects of the chemical are similar. Because of chemically induced toxicity, reduced survival, and incomplete documentation of the experimental data, the studies are considered inadequate for either comparing or assessing trichloroethylene-induced carcinogenesis in these strains of rats. Toxicology and carcinogenesis studies of trichloroethylene (more than 99% pure, stabilized with 8 ppm diisopropylamine) were conducted by administering the chemical in corn oil gavage at doses of 0, 500, or 1,000 mg/kg per day, 5 day per week, for 103 weeks to groups of 50 male and 50 female ACI, August, Marshall, and Osborne-Mendel rats. The doses were selected on the basis of results from 13-week gavage studies in which groups of 10 male and 10 female ACI, August, and Marshall rats received daily doses or trichloroethylene (male: 125-2,000 mg/kg; female: 63-1,000 mg/kg). Doses for Osborne-Mendel rats

  10. Studies on the mechanisms of action of modifiers of skin carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Slaga, T.J.

    1980-01-01

    Skin tumors can be induced by the sequential application of a subthreshold dose of a carcinogen (initiaton phase), followed by repetitive treatment with a weak or noncarcinogenic tumor promoter. There is a very good dose-response relationship between the induction of the number of papillomas per mouse at early times (10 to 20 weeks) by either tumor initiators and promoters and the final carcinoma incidence after a longer latency (20 to 50 weeks) in SENCAR mice. This system not only can be used to determine the tumor initiating and promoting activities of a compound but if the agent is given repeatedly by itself one can also determine if it is a complete carcinogen, i.e., if it has both tumor initiating and promoting activity. There is a good correlation between the tumor-initiating activities of PAH and their abilities to bind covalently to DNA. In addition, various inhibitors of PAH tumor initiation show a strong correlation with their abilities to inhibit the binding of the PAH to DNA and their anti-tumor initiating activities. There is also a good correlation between the promoting abilities of phorbil esters to promote tumors and their abilities to induce ornithine decarboxylase (ODC), cell proliferation and dark basal keratinocytes. However, when other nonpromoting hyperplastic agents are used only dark cell induction correlates. Certain polyamines and prostaglandins can enhance phorbol ester tumor promotion. Anti-inflammatory steroids, retinoids and protease inhibitors are potent inhibitors of tumor promotion. They inhibit tumor promotion by either inhibiting the 12-0-tetradecanoylphorbol-13-acetate (TPA)induced cell proliferation, ODC and/or dark basal keratinocytes. Certain weak promoters such as mezerein which mimics TPA in many biochemical and morphological effects are potent second step promoters in a two-stage promotion regimen.

  11. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

    Science.gov (United States)

    Park, Youn-hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo

    2015-01-01

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals-induced carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the mechanistic studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. PMID:26091798

  12. Final report on case studies

    DEFF Research Database (Denmark)

    Ljungberg, Daniel; McKelvey, Maureen; Lassen, Astrid Heidemann

    2012-01-01

    Case study as a research design means investigating a single or multiple instance(s) or setting(s) (i.e. a case) and its entire context to explain a phenomenon and its processes. This is achieved through detailed understanding, usually comprised of multiple sources of information. In this way, case...... studies attempt to provide as a complete an understanding of a (complex) phenomenon as possible. Within the AEGIS project, survey and case study research are complementary. They are complementary in the sense that the former can provide more generalizable evidence on a phenomenon in terms of cross......-sectional data, while the latter can provide more in-depth (qualitative) understanding on specific issues. In systematically examining the case studies, however, this report goes beyond a typical single case study. Here we provide a synthesis of 86 case studies. Multiple case studies, following similar focus...

  13. SKHIN/Sprd, a new genetically defined inbred hairless mouse strain for UV-induced skin carcinogenesis studies.

    Science.gov (United States)

    Perez, Carlos; Parker-Thornburg, Jan; Mikulec, Carol; Kusewitt, Donna F; Fischer, Susan M; Digiovanni, John; Conti, Claudio J; Benavides, Fernando

    2012-03-01

    Strains of mice vary in their susceptibility to ultra-violet (UV) radiation-induced skin tumors. Some strains of hairless mice (homozygous for the spontaneous Hr(hr) mutation) are particularly susceptible to these tumors. The skin tumors that develop in hairless mice resemble, both at the morphologic and molecular levels, UV-induced squamous cell carcinomas (SCC) and their precursors in human. The most commonly employed hairless mice belong to the SKH1 stock. However, these mice are outbred and their genetic background is not characterized, which makes them a poor model for genetic studies. We have developed a new inbred strain from outbred SKH1 mice that we named SKHIN/Sprd (now at generation F31). In order to characterize the genetic background of this new strain, we genotyped a cohort of mice at F30 with 92 microsatellites and 140 single nucleotide polymorphisms (SNP) evenly distributed throughout the mouse genome. We also exposed SKHIN/Sprd mice to chronic UV irradiation and showed that they are as susceptible to UV-induced skin carcinogenesis as outbred SKH1 mice. In addition, we proved that, albeit with low efficiency, inbred SKHIN/Sprd mice are suitable for transgenic production by classical pronuclear microinjection. This new inbred strain will be useful for the development of transgenic and congenic strains on a hairless inbred background as well as the establishment of syngeneic tumor cell lines. These new tools can potentially help elucidate a number of features of the cutaneous response to UV irradiation in humans, including the effect of genetic background and modifier genes.

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

    Energy Technology Data Exchange (ETDEWEB)

    Fabrikant, J.I.

    1982-08-01

    The present review provides an understanding of our current knowledge of the carcinogenic effect of low-dose radiation in man, and surveys the epidemiological studies of human populations exposed to nuclear explosions and medical radiation. Discussion centers on the contributions of quantitative epidemiology to present knowledge, the reliability of the dose-incidence data, and those relevant epidemiological studies that provide the most useful information for risk estimation of cancer-induction in man. Reference is made to dose-incidence relationships from laboratory animal experiments where they may obtain for problems and difficulties in extrapolation from data obtained at high doses to low doses, and from animal data to the human situation. The paper describes the methods of application of such epidemiological data for estimation of excess risk of radiation-induced cancer in exposed human populations, and discusses the strengths and limitations of epidemiology in guiding radiation protection philosophy and public health policy.

  15. Cost Benefit Studies. Final Report.

    Science.gov (United States)

    Weiner, Arthur; Marson, Arthur A.

    This document applies Dr. Mehar Aurora's method for conducting cost benefit studies to the Food Manufacturing Technology-Dairy and the Food Manufacturing Technology-Canning and Freezing programs offered by the Moraine Park Technical Institute. Costs to individual students enrolled in the programs include tuition, fees, housing, travel, books,…

  16. Laser fusion study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1975-06-01

    The following appendices are included: (1) sensor performance calculation techniques, (2) focus sensing, (3) purchased item data, (4) pointing and focusing configuration tradeoff studies, (5) false start centering sensor, (6) RCA application notes on quad delection, (7) elliptical flex pivot analysis, (8) servo mirrors cross coupling, (9) optical misalignment analysis, (10) stress induced birefrigent quarter-wave retarder, (11) data bulletin on incramute damping alloy, (12) the utilization of stepping motors, and (13) computer program listing for stepper motor load simulation. (MOW)

  17. NTP Toxicology and Carcinogenesis Studies of Roxarsone (CAS No. 121-19-7) in F344/N Rats and B6C3F1 Mice (Feed Studies).

    Science.gov (United States)

    1989-03-01

    Roxarsone is a veterinary drug used as a growth promoter and as an anticoccidial agent and for treatment of swine dysentery. Toxicology and carcinogenesis studies were conducted by administering roxarsone (greater than 99.4% pure) in feed to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 weeks, or 2 years. Fourteen-Day and Thirteen-Week Studies: In the 14-day studies, the diets fed to rats contained 0 or 100-1,600 ppm roxarsone, and those fed to mice contained 0 or 60-1,000 ppm. Deaths occurred in rats and mice that received the highest doses. Rats that received 800 or 1,600 ppm lost weight. Male mice that received 1,000 ppm and female mice that received 500 ppm lost weight. In the first 13-week studies, roxarsone was fed to rats and mice at dietary concentrations of 0 or 50-800 ppm. Decreases (more than 10%) in final mean body weights of dosed rats relative to those of controls were observed for males that received 200, 400, or 800 ppm and for females that received 400 or 800 ppm. Deaths occurred in groups that received 800 ppm. Clinical signs of toxicity (trembling, ataxia, and pale skin) were seen primarily in rats that received 800 ppm. Kidney lesions were observed in rats that received 800 ppm. These lesions were characterized by tubular necrosis and mineralization in the rats that died during the studies and by tubular dilatation and casts, interstitial inflammation, and tubular epithelial cell regeneration in the rats that lived to the end of the studies. Additional 13-week studies were conducted in rats at dietary concentrations of 0, 100, or 400 ppm to demonstrate the absorption of roxarsone from the gastrointestinal tract; to determine its distribution in liver, kidney, and blood; and to study its effects on various hematologic and clinical chemical values. No deaths occurred. Renal lesions of minimal severity observed in male rats that received 400 ppm were characterized by tubular epithelial cell degeneration and regeneration, tubular

  18. Human bronchial epithelial BEAS-2B cells, an appropriate in vitro model to study heavy metals induced carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Park, Youn-hee; Kim, Donghern; Dai, Jin; Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu

    2015-09-15

    Occupational and environmental exposure to arsenic (III) and chromium VI (Cr(VI)) have been confirmed to cause lung cancer. Mechanisms of these metals carcinogenesis are still under investigation. Selection of cell lines to be used is essential for the studies. Human bronchial epithelial BEAS-2B cells are the cells to be utilized by most of scientists. However, due to p53 missense mutation (CCG → TCG) at codon 47 and the codon 72 polymorphism (CGC → CCC) in BEAS-2B cells, its usage has frequently been questioned. The present study has examined activity and expression of 53 and its downstream target protein p21 upon acute or chronic exposure of BEAS-2B cells to arsenic and Cr(VI). The results show that short-term exposure of BEAS-2B cells to arsenic or Cr(VI) was able to activate both p53 and p21. Chronic exposure of BEAS-2B cells to these two metals caused malignant cell transformation and tumorigenesis. In arsenic-transformed BEAS-2B cells reductions in p53 promoter activity, mRNA expression, and phosphorylation of p53 at Ser392 were observed, while the total p53 protein level remained the same compared to those in passage-matched parent ones. p21 promoter activity and expression were decreased in arsenic-transformed cells. Cr(VI)-transformed cells exhibit elevated p53 promoter activity, mRNA expression, and phosphorylation at Ser15, but reduced phosphorylation at Ser392 and total p53 protein level compared to passage-matched parent ones. p21 promoter activity and expression were elevated in Cr(VI)-transformed cells. These results demonstrate that p53 is able to respond to exposure of arsenic or Cr(VI), suggesting that BEAS-2B cells are an appropriate in vitro model to investigate arsenic or Cr(VI) induced lung cancer. - Highlights: • Short-term exposure of BEAS-2B cells to arsenic or Cr(VI) activates p53 and p21. • Chronic exposure of BEAS-2B cells to arsenic or Cr(VI) causes cell transformation and tumorigenesis. • Arsenic-transformed cells exhibit

  19. Enhancement of Urinary Bladder Carcinogenesis by the Role of Chronic Bacterial Infection-induced Inflammation (Imunnohistochemical and Biochemical studies

    Directory of Open Access Journals (Sweden)

    Gabri MS*, Ashmawy AM**, Ibrahim MA*, Hosny RM

    2012-07-01

    Full Text Available Background: Bacterial infections traditionally have not been considered major causes of cancer. Recently, however, bacteria have been linked to cancer by two mechanisms: induction of chronic inflammation and production of carcinogenic bacterial metabolites. The most specific example of the inflammatory mechanism of carcinogenesis is Escherichia coli infection. E. coli has been epidemiologically linked to urothelial carcinoma of the urinary bladder by its propensity to cause lifelong inflammation. This inflammation is in turn thought to cause cancer by inducing cell proliferation and production of mutagenic free radicals and N-nitroso compounds.Material and methods: After each 3, 6 and 9 months of daily oral administration of dibutyl amine (DBA plus sodium nitrate (nitrosamine precursors in drinking water, curcuma in grinding diet and bladder injection with E. coli, rats were sacrificed. The excited bladder were dissected, processed and stained with H&E and anti-Ki67 immunohistochemical stains. This was followed by Elisa for caspse-3 and statistical analysis.Results: The current results indicated that E. coli infection in the bladder tissues increases the carcinogenic ability of nitrosamine precursors through caused marked alteration in the form hyperplastic, dysplastic and metaplastic urothelium. Also, there was a statistically significant increase in ki67 immunoreactivity in urothelium. However, a statistically significant decrease in the concentration of caspase-3 in bladder tissue consequently caused the process of carcinogenesis. All these changes were less marked after curcuma treatment when compared with the group that not treated with curcuma. Conclusion: Bacterial infection of the urinary bladder may play a major additive and possible role in bladder carcinogenesis. Rhizome of curcuma may have a protective action during induction of urinary bladder tumors.

  20. DNA methylation and carcinogenesis.

    Science.gov (United States)

    Lichtenstein, A V; Kisseljova, N P

    2001-03-01

    In the world of easy things truth is opposed to lie; in the world of complicated things one profound truth is opposed to another not less profound than the first. Neils Bohr The hypothesis of the exclusively genetic origin of cancer ("cancer is a disease of genes, a tumor without any damage to the genome does not exist") dominated in the oncology until recently. A considerable amount of data confirming this hypothesis was accumulated during the last quarter of the last century. It was demonstrated that the accumulation of damage of specific genes lies at the origin of a tumor and its following progression. The damage gives rise to structural changes in the respective proteins and, consequently, to inappropriate mitogenic stimulation of cells (activation of oncogenes) or to the inactivation of tumor suppressor genes that inhibit cell division, or to the combination of both (in most cases). According to an alternative (epigenetic) hypothesis that was extremely unpopular until recently, a tumor is caused not by a gene damage, but by an inappropriate function of genes ("cancer is a disease of gene regulation and differentiation"). However, recent studies led to the convergence of these hypotheses that initially seemed to be contradictory. It was established that both factors--genetic and epigenetic--lie at the origin of carcinogenesis. The relative contribution of each varies significantly in different human tumors. Suppressor genes and genes of repair are inactivated in tumors due to their damage or methylation of their promoters (in the latter case an "epimutation", an epigenetic equivalent of a mutation, occurs, producing the same functional consequences). It is becoming evident that not only the mutagens, but various factors influencing cell metabolism, notably methylation, should be considered as carcinogens.

  1. Radiogenic cell transformation and carcinogenesis

    Science.gov (United States)

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

    1995-01-01

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

  2. NTP Toxicology and Carcinogenesis Studies of Pentachloroanisole (CAS No. 1825-21-4) in F344 Rats and B6C3F1 Mice (Feed Studies).

    Science.gov (United States)

    1993-04-01

    Pentachloroanisole is a chlorinated aromatic compound which is widely distributed at low levels in the environment and in food products. Formation of pentachloroanisole in the environment may result from the degradation of structurally related, commercially important, ubiquitous chlorinated aromatic compounds such as pentachlorophenol and pentachloronitrobenzene which are known rodent toxins or carcinogens. Toxicology and carcinogenesis studies were conducted by administering pentachloroanisole (>99% pure) in corn oil by gavage to groups of male and female F344/N rats and B6C3F1 mice for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium strains, mouse lymphoma cells, and Chinese hamster ovary cells. 16-DAY STUDIES IN RATS: Groups of five male and five female F344/N rats were administered pentachloroanisole in corn oil by gavage once per day, 5 days per week, for 16 days at doses of 0, 100, 125, 150, 175, or 200 mg/kg body weight. Deaths occurred during days 2 and 3 in rats receiving doses of 125 mg/kg or greater; these deaths were considered directly related to pentachloroanisole administration. No biologically significant changes in mean body weight gains or final body weights were noted in the 100 mg/kg groups of rats. Because of the high early mortality rate, valid comparisons of body weight differences in other dose groups could not be made. Inactivity was noted in all dose groups. Rats administered doses of 125 mg/kg or greater also exhibited dyspnea. 16-DAY STUDIES IN MICE: Groups of five male and five female B6C3F1 mice were administered pentachloroanisole in corn oil by gavage once per day, 5 days per week, for 16 days at doses of 0, 100, 175, 250, 325, or 400 mg/kg. Deaths occurred during days 2 and 3 in mice receiving doses of 175 mg/kg or greater; these deaths were considered directly related to chemical administration. No biologically significant changes in mean body weight gains or final body weights

  3. Oxidative damage and carcinogenesis

    OpenAIRE

    2012-01-01

    Oxygen is an essential element to conduct life processes but some of the metabolic byproducts e.g. reactive oxygen species (ROS), are toxic for living organisms. Endogenous ROS are produced e.g. reduction of dioxygen; some exogenous sources of radicals also exist, including nicotine and ionizing radiation. Reactive oxygen species include superoxide anion, hydroxyl radical, singlet oxygen, hydrogen peroxide and hypochlorous acid. Carcinogenesis is a multistep process. The exact reasons for the...

  4. Sawmill chemicals and carcinogenesis.

    OpenAIRE

    Huff, J

    2001-01-01

    Workers in wood industries are exposed to variable medleys of chemicals, both natural and synthetic. Additional exposures include fungi, bacteria, bark and wood dusts, solvents, paints, and various other wood coatings. These individual and conglomerate exposures have been associated with diverse occupational illnesses and hazards, including cancers. In this commentary, I summarize both experimental and epidemiologic carcinogenesis results for several chemicals used in the wood industry, as we...

  5. [Cyclooxygenase 2 and carcinogenesis].

    Science.gov (United States)

    Rodrigues, Sylvie; Bruyneel, Erik; Rodrigue, Christelle M; Shahin, Emami; Gespach, Christian

    2004-05-01

    The membrane glycoprotein Cox2 is regulated at transcriptional and post-transcriptional levels by pro-inflammatory agents, cytokines, growth factors, oncogenes, and tumor-promoters. Cox2 is expressed during early stages of colorectal carcinogenesis from the premalignant adenoma stage, and adenocarcinomas of stomach, colon, breast, lung and prostate. Its expression is detected in neoplastic, inflammatory, endothelial and stromal cells. Cox2 is involved in the conversion of arachidonic acid into prostaglandins and thromboxanes, as well as the synthesis of malonaldehyde (MDA, a mutagen) and the production of hydrogen peroxide, which promotes carcinogenesis. The Cox2 products act in turn on serpentine receptors coupled to heterotrimeric G-proteins (R-TXA2, R-PG) that are connected to signaling elements implicated in oncogenesis. Thus, Cox2 plays a key role in early stages of carcinogenesis by promoting the proliferation of tumoral cells and their resistance to apoptosis, as well as angiogenesis, tumor cell invasion and setting up of the metastatic process. These mechanisms establish the rationale behind the therapeutic targeting of Cox2 in human solid tumors.

  6. NTP Toxicology and Carcinogenesis Studies of Glycidol (CAS No. 556-52-5) In F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1990-03-01

    Glycidol is a viscous liquid that is used as a stabilizer in the manufacture of vinyl polymers, as an additive for oil and synthetic hydraulic fluids, and as a diluent in some epoxy resins. NTP Toxicology and Carcinogenesis studies were conducted by administering glycidol (94% pure, containing 1.2% 3-methoxy-1,2-propanediol, 0.4% 3-chloro-1,2-propanediol, 2.8% diglycidyl ether, and 1.1% 2,6-dimethanol-1,4-dioxane) in water by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 16 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Chinese hamster ovary (CHO) cells, Drosophila melanogaster, and the bone marrow of male B6C3F1 mice. Sixteen-Day Studies: Glycidol doses for groups of five rats or five mice of each sex ranged from 37.5 to 600 mg/kg; vehicle controls received distilled water. All rats that received 600 mg/kg died between days 3 and 13. Edema and degeneration of the epididymal stroma, atrophy of the testis, and granulomatous inflammation of the epididymis occurred in males that received 300 mg/kg. All mice that received 600 mg/kg and two males and two females that received 300 mg/kg died by day 4 of the studies. Focal demyelination in the medulla and thalamus of the brain occurred in all female mice that received 300 mg/kg. Thirteen-Week Studies: Doses for groups of 10 rats ranged from 25 to 400 mg/kg, and doses for groups of 10 mice ranged from 19 to 300 mg/kg; vehicle controls received distilled water. All rats that received 400 mg/kg died by week 2; three males and one female that received 200 mg/kg died during weeks 11-12. Final mean body weights of male rats that received 50, 100, or 200 mg/kg were 96%-85% that of vehicle controls; final mean body weights of female rats receiving the same doses were 95%-89% that of vehicle controls. Sperm count and sperm motility were reduced in male rats that received 100 or 200 mg/kg. Necrosis of the cerebellum, demyelineation in the medulla of the brain

  7. Chemopreventive efficacy of Phyllanthus emblica L. (amla) fruit extract on 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis--a dose-response study.

    Science.gov (United States)

    Krishnaveni, Mani; Mirunalini, Sankaran

    2012-11-01

    Phyllanthus emblica L. (Euphorbiaceae), a novel natural fruit has long been used as a home remedy by the medical practitioners. In this report, we investigated the chemopreventive effect of P. emblica fruit methanolic extract (PFMet) on oxidant-antioxidant status in hamster buccal pouch carcinogenesis. Buccal pouch carcinoma was induced in hamsters by painting with DMBA (0.5% in mineral oil) on the left buccal pouch three times a week for 14 weeks. By means of HPLC analysis, ascorbic acid (24.13%), gallic acid (10.45%), ellagic acid (1.74%) and quercetin (0.009%) were identified and quantified in the PFMet. The results showed that depleted activities of SOD, CAT and TBARS level and significant elevation were observed in the levels of GSH, vitamin E and activity of GPx in DMBA group of buccal pouch. The level of TBARS was significantly enhanced and the activities of enzymatic (SOD, CAT and GPx) and non-enzymatic (vitamin E, vitamin C and GSH) antioxidants were diminished significantly in plasma of tumor bearing animals. The effects were dose dependent and the above noted parameters were renovated to near normal after supplementation with different doses of PFMet (50, 100 and 200 mg/kg BW). The data obtained in this study clearly indicate that PFMet at a dose of 200mg/kg BW possesses optimum chemopreventive effect against DMBA-induced buccal pouch carcinogenesis.

  8. 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.

  9. Study of the mechanism of carcinogenesis by carcinogens which are negative in the Ames test. Progress report, April 1-September 1, 1979

    Energy Technology Data Exchange (ETDEWEB)

    None

    1979-01-01

    Carcinogens ethionine, thioacetamide, and actinomycin D, all of which are negative in the Ames test and all of which raise the progesterone level in the chicken, were tested to determine their physiological role in carcinogenesis. The optimization of the carcinogenesis model also included evaluation of the chicken as the biological indicator of physiological changes relative to the above compounds. (PCS)

  10. Environmental and chemical carcinogenesis.

    Science.gov (United States)

    Wogan, Gerald N; Hecht, Stephen S; Felton, James S; Conney, Allan H; Loeb, Lawrence A

    2004-12-01

    People are continuously exposed exogenously to varying amounts of chemicals that have been shown to have carcinogenic or mutagenic properties in experimental systems. Exposure can occur exogenously when these agents are present in food, air or water, and also endogenously when they are products of metabolism or pathophysiologic states such as inflammation. It has been estimated that exposure to environmental chemical carcinogens may contribute significantly to the causation of a sizable fraction, perhaps a majority, of human cancers, when exposures are related to "life-style" factors such as diet, tobacco use, etc. This chapter summarizes several aspects of environmental chemical carcinogenesis that have been extensively studied and illustrates the power of mechanistic investigation combined with molecular epidemiologic approaches in establishing causative linkages between environmental exposures and increased cancer risks. A causative relationship between exposure to aflatoxin, a strongly carcinogenic mold-produced contaminant of dietary staples in Asia and Africa, and elevated risk for primary liver cancer has been demonstrated through the application of well-validated biomarkers in molecular epidemiology. These studies have also identified a striking synergistic interaction between aflatoxin and hepatitis B virus infection in elevating liver cancer risk. Use of tobacco products provides a clear example of cancer causation by a life-style factor involving carcinogen exposure. Tobacco carcinogens and their DNA adducts are central to cancer induction by tobacco products, and the contribution of specific tobacco carcinogens (e.g. PAH and NNK) to tobacco-induced lung cancer, can be evaluated by a weight of evidence approach. Factors considered include presence in tobacco products, carcinogenicity in laboratory animals, human uptake, metabolism and adduct formation, possible role in causing molecular changes in oncogenes or suppressor genes, and other relevant data

  11. Experimental radiation carcinogenesis: what have we learned

    Energy Technology Data Exchange (ETDEWEB)

    Fry, R.J.M.

    1980-01-01

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

  12. Cyclooxygenase-2 and prostate carcinogenesis.

    Science.gov (United States)

    Hussain, Tajamul; Gupta, Sanjay; Mukhtar, Hasan

    2003-03-10

    In recent years a dramatic surge has occurred on studies defining to the role of cyclooxygenase (COX)-2 in causation and prevention of cancer. Prostaglandin (PG) endoperoxidase synthase also commonly referred to as COX is a key enzyme involved in the conversion of arachidonic acid to PGs and other eicosanoids. COX exists as two isoforms, namely COX-1 and COX-2 with distinct tissue distribution and physiological functions. COX-1 is constitutively expressed in many tissues and cell types and is involved in normal cellular physiological functions whereas COX-2 is pro-inflammatory in nature and is inducible by mitogens, cytokines, tumor promoters and growth factors. A large volume of data exists showing that COX-2 is overexpressed in a large number of human cancers and cancer cell lines. The possibility of COX-2 as a candidate player in cancer development and progression evolved from the epidemiological studies which suggest that regular use of aspirin or other non-steroidal anti-inflammatory drugs could significantly decrease the risk of developing cancers in experimental animals and in humans. In our recently published study (Prostate, 42 2000 73-78), we provided the first evidence that COX-2 is overexpressed in human prostate adenocarcinoma. Many other studies verified our initial observation and reported that compared to normal tissue, COX-2 is overexpressed in human prostate cancer. It should be noted that some recent work has suggested that COX-2 is only up-regulated in proliferative inflammatory atrophy of the prostate, but not in prostate carcinoma. In this scenario, COX-2 inhibitors could afford their effects against prostate carcinogenesis by modulating COX-2 activity in other cells in prostate. An exciting corollary to this ongoing work is that selective COX-2 inhibitors may exhibit chemopreventive and even chemotherapeutic effects against prostate carcinogenesis in humans.

  13. A Systems Approach to Radiation Carcinogenesis

    Science.gov (United States)

    Hlatky, Lynn

    Understanding carcinogenesis risk is complicated by a number of factors, among these the lack of a common platform to integrate and analyze the available data, and the inherently systemsbiologic nature of the problem. We have investigated mechanistic approaches to radiogenic risk estimation that draw on unifying biological principles and incorporate data from multiscale sources. The resultant modeling takes into account that carcinogenesis is a multi-scale phenomenon, critically influenced by determinants not only at the molecular level, but at the cell and tissue-levels as well. To account for cell-level carcinogenesis progression as influenced by inter-tissue signaling, we have developed a dynamic carrying capacity construct that couples the growth of a tumor with the degree of induced vascularization. We have also characterized the molecular responses to radiation incorporating tissue-level angiogenesis implications, and have found striking radiation-quality-dependent responses. The molecular-level events of initiation and promotion are considered in our Two-Stage Logistic model, while incorporating in a rudimentary way the larger-scale growth-limiting role of cell-cell interactions. These and other recent studies undertaken to elaborate radiation-induced carcinogenesis are discussed, in pursuit of a more complete paradigm for understanding radiation induction of cancer and the consequent risk.

  14. Selenium in human mammary carcinogenesis

    DEFF Research Database (Denmark)

    Overvad, Kim; Grøn, P.; Langhoff, Otto;

    1991-01-01

    /l and TNM stage II 76 +/- 13 micrograms selenium/l), indicating disease-mediated changes. The evaluation of selenium as a risk indicator in human breast cancer was therefore restricted to TNM stage I patients (n = 36). Multiple logistic regression analyses including variables associated with selenium levels...... revealed no association between selenium levels and breast cancer risk.......In a case-referent study on the possible role of selenium in human mammary carcinogenesis, serum selenium was found to be 79 +/- 12 micrograms/l in 66 cases and 81 +/- 12 micrograms/l in 93 referents. An internal trend in serum selenium was observed among cases (TNM stage I 81 +/- 11 micrograms...

  15. [Iron function and carcinogenesis].

    Science.gov (United States)

    Akatsuka, Shinya; Toyokuni, Shinya

    2016-07-01

    Though iron is an essential micronutrient for humans, the excess state is acknowledged to be associated with oncogenesis. For example, iron overload in the liver of the patients with hereditary hemocromatosis highly increases the risk of hepatocellular carcinoma. Also, as to asbestos-related mesothelioma, such kinds of asbestos with a higher iron content are considered to be more carcinogenic. Iron is a useful element, which enables fundamental functions for life such as oxygen carrying and electron transport. However, in the situation where organisms are unable to have good control of it, iron turns into a dangerous element which catalyzes generation of reactive oxygen. In this review, I first outline the relationships between iron and cancer in general, then give an explanation about iron-related animal carcinogenesis models.

  16. Oxidative Stress and HPV Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Federico De Marco

    2013-02-01

    Full Text Available Extensive experimental work has conclusively demonstrated that infection with certain types of human papillomaviruses, the so-called high-risk human papillomavirus (HR-HPV, represent a most powerful human carcinogen. However, neoplastic growth is a rare and inappropriate outcome in the natural history of HPV, and a number of other events have to concur in order to induce the viral infection into the (very rare neoplastic transformation. From this perspective, a number of putative viral, host, and environmental co-factors have been proposed as potential candidates. Among them oxidative stress (OS is an interesting candidate, yet comparatively underexplored. OS is a constant threat to aerobic organisms being generated during mitochondrial oxidative phosphorylation, as well as during inflammation, infections, ionizing irradiation, UV exposure, mechanical and chemical stresses. Epithelial tissues, the elective target for HPV infection, are heavily exposed to all named sources of OS. Two different types of cooperative mechanisms are presumed to occur between OS and HPV: I The OS genotoxic activity and the HPV-induced genomic instability concur independently to the generation of the molecular damage necessary for the emergence of neoplastic clones. This first mode is merely a particular form of co-carcinogenesis; and II OS specifically interacts with one or more molecular stages of neoplastic initiation and/or progression induced by the HPV infection. This manuscript was designed to summarize available data on this latter hypothesis. Experimental data and indirect evidences on promoting the activity of OS in viral infection and viral integration will be reviewed. The anti-apoptotic and pro-angiogenetic role of NO (nitric oxide and iNOS (inducible nitric oxide synthase will be discussed together with the OS/HPV cooperation in inducing cancer metabolism adaptation. Unexplored/underexplored aspects of the OS interplay with the HPV-driven carcinogenesis

  17. STUDIES IN THE MECHANISM(S) OF ORTHO-PHENYLPHENOL INDUCED BLADDER CARCINOGENESIS IN F344 RATS. (R826408)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  18. 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.

  19. Fundamental studies of fusion plasmas. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Aamodt, R.E.

    1998-01-30

    Lodestar has carried out a vigorous research program in the areas of rf, edge plasma and divertor physics, with emphasis largely geared towards improving the understanding and performance of ion-cyclotron heating and current drive (ICRF) systems. Additionally, a research program in the field of edge plasma and divertor modeling was initiated. Theoretical work on high power rf sheath formation for multi-strap rf arrays was developed and benchmarked against recent experimental data from the new JET A2 antennas. Sophisticated modeling tools were employed to understand the sheath formation taking into account realistic three-dimensional antenna geometry. A novel physics explanation of an observed anomaly in the low power loading of antennas was applied to qualitatively interpret data on DIII-D in terms of rf sheaths, and potential applications of the idea to develop a near-field sheath diagnostic were explored. Other rf-wave related topics were also investigated. Full wave ICRF modeling studies were carried out in support of ongoing and planned tokamaks experiments, including the investigation of low frequency plasma heating and current drive regimes for IGNITOR. In a cross-disciplinary study involving both MHD and ICRF physics, ponderomotive feedback stabilization by rf was investigated as a potential means of controlling external kink mode disruptions. In another study, the instability of the ion hybrid wave (IHW) in the presence of fusion alpha particles was studied. In the field of edge plasma and divertor modeling studies, Lodestar began the development of a theory of generalized ballooning and sheath instabilities in the scrape off layer (SOL) of divertor tokamaks. A detailed summary of the technical progress in these areas during the contract period is included, as well as where references to published work can be found. A separate listing of publications, meeting abstracts, and other presentations is also given at the end of this final report.

  20. Diet-related DNA adduct formation in relation to carcinogenesis.

    Science.gov (United States)

    Hemeryck, Lieselot Y; Vanhaecke, Lynn

    2016-08-01

    The human diet contributes significantly to the initiation and promotion of carcinogenesis. It has become clear that the human diet contains several groups of natural foodborne chemicals that are at least in part responsible for the genotoxic, mutagenic, and carcinogenic potential of certain foodstuffs. Electrophilic chemicals are prone to attack nucleophilic sites in DNA, resulting in the formation of altered nucleobases, also known as DNA adducts. Since DNA adduct formation is believed to signal the onset of chemically induced carcinogenesis, the DNA adduct-inducing potential of certain foodstuffs has been investigated to gain more insight into diet-related pathways of carcinogenesis. Many studies have investigated diet-related DNA adduct formation. This review summarizes work on known or suspected dietary carcinogens and the role of DNA adduct formation in hypothesized carcinogenesis pathways.

  1. Additional EIPC Study Analysis. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Hadley, Stanton W [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gotham, Douglas J. [Purdue Univ., West Lafayette, IN (United States); Luciani, Ralph L. [Navigant Consultant Inc., Suwanee, GA (United States)

    2014-12-01

    Between 2010 and 2012 the Eastern Interconnection Planning Collaborative (EIPC) conducted a major long-term resource and transmission study of the Eastern Interconnection (EI). With guidance from a Stakeholder Steering Committee (SSC) that included representatives from the Eastern Interconnection States Planning Council (EISPC) among others, the project was conducted in two phases. Phase 1 involved a long-term capacity expansion analysis that involved creation of eight major futures plus 72 sensitivities. Three scenarios were selected for more extensive transmission- focused evaluation in Phase 2. Five power flow analyses, nine production cost model runs (including six sensitivities), and three capital cost estimations were developed during this second phase. The results from Phase 1 and 2 provided a wealth of data that could be examined further to address energy-related questions. A list of 14 topics was developed for further analysis. This paper brings together the earlier interim reports of the first 13 topics plus one additional topic into a single final report.

  2. Modifying effects of Soybean and Nigella Sativa against Experimental Hepato-carcinogenesis induced By Nitrosamine Precursor in Rats Histopathological and electron microscopically study

    Directory of Open Access Journals (Sweden)

    Hanaa F. Waer, **Abdel Baset EL Asser, ***Hamdy A. Ibrahim

    2005-03-01

    Full Text Available Cancer has become an important topic in medicine since it is a major cause of death in the developing countries and it is now only secondary to that of myocardial infraction. Nitrosamines precursors are known to be carcinogenic to humans, in various organs at relatively low levels of exposure. It induces benign and malignant tumors especially liver tumors following its administration by various routes, including ingestion and inhalation. Humans may be exposed to Nitrosamines through the ingestion of food that contains it, such as cured meat products, and smoked fish. Other exposures to Nitrosamines may be from drinking contaminated water and from breathing cigarette smoke and contaminated ambient air. Individual are most likely to be exposed to Nitrosamines in occupational settings such as in the rubber, tannery, fish processing, dyes, and surfactant industries. The prevalence of liver tumors throughout the world makes in imperative to seek chemo preventive agents. Vegetables, natural products of plant origin and numerous non-nutritive dietary constituents have been shown to play a salutary role in cancer chemoprevention. The present study aims to evaluate the chemo preventive efficacy of soy bean and Nigella sativa on hepato-carcinogenesis induced by dibuty1 nitrosamine (DEN. It could be observed that both soy bean and Nigella sativa have a good effect of amelioration against liver hepatoma induced by nitrosamine. Soy bean more or less showed more prerogative effect than Nigella 9 and 12 months after administration.

  3. Pipeline bottoming cycle study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1980-06-01

    The technical and economic feasibility of applying bottoming cycles to the prime movers that drive the compressors of natural gas pipelines was studied. These bottoming cycles convert some of the waste heat from the exhaust gas of the prime movers into shaft power and conserve gas. Three typical compressor station sites were selected, each on a different pipeline. Although the prime movers were different, they were similar enough in exhaust gas flow rate and temperature that a single bottoming cycle system could be designed, with some modifications, for all three sites. Preliminary design included selection of the bottoming cycle working fluid, optimization of the cycle, and design of the components, such as turbine, vapor generator and condensers. Installation drawings were made and hardware and installation costs were estimated. The results of the economic assessment of retrofitting bottoming cycle systems on the three selected sites indicated that profitability was strongly dependent upon the site-specific installation costs, how the energy was used and the yearly utilization of the apparatus. The study indicated that the bottoming cycles are a competitive investment alternative for certain applications for the pipeline industry. Bottoming cycles are technically feasible. It was concluded that proper design and operating practices would reduce the environmental and safety hazards to acceptable levels. The amount of gas that could be saved through the year 2000 by the adoption of bottoming cycles for two different supply projections was estimated as from 0.296 trillion ft/sup 3/ for a low supply projection to 0.734 trillion ft/sup 3/ for a high supply projection. The potential market for bottoming cycle equipment for the two supply projections varied from 170 to 500 units of varying size. Finally, a demonstration program plan was developed.

  4. 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.

  5. Helicobacter pylori in gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Hyo; Jun; Ahn; Dong; Soo; Lee

    2015-01-01

    Gastric cancer still is a major concern as the third most common cancer worldwide, despite declining rates of incidence in many Western countries. Helicobacter pylori(H. pylori) is the major cause of gastric carcinogenesis, and its infection insults gastric mucosa leading to theoccurrence of atrophic gastritis which progress to intestinal metaplasia, dysplasia, early gastric cancer, and advanced gastric cancer consequently. This review focuses on multiple factors including microbial virulence factors, host genetic factors, and environmental factors, which can heighten the chance of occurrence of gastric adenocarcinoma due to H. pylori infection. Bacterial virulence factors are key components in controlling the immune response associated with the induction of carcinogenesis, and cag A and vac A are the most well-known pathogenic factors. Host genetic polymorphisms contribute to regulating the inflammatory response to H. pylori and will become increasingly important with advancing techniques. Environmental factors such as high salt and smoking may also play a role in gastric carcinogenesis. It is important to understand the virulence factors, host genetic factors, and environmental factors interacting in the multistep process of gastric carcinogenesis. To conclude, prevention via H. pylori eradication and controlling environmental factors such as diet, smoking, and alcohol is an important strategy to avoid H. pylori-associated gastric carcinogenesis.

  6. Inhibition of carcinogenesis by tea.

    Science.gov (United States)

    Yang, Chung S; Maliakal, Pius; Meng, Xiaofeng

    2002-01-01

    Tea has received a great deal of attention because tea polyphenols are strong antioxidants, and tea preparations have inhibitory activity against tumorigenesis. The bioavailability and biotransformation of tea polyphenols, however, are key factors limiting these activities in vivo. The inhibition of tumorigenesis by green or black tea preparations has been demonstrated in animal models on different organ sites such as skin, lung, oral cavity, esophagus, forestomach, stomach, small intestine, colon, pancreas, and mammary gland. Epidemiological studies, however, have not yielded clear conclusions concerning the protective effects of tea consumption against cancer formation in humans. The discrepancy between the results from humans and animal models could be due to 1) the much higher doses of tea used in animals in comparison to human consumption, 2) the differences in causative factors between the cancers in humans and animals, and 3) confounding factors limiting the power of epidemiological studies to detect an effect. It is possible that tea may be only effective against specific types of cancer caused by certain etiological factors. Many mechanisms have been proposed for the inhibition of carcinogenesis by tea, including the modulation of signal transduction pathways that leads to the inhibition of cell proliferation and transformation, induction of apoptosis of preneoplastic and neoplastic cells, as well as inhibition of tumor invasion and angiogenesis. These mechanisms need to be evaluated and verified in animal models or humans in order to gain more understanding on the effect of tea consumption on human cancer.

  7. Final report for NIF chamber dynamics studies

    Energy Technology Data Exchange (ETDEWEB)

    Burnham, A; Peterson, P F; Scott, J M

    1998-09-01

    The National Ignition Facility (NIF), a 1.8 MJ, 192 laser beam facility, will have anticipated fusion yields of up to 20 MJ from D-T pellets encased in a gold hohlraum target. The energy emitted from the target in the form of x rays, neutrons, target debris kinetic energy, and target shrapnel will be contained in a 5 m. radius spherical target chamber. various diagnostics will be stationed around the target at varying distances from the target. During each shot, the target will emit x rays that will vaporize nearby target facing surfaces including those of the diagnostics, the target positioner, and other chamber structures. This ablated vapor will be transported throughout the chamber, and will eventually condense and deposit on surfaces in the chamber, including the final optics debris shields. The research at the University of California at Berkeley relates primarily to the NIF chamber dynamics. The key design issues are the ablation of the chamber structures, transport of the vapor through the chamber and the condensation or deposition processes of those vaporized materials. An understanding of these processes is essential in developing a concept for protecting the fina optics debris shields from an excessive coating (> 10 A) of target debris and ablated material, thereby prolonging their lifetime between change-outs. At Berkeley, we have studied the physical issues of the ablation process and the effects of varying materials, the condensation process of the vaporized material, and design schemes that can lower the threat posed to the debris shields by these processes. The work or portions of the work completed this year have been published in several papers and a dissertation [l-5].

  8. Carcinogenesis mechanisms of Fusobacterium nucleatum.

    Science.gov (United States)

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

    2017-03-07

    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.

  9. Neglected role of hookah and opium in gastric carcinogenesis : A cohort study on risk factors and attributable fractions

    NARCIS (Netherlands)

    Sadjadi, Alireza; Derakhshan, Mohammad H.; Yazdanbod, Abbas; Boreiri, Majid; Parsaeian, Mahbubeh; Babaei, Masoud; Alimohammadian, Masoomeh; Samadi, Fatemeh; Etemadi, Arash; Pourfarzi, Farhad; Ahmadi, Emad; Delavari, Alireza; Islami, Farhad; Farzadfar, Farshad; Sotoudeh, Masoud; Nikmanesh, Arash; Alizadeh, Behrooz Z.; de Bock, Geertruida H.; Malekzadeh, Reza

    2014-01-01

    A recent study showed an association between hookah/opium use and gastric cancer but no study has investigated the relationship with gastric precancerous lesions. We examined the association between hookah/opium and gastric precancerous lesions and subsequent gastric cancer. In a population-based co

  10. 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.

  11. Dose response problems in carcinogenesis.

    Science.gov (United States)

    Crump, K S

    1979-03-01

    The estimation of risks from exposure to carcinogens is an important problem from the viewpoint of protection of human health. It also poses some very difficult dose-response problems. Two dose-response models may fit experimental data about equally well and yet predict responses that differ by many orders of magnitude at low doses. Mechanisms of carcinogenesis are not sufficiently understood so that the shape of the dose-response curve at low doses can be satisfactorily predicted. Mathematical theories of carcinogenesis and statistical procedures can be of use with dose-reponse problems such as this and, in addition, can lead to a better understanding of the mechanisms of carcinogenesis. In this paper, mathematical dose-response models of carcinogenesis are considered as well as various proposed dose-response procedures for estimating carcinogenic risks at low doses. Areas are suggested in which further work may be useful. These areas include experimental design problems, statistical procedures for use with time-to-occurrence data, and mathematical models that incorporate such biological features as pharmacokinetics of carcinogens, synergistic effects, DNA repair, susceptible subpopulations, and immune reactions.

  12. [Monoamines stimulations in experimental carcinogenesis].

    Science.gov (United States)

    Popov, I; Spuzić, I; Rakić, Lj

    1994-01-01

    Facts about the role of CNS monoamines in cancerogenesis have been accumulated for many years. The aim of the present study was to investigate the effect of interaction of psychoactive drug (Piracetam) and other treatments on survival time of tumour-bearing rats. 138 Wistar rats were used in the experiment. The animals were injected 1% 3--Methilcholantren suspension in 10% Tylose, s.c. under the dorsal skin of the neck in a dose of 3 mg/animal. Within 4-9 months after a single injection, the rats developed tumours at the site of injection. The surgical removal was performed when tumours reached the size of 1-3 cm. After surgical extirpation of tumours different groups of animals were treated by cyclophosphamide (s.c. one-time dose of 50 mg/kg for female and 100 mg/kg for male) or by psychoactive drug (Piracetam) administrated by GE tube 5 time/week, 100 mg/kg. Autopsy and histological examinations were carried out in all animals. Survival time (> 120 days) was the greatest in group B (Piracetam, after surgical removal of tumours) 81.2%, and group C (Cyclophosphamid, after surgical removal of tumours) 68.8% and in group A (only surgical removal of tumours) 50%. In group B the incidence of metastases was the smallest (87.1% of animals were without metastases), compared with group C (45.4% of animals were without metastases) and group A (27.3% of animals were without metastases). The diference is statistically significant. The mechanism of antineoplastic effect of Piracetam consisted of the interaction of influences both on metabolism of the Central nervous system and the tumour. Probably, it is the neurotransmitter modulation that had its effect on carcinogenesis not only by regulation/disregulation of brain homeostasis, but also via direct effect on intracellular processes during cell development and differentation.

  13. NTP Toxicology and Carcinogenesis Studies of Tris(2-chloroethyl) Phosphate (CAS No. 115-96-8) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1991-05-01

    Tris(2-chloroethyl) phosphate (TRCP), a flame-retardant plasticizer used in plastics, polymeric foams, and synthetic fibers, was studied as part of the National Toxicology Program's class study of trisalkyl phosphate flame retardants. Toxicology and carcinogenesis studies were conducted by administering TRCP (approximately 98% pure) in corn oil by gavage to groups of F344/N rats and B6C3F1 mice of each sex for 16 days, 16 weeks, or 2 years. Genetic toxicology studies were performed in Salmonella typhimurium and Chinese hamster ovary (CHO) cells. 16-Day Studies: There were no chemical-related deaths, differences in final mean body weight, or histopathological lesions in rats receiving 22 to 350 mg/kg TRCP or in mice receiving 44 to 700 mg/kg TRCP for 12 doses over 16 days. Serum cholinesterase activity in female rats receiving 175 or 350 mg/kg TRCP was reduced slightly (80% of control levels), but enzyme activity in dosed male rats and in mice was similar to that in controls. 16-Week Studies: Rats received 22 to 350 mg/kg TRCP for 16 weeks (female) or 18 weeks (male). Several male and female rats in the 175 or 350 mg/kg dose groups died from chemical toxicity. Final mean body weights of female rats receiving 350 mg/kg were 20% greater than those of controls; final mean body weights of the remaining groups of dosed female rats and dosed male rats were similar. Chemical-related neuronal necrosis occurred in the hippocampus and thalamus of female rats and, to a lesser extent, of male rats. Serum cholinesterase activity was reduced in females receiving 175 or 350 mg/kg TRCP. There were no chemical-related deaths, differences in final mean body weight, or differences in cholinesterase activity in mice receiving 44 to 700 mg/kg TRCP for 16 weeks. Tubule epithelial cells with enlarged nuclei (cytomegaly and karyomegaly) were observed in the kidneys of high-dose (700 mg/kg) male and female mice. 2-Year Studies: The 2-year studies in rats were conducted by administering 0

  14. Effect of green tea catechins on breast carcinogenesis: a systematic review of in-vitro and in-vivo experimental studies.

    Science.gov (United States)

    Yiannakopoulou, Eugenia Ch

    2014-03-01

    Catechins (flavan-3-oils) are the main flavonoids present in green tea. The potential cancer chemopreventive and therapeutic properties of green tea catechins have been the focus of research efforts in the last two decades. This systematic review aims to generate in vitro and in vivo data on the effect of green tea catechins on breast carcinogenesis. Electronic databases were searched with the appropriate search terms. Existing evidence suggests that green tea catechins modulate breast cell carcinogenesis. The effect of green tea catechins on breast cell carcinogenesis has been investigated in different experimental models and under different experimental conditions, that is, carcinogen investigated, green tea catechin dosage regimen, treatment with green tea extract versus pure synthetic EGCG, and time point of treatment with green tea catechins in relation to the exposure to the carcinogen. Although the effect of green tea catechins was not always statistically significant, the protective effect of green tea catechins was demonstrated in all the trials, suggesting that treatment with green tea catechins should be further investigated in the clinical setting of chemoprevention of high-risk women. However, it should be emphasized that the reported actions of green tea catechins are observed in high concentrations that are difficult to achieve in the clinical setting. This drawback could be overcome by designing green tea catechins with better bioavailability and/or by cotreatment combining breast cancer endocrine treatment with green tea catechins.

  15. The role of TLR2, TLR4 and CD14 genetic polymorphisms in gastric carcinogenesis: a case-control study and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Natalia Castaño-Rodríguez

    Full Text Available BACKGROUND: In addition to Helicobacter pylori infection, host genetic factors contribute to gastric cancer (GC. Recognition of H. pylori is known to involve Toll-like receptors (TLR, which subsequently leads to activation of NF-κB. Thus, the overall aim of this study was to estimate for the first time the pooled effect size of polymorphisms in TLR2, TLR4 and CD14 on GC development through a meta-analysis. METHODS: A case-control study comprising 284 ethnic Chinese individuals (70 non-cardia GC cases and 214 functional dyspepsia controls was conducted for the genotyping of TLR2 -196 to -174del, CD14 -260 C/T and TLR4 rs11536889 using PCR, RT-PCR and mass spectrometry. Case-control studies of TLR2, TLR4 and CD14 polymorphisms and GC were searched up to June 2012. Pooled odds ratios and 95% confidence intervals were obtained by means of the random effects model. RESULTS: In our ethnic Chinese case-control study, the TLR4 rs11536889 C allele increased the risk of GC (OR: 1.89, 95%CI: 1.23-2.92 while the CD14 -260 T allele was protective (OR: 0.62, 95%CI: 0.42-0.91. TLR2 -196 to -174 increased the risk of GC only in H. pylori-infected individuals (OR: 3.10, 95%CI: 1.27-7.60. In the meta-analysis, TLR4 Asp299Gly showed borderline results in the general analysis (pooled OR: 1.58, 95%CI: 0.98-2.60, nevertheless, stratified analysis by ethnicity showed that the mutant allele was a definitive risk factor for GC in Western populations (pooled OR: 1.87, 95%CI: 1.31-2.65. There was a potential association between the TLR2 -196 to -174 deletion allele and GC in Japanese (pooled OR: 1.18, 95%CI: 0.96-1.45. TLR4 Thr399Ile did not provide significant results. CONCLUSIONS: TLR4 rs11536889 and CD14 -260 C/T are associated with non-cardia GC in Chinese. Based on our meta-analysis, the TLR signalling pathway is involved in gastric carcinogenesis, TLR4 Asp299Gly and TLR2 -196 to -174del showing associations with GC in an ethnic-specific manner.

  16. NTP Toxicology and Carcinogenesis Studies of o-Phenylphenol (CAS No. 90-43-7) Alone and with 7,12-Dimethylbenz(a)anthracene (CAS No. 57-97-6) in Swiss CD-1 Mice (Dermal Studies).

    Science.gov (United States)

    1986-03-01

    o-Phenylphenol is used primarily as a germicide and fungicide for citrus fruits and vegetables and was selected for carcinogenesis studies because of the potential for human exposure. Four-week studies were conducted in which groups of 10 male and 10 female Swiss Webster mice were given dermal applications to the dorsal interscapular region of 0, 6, 11, 21, 36, or 56 mg of o-phenylphenol in 0.1 ml of acetone. Doses were administered 3 days per week for 4 weeks, and animals were monitored for clinical changes. Reductions in body weights of acetone vehicle control were observed, but no compound-related changes in weight or survival occurred in male or female mice administered o-phenylphenol. o-Phenylphenol caused dose-related ulcerative lesions at the site of application. The severity of these lesions was judged not to be life threatening. Carcinogenesis studies were conducted to determine whether o-phenylphenol was a complete carcinogen for skin or a promoter in a two-stage initiation/promotion skin paint model. Groups of 50 Swiss CD-1 mice of each sex were used for up to 102 weeks. Five dose groups were used: an acetone vehicle control group; a positive control group initiated with 7,12-dimethylbenz(a)- anthracene (DMBA) and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA); an initiator control group that received DMBA plus acetone; a group that received repeated applications of o-phenylphenol. The following doses were applied dermally to a clipped area on the dorsal interscapular region 3 days per week: o-phenylphenol - 55.5 mg/0.1 ml acetone; or TPA - 0.005 mg/0.1 ml acetone. DMBA was administered as a single dose at a concentration of 0.05 mg/0.1 ml acetone to the dorsal interscapular region. In the 2-year studies, mean body weights of the o-phenylphenol, DMBA/o-phenylphenol, and DMBA/TPA groups were not markedly different from those of mice that received DMBA/acetone. Similarly, there were no significant group differences in survival except for a

  17. 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.

  18. 90% Compliance Pilot Studies Final Report

    Energy Technology Data Exchange (ETDEWEB)

    None

    2013-06-01

    In early 2010, the U.S. Department of Energy (DOE) announced an opportunity for states to participate in energy code compliance evaluation pilot studies. DOE worked with five Regional Energy Efficiency Organizations (REEOs, formerly referred to as Energy Efficiency Partnerships, or EEPs) to fund pilot studies covering nine states. This report details conclusions stated in individual state reports, as well as conclusions drawn by DOE based on their oversight of the pilot studies, and based on discussions held with the REEOs and representatives from the pilot study states and their contractors.

  19. Studies in genetic discrimination. Final progress report

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    We have screened 1006 respondents in a study of genetic discrimination. Analysis of these responses has produced evidence of the range of institutions engaged in genetic discrimination and demonstrates the impact of this discrimination on the respondents to the study. We have found that both ignorance and policy underlie genetic discrimination and that anti-discrimination laws are being violated.

  20. Gasohol: economic feasibility study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    David, M. L.; Hammaker, G. S.; Buzenberg, R. J.; Wagner, J. P.

    1978-07-01

    This report was prepared by Development Planning and Research Associates, Inc. under a contract with the Energy Research and Development Center of the University of Nebraska in cooperation with the Agricultural Products Industrial Utilization Committee and the State of Nebraska. Funding for this study was provided to the Energy Research and Development Center by the U.S. Department of Energy and the Old West Regional Commission. The primary objective of the study was to: determine the fiscal and market conditions under which the production of gasohol would be profitable for private producers. For purposes of this study, gasohol is a motor fuel consisting of 10 percent agriculturally-derived anhydrous ethanol and 90 percent unleaded gasoline. The study assumes that gasohol can be a fuel substitute for gasoline; indeed, the cost of gasoline will significantly influence that for gasohol. Gasoline prices are determined by factors external to ethanol; thus, the economic feasibility study of gasohol is in large part an economic feasibility study of fuel-grade ethanol production. More specifically, the study examined the following: the technical aspects of distributing, marketing, and using gasohol; the costs of the distribution and marketing of ethanol and gasohol; the energy balance of ethanol production; the cost of producing ethanol; the factors influencing ehtanol plant size and location; and the conditions that would make ethanol economicaly feasible for private producers.

  1. Poly(ADP-ribosyl)ation in carcinogenesis.

    Science.gov (United States)

    Masutani, Mitsuko; Fujimori, Hiroaki

    2013-12-01

    Cancer develops through diverse genetic, epigenetic and other changes, so-called 'multi-step carcinogenesis', and each cancer harbors different alterations and properties. Here in this article we review how poly(ADP-ribosyl)ation is involved in multi-step and diverse pathways of carcinogenesis. Involvement of poly- and mono-ADP-ribosylation in carcinogenesis has been studied at molecular and cellular levels, and further by animal models and human genetic approaches. PolyADP-ribosylation acts in DNA damage repair response and maintenance mechanisms of genomic stability. Several DNA repair pathways, including base-excision repair and double strand break repair pathways, involve PARP and PARG functions. These care-taker functions of poly(ADP-ribosyl)ation suggest that polyADP-ribosyation may mainly act in a tumor suppressive manner because genomic instability caused by defective DNA repair response could serve as a driving force for tumor progression, leading to invasion, metastasis and relapse of cancer. On the other hand, the new concept of 'synthetic lethality by PARP inhibition' suggests the significance of PARP activities for survival of cancer cells that harbor defects in DNA repair. Accumulating evidence has revealed that some PARP family molecules are involved in various signaling cascades other than DNA repair, including epigenetic and transcriptional regulations, inflammation/immune response and epithelial-mesenchymal transition, suggesting that poly(ADP-ribosyl)ation both promotes and suppresses carcinogenic processes depending on the conditions. Expanding understanding of poly(ADP-ribosyl)ation suggests that strategies to achieve cancer prevention targeting poly(ADP-ribosyl)ation for genome protection against life-long exposure to environmental carcinogens and endogenous carcinogenic stimuli.

  2. Forecast Master Program case studies: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Engle, R.; Granger, C.; Ramanathan, R. (ed.)

    1987-04-01

    This report presents a number of case studies using the computer software package FORECAST MASTER (FM). The series studied and forecast are, aggregate monthly California Electricity Sales, system energy demand data from Ontario Hydro, peak demand data for the residential and commercial customers of Georgia Power Company, Massachusetts Electric commercial sales, Narragansett Electric commercial sales, average and peak demand using Georgia Power Company data. A variety of methods have been studied by each of the contributing authors; trend line fitting, exponential smoothing, Box-Jenkins univariate forecasting, vector autoregression, state space modeling, dynamic econometric models including time-varying parameters and general order serial correlation corrections. Thus both the data sets and the modeling/forecasting methodologies are varied. A number of conclusions emerge from these case studies: FM provides a powerful set of tools to aid a utility forecaster, a great deal of caution should be exercised in pre-processing the data; it can have unintended side effects, diagnostic tests are very useful in econometric models, the Akaike Information Criterion is a useful measure for selecting the best state space model, and state space and econometric approaches both need equal amounts of care in model analysis and presentation.

  3. Geothermal reservoir insurance study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1981-10-09

    The principal goal of this study was to provide analysis of and recommendations on the need for and feasibility of a geothermal reservoir insurance program. Five major tasks are reported: perception of risk by major market sectors, status of private sector insurance programs, analysis of reservoir risks, alternative government roles, and recommendations.

  4. Advanced Multiple Processor Configuration Study. Final Report.

    Science.gov (United States)

    Clymer, S. J.

    This summary of a study on multiple processor configurations includes the objectives, background, approach, and results of research undertaken to provide the Air Force with a generalized model of computer processor combinations for use in the evaluation of proposed flight training simulator computational designs. An analysis of a real-time flight…

  5. Packaging Materials Outgassing Study Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Smith, R. A. [Oak Ridge Y-12 Plant (Y-12), Oak Ridge, TN (United States)

    2006-09-26

    An outgassing study was conducted on two polyurethane packaging foams, two polymer bottles (polytetrafluoroethylene and polyethylene), and two polymer lids. The purpose was to measure the volume of gases that diffuse from these packaging materials at a maximum of 400-degrees F when stored in ambient air within sealed containers.

  6. Renewable Energy Feasibility Study Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Rooney, Tim [Antares Group Inc.

    2013-10-30

    The Gila River Indian Community (GRIC or the Community) contracted the ANTARES Group, Inc. (“ANTARES”) to assess the feasibility of solar photovoltaic (PV) installations. A solar energy project could provide a number of benefits to the Community in terms of potential future energy savings, increased employment, environmental benefits from renewable energy generation and usage, and increased energy self-sufficiency. The study addresses a number of facets of a solar project’s overall feasibility, including: Technical appropriateness; Solar resource characteristics and expected system performance; Levelized cost of electricity (LCOE) economic assessment. The Gila River Indian Community (GRIC or the Community) contracted the ANTARES Group, Inc. (“ANTARES”) to prepare a biomass resource assessment study and evaluate the feasibility of a bioenergy project on Community land. A biomass project could provide a number of benefits to the Community in terms of increased employment, environmental benefits from renewable energy generation and usage, and increased energy self-sufficiency. The study addresses a number of facets of a biomass project’s overall feasibility, including: Resource analysis and costs; Identification of potential bioenergy projects; Technical and economic (levelized cost of energy) modeling for selected project configuration.

  7. Geochemistry studies in Eastern Kentucky. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Negus-de Wys, J.

    1981-04-01

    Presented here are the results of inorganic geochemical studies on well cuttings from fourteen wells in the Big Sandy Gas Field. Both x-ray fluorescence and x-ray diffraction were used in analysis. Resultant mineralic data and elemental data were mapped by computer and by hand for five intervals of Ohio Shale and for the Berea/Bedford sequence. Comparisons of the geochemistry trend maps were made with lithology, structure, thermal maturation, gas open flow, and paleoenvironment. Techniques used included visual map comparison, computer map comparison programs utilizing correlation coefficients based on grid derived data sets, cluster analysis, x-y plots, and r/sup 2/ (coefficient of determination). A limited number of regional maps are included. It is concluded that inorganic geochemical analysis can be useful in: (1) suggesting paleoenvironmental trends; (2) establishing depositional trends; (3) enhancing exploration in terms of setting limits and pinpointing potential areas for hydrocarbon recovery; and (4) identification of likely locations for large gas fields when used with other geological studies. Elemental data analysis is the most accurate, and can be done quickly and inexpensively. It is concluded that the Big Sandy gas field area is a unique stratigraphic-structural gas trap, in which sedimentary factors, depositional basin features, plant evolution and occurrence, and structural elements all played important roles. Combinations of certain of these ingredients in different amounts may exist in other parts of the basin, and thus, suggest areas for hydrocarbon accumulation and potential recovery.

  8. Effect of luteolin on glycoproteins metabolism in 1, 2-dimethylhydrazine induced experimental colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Manju Vaiyapuri

    2008-12-01

    carcinogenesis. Thus, the present study indicates that luteolin has protected the cell surface and maintained the structural integrity of the cell membranes during DMH induced colon carcinogenesis. Keywords: Colon cancer, 1, 2-dimethylhydrazine, luteolin, glycoproteins Received: 23 January 2009 / Received in revised form: 17 February 2009, Accepted: 28 February 2009, Published online: 3 March 2009

  9. Bern clothes washer study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Tomlinson, J.J.; Rizy, D.T.

    1998-03-01

    The US market for domestic clothes washers is currently dominated by conventional, vertical axis washers, which typically require about 40 gallons of water for each load. Although small for an individual load, the fact that 35 billion loads of laundry are washed annually in the US results in a substantial quantity of water and energy use. Although much smaller, today`s market for high-efficiency clothes washers which use much less water and energy is growing albeit slowly as manufacturers are making washers based around tumble-action, horizontal axis designs available, information about their performance and benefits is being developed, and consumers are made aware of these benefits. To help build awareness of these benefits and to accelerate markets for high-efficiency washers, DOE, under its Energy Star Program and in cooperation with Maytag Appliances, conducted a field-evaluation of high-efficiency washers using Bern, Kansas (population approximately 200) as a test bed. Baseline washer performance data as well as customer washing behavior were obtained from data collected on the existing washers of more than 100 participants in this instrumented study. Following a 2-month initial study period, all conventional washers were replaced by high-efficiency, tumble action washers, and the experiment continued for another 3-month period. Based on measured data from over 20,000 loads of laundry, the impact of the washer replacement on (1) individual customers` energy and water consumption, (2) customers` laundry habits and perceptions, and (3) the community`s water supply and waste water systems were determined and reported.

  10. Oral Carcinogenesis and Oral Cancer Chemoprevention: A Review

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2011-01-01

    Full Text Available Oral cancer is one of the major global threats to public health. The development of oral cancer is a tobacco-related multistep and multifocal process involving field cancerization and carcinogenesis. The rationale for molecular-targeted prevention of oral cancer is promising. Biomarkers of genomic instability, including aneuploidy and allelic imbalance, are possible to measure the cancer risk of oral premalignancies. Understanding of the biology of oral carcinogenesis will yield important advances for detecting high-risk patients, monitoring preventive interventions, and assessing cancer risk and pharmacogenomics. In addition, novel chemopreventive agents based on molecular mechanisms and targets against oral cancers will be derived from studies using appropriate animal carcinogenesis models. New approaches, such as molecular-targeted agents and agent combinations in high-risk oral individuals, are undoubtedly needed to reduce the devastating worldwide consequences of oral malignancy.

  11. Dietary fat and carcinogenesis

    NARCIS (Netherlands)

    Woutersen, R.A.; Appel, M.J.; Garderen-Hoetmer, A. van; Wijnands, M.V.W.

    1999-01-01

    Epidemiologic investigations have suggested a relationship between dietary fat intake and various types of cancer incidences. Furthermore, epidemiologic studies as well as studies with animal models have demonstrated that not only the amount but also the type of fat consumed is important. At present

  12. Adsorption isotherm special study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-05-01

    The study was designed to identify methods to determine adsorption applicable to Uranium Mill Tailings Remedial Action (UMTRA) Project sites, and to determine how changes in aquifer conditions affect metal adsorption, resulting retardation factors, and estimated contaminant migration rates. EPA and ASTM procedures were used to estimate sediment sorption of U, As, and Mo under varying groundwater geochemical conditions. Aquifer matrix materials from three distinct locations at the DOE UMTRA Project site in Rifle, CO, were used as the adsorbents under different pH conditions; these conditions stimulated geochemical environments under the tailings, near the tailings, and downgradient from the tailings. Grain size, total surface area, bulk and clay mineralogy, and petrography of the sediments were characterized. U and Mo yielded linear isotherms, while As had nonlinear ones. U and Mo were adsorbed strongly on sediments acidified to levels similar to tailings leachate. Changes in pH had much less effect on As adsorption. Mo was adsorbed very little at pH 7-7.3, U was weakly sorbed, and As was moderately sorbed. Velocities were estimated for metal transport at different pHs. Results show that the aquifer materials must be characterized to estimate metal transport velocities in aquifers and to develop groundwater restoration strategies for the UMTRA project.

  13. Study of brine treatment. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1977-11-01

    Available information pertinent to the treatment of geothermal brines was collected by literature search and then evaluated and summarized for use by the electric utility and geothermal industries. The information was screened from the geothermal, oil and gas, wastewater disposal, and boiler water treatment industries. The current state of knowledge and methodology concerning the treatment of geothermal brines to control scaling and corrosion in geothermal electric power production was assessed. Currently, geothermal scale in pipes and wells is removed by physical or chemical methods. There is a growing effort on developing methods to control scale formation for both fresh and spent brines, including pH adjustment and application of an electrical potential for fresh fluids, and coagulation to treat spent fluids. Current methods of corrosion control center around planned replacement of piping and other plant components, with efforts focused primarily on development of materials with improved corrosion resistance. Recommendations for additional work to improve brine treatment include the following: (1) chemical and physical characterization of brine and scale compositions, (2) basic data on the mechanism of scale formation and the effects of inhibitors, (3) development of instrumentation to monitor geothermal brine constituents, (4) correlation of laboratory results with field test data, and (5) screening of currently available commercial inhibitors for application to geothermal brines. An annotated bibliography of the reference material used in this study is included.

  14. Study of The Final Customer Loyalty Process

    Directory of Open Access Journals (Sweden)

    Juan Carlos Fandos

    2013-12-01

    Full Text Available For any business is important to maintain a loyal customer base to help they to survive over time. This situation is accentuated even to the extent that increases competition and increases uncertainty. At present these are two features that are really developed. Because of the deep crisis in which we are, and other elements such as globalization and the development of new technologies and communication systems, we are faced with a scenario of intense competition and uncertainty manifest. It is therefore more necessary than ever to know in depth how to get customers to be faithful, and develop true loyalty strategies.In this paper, we present the sequential approach to the formation of consumer loyalty in order to deepen understanding of the concept. It is supplemented by studying the combined effect of switching costs as an element that promotes the continuity of the relationship. The results shows that the consumer takes a more cognitive process information in their initial assessments of the service and therefore in the early stages of loyalty. As advances in consumer behavior process becomes more direct and mechanic, so we can say that the customer-company bond is stronger.

  15. New Particle Formation Study Final Campaign Report

    Energy Technology Data Exchange (ETDEWEB)

    Smith, JN; McMurry, PH [University of Minnesota

    2015-01-01

    The scientific foci of the New Particle Formation Study were the formation and evolution of atmospheric aerosols and the impacts of newly formed particles on cloud processes. Specifically, we planned to: (1) to identify the species and mechanisms responsible for the initial steps of new particle formation, i.e., the formation of thermodynamically stable clusters; (2) investigate the role of acid-base chemistry in new particle growth through measurements of ammonia and amines as well as organic and inorganic acids in both atmospheric nanoparticles and the gas phase; (3) investigate the contribution of other surface area or volume-controlled processes to nanoparticle formation and growth; (4) create a comprehensive dataset related to new particle formation and growth that can be used as input for our own thermodynamic models as well as the modeling efforts by our Department of Energy (DOE) Aerosol Life Cycle working group collaborators; (5) characterize the increase of the number and activity of cloud condensation nuclei (CCN) due to particle formation and growth; (6) determine the regional extent of new particle formation to address the role that atmospheric transport plays in determining the impacts, if any, of new particle formation on cloud number and properties.

  16. Pinellas Plant feasibility study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-09-01

    The Pinellas Plant was built in 1956 to manufacture neutron generators, a principal component in nuclear weapons. In September 1990, the Department of Health and Rehabilitative Services (HRS) entered into an agreement with DOE to independently examine environmental monitoring data from the plant and health data from Pinellas County to determine if an epidemiological study is technically feasible to measure possible off-site health effects from ionizing radiation. Through normal plant operations, some radioactive materials have been released to the environment. Eighty percent of the total plant releases of 107,707 curies occurred in the early years of plant operation (1957--1960). The primary materials released were tritium gas, tritium oxide and krypton-85. Environmental monitoring for radioactive releases from the plant has been done regularly since 1975. The US Public Health Service Centers for Disease Control and Prevention (CDC), in assisting HRS, has determined that sufficient radiological data exist by which a dose reconstruction can be done. A dose reconstruction can provide an estimate of how much radiological exposure someone living in the vicinity of the Pinellas Plant may have suffered from environmental releases.

  17. Microbial field pilot study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, R.M.; McInerney, M.J.; Menzie, D.E.; Coates, J.D.; Chisholm, J.L.

    1993-05-01

    A multi-well microbially enhanced oil recovery field pilot has been performed in the Southeast Vassar Vertz Sand Unit in Payne County, Oklahoma. The primary emphasis of the experiment was preferential plugging of high permeability zones for the purpose of improving waterflood sweep efficiency. Studies were performed to determine reservoir chemistry, ecology, and indigenous bacteria populations. Growth experiments were used to select a nutrient system compatible with the reservoir that encouraged growth of a group of indigenous nitrate-using bacteria and inhibit growth of sulfate-reducing bacteria. A specific field pilot area behind an active line drive waterflood was selected. Surface facilities were designed and installed. Injection protocols of bulk nutrient materials were prepared to facilitate uniform distribution of nutrients within the pilot area. By the end of December, 1991, 82.5 tons (75.0 tonnes) of nutrients had been injected in the field. A tracer test identified significant heterogeneity in the SEVVSU and made it necessary to monitor additional production wells in the field. The tracer tests and changes in production behavior indicate the additional production wells monitored during the field trial were also affected. Eighty two and one half barrels (13.1 m{sup 3}) of tertiary oil have been recovered. Microbial activity has increased CO{sub 2} content as indicated by increased alkalinity. A temporary rise in sulfide concentration was experienced. These indicate an active microbial community was generated in the field by the nutrient injection. Pilot area interwell pressure interference test results showed that significant permeability reduction occurred. The interwell permeabilities in the pilot area between the injector and the three pilot production wells were made more uniform which indicates a successful preferential plugging enhanced oil recovery project.

  18. Modeling Multiple Causes of Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Jones, T D

    1999-01-24

    An array of epidemiological results and databases on test animal indicate that risk of cancer and atherosclerosis can be up- or down-regulated by diet through a range of 200%. Other factors contribute incrementally and include the natural terrestrial environment and various human activities that jointly produce complex exposures to endotoxin-producing microorganisms, ionizing radiations, and chemicals. Ordinary personal habits and simple physical irritants have been demonstrated to affect the immune response and risk of disease. There tends to be poor statistical correlation of long-term risk with single agent exposures incurred throughout working careers. However, Agency recommendations for control of hazardous exposures to humans has been substance-specific instead of contextually realistic even though there is consistent evidence for common mechanisms of toxicological and carcinogenic action. That behavior seems to be best explained by molecular stresses from cellular oxygen metabolism and phagocytosis of antigenic invasion as well as breakdown of normal metabolic compounds associated with homeostatic- and injury-related renewal of cells. There is continually mounting evidence that marrow stroma, comprised largely of monocyte-macrophages and fibroblasts, is important to phagocytic and cytokinetic response, but the complex action of the immune process is difficult to infer from first-principle logic or biomarkers of toxic injury. The many diverse database studies all seem to implicate two important processes, i.e., the univalent reduction of molecular oxygen and breakdown of aginuine, an amino acid, by hydrolysis or digestion of protein which is attendant to normal antigen-antibody action. This behavior indicates that protection guidelines and risk coefficients should be context dependent to include reference considerations of the composite action of parameters that mediate oxygen metabolism. A logic of this type permits the realistic common-scale modeling of

  19. The Dual Role of Inflammation in Colon Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Carmine Stolfi

    2012-09-01

    Full Text Available Chronic inflammation characterizing patients with inflammatory bowel disease (IBD represents a major risk factor for the development of colorectal cancer. Mechanisms underlying this neoplastic transformation are not fully understood though studies in experimental models of colon carcinogenesis suggest that inflammatory cell-derived cytokines either directly or indirectly stimulate the uncontrolled growth of cancer cells. Nevertheless, under specific inflammatory conditions, immune cells can boost an anti-tumor immune response with the down-stream effect of eliminating dysplastic and cancerous cells. This review outlines the beneficial and detrimental role of inflammation in colon carcinogenesis.

  20. Final Report on Pilot Studies / Final Report on Classroom Research with STEM and TESL Assessment

    DEFF Research Database (Denmark)

    Biel, Carmen; Wake, Jo Dugstad; Hesse, Friedrich

    This Deliverable is the final report on pilot studies within the NEXT-TELL project (D6.7) and furthermore comprises the Deliverable on Classroom Research with STEM and TESL Assessment (D2.9) in order to avoid redundancies between those two Deliverables.......This Deliverable is the final report on pilot studies within the NEXT-TELL project (D6.7) and furthermore comprises the Deliverable on Classroom Research with STEM and TESL Assessment (D2.9) in order to avoid redundancies between those two Deliverables....

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

    Energy Technology Data Exchange (ETDEWEB)

    Samet, J.; Gilliland, F.D.

    1998-08-13

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

  2. NTP Toxicology and Carcinogenesis Studies of Tetrafluoroethylene (CAS No. 116-14-3) in F344 Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1997-04-01

    Tetrafluoroethylene is used in the production of polytetrafluoroethylene (Teflon(R)) and other polymers. Tetrafluoroethylene was nominated by the National Cancer Institute for toxicity and carcinogenicity studies based on the potential for human exposure to the chemical due to the large production volume and on the lack of adequate data for tetrafluoroethylene in the literature. Male and female F344/N rats and B6C3F1 mice were exposed to tetrafluoroethylene (98% to 99% pure) by whole body inhalation exposure for 16 days, 13 weeks, or 2 years. Genetic toxicity studies were conducted in mouse peripheral blood erythrocytes. 16-DAY STUDY IN RATS: Groups of five male and five female F344/N rats were exposed to 0, 312, 625, 1,250, 2,500, or 5,000 ppm tetrafluoroethylene by inhalation for 6 hours per day, 5 days per week for a total of 12 exposures during a 16-day period. All rats survived to the end of the study. The final mean body weights and body weight gains of males and females exposed to 5,000 ppm were significantly less than those of the controls. The mean body weight gain of females exposed to 2,500 ppm was also significantly less than that of the controls. There were no exposure-related clinical findings in male or female rats. There were no significant differences in hematology parameters that were considered to be related to tetrafluoroethylene exposure. Absolute and relative kidney weights of all exposed groups of males were significantly greater than those of the controls, as were those of females in the 2,500 and 5,000 ppm groups. The absolute kidney weight of females exposed to 1,250 ppm was also significantly greater than that of the controls. The relative liver weights of all exposed groups of males and the absolute liver weights of males in the 625 and 2,500 ppm groups were significantly greater than those of the controls. Increased incidences of renal tubule degeneration occurred in males and females exposed to 625 ppm or greater; this lesion was

  3. 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 o

  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...

  5. The glutathione biotransformation system and colon carcinogenesis in human

    NARCIS (Netherlands)

    Grubben, M.J.A.L.; Nagengast, F.M.; Katan, M.B.; Peters, W.H.M.

    2001-01-01

    Evidence for a protective role of the glutathione biotransformation system in carcinogenesis is growing. However, most data on this system in relation to colorectal cancer originate from animal studies. Here we review the human data. In humans, a significant association was found between glutathione

  6. NTP Toxicology and Carcinogenesis Studies of Salicylazosulfapyridine (CAS No. 599-79-1) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1997-05-01

    Salicylazosulfapyridine is widely used for the treatment of ulcerative colitis and Crohn's disease. It has been beneficial in the treatment of psoriasis and rheumatoid arthritis, and it has been used in veterinary medicine for the treatment of granulomatous colitis. Salicylazosulfapyridine was nominated for toxicity and carcinogenicity testing by the National Cancer Institute on the basis of its widespread use in humans and because it is a representative chemical from a class of aryl sulfonamides. Salicylazosulfapyridine is a suspect carcinogen because reductive cleavage of the azo linkage yields a p-amino aryl sulfonamide (sulfapyridine), and a related p-amino aryl sulfonamide (sulfamethoxazole) has been shown to produce thyroid neoplasms in rats. Toxicology and carcinogenicity studies were conducted in F344/N rats and B6C3F1 mice. Rats and mice were administered salicylazosulfapyridine (96% to 98% pure) in corn oil by gavage for 16 days, 13 weeks, or 2 years. The gavage route of administration was selected for these studies because it approximates the typical route of human exposure to the chemical. Genetic toxicology studies were conducted in vitro in Salmonella typhimurium and cultured Chinese hamster ovary cells and in vivo in rat and mouse bone marrow and mouse peripheral blood cells. 16-DAY STUDY IN RATS: Groups of five male and five female rats were administered 0, 675, 1,350, or 2,700 mg salicylazosulfapyridine/kg body weight in corn oil by gavage for 16 days excluding weekends. All rats survived to the end of the study. With the exception of the 675 mg/kg male group, the final mean body weights of all dosed groups of males and females were significantly lower than those of controls. Mean body weight gains of all dosed groups were less than those of controls. Clinical findings included ruffled fur and distended abdomens in male and female rats receiving 2,700 mg/kg. Hypothyroidism, evidenced by decreased serum triiodothyronine and thyroxine concentrations

  7. Role of colonic microbiota in colorectal carcinogenesis: a systematic review

    Directory of Open Access Journals (Sweden)

    Marta Borges-Canha

    2015-11-01

    Full Text Available Background and aim: The human colonic mucosa is populated by a wide range of microorganisms, usually in a symbiotic relation with the host. Sometimes this balance is lost and a state of dysbiosis arises, exposing the colon to different metabolic and inflammatory stimuli (according to the microbiota's changing profile. Recent findings lead to hypothesize that this unbalance may create a subclinical pro-inflammatory state that increases DNA mutations and, therefore, colorectal carcinogenesis. In this article we aim to systematically review the scientific evidence regarding colonic microbiota and its role in colorectal carcinogenesis. Methods: Systematic review of PubMed searching results for original articles studying microbiota and colorectal cancer until November 2014. Results: Thirty-one original articles studied the role of colon microbiota in colorectal carcinoma including both human and animal studies. Different and heterogeneous methods were used and different bacteria were considered. Nevertheless, some bacteria are consistently augmented (such as Fusobacteria, Alistipes, Porphyromonadaceae, Coriobacteridae, Staphylococcaceae, Akkermansia spp. and Methanobacteriales, while other are constantly diminished in colorectal cancer (such as Bifidobacterium, Lactobacillus, Ruminococcus, Faecalibacterium spp., Roseburia, and Treponema. Moreover, bacteria metabolites amino acids are increased and butyrate is decreased throughout colonic carcinogenesis. Conclusion: Conclusive evidence shows that colorectal carcinogenesis is associated with microbial dysbiosis. This information may be used to create new prophylactic, diagnostic and therapeutic strategies for colorectal cancer.

  8. Expanded studies of linear collider final focus systems at the Final Focus Test Beam

    Energy Technology Data Exchange (ETDEWEB)

    Tenenbaum, P.G.

    1995-12-01

    In order to meet their luminosity goals, linear colliders operating in the center-of-mass energy range from 3,50 to 1,500 GeV will need to deliver beams which are as small as a few Manometers tall, with x:y aspect ratios as large as 100. The Final Focus Test Beam (FFTB) is a prototype for the final focus demanded by these colliders: its purpose is to provide demagnification equivalent to those in the future linear collider, which corresponds to a focused spot size in the FFTB of 1.7 microns (horizontal) by 60 manometers (vertical). In order to achieve the desired spot sizes, the FFTB beam optics must be tuned to eliminate aberrations and other errors, and to ensure that the optics conform to the desired final conditions and the measured initial conditions of the beam. Using a combination of incoming-beam diagnostics. beam-based local diagnostics, and global tuning algorithms, the FFTB beam size has been reduced to a stable final size of 1.7 microns by 70 manometers. In addition, the chromatic properties of the FFTB have been studied using two techniques and found to be acceptable. Descriptions of the hardware and techniques used in these studies are presented, along with results and suggestions for future research.

  9. Cadmium carcinogenesis – some key points

    OpenAIRE

    2011-01-01

    The article presents briefly the main mechanisms of cadmium carcinogenesis and the most important sites of cancer (lung, breast, prostate, testes, kidney) induced by cadmium. In spite of some evidence showing carcinogenic potential of cadmium, further research is still required to elucidate the relative contributions of various molecular mechanisms involved in cadmium carcinogenesis

  10. Cadmium carcinogenesis – some key points

    Directory of Open Access Journals (Sweden)

    Loreta Strumylaite

    2011-09-01

    Full Text Available The article presents briefly the main mechanisms of cadmium carcinogenesis and the most important sites of cancer (lung, breast, prostate, testes, kidney induced by cadmium. In spite of some evidence showing carcinogenic potential of cadmium, further research is still required to elucidate the relative contributions of various molecular mechanisms involved in cadmium carcinogenesis

  11. Carcinogenesis explained within the context of a theory of organisms.

    Science.gov (United States)

    Sonnenschein, Carlos; Soto, Ana M

    2016-10-01

    For a century, the somatic mutation theory (SMT) has been the prevalent theory to explain carcinogenesis. According to the SMT, cancer is a cellular problem, and thus, the level of organization where it should be studied is the cellular level. Additionally, the SMT proposes that cancer is a problem of the control of cell proliferation and assumes that proliferative quiescence is the default state of cells in metazoa. In 1999, a competing theory, the tissue organization field theory (TOFT), was proposed. In contraposition to the SMT, the TOFT posits that cancer is a tissue-based disease whereby carcinogens (directly) and mutations in the germ-line (indirectly) alter the normal interactions between the diverse components of an organ, such as the stroma and its adjacent epithelium. The TOFT explicitly acknowledges that the default state of all cells is proliferation with variation and motility. When taking into consideration the principle of organization, we posit that carcinogenesis can be explained as a relational problem whereby release of the constraints created by cell interactions and the physical forces generated by cellular agency lead cells within a tissue to regain their default state of proliferation with variation and motility. Within this perspective, what matters both in morphogenesis and carcinogenesis is not only molecules, but also biophysical forces generated by cells and tissues. Herein, we describe how the principles for a theory of organisms apply to the TOFT and thus to the study of carcinogenesis.

  12. Role of retinoic receptors in lung carcinogenesis

    Directory of Open Access Journals (Sweden)

    Renyi-Vamos Ferenc

    2008-07-01

    Full Text Available Abstract Several in vitro and in vivo studies have examined the positive and negative effects of retinoids (vitamin A analogs in premalignant and malignant lesions. Retinoids have been used as chemopreventive and anticancer agents because of their pleiotropic regulator function in cell differentiation, growth, proliferation and apoptosis through interaction with two types of nuclear receptors: retinoic acid receptors and retinoid X receptors. Recent investigations have gradually elucidated the function of retinoids and their signaling pathways and may explain the failure of earlier chemopreventive studies. In this review we have compiled basic and recent knowledge regarding the role of retinoid receptors in lung carcinogenesis. Sensitive and appropriate biological tools are necessary for screening the risk population and monitoring the efficacy of chemoprevention. Investigation of retinoid receptors is important and may contribute to the establishment of new strategies in chemoprevention for high-risk patients and in the treatment of lung cancer.

  13. NTP Toxicology and Carcinogenesis Studies of Two Pentachlorophenol Technical-Grade Mixtures (CAS No. 87-86-5) in B6C3F1 Mice (Feed Studies).

    Science.gov (United States)

    1989-03-01

    pure pentachlorophenol for 26-27 weeks. Common control groups of 10 male and 10 female mice were fed control diets. Additional groups of male mice were examined for behavioral, histopathologic, clinical pathology, biochemical, and immunologic effects. All mice exposed at the highest dose of technical-grade pentachlorophenol died, as did 2/10 male mice exposed at the highest dose of DP-2. No deaths were observed in mice exposed to EC-7 or pure pentachlorophenol. Markedly lower final body weights were observed in the high dose groups only (all grades of pentachlorophenol). No chemical-relatedclinical signs were observed at sublethal doses. No major behavioral changes were observed after 5 weeks' exposure, but increased motor activity and heightened startle responses were present at the end of the study in female mice exposed to all four grades of pentachlorophenol. All grades of pentachlorophenol caused increases in serum enzymes associated with liver injury. All grades of pentachlorophenol also resulted in a dose-related induction of aryl hydrocarbon hydroxylase and an increase in cytochrome P450. However, the technical grade was a more powerful inducer than the other grades of pentachlorophenol. Pure pentachlorophenol had no effect on humoral or cell-mediated immunity. However, DP-2 and particularly technical-grade pentachlorophenol depressed humoral immune function. A dose-related increase in liver weight was observed in mice exposed to all grades of pentachlorophenol. A dose-related increase in spleen weight was observed in male mice exposed to all grades of pentachlorophenol; a decrease in spleen weight was observed in female mice exposed to all grades of pentachlorophenol except pure. After 6 months' exposure, histopathologic examination consistently revealed effects in the liver and urinary bladder. The liver lesions were present at all doses with all four grades of pentachlorophenol but were less severe at comparable doses in the mice exposed to pure

  14. NTP Toxicology and Carcinogenesis Studies of Isobutene (CAS No. 115-11-7) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1998-12-01

    Isobutene is produced during the fractionation of refinery gases or through the catalytic cracking of methyl-t-butyl ether. Isobutene is primarily used to produce diisobutylene, trimers, butyl rubber, and other polymers. In addition, it is used in the production of isooctane, high-octane aviation gasoline, methyl-t-butyl ether, and copolymer resins with butadiene and acrylonitrile. Isobutene was selected for evaluation because of the potential for human exposure due to its large production volume and the lack of adequate data on its carcinogenic potential. The toxicity and carcinogenicity of isobutene were determined in male and female F344/N rats and B6C3F1 mice exposed to isobutene (greater than 98% pure) by inhalation for 14 weeks or 2 years. The mutagenicity of isobutene was assessed in Salmonella typhimurium, and the frequency of micronuclei was determined in the peripheral blood of mice exposed by inhalation for 14 weeks. 14-WEEK STUDIES: Groups of 10 male and 10 female F344/N rats and B6C3F1 mice were exposed to isobutene at concentrations of 0, 500, 1,000, 2,000, 4,000, or 8,000 ppm 6 hours per day, 5 days per week, for 14 weeks. Concentrations greater than 8,000 ppm isobutene were not used because of the danger of explosion. All rats and mice survived to the end of the study. The final mean body weights and body weight gains of all exposed groups were similar to those of the chamber controls. No exposure-related gross lesions were observed in male or female rats or mice at necropsy. Microscopically, minimal hypertrophy of goblet cells lining the nasopharyngeal duct in the most caudal nose section was observed in some rats in each exposed group of males and females. 2-YEAR STUDIES: Based on the lack of significant exposure-related toxicologic effects in the 14-week rat and mouse studies, 8,000 ppm was selected as the highest exposure concentration in the 2-year studies. Concentrations of 0, 500, 2,000, and 8,000 ppm were selected for rats and mice with the

  15. (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.

  16. NTP Toxicology and Carcinogenesis Studies of Tetrachloroethylene (Perchloroethylene) (CAS No. 127-18-4) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    1986-08-01

    Tetrachloroethylene is used primarily as a dry cleaning agent, an industrial solvent for fats, oils, tars, rubber, and gums, and a metal degreasing agent. Tetrachloroethylene had antihelminthic uses, particularly for hookworms (1.6-8 g/60 kg), and was formerly used in combination with some grain protectants and fumigants. Toxicology and carcinogenesis studies of tetrachloroethylene (99.9% pure) were conducted by inhalation exposure of groups of 50 male and 50 female F344/N rats and B6C3F1 mice 6 hours per day, 5 days per week, for 103 weeks. The exposure concentrations used (0, 200, or 400 ppm for rats and 0, 100, or 200 ppm for mice) were selected on the basis of results from 13-week inhalation studies in which groups of 10 rats and 10 mice of each sex were exposed to tetrachloroethylene at 100-1,600 ppm for 6 hours per day, 5 days per week. During the 13-week studies, 1,600 ppm tetrachloroethylene was lethal to 20%-70% of the rats and mice and reduced the final body weights of survivors. In rats, tetrachloroethylene at 200-800 ppm caused minimal to mild hepatic congestion. In dosed male and female mice, minimal to mild hepatic leukocytic infiltration, centrilobular necrosis, bile stasis (400-1,600 ppm), and mitotic alteration (200-1,600 ppm) were produced. Tetrachloroethylene exposure also caused minimal renal tubular cell karyomegaly in mice at concentrations as low as 200 ppm. During the 2-year studies, exposure to tetrachloroethylene did not consistently affect body weight gains in either rats or mice. Exposure at 400 ppm tetrachloroethylene reduced the survival of male rats (control, 23/50; low dose, 20/50; high dose, 12/50). This reduced survival may have been related to an increased incidence of mononuclear cell leukemia. Tetrachloroethylene at both exposure concentrations reduced the survival of male mice (46/50; 25/50; 32/50), whereas exposure at 200 ppm reduced female mouse survival (36/50; 31/50; 19/50). Early deaths in mice may have been related to the

  17. Dose-response relationship in multistage carcinogenesis: promoters.

    OpenAIRE

    Kitchin, K T; Brown, J. L.; Setzer, R.W.

    1994-01-01

    Published dose-response curves of promoters of multistage carcinogenesis were selected that met the combined criteria of long study times, multiple doses, and low doses. In rat liver, 12 dose-response studies of 7 different promoters (phenobarbital, 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], clophen A-50 (a polychlorinated biphenyl), alpha-, beta-, and gamma-hexachlorocyclohexane [HCH], and chloroform) were selected. These promoters were studied for 7-86 weeks and either altered hepatic foci...

  18. Model validation studies of solar systems, Phase III. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Lantz, L.J.; Winn, C.B.

    1978-12-01

    Results obtained from a validation study of the TRNSYS, SIMSHAC, and SOLCOST solar system simulation and design are presented. Also included are comparisons between the FCHART and SOLCOST solar system design programs and some changes that were made to the SOLCOST program. Finally, results obtained from the analysis of several solar radiation models are presented. Separate abstracts were prepared for ten papers.

  19. Plant systems/components modularization study. Final report. [PWR

    Energy Technology Data Exchange (ETDEWEB)

    1977-07-01

    The final results are summarized of a Plant Systems/Components Modularization Study based on Stone and Webster's Pressurized Water Reactor Reference Design. The program has been modified to include evaluation of the most promising areas for modular consideration based on the level of the Sundesert Project engineering design completion and the feasibility of their incorporation into the plant construction effort.

  20. Bay of Bengal Process Studies (BOBPS) Final Report

    Digital Repository Service at National Institute of Oceanography (India)

    PrasannaKumar, S.; Sardessai, S.; Ramaiah, N.; Bhosle, N.B.; Ramaswamy, V.; Ramesh, R.; Sharada, M.K.; Sarin, M.M.; Sarupria, J.S.; Muraleedharan, U.

    , Distinguished Scientist, C-MMACS, Bangalore and Prof. S. Krishnaswamy, PRL, Ahemdabad with the Department of Ocean Development (DOD), New Delhi right from the time of convening the National Brain Storming Session at Goa on 20 November 1997 to the final... the major questions to be addressed in their studies, their anticipated results and budget needs and (2) to convene a National Brain Storming Meeting to evolve a suitable proposal for studies of biogeochemical process in the Bay of Bengal. Subsequently, a...

  1. 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.

  2. Role of MicroRNAs in carcinogenesis that potential for biomarker of endometrial cancer

    OpenAIRE

    Widodo1); Djati, Muhammad Sasmito; Rifa'i, Muhaimin

    2016-01-01

    The non-invasive diagnostic tool for early detection of endometrial cancer still limited. The etiology of this disease is believed to be associated with disharmony hormone production. One predominant factor that regulate hormone production is microRNA (miRNAs). Some studies reported that miRNAs play a significant role in the process carcinogenesis. We have identified 12 of miRNAs that potentially have a role in controlling endometrial carcinogenesis pathways. Further analysis suggested that t...

  3. P-Nitrobenzoic acid alpha2u nephropathy in 13-week studies is not associated with renal carcinogenesis in 2-year feed studies.

    Science.gov (United States)

    Williams, K D; Dunnick, J; Horton, J; Greenwell, A; Eldridge, S R; Elwell, M; Sills, R C

    2001-01-01

    The objective of this study was to characterize the renal toxicity and carcinogenicity of p-nitrobenzoic acid in F344 rats. Dose levels in 13-week and 2-year studies ranged from 630-10,000 ppm and 1,250-5,000 ppm, respectively. At 13 weeks, renal lesions included minimal to mild hyaline droplet accumulation in male rats and karyomegaly in male and female rats. At 2 years, renal lesions included proximal tubule epithelial cell hyperplasia in male rats and oncocytic hyperplasia in high-dose male and female rats, and a decreased severity of nephropathy in males and females. The hvaline droplets in renal tubular epithelial cells of male rats at 13 weeks were morphologically similar to those described in alpha2u-globulin nephropathy. Using immunohistochemical methods, alpha2u-globulin accumulation was associated with the hyaline droplets. In addition, at 13 weeks, cell proliferation as detected by PCNA immunohistochemistry was significantly increased in males exposed to 5,000 and 10,000 ppm when compared to controls. Cytotoxicity associated with alpha2U-globulin nephropathy such as single-cell necrosis of the P2 segment epithelium or accumulation of granular casts in the outer medulla did not occur in the 13-week study. In addition, chronic treatment related nephrotoxic lesions attributed to accumulation of alpha2u-globulin such as linear foci of mineralization within the renal papilla, hyperplasia of the renal pelvis urothelium and kidney tumors were not observed. Although there was histologic evidence of alpha2u-globulin accumulation in male rats at 13 weeks, the minimal severity of nephropathy suggests that the degree of cytotoxicity was below the threshold, which would contribute to the development of renal tumors at 2 years.

  4. Epstein-Barr virus in hepatocellular carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Wei Li; Bao-An Wu; Yong-Ming Zeng; Guang-Can Chen; Xin-Xin Li; Jun-Tian Chen; Yu-Wen Guo; Man-Hong Li; Yi Zeng

    2004-01-01

    AIM: In recent years, studies have suggested that EpsteinBart virus (EBV) is associated with HCC. The present study was to determine the prevalence of EBV in HCC patients,and whether EBV acted synergistically with hepatitis viruses in HCC carcinogenesis.METHODS: Liver tissue 115 HCC patients and 26 noncarcinoma patients were studied. Polymerase chain reaction (PCR) was performed to detect EBV BamHI W DNA, EBV LMP1 DNA, HBV X DNA, and HBV S DNA. Reverse transcription PCR (RT-PCR) was performed to detect HCV RNA and HDV RNA. Immunohistochemistry was performed to detect LMP1,HBsAg, HBcAg and HCV. The positive ratios were compared between HCC group and control group by χ2 test.RESULTS: Totally, 78 HCC samples whose β-globulin DNA was positively detected by amplified PCR were selected.PCR was performed in all cases for EBV DNA and HBV DNA.RT-PCR was performed in 18 cases for HCV RNA and HDV RNA. EBV BanHI W and EBV LMP1 were positive in 18 and 6 cases, respectively. HBV X gene and HBV S gene were positive in 42 and 27 cases respectively. HCV was positive in one of the 18 cases, and none was positive for HDV. The positive rates were 28.2% (22 of 78) for EBV DNA (BamHI W and/or LMP1) and 56.4% (44 of 78) for HBV DNA (X gene and/or S gene) respectively. In addition, 12 cases were positive for both EBV DNA and HBV DNA. Among the 26 cases in the control group, 2 cases were positive for EBV BamHI W, 4positive for HBV X gene and 3 positive for HBV S gene. The positive rates were 8.0% (2 of 26) and 23.1% (6 of 26),respectively, for EBV DNA and HBV DNA. The result of DNA sequencing of BamHI W was 100% homologous with the corresponding sequence of B95-8. There was significant difference in EBV infection rate between HCC patients and controls (χ2 = 4.622, P<0.05). The difference in HBV infection rate was also significant (χ2 = 8.681, P<0.05). However, there was no obvious correlation between HBV and EBV in HCC patients (χ2 = 0.835,P>0.05). LMP1, HBV (HBsAg, HBc

  5. Toxicology and carcinogenesis studies of 1-bromopropane (CAS No. 106-94-5) in F344/N rats and B6C3F1 mice (inhalation studies).

    Science.gov (United States)

    2011-08-01

    In the early to mid 1990s, 1-bromopropane was used primarily as an intermediate in the production of pesticides, quaternary ammonium compounds, flavors and fragrances, pharmaceuticals, and other chemicals in well-controlled, closed processes. In the mid to late 1990s, it was introduced as a less toxic replacement for methylene chloride in emissive applications such as vapor and immersion degreasing operations and critical cleaning of electronics and metals. 1-Bromopropane was also introduced as a nonflammable, nontoxic, fast-drying, and inexpensive solvent for adhesive resins, and has been marketed as a replacement for ozone depleting refrigerants. 1-Bromopropane was nominated for study by the Occupational Safety and Health Administration based on the potential for widespread occupational and environmental exposure and a lack of toxicity and carcinogenicity data. Male and female F344/N rats and B6C3F1 mice were exposed to 1-bromopropane (99% or greater pure) by inhalation for 2 weeks, 3 months, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Escherichia coli and mouse peripheral blood. 2-WEEK STUDY IN RATS: Groups of five male and five female rats were exposed to 1-bromopropane vapor at concentrations of 0, 125, 250, 500, 1,000, or 2,000 ppm, 6 hours plus T90 (12 minutes) per day, 5 days per week for 16 days. All rats survived to the end of the study except one 500 ppm male. Mean body weights of 2,000 ppm rats were significantly less than those of the chamber controls. The absolute kidney weight of 1,000 ppm males, relative kidney weights of all exposed groups of males, and absolute and relative kidney weights of all exposed groups of females were significantly increased. The absolute and relative liver weights of 1,000 ppm males, relative liver weights of 500 and 2,000 ppm males, and absolute and relative liver weights of 500 ppm or greater females were significantly increased. Nasal lesions included suppurative inflammation in

  6. 32nd European Study Group with Industry, Final Report

    DEFF Research Database (Denmark)

    . The coordiantion of the study groups is now done by the European Consortium for Mathematics in Industry (ECMI).This is the final report for the first study group in Denmark, (and the first ESGI outside Great Britain). Six Danish companies brought problems to the Study Group, requiring a wide range of mathematical...... a model describing the chlorination of swimming pools.LEGO wanted an algorithm for building an arbitrary model with LEGO bricks in stable manner.SCANtechnology wanted an algorithm to identify features in an image from a 3D laser scanning....

  7. Epigenetic targets of arsenic: emphasis on epigenetic modifications during carcinogenesis.

    Science.gov (United States)

    Roy, Ram Vinod; Son, Young-Ok; Pratheeshkumar, Poyil; Wang, Lei; Hitron, John Andrew; Divya, Sasidharan Padmaja; D, Rakesh; Kim, Donghern; Yin, Yuanqin; Zhang, Zhuo; Shi, Xianglin

    2015-01-01

    DNA methylation and histone modification promote opening and closure of chromatin structure, which affects gene expression without altering the DNA sequence. Epigenetic markers regulate the dynamic nature of chromatin structure at different levels: DNA, histone, noncoding RNAs, as well as the higher-order chromatin structure. Accumulating evidence strongly suggests that arsenic-induced carcinogenesis involves frequent changes in the epigenetic marker. However, progress in identifying arsenic-induced epigenetic changes has already been made using genome-wide approaches; the biological significance of these epigenetic changes remains unknown. Moreover, arsenic-induced changes in the chromatin state alter gene expression through the epigenetic mechanism. The current review provides a summary of recent literature regarding epigenetic changes caused by arsenic in carcinogenesis. We highlight the transgenerational studies needed to explicate the biological significance and toxicity of arsenic over a broad spectrum.

  8. Mathematical Modeling of Carcinogenesis Based on Chromosome Aberration Data

    Institute of Scientific and Technical Information of China (English)

    Xiao-bo Li

    2009-01-01

    Objective: The progression of human cancer is characterized by the accumulation of genetic instability. An increasing number of experimental genetic molecular techniques have been used to detect chromosome aberrations. Previous studies on chromosome abnormalities often focused on identifying the frequent loci of chromosome alterations, but rarely addressed the issue of interrelationship of chromosomal abnormalities. In the last few years, several mathematical models have been employed to construct models of carcinogenesis, in an attempt to identify the time order and cause-and-effect relationship of chromosome aberrations. The principles and applications of these models are reviewed and compared in this paper. Mathematical modeling of carcinogenesis can contribute to our understanding of the molecular genetics of tumor development, and identification of cancer related genes, thus leading to improved clinical practice of cancer.

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

    Science.gov (United States)

    Mooij, Merel

    2017-01-01

    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. PMID:28280748

  10. 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.

  11. The Thymus in Experimental Mammary Carcinogenesis and Polychemotherapy.

    Science.gov (United States)

    Kazakov, O V; Kabakov, A V; Ishchenko, I Yu; Poveshchenko, A F; Raiter, T V; Strunkin, D N; Michurina, S V; Konenkov, V I

    2017-02-01

    Histological study of structural transformations in the thymus of Wistar females in induced carcinogenesis (N-methyl-N-nitrosourea injection in the right 2-nd mamma) and polychemotherapy (6 months after tumor growth initiation; cyclophosphamide, methotrexate, and 5-fluorouracyl) was carried out. The area of the cortical matter in the thymus decreased 6 months after carcinogenesis induction, the percentage of connective tissue elements and glandular tissue and the counts of immunoblasts and cells with pyknotic nuclei increased, this indicating the development of accidental involution of the thymus. Animals of the experimental tumor+chemotherapy group exhibited morphological signs of lymphocyte migration from the thymus and suppressed activities of the lymphoid and epithelial components (lesser area of connective tissue elements and glandular tissue, lesser density of parenchymatous cell elements, lesser counts of immunoblasts and small lymphocytes, and larger area of the medulla) in comparison with animals without chemotherapy.

  12. 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.

  13. NTP Toxicology and Carcinogenesis Studies of Diethanolamine (CAS No. 111-42-2) in F344/N Rats and B6C3F1 Mice (Dermal Studies).

    Science.gov (United States)

    1999-07-01

    Diethanolamine is widely used in the preparation of diethanolamides and diethanolamine salts of long-chain fatty acids that are formulated into soaps and surfactants used in liquid laundry and dishwashing detergents, cosmetics, shampoos, and hair conditioners. Diethanolamine is also used in textile processing, in industrial gas purification to remove acid gases, as an anticorrosion agent in metalworking fluids, and in preparations of agricultural chemicals. Aqueous diethanolamine solutions are used as solvents for numerous drugs that are administered intravenously. Diethanolamine was selected for evaluation because its large-scale production and pattern of use indicate the potential for widespread human exposure. Male and female F344/N rats and B6C3F1 mice received dermal applications of diethanolamine in 95% ethanol for 2 years. Genetic toxicology studies were performed in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, and B6C3F1 mouse peripheral blood erythrocytes. RATS: Groups of 50 male rats were administered 0, 16, 32, or 64 mg diethanolamine/kg body weight in ethanol dermally for 2 years. Groups of 50 female rats were administered 0, 8, 16, or 32 mg/kg in ethanol dermally for 2 years. Survival, Body Weights, and Clinical Findings Survival of vehicle control and dosed male and female rats was similar. Mean body weights of 64 mg/kg males were less than those of the vehicle controls beginning week 8, and mean body weights of females were generally similar to those of the vehicle control group. The only clinical finding attributed to diethanolamine administration was irritation of the skin at the site of application. Pathology Findings: Minimal to mild nonneoplastic lesions occurred at the site of application in the epidermis of dosed male and female rats. The incidence of acanthosis in 64 mg/kg males, the incidences of hyperkeratosis in 32 and 64 mg/kg males and in all dosed female groups, and the incidences of exudate

  14. CYTOTOXICITY STUDIES INTO THE ROLE OF PH-DEPENDENT AUTOXIDATION OF PHENYLHYDROQUINONE IN ORTHO-PHENYLPHENOL INDUCED URINARY BLADDER CARCINOGENESIS IN MALE F344 RATS. (R826408)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  15. Modelo de carcinogênese gástrica utilizando piloroplastia de Finney: estudo experimental em ratos Gastric carcinogenesis model using Finney pyloroplasty: experimental study in rats

    Directory of Open Access Journals (Sweden)

    Eliane de Marco Ferreira Kaminski

    2011-12-01

    estudados. CONCLUSÃO: 1 A piloroplastia à Finney é modelo experimental adequado de carcinogênese gástrica; 2 ela induziu refluxo duodenogástrico; 3 o refluxo duodenogástrico atuou como carcinógeno para o estômago; 4 não houve relação entre o pH gástrico e o desenvolvimento de carcinoma; 5 o nitrito de sódio não atuou como carcinógeno para o estômago dos ratos.BACKGROUND: The duodenogastric reflux has been implicated as a potential carcinogen for the stomach and esophagus and is one of the factors that may explain the development of gastric stump cancer. Experimental models of carcinogenesis in the stomach stump or in the duodenogastric anastomosis are well defined. AIM: To develop an experimental model of gastric carcinogenesis through the Finney pyloroplasty, evaluate the influence of ingestion of sodium nitrite in this model, analyze the concentrations of bile acids and the pH of the stomach. METHODS: A hundred and ten Wistar rats were operated and divided into four groups: Group I (15 rats underwent laparotomy (Sham group; Group II (15 rats underwent laparotomy (Sham and ingestion of sodium nitrite in drinking water; Group III (40 rats submitted to the Finney pyloroplasty and Group IV (40 rats submitted to the Finney pyloroplasty and ingestion of sodium nitrite in drinking water. After 50 weeks of surgery, the rats were sacrificed and samples collected for analysis of gastric pH, dosing of bile acids and histological analysis. RESULTS: The immediate postoperative mortality was 9%, and during the experiment, 10 rats died. The control group (I did not show gastric lesions; the control group with sodium nitrite (II developed papillomas in the pre-stomach in 16.6%; the operated groups with pyloroplasty had adenomas in 10.3% in Group III and 14.2 % in Group IV, and adenocarcinoma in 55.1% in group III and 14.2% in Group IV. The implementation of glands into the submucosa and muscle in the area of anastomosis (mucosa deployment was not sufficient criterion for

  16. Experimental gastric carcinogenesis in Cebus apella nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Joana de Fátima Ferreira Borges da Costa

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

  17. Experimental Gastric Carcinogenesis in Cebus apella Nonhuman Primates

    Science.gov (United States)

    Silva, Tanielly Cristina Raiol; Andrade Junior, Edilson Ferreira; Rezende, Alexandre Pingarilho; Carneiro Muniz, José Augusto Pereira; Lacreta Junior, Antonio Carlos Cunha; Assumpção, Paulo Pimentel; Calcagno, Danielle Queiroz; Demachki, Samia; Rabenhorst, Silvia Helena Barem; Smith, Marília de Arruda Cardoso; Burbano, Rommel Rodriguez

    2011-01-01

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

  18. Shikonin Suppresses Skin Carcinogenesis via Inhibiting Cell Proliferation.

    Science.gov (United States)

    Li, Wenjuan; Zhang, Chunjing; Ren, Amy; Li, Teena; Jin, Rong; Li, Guohong; Gu, Xin; Shi, Runhua; Zhao, Yunfeng

    2015-01-01

    The M2 isoform of pyruvate kinase M2 (PKM2) has been shown to be up-regulated in human skin cancers. To test whether PKM2 may be a target for chemoprevention, shikonin, a natural product from the root of Lithospermum erythrorhizon and a specific inhibitor of PKM2, was used in a chemically-induced mouse skin carcinogenesis study. The results revealed that shikonin treatment suppressed skin tumor formation. Morphological examinations and immunohistochemical staining of the skin epidermal tissues suggested that shikonin inhibited cell proliferation without inducing apoptosis. Although shikonin alone suppressed PKM2 activity, it did not suppress tumor promoter-induced PKM2 activation in the skin epidermal tissues at the end of the skin carcinogenesis study. To reveal the potential chemopreventive mechanism of shikonin, an antibody microarray analysis was performed, and the results showed that the transcription factor ATF2 and its downstream target Cdk4 were up-regulated by chemical carcinogen treatment; whereas these up-regulations were suppressed by shikonin. In a promotable skin cell model, the nuclear levels of ATF2 were increased during tumor promotion, whereas this increase was inhibited by shikonin. Furthermore, knockdown of ATF2 decreased the expression levels of Cdk4 and Fra-1 (a key subunit of the activator protein 1. In summary, these results suggest that shikonin, rather than inhibiting PKM2 in vivo, suppresses the ATF2 pathway in skin carcinogenesis.

  19. Multnomah County Hydrokinetic Feasibility Study: Final Feasibility Study Report

    Energy Technology Data Exchange (ETDEWEB)

    Spain, Stephen

    2012-03-15

    HDR has completed a study of the technical, regulatory, and economic feasibility of installing hydrokinetic turbines under the Morrison, Broadway, and Sellwood bridges. The primary objective of installing hydrokinetic turbines is a demonstration of in-stream hydrokinetic technologies for public education and outreach. Due to the low gradient of the Lower Willamette and the effects of the tide, velocities in the area in consideration are simply not high enough to economically support a commercial installation. While the velocities in the river may at times provide enough energy for a commercial turbine to reach capacity, the frequency and duration of high flow events which provide suitable velocities is not sufficient to support a commercial hydrokinetic installation. We have observed that over an 11 year period, daily average velocities in the Lower Willamette exceeded a nominal cut-in speed of 0.75 m/s only 20% of the time, leaving net zero power production for the remaining 80% of days. The Sellwood Bridge site was estimated to have the best hydrokinetic resource, with an estimated average annual production of about 9,000 kWh. The estimated production could range from 2,500 kWh to 15,000 kWh. Based on these energy estimates, the amount of revenue generated through either a power purchase agreement (PPA) or recovered through net metering is not sufficient to repay the project costs within the life of the turbine. The hydrokinetic resource at the Morrison and Broadway Bridges is slightly smaller than at the Sellwood Bridge. While the Broadway and Morrison Bridges have existing infrastructure that could be utilized, the project is not expected to generate enough revenue to repay the investment. Despite low velocities and energy production, the sites themselves are favorable for installation of a demonstration or experimental project. With high public interest in renewable energy, the possibility exists to develop a hydrokinetic test site which could provide

  20. Biomechanical study of the final push-pull in archery.

    Science.gov (United States)

    Leroyer, P; Van Hoecke, J; Helal, J N

    1993-02-01

    The purpose of this study was to analyse archery performance among eight archers of different abilities by means of displacement pull-hand measurements during the final push-pull phase of the shoot. The archers showed an irregular displacement negatively related to their technical level. Displacement signal analysis showed high power levels in both the 0-5 Hz and 8-12 Hz ranges. The latter peak corresponds to electromyographic tremor observed during a prolonged push-pull effort. The results are discussed in relation to some potentially helpful training procedures such as biofeedback and strength conditioning.

  1. Stress and radiation carcinogenesis in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kalisnik, M.; Vraspir-Porenta, O.; Kham-Lindtner, T.; Logonder-Mlinsek, M.; Skrk, J.; Pajntar, M. (Ljubljana Univ. (Yugoslavia). Medicinski Fakultet)

    1981-01-01

    In the present experiment irritation consisting of the combination of an optic signal followed by a mild electric shock administered at regular intervals was started in 2 groups of animals at the age of 3 months. At 4 months of age, one of the irritated and one of the non-irritated groups were exposed to whole-body gamma irradiation with 20 daily doses of 0.5 Gy (50 rad), 1.4 Gy/min (140 rad/min), while the other 2 groups were sham-irradiated. The animals were autopsied and the specimens were microscopically studied for the presence of malignant tumors. Malignant tumors particularly involving the testes and lungs, and leukosis were found in 29% of males, whereas in females the tumor incidence with mammary, pulmonary and ovarian involvement and leukosis was 39%. The irradiation decreased the minimum latency time in the irritated males and both female groups. In males, the irritation lowered the cumulative prevalence of malignant tumors, a significant decrease being noted at the age of 15 months. In females, it was increased, with a significant rise observed to occur at the end of the experiment. The opposite effects of irritation on the radiation carcinogenesis in males and females can be attributed to the radiation-induced specific alterations of the gonads in females and, in part, to a longer survival time observed in the irradiated females.

  2. Study on Cell Cycle Regulatory Mechanism in Rat Bladder Carcinogenesis Promoted by Terephthalic Acid%对苯二甲酸促进大鼠膀胱癌发生的细胞周期调节机制研究

    Institute of Scientific and Technical Information of China (English)

    石远; 唐建梅

    2011-01-01

    [ Objective ] To study the cell cycle regulatory mechanism in rat bladder carcinogenesis promoted by terephthalic acid (TPA). [ Methods ] A total of 50 male Wister rats were divided into test group (30 rats) and control group (20 rats), respectively intraperitoneally injected with N-methyl-N-nitrosourea (MNU) and citrate buffer twice a week for 4 weeks, and then basal diet containing 5%TPA were given to the test group and basal diet to the control group separately for the next 22 weeks. Major regulatory proteins in Gl cell cycle checkpoint including pl6INK4a, cyclin-dependent kinase 4 (Cdk4), cyclin Dl, and retinoblastoma protein (pRb) were determined during various stages of urinary bladder carcinogenesis by immunohistochemistry. [ Results ] In MNU-5% TPA treated group, the incidences of overexpression of Cdk4, cyclin Dl and pRb in papilloma were significantly higher than those in epithelial simple hyperplasia (P=0.023, .P<0.001 and P< 0.001, respectively) and in papillary or nodular (PN) hyperplasia (P=0.042, ^=0.012 and P=0.002, respectively). The incidence of absent expression of pl61NK4 in papilloma was much higher than that in epithelial simple hyperplasia {P=0.004) and in PN hyperplasia (P=0.02). [ Conclusion ] Our results clearly reveal that the disorder of pl6INK4-cyclin Dl/Cdk4-pRb pathway is associated with bladder carcinogenesis promoted by TPA-stone.%[目的]研究对苯二甲酸(terephthalic acid,TPA)促进膀胱癌发生的细胞周期调节机制.[方法]50只blister大鼠分为实验组(30只)及对照组(20只),每周两次分别腹腔注射甲基亚硝墓脲(MNU)和冰柠檬酸盐缓冲液,持续4周.在随后的22周,分别给大鼠饲以含5%TPA和0%TPA的饲料.利用免疫组织化学方法检查G1细胞周期关卡的主要调节蛋白包括抑癌基因p16(INK4a)蛋白(pl6(INK4a))、周期素依赖性蛋白激酶4(Cdk4)、细胞周期蛋白D1(cyclin Dl)和成视网膜细胞瘤蛋白(pRb)在大鼠膀胱癌发生各

  3. 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

  4. NTP Carcinogenesis Bioassay of Propyl Gallate (CAS No. 121-79-9) in F344/N Rats and B6C3F1 Mice (Feed Study).

    Science.gov (United States)

    1982-12-01

    Propyl gallate is a white to nearly white odorless powder having a slightly bitter taste. Solutions of propyl gallate turn dark in the presence of iron or iron salts. Propyl gallate has been used since 1948 as an antioxidant to stabilize cosmetics, food packaging materials, and foods containing fats. As an additive, it may be found in edible fats, oils, mayonnaise, shortening, baked goods, candy, dried meat, fresh pork sausage, and dried milk, and it is used in hair grooming products, pressure-sensitive adhesives, lubricating oil additives, and transforming oils. A NTP Carcinogenesis bioassay of propyl gallate was conducted by feeding diets containing 6,000 or 12,000 ppm propyl gallate to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex for 103 weeks. Groups of 50 untreated rats and 50 untreated mice of each sex served as controls. Survival of rats and mice was not adversely affected by propyl gallate, but mean body weights of dosed rats and mice of each sex were lower than those of the controls. At 104 weeks, mean body weights of low-and high-dose rats were 4% and 8% lower than those of the controls for males and 11% and 19% lower than those of the controls for females. Similarly, mean body weights of low-and high-dose mice were 5% and 8% lower than those of the controls for males and 11% (both dose groups) lower than those of the controls for females. Thyroid follicular-cell adenomas or carcinomas (combined) occurred in male rats with a statistically significant (P<0.05) positive trend, but the incidences in the dosed groups were not statistically significant in direct comparisons with the control groups. Moreover, the incidence of high-dose male rats with follicular-cell tumors (3/50, 6%) was not statistically different from the historical control rate (14/584, 2.4%) for the laboratory that conducted this bioassay. Rare tumors (an astrocytoma or a glioma) were found in the brains of two low-dose female rats. The incidence of all brain tumors in the

  5. Ripeness sensor development. Final report of a Phase 2 study

    Energy Technology Data Exchange (ETDEWEB)

    Stroshine, R.

    1995-08-01

    This is a final report for the Phase II study entitled ``Ripeness Sensor Development.`` The overall objective of the study was the development of a prototype device capable of testing whole fruits for sugar content. Although ripeness and sugar content are not synonymous, they are closely related. Furthermore, the consumer`s acceptance of or preference for fruits is strongly influenced by sugar content. Therefore, the device was called a ripeness sensor. The principle behind the measurement is proton magnetic resonance ({sup 1}H-MR). For several decades, chemists, pharmacists and other scientists have been using {sup 1}H-MR to investigate chemical structure and composition. More recently, the technique has been used in laboratories of the food industry for quality control. This effort represents one of the first attempts to adapt {sup 1}H-MR to use in a commercial facility. 28 refs., 36 figs., 7 tabs.

  6. Sirt3, Mitochondrial ROS, Ageing, and Carcinogenesis

    Directory of Open Access Journals (Sweden)

    David Gius

    2011-09-01

    Full Text Available One fundamental observation in cancer etiology is that the rate of malignancies in any mammalian population increases exponentially as a function of age, suggesting a mechanistic link between the cellular processes governing longevity and carcinogenesis. In addition, it is well established that aberrations in mitochondrial metabolism, as measured by increased reactive oxygen species (ROS, are observed in both aging and cancer. In this regard, genes that impact upon longevity have recently been characterized in S. cerevisiae and C. elegans, and the human homologs include the Sirtuin family of protein deacetylases. Interestingly, three of the seven sirtuin proteins are localized into the mitochondria suggesting a connection between the mitochondrial sirtuins, the free radical theory of aging, and carcinogenesis. Based on these results it has been hypothesized that Sirt3 functions as a mitochondrial fidelity protein whose function governs both aging and carcinogenesis by modulating ROS metabolism. Sirt3 has also now been identified as a genomically expressed, mitochondrial localized tumor suppressor and this review will outline potential relationships between mitochondrial ROS/superoxide levels, aging, and cell phenotypes permissive for estrogen and progesterone receptor positive breast carcinogenesis.

  7. Molecular aspects of carcinogenesis in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Alexandros Koliopanos; Constantinos Avgerinos; Constantina Paraskeva; Zisis Touloumis; Dionisisa Kelgiorgi; Christos Dervenis

    2008-01-01

    BACKGROUND: Pancreatic cancer (PCa) is one of the most aggressive human solid tumors, with rapid growth and metastatic spread as well as resistance to chemotherapeutic drugs, leading rapidly to virtually incurable disease. Over the last 20 years, however, signiifcant advances have been made in our understanding of the molecular biology of PCa, with a focus on the cytogenetic abnormalities in PCa cell growth and differentiation. DATA SOURCES: A MEDLINE search and manual cross-referencing were utilized to identify published data for PCa molecular biology studies between 1986 and 2008, with emphasis on genetic alterations and developmental oncology. RESULTS: Activation of oncogenes, deregulation of tumor suppressor and genome maintenance genes, upregulation of growth factors/growth factor receptor signaling cascade systems, and alterations in cytokine expression, have been reported to play important roles in the process of pancreatic carcinogenesis. Alterations in the K-ras proto-oncogene and the p16INK4a, p53, FHIT, and DPC4 tumor suppressor genes occur in a high percentage of tumors. Furthermore, a variety of growth factors are expressed at increased levels. In addition, PCa often exhibits alterations in growth inhibitory pathways and evades apoptosis through p53 mutations and aberrant expression of apoptosis-regulating genes, such as members of the Bcl family. Additional pathways in the development of an aggressive phenotype, local inifltration and metastasis are still under ongoing genetic research. The present paper reviews recent studies on the pathogenesis of PCa, and includes a brief reference to alterations reported for other types of pancreatic tumor. CONCLUSIONS: Advances in molecular genetics and biology have improved our perception of the pathogenesis of PCa. However, further studies are needed to better understand the fundamental changes that occur in PCa, thus leading to better diagnostic and therapeutic management.

  8. Waste package/repository impact study: Final report

    Energy Technology Data Exchange (ETDEWEB)

    1985-09-01

    The Waste Package/Repository Impact Study was conducted to evaluate the feasibility of using the current reference salt waste package in the salt repository conceptual design. All elements of the repository that may impact waste package parameters, i.e., (size, weight, heat load) were evaluated. The repository elements considered included waste hoist feasibility, transporter and emplacement machine feasibility, subsurface entry dimensions, feasibility of emplacement configuration, and temperature limits. The evaluations are discussed in detail with supplemental technical data included in Appendices to this report, as appropriate. Results and conclusions of the evaluations are discussed in light of the acceptability of the current reference waste package as the basis for salt conceptual design. Finally, recommendations are made relative to the salt project position on the application of the reference waste package as a basis for future design activities. 31 refs., 11 figs., 11 tabs.

  9. Energy study of pipeline transportation systems. Executive summary. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Banks, W. F.

    1977-12-31

    The basic objectives of the overall study were to (1) characterize the pipeline industry and understand its energy consumption in each of the five major pipeline-industry segments: gas, oil, slurry, fresh water, and waste water; (2) identify opportunities for energy conservation in the pipeline industry, and to recommend the necessary R, D, and D programs to exploit those opportunities; (3) characterize and understand the influence of the Federal government on introduction of energy conservative innovations into the pipeline industry; and (4) assess the future potential of the pipeline industry for growth and for contribution to the national goal of energy conservation. This project final report is an executive summary presenting the results from the seven task reports.

  10. Magnesium: its role in nutrition and carcinogenesis.

    Science.gov (United States)

    Blaszczyk, Urszula; Duda-Chodak, Aleksandra

    2013-01-01

    Magnesium (Mg2+) plays a key role in many essential cellular processes such as intermediary metabolism, DNA replication and repair, transporting potassium and calcium ions, cell proliferation together with signalling transduction. Dietary sources rich in magnesium are whole and unrefined grains, seeds, cocoa, nuts, almonds and green leafy vegetables. Hard water is also considered to be an important source of magnesium beneficial to human health. The daily dietary intake of magnesium is however frequently found to be below that recommended in Western countries. Indeed, it is recognised that magnesium deficiency may lead to many disorders of the human body, where for instance magnesium depletion is believed to play an important role in the aetiology of the following; cardiovascular disease (including thrombosis, atherosclerosis, ishaemic heart disease, myocardial infarction, hypertension, arrhythmias and congestive heart failure in human), as well as diabetes mellitus, gastrointestinal (GI) tract disease, liver cirrhosis and diseases of the thyroid and parathyroid glands. Insufficient dietary intake of magnesium may also significantly affect the development and exacerbation ofADHD (Attention Deficit- Hyperactivity Disorder) symptoms in children. The known links between magnesium and carcinogenesis still remain unclear and complex, with conflicting results being reported from many experimental, epidemiological and clinical studies; further knowledge is thus required. Mg2+ ions are enzyme cofactors involved in DNA repair mechanisms that maintain genomic stability and fidelity. Any magnesium deficiencies could thereby cause a dysfunction of these systems to occur leading to DNA mutations. Magnesium deficiency may also be associated with inflammation and increased levels of free radicals where both inflammatory mediators and free radicals so arising could cause oxidative DNA damage and therefore tumour formation. The presented review article now provides a summary

  11. Study of $\\pi^{-}$p Interactions with Neutral Final States

    CERN Multimedia

    2002-01-01

    This experiment is a study of the production of neutral particles or states decaying into photons in the reaction @p|- + p @A M|0 + n at SPS energies. \\\\ \\\\ Special attention is paid to the measurement of the production of heavy particles with hidden quantum numbers and of possible new heavy spinless states decaying into two photons. \\\\ \\\\ The large four-momentum transfer behaviour of binary processes involving known neutral mesons and the production of new meson resonances with high mass and spin will also be studied. Complex multiparticle final states will be analysed as a by-product.\\\\ \\\\ The central unit of the experimental set-up is a 4000 cell Cerenkov hodoscope spectrometer (GAMS) which allows the measurement of the momentum vector of each $\\gamma$ in a multigamma event. \\\\ \\\\ The longitudinal position of the interaction point in the liquid hydrogen target is measured by the Cerenkov light intensity. \\\\ \\\\ A guard system, made of scintillation counters and lead-glass Cerenkov counters, is used to trigg...

  12. Age-Related Differences in Susceptibility to Carcinogenesis: A Quantitative Analysis of Empirical Animal Bioassay Data

    Science.gov (United States)

    Hattis, Dale; Goble, Robert; Russ, Abel; Chu, Margaret; Ericson, Jen

    2004-01-01

    In revising cancer risk assessment guidelines, the U.S. Environmental Protection Agency (EPA) analyzed animal cancer bioassay data over different periods of life. In this article, we report an improved analysis of these data (supplemented with some chemical carcinogenesis observations not included in the U.S. EPA’s original analysis) and animal bioassay studies of ionizing radiation. We use likelihood methods to avoid excluding cases where no tumors were observed in specific groups. We express dosage for animals of different weights on a metabolically consistent basis (concentration in air or food, or per unit body weight to the three-quarters power). Finally, we use a system of dummy variables to represent exposures during fetal, preweaning, and weaning–60-day postnatal periods, yielding separate estimates of relative sensitivity per day of dosing in these intervals. Central estimate results indicate a 5- to 60-fold increased carcinogenic sensitivity in the birth–weaning period per dose ÷ (body weight0.75-day) for mutagenic carcinogens and a somewhat smaller increase—centered about 5-fold—for radiation carcinogenesis per gray. Effects were greater in males than in females. We found a similar increased sensitivity in the fetal period for direct-acting nitrosoureas, but no such increased fetal sensitivity was detected for carcinogens requiring metabolic activation. For the birth–weaning period, we found an increased sensitivity for direct administration to the pups similar to that found for indirect exposure via lactation. Radiation experiments indicated that carcinogenic sensitivity is not constant through the “adult” period, but the dosage delivered in 12- to 21-month-old animals appears a few-fold less effective than the comparable dosage delivered in young adults (90–105 days of age). PMID:15289159

  13. 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...... 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...

  14. Study of Final States in Deep Inelastic Muon Scattering

    CERN Multimedia

    2002-01-01

    The aim of this experiment is to study the different possible final states in deep inelastic muon scattering from hydrogen in connection with the detection of the scattered muon in a forward spectrometer (Experiment NA2).\\\\ \\\\ A vertex detector will be used which extends the hadron detection capabilities into the backward hemisphere of the centre-of-mass system. Particle momenta can be measured down to 200 MeV/c in a vertex magnet, which contains a streamer chamber (SC Particle identification will be done in a series of wide angle Cerenkov counters (C^0,C^1,CA) and at low momenta in time-of-flight counter hodoscopes (F1-F4). An 8-plane module of MWPC chambers (PV) will be used in conjunction with the streamer chamber and the drift chambers WV1, WV2 and WV3. \\\\ \\\\ The vertex magnet is a C magnet with circular pole tips of 2 m diameter and 1 m gap width. The central magnetic field will be 1.5 T. The streamer chamber (2m x 1.2m x 0.72m) will contain a 1 m liquid H^2 target.\\\\ \\\\ As a natural extension of the for...

  15. Study of post-natal effect of chemopreventive agents on ethylnitrosourea-induced transplacental carcinogenesis in rats. III. Inhibitory action of indomethacin, voltaren, theophylline and epsilon-aminocaproic acid.

    Science.gov (United States)

    Alexandrov, V A; Bespalov, V G; Petrov, A S; Troyan, D N; Lidaks MYu

    1996-09-01

    The influence of the arachidonic acid metabolism inhibitors, indomethacin and voltaren; an inhibitor of phosphodiesterase activity, theophylline and the protease inhibitor epsilonaminocaproic acid (EACA) on N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was studied in rats. ENU was given to pregnant rats as a single i.v. exposure at a dose of 75 mg/kg body weight on the 21st day after conception. Indomethacin and voltaren (20 p.p.m. in drinking water), theophylline (0.01% in diet) and EACA (1000 p.p.m. in drinking water) were given to the offspring throughout their post-natal life until all survivors were killed at 12 months. In the ENU-only control groups, 100% of the offspring developed tumors of brain, spinal cord, peripheral nervous system or kidneys, with a total average number of 3.1 tumors per rat. The most marked inhibitory effect was exerted by theophylline, which significantly decreased the incidence and multiplicity of total tumors, and at all main sites selectively (brain, spinal cord, peripheral nerves and kidneys). It also prolonged average survival time of the offspring. Indomethacin and voltaren significantly decreased total tumor incidence and multiplicity and brain tumor incidence and multiplicity. Indomethacin also decreased kidney tumor multiplicity and voltaren diminished spinal cord tumor multiplicity. EACA decreased multiplicities of total, brain, peripheral nerve and kidney tumors, and diminished the incidence of brain tumors. These chemopreventive agents decreased tumor incidences 20-33% and tumor multiplicities 1.4-2.7 times, compared with the ENU-only controls.

  16. Genetic and epigenetic alterations in pancreatic carcinogenesis.

    Science.gov (United States)

    Delpu, Yannick; Hanoun, Naïma; Lulka, Hubert; Sicard, Flavie; Selves, Janick; Buscail, Louis; Torrisani, Jérôme; Cordelier, Pierre

    2011-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Despite significant progresses in the last decades, the origin of this cancer remains unclear and no efficient therapy exists. PDAC does not arise de novo: three remarkable different types of pancreatic lesions can evolve towards pancreatic cancer. These precursor lesions include: Pancreatic intraepithelial neoplasia (PanIN) that are microscopic lesions of the pancreas, Intraductal Papillary Mucinous Neoplasms (IPMN) and Mucinous Cystic Neoplasms (MCN) that are both macroscopic lesions. However, the cellular origin of these lesions is still a matter of debate. Classically, neoplasm initiation or progression is driven by several genetic and epigenetic alterations. The aim of this review is to assemble the current information on genetic mutations and epigenetic disorders that affect genes during pancreatic carcinogenesis. We will further discuss the interest of the genetic and epigenetic alterations for the diagnosis and prognosis of PDAC. Large genetic alterations (chromosomal deletion/amplification) and single point mutations are well described for carcinogenesis inducers. Mutations classically occur within key regions of the genome. Consequences are various and include activation of mitogenic pathways or silencing of apoptotic processes. Alterations of K-RAS, P16 and DPC4 genes are frequently observed in PDAC samples and have been described to arise gradually during carcinogenesis. DNA methylation is an epigenetic process involved in imprinting and X chromosome inactivation. Alteration of DNA methylation patterns leads to deregulation of gene expression, in the absence of mutation. Both genetic and epigenetic events influence genes and non-coding RNA expression, with dramatic effects on proliferation, survival and invasion. Besides improvement in our fundamental understanding of PDAC development, highlighting the molecular alterations that occur in pancreatic carcinogenesis could

  17. Study of B Meson Decays to ppbarh Final States

    Energy Technology Data Exchange (ETDEWEB)

    Hryn' ova, Tetiana B.; /SLAC

    2006-03-22

    B mesons are unique among well-established non-quarkonium mesons in their ability to decay into baryons. Baryonic B decays offer a wide range of interesting areas of study: they can be used to test our theoretical understanding of rare decay processes involving baryons, search for direct CP violation and study low-energy QCD. This thesis presents measurements of branching fractions and a study of the decay dynamics of the charmless three-body decays of B meson into p{bar p}h final states, where h = {pi}{sup +}, K{sup +}, K{sub S}{sup 0}, K*{sup 0} or K*{sup +}. With a sample of 232 million {Upsilon}(4S) {yields} B{bar B} events collected with the BaBar detector, we report the first observation of the B {yields} p{bar p}K*{sup 0} decay, and provide improved measurements of branching fractions of the other modes. The distribution of the three final-state particles is of particular interest since it provides dynamical information on the possible presence of exotic intermediate states such as the hypothetical pentaquark states {Theta}*{sup ++} and {Theta}{sup +}in the m{sub pK{sup +}} and m{sub pK{sub S}{sup 0}} spectra, respectively, or glueball states (such as the tensor glueball f{sub J}(2220)) in the m{sub p{bar p}} spectrum. No evidence for exotic states is found and upper limits on the branching fractions are set. An enhancement at low p{bar p} mass is observed in all the B {yields} p{bar p}h modes, and its shape is compared between the decay modes and with the shape of the time-like proton form factor. A Dalitz plot asymmetry in B {yields} p{bar p}K{sup +} mode suggests dominance of the penguin amplitude in this decay and disfavors the possibility that the low mass p{bar p} enhancement originates from the presence of a resonance below threshold (such as the recently seen baryonium candidate at 1835 MeV/c{sup 2}). We also identify decays of the type B {yields} X{sub c{bar c}}h {yields} p{bar p}h, where h = K{sup +}, K{sub S}{sup 0}, K*{sup 0} or K*{sup +}, and X

  18. EXPRESSION OF GST-π GENE IN HUMAN ESOPHAGEAL CARCINOGENESIS

    Institute of Scientific and Technical Information of China (English)

    FU Baojin; ZHANG Yunhan; WANG Yaohe; GAO Dongling; FU Shuli; WEN Xiaogang; ZHANG Sanshen; WANG Jiang

    1999-01-01

    Objective: To investigate the possible role of GSTπ in esophageal carcinogenesis. Methods: GST-πexpression at mRNA level was studied by in situ hybridization (ISH) and at protein level by immunohistochemistry (IHC). GST-π expression in normal epithelial cells (NC) of the esophagus,hyperplastic cells (HC), dysplastic cells (DC) from grade Ⅰ to Ⅲ, carcinoma in situ (CIS) and all the cells in squamous cell carcinomas (SCC) were examined in the same esophageal cancer specimens (n=48) which provided a model reflecting the process of esophageal carcinogenesis. Results: The positive rate of IHC staining was 87. 5% for NC, 95.3% for HC, 55.9% for DC (grade Ⅰ: 73.9%, grade Ⅱ: 47.4%, grade Ⅲ: 41.2%),36.4% for CIS and 45.8% for SCC. The positive rate of GST-π mRNA expression was 81.2% for NC, 94.4% for HC, 61.9% for DC (grade Ⅰ: 76.5%, grade Ⅱ: 61.5%,grade Ⅲ: 41.7%), 44.4% for CIS and 83.3% for grade ⅠSCC, 30.0% for grade Ⅱ SCC and 0% for grade ⅢSCC. There was no statistically significant difference in GST-π expression at the mRNA and the protein level.Conclusion: There is a decreasing tendency of GST-πexpression from dysplasia to CIS and SCC. The decrease in GST-π expression is an early event in esophageal carcinogenesis.

  19. Plausible Mechanisms of Cadmium Carcinogenesis

    Science.gov (United States)

    Cadmium is a transition metal and an ubiquitous environmental and industrial pollutant. Laboratory animal studies and epidemiological studies have shown that exposure to cadmium is associated with various organ toxicities and carcinogenic effects. Several national and internation...

  20. Pulsed Neutron Scattering Studies of Strongly Fluctuating solids, Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Collin Broholm

    2006-06-22

    The conventional description of a solid is based on a static atomic structure with small amplitude so-called harmonic fluctuations about it. This is a final technical report for a project that has explored materials where fluctuations are sufficiently strong to severely challenge this approach and lead to unexpected and potentially useful materials properties. Fluctuations are enhanced when a large number of configurations share the same energy. We used pulsed spallation source neutron scattering to obtain detailed microscopic information about structure and fluctuations in such materials. The results enhance our understanding of strongly fluctuating solids and their potential for technical applications. Because new materials require new experimental techniques, the project has also developed new techniques for probing strongly fluctuating solids. Examples of material that were studied are ZrW2O8 with large amplitude molecular motion that leads to negative thermal expansion, NiGa2S4 where competing interactions lead to an anomalous short range ordered magnet, Pr1- xBixRu2O7 where a partially filled electron shell (Pr) in a weakly disordered environment produces anomalous metallic properties, and TbMnO3 where competing interactions lead to a magneto-electric phase. The experiments on TbMnO3 exemplify the relationship between research funded by this project and future applications. Magneto-electric materials may produce a magnetic field when an electric field is applied or vise versa. Our experiments have clarified the reason why electric and magnetic polarization is coupled in TbMnO3. While this knowledge does not render TbMnO3 useful for applications it will focus the search for a practical room temperature magneto-electric for applications.

  1. NTP Toxicology and Carcinogenesis Studies of d-Limonene (CAS No. 5989-27-5) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1990-01-01

    Toxicology and carcinogenesis studies of d-limonene, a naturally occurring monoterpene found in many volatile oils, especially in citrus oils, were conducted because of its widespread use as a flavor and fragrance additive for food and household cleaning products and its increasing use as an industrial solvent. The d-limonene used in these studies was more than 99% pure and was administered in corn oil by gavage. Short-term studies were conducted in F344/N rats and B6C3F1 mice to identify toxic effects and affected sites and to help establish doses for the 2-year studies. Genetic toxicology studies were conducted in Salmonella typhimurium, mouse L5178Y cells, and Chinese hamster ovary (CHO) cells. The doses selected for the 16-day studies ranged from 413 to 6,600 mg/kg for both rats and mice; deaths and reduction in body weight gain occurred at the two highest doses. No compound-related clinical signs or histopathologic lesions were observed in any of the surviving dose groups. In the 13-week studies, doses of d-limonene ranged from 150 to 2,400 mg/kg for rats and from 125 to 2,000 mg/kg for mice. Deaths occurred in the high dose group of each species and sex. Greater than 10% reductions in body weight gain were observed in the two highest dose groups of male rats and male mice and the high dose female rats. Rough hair coats and decreased activity were observed at the two highest doses in both rats and mice. There were no chemical-related histopathologic lesions in female rats or in mice of either sex. A compound-related increased severity of nephropathy was observed in the kidney of male rats. This lesion was characterized by degeneration of epithelial cells in the convoluted tubules, granular casts in the outer stripe of the outer medulla, and epithelial regeneration. These lesions have been described as reasonably characteristic of the hyaline droplet nephropathy that is associated with an accumulation of liver-generated a2u-globulin in the cytoplasm of tubular

  2. A review of dietary factors and its influence on DNA methylation in colorectal carcinogenesis.

    Science.gov (United States)

    Arasaradnam, R P; Commane, D M; Bradburn, D; Mathers, J C

    2008-01-01

    Colorectal cancer (CRC) is the most common cancer in non-smokers posing a significant health burden in the UK. Observational studies lend support to the impact of environmental factors especially diet on colorectal carcinogenesis. Significant advances have been made in understanding the biology of CRC carcinogenesis in particular epigenetic modifications such as DNA methylation. DNA methylation is thought to occur at least as commonly as inactivation of tumor suppressor genes. In fact compared with other human cancers, promoter gene methylation occurs most commonly within the gastrointestinal tract. Emerging data suggest the direct influence of certain micronutrients for example folic acid, selenium as well as interaction with toxins such as alcohol on DNA methylation. Such interactions are likely to have a mechanistic impact on CRC carcinogenesis through the methylation pathway but also, may offer possible therapeutic potential as nutraceuticals.

  3. Receptor activator for nuclear factor-κB ligand signaling promotes progesterone-mediated estrogen-induced mammary carcinogenesis

    OpenAIRE

    Boopalan, Thiyagarajan; Arumugam, Arunkumar; Parada, Jacqueline; Saltzstein, Edward; Lakshmanaswamy, Rajkumar

    2015-01-01

    Breast cancer is a leading cause of cancer-related death in women. Prolonged exposure to the ovarian hormones estrogen and progesterone increases the risk of breast cancer. Although estrogen is known as a primary factor in mammary carcinogenesis, very few studies have investigated the role of progesterone. Receptor activator for nuclear factor-κB (NF-κB) ligand (RANKL) plays an important role in progesterone-induced mammary carcinogenesis. However, the molecular mechanism underlying RANKL-ind...

  4. The dog as a natural animal model for study of the mammary myoepithelial basal cell lineage and its role in mammary carcinogenesis.

    Science.gov (United States)

    Rasotto, R; Goldschmidt, M H; Castagnaro, M; Carnier, P; Caliari, D; Zappulli, V

    2014-01-01

    Basal-like tumours constitute 2-18% of all human breast cancers (HBCs). These tumours have a basal myoepithelial phenotype and it has been hypothesized that they originate from either myoepithelial cells or mammary progenitor cells. They are heterogeneous in morphology, clinical presentation, outcome and response to therapy. Canine mammary carcinomas (CMCs) have epidemiological and biological similarities to HBCs, are frequently biphasic and are composed of two distinct neoplastic populations (epithelial and myoepithelial). The present study evaluates the potential of CMCs as a natural model for basal-like HBCs. Single and double immunohistochemistry was performed on serial sections of 10 normal canine mammary glands and 65 CMCs to evaluate expression of cytokeratin (CK) 8/18, CK5, CK14, α-smooth muscle actin (SMA), calponin (CALP), p63 and vimentin (VIM). The tumours were also evaluated for Ki67 and human epidermal growth factor receptor (HER)-2 expression. A hierarchical model of cell differentiation was established, similar to that for the human breast. We hypothesized that progenitor cells (CK5(+), CK14(+), p63(+) and VIM(+)) differentiate into terminally-differentiated luminal glandular (CK8/18(+)) and myoepithelial (CALP(+), SMA(+) and VIM(+)) cells via intermediary luminal glandular cells (CK5(+), CK14(+) and CK8/CK18(+)) and intermediary myoepithelial cells (CK5(+), CK14(+), p63(+), SMA(+), CALP(+) and VIM(+)). Neoplastic myoepithelial cells in canine complex carcinomas had labelling similar to that of terminally-differentiated myoepithelial cells, while those of carcinomas-and-malignant myoepitheliomas with a more aggressive biological behaviour (i.e. higher frequency of vascular/lymph node invasion and visceral metastases and higher risk of tumour-related death) were comparable with intermediary myoepithelial cells and had significantly higher Ki67 expression. The majority of CMCs examined were negative for expression of HER-2. The biphasic appearance of

  5. Green tea catechin extract in intervention of chronic breast cell carcinogenesis induced by environmental carcinogens.

    Science.gov (United States)

    Rathore, Kusum; Wang, Hwa-Chain Robert

    2012-03-01

    Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that green tea components may be used as preventive agents for breast cancer control. In our research, we have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. In this study, we used our chronic carcinogenesis model as a target system to investigate the activity of green tea catechin extract (GTC) at non-cytotoxic levels in intervention of cellular carcinogenesis induced by cumulative exposures to pico-molar 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P). We identified that GTC, at a non-cytotoxic, physiologically achievable concentration of 2.5 µg/mL, was effective in suppressing NNK- and B[a]P-induced cellular carcinogenesis, as measured by reduction of the acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, increased cell mobility, and acinar-conformational disruption. We also detected that intervention of carcinogen-induced elevation of reactive oxygen species (ROS), increase of cell proliferation, activation of the ERK pathway, DNA damage, and changes in gene expression may account for the mechanisms of GTC's preventive activity. Thus, GTC may be used in dietary and chemoprevention of breast cell carcinogenesis associated with long-term exposure to low doses of environmental carcinogens.

  6. FINAL REPORT ON THE AQUATIC MERCURY ASSESSMENT STUDY

    Energy Technology Data Exchange (ETDEWEB)

    Halverson, N

    2008-09-30

    In February 2000, the United States Environmental Protection Agency (EPA) Region 4 issued a proposed Total Maximum Daily Load (TMDL) for total mercury in the middle and lower Savannah River. The initial TMDL, which would have imposed a 1 ng/l mercury limit for discharges to the middle/lower Savannah River, was revised to 2.8 ng/l in the final TMDL released in February 2001. The TMDL was intended to protect people from the consumption of contaminated fish, which is the major route of mercury exposure to humans. The most bioaccumulative form of mercury is methylmercury, which is produced in aquatic environments by the action of microorganisms on inorganic mercury. Because of the environmental and economic significance of the mercury discharge limits that would have been imposed by the TMDL, the Savannah River Site (SRS) initiated several studies concerning: (1) mercury in SRS discharges, SRS streams and the Savannah River, (2) mercury bioaccumulation factors for Savannah River fish, (3) the use of clams to monitor the influence of mercury from tributary streams on biota in the Savannah River, and (4) mercury in rainwater falling on the SRS. The results of these studies are presented in detail in this report. The first study documented the occurrence, distribution and variation of total and methylmercury at SRS industrial outfalls, principal SRS streams and the Savannah River where it forms the border with the SRS. All of the analyses were performed using the EPA Method 1630/31 ultra low-level and contaminant-free techniques for measuring total and methylmercury. Total mercury at National Pollutant Discharge Elimination System (NPDES) outfalls ranged from 0.31-604 ng/l with a mean of 8.71 ng/l. Mercury-contaminated groundwater was the source for outfalls with significantly elevated mercury concentrations. Total mercury in SRS streams ranged from 0.95-15.7 ng/l. Mean total mercury levels in the streams varied from 2.39 ng/l in Pen Branch to 5.26 ng/l in Tims Branch

  7. Chronic exposure to combined carcinogens enhances breast cell carcinogenesis with mesenchymal and stem-like cell properties.

    Directory of Open Access Journals (Sweden)

    Lenora Ann Pluchino

    Full Text Available Breast cancer is the most common type of cancer affecting women in North America and Europe. More than 85% of breast cancers are sporadic and attributable to long-term exposure to small quantities of multiple carcinogens. To understand how multiple carcinogens act together to induce cellular carcinogenesis, we studied the activity of environmental carcinogens 4-(methylnitrosamino-1-(3-pyridyl-1-butanone (NNK and benzo[a]pyrene (B[a]P, and dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP using our breast cell carcinogenesis model. Our study revealed, for the first time, that combined NNK and B[a]P enhanced breast cell carcinogenesis chronically induced by PhIP in both non-cancerous and cancerous breast cells. Co-exposure was more potent than sequential exposure to combined NNK and B[a]P followed by PhIP in inducing carcinogenesis. Initiation of carcinogenesis was measured by transient endpoints induced in a single exposure, while progression of carcinogenesis was measured by acquisition of constitutive endpoints in cumulative exposures. Transient endpoints included DNA damage, Ras-Erk-Nox pathway activation, reactive oxygen species elevation, and increased cellular proliferation. Constitutive endpoints included various cancer-associated properties and signaling modulators, as well as enrichment of cancer stem-like cell population and activation of the epithelial-to-mesenchymal transition program. Using transient and constitutive endpoints as targets, we detected that a combination of the green tea catechins ECG and EGCG, at non-cytotoxic levels, was more effective than individual agents in intervention of cellular carcinogenesis induced by combined NNK, B[a]P, and PhIP. Thus, use of combined ECG and EGCG should be seriously considered for early intervention of breast cell carcinogenesis associated with long-term exposure to environmental and dietary carcinogens.

  8. 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.

  9. [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.

  10. A review of molecular events of cadmium-induced carcinogenesis.

    Science.gov (United States)

    Luevano, Joe; Damodaran, Chendil

    2014-01-01

    Cadmium (Cd) is a toxic, heavy industrial metal that poses serious environmental health hazards to both humans and wildlife. Recently, Cd and Cd-containing compounds have been classified as known human carcinogens, and epidemiological data show causal associations with prostate, breast, and lung cancer. The molecular mechanisms involved in Cd-induced carcinogenesis are poorly understood and are only now beginning to be elucidated. The effects of chronic exposure to Cd have recently attracted great interest due to the development of malignancies in Cd-induced tumorigenesis in animals models. Briefly, various in vitro studies demonstrate that Cd can act as a mitogen, can stimulate cell proliferation and inhibit apoptosis and DNA repair, and can induce carcinogenesis in several mammalian tissues and organs. Thus, the various mechanisms involved in chronic Cd exposure and malignant transformations warrant further investigation. In this review, we focus on recent evidence of various leading general and tissue-specific molecular mechanisms that follow chronic exposure to Cd in prostate-, breast-, and lung-transformed malignancies. In addition, in this review, we consider less defined mechanisms such as epigenetic modification and autophagy, which are thought to play a role in the development of Cd-induced malignant transformation.

  11. Egyptian wind energy resources study. Phase II. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, W.L.

    1979-11-01

    The data gathered in Egypt in Phase I of the program indicated favorable wind energy possibilities along the Mediterranean Coast west of Alexandria and along the Red Sea south of Suez. There did not appear to be inland areas of high promise. It was decided that in Phase II, several continuous wind recording instruments would be established on the North Coast and Red Sea Coasts. Locations finally selected for the North Coast (South Coast of the Mediterranean) were distributed from Mersa Matruh to Borg El Arab, a coastal community about seventy kilometers west of Alexandria. The recorded data from the monitoring stations are presented.

  12. Final Report for Studies in Elementary Particle Physics

    Energy Technology Data Exchange (ETDEWEB)

    Piilonen, Leo; Takeuchi, Tatsu; Minic, Djordje; Link, Jonathan

    2013-11-01

    This is the final report of DOE Grant DE-FG05-92ER40709 awarded to the Virginia Tech high energy physics group. It covers the period February 1, 2010 through April 30, 2013. The high energy physics program at Virginia Tech supported by this grant is organized into three tasks: A for theory (Profs. Tatsu Takeuchi and Djordje Minic), B for heavy flavor physics with the Belle and Belle II experiments (Prof. Leo Piilonen), and N for neutrino physics (Profs. Jonathan Link and Piilonen).

  13. 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 1

  14. Studies of final state interactions via femtoscopy in ALICE

    CERN Document Server

    ,

    2016-01-01

    Femtoscopy is a technique enabling measurements of the space-time characteristics of particle-emitting sources. However, the femtoscopic analysis is also sensitive to the interaction cross-section. In this paper we show the first preliminary measurements of $\\rm K^0_SK^{\\pm}$ correlation functions in Pb-Pb collisions at $\\sqrt{s_{\\rm NN}}=5.02$ TeV. These correlations originate from the final-state interactions which proceed through the $a_0(980)$ resonance only and can be employed to constrain its parameters. A similar approach can be applied to baryon pairs to extract the unknown interaction cross-sections for some (anti-)baryon-(anti-)baryon pairs. We show baryon--baryon and baryon--anti-baryon correlation functions of protons and lambdas, as well as discuss shortly the fitting method.

  15. Carcinogenesis--a new point of view.

    Science.gov (United States)

    Gevorkyan, L; Gambashidze, K

    2014-04-01

    Presented article suggests the novel hypothesis of carcinogenesis, where the key moment for all types (biological, physical, chemical) of carcinogenesis has been discussed. For confirmation of the hypothesis thorough theoretical analysis of the mechanisms of malignant transformation of cells after influence of any type of carcinogens and results of experiments have been presented. Hypothesis highlights are formulated as follows: 1) Covalent bond disorders between S+-methionine and Fe3+ atoms in cytochrome; 2) Electron transport chain blockade with certain ligand after its penetration in cytochrome pocket with further formation of 6th coordination bond between ligand and Fe atom (in one case increase in mitochondrial pH precede-, and in other, it follows electron transport chain blockade in cytochromes); 3) Fe3+ reduction up to Fe2+ leading to blockade of aerobic glycolysis; 4) Decrease in enzyme (Е1-TDP, oxidases etc.) activity due to mitochondrial pH alterations; 5) Production of S-adenosylmethionine owing to lipoic acid amide leading to accumulation of homocysteine in cytoplasm with further penetration in cell nucleus producing DNA mutations; 6) Fe2+ wash-out from cytochrome and its deposition in ferritin.

  16. Aberrant DNA methylation in cervical carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Hui-Juan Yang

    2013-01-01

    Persistent infection with high-risk types of human papillomavirus(HPV) is known to cause cervical cancer; however,additional genetic and epigenetic alterations are required for progression from precancerous disease to invasive cancer.DNA methylation is an early and frequent molecular alteration in cervical carcinogenesis.In this review,we summarize DNA methylation within the HPV genome and human genome and identify its clinical implications.Methylation of the HPV long control region (LCR) and L1 gene is common during cervical carcinogenesis and increases with the severity of the cervical neoplasm.The L1 gene of HPV16 and HPV18 is consistently hypermethylated in invasive cervical cancers and can potentially be used as a clinical marker of cancer progression.Moreover,promoters of tumor suppressor genes (TSGs) involved in many cellular pathways are methylated in cervical precursors and invasive cancers.Some are associated with squamous cell carcinomas,and others are associated with adenocarcinomas.Identification of methylated TSGs in Pap smear could be an adjuvant test in cervical cancer screening for triage of women with high-risk HPV,atypical squamous cells of undetermined significance,or low grade squamous intraepithelial lesion (LSIL).However,consistent panels must be validated for this approach to be translated to the clinic.Furthermore,reversion of methylated TSGs using demethylating drugs may be an alternative anticancer treatment,but demethylating drugs without toxic carcinogenic and mutagenic properties must be identified and validated.

  17. AM(VI) partitioning studies. FY14 final report

    Energy Technology Data Exchange (ETDEWEB)

    Mincher, Bruce J. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2014-10-01

    The use of higher oxidation states of americium in partitioning from the lanthanides is under continued investigation by the sigma team. This is based on the hypothesis that Am(VI) can be produced and remain stable in irradiated first cycle raffinate solution long enough to perform solvent extraction for separations. The stability of Am(VI) to autoreduction was measured using millimolar americium concentrations in a 1-cm cell with a Cary 6000 UV/Vis spectrophotometer for data acquisition. At millimolar americium concentrations, Am(VI) is stable enough against its own autoreduction for separations purposes. A second major accomplishment during FY14 was the hot test. Americium oxidation and extraction was performed using a centrifugal contactor-based test bed consisting of an extraction stage and two stripping stages. Sixty-three percent americium extraction was obtained in one extraction stage, in agreement with batch contacts. Promising electrochemical oxidation results have also been obtained, using terpyridine ligand derivatized electrodes for binding of Am(III). Approximately 50 % of the Am(III) was oxidized to Am(V) over the course of 1 hour. It is believed that this is the first demonstration of the electrolytic oxidation of americium in a non-complexing solution. Finally, an initial investigation of Am(VI) extraction using diethylhexylbutyramide (DEHBA) was performed.

  18. Translesion Synthesis Polymerases in the Prevention and Promotion of Carcinogenesis

    Directory of Open Access Journals (Sweden)

    L. Jay Stallons

    2010-01-01

    Full Text Available A critical step in the transformation of cells to the malignant state of cancer is the induction of mutations in the DNA of cells damaged by genotoxic agents. Translesion DNA synthesis (TLS is the process by which cells copy DNA containing unrepaired damage that blocks progression of the replication fork. The DNA polymerases that catalyze TLS in mammals have been the topic of intense investigation over the last decade. DNA polymerase η (Pol η is best understood and is active in error-free bypass of UV-induced DNA damage. The other TLS polymerases (Pol ι, Pol κ, REV1, and Pol ζ have been studied extensively in vitro, but their in vivo role is only now being investigated using knockout mouse models of carcinogenesis. This paper will focus on the studies of mice and humans with altered expression of TLS polymerases and the effects on cancer induced by environmental agents.

  19. Washoe Tribe Alternative Energy Feasibility Study Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Jennifer [Washoe Tribe of NV and CA

    2014-10-01

    The Washoe Tribe of Nevada and California was awarded funding to complete the Washoe Tribe Alternative Energy Feasibility Study project. The main goal of the project was to complete an alternative energy feasibility study. This study was completed to evaluate “the potential for development of a variety of renewable energy projects and to conduct an alternative energy feasibility study that determines which alternative energy resources have the greatest economic opportunity for the Tribe, while respecting cultural and environmental values” (Baker-Tilly, 2014). The study concluded that distributed generation solar projects are the best option for renewable energy development and asset ownership for the Washoe Tribe. Concentrating solar projects, utility scale wind projects, geothermal, and biomass resource projects were also evaluated during the study and it was determined that these alternatives would not be feasible at this time.

  20. Industrial Education Ventilation Study. Volume 1: Final Report.

    Science.gov (United States)

    Stanley Associates, Edmonton (Alberta).

    A study assessed aspects of ventilation in industrial education facilities in selected junior and senior highs schools in Alberta (Canada). This report describes the purpose of the study and the four test methods used to acquire school specific information. Also discussed are (1) the results of the instructors' perception survey, the ventilation…

  1. Educational Resources Information Center (ERIC) File Partition Study: Final Report.

    Science.gov (United States)

    Hull, Cynthia C.; Wanger, Judith

    A study to provide the National Center for Educational Communication (NCE) with information that could be useful in making the ERIC data base more relevant to the needs of educators and more efficiently usable by them is discussed. Specific purposes of this project were to use an empirical field-survey study as an armature around which to: (1)…

  2. Report of the Comprehensive Service Needs Study. [Final Report.

    Science.gov (United States)

    Urban Inst., Washington, DC.

    Presented is the report of the comprehensive service needs study for the severely handicapped as authorized by section 130 of the Rehabilitation Act of 1973. Chapters focus on the following aspects of the study: definitions; the vocational rehabilitation (VR) system; estimates of the severely disabled population not in institutions; the most…

  3. Eastern Region Renewable Energy Planning Study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-07-01

    For planning authorities to address renewable energy through development plan policies and in the development control process, it is important to have clear and reliable information on the resource potential within their area. A number of studies have been undertaken in England and Wales to assess the potential for the development and utilisation of renewable energy resources. The studies have addressed the practicalities of how and why a certain resource might be suitable for exploitation in a particular county or region, in conjunction with consideration of the specific planning and environmental issues which may arise. The Eastern Region Renewable Energy Planning Study (ERREPS) is one of the last of these studies to be commissioned and, together with a concurrent study of the Lancashire and Yorkshire area, will substantially complete study coverage of England and Wales. The study area comprises the counties of Bedfordshire, Buckinghamshire, Cambridgeshire, Essex, Hertfordshire, Norfolk and Suffolk. It generally coincides with the area covered by Eastern Electricity. The area covers the majority of the land north of the River Thames to The Wash. (author)

  4. NTP Toxicology and Carcinogenesis Studies of alpha-Methyldopa Sesquihydrate (CAS No. 41372-08-1) in F344/N Rats and B6C3F1 Mice (Feed Studies).

    Science.gov (United States)

    1989-03-01

    a-Methyldopa sesquihydrate is used in the treatment of hypertension; over 20 million prescriptions are written annually for a -methyldopa or a-methyldopa sesquihydrate in the United States. a-Methyldopa sesquihydrate (USP grade, greater than 99% pure) was selected for study because of widespread human exposure and the lack of carcinogenicity studies on this compound. Fourteen-day, 13-week, and 2-year studies were conducted in F344/N rats and B6C3F1 mice. The chemical was administered in feed because human exposure is primarily by the oral route. Short-term studies were performed in bacteria and mammalian cells to evaluate the potential for genetic damage. Fourteen-Day and Thirteen-Week Studies: In the 14-day studies, the chemical was administered at dietary concentrations of 0 and 6,250-100,000 ppm. All rats receiving 100,000 ppm and 2/5 female rats receiving 50,000 ppm died. All mice lived until the end of the studies. Final mean body weights of dosed male rats were 14%-43% lower than that of controls, and those of dosed female rats were 9%-24% lower. Feed consumption by dosed male and female rats was reduced. Final mean body weights of dosed mice were generally within 10% of those of controls; feed consumption by dosed groups was lower than that by controls during the first week of the studies. In the 13-week studies, the chemical was administered at dietary concentrations of 0 and 3,100-50,000 ppm. Deaths occurred in 4/10 male rats, 7/10 female rats, and 2/10 female mice at 50,000 ppm and in 1/10 female rats at 25,000 ppm. Final mean body weights of dosed rats were 6%-46% lower than those of controls. Feed consumption by dosed rat groups was lower than that by controls. Final mean body weights of male mice at 25,000 and 50,000 ppm and female mice at 50,000 ppm were reduced 12%-19%. Feed consumption by dosed and control mice was comparable. Rats and mice receiving 25,000 and 50,000 ppm exhibited clinical signs of toxicity including lethargy, hyperexcitability

  5. 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.

  6. Final Report: Feasibility Study of Biomass in Snohomish County, Washington

    Energy Technology Data Exchange (ETDEWEB)

    Daryl Williams (Tulalip Tribes); Ray Clark (Clark Group)

    2005-01-31

    This report and its attachments summarizes the results of a unique tribal-farmer cooperative study to evaluate the feasibility of building one or more regional anaerobic digestion systems in Snohomish County, Washington.

  7. Networking and Information Technology Workforce Study: Final Report

    Data.gov (United States)

    Networking and Information Technology Research and Development, Executive Office of the President — This report presents the results of a study of the global Networking and Information Technology NIT workforce undertaken for the Networking and Information...

  8. PSRO (Professional Standards Review Organization) pelvimetry study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    McCue, S.M.

    1983-03-31

    A randomized controlled experimental study of the use x-ray pelvimetry in 151 hospitals in seven PSROs across the United States from June 1977 through March 1982 was conducted. The study was designed to test the impact of a physician educational intervention program on the utilization of a diagnostic procedure of questionable efficacy. Further, special studies were designed to assess substitution and quality effects by measuring changes in the utilization of caesarean section, electronic fetal monitoring and ultrasound; to assess the degree to which justification for the use of pelvimetry is recorded on the patient record; and to measure the utilization of pelvimetry in private radiologists' offices. The report contains a narrative discussion of the PSRO program; ancillary services review; a literature review of studies on the efficacy of pelvimetry and educational intervention strategies; and a detailed discussion of the design, methodology, and findings. The results of the study, a substantive drop in the pelvimetry rate in study hospitals vis-a-vis that in control hospitals pre and postintervention demonstrates that physician practice patterns changed due to the educational intervention.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Daniel Sliva

    Full Text Available 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.

  11. Mirror Fusion Test Facility data compression study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1979-11-01

    This report is organized as follows. Discussions are given of three of the most important data compression methods that have been developed and studied over the years: coding, transforms, and redundancy reduction. (A brief discussion of how to combine and synthesize these ideas, and others, into a system is given). Specific ideas for compressing MFTF diagnostics and control data are developed. Listings and instructions for using FORTRAN programs that were compiled on the Livermore MFTF computers during the course of the study are also given.

  12. Dark Energy Studies with LSST Image Simulations, Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, John Russell [Purdue Univ., West Lafayette, IN (United States)

    2016-07-26

    This grant funded the development and dissemination of the Photon Simulator (PhoSim) for the purpose of studying dark energy at high precision with the upcoming Large Synoptic Survey Telescope (LSST) astronomical survey. The work was in collaboration with the LSST Dark Energy Science Collaboration (DESC). Several detailed physics improvements were made in the optics, atmosphere, and sensor, a number of validation studies were performed, and a significant number of usability features were implemented. Future work in DESC will use PhoSim as the image simulation tool for data challenges used by the analysis groups.

  13. Lead and cadmium exposure study, Galena, Kansas. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Dhara, R.J.; Stallings, F.L.; Feese, D.

    1996-01-01

    A total of 167 residents from Galena, Kansas, and 283 residents from the southern portions of Neosho and Goodman, Missouri, participated in the study. Residents from the southern portions of Neosho and Goodman, Missouri, area served as the comparison population. Biological, environmental, and questionnaire information collected from residents of the Galena, Kansas, was compared with similar information collected from residents of the comparison area.

  14. Final Technical Report: Renewable Energy Feasibility Study and Resources Assessment

    Energy Technology Data Exchange (ETDEWEB)

    Rivero, Mariah [BEC Environmental, Inc., Las Vegas, NV (United States)

    2016-02-28

    In March 2011, the U.S. Department of Energy (DOE) awarded White Pine County, Nevada, a grant to assess the feasibility of renewable resource-related economic development activities in the area. The grant project included a public outreach and training component and was to include a demonstration project; however, the demonstration project was not completed due to lack of identification of an entity willing to locate a project in White Pine County. White Pine County completed the assessment of renewable resources and a feasibility study on the potential for a renewable energy-focused economic sector within the County. The feasibility study concluded "all resources studied were present and in sufficient quantity and quality to warrant consideration for development" and there were varying degrees of potential economic impact based on the resource type and project size. The feasibility study and its components were to be used as tools to attract potential developers and other business ventures to the local market. White Pine County also marketed the County’s resources to the renewable energy business community in an effort to develop contracts for demonstration projects. The County also worked to develop partnerships with local educational institutions, including the White Pine County School District, conducted outreach and training for the local community.

  15. Preliminary study Malaa. Final report; Foerstudie Malaa. Slutrapport

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    Factors of importance for a possible localization of a deep nuclear waste repository at Malaa in northern Sweden are mapped in this study. The geologic structures in the area have been reviewed, mostly from already existing knowledge. Existing infrastructure and necessary improvements are discussed, as well as land use and environment, employment and other social effects. 47 refs, 41 figs, 8 tabs.

  16. Study of Visual Factors in Concept Formation. Final Report.

    Science.gov (United States)

    Arnheim, Rudolf

    The study undertakes to clarify and redefine some of the concepts underlying the relations between visual perception and thinking. A sample bibliography suggests sources for future research. Psychological and psysiological theory is shown historically to have separated the two mental functions in principle. Correspondingly, present-day education,…

  17. STUDY OF VARIABLES ASSOCIATED WITH FINAL GRADES IN MATHEMATICS COURSES.

    Science.gov (United States)

    DAVIS, ELTON C.; RISSER, JOHN J.

    THIS STUDY WAS CONDUCTED IN ORDER TO DETERMINE THE RELATIVE VALUE OF PREVIOUS GRADES IN MATHEMATICS COURSES, THE OVERALL HIGH SCHOOL GRADE POINT AVERAGE, AND THE PLACEMENT TEST IN MATHEMATICS DEVELOPED AT THE COLLEGE AS PREDICTORS OF ACHIEVEMENT IN INTRODUCTORY AND INTERMEDIATE ALGEBRA, IN COLLEGE ALGEBRA, IN TRIGONOMETRY, AND IN ANALYTIC GEOMETRY…

  18. Psychological and Educational Studies with Spina Bifida Children. Final Report.

    Science.gov (United States)

    Diller, Leonard; And Others

    To measure school achievements in spina bifida children, to relate these measures to certain variables, to obtain information on educational problems, and to study facets of cognition and its changes with age, 77 spina bifida children and 53 amputees (all aged 5 to 15) were tested. Sixty non-disabled children were at times used for controls. The…

  19. Staging and storage facility feasibility study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Swenson, C.E. [Westinghouse Hanford Co., Richland, WA (United States)

    1995-02-01

    This study was performed to investigate the feasibility of adapting the design of the HWVP Canister Storage Building (CSB) to meet the needs of the WHC Spent Nuclear Fuel Project for Staging and Storage Facility (SSF), and to develop Rough Order of Magnitude (ROM) cost and schedule estimates.

  20. DOE final report: Studies on the microbial formation of methane

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, Ralph S.

    2001-04-01

    The microbial formation of methane is carried out by methanogens which are found wherever active anaerobic degradation of organic matter occurs. We developed a procedure for reliable culture of 'Methanococus jannaschii' which yields 8 g wet weight of cells per liter of medium. To initiate a study of proteomics, this organism was grown at two levels of hydrogen partial pressure, very low (650 Pa) and high (178 kPa). When cells were exposed to hydrogen excess conditions, they possessed very low or undetectable levels of four flagella-related polypeptides, whereas, when hydrogen became limiting, these proteins were synthesized. Thus, use of proteomics showed, for the first time, that this methanogen can regulate expression of proteins, and these experiments open the door for general studies of regulation in this hyperthermophile.

  1. VHTR engineering design study: intermediate heat exchanger program. Final report

    Energy Technology Data Exchange (ETDEWEB)

    None

    1976-11-01

    The work reported is the result of a follow-on program to earlier Very High Temperature Reactor (VHTR) studies. The primary use of the VHTR is to provide heat for various industrial processes, such as hydrocarbon reforming and coal gasification. For many processes the use of an intermediate heat transfer barrier between the reactor coolant and the process is desirable; for some processes it is mandatory. Various intermediate heat exchanger (IHX) concepts for the VHTR were investigated with respect to safety, cost, and engineering design considerations. The reference processes chosen were steam-hydrocarbon reforming, with emphasis on the chemical heat pipe, and steam gasification of coal. The study investigates the critically important area of heat transfer between the reactor coolant, helium, and the various chemical processes.

  2. Study on distributed energy options in Skaftkaerr testbed. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Pesola, A.; Hagstroem, M.; Vanhanen, J. (Gaia Consulting Oy, Helsinki (Finland))

    2011-07-01

    In the distributed energy production model electricity or heat is produced near the end-user in relatively small units - using very often local renewable energy sources. These are e.g. solar thermal or photovoltaic applications, wind power, fuel cells or other small-scale CHP technologies using e.g. bio-based fuels. Locally produced intermittent renewable electricity can be optimized by storing produced electricity and using it when electricity price is high. Electricity storage is an important part of smart grid development from the perspective of supply-demand flexibility. Heat can be stored as well using e.g. water tank placed either under or above the ground. Distributed energy production technologies are already utilized in domestic residential areas and the trend is emerging. Designing and planning needs to be emphasized in order to build and maintain technically and economically sustainable energy system. The objective of this study is to present the possibilities of distributed energy production and storage technologies. The study highlights available technologies and services of distributed energy production and helps to build up a testbed solution that could lead to demonstration-scale application in near future. This testbed is a part of developing process of Skaftkaerr area where energy efficiency and environmental issues are emphasized. In this report, feasible production and storage technologies are presented in Chapter 2. Chapter 3 introduces economical characteristics of studied technologies. Chapter 4 points out suitable technologies for Skaftkaerr area and presents profitability analysis of these technologies via two cases. Domestic actors in technology value chains are also presented in Chapter 4. Chapter 5 summarizes the study and its findings

  3. Yakima River Spring Chinook Enhancement Study Appendices, 1991 Final Report.

    Energy Technology Data Exchange (ETDEWEB)

    Fast, David E.

    1991-05-01

    This document consists of the appendices for annual report DOE/BP/39461--9 which is summarized as follows. The population of Yakima River spring chinook salmon (Oncorhynchus tschawytscha) has been drastically reduced from historic levels reported to be as high as 250,000 adults (Smoker 1956). This reduction is the result of a series of problems including mainstem Columbia dams, dams within the Yakima itself, severely reduced flows due to irrigation diversions, outmigrant loss in irrigation canals, increased thermal and sediment loading, and overfishing. Despite these problems, the return of spring chinook to the Yakima River has continued at levels ranging from 854 to 9,442 adults since 1958. In October 1982, the Bonneville Power Administration contracted the Yakima Indian Nation to develop methods to increase production of spring chinook in the Yakima system. The Yakima Nation's current enhancement policy attempts to maintain the genetic integrity of the spring chinook stock native to the Yakima Basin. Relatively small numbers of hatchery fish have been released into the basin in past years. The goal of this study was to develop data that will be used to present management alternatives for Yakima River spring chinook. A major objective of this study is to determine the distribution, abundance and survival of wild Yakima River spring chinook. The second major objective of this study is to determine the relative effectiveness of different methods of hatchery supplementation. The last three major objectives of the study are to locate and define areas in the watershed that may be used for the rearing of spring chinook; to define strategies for enhancing natural production of spring chinook in the Yakima River; and to determine the physical and biological limitations on production within the system.

  4. Nuclear electric propulsion mission engineering study. Volume 2: Final report

    Science.gov (United States)

    1973-01-01

    Results of a mission engineering analysis of nuclear-thermionic electric propulsion spacecraft for unmanned interplanetary and geocentric missions are summarized. Critical technologies associated with the development of nuclear electric propulsion (NEP) are assessed, along with the impact of its availability on future space programs. Outer planet and comet rendezvous mission analysis, NEP stage design for geocentric and interplanetary missions, NEP system development cost and unit costs, and technology requirements for NEP stage development are studied.

  5. White phosphorus pits focused feasibility study final July 2007.

    Energy Technology Data Exchange (ETDEWEB)

    Davis, B.; Martino, L.

    2007-08-21

    The White Phosphorus Burning Pits (WPP) Area of Concern (AOC) is a site of about 5.5 acres (2.2 ha) located in the J-Field Study Area, in the Edgewood Area of Aberdeen Proving Ground (APG), Maryland (Figure 1.1). Considerable information about the WPP exists as a result of efforts to characterize the hazards associated with J-Field. Contamination in the J-Field Study Area was first detected during an environmental survey of the APG Edgewood Area conducted in 1977 and 1978 (Nemeth et al. 1983) by the U.S. Army Toxic and Hazardous Materials Agency (USATHAMA; predecessor to the U.S. Army Environmental Center). As part of a subsequent USATHAMA environmental survey, 11 wells were installed and sampled at J-Field (three of them at the WPP) (Nemeth 1989). Contamination was also detected in 1983 during a munitions disposal survey conducted by Princeton Aqua Science (1984). The Princeton Aqua Science investigation involved installing and sampling nine wells (four at the WPP) and collecting and analyzing surficial and deep composite soil samples (including samples from the WPP area). In 1986, the U.S. Environmental Protection Agency (EPA) issued a Resource Conservation and Recovery Act (RCRA) Permit (MD3-21-002-1355) requiring a post-wide RCRA Facility Assessment (RFA) and a hydrogeologic assessment of J-Field. In 1987, the U.S. Geological Survey (USGS) began a two-phase hydrogeologic assessment in which data were collected to model groundwater flow at J-Field. Soil-gas investigations were conducted, several well clusters were installed (four at the WPP), a groundwater flow model was developed, and groundwater and surface water monitoring programs were established that continue today. The results of the USGS study were published by Hughes (1993).

  6. The Industry Coupled Case Study Program final report

    Energy Technology Data Exchange (ETDEWEB)

    Stringfellow, J. [ed.

    1982-10-01

    The Industry Coupled Case Study Program was conceived as a short-term cooperative program between the Federal government and private industry. Federal funds were committed to stimulate geothermal exploration and development between 1977 and 1979, although some work under the program continues into 1982. Federal funding has been phased out and the remaining information developed during the program is being disseminated and reported. This report presents an overview of the program and documents the technical results and open-file data base resulting from the program.

  7. The molecular mechanisms of hazardous metals for carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    ChenJK; LeiYX

    2002-01-01

    The available experimental and epidemiological data have shown that nickel (Ni) and cadmium (Dd) and their compounds are carcinogenic to experimental animals and human.These two metals have been classified as human carcinogens bythe International Agency for Research on Cancer (IARC).However,Their underlying molecular mechanisms remain unknown.The objective of this research was to investigate the molecular mechanisms responsible for Ni and Cd carcinogenesis through epidemiological study in human exposure,transformation expreiments in human epithelial cells (16HBE) and BALB/c-3T3 cell lines in vitro,DNA damage detections (comet,DNA-protein crosslinks) as well as telomerase activity and apoptosis assay,and analysis of oncogens,tumor suppressor genes and their mutation (including genomic instability,k-ras,p15,p16,p53,FHIT) in transformed cell lines or tumor cells/tissue.Furthermore,we also detected and analyses the methylation,related novel genes and encoded protein in Cd transformed cells.The results and conclusion are as follows:(1)There is significant relationship between some hazardous metals and lung cancer (OR=8.76),especially for nickel(OR=11.25).(2)Ni and Cd and their compounds could induce malignant transformation in mammalian cell lines and human epithelial cells,and induce tumorigenesis in nude mice.(3)There is obvious DNA damage during cell transformation and tumorigenesis induced by Ni.(4) Significant genomic instability has been shown during cell transformation and tumorigenesis induced by Ni.(5)Detection of k-ras,p15,p16 genes in point mutation have demonstrated no changes during cell transformation and tumorigenesis induced by hazardous medals,suggesting that gene mutation is not the main way to metal carcinogenesis.(6)There are some aberrant DNA methylation in Cdtransformed cell lines.(7)We found two novel Cd-responsive proto-oncogenes and their encoded proteins in Cd-transformed cell lines.

  8. 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.

  9. Energy conserving site design case study: Shenandoah, Georgia. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1980-01-01

    The case study examines the means by which energy conservation can be achieved at an aggregate community level by using proper planning and analytical techniques for a new town, Shenandoah, Georgia, located twenty-five miles southwest of Atlanta's Hartsfield International Airport. A potentially implementable energy conservation community plan is achieved by a study team examining the land use options, siting characteristics of each building type, alternate infrastructure plans, possible decentralized energy options, and central utility schemes to determine how community energy conservation can be achieved by use of pre-construction planning. The concept for the development of mixed land uses as a passively sited, energy conserving community is based on a plan (Level 1 Plan) that uses the natural site characteristics, maximizes on passive energy siting requirement, and allows flexibility for the changing needs of the developers. The Level 2 Plan is identical with Level 1 plan plus a series of decentraized systems that have been added to the residential units: the single-family detached, the apartments, and the townhouses. Level 3 Plan is similar to the Level 1 Plan except that higher density dwellings have been moved to areas adjacent to central site. The total energy savings for each plan relative to the conventional plan are indicated. (MCW)

  10. Solair heater program: solair applications study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1977-12-01

    General Electric has designed and tested a low-cost solar system using a vacuum tube solar air heater under ERDA Contract E(11-1)-2705. This contract extension has been provided to evaluate various applications of this solar collector. The evaluation identified attractive applications, evaluated corresponding control procedures, estimated system performance, compared economically insolation and insulation, and evaluated the repackaging of off-the-shelf equipment for improved cost effectiveness. The results of this study prompted General Electric's marketing group to do a detailed commercialization study of a residential domestic water heating system using the Solair concept which has been selected as the most attractive application. Other attractive applications are space/domestic water heating and a heat pump assisted solar system/domestic water heating where the heat pump and the solar system function in parallel. A prime advantage of heated air solar systems over liquid systems is cost and longer life which results in higher BTU's/dollar. Other air system advantages are no liquid leakage problems, no toxicity of freezing problems, and less complicated equipment. A hybrid solar system has been identified that can improve the market penetration of solar energy. This system would use the existing mass of the house for energy storage thereby reducing solar cost and complexity. Adequate performance can be obtained with house temperature swings comparable to those used in nighttime setback of the thermostat. Details of this system are provided.

  11. Refueling outage availability study. Phase 1 final report

    Energy Technology Data Exchange (ETDEWEB)

    Thomasson, F.R.

    1977-11-01

    Babcock and Wilcox entered into a contract with the Department of Energy (formerly the Energy Research and Development Administration) for the performance of a refueling outage availability study with the cooperation of Duke Power Company and Arkansas Power and Light Company. The objective was to improve plant availability through reduction of refueling outage time. The conclusions of the study were drawn from data gathered during the 1976 Oconee 3 and 1977 Arkansas Unit One refueling outages. The onsite effort was one of observation and data recording, which included time-lapsed photography and video tape. The collected data were then evaluated and analyzed for potential improvements and to identify in detail where resources were consumed. The overall result was a listing of (1) specific recommendations for implementing improvements in the facilities, equipment, tools, procedures, and techniques for the participating utilities; (2) generic recommendations of immediate benefit to other applicable utilities; and (3) recommendations for further work in the succeeding phases of the DOE program. The results indicate that, by incorporating the recommendations and taking credit for the time savings, an ideal refueling outage length of 21 to 22 days for the nuclear steam system (NSS) could be realized. Additional benefits would be a reduction in man-Rem exposure and manpower requirements.

  12. Beam Loss Studies for Rare Isotope Driver Linacs Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Wangler, T P; Kurennoy, S S; Billen, J H; Crandall, K R; Qiang, J; Ryne, R D; Mustapha, B; Ostroumov, P; Zhao, Q; York, and R. C.

    2008-03-26

    The Fortran 90 RIAPMTQ/IMPACT code package is a pair of linked beam-dynamics simulation codes that have been developed for end-to-end computer simulations of multiple-charge-state heavy-ion linacs for future exotic-beam facilities. These codes have multiple charge-state capability, and include space-charge forces. The simulations can extend from the low-energy beam-transport line after an ECR ion source to the end of the linac. The work has been performed by a collaboration including LANL, LBNL, ANL, and MSU. The code RIAPMTQ simulates the linac front-end beam dynamics including the LEBT, RFQ, and MEBT. The code IMPACT simulates the beam dynamics of the main superconducting linac. The codes have been benchmarked for rms beam properties against previously existing codes at ANL and MSU. The codes allow high-statistics runs on parallel supercomputing platforms, particularly at NERSC at LBNL, for studies of beam losses. The codes also run on desktop PC computers for low-statistics work. The code package is described in more detail in a recent publication [1] in the Proceedings of PAC07 (2007 US Particle Accelerator Conference). In this report we describe the main activities for the FY07 beam-loss studies project using this code package.

  13. Blade System Design Study. Part II, final project report (GEC).

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, Dayton A. (DNV Global Energy Concepts Inc., Seattle, WA)

    2009-05-01

    As part of the U.S. Department of Energy's Low Wind Speed Turbine program, Global Energy Concepts LLC (GEC)1 has studied alternative composite materials for wind turbine blades in the multi-megawatt size range. This work in one of the Blade System Design Studies (BSDS) funded through Sandia National Laboratories. The BSDS program was conducted in two phases. In the Part I BSDS, GEC assessed candidate innovations in composite materials, manufacturing processes, and structural configurations. GEC also made recommendations for testing composite coupons, details, assemblies, and blade substructures to be carried out in the Part II study (BSDS-II). The BSDS-II contract period began in May 2003, and testing was initiated in June 2004. The current report summarizes the results from the BSDS-II test program. Composite materials evaluated include carbon fiber in both pre-impregnated and vacuum-assisted resin transfer molding (VARTM) forms. Initial thin-coupon static testing included a wide range of parameters, including variation in manufacturer, fiber tow size, fabric architecture, and resin type. A smaller set of these materials and process types was also evaluated in thin-coupon fatigue testing, and in ply-drop and ply-transition panels. The majority of materials used epoxy resin, with vinyl ester (VE) resin also used for selected cases. Late in the project, testing of unidirectional fiberglass was added to provide an updated baseline against which to evaluate the carbon material performance. Numerous unidirectional carbon fabrics were considered for evaluation with VARTM infusion. All but one fabric style considered suffered either from poor infusibility or waviness of fibers combined with poor compaction. The exception was a triaxial carbon-fiberglass fabric produced by SAERTEX. This fabric became the primary choice for infused articles throughout the test program. The generally positive results obtained in this program for the SAERTEX material have led to its

  14. Hycom Pre - Feasibility study. Final report[Hydrogen communities

    Energy Technology Data Exchange (ETDEWEB)

    Lacobazzi, A.; Mario, F di [ENEA, (Italy); Hasenauer, U. [Fraunhofer IS, (Germany); Joergensen, B.H.; Bromand Noergaard, P. [Risoe National Lab., (Denmark)

    2005-07-01

    The Quick-start Programme of the European Union Initiative for Growth identifies the hydrogen economy as one of the key areas for investment in the medium term (2004-2015). In this context the HyCOM (Hydrogen Communities) programme has been initiated. The main goal of this programme is the creation of a limited number of strategically sited stand-alone hydrogen communities producing hydrogen from various primary sources (mostly renewables) and using it for heat and electricity production and as fuel for vehicles. This report looks at the establishment of such hydrogen communities, analysing the main technical, economic, social, and environmental aspects as well as financial and regulatory barriers associated with the creation and operation of hydrogen communities. It also proposes a number of concepts for Hydrogen Communities and criteria with which a Hydrogen Community should be evaluated. The study is not in any way intended to be prescriptive. (ln)

  15. Gas recombination device design and cost study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1980-07-01

    Under a contract with Argonne National Laboratory, VARTA Batterie AG. conducted a design and cost study of hydrogen-oxygen recombination devices (HORD) for use with utility load-leveling lead-acid cells. Design specifications for the devices, through extensive calculation of the heat-flow conditions of the unit, were developed. Catalyst and condenser surface areas were specified. The exact dimensions can, however, be adjusted to the cell dimension and the space available above the cell. Design specifications were also developed for additional components required to ensure proper function of the recombination device, including metal hydride compound decomposer, aerosol retainer, and gas storage component. Costs for HORD were estimated to range from $4 to $10/kWh cell capacity for the production of a large number of units (greater than or equal to 10,000 units). The cost is a function of cell size and positive grid design. 21 figures, 2 tables.

  16. Extraction studies. Final report, May 6, 1996--September 30, 1997

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-10-09

    During the first week of this effort, an Alpkem RFA-300 4-channel automated chemical analyzer was transferred to the basement of building 42 at TA-46 for the purpose of performing extraction studies. Initially, this instrumentation was applied to soil samples known to contain DNA. Using the SFA (Segmented Flow Analysis) technique, several fluidic systems were evaluated to perform on-line filtration of several varieties of soil obtained from Cheryl Kuske and Kaysie Banton (TA-43, Bldg. 1). Progress reports were issued monthly beginning May 15, 1996. Early in 1997 there was a shift from the conventional 2-phase system (aqueous + air) to a 3-phase system (oil + aqueous + air) to drastically reduce sample size and reagent consumption. Computer animation was recorded on videotape for presentations. The time remaining on the subcontract was devoted to setting up existing equipment to incorporate the 3rd phase (a special fluorocarbon oil obtained from DuPont).

  17. Blanket comparison and selection study. Final report. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    1984-09-01

    The study focused on: (1) Development of reference design guidelines, evaluation criteria, and a methodology for evaluating and ranking candidate blanket concepts. (2) Compilation of the required data base and development of a uniform systems analysis for comparison. (3) Development of conceptual designs for the comparative evaluation. (4) Evaluation of leading concepts for engineering feasibility, economic performance, and safety. (5) Identification and prioritization of R and D requirements for the leading blanket concepts. Sixteen concepts (nine TMR and seven tokamak) which were identified as leading candidates in the early phases of the study, were evaluated in detail. The overall evaluation concluded that the following concepts should provide the focus for the blanket R and D program: (Breeder/Coolant/Structure), Lithium/Lithium/Vanadium Alloy, Li/sub 2/O/Helium/Ferritic Steel, LiPb Alloy/LiPb Alloy/Vanadium Alloy, and Lithium/Helium/Ferritic Steel. The primary R and D issues for the Li/Li/V concept are the development of an advanced structural alloy, resolution of MHD and corrosion problems, provision for an inert atmosphere (e.g., N/sub 2/) in the reactor building, and the development of non-water cooled near-plasma components, particularly for the tokamak. The main issues for the LiPb/LiPb/V concept are similar to the Li/Li/V blanket with the addition of resolving the tritium recovery issue. The R and D issues for Li/sub 2/O/He/FS concept include resolution of the tritium recovery/containment issue, achieving adequate tritium breeding and resolving other solid breeder issues such as swelling and fabrication concerns. Major concerns for the Li/He/FS concept are related to its rather poor economic performance. Improvement of its economic performance will be somewhat concept-dependent and will be more of a systems engineering issue.

  18. Blanket comparison and selection study. Final report. Volume 3

    Energy Technology Data Exchange (ETDEWEB)

    1984-09-01

    The study focused on: (1) Development of reference design guidelines, evaluation criteria, and a methodology for evaluating and ranking candidate blanket concepts. (2) Compilation of the required data base and development of a uniform systems analysis for comparison. (3) Development of conceptual designs for the comparative evaluation. (4) Evaluation of leading concepts for engineering feasibility, economic performance, and safety. (5) Identification and prioritization of R and D requirements for the leading blanket concepts. Sixteen concepts (nine TMR and seven tokamak) which were identified as leading candidates in the early phases of the study, were evaluated in detail. The overall evaluation concluded that the following concepts should provide the focus for the blanket R and D program: (Breeder/Coolant/Structure), Lithium/Lithium/Vanadium Alloy, Li/sub 2/O/Helium/Ferritic Steel, LiPb Alloy/LiPb Alloy/Vanadium Alloy, and Lithium/Helium/Ferritic Steel. The primary R and D issues for the Li/Li/V concept are the development of an advanced structural alloy, resolution of MHD and corrosion problems, provision for an inert atmosphere (e.g., N/sub 2/) in the reactor building, and the development of non-water cooled near-plasma components, particularly for the tokamak. The main issues for the LiPb/LiPb/V concept are similar to the Li/Li/V blanket with the addition of resolving the tritium recovery issue. The R and D issues for Li/sub 2/O/He/FS concept include resolution of the tritium recovery/containment issue, achieving adequate tritium breeding and resolving other solid breeder issues such as swelling and fabrication concerns. Major concerns for the Li/He/FS concepts are related to its rather poor economic performance. Improvement of its economic performance will be somewhat concept-dependent and will be more of a systems engineering issue.

  19. Blanket comparison and selection study. Final report. Volume 2

    Energy Technology Data Exchange (ETDEWEB)

    1984-09-01

    The study focused on: (1) Development of reference design guidelines, evaluation criteria, and a methodology for evaluating and ranking candidate blanket concepts. (2) Compilation of the required data base and development of a uniform systems analysis for comparison. (3) Development of conceptual designs for the comparative evaluation. (4) Evaluation of leading concepts for engineering feasibility, economic performance, and safety. (5) Identification and prioritization of R and D requirements for the leading blanket concepts. Sixteen concepts (nine TMR and seven tokamak) which were identified as leading candidates in the early phases of the study, were evaluated in detail. The overall evaluation concluded that the following concepts should provide the focus for the blanket R and D program: (Breeder/Coolant/Structure), Lithium/Lithium/Vanadium Alloy, Li/sub 2/O/Helium/Ferritic Steel, LiPb Alloy/LiPb Alloy/Vanadium Alloy, and Lithium/Helium/Ferritic Steel. The primary R and D issues for the Li/Li/V concept are the development of an advanced structural alloy, resolution of MHD and corrosion problems, provision for an inert atmosphere (e.g., N/sub 2/) in the reactor building, and the development of non-water cooled near-plasma components, particularly for the tokamak. The main issues for the LiPb/LiPb/V concepts are similar to the Li/Li/V blanket with the addition of resolving the tritium recovery issue. The R and D issues for Li/sub 2/O/He/FS concept include resolution of the tritium recovery/containment issue, achieving adequate tritium breeding and resolving other solid breeder issues such as swelling and fabrication concerns. Major concerns for the Li/He/FS concept are related to its rather poor economic performance. Improvement of its economic performance will be somewhat concept-dependent and will be more of a systems engineering issue.

  20. Treatability study Number PDC-1-O-T. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-04-22

    Los Alamos National Laboratory provided treatability study samples from four waste streams, designated Stream {number_sign}1, Stream {number_sign}3, Stream {number_sign}6, and Stream {number_sign}7. Stream {number_sign}1 consisted of one 55-gallon drum of personal protective equipment (PPE), rags, and neutralizing agent (bicarbonate) generated during the cleanup of a sodium dichromate solution spill. Stream {number_sign}3 was one 55-gallon drum of paper, rags, lab utensils, tools, and tape from the decontamination of a glovebox. The sample of Stream {number_sign}6 was packaged in three 30-gallon drums and a 100 ft{sup 3} wooden box. It consisted of plastic sheeting, PPE, and paper generated from the cleanup of mock explosive (barium nitrate) from depleted uranium parts. Stream {number_sign}7 was scrap metal (copper, stainless and carbon steel joined with silver solder) from the disassembly of gas manifolds. The objective of the treatability study is to determine: (1) whether the Perma-Fix stabilization/solidification process can treat the waste sample to meet Land Disposal Restrictions and the Waste Acceptance Criteria for LANL Technical Area 54, Area G, and (2) optimum loading and resulting weight and volume of finished waste form. The stabilized waste was mixed into grout that had been poured into a lined drum. After each original container of waste was processed, the liner was closed and a new liner was placed in the same drum on top of the previous closed liner. This allowed an overall reduction in waste volume but kept waste segregated to minimize the amount of rework in case analytical results indicated any batch did not meet treatment standards. Samples of treated waste from each waste stream were analyzed by Perma-Fix Analytical Services to get a preliminary approximation of TCLP metals. Splits of these samples were sent to American Environmental Network`s mixed waste analytical lab in Cary, NC for confirmation analysis. Results were all below applicable

  1. Second-generation-heliostat optimization studies. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1982-05-01

    The objective of this study was to define and quantify cost reductions in the Martin Marietta Denver Aerospace Second Generation Heliostat resulting from design and cost optimization. These cost reductions were based on optimizing the heliostat performance vs. cost and engineering design, and reviewing the design specification in selected technological areas with a goal of removing nonrealistic requirements and eliminating or minimizing overdesign. Specific technological areas investigated were: (1) designing the heliostat for survival strength rather than stiffness and reducing the operational wind requirements as dictated by this design approach; (2) reducing the pointing accuracy and/or beam quality required for some fraction or all of the heliostat field; (3) modifying the operational temperature range; (4) relaxing the rate at which the heliostat must move in the slew mode; (5) using alternate beam safety strategies; (6) analyzing actual wind data for selected sites in the southwest United States vs. the heliostat design specification survival wind requirements; (7) estimating heliostat damage for winds in excess of the design specification over a 30 year period; (8) evaluating the impact of designing the heliostat for higher wind loads; and (9) investigating the applicability to heliostat design of the standard engineering practices for designing buildings.

  2. Anticipatory precrash restraint sensor feasibility study: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Kercel, S.W.; Dress, W.B.

    1995-08-01

    This report explores feasibility of an anticipatory precrash restraint sensor. The foundation principle is the anticipation mechanism found at a primitive level of biological intelligence and originally formalized by the mathematical biologist Robert Rosen. A system based on formal anticipatory principles should significantly outperform conventional technologies. It offers the prospect of high payoff in prevention of death and injury. Sensors and processes are available to provide a good, fast, and inexpensive description of the present dynamical state of the vehicle to the embedded system model in the anticipation engine. The experimental part of this study found that inexpensive radar in a real-world setting does return useful data on target dynamics. The data produced by a radar system can be converted to target dynamical information by good, fast and inexpensive signal-processing techniques. Not only is the anticipatory sensor feasible, but further development under the sponsorship of the National Highway Traffic Safety Administration is necessary and desirable. There are a number of possible lines of follow-on investigation. The level of effort and expected benefits of various alternatives are discussed.

  3. Barrow Black Carbon Source and Impact Study Final Campaign Report

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, Tate [Baylor Univ., Waco, TX (United States)

    2014-07-01

    The goal of the Barrow Black Carbon Source and Impact (BBCSI) Study was to characterize the concentration and isotopic composition of carbonaceous atmospheric particulate matter (PM) at the Atmospheric Radiation Measurement site in Barrow, AK. The carbonaceous component was characterized via measurement of the organic and black carbon (OC and BC) components of the total PM. To facilitate complete characterization of the particulate matter, filter-based collections were used, including a medium volume PM2.5 sampler and a high volume PM10 sampler. Thirty-eight fine (PM2.5) and 49 coarse (PM10) particulate matter fractions were collected at weekly and bi-monthly intervals. The PM2.5 sampler operated with minimal maintenance during the 12 month campaign. The PM10 sampler used for the BBCSI used standard Tisch hi-vol motors which have a known lifetime of ~1 month under constant use; this necessitated monthly maintenance and it is suggested that the motors be upgraded to industrial blowers for future deployment in the Arctic. The BBCSI sampling campaign successfully collected and archived 87 ambient atmospheric particulate matter samples from Barrow, AK from July 2012 to June 2013. Preliminary analysis of the organic and black carbon concentrations has been completed. This campaign confirmed known trends of high BC lasting from the winter through to spring haze periods and low BC concentrations in the summer.

  4. Revised CTUIR Renewable Energy Feasibility Study Final Report

    Energy Technology Data Exchange (ETDEWEB)

    John Cox; Thomas Bailor; Theodore Repasky; Lisa Breckenridge

    2005-10-31

    This preliminary assessment of renewable energy resources on the Umatilla Indian Reservation (UIR) has been performed by CTUIR Department of Science and Engineering (DOSE). This analysis focused primarily identifying renewable resources that may be applied on or near the Umatilla Indian Reservation. In addition preliminary technical and economic feasibility of developing renewable energy resources have been prepared and initial land use planning issues identified. Renewable energies examined in the course of the investigation included solar thermal, solar photovoltaic, wind, bioethanol, bio-diesel and bio-pellet fuel. All renewable energy options studied were found to have some potential for the CTUIR. These renewable energy options are environmentally friendly, sustainable, and compliment many of the policy goals of the CTUIR. This report seeks to provide an overall review of renewable energy technologies and applications. It tries to identify existing projects near to the CTUIR and the efforts of the federal government, state government and the private sector in the renewable energy arena. It seeks to provide an understanding of the CTUIR as an energy entity. This report intends to provide general information to assist tribal leadership in making decisions related to energy, specifically renewable energy deve lopment.

  5. Studies of Transport Properties of Fractures: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Stephen R. Brown

    2006-06-30

    We proposed to study several key factors controlling the character and evolution of fracture system permeability and transport processes. We suggest that due to surface roughness and the consequent channeling in single fractures and in fracture intersections, the tendency of a fracture system to plug up, remain permeable, or for permeability to increase due to chemical dissolution/precipitation conditions will depend strongly on the instantaneous flow channel geometry. This geometry will change as chemical interaction occurs, thus changing the permeability through time. To test this hypothesis and advance further understanding toward a predictive capability, we endeavored to physically model and analyze several configurations of flow and transport of inert and chemically active fluids through channels in single fractures and through fracture intersections. This was an integrated program utilizing quantitative observations of fractures and veins in drill core, quantitative and visual observations of flow and chemical dissolution and precipitation within replicas of real rough-walled fractures and fracture intersections, and numerical modeling via lattice Boltzmann methods.

  6. Mini-Brayton economic RTG study. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1974-01-01

    The objective of this study is to demonstrate the applicability of a radioisotope heated Mini-Brayton power system to the 1973 USAF/AEC requirements established for the SURVSATCOM Mission. The principal requiremenets of the power system, are: 400 We power level; maximum weight 205 lbs.; $1.2 to 2.0 million per unit cost; and 5y mission duration. A radioisotope heat source that meets the ACE Nuclear Safety Criteria is presented. The major aspects of the Reference Design MB-ERTG are summarized. The Reference Design, utilizes a flexible Brayton rotating unit (BRU), a /sup 244/Cm heat source with ceramic clad fuel cylinders and an aluminum radiator. The flexible BRU has a variable power output capability, from 400 We to 3000 We, and is an important factor in the formulation of a cost effective development plan. The system weight is 186 lb and unit cost, including the /sup 244/Cm fuel, acceptance testing and delivery is $748,000. The total development cost for the 5-yr program is estimated at $16.4M with an additional $6.5M required for /sup 244/Cm heat source development support, /sup 244/Cm fuel, heat source fabrication and capital equipment expenditures. (LCL)

  7. California Basin Studies (CaBS). Final contract report

    Energy Technology Data Exchange (ETDEWEB)

    Gorsline, D.S.

    1991-12-31

    The California Continental Borderland`s present configuration dates from about 4 to 5 X 10{sup 6} years Before Present (B.P.) and is the most recent of several configurations of the southern California margin that have evolved after the North America Plate over-rode the East Pacific Rise about 30 X 10{sup 6} years ago. The present morphology is a series of two to three northwest-southeast trending rows of depressions separated by banks and insular ridges. Two inner basins, Santa Monica and San Pedro, have been the site for the Department of Energy-funded California Basin Study (CaBS) Santa Monica and San Pedro Basins contain post-Miocene sediment thicknesses of about 2.5 and 1.5 km respectively. During the Holocene (past 10,000 years) about 10-12 m have accumulated. The sediment entered the basin by one or a combination of processes including particle infall (mainly as bioaggregates) from surface waters, from nepheloid plumes (surface, mid-depths and near-bottom), from turbidity currents, mass movements, and to a very minor degree direct precipitation. In Santa Monica Basin, during the last century, particle infall and nepheloid plume transport have been the most common processes. The former dominates in the central basin floor in water depths from 900 to 945 m. where a characteristic silt-clay with a typical mean diameter of about 0.006 mm, phi standard deviation.

  8. The diffuse endocrine system: from embryogenesis to carcinogenesis.

    Science.gov (United States)

    Montuenga, Luis M; Guembe, Laura; Burrell, M Angela; Bodegas, M Elena; Calvo, Alfonso; Sola, Jesús J; Sesma, Pilar; Villaro, Ana C

    2003-01-01

    In the present review we will summarise the current knowledge about the cells comprising the Diffuse Endocrine System (DES) in mammalian organs. We will describe the morphological, histochemical and functional traits of these cells in three major systems gastrointestinal, respiratory and prostatic. We will also focus on some aspects of their ontogeny and differentiation, as well as to their relevance in carcinogenesis, especially in neuroendocrine tumors. The first chapter describes the characteristics of DES cells and some of their specific biological and biochemical traits. The second chapter deals with DES in the gastrointestinal organs, with special reference to the new data on the differentiation mechanisms that leads to the appearance of endocrine cells from an undifferentiated stem cell. The third chapter is devoted to DES of the respiratory system and some aspects of its biological role, both, during development and adulthood. Neuroendocrine hyperplasia and neuroendocrine lung tumors are also addressed. Finally, the last chapter deals with the prostatic DES, discussing its probable functional role and its relevance in hormone-resistant prostatic carcinomas.

  9. Volcanism Studies: Final Report for the Yucca Mountain Project

    Energy Technology Data Exchange (ETDEWEB)

    Bruce M. Crowe; Frank V. Perry; Greg A. Valentine; Lynn M. Bowker

    1998-12-01

    This report synthesizes the results of volcanism studies conducted by scientists at the Los Alamos National Laboratory and collaborating institutions on behalf of the Department of Energy's Yucca Mountain Project. An assessment of the risk of future volcanic activity is one of many site characterization studies that must be completed to evaluate the Yucca Mountain site for potential long-term storage of high-level radioactive waste. The presence of several basaltic volcanic centers in the Yucca Mountain region of Pliocene and Quaternary age indicates that there is a finite risk of a future volcanic event occurring during the 10,000-year isolation period of a potential repository. Chapter 1 introduces the volcanism issue for the Yucca Mountain site and provides the reader with an overview of the organization, content, and significant conclusions of this report. The risk of future basaltic volcanism is the primary topic of concern including both events that intersect a potential repository and events that occur near or within the waste isolation system of a repository. Future volcanic events cannot be predicted with certainty but instead are estimated using formal methods of probabilistic volcanic hazard assessment (PVHA). Chapter 2 describes the volcanic history of the Yucca Mountain region (YMR) and emphasizes the Pliocene and Quaternary volcanic record, the interval of primary concern for volcanic risk assessment. The distribution, eruptive history, and geochronology of Plio-Quaternary basalt centers are described by individual center emphasizing the younger postcaldera basalt (<5 Ma). The Lathrop Wells volcanic center is described in detail because it is the youngest basalt center in the YMR. The age of the Lathrop Wells center is now confidently determined to be about 75 thousand years old. Chapter 3 describes the tectonic setting of the YMR and presents and assesses the significance of multiple alternative tectonic models. The Crater Flat volcanic zone is

  10. Volcanism Studies: Final Report for the Yucca Mountain Project

    Energy Technology Data Exchange (ETDEWEB)

    Bruce M. Crowe; Frank V. Perry; Greg A. Valentine; Lynn M. Bowker

    1998-12-01

    This report synthesizes the results of volcanism studies conducted by scientists at the Los Alamos National Laboratory and collaborating institutions on behalf of the Department of Energy's Yucca Mountain Project. An assessment of the risk of future volcanic activity is one of many site characterization studies that must be completed to evaluate the Yucca Mountain site for potential long-term storage of high-level radioactive waste. The presence of several basaltic volcanic centers in the Yucca Mountain region of Pliocene and Quaternary age indicates that there is a finite risk of a future volcanic event occurring during the 10,000-year isolation period of a potential repository. Chapter 1 introduces the volcanism issue for the Yucca Mountain site and provides the reader with an overview of the organization, content, and significant conclusions of this report. The risk of future basaltic volcanism is the primary topic of concern including both events that intersect a potential repository and events that occur near or within the waste isolation system of a repository. Future volcanic events cannot be predicted with certainty but instead are estimated using formal methods of probabilistic volcanic hazard assessment (PVHA). Chapter 2 describes the volcanic history of the Yucca Mountain region (YMR) and emphasizes the Pliocene and Quaternary volcanic record, the interval of primary concern for volcanic risk assessment. The distribution, eruptive history, and geochronology of Plio-Quaternary basalt centers are described by individual center emphasizing the younger postcaldera basalt (<5 Ma). The Lathrop Wells volcanic center is described in detail because it is the youngest basalt center in the YMR. The age of the Lathrop Wells center is now confidently determined to be about 75 thousand years old. Chapter 3 describes the tectonic setting of the YMR and presents and assesses the significance of multiple alternative tectonic models. The Crater Flat volcanic zone is

  11. Barrow Black Carbon Source and Impact Study Final Campaign Report

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, Tate

    2014-07-01

    The goal of the Barrow Black Carbon Source and Impact campaign was to characterize the concentration and isotopic composition of carbonaceous atmospheric particulate matter (PM) at the Atmospheric Radiation Measurement (ARM) Climate Research Facility site in Barrow, Alaska. The carbonaceous component was characterized by measuring the organic and black carbon (OC and BC) components of the total PM. To facilitate complete characterization of the PM, filter-based collections were used, including a medium volume PM2.5 sampler and a high volume PM10 sampler. Thirty-eight fine PM fractions (PM2.5) and 49 coarse (PM10) PM fractions were collected at weekly and bi-monthly intervals. The PM2.5 sampler operated with minimal maintenance during the 12 month campaign. The PM10 sampler used for the Barrow Black Carbon Source and Impact (BBCSI) study used standard Tisch “hi-vol” motors that have a known lifetime of approximately 1 month under constant use; this necessitated monthly maintenance, and it is suggested that, for future deployment in the Arctic, the motors be upgraded to industrial blowers. The BBCSI sampling campaign successfully collected and archived 87 ambient atmospheric PM samples from Barrow, Alaska, from July 2012 to June 2013. Preliminary analysis of the OC and BC concentrations has been completed. This campaign confirmed known trends of high BC lasting from the winter through to spring haze periods and low BC concentrations in the summer. However, the annual OC concentrations had a very different seasonal pattern with the highest concentrations during the summer, lowest concentrations during the fall, and increased concentrations during the winter and spring (Figure 1).

  12. Oxidative stress and inflammation in liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Natalia Olaya

    2007-02-01

    series of transcription factors. Moreover, in addition to direct production of ROS by these pathogens, liver infiltration by activated phagocytic cells provides an additional source of ROS production that promotes oxidative stress via interleukin or NO production that can damage proteins, lipids and DNA.

    Nuclear MSI was demonstrated first in familial hereditary colorectal cancer (HNPCC and then in sporadic cancers, primarily digestive tract cancers such as colorectal, gastric and pancreatic cancers.In HCC, although nuclear MSI has been shown in some studies (15,18, there is as yet no direct evidence of alteration of the MMR genes and the biological and the clinicopathological significance of the lowlevel MSI seen in HCC is unclear. MSI has also been shown to occur in inflammatory tissues such as chronic hepatitis and cirrhosis as well as in ulcerative colitis, chronic pancreatitis and in non digestive inflammatory diseases such as rheumatoid arthritis.

    Recently, the role of mitochondria in carcinogenesis has been under numerous investigation, in part because their prominent role in apoptosis, ROS production and other aspects of tumour biology. The mitochondrial genome is particularly susceptible to mutations because of the high level of ROS generation in this organelle, coupled with a relatively low level of DNA repair. Somatic mutations of mitochondrial DNA (mtDNA have been shown in HCC as was also observed MSI. These findings suggest a potential role for mitochondrial genome instability in the early steps of tumorigenesis.

    Ischemia-reperfusion injury can occur in several situations and is a major cause of cell damage during surgery. Cells and tissues subjected to hypoxia by prolonged ischemia become acidic

  13. Cell Selection as Driving Force in Lung and Colon Carcinogenesis

    OpenAIRE

    Schöllnberger, Helmut; Beerenwinkel, Niko; Hoogenveen, Rudolf; Vineis, Paolo

    2010-01-01

    Carcinogenesis is the result of mutations and subsequent clonal expansions of mutated, selectively advantageous cells. To investigate the relative contributions of mutation versus cell selection in tumorigenesis, we compared two mathematical models of carcinogenesis in two different cancer types: lung and colon. One approach is based on a population genetics model, the Wright-Fisher process, whereas the other approach is the two-stage clonal expansion model. We compared the dynamics of tumori...

  14. Genomic Instability and Colon Carcinogenesis: From the Perspective of Genes

    OpenAIRE

    RAO, CHINTHALAPALLY V.; Yamada, Hiroshi Y.

    2013-01-01

    Colon cancer is the second most lethal cancer; approximately 600,000 people die of it annually in the world. Colon carcinogenesis generally follows a slow and stepwise process of accumulation of mutations under the influence of environmental and epigenetic factors. To adopt a personalized (tailored) cancer therapy approach and to improve current strategies for prevention, diagnosis, prognosis, and therapy overall, advanced understanding of molecular events associated with colon carcinogenesis...

  15. 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.

  16. 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.

  17. Wnt signaling and colon carcinogenesis: Beyond APC

    Directory of Open Access Journals (Sweden)

    Rani Najdi

    2011-01-01

    Full Text Available Activation of the Wnt signaling pathway via mutation of the adenomatous polyposis coli gene (APC is a critical event in the development of colon cancer. For colon carcinogenesis, however, constitutive signaling through the canonical Wnt pathway is not a singular event. Here we review how canonical Wnt signaling is modulated by intracellular LEF/TCF composition and location, the action of different Wnt ligands, and the secretion of Wnt inhibitory molecules. We also review the contributions of non-canonical Wnt signaling and other distinct pathways in the tumor micro environment that cross-talk to the canonical Wnt pathway and thereby influence colon cancer progression. These ′non-APC′ aspects of Wnt signaling are considered in relation to the development of potential agents for the treatment of patients with colon cancer. Regulatory pathways that influence Wnt signaling highlight how it might be possible to design therapies that target a network of signals beyond that of APC and β-catenin.

  18. NTP Toxicology and Carcinogenesis Studies of Oleic Acid Diethanolamine Condensate (CAS No. 93-83-4) in F344/N Rats and B6C3F1 Mice (Dermal Studies).

    Science.gov (United States)

    1999-07-01

    Oleic acid diethanolamine condensate is widely used as an emollient, thickener, and foam stabilizer present in cosmetic formulations of bath additives, shampoos, conditioners, lipsticks, and hair dyes. Male and female F344/N rats and B6C3F1 mice received dermal applications of diethanolamine in 95% ethanol for 13 weeks or 2 years. Genetic toxicology studies were performed in Salmonella typhimurium and L5178Y mouse lymphoma cells. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were admin istered 0, 25, 50, 100, 200, or 400 mg oleic acid diethanolamine condensate/kg body weight in ethanol dermally for 13 weeks. All male and female rats survived until the end of the study. The final mean body weights and body weight gains of 200 and 400 mg/kg males and the mean body weight gain of 400 mg/kg females were significantly less than those of the vehicle controls. The only chemical-related clinical finding was irritation of the skin at the site of application in most males administered 100 mg/kg or greater and in all females administered 50 mg/kg or greater. Segmented neutrophil counts were increased relative to the vehicle controls in the 400 mg/kg male group on days 5 and 19, in the 200 mg/kg female group on day 19 and at week 13, and in the 400 mg/kg female group on days 5 and 19 and at week 13. Alkaline phosphatase concentrations were significantly increased in the 200 mg/kg male group on day 19, the 200 mg/kg female group at week 13, and in the 400 mg/kg groups of males and females at week 13. Kidney weights of 200 and 400 mg/kg females were significantly greater than those of the vehicle controls. Lesions of the skin at the site of application included epidermal hyperplasia, parakeratosis, chronic active dermal inflammation, suppurative epidermal inflammation, and sebaceous gland hypertrophy in dosed rats. The severities of these lesions generally increased with increasing dose. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were admin istered

  19. NTP Toxicology and Carcinogenesis Studies of Lauric Acid Diethanolamine Condensate (CAS NO. 120-40-1) in F344/N Rats and B6C3F1 Mice (Dermal Studies).

    Science.gov (United States)

    1999-07-01

    Lauric acid diethanolamine condensate is widely used in cosmetics, shampoos, soaps, and related consumer products, to which there is extensive human exposure. Because of the lack of information about potential risks associated with long-term exposure, lauric acid diethanolamine condensate, coconut oil acid diethanolamine condensate, and oleic acid diethanolamine condensate were selected as representative of the class of diethanolamides for evaluation of prechronic toxicity and carcinogenic potential. Male and female F344/N rats and B6C3F1 mice were exposed to lauric acid diethanolamine condensate dermally for 14 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, and mouse peripheral blood erythrocytes. 14-WEEK STUDY IN RATS: Groups of 10 male and 10 female rats were admin istered 0, 25, 50, 100, 200, or 400 mg lauric acid diethanolamine condensate/kg body weight in ethanol by dermal application for 14 weeks. All animals survived until study termination. Final mean body weights and body weight gains of males receiving 200 or 400 mg/kg were significantly less than those of the vehicle control group. Irritation of the skin at the site of application was observed in males receiving 100 mg/kg or greater and in females receiving 200 or 400 mg/kg. Kidney weights of females administered 200 or 400 mg/kg were significantly greater than those of the vehicle control group. There were dose-dependent increases in the incidences of nonneoplastic lesions of the skin at the site of application, including epidermal and sebaceous gland hyperplasia, chronic inflammation, parakeratosis, and ulcer. 14-WEEK STUDY IN MICE: Groups of 10 male and 10 female mice were admin istered 0, 50, 100, 200, 400, or 800 mg lauric acid diethanolamine condensate/kg body weight in ethanol by dermal application for 14 weeks. All animals survived until the end of the study, and final mean body weights and

  20. NTP Toxicology and Carcinogenesis Studies of Gallium Arsenide (CAS No. 1303-00-0) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

    Science.gov (United States)

    2000-09-01

    Gallium arsenide is used primarily to make light- emitting diodes, lasers, laser windows, and photodetectors and in the photoelectronic transmission of data through optical fibers. Gallium arsenide was nominated for study because of its widespread use in the microelectronics industry, the potential for worker exposure, and the absence of chronic toxicity data. Male and female F344/N rats and B6C3F1 mice were exposed to gallium arsenide particles (greater than 98% pure; mass median aerodynamic diameter = 0.8 to 1.0 &mgr;m) by inhalation for 16 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, and the frequency of micronuclei was determined in the peripheral blood of mice exposed to gallium arsenide for 14 weeks. 16-DAY STUDY IN RATS: Groups of five male and five female rats were exposed to particulate aerosols of gallium arsenide with a mass median aerodynamic diameter of approximately 1 &mgr;m at concentrations of 0, 1, 10, 37, 75, or 150 mg/m(3) by inhalation, 6 hours per day, 5 days per week, for 16 days. All rats survived to the end of the study. The final mean body weights of all exposed groups of males and females were similar to those of the chamber controls. Compared to chamber controls, the liver and lung weights of males exposed to 1 mg/m(3) or greater and females exposed to 10 mg/m(3) or greater were increased; the thymus weights of all exposed groups of males were decreased. Gallium arsenide particles were visible in the alveolar spaces and, to a lesser extent, within alveolar macrophages of exposed rats. Moderate proteinosis (surfactant mixed with small amounts of fibrin) and minimal histiocytic cellular infiltrate were observed in the alveoli of exposed males and females. Epithelial hyperplasia and squamous metaplasia of the larynx were observed primarily in males exposed to 150 mg/m(3). 16-DAY STUDY IN MICE: Groups of five male and four or five female mice were exposed to particulate aerosols of gallium

  1. Climate Change Vulnerability Assessments: Four Case Studies of Water Utility Practices (2011 Final)

    Science.gov (United States)

    EPA has released the final report titled, Climate Change Vulnerability Assessments: Four Case Studies of Water Utility Practices. This report was prepared by the National Center for Environmental Assessment's Global Climate Research Staff in the Office of Research and D...

  2. 75 FR 77897 - Long Walk National Historic Trail Feasibility Study, Abbreviated Final Environmental Impact...

    Science.gov (United States)

    2010-12-14

    ... trail would be designated, emphasizing the removal experiences common to both tribes. An auto tour route... National Park Service Long Walk National Historic Trail Feasibility Study, Abbreviated Final Environmental Impact Statement, National Trails Intermountain Region, NM AGENCY: National Park Service,...

  3. A molecular-genetic approach to studying source-sink interactions in Arabidopsis thalian. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, S. I.

    2000-06-01

    This is a final report describing the results of the research funded by the DOE Energy Biosciences Program grant entitled ''A Molecular-Genetic Approach to Studying Source-Sink Interactions in Arabidiopsis thaliana''.

  4. Master plan study - District heating Sillamaee municipality. Estonia. Final report. Appendices for chapter 9

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The appendices to the final report on the master plan study on district heating in the municipality in Estonia, chapter nine, gives data related to general economic assumptions for financial and economic calculations, fuel consumption, financing, prices, fuel consumption. (ARW)

  5. JAK-STAT pathway in carcinogenesis: Is it relevant to cholangiocarcinoma progression?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The features of JAK-STAT signaling in liver cells are discussed in the current review. The role of this signaling cascade in carcinogenesis is accentuated. The possible involvement of this pathway and alteration of its elements are compared for normal cholangiocytes,cholangiocarcinoma predisposition and development.Prolactin and interleukin-6 are described in detail as the best studied examples. In addition, the non-classical nuclear translocation of cytokine receptors is discussed in terms of its possible implication to cholangiocarcinoma development.

  6. Chemomodulatory Potential of Flaxseed Oil Against DMBA/Croton Oil-Induced Skin Carcinogenesis in Mice.

    Science.gov (United States)

    Sharma, Jyoti; Singh, Ritu; Goyal, P K

    2016-09-01

    The present study was conducted to evaluate the potential of flaxseed oil to prevent chemically induced skin cancer in mice. Cancer was induced on 2-stage skin carcinogenesis model by single topical application of 7,12 dimethylbenz [a]anthracene (DMBA), as, initiator, and two weeks later it was promoted by croton oil treatment thrice a week on the dorsal surface of mice for 16 weeks. Flaxseed oil (FSO; 100µL/animal/d) was orally administered 1 week before and 1 week after DMBA application (Peri-initiation stage). The animals of the FSO-administered group showed a significant reduction in tumor incidence (76.67%), cumulative number of tumors (37), tumor yield (3.7), and tumor burden (4.81) when compared with the carcinogen-treated control animals. Biochemical parameters in skin and liver tissue such as LPO and phase I enzymes were significantly (P croton oil-induced skin carcinogenesis in mice.

  7. 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.

  8. Histone acetyltransferases and deacetylases: molecular and clinical implications to gastrointestinal carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Wei-Jian Sun; Xiang Zhou; Ji-Hang Zheng; Ming-Dong Lu; Jian-Yun Nie; Xiang-Jiao Yang; Zhi-Qiang Zheng

    2012-01-01

    Histone acetyltransferases and deacetylases are two groups of enzymes whose opposing activities govern the dynamic levels of reversible acetylation on specific lysine residues of histones and many other proteins.Gastrointestinal (GI) carcinogenesis is a major cause of morbidity and mortality worldwide.In addition to genetic and environmental factors,the role of epigenetic abnormalities such as aberrant histone acetylation has been recognized to be pivotal in regulating benign tumorigenesis and eventual malignant transformation.Here we provide an overview of histone acetylation,list the major groups of histone acetyltransferases and deacetylases,and cover in relatively more details the recent studies that suggest the links of these enzymes to GI carcinogenesis.As potential novel therapeutics for GI and other cancers,histone deacetylase inhibitors are also discussed.

  9. Apoptotic cell death and its relationship to gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Ferda Bir; Nese Calli-Demirkan; A Cevik Tufan; Metin Akbulut; N Lale Satiroglu-Tufan

    2007-01-01

    AIM: To investigate the apoptotic process of cells within the intestinal metaplasia areas co-localizing with chronic gastritis and gastric carcinomas and to analyze the involvement of proteins regulating apoptosis in the process of intestinal metaplasia related gastric carcinogenesis.METHODS: Forty-two gastric carcinoma and seventeen chronic gastritis cases were included in this study. All cases were examined for the existence of intestinal metaplasia. Ten cases randomly selected from each group were processed for TUNEL assay. TUNEL positive cells within the intestinal metaplasia areas, colocalizing either to gastric carcinoma or chronic gastritis,were counted and converted to apoptotic indices.In addition, p53, bcl-2 and bax expression patterns within these tissues were analyzed on the basis of immunohistochemistry.RESULTS: Twenty-eight of the cases were intestinal and 14 of the cases were diffuse type adenocarcinomas.64% (27/42) of the gastric carcinoma cases had intestinal metaplasia. Intestinal metaplasia co-localized more with intestinal type carcinomas compared with diffuse type carcinomas [75% (21/28) vs 42% (6/14),respectively; P≤0.05]. The mean apoptotic index in tumor cells was 0.70±0.08. The mean apoptotic index in intestinal metaplasias co-localizing to tumors was significantly higher than that of intestinal metaplasias co-localizing to chronic gastritis (0.70±0.03 vs 0.09±0.01, respectively; P≤0.05). P53 positivity was not observed in areas of intestinal metaplasia adjacent to tumors or chronic gastritis. Intestinal metaplasia areas adjacent to tumors showed lower cytoplasmic bcl-2 positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [55.5% (15/27) vs 70.5%(12/17), respectively]. On the other hand, intestinal metaplasia areas adjacent to tumors showed significantly higher cytoplasmic bax positivity compared to intestinal metaplasia areas adjacent to chronic gastritis [44.4%(12/27) vs 11.7% (2/17), respectively; P≤0

  10. 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.

  11. Peroxisome proliferator-activated receptor γ ligands suppress liver carcinogenesis induced by diethylnitrosamine in rats

    Institute of Scientific and Technical Information of China (English)

    Yan-Tong Guo; Xi-Sheng Leng; Tao Li; Jing-Ming Zhao; Xi-Hou Lin

    2004-01-01

    AIM: Peroxisome proliferator-activated receptor γ (PPARγ)is known to regulate growth arrest and terminal differentiation of adipocytes and is used clinically as a new class of antidiabetic drugs. Recently, several studies have reported that treatment of cancer cells with PPARγ ligands could induce cell differentiation and apoptosis, suggesting a potential application as chemopreventive agents against carcinogenesis. In the present study, 3 different kinds of PPARγ ligands were subjected to the experiments to confirm their suppressive effects on liver carcinogenesis.METHODS: Three PPARγ ligands, pioglitazone (Pio) (200 ppm),rosiglitazone (Rosi) (200 ppm), and troglitazone (Tro)(1 000 ppm) were investigated on the induction of the placental form of rat glutathione S-transferase (rGST P)positive foci, a precancerous lesion of the liver, and liver cancer formation using a diethylnitrosamine-induced liver cancer model in Wistar rats, and dose dependency of a PPARγ ligand was also examined.RESULTS: PPARγ ligands reduced the formation of rGST P-positive foci by diethylnitrosamine and induction of liver cancers was also markedly suppressed by a continuous feeding of Pio at 200 ppm.CONCLUSION: PPARγ ligands are potential chemopreventive agents for liver carcinogenesis.

  12. Senescence and apoptosis in carcinogenesis of cervical squamous carcinoma.

    Science.gov (United States)

    Feng, Wei; Xiao, Jianguo; Zhang, Zhihong; Rosen, Daniel G; Brown, Robert E; Liu, Jinsong; Duan, Xiuzhen

    2007-09-01

    Senescence and apoptosis are two key mechanisms that protect against cancer development. Many cell cycle regulators, such as p14(ARF), p15(INK4b) and p16(INK4a), are important in G1 cell cycle arrest and oncogene-induced senescence. The bcl-2 protein is one of the key components that control apoptosis, while the p53 protein plays key roles in both mechanisms. The genes of these key regulator proteins are often mutated or deleted in various malignancies. It is unknown how senescence and apoptosis are regulated in one of the most common tumors of the female genital tract, cervical squamous cell carcinoma (SCC). In this study the, expression of senescence, apoptosis and proliferation markers in normal cervical epithelium, cervical intraepithelial neoplasia (CIN) and SCC are characterized via immunohistochemical staining for p14(ARF), p15(INK4b), p16(INK4a), bcl-2, p53 and Ki-67 in tissue microarray blocks containing 20 samples each of normal cervix, moderate-to-severe cervical dysplasia (CIN II-III) and invasive SCC. Samples are derived from 60 total cases of cervical biopsies and cervical conizations. Results showed that the proliferation marker, Ki-67, is markedly increased, and the senescence markers, p15(INK4b), p16(INK4a) and p14(ARF) are overexpressed in both dysplasia and carcinoma. P53 immunostain is negative in all normal cervical tissue, and positive in dysplasia and carcinoma. Although the expression of bcl-2 is increased in dysplasia, this marker is negative in approximately half of SCC cases. These results suggest that some senescence pathways are activated and are still maintained in cervical dysplasia and carcinoma. However proliferation is increased and carcinogenesis is not thwarted, leading to eventual development of cervical cancer. Other mechanisms, such as those that account for the apparent overexpression of p53 and paradoxical loss of bcl-2 expression in some SCC cases, as well as additional senescence and apoptotic pathways, may play key roles

  13. Monitoring pancreatic carcinogenesis by the molecular imaging of cathepsin E in vivo using confocal laser endomicroscopy.

    Directory of Open Access Journals (Sweden)

    Hui Li

    Full Text Available The monitoring of pancreatic ductal adenocarcinoma (PDAC in high-risk populations is essential. Cathepsin E (CTSE is specifically and highly expressed in PDAC and pancreatic intraepithelial neoplasias (PanINs, and its expression gradually increases along with disease progression. In this study, we first established an in situ 7,12-dimethyl-1,2-benzanthracene (DMBA-induced rat model for PanINs and PDAC and then confirmed that tumorigenesis properties in this model were consistent with those of human PDAC in that CTSE expression gradually increased with tumor development using histology and immunohistochemistry. Then, using in vivo imaging of heterotopically implanted tumors generated from CTSE- overexpressing cells (PANC-1-CTSE in nude mice and in vitro imaging of PanINs and PDAC in DMBA-induced rats, the specificity of the synthesized CTSE-activatable probe was verified. Quantitative determination identified that the fluorescence signal ratio of pancreatic tumor to normal pancreas gradually increased in association with progressive pathological grades, with the exception of no significant difference between PanIN-II and PanIN-III grades. Finally, we monitored pancreatic carcinogenesis in vivo using confocal laser endomicroscopy (CLE in combination with the CTSE-activatable probe. A prospective double-blind control study was performed to evaluate the accuracy of this method in diagnosing PDAC and PanINs of all grades (>82.7%. This allowed us to establish effective diagnostic criteria for CLE in PDAC and PanINs to facilitate the monitoring of PDAC in high-risk populations.

  14. Inflammation-Related Carcinogenesis and Prevention in Esophageal Adenocarcinoma Using Rat Duodenoesophageal Reflux Models

    Energy Technology Data Exchange (ETDEWEB)

    Fujimura, Takashi, E-mail: tphuji@staff.kanazawa-u.ac.jp; Oyama, Katsunobu; Sasaki, Shozo; Nishijima, Koji; Miyashita, Tomoharu; Ohta, Tetsuo [Gastroenterologic Surgery, Kanazawa University Hospital, Kanazawa, Japan, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641 (Japan); Koichi, Miwa [Houju Memorial Hospital, Nomi, Japan, 11-71 Midorigaoka, Nomi, Ishikawa 923-1226 (Japan); Takanori, Hattori [Division of Molecular and Diagnostic Pathology, Shiga University of Medical Science, Otsu, Japan, Seta Tsukinowa-cho, Otsu, Shiga 520-2192 (Japan)

    2011-08-10

    Development from chronic inflammation to Barrett's adenocarcinoma is known as one of the inflammation-related carcinogenesis routes. Gastroesophageal reflux disease induces regurgitant esophagitis, and esophageal mucosa is usually regenerated by squamous epithelium, but sometimes and somewhere replaced with metaplastic columnar epithelium. Specialized columnar epithelium, so-called Barrett's epithelium (BE), is a risk factor for dysplasia and adenocarcinoma in esophagus. Several experiments using rodent model inducing duodenogastroesophageal reflux or duodenoesophageal reflux revealed that columnar epithelium, first emerging at the proliferative zone, progresses to dysplasia and finally adenocarcinoma, and exogenous carcinogen is not necessary for cancer development. It is demonstrated that duodenal juice rather than gastric juice is essential to develop esophageal adenocarcinoma in not only rodent experiments, but also clinical studies. Antireflux surgery and chemoprevention by proton pump inhibitors, nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, green tea, retinoic acid and thioproline showed preventive effects on the development of Barrett's adenocarcinoma in rodent models, but it remains controversial whether antireflux surgery could regress BE and prevent esophageal cancer in clinical observation. The Chemoprevention for Barrett's Esophagus Trial (CBET), a phase IIb, multicenter, randomized, double-masked study using celecoxib in patients with Barrett's dysplasia failed to prove to prevent progression of dysplasia to cancer. The AspECT (Aspirin Esomeprazole Chemoprevention Trial), a large multicenter phase III randomized trial to evaluate the effects of esomeprazole and/or aspirin on the rate of progression to high-grade dysplasia or adenocarcinoma in patients with BE is now ongoing.

  15. Influence of caloric intake on experimental carcinogenesis: a review.

    Science.gov (United States)

    Kritchevsky, D; Klurfeld, D M

    1986-01-01

    The effect of caloric intake on tumor growth has been recognized for over 70 years. Inhibition of tumor growth depends primarily on the extent of caloric restriction, but tumor type, animal strain, and dietary composition all exert some influence. Caloric restriction is most effective when maintained during both initiation and promotion, but if limited to one of these phases, restriction during promotion appears to be the more effective modality. The types of tumor that have been studied include spontaneous mammary and lung tumors as well as tumors induced by organ-specific carcinogens or irradiation with ultraviolet light. Numerous investigators have studied the effects of fat, and a diet low in calories but high in fat is generally significantly more effective in inhibiting carcinogenesis than is a diet high in calories but low in fat. Mice fed high fat, low calorie diets exhibited 48% fewer chemically induced skin tumors and 61% fewer tumors induced by ultraviolet irradiation than did mice fed low fat, high calorie diets. Mice fed a diet containing 2% fat exhibited a 66% incidence of skin tumors, whereas mice fed an isocaloric diet containing 61% fat showed a 78% incidence. Rats whose diet was restricted in calories by 40% exhibited no mammary tumors (coconut oil as primary dietary fat) or 75% fewer tumors (corn oil as dietary fat) compared to ad libitum-fed controls; they also exhibited 47% fewer colonic tumors. The mechanism by which caloric restriction exerts its tumor-inhibiting effects remains to be elucidated.

  16. 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.

  17. Type 2 Diabetes Mellitus and Its Association with the Risk of Pancreatic Carcinogenesis: A Review.

    Science.gov (United States)

    Biadgo, Belete; Abebe, Molla

    2016-04-25

    The prevalence of diabetes mellitus (DM) and associated diseases such as cancers are substantially increasing worldwide. About 80% of the patients with pancreatic cancer have glucose metabolism alterations. This suggests an association between type 2 DM and pancreatic cancer risk and progression. There are hypotheses that show metabolic links between the diseases, due to insulin resistance, hyperglycemia, hyperinsulinemia, low grade chronic inflammation, and alteration in the insulin-insulin-like growth factor axis. The use of diabetes medications can influence the extent of carcinogenesis of the pancreas. This study briefly reviews recent literature on investigation of metabolic link of type 2 DM, risk of carcinogenesis of the pancreas and their association, as well as the current understanding of metabolic pathways implicated in metabolism and cellular growth. The main finding of this review, although there are discrepancies, is that according to most research long-term DM does not raise the risk of pancreatic cancer. The longest duration of DM may reflect hypoinsulinemia due to treatment for hyperglycemia, but recent onset diabetes was associated with increased risk for pancreatic cancer due to hyperinsulinemia and hyperglycemia. In conclusion, the review demonstrates that type 2 DM and the duration of diabetes pose a risk for pancreatic carcinogenesis, and that there is biological link between the diseases.

  18. Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by azoxymethane in mice

    Institute of Scientific and Technical Information of China (English)

    Tamao Nishihara; Shinji Tamura; Norio Hayashi; Hiroyasu Iishi; Iichiro Shimornura; Miyako Baba; Morihiro Matsuda; Masahiro Inoue; Yasuko Nishizawa; Atsunori Fukuhara; Hiroshi Arald; Shinji Kihara; Tohru Funahashi

    2008-01-01

    AIM: To investigate the causal relationship between hypoadiponectinemia and colorectal carcinogenesis in in vivo experimental model, and to determine the con-tribution of adiponectin deficiency to colorectal cancer development and proliferation. METHODS: We examined the influence of adiponectin deficiency on colorectal carcinogenesis induced by the administration of azoxymethane (AOM) (7.5 mg/kg, in-traperitoneal injection once a week for 8 wk), by using adiponectin-knockout (KO) mice. RESULTS: At 53 wk after the first AOM treatment, KOmice developed larger and histologically more progres-sive colorectal tumors with greater frequency com-pared with wild-type (WT) mice, although the tumor incidence was not different between WT and KO mice. KO mice showed increased cell proliferation of colorec-tal tumor cells, which correlated with the expression levels of cyclooxygenase-2 (COX-2) in the colorectal tumors. In addition, KO mice showed higher incidence and frequency of liver tumors after AOI treatment. Thirteen percent of WT mice developed liver tumors, and these WT mice had only a single tumor. In contrast, 50% of K.O mice developed liver tumors, and 58% of these KO mice had multiple tumors. CONCLUSION: Adiponectin deficiency enhances colorectal carcinogenesis and liver tumor formation induced by AOM in mice. This study strongly suggests that hypoadiponectinemia could be involved in the pathogenesis for colorectal cancer and liver tumor in human subjects.

  19. Effect of Cu supplementation on genomic instability in chemically-induced mammary carcinogenesis in the rat

    Directory of Open Access Journals (Sweden)

    Bobrowska Barbara

    2011-12-01

    Full Text Available Abstract Backround The aim of the present study was to assess the effect of dietary supplementation (copper or copper and resveratrol on the intensity of carcinogenesis and the frequency of microsatellite instability in a widely used model of mammary carcinogenesis induced in the rat by treatment with 7,12-dimethylbenz[a]anthracene (DMBA. Methods DNA was extracted from rat mammary cancers and normal tisues, amplified by PCR, using different polymorphic DNA markers and the reaction products were analyzed for microsatellite instability. Results It was found that irrespectively of the applied diet there was no inhibition of mammary carcinogenesis in the rats due to DMBA. Besides, in the groups supplemented with Cu (II or Cu (II and resveratrol the tumor formation was clearly accelerated. Unlike the animals that were fed with standard diet, the supplemented rats were characterized by the loss of heterozygosity of microsatellite D3Mgh9 in cancer tumors (by respectively 50 and 40%. When the animals received Cu (II and resveratrol supplemented diet the occurrence of genomic instability was additionally found in their livers in the case of microsatellite D1Mgh6 (which was stable in the animals without dietary supplementation. Conclusions Identification of the underlying mechanisms by which dietary factors affect genomic stability might prove useful in the treatment of mammary cancer as well as in the incorporation of dietary factors into mammary cancer prevention strategies.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Tveit Kjell M

    2011-02-01

    Full Text Available Abstract Background Compromised epithelial barriers are found in dysplastic tissue of the gastrointestinal tract. Claudins are transmembrane proteins important for tight junctions. Claudins regulate the paracellular transport and are crucial for maintaining a functional epithelial barrier. Down-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. Methods The mRNA level of claudin-7 (CLDN7 was determined in samples from 18 healthy individuals, 100 individuals with dysplasia and 121 colorectal cancer patients using quantitative real time RT-PCR. In addition, immunohistochemical stainings were performed on colorectal adenomas and carcinomas, to confirm the mRNA findings. Results A 2.7-fold reduction in the claudin-7 mRNA level was found when comparing the biopsies from healthy individuals with the biopsies of carcinomas (p claudin-7 mRNA levels were also detected in mild/moderate dysplasia (p Conclusions Our results show that the claudin-7 mRNA level is decreased already as an early event in colorectal carcinogenesis, probably contributing to the compromised epithelial barrier in adenomas.

  2. Causal role of Helicobacter pylori infection and eradication therapy in gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Masanori Ito; Shinji Tanaka; Tomoari Kamada; Ken Haruma; Kazuaki Chayama

    2006-01-01

    Many epidemiological reports indicate that Helicobacter pylori(H pylori) infection plays an important role in gastric carcinogenesis. Several genetic and epigenetic alterations contribute to the initiation, promotion, and progression of the cancer cells in a multi-step manner.H pyloriis known to induce chronic inflammation in the gastric mucosa. Its products, including superoxides,participate in the DNA damage followed by initiation, and the inflammation-derived cytokines and growth factors contribute to the promotion of gastric carcinogenesis.By eradicating H pylori, gastric inflammation can be cured; the therapy diminishes the levels not only of inflammatory cell infiltration, but also atrophyl intestinal metaplasia in part. A randomized controlled trial revealed that the eradication therapy diminished the gastric cancer prevalence in cases without precancerous conditions. In addition, recent epidemiological studies from Japanese groups demonstrated that the development of gastric cancer, especially of the intestinal type, was decreased by successful eradication therapy, although these were designed in a nonrandomized manner. However, it should be mentioned that endoscopic detection is the only way to evaluate the degree of gastric carcinogenesis. We have reported that the endoscopic and histological morphologies could be modified by eradication therapy and it might contribute to the prevalence of gastric cancer development.Considering the biological nature of cancer cell proliferation, it is considered that a sufficiently long-term follow-up would be essential to discuss the anticancer effect of eradication therapy.

  3. Cohort profile of the Japan Collaborative Cohort Study at final follow-up.

    Science.gov (United States)

    Tamakoshi, Akiko; Ozasa, Kotaro; Fujino, Yoshihisa; Suzuki, Koji; Sakata, Kiyomi; Mori, Mitsuru; Kikuchi, Shogo; Iso, Hiroyasu; Sakauchi, Fumio; Motohashi, Yutaka; Tsuji, Ichiro; Nakamura, Yosikazu; Mikami, Haruo; Kurosawa, Michiko; Hoshiyama, Yoshiharu; Tanabe, Naohito; Tamakoshi, Koji; Wakai, Kenji; Tokudome, Shinkan; Hashimoto, Shuji; Wada, Yasuhiko; Kawamura, Takashi; Watanabe, Yoshiyuki; Miki, Tsuneharu; Date, Chigusa; Kurozawa, Yoichi; Yoshimura, Takesumi; Shibata, Akira; Okamoto, Naoyuki; Shio, Hideo

    2013-01-01

    The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was established in the late 1980s to evaluate the risk impact of lifestyle factors and levels of serum components on human health. During the 20-year follow-up period, the results of the study have been published in almost 200 original articles in peer-reviewed English-language journals. However, continued follow-up of the study subjects became difficult because of the retirements of principal researchers, city mergers throughout Japan in the year 2000, and reduced funding. Thus, we decided to terminate the JACC Study follow-up at the end of 2009. As a final point of interest, we reviewed the population registry information of survivors. A total of 207 (0.19%) subjects were ineligible, leaving 110 585 eligible participants (46 395 men and 64 190 women). Moreover, errors in coding date of birth and sex were found in 356 (0.32%) and 59 (0.05%) cases, respectively, during routine follow-up and final review. Although such errors were unexpected, their impact is believed to be negligible because of the small numbers relative to the large total study population. Here, we describe the final cohort profile at the end of the JACC Study along with selected characteristics of the participants and their status at the final follow-up. Although follow-up of the JACC Study participants is finished, we will continue to analyze and publish study results.

  4. 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 enl

  5. Melanoma: Stem cells, sun exposure and hallmarks for carcinogenesis, molecular concepts and future clinical implications

    Directory of Open Access Journals (Sweden)

    Kyrgidis Athanassios

    2010-01-01

    Full Text Available Background :The classification and prognostic assessment of melanoma is currently based on morphologic and histopathologic biomarkers. Availability of an increasing number of molecular biomarkers provides the potential for redefining diagnostic and prognostic categories and utilizing pharmacogenomics for the treatment of patients. The aim of the present review is to provide a basis that will allow the construction-or reconstruction-of future melanoma research. Methods: We critically review the common medical databases (PubMed, EMBASE, Scopus and Cochrane CENTRAL for studies reporting on molecular biomarkers for melanoma. Results are discussed along the hallmarks proposed for malignant transformation by Hanahan and Weinberg. We further discuss the genetic basis of melanoma with regard to the possible stem cell origin of melanoma cells and the role of sunlight in melanoma carcinogenesis. Results: Melanocyte precursors undergo several genome changes -UV-induced or not- which could be either mutations or epigenetic. These changes provide stem cells with abilities to self-invoke growth signals, to suppress anti-growth signals, to avoid apoptosis, to replicate without limit, to invade, proliferate and sustain angiogenesis. Melanocyte stem cells are able to progressively collect these changes in their genome. These new potential functions, drive melanocyte precursors to the epidermis were they proliferate and might cause benign nevi. In the epidermis, they are still capable of acquiring new traits via changes to their genome. With time, such changes could add up to transform a melanocyte precursor to a malignant melanoma stem cell. Conclusions : Melanoma cannot be considered a "black box" for researchers anymore. Current trends in the diagnosis and prognosis of melanoma are to individualize treatment based on molecular biomarkers. Pharmacogenomics constitute a promising field with regard to melanoma patients′ treatment. Finally, development of novel

  6. On the role of final-state interactions in Dalitz plot studies

    CERN Document Server

    Kubis, Bastian; Schneider, Sebastian P

    2011-01-01

    The study of Dalitz plots of heavy-meson decays to multi-hadron final states has received intensified interest by the possibility to gain access to precision investigations of CP violation. A thorough understanding of the hadronic final-state interactions is a prerequisite to achieve a highly sensitive, model-independent study of such Dalitz plots. We illustrate some of the theoretical tools, predominantly taken from dispersion theory, available for these and related purposes, and discuss the low-energy decays omega, phi --> 3pi in some more detail.

  7. NTP Toxicology and Carcinogenesis of 1,2,3-Trichloropropane (CAS No. 96-18-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

    Science.gov (United States)

    1993-08-01

    1,2,3-Trichloropropane is a colorless liquid used as a paint and varnish remover, solvent, and degreasing agent, and as a crosslinking agent in the synthesis of polysulfides and hexafluoropropylene. 1,2,3-Trichloropropane may be found as an impurity in certain nematocides and soil fumigants and as a contaminant of drinking and ground water. Studies on the toxic and carcinogenic effects of 1,2,3-trichloropropane were initiated because of the close structural relationship of this chemical to other short-chain halogenated compounds that were demonstrated to be carcinogenic in experimental animals, and because of the potential for human exposure. Toxicology and carcinogenicity studies were conducted by administering 1,2,3-trichloropropane (greater than 99% pure) in corn oil by gavage to groups of F344/N rats and B6C3FI mice for 17 weeks and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium strains, mouse lymphoma cells, and Chinese hamster ovary cells. 17-Week Studies: Groups of 20 male and 20 female rats received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg body weight 5 days per week for up to 17 weeks; 30 male and 30 female rats received corn oil alone and served as controls. Animals were evaluated at 8 or 17 weeks. All rats in the 250 mg/kg groups died by week 5. One male and four female rats in the 125 mg/kg groups died during the study. The mean body weight gains and final mean body weights of males receiving 63 mg/kg and of males and females receiving 125 mg/kg were lower than those of the controls. Hematocrit values, hemoglobin concentrations, and erythrocyte counts decreased with dose in males and females. Serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase activities were significantly increased in some female rats receiving 125 mg/kg. Serum pseudocholinesterase activity decreased with dose in females. Increases in kidney and liver weights were related

  8. Synchrotron Studies of Quantum Emergence in Non-Low Dimensional Materials Final Report

    Energy Technology Data Exchange (ETDEWEB)

    James W. Allen

    2011-08-26

    This document is the final report of research performed under U.S. DOE Award Number DE-FG02-07ER46379, entitled Synchrotron Studies of Quantum Emergence in Non-Low Dimensional Materials. It covers the full period of the award, from June 1, 2007 through May 31, 2011.

  9. Communication Skills in Standardized-Patient Assessment of Final-Year Medical Students: A Psychometric Study

    Science.gov (United States)

    Guiton, Gretchen; Hodgson, Carol S.; Delandshere, Ginett; Wilkerson, Luann

    2004-01-01

    The purpose of this study is to investigate the content-specificity of communication skills. It investigates the reliability and dimensionality of standardized patient (SP) ratings of communication skills in an Objective Structured Clinical Examination(OSCE) for final year medical students. An OSCE consisting of seven standardized patient(SP)…

  10. Nanomaterial Case Studies: Nanoscale Titanium Dioxide in Water Treatment and in Topical Sunscreen (Final)

    Science.gov (United States)

    EPA announced the availability of the final report, Nanomaterial Case Studies: Nanoscale Titanium Dioxide in Water Treatment and in Topical Sunscreen. This report is a starting point to determine what is known and what needs to be known about selected nanomaterials as par...

  11. Master plan study - District heating Sillamaee municipality. Estonia. Final report. Appendices for chapter 7

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The appendices to the final report on the master plan study on the cogenerating district heating system in the municipality of Sillamae (Estonia) gives technical and costs data on existing conditions and on possible new facilities. The data relates to energy output, the energy budget, heat load duration curves, and to suggestions for improvement. (ARW)

  12. 细胞周期调控因子与喉癌癌变的相关性研究%Study on the relation between the cell cycle regulators and laryngeal carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    王建波; 娄卫华; 董明敏

    2001-01-01

    目的:探讨喉癌癌变过程中CyclinE、p21WAF1/CIP1和p53表达的临床病理学意义。方法:用免疫组化检测20例喉正常粘膜、40例喉不典型增生病变和60例喉癌组织中CyclinE、p21WAF1/CIP1和p53的表达。结果:①CyclinE阳性表达率在正常组、不典型增生组和喉癌组分别为5.0%(1/20)、20.0%(8/40)、45.0%(27/60),喉癌组与正常组比较,其差异有极显著性意义(P<0.01);p21WAF1/CIP1阳性表达率分别为95.0%(19/20)、75.0%(30/40)和63.3%(38/60),喉癌组与正常组比较,其差异亦有显著性意义(P<0.05);p53阳性表达率分别为0(0/20)、30.0%(12/40)和61.7%(37/60),喉癌组与正常组比较,其差异有极显著性意义(P<0.01)。②p21WAF1/CIP1在高、中、低分化的喉癌中阳性表达率逐渐降低,其差异有显著性意义(P<0.05)。③CyclinE和p53阳性表达显著相关,p21WAF1/CIP1与p53阳性表达无相关性。结论:①CyclinE和p53异常表达是喉癌发生中早期分子事件。②p21WAF1/CIP1表达与喉癌细胞分化程度有关。③细胞周期因子相互调控机制在喉癌发展中起重要作用。%Objective:To investigate the clinicopathlogical significance of the CyclinE,p21WAF1/CIP1 and p53 expression in laryngeal carcinogenesis.Method:The expression of CyclinE,p21WAF1/CIP1 and p53 was examined by using immunohistochemical method in normal epithlia (20),dysplastic epithlia (40) and laryngeal cancers (60).Result:①In normal epithlium,dysplastic squamous epithlium and in squamous cell carcinoma of the larynx,the positive immunostaining rate of CyclinE protein was 5.0%(1/20),20.0%(8/40) and 45.0%(27/60) respectively (P<0.001),and p21WAF1/CIP1 protein was 95.0%(19/20),75.0%(30/40) and 63.3%(38/60) respectively (P<0.01),while the rate of p53 was 0,30.0%(12/40) and 61.7%(37/60)(P<0.001) respectively.②p21WAF1/CIP1 positive expression in highly、moderately and poorly differtiated carcinomas were 76.2%(16/21)、66

  13. Study of D 0 and D + decays into final states with two or three kaons

    Science.gov (United States)

    Albrecht, H.; Hamacher, T.; Hofmann, R. P.; Kirchhoff, T.; Mankel, R.; Nau, A.; Nowak, S.; Reßing, D.; Schröder, H.; Schulz, H. D.; Walter, M.; Wurth, R.; Hast, C.; Kapitza, H.; Kolanoski, H.; Kosche, A.; Lange, A.; Lindner, A.; Schieber, M.; Siegmund, T.; Spaan, B.; Thurn, H.; Töpfer, D.; Wegener, D.; Eckstein, P.; Schmidtler, M.; Schramm, M.; Schubert, K. R.; Schwierz, R.; Waldi, R.; Reim, K.; Wegener, H.; Eckmann, R.; Kuipers, H.; Mai, O.; Mundt, R.; Oest, T.; Reiner, R.; Schmidt-Parzefall, W.; Stiewe, J.; Werner, S.; Ehret, K.; Hofmann, W.; Hüpper, A.; Knöpfle, K. T.; Spengler, J.; Krieger, P.; Macfarlane, D. B.; Prentice, J. D.; Saull, P. R. B.; Tzamariudaki, K.; van de Water, R. G.; Yoon, T.-S.; Frankl, C.; Schneider, M.; Weseler, S.; Kernel, G.; Križan, P.; Križnič, E.; Podobnik, T.; Živko, T.; Balagura, V.; Barsuk, S.; Belyaev, I.; Chechelnitsky, S.; Chistov, R.; Danilov, M.; Droutskoy, A.; Gershtein, Yu.; Golutvin, A.; Korolko, I.; Kostina, G.; Litvintsev, D.; Lubimov, V.; Pakhlov, P.; Semenov, S.; Snizhko, A.; Tichomirov, I.; Zaitsev, Yu.

    1994-09-01

    Using the ARGUS detector at the e + e - storage ring DORIS II, we have studied Cabibbo-suppressed D 0 decay modes resulting in the K + K - π + π - final state and two-body D 0 decay modes with a ϕ meson in the final state. The BR( D 0→ K {/S 0} K {/S 0}π+π- was measured for the first time. We also present a measurement of the D + →K {/S 0} K {/S 0} K + branching ratio. The values are compared with other experimental results and model predictions.

  14. Lupeol, a bioactive triterpene, prevents tumor formation during 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis.

    Science.gov (United States)

    Palanimuthu, D; Baskaran, N; Silvan, S; Rajasekaran, D; Manoharan, S

    2012-10-01

    The oral cancer chemopreventive efficacy of lupeol, a bioactive triterpene, was assessed by monitoring the tumor incidence and using the status of phase I and II xenobiotic metabolizing enzymes, lipid peroxidation and antioxidants as biochemical end points during 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the buccal pouch of golden Syrian hamsters by painting with 0.5 % DMBA three times a week for 14 weeks. Well differentiated oral squamous cell carcinoma with marked abnormalities in the status of biochemical markers were noticed in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50 mg/kg bw completely inhibited the formation of oral tumors and restored the status of biochemical markers during DMBA induced oral carcinogenesis. The present study thus demonstrates the chemopreventive potential of lupeol in DMBA induced oral carcinogenesis. The chemopreventive potential of lupeol is probably due to its antioxidant or free radical scavenging property and modulating effect on phase I and II xenobiotic metabolizing enzymes in favour of the excretion of carcinogenic metabolites during DMBA induced hamster buccal pouch carcinogenesis.

  15. Biomolecular and epidemiological aspects of human papillomavirus induced cervical carcinogenesis

    NARCIS (Netherlands)

    Vermeulen, Christine Frederike Wilhelmine

    2007-01-01

    Cervical cancer remains one of the leading causes of death from cancer among women worldwide. Organised screening programmes aim to trace precursor lesions in order to reduce cervical cancer incidence. Human papillomavirus (HPV) is a necessary cause for cervical carcinogenesis. Most HPV infections a

  16. NTP technical report on the toxicology and carcinogenesis studies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (CAS No. 1746-01-6) in female Harlan Sprague-Dawley rats (Gavage Studies).

    Science.gov (United States)

    2006-04-01

    manufacturing and processing; biological and photochemical processes; and existing reservoir sources that reflect past releases. TCDD (dioxin) was selected for study by the National Toxicology Program as a part of the dioxin TEF evaluation to assess the cancer risk posed by complex mixtures of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and PCBs. The dioxin TEF evaluation includes conducting multiple 2-year rat bioassays to evaluate the relative chronic toxicity and carcinogenicity of DLCs, structurally related PCBs, and mixtures of these compounds. While one of the aims of the dioxin TEF evaluation was a comparative analysis across studies, in this Technical Report, only the TCDD results are presented and discussed. TCDD was included because it is the reference compound for the dioxin TEF methodology. Female Harlan Sprague-Dawley rats were administered TCDD (at least 98% pure) in corn oil:acetone (99:1) by gavage for 14, 31, or 53 weeks or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, L5178Y mouse lymphoma cells, cultured Chinese hamster ovary cells, Drosophila melanogaster, and mouse bone marrow cells. 2-YEAR STUDY: Groups of 81 or 82 female rats were administered 3, 10, 22, 46, or 100 ng TCDD/kg body weight in corn oil:acetone (99:1) by gavage, 5 days per week, for up to 105 weeks; a group of 81 vehicle control female rats received the corn oil/acetone vehicle alone. Up to 10 rats per group were evaluated at 14, 31, or 53 weeks. A stop-exposure group of 50 female rats was administered 100 ng/kg TCDD in corn oil:acetone (99:1) by gavage for 30 weeks and then just the vehicle for the remainder of the study. Survival of dosed groups was similar to that of the vehicle control group. Mean body weights of 100 ng/kg core study and stop-exposure groups were less than those of the vehicle control group after week 13 of the study. Mean body weights of 46 ng/kg rats were less than those of the vehicle controls during

  17. Widespread hypomethylation occurs early and synergizes with gene amplification during esophageal carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Hector Alvarez

    2011-03-01

    Full Text Available Although a combination of genomic and epigenetic alterations are implicated in the multistep transformation of normal squamous esophageal epithelium to Barrett esophagus, dysplasia, and adenocarcinoma, the combinatorial effect of these changes is unknown. By integrating genome-wide DNA methylation, copy number, and transcriptomic datasets obtained from endoscopic biopsies of neoplastic progression within the same individual, we are uniquely able to define the molecular events associated progression of Barrett esophagus. We find that the previously reported global hypomethylation phenomenon in cancer has its origins at the earliest stages of epithelial carcinogenesis. Promoter hypomethylation synergizes with gene amplification and leads to significant upregulation of a chr4q21 chemokine cluster and other transcripts during Barrett neoplasia. In contrast, gene-specific hypermethylation is observed at a restricted number of loci and, in combination with hemi-allelic deletions, leads to downregulatation of selected transcripts during multistep progression. We also observe that epigenetic regulation during epithelial carcinogenesis is not restricted to traditionally defined "CpG islands," but may also occur through a mechanism of differential methylation outside of these regions. Finally, validation of novel upregulated targets (CXCL1 and 3, GATA6, and DMBT1 in a larger independent panel of samples confirms the utility of integrative analysis in cancer biomarker discovery.

  18. NTP toxicology and carcinogenesis studies of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) (CAS No. 57465-28-8) in female Harlan Sprague-Dawley rats (Gavage Studies).

    Science.gov (United States)

    2006-01-01

    PCB residues in the environment, but it continues to be released into the environment through the use and disposal of products containing PCBs, as by-products during the manufacture of certain organic chemicals, and during combustion of some waste materials. Bioaccumulation of PCB 126 results in persistent levels in animal and human tissues and the biological responses to PCB 126 are similar to those of TCDD, a known human carcinogen. PCB 126 was selected for study by the National Toxicology Program as a part of the dioxin TEF evaluation to assess the cancer risk posed by complex mixtures of polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and PCBs. The dioxin TEF evaluation includes conducting multiple 2-year rat bioassays to evaluate the relative chronic toxicity and carcinogenicity of DLCs, structurally related PCBs, and mixtures of these compounds. PCB 126 was included since this is the most potent coplanar PCB that has dioxin-like activities. While one of the aims of the dioxin TEF evaluation was a comparative analysis across studies, in this Technical Report only the results of the PCB 126 study are presented and discussed. Female Harlan Sprague-Dawley rats were administered PCB 126 (99% pure) in corn oil with acetone by gavage for 14, 31, or 53 weeks or 2 years. 2-YEAR STUDY: Groups of 81 female rats were administered 30, 100, 175, 300, 550, or 1,000 ng PCB 126/kg body weight in corn oil:acetone (99:1) by gavage, 5 days per week, for up to 104 weeks; a group of 81 vehicle control female rats received the corn oil/acetone vehicle alone. A group of 28 rats received 10 ng/kg for up to 53 weeks only. Up to 10 rats per group were evaluated at 14, 31, or 53 weeks. A stop-exposure group of 50 female rats was administered 1,000 ng/kg PCB 126 in corn oil:acetone (99:1) by gavage for 30 weeks then the vehicle for the remainder of the study. Mean body weights of 30 and 100 ng/kg rats were similar to those of the vehicle controls during most

  19. Copper and resveratrol attenuates serum catalase, glutathione peroxidase, and element values in rats with DMBA-induced mammary carcinogenesis.

    Science.gov (United States)

    Skrajnowska, Dorota; Bobrowska-Korczak, Barbara; Tokarz, Andrzej; Bialek, Slawomir; Jezierska, Ewelina; Makowska, Justyna

    2013-12-01

    In this paper, a hypothesis was assessed whether or not the intoxication with copper and supplementation with copper plus resveratrol would result in changes in the activities of catalase and glutathione peroxidase and moreover if the characteristic changes would appear in concentrations of copper, iron, calcium, magnesium, and zinc in the serum of rats with chemically induced carcinogenesis. Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet, were treated with copper (42.6 mg Cu/kg food as CuSO4·5H2O) or copper plus resveratrol (0.2 mg/kg body) via gavage for a period from 40 days until 20 weeks of age. In cancer groups, the rats were treated with a dose of 80 mg/body weight of 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) given in rapeseed oil at 50 and 80 days of age to induce mammary carcinogenesis. The control groups included the rats kept in the same conditions and fed with the same diet as the animals from the study groups, but not DMBA-treated. The activity of catalase significantly decreased in groups of rats with mammary carcinogenesis that were supplemented with copper (p copper plus resveratrol (p cancer groups of nonsupplemented rats, the increase of glutathione peroxidase activity was observed. The process of carcinogenesis and the applied supplementation significantly altered the concentrations of trace elements in serum, in particular as concerns iron and copper. The mean serum iron levels in rats with breast cancer were significantly lower than those in the control groups (p copper levels significantly decreased in the groups of rats with mammary carcinogenesis that were supplemented with copper or copper plus resveratrol in comparison with the control groups that received the same diets (p copper and zinc/iron ratios in blood may be used as one of the prognostic factors in breast cancer research.

  20. Toxicology and carcinogenesis studies of Ginkgo biloba extract (CAS No. 90045-36-6) in F344/N rats and B6C3F1/N mice (Gavage studies).

    Science.gov (United States)

    2013-03-01

    Ginkgo biloba extract has been used primarily as a medicinal agent in the treatment or prevention of cardiovascular and cerebrovascular dysfunction. Ginkgo biloba extract was nominated for study by the National Cancer Institute because of its widespread use as an herbal supplement to promote mental function and the limited availability of toxicity and carcinogenicity data. Furthermore, one of the major ingredients in Ginkgo biloba extract, quercetin, is a known mutagen. The Ginkgo biloba extract used in the current studies was procured from a supplier known to provide material to United States companies and contained 31.2% flavonol glycosides, 15.4% terpene lactones (6.94% bilo-balide, 3.74% ginkgolide A, 1.62% ginkgolide B, 3.06% ginkgolide C), and 10.45 ppm ginkgolic acid. Male and female F344/N rats and B6C3F1/N mice were administered Ginkgo biloba extract in corn oil by gavage for 3 months or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female rats were administered 0, 62.5, 125, 250, 500, or 1,000 mg Ginkgo biloba extract/kg body weight in corn oil by gavage, 5 days per week for 14 weeks. Additional groups of 10 male and 10 female rats (clinical pathology study) were administered the same doses, 5 days per week for 23 days. All rats survived to the end of the study. Mean body weights of all dosed groups were similar to those of the vehicle control groups. Liver weights of all dosed groups of males and females were significantly greater than those of the vehicle control groups. The incidences of hepatocyte hypertrophy in all dosed groups of males and in 500 and 1,000 mg/kg females were significantly greater than those in the vehicle control groups; there was a dose-related increase in severity of this lesion in males. Hepatocyte fatty change occurred in all dosed males. The incidences of thyroid gland follicular cell

  1. 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.

  2. Possible Involvement of Pancreatic Fatty Infiltration in Pancreatic Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Mika Hori

    2016-03-01

    Full Text Available Pancreatic cancer is difficult to diagnose in its early stage and is one of the most lethal human cancers. Thus, it is important to clarify its major risk factors, predictive factors and etiology. Here, we focus on fatty infiltration of the pancreas and suggest that it could be a risk factor for pancreatic cancer. Fatty infiltration of the pancreas is observed as ectopic adipocytes infiltrating the pancreatic tissue and is positively correlated with obesity and the prevalence of diabetes mellitus, which are risk factors for pancreatic cancer. However, whether fatty infiltration is a major risk factor for pancreatic cancer has not been established. Recent clinical studies show there is a positive correlation between fatty infiltration of the pancreas and pancreatic precancerous lesions or ductal adenocarcinomas. Animal experimental studies also show an association between fatty infiltration of the pancreas and pancreatic precancerous lesions or ductal adenocarcinomas development. Syrian golden hamsters, which are sensitive to chemical carcinogens in the pancreas, develop fatty infiltration of the pancreas with age. The combination of a high-fat diet and a chemical carcinogen that induces a K-ras mutation increases the severity of fatty infiltration of the pancreas. Thus, fatty infiltration of the pancreas is suggested to promote pancreatic carcinogenesis via a K-ras activating mutation. It is assumed that increased expression of adipokines and of inflammatory and proliferation-associated factors elicited by fatty infiltration of the pancreas may contribute to pancreatic precancerous lesions or ductal adenocarcinomas development. Accumulating evidence suggests that in addition to suppression of Ras activation, methods to modulate fatty infiltration in the pancreas can be considered as a strategy for preventing pancreatic cancer.

  3. Toxicology and carcinogenesis studies of acrylamide (CASRN 79-06-1) in F344/N rats and B6C3F1 mice (feed and drinking water studies).

    Science.gov (United States)

    2012-07-01

    Acrylamide, a water-soluble α,β-unsaturated amide, is a contaminant in baked and fried starchy foods, including french fries, potato chips, and bread, as a result of Maillard reactions involving asparagine and reducing sugars. Additional sources of acrylamide exposure include cigarettes, laboratory procedures involving polyacrylamide gels, and various occupations (e.g, monomer production and polymerization processes). Acrylamide is carcinogenic in experimental animals. To obtain data for developing quantitative risk assessments for dietary exposures to acrylamide, the Food and Drug Administration nominated acrylamide for an in-depth toxicological evaluation by the National Toxicology Program. As part of this evaluation, male and female B6C3F1/Nctr (C57BL/6N x C3H/HeN MTV-) mice and male and female F344/N Nctr rats were exposed to acrylamide (at least 99.4% pure) in drinking water for 2 years. 2-WEEK STUDY IN RATS: Groups of four male and four female F344/N rats were administered 0, 0.14, 0.35, 0.70, 1.41, 3.52, or 7.03 mM acrylamide in the drinking water (0, 10, 25, 50, 100, 250, or 500 ppm acrylamide) or 0.0, 7.4, 18.5, 37, 74, 185, or 370 mg acrylamide per kg diet for 14 days. One male rat administered 7.03 mM acrylamide in the drinking water died on day 14. Male and female rats receiving 7.03 mM acrylamide weighed 56% and 64% of controls, respectively. Male and female rats fed 370 mg acrylamide per kg diet weighed 74% and 83% of controls, respectively. Female rats receiving 3.52 mM acrylamide in drinking water and male rats fed 185 mg acrylamide per kg diet weighed 85% and 89% of controls, respectively. Rats receiving 7.03 mM acrylamide in drinking water or 370 mg acrylamide per kg diet exhibited hind-leg paralysis on day 14. Mild to moderate dilatation of the urinary bladder was observed in all rats given 370 mg acrylamide per kg diet, and in three of four male rats and all four female rats given 7.03 mM acrylamide in drinking water, and in one of four male

  4. 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.

  5. Role of gastrin-peptides in Barrett's and colorectal carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Eduardo Chueca; Angel Lanas; Elena Piazuelo

    2012-01-01

    Gastrin is the main hormone responsible for the stimulation of gastric acid secretion; in addition,gastrin and its derivatives exert proliferative and antiapoptotic effects on several cell types.Gastrin synthesis and secretion are increased in certain situations,for example,when proton pump inhibitors are used.The impact of sustained hypergastrinemia is currently being investigated.In vitro experiments and animal models have shown that prolonged hypergastrinemia may be related with higher cancer rates; although,this relationship is less clear in human beings.Higher gastrin levels have been shown to cause hyperplasia of several cell types; yet,the risk for developing cancer seems to be the same in normo-and hypergastrinemic patients.Some tumors also produce their own gastrin,which can act in an autocrine manner promoting tumor growth.Certain cancers are extremely dependent on gastrin to proliferate.Initial research focused only on the effects of amidated gastrins,but there has been an interest in intermediates of gastrin in the last few decades.These intermediates aren't biologically inactive;in fact,they may exert greater effects on proliferation and apoptosis than the completely processed forms.In certain gastrin overproduction states,they are the most abundant gastrin peptides secreted.The purpose of this review is to examine the gastrin biosynthesis process and to summarize the results from different studies evaluating the production,levels,and effects of the main forms of gastrin in different overexpression states and their possible relationship with Barrett's and colorectal carcinogenesis.

  6. Carcinogenesis ofnasopharyngeal carcinoma:an alternate hypothetical mechanism

    Institute of Scientific and Technical Information of China (English)

    Sharon Shuxian Poh; Melvin Lee Kiang Chua; Joseph TS Wee

    2016-01-01

    Current proposed mechanisms implicate both early and latent Epstein–Barr virus (EBV) infection in the carcinogenic cascade, whereas epidemiological studies have always associated nasopharyngeal carcinoma (NPC) with early child-hood EBV infection and with chronic ear, nose, and sinus conditions. Moreover, most patients with NPC present with IgA antibody titers to EBV capsid antigen (VCA-IgA), which can precede actual tumor presentation by several years. If early childhood EBV infection indeed constitutes a key event in NPC carcinogenesis, one would have to explain the inability to detect the virus in normal nasopharyngeal epithelium of patients at a high risk for EBV infection. It is perhaps possible that EBV resides within the salivary glands, instead of the epithelium, during latency. This claim is indirectly supported by observations that the East Asian phenotype shares the characteristics of an increased sus-ceptibility to NPC and immature salivary gland morphogenesis, the latter of which is inlfuenced by the association of salivary gland morphogenesis with an evolutionary variant of the human ectodysplasin receptor gene (EDAR), EDARV370A. Whether the immature salivary gland represents a more favorable nidus for EBV is uncertain, but in patients with infectious mononucleosis, EBV has been isolated in this anatomical organ. The presence of EBV-induced lymphoepitheliomas in the salivary glands and lungs further addresses the possibility of submucosal spread of the virus. Adding to the fact that the fossa of Rosen Müller contains a transformative zone active only in the ifrst decade of life, one might be tempted to speculate the possibility of an alternative carcinogenic cascade for NPC that is perhaps not dissimilar to the model of human papillomavirus and cervical cancer.

  7. The role of immediate and final goals in action planning: an fMRI study.

    Science.gov (United States)

    Majdandzić, Jasminka; Grol, Meike J; van Schie, Hein T; Verhagen, Lennart; Toni, Ivan; Bekkering, Harold

    2007-08-15

    To interact effectively with our environment, we need to specify the intended outcomes (goals) of our actions. In this process, immediate goals and final goals can be regarded as different levels within a hierarchically organized system for action planning: immediate goals and movement details are selected to accomplish more remote goals. Behavioral studies support this notion of different levels of action planning, but the neurophysiological basis remains unclear. Using fMRI, we examined the neural correlates of preparing object manipulations based on either the desired end-state (the final goal) or the initial movement towards a target (the immediate goal). Subjects had to insert an object (consisting of a large and a small cube) into one of two corresponding large and small slots. The subjects were cued on either which slot to fill (Final Goal trials) or which object part to grasp (Immediate Goal trials). These actions required similar movements, but different planning. During Final Goal trials, there was differential preparatory activity along the superior frontal gyrus (bilaterally) and in left inferior parietal cortex. Immediate Goal trials evoked differential activity in occipito-parietal and occipito-temporal cortex. These findings support the notion that actions can be planned at different levels. We show that different fronto-parietal circuits plan the same action, by a relative emphasis on either selecting a sequence of movements to achieve a desired end-state, or selecting movements spatially compatible with given object properties.

  8. Roles of FGFR in oral carcinogenesis.

    Science.gov (United States)

    Xie, Xiaoyan; Wang, Zhiyong; Chen, Fangman; Yuan, Yao; Wang, Jiayi; Liu, Rui; Chen, Qianming

    2016-06-01

    Fibroblast growth factor receptors (FGFRs) play essential roles in organ development during the embryonic period, and regulate tissue repair in adults. Accumulating evidence suggests that alterations in FGFR signalling are involved in diverse types of cancer. In this review, we focus on aberrant regulation of FGFRs in pathogenesis of oral squamous cell carcinoma (OSCC), including altered expression and subcellular location, aberrant isoform splicing and mutations. We also provide an overview of oncogenic roles of each FGFR and its downstream signalling pathways in regulating OSCC cell proliferation and metastasis. Finally, we discuss potential application of FGFRs as anti-cancer targets in the preclinical environment and in clinical practice.

  9. The role of final-state interactions in Dalitz plot studies

    CERN Document Server

    Kubis, Bastian

    2011-01-01

    Dalitz plot studies for multi-hadron decays of heavy mesons are expected to become very important tools for precision investigations of CP violation. A thorough understanding of the hadronic final-state interactions is a prerequisite to achieve a highly sensitive, model-independent study of CP-violating phases in such processes. We illustrate the theoretical tools available, as well as still to be developed, from low-to-medium-energy hadron physics for this purpose, and the goals of the informal "Les Nabis" network studying these and related problems.

  10. 52. INHIBITORY EFFECTS OF VITAMIN E SUCCINATE ON BENZO(A) PYRENE-INDUCED FORESTOMACH CARCINOGENESIS IN FEMALE MICE

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@This study is a part of an effort to develop effective chemoprevention for carcinogenesis of the forestomach. Vitamin E succinate(VES) administered by oral gavage and by intraperitioneal (IP) injections was used for the studies. Experimental design involved treating mice with Benzo(a) pyrene and VES(1.25 g/kg and 2.5 g/kg for gavage; 20 mg/kg for IP injections) for 4 weeks in order to study the

  11. Myenteric denervation in gastric carcinogenesis: differential modulation of nitric oxide and annexin-A1

    OpenAIRE

    2012-01-01

    This study evaluated the properties of endogenous nitric oxide synthases (NOS) and annexin-A1 (ANXA1) and determined how they can be exploited in the N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced gastric carcinogenesis and myenteric denervation model. Male Wistar rats were treated with MNNG and/or aminoguanidine (AG) for 20 weeks. In another set of experiments, rats with nondenervated and denervated stomachs were treated with MNNG or water for 28 weeks. Fragments of the pyloric region we...

  12. 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.

  13. High Dietary Salt Intake Exacerbates Helicobacter pylori-Induced Gastric Carcinogenesis

    OpenAIRE

    Gaddy, Jennifer A.; Radin, Jana N.; Loh, John T.; Zhang, Feng; Washington, M. Kay; Peek, Richard M.; Algood, Holly M. Scott; Cover, Timothy L.

    2013-01-01

    Persistent colonization of the human stomach with Helicobacter pylori is a risk factor for gastric adenocarcinoma, and H. pylori-induced carcinogenesis is dependent on the actions of a bacterial oncoprotein known as CagA. Epidemiological studies have shown that high dietary salt intake is also a risk factor for gastric cancer. To investigate the effects of a high-salt diet, we infected Mongolian gerbils with a wild-type (WT) cagA+ H. pylori strain or an isogenic cagA mutant strain and main...

  14. Identification problem for stochastic models with application to carcinogenesis, cancer detection and radiation biology

    Directory of Open Access Journals (Sweden)

    L. G. Hanin

    2002-01-01

    Full Text Available A general framework for solving identification problem for a broad class of deterministic and stochastic models is discussed. This methodology allows for a unified approach to studying identifiability of various stochastic models arising in biology and medicine including models of spontaneous and induced Carcinogenesis, tumor progression and detection, and randomized hit and target models of irradiated cell survival. A variety of known results on parameter identification for stochastic models is reviewed and several new results are presented with an emphasis on rigorous mathematical development.

  15. 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.

  16. Studies of beauty baryon decays to $D^0 ph^-$ and $\\Lambda_c^+ h^-$ final states

    CERN Document Server

    Aaij, Roel; Adinolfi, Marco; Adrover, Cosme; Affolder, Anthony; Ajaltouni, Ziad; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; Anderlini, Lucio; Anderson, Jonathan; Andreassen, Rolf; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Balagura, Vladislav; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Bauer, Thomas; Bay, Aurelio; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Belogurov, Sergey; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Bjørnstad, Pål Marius; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borgia, Alessandra; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Brambach, Tobias; van den Brand, Johannes; Bressieux, Joël; Brett, David; Britsch, Markward; Britton, Thomas; Brook, Nicholas; Brown, Henry; Bursche, Albert; Busetto, Giovanni; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Callot, Olivier; Calvi, Marta; Calvo Gomez, Miriam; Camboni, Alessandro; Campana, Pierluigi; Campora Perez, Daniel; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carranza-Mejia, Hector; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Ciba, Krzystof; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coca, Cornelia; Coco, Victor; Cogan, Julien; Cogneras, Eric; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pascal; David, Pieter; Davis, Adam; De Bonis, Isabelle; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Di Canto, Angelo; Dijkstra, Hans; Dogaru, Marius; Donleavy, Stephanie; Dordei, Francesca; Dorosz, Piotr; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; van Eijk, Daan; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farry, Stephen; Ferguson, Dianne; Fernandez Albor, Victor; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Fitzpatrick, Conor; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; Garofoli, Justin; Garosi, Paola; Garra Tico, Jordi; Garrido, Lluis; Gaspar, Clara; Gauld, Rhorry; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gordon, Hamish; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Hafkenscheid, Tom; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; Hartmann, Thomas; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hicks, Emma; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Hunt, Philip; Huse, Torkjell; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Iakovenko, Viktor; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jans, Eddy; Jaton, Pierre; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kaballo, Michael; Kandybei, Sergii; Kanso, Wallaa; Karacson, Matthias; Karbach, Moritz; Kenyon, Ian; Ketel, Tjeerd; Khanji, Basem; Klaver, Suzanne; Kochebina, Olga; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kozlinskiy, Alexandr; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanciotti, Elisa; Lanfranchi, Gaia; Langenbruch, Christoph; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leo, Sabato; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Li Gioi, Luigi; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Guoming; Lohn, Stefan; Longstaff, Ian; Lopes, Jose; Lopez-March, Neus; Lu, Haiting; Lucchesi, Donatella; Luisier, Johan; Luo, Haofei; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Machikhiliyan, Irina V; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Manca, Giulia; Mancinelli, Giampiero; Maratas, Jan; Marconi, Umberto; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martens, Aurelien; Martín Sánchez, Alexandra; Martinelli, Maurizio; Martinez Santos, Diego; Martins Tostes, Danielle; Martynov, Aleksandr; Massafferri, André; Matev, Rosen; Mathe, Zoltan; Matteuzzi, Clara; Maurice, Emilie; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; McSkelly, Ben; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Molina Rodriguez, Josue; Monteil, Stephane; Moran, Dermot; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Mountain, Raymond; Mous, Ivan; Muheim, Franz; Müller, Katharina; Muresan, Raluca; Muryn, Bogdan; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neubert, Sebastian; Neufeld, Niko; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Nicol, Michelle; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Nomerotski, Andrey; Novoselov, Alexey; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Oggero, Serena; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Orlandea, Marius; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Arantza; Pal, Bilas Kanti; Palano, Antimo; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Parkes, Christopher; Parkinson, Christopher John; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pavel-Nicorescu, Carmen; Pazos Alvarez, Antonio; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perez Trigo, Eliseo; Pérez-Calero Yzquierdo, Antonio; Perret, Pascal; Perrin-Terrin, Mathieu; Pescatore, Luca; Pesen, Erhan; Pessina, Gianluigi; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Polok, Grzegorz; Poluektov, Anton; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Powell, Andrew; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redford, Sophie; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Alexander; Rinnert, Kurt; Rives Molina, Vincente; Roa Romero, Diego; Robbe, Patrick; Roberts, Douglas; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruffini, Fabrizio; Ruiz, Hugo; Ruiz Valls, Pablo; Sabatino, Giovanni; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sapunov, Matvey; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Savrie, Mauro; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Seco, Marcos; Semennikov, Alexander; Senderowska, Katarzyna; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Oksana; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Sparkes, Ailsa; Spradlin, Patrick; Stagni, Federico; Stahl, Sascha; Steinkamp, Olaf; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Subbiah, Vijay Kartik; Sun, Liang; Sutcliffe, William; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szilard, Daniela; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teodorescu, Eliza; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Tran, Minh Tâm; Tresch, Marco; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ubeda Garcia, Mario; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; Voss, Helge; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Webber, Adam Dane; Websdale, David; Whitehead, Mark; Wicht, Jean; Wiechczynski, Jaroslaw; Wiedner, Dirk; Wiggers, Leo; Wilkinson, Guy; Williams, Matthew; Williams, Mike; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wu, Suzhi; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Feng; Zhang, Liming; Zhang, Wen Chao; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zvyagin, Alexander

    2014-01-01

    Decays of beauty baryons to the $D^0 p h^-$ and $\\Lambda_c^+ h^-$ final states (where $h$ indicates a pion or a kaon) are studied using a data sample of $pp$ collisions, corresponding to an integrated luminosity of 1.0 fb$^{-1}$, collected by the LHCb detector. The Cabibbo-suppressed decays $\\Lambda_b^0\\to D^0 p K^-$ and $\\Lambda_b^0\\to \\Lambda_c^+ K^-$ are observed and their branching fractions are measured with respect to the decays $\\Lambda_b^0\\to D^0 p \\pi^-$ and $\\Lambda_b^0\\to \\Lambda_c^+ \\pi^-$. In addition, the first observation is reported of the decay of the neutral beauty-strange baryon $\\Xi_b^0$ to the $D^0 p K^-$ final state, and a measurement of the $\\Xi_b^0$ mass is performed. Evidence of the $\\Xi_b^0\\to \\Lambda_c^+ K^-$ decay is also reported.

  17. The Role of Ubiquitine Proteasome Pathway in Carcinogenesis

    Directory of Open Access Journals (Sweden)

    N.Ceren Sumer Turanligil

    2010-02-01

    Full Text Available Ubiquitin works as a marker protein which targets misfolded or injured proteins to cellular degradation. It brings the abnormal proteins to a subcellular organelle named proteasome and it maintains the degradation of proteins in limited lenghts of peptides by leaving the process withuout being changed. Mistakes in ubiquitin-dependent proteolysis in various steps of carcinogenesis is known. In this review, we dealed with the effects of ubiquitin-proteasome pathway (UPP on carcinogenesis via intercellular signaling molecules like Ras, transcription factors like NF-kB, cytokines like TNF-alfa Tumor necrosis factor, protooncogenes like p53 and MDM2(murine double minute 2, components of cell cycle and DNA repair proteins like BRCA1. We also focused on the relationship of UPP on antigen presentation which is active in immune response and its place in the aetiology of colon cancer to provide a specific example. [Archives Medical Review Journal 2010; 19(1.000: 36-55

  18. Carcinogenesis of the Oral Cavity: Environmental Causes and Potential Prevention by Black Raspberry.

    Science.gov (United States)

    El-Bayoumy, Karam; Chen, Kun-Ming; Zhang, Shang-Min; Sun, Yuan-Wan; Amin, Shantu; Stoner, Gary; Guttenplan, Joseph B

    2017-01-17

    Worldwide, cancers of the oral cavity and pharynx comprise the sixth most common malignancies. Histologically, more than 90% of oral cancers are squamous cell carcinoma (SCC). Epidemiologic data strongly support the role of exogenous factors such as tobacco, alcohol, and human papilloma virus infection as major causative agents. Avoidance of risk factors has only been partially successful, and survival rates have not improved despite advances in therapeutic approaches. Therefore, new or improved approaches to prevention and/or early detection are critical. Better understanding of the mechanisms of oral carcinogenesis can assist in the development of novel biomarkers for early detection and strategies for disease prevention. Toward this goal, several animal models for carcinogenesis in the oral cavity have been developed. Among these are xenograft, and transgenic animal models, and others employing the synthetic carcinogens such as 7,12-dimethylbenz[a]anthracene in hamster cheek pouch and 4-nitroquinoline-N-oxide in rats and mice. Additional animal models employing environmental carcinogens such as benzo[a]pyrene and N'-nitrosonornicotine have been reported. Each model has certain advantages and disadvantages. Models that (1) utilize environmental carcinogens, (2) reflect tumor heterogeneity, and (3) accurately represent the cellular and molecular changes involved in the initiation and progression of oral cancer in humans could provide a realistic platform. To achieve this goal, we introduced a novel nonsurgical mouse model to study oral carcinogenesis induced by dibenzo[a,l]pyrene (DB[a,l]P), an environmental pollutant and tobacco smoke constituent, and its diol epoxide metabolite (±)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]pyrene [(±)-anti-DB[a,l]PDE]. On the basis of a detailed comparison of oral cancer induced by DB[a,l]P with that induced by the other above-mentioned oral carcinogens with respect to dose, duration, species and

  19. Maine firewood study. Final report, 1 November 1978-15 January 1980

    Energy Technology Data Exchange (ETDEWEB)

    Swain, E.W.

    1980-06-01

    The barriers and incentives to fuelwood use were examined with particular emphasis on woodburners, woodlot owners and firewood dealers. A draft guide for woodlot owners managing for firewood production was prepared, along with a handbook for fuelwood dealers. Cost-benefit studies were completed for three fuelwood businesses in addition to an analysis of firewood marketing systems. The analysis revealed marginal though distinct opportunity for profit during the first year of a firewood venture. Landowner attitudes were also studied and programmatic suggestions offered to improve the effectiveness of existing services. Finally, legislative barriers to increased wood energy use were targetted and remedies proposed.

  20. Studies of hadronic B decays to final states containing open charm mesons at LHCb

    CERN Document Server

    Martín Sánchez, A

    2012-01-01

    The LHCb experiment is a general purpose forward spectrometer operating at the Large Hadron Collider, optimized for the study of B and D hadrons. LHCb recorded 1.0 fb$^{-1}$ of integrated luminosity during 2011 data taking, collecting unprecedented large samples of B decays to final states involving charmed mesons. These decays offer several complementary measurements of CP violation and CKM matrix parameters, and serve as a laboratory for testing effective theories of hadron decays. We present a selection of new world leading results in these types of decays, including first observations of new modes, world best branching ratio measurements and studies of resonant substructures.

  1. Charm Decays With Photons In The Final State And Trigger Counter Efficiencies Study

    CERN Document Server

    Paris Davila, A

    2003-01-01

    This thesis presents a study done on the strong decay of the D0* meson using data taken with the FOCUS spectrometer at Fermi National Laboratory Accelerator at Batavia, IL. FOCUS is a fixed target experiment designed to study photo-production of charmed states. The D0* branching ratio is measured to understand D meson decays with photons in the final state. The work done in the calibration and simulation of the trigger counter efficiencies for the HxV and OH detectors that form part of the first level trigger of the spectrometer is also presented.

  2. Role of oxidative stress in cadmium toxicity and carcinogenesis

    OpenAIRE

    2009-01-01

    Cadmium (Cd) is a toxic metal, targeting the lung, liver, kidney, and testes following acute intoxication, and causing nephrotoxicity, immunotoxicity, osteotoxicity and tumors after prolonged exposures. Reactive oxygen species (ROS) are often implicated in Cd toxicology. This minireview focused on direct evidence for the generation of free radicals in intact animals following acute Cd overload and discussed the association of ROS in chronic Cd toxicity and carcinogenesis. Cd-generated superox...

  3. Transcriptional regulation of cadherins during development and carcinogenesis

    OpenAIRE

    2004-01-01

    The cadherin superfamily of Ca2+-dependent homophilic adhesion molecules plays a critical role in regulating cell-to-cell interactions. During development, the expression of different cadherins is highly dynamic, since they are associated with the morphogenesis, establishment and/or maintenance of different tissues. Alterations in cadherin expression or function occur frequently during carcinogenesis, such as the loss of the epithelial cadherin (E-cadherin) and/or the aberrant expression of o...

  4. Modulation of carcinogenesis in the urinary bladder by retinoids.

    Science.gov (United States)

    Hicks, R M; Turton, J A; Chowaniec, J; Tomlinson, C N; Gwynne, J; Nandra, K; Chrysostomou, E; Pedrick, M

    1985-01-01

    Bladder cancer has a 70% recurrence rate within five years and a high associated mortality. It commonly occurs in one or both of two predominant growth/behaviour patterns: either well-differentiated, relatively benign exophytic papillary lesions, or flat, poorly differentiated invasive carcinoma usually arising from carcinoma-in-situ. We have used the F344 rat treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as a model for the papillary disease, and the BBN-treated B6D2F1 mouse for flat, invasive bladder carcinoma. In the rat, carcinogenesis is a multistage process and several retinoids will delay or even halt the development of bladder cancer. Inhibition of carcinogenesis is not complete, but there is a consistent reduction in the time-related incidence of papillomas and carcinomas and a concomitant improvement in the overall differentiation of the urothelium. In the BBN/mouse model, retinoids also have anticarcinogenic activity but interpretation of the results is more complicated. Unlike the F344 rat, the B6D2F1 mouse has a non-uniform response to BBN; not all mice develop bladder cancer even after treatment with very high doses of BBN and in those that do, more than one mechanism of carcinogenesis may be involved. Individual retinoids differ markedly in their ability to modulate bladder carcinogenesis in rodents; the behaviour of one analogue cannot be predicted automatically from data obtained with another. Combined data from rodent trials in this and other laboratories have identified N-(4-hydroxyphenyl)retinamide (HPR) as the most anticarcinogenic retinoid tested so far for the rodent bladder. It is also less toxic in rodents and better tolerated in humans than either 13-cis-retinoic acid or etretinate, two retinoids currently used in dermatological practice. A prophylactic chemopreventive trial of HPR in bladder cancer patients starting in 1985 will be centered on the Middlesex Hospital, London.

  5. Differences in proximal (cardia) versus distal (antral) gastric carcinogenesis via retinoblastoma pathway

    Institute of Scientific and Technical Information of China (English)

    Christian Gulmann; Helen Hegarty; Antoinette Grace; Mary Leader; Stephen Patchett; Elaine Kay

    2004-01-01

    AIM: Disruption of cell cycle regulation is a critical event in carcinogenesis, and alteration of the retinoblastoma (pRb)tumour suppressor pathway is frequent. The aim of this study was to compare alterations in this pathway in proximal and distal gastric carcinogenesis in an effort to explain the observed striking epidemiological differences.METHODS: Immunohistochemistry was performed to investigate expression of p16 and pRb in the following groups of both proximal (cardia) and distal (antral) tissue samples: (a) biopsies showing normal mucosa, (b) biopsies showing intestinal metaplasia and, (c) gastric cancer resection specimens including uninvolved mucosa and tumour.RESULTS: In the antrum there were highly significant trends for increased p16 expression with concomitant (and in the group of carcinomas inversely proportional)decreased pRb expression from normal mucosa to intestinal metaplasia to uninvolved mucosa (from cancer resections)to carcinoma. In the cardia, there were no differences in p16 expression between the various types of tissue samples whereas pRb expression was higher in normal mucosa compared with intestinal metaplasia and tissue from cancer resections.CONCLUSION: Alterations in the pRb pathway appear to play a more significant role in distal gastric carcinogenesis.Tt may be an early event in the former location since the trend towards p16 overexpression with concomitant pRb underexpression was seen as early as between normal mucosa and intestinal metaplasia. Importantly, the marked differences in expression of pRb and p16 between the cardia and antrum strongly support the hypothesis that tumours of the two locations are genetically different which may account for some of the observed epidemiological differences.

  6. Midkine translocated to nucleoli and involved in carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Li-Cheng Dai

    2009-01-01

    Midkine (MK) is a heparin-binding growth factor with its gene first identified in embryonal carcinoma cells at early stages of retinoic acid-induced differentiation.MK is frequently and highly expressed in a variety of human carcinomas. Furthermore, the blood MK level is frequently elevated with advance of human carcinomas, decreased after surgical removal of the tumors. Thus, it is expected to become a promising marker for evaluating the progress of carcinomas.There is mounting evidence that MK plays a significant role in carcinogenesis-related activities, such as proliferation, migration, anti-apoptosis, mitogenesis,transforming, and angiogenesis. In addition, siRNA and anti-sense oligonucleotides for MK have yielded great effects in anti-tumor activities. Therefore, MK appears to be a potential candidate molecular target of therapy for human carcinomas. In this paper, we review MK targeting at nucleoli in different tumor cells and its role in carcinogenesis to deepen our understanding of the mechanism of MK involved in carcinogenesis.

  7. Radiation carcinogenesis and acute radiation mortality in the rat as produced by 2.2 GeV protons

    Science.gov (United States)

    Shellabarger, C. J.; Straub, R. F.; Jesseph, J. E.; Montour, J. L.

    1972-01-01

    Biological studies, proton carcinogenesis, the interaction of protons and gamma-rays on carcinogenesis, proton-induced acute mortality, and chemical protection against proton-induced acute mortality were studied in the rat and these proton-produced responses were compared to similar responses produced by gamma-rays or X-rays. Litter-mate mice were assigned to each experimental and control group so that approximately equal numbers of litter mates were placed in each group. Animals to be studied for mammary neoplasia were handled for 365 days post-exposure when all animals alive were killed. All animals were examined frequently for mammary tumors and as these were found, they were removed, sectioned and given a pathologic classification.

  8. Clinical observed performance evaluation: a prospective study in final year students of surgery.

    LENUS (Irish Health Repository)

    Markey, G C

    2010-06-24

    We report a prospective study of clinical observed performance evaluation (COPE) for 197 medical students in the pre-qualification year of clinical education. Psychometric quality was the main endpoint. Students were assessed in groups of 5 in 40-min patient encounters, with each student the focus of evaluation for 8 min. Each student had a series of assessments in a 25-week teaching programme. Over time, several clinicians from a pool of 16 surgical consultants and registrars evaluated each student by direct observation. A structured rating form was used for assessment data. Variance component analysis (VCA), internal consistency and inter-rater agreement were used to estimate reliability. The predictive and convergent validity of COPE in relation to summative OSCE, long case, and overall final examination was estimated. Median number of COPE assessments per student was 7. Generalisability of a mean score over 7 COPE assessments was 0.66, equal to that of an 8 x 7.5 min station final OSCE. Internal consistency was 0.88-0.97 and inter-rater agreement 0.82. Significant correlations were observed with OSCE performance (R = 0.55 disattenuated) and long case (R = 0.47 disattenuated). Convergent validity was 0.81 by VCA. Overall final examination performance was linearly related to mean COPE score with standard error 3.7%. COPE permitted efficient serial assessment of a large cohort of final year students in a real world setting. Its psychometric quality compared well with conventional assessments and with other direct observation instruments as reported in the literature. Effect on learning, and translation to clinical care, are directions for future research.

  9. Selected Area Fishery Evaluation Project Economic Analysis Study Final Report, Final Draft Revision 4: November 10, 2006.

    Energy Technology Data Exchange (ETDEWEB)

    Bonneville Power Administration; Washington Department of Fish and Wildlife; Oregon Department of Fish and Wildlife

    2006-11-01

    The purpose of this Study is to provide an economic review of current and proposed changes to the Select Area Fishery Evaluation Project (SAFE or Project). The Study results are the information requested in comments made on the Project by a joint review dated March 2005 by the Northwest Power and Conservation Council (NPCC) Independent Scientific Review Panel (ISRP) and Independent Economic Analysis Board (IEAB). North et al. (2006) addressed technical questions about operations and plans, and this report contains the response information for comments concerning Project economics. This report can be considered an economic feasibility review meeting guidelines for cost-effective analysis developed by the IEAB (2003). It also contains other economic measurement descriptions to illustrate the economic effects of SAFE. The SAFE is an expansion of a hatchery project (locally called the Clatsop Economic Development Council Fisheries Project or CEDC) started in 1977 that released an early run coho (COH) stock into the Youngs River. The Youngs River entrance to the Columbia River at River Mile 12 is called Youngs Bay, which is located near Astoria, Oregon. The purpose of the hatchery project was to provide increased fishing opportunities for the in-river commercial fishing gillnet fleet. Instead of just releasing fish at the hatchery, a small scale net pen acclimation project in Youngs Bay was tried in 1987. Hirose et al. (1998) found that 1991-1992 COH broodstock over-wintered at the net pens had double the smolt-to-adult return rate (SAR) of traditional hatchery release, less than one percent stray rates, and 99 percent fishery harvests. It was surmised that smolts from other Columbia River hatcheries could be hauled to the net pens for acclimation and release to take advantage of the SAR's and fishing rates. Proposals were tendered to Bonneville Power Administration (BPA) and other agencies to fund the expansion for using other hatcheries smolts and other off

  10. Selected Area Fishery Evaluation Project Economic Analysis Study Final Report, Final Draft Revision 4: November 10, 2006.

    Energy Technology Data Exchange (ETDEWEB)

    Bonneville Power Administration; Washington Department of Fish and Wildlife; Oregon Department of Fish and Wildlife

    2006-11-01

    The purpose of this Study is to provide an economic review of current and proposed changes to the Select Area Fishery Evaluation Project (SAFE or Project). The Study results are the information requested in comments made on the Project by a joint review dated March 2005 by the Northwest Power and Conservation Council (NPCC) Independent Scientific Review Panel (ISRP) and Independent Economic Analysis Board (IEAB). North et al. (2006) addressed technical questions about operations and plans, and this report contains the response information for comments concerning Project economics. This report can be considered an economic feasibility review meeting guidelines for cost-effective analysis developed by the IEAB (2003). It also contains other economic measurement descriptions to illustrate the economic effects of SAFE. The SAFE is an expansion of a hatchery project (locally called the Clatsop Economic Development Council Fisheries Project or CEDC) started in 1977 that released an early run coho (COH) stock into the Youngs River. The Youngs River entrance to the Columbia River at River Mile 12 is called Youngs Bay, which is located near Astoria, Oregon. The purpose of the hatchery project was to provide increased fishing opportunities for the in-river commercial fishing gillnet fleet. Instead of just releasing fish at the hatchery, a small scale net pen acclimation project in Youngs Bay was tried in 1987. Hirose et al. (1998) found that 1991-1992 COH broodstock over-wintered at the net pens had double the smolt-to-adult return rate (SAR) of traditional hatchery release, less than one percent stray rates, and 99 percent fishery harvests. It was surmised that smolts from other Columbia River hatcheries could be hauled to the net pens for acclimation and release to take advantage of the SAR's and fishing rates. Proposals were tendered to Bonneville Power Administration (BPA) and other agencies to fund the expansion for using other hatcheries smolts and other off

  11. Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats

    Institute of Scientific and Technical Information of China (English)

    Salim S Al-Rejaie; Abdulaziz M Aleisa; Abdulaziz A Al-Yahya; Saleh A Bakheet; Abdulmalik Alsheikh; Amal G Fatani; Othman A Al-Shabanah; Mohamed M Sayed-Ahmed

    2009-01-01

    carcinogenesis while D-carnitine-mildronate aggravated DENA-induced hepatic damage.CONCLUSION: Data from this study suggest for the first time that: (1) carnitine deficiency is a risk factor and should be viewed as a mechanism in DENAinduced hepatic carcinogenesis; (2) oxidative stress plays an important role but is not the only cause of DENA-induced hepatic carcinogenesis; and (3) long-term L-carnitine supplementation prevents the development of DENA-induced liver cancer.

  12. Downregulation of keratin 76 expression during oral carcinogenesis of human, hamster and mouse.

    Directory of Open Access Journals (Sweden)

    Srikant Ambatipudi

    Full Text Available BACKGROUND: Keratins are structural marker proteins with tissue specific expression; however, recent reports indicate their involvement in cancer progression. Previous study from our lab revealed deregulation of many genes related to structural molecular integrity including KRT76. Here we evaluate the role of KRT76 downregulation in oral precancer and cancer development. METHODS: We evaluated KRT76 expression by qRT-PCR in normal and tumor tissues of the oral cavity. We also analyzed K76 expression by immunohistochemistry in normal, oral precancerous lesion (OPL, oral squamous cell carcinoma (OSCC and in hamster model of oral carcinogenesis. Further, functional implication of KRT76 loss was confirmed using KRT76-knockout (KO mice. RESULTS: We observed a strong association of reduced K76 expression with increased risk of OPL and OSCC development. The buccal epithelium of DMBA treated hamsters showed a similar trend. Oral cavity of KRT76-KO mice showed preneoplastic changes in the gingivobuccal epithelium while no pathological changes were observed in KRT76 negative tissues such as tongue. CONCLUSION: The present study demonstrates loss of KRT76 in oral carcinogenesis. The KRT76-KO mice data underlines the potential of KRT76 being an early event although this loss is not sufficient to drive the development of oral cancers. Thus, future studies to investigate the contributing role of KRT76 in light of other tumor driving events are warranted.

  13. St. John's Wort Attenuates Colorectal Carcinogenesis in Mice through Suppression of Inflammatory Signaling.

    Science.gov (United States)

    Manna, Soumen K; Golla, Srujana; Golla, Jaya Prakash; Tanaka, Naoki; Cai, Yan; Takahashi, Shogo; Krausz, Kristopher W; Matsubara, Tsutomu; Korboukh, Ilia; Gonzalez, Frank J

    2015-09-01

    Despite widespread use as well as epidemiologic indications, there have been no investigations into the effect of St. John's wort (SJW) extract on colorectal carcinogenesis in vivo. This study reports a systematic evaluation of the impact of dietary supplementation of SJW extract on azoxymethane-induced colorectal carcinogenesis in mice. Mice were fed with either AIN-93G (control) diet or SJW extract-supplemented diet (SJW diet) prior to azoxymethane treatment. SJW diet was found to significantly improve the overall survival of azoxymethane-treated mice. Pretreatment with the SJW diet significantly reduced body weight loss as well as decrease of serum albumin and cholesterol levels associated with azoxymethane-induced colorectal tumorigenesis. SJW diet-fed mice showed a significant decrease in tumor multiplicity along with a decrease in incidence of large tumors and a trend toward decreased total tumor volume in a dose-dependent manner. A short-term study, which examined the effect of SJW prior to rectal bleeding, also showed decrease in colorectal polyps in SJW diet-fed mice. Nuclear factor kappa B (NF-κB) and extracellular signal-regulated kinase (ERK1/2) pathways were attenuated by SJW administration. SJW extract resulted in early and continuous attenuation of these pathways in the colon epithelium of SJW diet-fed mice under both short-term and long-term treatment regimens. In conclusion, this study demonstrated the chemopreventive potential of SJW extract against colorectal cancer through attenuation of proinflammatory processes.

  14. Downstream carcinogenesis signaling pathways by green tea polyphenols: a translational perspective of chemoprevention and treatment for cancers.

    Science.gov (United States)

    Hu, Guohua; Zhang, Lei; Rong, Yefei; Ni, Xiaoling; Sun, Yihong

    2014-01-01

    Green tea is one of the most popular beverages around the world. For several decades, numerous epidemiological, preclinical and clinical studies have demonstrated that green tea polyphenols (GTPs), especially epigallocatechin-3-gallate (EGCG) have cancer-preventing effects on various cancers. In this review, we present inhibition of carcinogenesis in different animal models by GTPs or EGCG, including prostate cancer, bladder cancer, breast cancer, intestinal cancer, colon cancer, gastric cancer, lung cancer, oral cancer and skin cancer. In vitro studies showed that GTPs/EGCG potently induces apoptosis, cell cycle arrest and suppresses metastasis in tumor cells but not in their normal cell counterparts. The molecular mechanisms of these activities are discussed in detail to elucidate GTPs/EGCG downstream carcinogenesis signaling pathways and their values of perspective of chemoprevention and treatment for cancers.

  15. Circadian variations of clock gene Per2 and cell cycle genes in different stages of carcinogenesis in golden hamster buccal mucosa.

    Science.gov (United States)

    Tan, Xue-Mei; Ye, Hua; Yang, Kai; Chen, Dan; Wang, Qing-Qing; Tang, Hong; Zhao, Ning-Bo

    2015-05-07

    Previous studies have suggested that the expression of clock genes have circadian rhythms, and many cell cycle genes are regulated by clock genes. The disruption of circadian rhythms appears to be associated with the acceleration of cancer development. To investigate the circadian patterns of the clock gene Per2 and of cell cycle genes p53, Cyclin D1, CDK1 and Cyclin B1 in different stages of carcinogenesis, the daily mRNA profiles of these genes were detected by real-time RT-PCR in dimethylbenzanthracene-induced cancer, in precancerous lesions and in normal tissues. Per2, p53, Cyclin D1 and CDK1 showed circadian rhythms in the 3 different stages of carcinogenesis, whereas the circadian rhythm of Cyclin B1 was absent in the precancerous lesions. The mesors and amplitudes of Per2 and p53 were decreased (P circadian pattern variations of these genes in different stages of carcinogenesis.

  16. Long-term treatment with Sitagliptin, a dipeptidyl peptidase-4 inhibitor, reduces colon carcinogenesis and reactive oxygen species in 1,2-dimethylhydrazine-induced rats

    DEFF Research Database (Denmark)

    Femia, Angelo Pietro; Raimondi, Laura; Maglieri, Giulia

    2013-01-01

    studied whether long-term administration of the DPP4i Sitagliptin (SITA) affects 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Male F344 rats fed a high-fat (HF) diet promoting colon carcinogenesis and IR, were induced with DMH (100 mg/kg × 2 times). One week later, the animals were allocated......Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) increase colon cancer risk. Antidiabetic drugs stabilizing incretin hormones, such as inhibitors of dipeptidyl peptidase-4 activity (DPP4i), may affect colon carcinogenesis; however, the data remain controversial. Therefore, the authors...... in rats treated with SITA [MDF/colon: 9.5 ± 0.9 and 6.4 ± 0.9 in controls (n = 8) and SITA groups (n = 8), respectively; means ± SE, p

  17. Performance studies of the final prototype for the CASTOR forward calorimeter at the CMS experiment

    CERN Document Server

    Aslanoglou, Xenofon; Bakirci, Mustafa Numan; Basegmez, Suzan; Beaumont, Willem; Blocki, Jacek; Borras, Kerstin; Campbell, Alan; Çerçi, Salim; d'Enterria, David; de Silva, M; Dumanoglu, Isa; Erturk, Sefa; Eskut, Eda; Erchov, Y; Göttlicher, P; Gouskos, Loukas; Onengüt, G; Gusev, Yuri; Jung, Hannes; Katkov, Igor; Katsas, Panagiotis; Khein, Lev; Kisoglu, F; Knutsson, Albert; Kuleshov, Sergey; Kuznetsov, Andrey; Lebeau, Michel; McCauley, Thomas; Muhl, Carsten; Musienko, Yuri; Ochesanu, Silvia; Oroku, M; Ozdemir, Kadri; Ozturk, Sertac; Panagiotou, Apostolos; Shileev, K; Sogut, Kenan; Swain, John; Reucroft, Steve; Ripert, Marion; Tiflov, V; Kayis-Topaksu, A; Van Haevermaet, Hans; Van Mechelen, Pierre

    2008-01-01

    We present performance results of the final prototype for the CASTOR quartz-tungsten sampling calorimeter, to be installed in the very forward region of the CMS experiment at the LHC. The energy linearity and resolution, the uniformity, as well as the spatial resolution of the prototype to electromagnetic and hadronic showers are studied with $E=$ 10--200 GeV electrons, $E=$ 20--350 GeV pions, and $E=$ 50, 150 GeV muons in beam tests carried out at CERN/SPS in 2007.

  18. Modulation of pancreatic carcinogenesis by antioxidants

    NARCIS (Netherlands)

    Woutersen, R.A.; Appel, M.J.; Garderen van -Hoetmer, A.

    1999-01-01

    Previously performed short-term (4-month) studies demonstrated that vitamins C and E, β-carotene and selenium modulate growth of early putative preneoplastic acinar lesions induced in rat pancreas by azaserine. The present paper summarizes the results of long-term studies performed with azaserine-tr

  19. A Study of a Geo-Historical Structure for a Social Studies Curriculum. Final Report.

    Science.gov (United States)

    Shinn, Ridgway F., Jr.

    This study in curriculum revision examined two problems: the possibility of using geography and history as integrating disciplines for K-12 social studies program; and, the ways a public college and school system might cooperatively bring about curriculum change. Other objectives included development of materials and implementation of the program.…

  20. Does doctors’ workload impact supervision and ward activities of final-year students? A prospective study

    Directory of Open Access Journals (Sweden)

    Celebi Nora

    2012-06-01

    Full Text Available Abstract Background Hospital doctors face constantly increasing workloads. Besides caring for patients, their duties also comprise the education of future colleagues. The aim of this study was to objectively investigate whether the workload arising from increased patient care interferes with student supervision and is associated with more non-medical activities of final-year medical students. Methods A total of 54 final-year students were asked to keep a diary of their daily activities over a three-week period at the beginning of their internship in Internal Medicine. Students categorized their activities – both medical and non-medical - according to whether they had: (1 only watched, (2 assisted the ward resident, (3 performed the activity themselves under supervision of the ward resident, or (4 performed the activity without supervision. The activities reported on a particular day were matched with a ward specific workload-index derived from the hospital information system, including the number of patients treated on the corresponding ward on that day, a correction factor according to the patient comorbidity complexity level (PCCL, and the number of admissions and discharges. Both students and ward residents were blinded to the study question. Results A total of 32 diaries (59 %, 442 recorded working days were handed back. Overall, the students reported 1.2 ± 1.3 supervised, 1.8 ±1.6 medical and 3.6 ± 1.7 non-medical activities per day. The more supervised activities were reported, the more the number of reported medical activities increased (p  Conclusions There was a significant association between ward doctors’ supervision of students and the number of medical activities performed by medical students. The workload had no significant effect on supervision or the number of medical or non-medical activities of final-year students.

  1. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats

    OpenAIRE

    Anna Kakehashi; Midori Yoshida; Yoshiyuki Tago; Naomi Ishii; Takahiro Okuno; Min Gi; Hideki Wanibuchi

    2016-01-01

    Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in u...

  2. The Michigan regulatory incentives study for electric utilities. Phase 1, Final report

    Energy Technology Data Exchange (ETDEWEB)

    Reid, M.W.; Weaver, E.M. [Barakat and Chamberlin, Inc., Oakland, CA (United States)

    1991-06-17

    This is the final report of Phase I of the Michigan Regulatory Incentives Study for Electric Utilities, a three-phase review of Michigan`s regulatory system and its effects on resource selection by electric utilities. The goal of Phase I is to identify and analyze financial incentive mechanisms that encourage selection of resources in accord with the principles of integrated resource planning (IRP) or least-cost planning (LCP). Subsequent study phases will involve further analysis of options and possibly a collaborative formal effort to propose regulatory changes. The Phase I analysis proceeded in three steps: (1) identification and review of existing regulatory practices that affect utilities; selection of resources, particularly DSM; (2) preliminary analysis of ten financial mechanisms, and selection of three for further study; (3) detailed analysis of the three mechanisms, including consideration of how they could be implemented in Michigan and financial modeling of their likely impacts on utilities and ratepayers.

  3. Experimental geothermal research facilities study (Phase O). Final report No. 26405-6001-RU-00

    Energy Technology Data Exchange (ETDEWEB)

    1974-12-31

    This study focuses on identification of a representative liquid-dominated geothermal reservoir of moderate temperature and salinity, preliminary design of an appropriate energy conversion system, identification of critical technology and planning for the implementation of experimental facilities. Results of Phase O of the project are reported in two volumes. Volume II presents detailed results of studies and analyses arranged in nine appendices including the final report by a subcontractor on the study. The specific appendices are: Appendix A: Geothermal Resources of the Western United States; Appendix B: Site Selection Process and the East Mesa Geothermal Field; Appendix C: East Mesa Geothermal Field Reservoir Characteristics; Appendix D: Advisor's Views and Comments; Appendix E: Thermodynamic Analyses; Appendix F: Material and Corrosion Factors; Appendix G: Preliminary Reliability/Maintainability Analyses; Appendix H: Environmental Impact Analysis Guidelines; and Appendix I: Report to the National Science Foundation/TRW Systems Group by Rogers Engineering Company, Inc., San Francisco, California.

  4. In Vivo Antineoplastic Effects of the NSAID Sulindac in an Oral Carcinogenesis Model.

    Science.gov (United States)

    Katoumas, Konstantinos; Nikitakis, Nikolaos; Perrea, Despina; Dontas, Ismene; Sklavounou, Alexandra

    2015-07-01

    The antineoplastic properties of the NSAID sulindac have long been studied. The purpose of this study was to explore sulindac's in vivo effects on oral squamous cell carcinoma (SCC) oncogenesis using the hamster cheek pouch oral carcinogenesis model (HOCM). Thirty Syrian golden hamsters were divided into three experimental and two control groups (n = 6 each). The animals' right buccal pouches were treated with carcinogen for 9 weeks in one experimental and one control group and for 14 weeks in all other three groups. The animals of two experimental groups received sulindac from the 1st week and those of the third experimental group from the 10th week. After the end of carcinogenesis, treated buccal pouches were removed and examined. In animals treated with carcinogen for 14 weeks, development of oral SCC and tumor volume were significantly lower in animals that received sulindac from the first week of the experiment. Oral SCC developing in animals that received sulindac were more frequently well differentiated compared with the control group. In animals treated with carcinogen for 9 weeks, the animals that received sulindac developed lower grade of epithelial dysplasia. Proliferation index Ki-67 and positivity for the antiapoptotic molecule survivin were lower in the animals that received sulindac. Treatment with sulindac appears to delays the progression of oral premalignant lesions to oral SCC in the HOCM, also resulting in smaller and better differentiated tumors. These in vivo antineoplastic effects may be related to sulindac's ability to decrease cell proliferation and to prevent survivin expression.

  5. Inhibition of N-nitrosodiethylamine carcinogenesis in mice by naturally occurring organosulfur compounds and monoterpenes.

    Science.gov (United States)

    Wattenberg, L W; Sparnins, V L; Barany, G

    1989-05-15

    Naturally occurring compounds belonging to two chemical groups were studied for their capacities to inhibit N-nitrosodiethylamine (NDEA)-induced carcinogenesis in female A/J mice. One group consists of organosulfur compounds found in Allium species, including garlic, onions, leeks, and shallots, and the other, two monoterpenes, i.e., D-limonene and D-carvone. In an initial experiment, in which organosulfur compounds were investigated, diallyl disulfide, allyl mercaptan, and allyl methyl disulfide were found to produce a marked inhibition of NDEA-induced neoplasia of the forestomach when the test compounds were administered p.o. 96 and 48 h prior to NDEA. The most potent was diallyl disulfide which reduced forestomach tumor formation by more than 90%. Pulmonary adenoma formation also was inhibited but to a considerably lesser extent, i.e., about 30%. In three additional experiments, test compounds were given p.o. either 15 min or 1 h prior to NDEA. Under these conditions diallyl disulfide and allyl mercaptan again inhibited forestomach tumor formation substantially, i.e., greater than 75%, and pulmonary adenoma formation marginally, i.e., less than 20%. In these experiments D-limonene and D-carvone were tested and reduced forestomach tumor formation by slightly over 60% and pulmonary adenoma formation by about 35%. The results of these studies provide evidence of an increasing diversity of naturally occurring compounds having the capacity to inhibit nitrosamine carcinogenesis.

  6. Possible mechanisms by which pro- and prebiotics influence colon carcinogenesis and tumor growth.

    Science.gov (United States)

    Reddy, B S

    1999-07-01

    Oligofructose and inulin, selective fermentable chicory fructans, have been shown to stimulate the growth of bifidobacteria, which are regarded as beneficial strains in the colon. Studies were designed to evaluate inulin (Raftiline) and oligofructose (Raftilose) for their potential inhibitory properties against the development of colonic aberrant crypt foci (ACF) in rats. ACF are putative preneoplastic lesions from which adenomas and carcinomas may develop in the colon. The results of this study indicate that dietary administration of oligofructose and inulin inhibits the development of ACF in the colon, suggesting the potential colon tumor inhibitory properties of chicory fructans. The degree of ACF inhibition was more pronounced in animals given inulin than in those fed oligofructose. Because these prebiotics selectively stimulate the growth of bifidobacteria, ornithine decarboxylase (ODC) activities, ras-p21 ontoprotein expressions and tumor inhibitory activity of lyophilized cultures of Bifidobacterium longum against chemically induced colon and mammary carcinogenesis and against colonic tumor cell proliferation were examined. Dietary administration of lyophilized cultures of B. longum strongly suppressed colon and mammary tumor development and tumor burden. Inhibition of colon carcinogenesis was associated with a decrease in colonic mucosal cell proliferation and activities of colonic mucosal and tumor ornithine decarboxylase and ras-p21. Human clinical trials are likely to broaden our insight into the importance of the pre- and probiotics in health and disease.

  7. Luteolin supplementation adjacent to aspirin treatment reduced dimethylhydrazine-induced experimental colon carcinogenesis in rats.

    Science.gov (United States)

    Osman, Neamt H A; Said, Usama Z; El-Waseef, Ahmed M; Ahmed, Esraa S A

    2015-02-01

    Previous studies have shown that aspirin is used in colon cancer treatment. However, long-term of Aspirin usage is limited to gastric and renal toxicity. Luteolin (LUT) has cancer prevention and anti-inflammatory effects. The present study was designed to investigate the effect of LUT supplementation and Aspirin treatment in dimethylhydrazine (DMH)-induced carcinogenesis in rats. DMH (20 mg/kg BW/week) treated rats received gavages with Aspirin (50 mg/kg BW/week) and LUT (0.2 mg/kg BW/day) for 15 weeks. DMH injections induce colon polyps and renal bleeding, significantly increasing carcinoembryonic antigen (CEA), cyclooxygenase-2 (COX-2), oxidative stress, and kidney function tests and reducing antioxidant markers. Either Aspirin or LUT gavages alone or combined produce a significant decrease in colon polyp number and size, significantly decreasing CEA, COX-2, and oxidative stress and increasing antioxidant markers. In conclusion, the supplementations of LUT adjacent to Aspirin in the treatment of DMH-induced carcinogenesis in rats reflect a better effect than the use of Aspirin alone.

  8. Helicobacter pylori-infected animal models are extremely suitable for the investigation of gastric carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Masaaki Kodama; Kazunari Murakami; Ryugo Sato; Tadayoshi Okimoto; Akira Nishizono; Toshio Fujioka

    2005-01-01

    Although various animal models have been developed to clarify gastric carcinogenesis, apparent mechanism of gastric cancer was not clarified in recent years. Since the recognition of the pathogenicity of Helicobacter pylori (Hpylori), several animal models with Hpylori infection have been developed to confirm the association between Hpylori and gastric cancer. Nonhuman primate and rodent models were suitable for this study. Japanese monkey model revealed atrophic gastritis and p53mutation after long-term infection of Hpylori. Mongolian gerbil model showed the development of gastric carcinoma with H pylori infection alone, as well as with combination of chemical carcinogens, such as N-methylN-nitrosourea and N-methyl-N-nitro-N'-nitrosoguanidine.The histopathological changes of these animal models after Hpylori inoculation are closely similar to those in human beings with Hpylori infection. Eradication therapy attenuated the development of gastric cancer in Hpyloriinfected Mongolian gerbil. Although several features of animal models differ from those seen in human beings,these experimental models provide a starting point for further studies to clarify the mechanism of gastric carcinogenesis as a result of Hpylori infection and assist the planning of eradication therapy to prevent gastric carcinoma.

  9. Investigating evolutionary perspective of carcinogenesis with single-cell transcriptome analysis

    Institute of Scientific and Technical Information of China (English)

    Xi Zhang; Cheng Zhang; Zhongjun Li; Jiangjian Zhong; Leslie P. Weiner; Jiang F. Zhong

    2013-01-01

    We developed phase-switch microfluidic devices for molecular profiling of a large number of single cells. Whole genome microarrays and RNA-sequencing are commonly used to determine the expression levels of genes in cell lysates (a physical mix of millions of cells) for inferring gene functions. However, cellular heterogeneity becomes an inherent noise in the measurement of gene expression. The unique molecular characteristics of individual cells, as well as the temporal and quantitative information of gene expression in cells, are lost when averaged among all cells in cell lysates. Our single-cell technology overcomes this limitation and enables us to obtain a large number of single-cell transcriptomes from a population of cells. A collection of single-cell molecular profiles allows us to study carcinogenesis from an evolutionary perspective by treating cancer as a diverse population of cells with abnormal molecular characteristics. Because a cancer cellpopulation contains cells at various stages of development toward drug resistance, clustering similar single-cell molecular profiles could reveal how drug-resistant sub-clones evolve during cancer treatment. Here, we discuss how single-celltranscriptome analysis technology could enable the study of carcinogenesis from an evolutionary perspective and the development of drug-resistance in leukemia. The single-cell transcriptome analysis reported here could have a direct and significant impact on current cancer treatments and future personalized cancer therapies.

  10. Intergenerational Living - A Pilot Study in a University Setting. Final Report. Student Originated Studies.

    Science.gov (United States)

    Oklahoma State Univ., Stillwater.

    Results of a feasibility study to integrate the elderly into the university community are reported. The program occurred during the 1975 summer session at Oklahoma State University. Twenty retired persons attended classes, participated in other phases of campus life, and lived in a university dormitory. Twenty-three students acted as surrogate…

  11. Inhalation developmental toxicology studies: Teratology study of tetrahydrofuran in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1988-08-01

    Tetrahydrofuran (THF), a four-carbon cyclic ether, is widely used as an industrial solvent. Although it has been used in large quantities for many years, few long-term toxicology studies, and no reproductive or developmental studies, have been conducted on THF. This study addresses the potential for THF to cause developmental toxicity in rodents by exposing Sprague-Dawley rats and Swiss (CD-1) mice to 0, 600, 1800, or 5000 ppm tetrahydrofuran (THF) vapors, 6 h/day, 7 dy/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.33 positively mated rats or mice. Positively mated mice were exposed on days 6--17 of gestation (dg), and rats on 6--19 dg. The day of plug or sperm detection was designated as O dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded and live fetuses were examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 27 refs., 6 figs., 23 tabs.

  12. Central magnetic cooling and refrigeration machines (chiller) and their assessment. A feasibility study - Final report

    Energy Technology Data Exchange (ETDEWEB)

    Egolf, P. W.; Gonin, C. [University of Applied Sciences of Western Switzerland, HEIG-VD, Yverdon-les Bains (Switzerland); Kitanovski, A. [University of Ljubljana, Ljubljana (Slovenia)

    2010-03-15

    This final report for the Swiss Federal Office of Energy (SFOE) presents the results of a feasibility study made concerning magnetic cooling and refrigeration machines. This report presents a comprehensive thermodynamic and economic analysis of applications of rotary magnetic chillers. The study deals with magnetic chillers based on permanent magnets and superconducting magnets, respectively. The numerical design of permanent magnet assemblies with different magnetic flux densities is discussed. The authors note that superconducting magnetic chillers are feasible only in large-scale applications with over 1 MW of cooling power. This report describes new ideas for magnetic refrigeration technologies, which go beyond the state of the art. They show potential for a substantial reduction of costs and further improvements in efficiency. Rotary magnetic liquid chillers with 'wavy' structures and using micro tubes are discussed, as are superconducting magnetic chillers and future magneto-caloric technologies.

  13. [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.

  14. 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.

  15. Alterations of global histone H4K20 methylation during prostate carcinogenesis

    Directory of Open Access Journals (Sweden)

    Behbahani Turang E

    2012-03-01

    Full Text Available Abstract Background Global histone modifications have been implicated in the progression of various tumour entities. Our study was designed to assess global methylation levels of histone 4 lysine 20 (H4K20me1-3 at different stages of prostate cancer (PCA carcinogenesis. Methods Global H4K20 methylation levels were evaluated using a tissue microarray in patients with clinically localized PCA (n = 113, non-malignant prostate disease (n = 27, metastatic hormone-naive PCA (mPCA, n = 30 and castration-resistant PCA (CRPC, n = 34. Immunohistochemistry was performed to assess global levels of H4K20 methylation levels. Results Similar proportions of the normal, PCA, and mPCA prostate tissues showed strong H4K20me3 staining. CRPC tissue analysis showed the weakest immunostaining levels of H4K20me1 and H4K20me2, compared to other prostate tissues. H4K20me2 methylation levels indicated significant differences in examined tissues except for normal prostate versus PCA tissue. H4K20me1 differentiates CRPC from other prostate tissues. H4K20me1 was significantly correlated with lymph node metastases, and H4K20me2 showed a significant correlation with the Gleason score. However, H4K20 methylation levels failed to predict PSA recurrence after radical prostatectomy. Conclusions H4K20 methylation levels constitute valuable markers for the dynamic process of prostate cancer carcinogenesis.

  16. 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.

  17. Implication of human telomerase reverse transcriptase in cervical carcinogenesis and cancer recurrence.

    Science.gov (United States)

    Wang, P-H; Ko, J-L

    2006-01-01

    The objective of this study was to evaluate the implication of human telomerase reverse transcriptase (hTERT) in cervical carcinogenesis and cancer recurrence. One hundred three cases of uterine cervix, including 20 normal, 13 low-grade squamous intraepithelial lesion (LSIL), 30 high-grade squamous intraepithelial lesion (HSIL), and 40 squamous cell carcinoma (SCC) tissues, were evaluated for hTERT immunoreactivity. The expressions of hTERT in normal, LSIL, HSIL, and SCC tissues were compared by Fisher exact or Chi-square test. The relationships between hTERT and clinicopathologic variables of SCC were also assessed. Furthermore, SCC patients were subdivided into negative and positive hTERT expression subgroups, and Kaplan-Meier curves were used to plot the cumulative recurrence hazard for 5 years. There was a significant difference for hTERT expression between LSIL and HSIL subgroups (P recurrence hazard for 5 years was about 29% in positive hTERT expression subgroup compared to 0% in negative hTERT subgroup (P = 0.2866). In conclusion, a point stage of HSIL exists in the progression of cervical carcinogenesis when the hTERT expression increases significantly. Moreover, SCC patients with positive hTERT expression may have higher cumulative recurrence hazard.

  18. Strawberry phytochemicals inhibit azoxymethane/dextran sodium sulfate-induced colorectal carcinogenesis in Crj: CD-1 mice.

    Science.gov (United States)

    Shi, Ni; Clinton, Steven K; Liu, Zhihua; Wang, Yongquan; Riedl, Kenneth M; Schwartz, Steven J; Zhang, Xiaoli; Pan, Zui; Chen, Tong

    2015-03-10

    Human and experimental colon carcinogenesis are enhanced by a pro-inflammatory microenvironment. Pharmacologically driven chemopreventive agents and dietary variables are hypothesized to have future roles in the prevention of colon cancer by targeting these processes. The current study was designed to determine the ability of dietary lyophilized strawberries to inhibit inflammation-promoted colon carcinogenesis in a preclinical animal model. Mice were given a single i.p. injection of azoxymethane (10 mg kg-1 body weight). One week after injection, mice were administered 2% (w/v) dextran sodium sulfate in drinking water for seven days and then an experimental diet containing chemically characterized lyophilized strawberries for the duration of the bioassay. Mice fed control diet, or experimental diet containing 2.5%, 5.0% or 10.0% strawberries displayed tumor incidence of 100%, 64%, 75% and 44%, respectively (p < 0.05). The mechanistic studies demonstrate that strawberries reduced expression of proinflammatory mediators, suppressed nitrosative stress and decreased phosphorylation of phosphatidylinositol 3-kinase, Akt, extracellular signal-regulated kinase and nuclear factor kappa B. In conclusion, strawberries target proinflammatory mediators and oncogenic signaling for the preventive efficacies against colon carcinogenesis in mice. This works supports future development of fully characterized and precisely controlled functional foods for testing in human clinical trials for this disease.

  19. Mouse Genetic Models Reveal Surprising Functions of IκB Kinase Alpha in Skin Development and Skin Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Xiaojun [The Methodist Hospital Research Institute, Houston, TX 77030 (United States); Park, Eunmi [Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Fischer, Susan M. [Department of Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, TX 78967 (United States); Hu, Yinling, E-mail: huy2@mail.nih.gov [Cancer and Inflammation Program, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD 21701 (United States)

    2013-02-15

    Gene knockout studies unexpectedly reveal a pivotal role for IκB kinase alpha (IKKα) in mouse embryonic skin development. Skin carcinogenesis experiments show that Ikkα heterozygous mice are highly susceptible to chemical carcinogen or ultraviolet B light (UVB) induced benign and malignant skin tumors in comparison to wild-type mice. IKKα deletion mediated by keratin 5 (K5).Cre or K15.Cre in keratinocytes induces epidermal hyperplasia and spontaneous skin squamous cell carcinomas (SCCs) in Ikkα floxed mice. On the other hand, transgenic mice overexpressing IKKα in the epidermis, under the control of a truncated loricrin promoter or K5 promoter, develop normal skin and show no defects in the formation of the epidermis and other epithelial organs, and the transgenic IKKα represses chemical carcinogen or UVB induced skin carcinogenesis. Moreover, IKKα deletion mediated by a mutation, which generates a stop codon in the Ikkα gene, has been reported in a human autosomal recessive lethal syndrome. Downregulated IKKα and Ikkα mutations and deletions are found in human skin SCCs. The collective evidence not only highlights the importance of IKKα in skin development, maintaining skin homeostasis, and preventing skin carcinogenesis, but also demonstrates that mouse models are extremely valuable tools for revealing the mechanisms underlying these biological events, leading our studies from bench side to bedside.

  20. Strawberry Phytochemicals Inhibit Azoxymethane/Dextran Sodium Sulfate-Induced Colorectal Carcinogenesis in Crj: CD-1 Mice

    Directory of Open Access Journals (Sweden)

    Ni Shi

    2015-03-01

    Full Text Available Human and experimental colon carcinogenesis are enhanced by a pro-inflammatory microenvironment. Pharmacologically driven chemopreventive agents and dietary variables are hypothesized to have future roles in the prevention of colon cancer by targeting these processes. The current study was designed to determine the ability of dietary lyophilized strawberries to inhibit inflammation-promoted colon carcinogenesis in a preclinical animal model. Mice were given a single i.p. injection of azoxymethane (10 mg kg−1 body weight. One week after injection, mice were administered 2% (w/v dextran sodium sulfate in drinking water for seven days and then an experimental diet containing chemically characterized lyophilized strawberries for the duration of the bioassay. Mice fed control diet, or experimental diet containing 2.5%, 5.0% or 10.0% strawberries displayed tumor incidence of 100%, 64%, 75% and 44%, respectively (p < 0.05. The mechanistic studies demonstrate that strawberries reduced expression of proinflammatory mediators, suppressed nitrosative stress and decreased phosphorylation of phosphatidylinositol 3-kinase, Akt, extracellular signal-regulated kinase and nuclear factor kappa B. In conclusion, strawberries target proinflammatory mediators and oncogenic signaling for the preventive efficacies against colon carcinogenesis in mice. This works supports future development of fully characterized and precisely controlled functional foods for testing in human clinical trials for this disease.

  1. WMU Power Generation Study Task 2.0 Corn Cob Co-Combustion Study: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Folkedahl, Bruce [Folkedahl Consulting, Inc., Willmar, MN (United States)

    2009-12-01

    Much attention has been focused on renewable energy use in large-scale utilities and very small scale distributed energy systems. However, there is little information available regarding renewable energy options for midscale municipal utilities. The Willmar Municipal Utilities Corn Cob-Coal Co-Combustion Project was initiated to investigate opportunities available for small to midscale municipal utilities to "go green". The overall goal of the Project was to understand the current t'enewable energy research and energy efficiency projects that are or have been implemented at both larger and smaller scale and determine the applicability to midscale municipal utilities. More specific objectives for Task 2.0 of this project were to determine the technical feasibility of co-combusting com cobs with coal in the existing WMU boiler, and to identify any regulatory issues that might need to be addressed if WMU were to obtain a significant portion of its heat from such co-combustion. This report addresses the issues as laid out in the study proposal. The study investigated the feasibility of and demonstrated the technical effectiveness of co-combusting corn cobs with coal in the Willmar Municipal Utilities stoker boiler steam generation power plant. The results of the WMU Co-Combustion Project will serve as a model for other midscale utilities who wish to use corn cobs to generate renewable electrical energy. As a result of the Co-Combustion Project, the WMU plans to upgrade their stoker boiler to accept whole corn cobs as well as other types of biomass, while still allowing the fuel delivery system to use 100% coal as needed. Benefits of co-combustion will include: energy security, reduced Hg and CO2 air emissions, improved ash chemistry, potential future carbon credit sales, an immediate positive effect on the local economy, and positive attention focused on the WMU and the City of Willmar. The first step in the study was to complete a feasibility analysis

  2. Lower Flathead System Fisheries Study, Executive Summary, Volume I, 1983-1987 Final Report.

    Energy Technology Data Exchange (ETDEWEB)

    Cross, David; DosSantos, Joseph M.

    1988-06-01

    This Executive Summary, Volume I, of the lower Flathead System Fisheries Study Final Report, was prepared to provide a study overview for persons who are not fisheries scientists. The contents provide an introduction to the study and its objectives, a short description of the study area, a discussion of the major findings and conclusions of the study, and the description of fisheries management alternatives available to managers of the lower Flathead system. Technical reports were prepared for those portions of the study dealing with the lower Flathead River and its tributaries, Volume II, and the South Bay of Flathead Lake, Volume III. The annual hydrographic regime of the Flathead system, consisting of upper rivers, lake and lower river, has been modified by the construction and operation of two major hydroelectric facilities, Hungry Horse Dam on the south fork Flathead River and Kerr Dam at the outlet of Flathead Lake. The modified hydrographic regime has resulted in significant impacts to kokanee (Oncorhynchus nerka) and several species of trout. Kerr Dam, closed in 1938, controls Flathead Lake levels between 878.7 m (2883 ft) and 881.8 m (2893 ft) and discharges into the lower Flathead River. Kerr Dam is a 63.4 m (208 ft) high concrete arch structure located 7.2 km (4.5 miles) downstream from the outlet of Flathead Lake. The facility is used by Montana Power Company primarily for system frequency load control with some use for low level base load. 77 refs., 5 figs.

  3. Mechanisms linking excess adiposity and carcinogenesis promotion

    Directory of Open Access Journals (Sweden)

    Ana I. Pérez-Hernández

    2014-05-01

    Full Text Available Obesity constitutes one of the most important metabolic diseases being associated to insulin resistance development and increased cardiovascular risk. Association between obesity and cancer has also been well-established for several tumor types, such as breast cancer in postmenopausal women, colorectal and prostate cancer. Cancer is the first death cause in developed countries and the second one in developing countries, with high incidence rates around the world. Furthermore, it has been estimated that 15-20% of all cancer deaths may be attributable to obesity. Tumor growth is regulated by interactions between tumor cells and their tissue microenvironment. In this sense, obesity may lead to cancer development through dysfunctional adipose tissue and altered signaling pathways. In this review, three main pathways relating obesity and cancer development are examined: i inflammatory changes leading to macrophage polarization and altered adipokine profile; ii insulin resistance development; and iii adipose tissue hypoxia. Since obesity and cancer present a high prevalence, the association between these conditions is of great public health significance and studies showing mechanisms by which obesity lead to cancer development and progression are needed to improve prevention and management of these diseases.

  4. Animal Models of Colitis-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Manasa Kanneganti

    2011-01-01

    Full Text Available Inflammatory bowel disease (IBD is a group of chronic inflammatory disorders that affect individuals throughout life. Although the etiology and pathogenesis of IBD are largely unknown, studies with animal models of colitis indicate that dysregulation of host/microbial interactions are requisite for the development of IBD. Patients with long-standing IBD have an increased risk for developing colitis-associated cancer (CAC, especially 10 years after the initial diagnosis of colitis, although the absolute number of CAC cases is relatively small. The cancer risk seems to be not directly related to disease activity, but is related to disease duration/extent, complication of primary sclerosing cholangitis, and family history of colon cancer. In particular, high levels and continuous production of inflammatory mediators, including cytokines and chemokines, by colonic epithelial cells (CECs and immune cells in lamina propria may be strongly associated with the pathogenesis of CAC. In this article, we have summarized animal models of CAC and have reviewed the cellular and molecular mechanisms underlining the development of carcinogenic changes in CECs secondary to the chronic inflammatory conditions in the intestine. It may provide us some clues in developing a new class of therapeutic agents for the treatment of IBD and CAC in the near future.

  5. Inhalation developmental toxicology studies: Teratology study of n-hexane in rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.

    1987-12-01

    The straight chain hydrocarbon, n-hexane, is a volatile, ubiquitous solvent used in industrial, academic, and smaller commercial environments. The significant opportunity for women of child-bearing age to be exposed to this chemical prompted the undertaking of a study to assess the developmental toxicity of n-hexane in an animal model. Timed-pregnant (30 animals per group) and virgin (10 animals per group) Sprague-Dawley rats were exposed to 0 (filtered air), 200, 1000, and 5000 ppM n-hexane (99.9% purity) vapor in inhalation chambers for 20 h/day for a period of 14 consecutive days. Sperm-positive females were exposed for 6 to 19 days of gestation (dg) and virgins were exposed concurrently for 14 consecutive days. The day of sperm detection was designated as 0 dg for mated females. Adult female body weights were monitored prior to, throughout the exposure period, and at sacrifice. Uterine, placental, and fetal body weights were obtained for gravid females at sacrifice. Implants were enumerated and their status recorded as live fetus, early or late resorption, or dead. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 16 refs., 3 figs., 7 tabs.

  6. Inhalation developmental toxicology studies: Teratology study of methyl ethyl ketone in mice: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Dill, J.A.; Evanoff, J.J.; Rommereim, R.L.; Weigel, R.J.; Westerberg, R.B.

    1989-02-01

    Methyl ethyl ketone (MEK) is a widely used industrial solvent which results in considerable human exposure. In order to assess the potential for MEK to cause developmental toxicity in rodents, four groups of Swiss (CD-1) mice were exposed to 0, 400, 1000 or 3000 ppM MEK vapors, 7 h/day, 7 dy/wk. Ten virgin females and approx.30 plug-positive females per group were exposed concurrently for 10 consecutive days (6--15 dg for mated mice). Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice on 18 dg. Uterine implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. Exposure of pregnant mice to these concentrations of MEK did not result in apparent maternal toxicity, although there was a slight, treatment-correlated increase in liver to body weight ratios which was significant for the 3000-ppM group. Mild developmental toxicity was evident at 3000-ppM as a reduction in mean fetal body weight. This reduction was statistically significant for the males only, although the relative decrease in mean fetal body weight was the same for both sexes. 17 refs., 4 figs., 10 tabs.

  7. Inhalation developmental toxicology studies: Teratology study of isoprene in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Stoney, K.H.; Westerberg, R.B.; Rommereim, R.L.; Weigel, R.J.

    1989-01-01

    Isoprene, a reactive, branched diene, is used in large quantities in the manufacture of polyisoprene and as a copolymer in the synthesis of butyl rubber. The potential for isoprene to cause developmental toxicity was assessed in rodents, by exposing four groups each of Sprague-Dawley rats and Swiss (CD-1) mice to 0, 280, 1400, or 7000 ppM isoprene vapors, 6 h/day, 7 day/wk. Each treatment group consisted of 10 virgin females (for comparison), and approx.30 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 31 refs., 6 figs., 19 tabs.

  8. Inhalation developmental toxicology studies: Teratology study of acetone in mice and rats: Final report

    Energy Technology Data Exchange (ETDEWEB)

    Mast, T.J.; Evanoff, J.J.; Rommereim, R.L.; Stoney, K.H.; Weigel, R.J.; Westerberg, R.B.

    1988-11-01

    Acetone, an aliphatic ketone, is a ubiquitous industrial solvent and chemical intermediate; consequently, the opportunity for human exposure is high. The potential for acetone to cause developmental toxicity was assessed in Sprague-Dawley rats exposed to 0, 440, 2200, or 11000 ppm, and in Swiss (CD-1) mice exposed to 0, 440, 2200, and 6600 ppm acetone vapors, 6 h/day, 7 days/week. Each of the four treatment groups consisted of 10 virgin females (for comparison), and approx.32 positively mated rats or mice. Positively mated mice were exposed on days 6-17 of gestation (dg), and rats on 6-19 dg. The day of plug or sperm detection was designated as 0 dg. Body weights were obtained throughout the study period, and uterine and fetal body weights were obtained at sacrifice (rats, 20 dg; mice, 18 dg). Implants were enumerated and their status recorded. Live fetuses were sexed and examined for gross, visceral, skeletal, and soft-tissue craniofacial defects. 46 refs., 6 figs., 27 tabs.

  9. Iron:An emerging factor in colorectal carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Anita; CG; Chua; Borut; Klopcic; Ian; C; Lawrance; John; K; Olynyk; Debbie; Trinder

    2010-01-01

    The carcinogenic potential of iron in colorectal cancer(CRC) is not fully understood.Iron is able to undergo reduction and oxidation,making it important in many physiological processes.This inherent redox property of iron,however,also renders it toxic when it is present in excess.Iron-mediated generation of reactive oxygen species via the Fenton reaction,if uncontrolled,may lead to cell damage as a result of lipid peroxidation and oxidative DNA and protein damage.This may promote carcinogenesis through incr...

  10. Contribution of bone marrow derived cells to pancreatic carcinogenesis

    Directory of Open Access Journals (Sweden)

    Christopher J Scarlett

    2013-03-01

    Full Text Available Pancreatic cancer is a complex, aggressive and heterogeneous malignancy driven by the multifaceted interactions within the tumor microenvironment. While it is known that the tumor microenvironment accommodates many cell types, each playing a key role in tumorigenesis, the major source of these stromal cells is not well understood. This review examines the contribution of bone marrow-derived cells (BMDC to pancreatic carcinogenesis, with respect to their role in constituting the tumor microenvironment. In particular, their role in supporting fibrosis, immunosuppression and neovascularisation will be discussed.

  11. Apc-Mutant Kyoto Apc Delta (KAD) Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takuji, E-mail: tmntt08@gmail.com [Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-Cho, Gifu 500-8513 (Japan); Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Shimizu, Masahito; Kochi, Takahiro; Shirakami, Yohei [Department of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Mori, Takayuki [Department of Pharmacy, Ogaki Municipal Hospital, 4-86 Minaminokawa-cho, Ogaki 503-8502 (Japan); Watanabe, Naoki [Department of Diagnostic Pathology (DDP) & Research Center of Diagnostic Pathology (RC-DiP), Gifu Municipal Hospital, 7-1 Kashima-Cho, Gifu 500-8513 (Japan); Naiki, Takafumi [Department of Clinical Laboratory, Gifu Municipal Hospital, 7-1 Kashima-cho, Gifu 500-8513 (Japan); Moriwaki, Hisataka [Department of Internal Medicine/Gastroenterology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194 (Japan); Yoshimi, Kazuto; Serikawa, Tadao; Kuramoto, Takashi [The Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501 (Japan)

    2014-07-21

    Despite widening interest in the possible association between infection/inflammation and cancer development, knowledge of this issue in relation to oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD) rats, which are vulnerable to developing inflammation-associated colorectal carcinogenesis, to 4-nitroquinoline 1-oxide (4-NQO)-induced tongue carcinogenesis in order to clarify the role of inflammation in oral cancer. KAD (20 males and 22 females) and F344/NS1c (22 males and 23 females) rats received drinking water with or without 4-NQO (20 ppm) for eight weeks. Histopathological and immunohistochemical analyses of the tongue were performed at week 20. Additionally, the mRNA expression of inflammatory cytokines in the tongue mucosa was determined at week 8. Tongue squamous cell carcinoma (SCC) developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the female KAD rats was significantly greater than that observed in the male KAD (p < 0.01) and female F344/NS1c rats (p < 0.05). The levels of inflammation and the mRNA expression of inflammatory cytokines in the tongue in the 4-NQO-treated female KAD rats were the highest among the rats given 4-NQO. These results show that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue carcinogenesis, suggesting the utility of models employing KAD rats for investigating the pathobiology of oral (tongue) carcinogenesis associated with inflammation.

  12. Apc-Mutant Kyoto Apc Delta (KAD Rats Are Susceptible to 4-NQO-Induced Tongue Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2014-07-01

    Full Text Available Despite widening interest in the possible association between infection/ inflammation and cancer development, knowledge of this issue in relation to oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD rats, which are vulnerable to developing inflammation-associated colorectal carcinogenesis, to 4-nitroquinoline 1-oxide (4-NQO-induced tongue carcinogenesis in order to clarify the role of inflammation in oral cancer. KAD (20 males and 22 females and F344/NS1c (22 males and 23 females rats received drinking water with or without 4-NQO (20 ppm for eight weeks. Histopathological and immunohistochemical analyses of the tongue were performed at week 20. Additionally, the mRNA expression of inflammatory cytokines in the tongue mucosa was determined at week 8. Tongue squamous cell carcinoma (SCC developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the female KAD rats was significantly greater than that observed in the male KAD (p < 0.01 and female F344/NS1c rats (p < 0.05. The levels of inflammation and the mRNA expression of inflammatory cytokines in the tongue in the 4-NQO-treated female KAD rats were the highest among the rats given 4-NQO. These results show that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue carcinogenesis, suggesting the utility of models employing KAD rats for investigating the pathobiology of oral (tongue carcinogenesis associated with inflammation.

  13. Interdisciplinary study of reservoir compartments and heterogeneity. Final report, October 1, 1993--December 31, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Van Kirk, C.

    1998-01-01

    A case study approach using Terry Sandstone production from the Hambert-Aristocrat Field, Weld County, Colorado was used to document the process of integration. One specific project goal is to demonstrate how a multidisciplinary approach can be used to detect reservoir compartmentalization and improve reserve estimates. The final project goal is to derive a general strategy for integration for independent operators. Teamwork is the norm for the petroleum industry where teams of geologists, geophysicists, and petroleum engineers work together to improve profits through a better understanding of reservoir size, compartmentalization, and orientation as well as reservoir flow characteristics. In this manner, integration of data narrows the uncertainty in reserve estimates and enhances reservoir management decisions. The process of integration has proven to be iterative. Integration has helped identify reservoir compartmentalization and reduce the uncertainty in the reserve estimates. This research report documents specific examples of integration and the economic benefits of integration.

  14. An archival study of eyewitness memory of the Titanic's final plunge.

    Science.gov (United States)

    Riniolo, Todd C; Koledin, Myriah; Drakulic, Gregory M; Payne, Robin A

    2003-01-01

    A handful of real-life studies demonstrate that most eyewitnesses accurately recall central details (i.e., the gist of what happened) from traumatic events. The authors evaluated the accuracy of archival eyewitness testimony from survivors of the Titanic disaster who witnessed the ship's final plunge. The results indicate that most eyewitness testimony (15 eyewitnesses of 20) is consistent with forensic evidence that demonstrates that the Titanic was breaking apart while it was still on the ocean's surface. Despite the methodological limitations of archival research, the authors provide evidence from a single-occurrence traumatic event (with a large-scale loss of life) that the majority of eyewitnesses accurately recall central details.

  15. Distinct response of the hepatic transcriptome to Aflatoxin B1 induced hepatocellular carcinogenesis and resistance in rats

    Science.gov (United States)

    Shi, Jiejun; He, Jiangtu; Lin, Jing; Sun, Xin; Sun, Fenyong; Ou, Chao; Jiang, Cizhong

    2016-01-01

    Aflatoxin is a natural potent carcinogen and a major cause of liver cancer. However, the molecular mechanisms of hepatocellular carcinogenesis remain largely unexplored. In this study, we profiled global gene expression in liver tissues of rats that developed hepatocellular carcinoma (HCC) from aflatoxin B1 (AFB1) administration and those that were AFB1-resistant, as well as rats without AFB1 exposure as a control. AFB1 exposure resulted in extensive perturbation in gene expression with different functions in HCC and AFB1 resistance (AR) samples. The differentially expressed genes (DEGs) in HCC sample were enriched for cell proliferation, cell adhesion and vasculature development that largely contribute to carcinogenesis. Anti-apoptosis genes were up-regulated in HCC sample whereas apoptosis-induction genes were up-regulated in AR sample. AFB1 exposure also caused extensive alteration in expression level of lncRNAs. Among all the 4511 annotated lncRNAs, half of them were highly expressed only in HCC sample and up-regulated a group of protein-coding genes with cancer-related functions: apoptosis regulation, DNA repair, and cell cycle. Intriguingly, these genes were down-regulated by lncRNAs highly expressed in AR sample. Collectively, apoptosis is the critical biological process for carcinogenesis in response to AFB1 exposure through changes in expression level of both protein-coding and lncRNA genes. PMID:27545718

  16. Insights into the field carcinogenesis of ovarian cancer based on the nanocytology of endocervical and endometrial epithelial cells

    Science.gov (United States)

    Damania, Dhwanil; Roy, Hemant K.; Kunte, Dhananja; Hurteau, Jean A.; Subramanian, Hariharan; Cherkezyan, Lusik; Krosnjar, Nela; Shah, Maitri; Backman, Vadim

    2013-01-01

    Ovarian cancer ranks fifth in cancer fatalities among American women. Although curable at early stages with surgery, most women are diagnosed with symptoms of late-stage metastatic disease. Moreover, none of the current diagnostic techniques are clinically recommended for at-risk women as they preferentially target low-grade tumors (which do not affect longevity) and fail to capture early signatures of more lethal serous tumors which originate in the fimbrae region of the fallopian tubes. Hence, the early detection of ovarian cancer is challenging given the current strategy. Recently, our group has developed a novel optical imaging technique, partial wave spectroscopic (PWS) microscopy, that can quantify the nanoscale macromolecular density fluctuations within biological cells via a biomarker, disorder strength (Ld). Using the concept of field carcinogenesis, we propose a method of detecting ovarian cancer by PWS assessment of endometrial and endocervical columnar cells. The study includes 26 patients (controls = 15, cancer = 11) for endometrium and 23 (controls = 13, cancer = 10) for endocervix. Our results highlight a significant increase in Ld (% fold-increase > 50%, P-value < 0.05) for columnar epithelial cells obtained from cancer patients compared to controls for both endocervix and endometrium. Overall, the quantification of field carcinogenic events in the endometrium and the novel observation of its extension to the cervix are unique findings in the understanding of ovarian field carcinogenesis. We further show independent validation of the presence of cervical field carcinogenesis with mico-RNA expression data. PMID:23436651

  17. Inhibitory effects of polysaccharides isolated from Phellinus gilvus on benzo(a)pyrene-induced forestomach carcinogenesis in mice

    Institute of Scientific and Technical Information of China (English)

    Jae-Sung Bae; Kwang-Ho Jang; Hyunee Yim; Seung-Chun Park; Hee-Kyung Jin

    2005-01-01

    AIM: Although polysaccharides from Phellinus mushrooms are a well-known material with anti-tumor properties, there is no information about the effect of polysaccharides from Phellinus gilvus (PG) on tumor. The modulating effect of polysaccharides isolated from PG on the benzo(a)pyrene (BaP)-induced forestomach carcinogenesis in ICR female mice was investigated in this study.METHODS: A forestomach carcinogenesis model was established in 40 ICR female mice receiving oral administration of BaP for 4 wk. The mice were randomly assigned to 4 groups (10 each). The mice in each group were treated with sterile water or PG for 4 and 8 wk (SW4,PGW4, SW8, and PGW8 groups). Eight or 12 wk after the first dose of BaP, forestomachs were removed for histopathological and RT-PCR analysis.RESULTS: In histopathological changes and RT-PCR analysis, sterile water-treated mice showed significant hyperplasia of the gastric mucosa with a significantly increased expression of mutant p53 mRNA compared to mice treated with PG for 8 wk.CONCLUSION: Polysaccharides isolated from PG may inhibit BaP-induced forestomach carcinogenesis in mice bydown-regulating mutant p53 expression.

  18. Systems study of fuels from grains and grasses. Phase I. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Benson, W.; Allen, A.; Athey, R.; McElroy, A.; Davis, M.; Bennett, M.

    1978-02-24

    The program reported on herein consists of a first phase analysis of the potential for significant and economically viable contributions to U.S. energy needs from grasses and grains by the photosynthetic production of biomass. The study does not include other cultivated crops such as sugar cane, sugar beets, cotton, tobacco, vegetables, fruits, etc. The scope of the study encompasses grain crop residues, whole plant biomass from grain crops and nongrain crops on cropland, and whole plant biomass from grasses on pasture, rangeland, and federal range. The basic approach to the study involves first an assessment of current total biomass generation from the various grasses and grains on cropland, pasture, range, and federal range, and aggregating the production by combinations of crop residues and whole plant biomass; second, evaluation of possibilities for introduction of new crops and expanding production to marginal or presently idle land; third, development of proposed reasonable scenarios for actually harvesting biomass from selected combinations of crop residues, forages and hays, and new crops from land now in production, plus additional marginal or underutilized land brought into production; and finally, assessment on national and regional or local scales of the production that might be affected by reasonable scenarios. This latter effort includes analysis of tentative possibilities for reallocating priorities and needs with regard to production of grain for export or for livestock production. The overall program includes a case study analysis of production economics for a representative farm of about 1,000 acres (405 ha) located in Iowa.

  19. Study supporting the phasing out of environmentally harmful subsidies. Annexes to Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Withana, S.; Ten Brink, P.; Franckx, L.; Hirschnitz-Garbers, M.; Mayeres, I.; Oosterhuis, F.; Porsch, L.

    2012-10-15

    The need to reform ineffective or harmful public subsidies has long been recognised and has been a contentious point of discussion for several years. The EU has a long-standing commitment to removing or phasing out environmentally harmful subsidies (EHS). Most recently, the need to phase out EHS is reiterated in the 'Roadmap for a resource efficient Europe' which includes a milestone that 'by 2020 EHS will be phased out, with due regard to the impact on people in need'. Despite several commitments, progress has been slow and subsidies remain an issue in most EU countries. This study focuses specifically on EHS at the level of EU Member States; it identifies key types of EHS and examines cases of existing EHS across a range of environmental sectors and issues, including subsidies from non-action. The study also analyses examples of good practices in the reform of EHS in EU Member States and the lessons that can be learnt from these cases. Finally, based on this analysis, it develops practical recommendations on phasing out and reforming EHS to support the objectives of the Europe 2020 Strategy and the resource efficiency agenda. The study was carried out between January and October 2012 and is based on an analysis of literature and consultation with experts and policy makers. The sectoral cases studied are listed and discussed in this annex report: agriculture, climate and energy, fisheries, food, forestry, materials, transport, waste, and water.

  20. Modulation of dietary fat-enhanced colorectal carcinogenesis in N-methyl-N'-nitro-N-nitrosoguanidine-treated rats by a vegetables-fruit mixture

    NARCIS (Netherlands)

    Rijnkels, J.M.; Hollanders, V.H.M.; Woutersen, R.A.; Koeman, J.H.; Alink, G.M.

    1997-01-01

    The modulation of a vegetables-fruit mixture on N-methyl-N'-nitro-N- nitrosoguanidine (MNNG)-induced colorectal carcinogenesis was studied in rats maintained on a low- or a high-fat diet. Far this purpose, 120 rats received a semisynthetic diet without (Groups A and C) or with a vegetables-fruit mix

  1. Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Zenaida P Lopez-Dee

    Full Text Available Colorectal Cancer (CRC is one of the late complications observed in patients suffering from inflammatory bowel diseases (IBD. Carcinogenesis is promoted by persistent chronic inflammation occurring in IBD. Understanding the mechanisms involved is essential in order to ameliorate inflammation and prevent CRC. Thrombospondin 1 (TSP-1 is a multidomain glycoprotein with important roles in angiogenesis. The effects of TSP-1 in colonic tumor formation and growth were analyzed in a model of inflammation-induced carcinogenesis. WT and TSP-1 deficient mice (TSP-1-/- of the C57BL/6 strain received a single injection of azoxymethane (AOM and multiple cycles of dextran sodium sulfate (DSS to induce chronic inflammation-related cancers. Proliferation and angiogenesis were histologically analyzed in tumors. The intestinal transcriptome was also analyzed using a gene microarray approach. When the area containing tumors was compared with the entire colonic area of each mouse, the tumor burden was decreased in AOM/DSS-treated TSP-1-/- versus wild type (WT mice. However, these lesions displayed more angiogenesis and proliferation rates when compared with the WT tumors. AOM-DSS treatment of TSP-1-/- mice resulted in significant deregulation of genes involved in transcription, canonical Wnt signaling, transport, defense response, regulation of epithelial cell proliferation and metabolism. Microarray analyses of these tumors showed down-regulation of 18 microRNAs in TSP-1-/- tumors. These results contribute new insights on the controversial role of TSP-1 in cancer and offer a better understanding of the genetics and pathogenesis of CRC.

  2. Viral Carcinogenesis: Factors Inducing DNA Damage and Virus Integration

    Directory of Open Access Journals (Sweden)

    Yan Chen

    2014-10-01

    Full Text Available Viruses are the causative agents of 10%–15% of human cancers worldwide. The most common outcome for virus-induced reprogramming is genomic instability, including accumulation of mutations, aberrations and DNA damage. Although each virus has its own specific mechanism for promoting carcinogenesis, the majority of DNA oncogenic viruses encode oncogenes that transform infected cells, frequently by targeting p53 and pRB. In addition, integration of viral DNA into the human genome can also play an important role in promoting tumor development for several viruses, including HBV and HPV. Because viral integration requires the breakage of both the viral and the host DNA, the integration rate is believed to be linked to the levels of DNA damage. DNA damage can be caused by both endogenous and exogenous factors, including inflammation induced by either the virus itself or by co-infections with other agents, environmental agents and other factors. Typically, cancer develops years to decades following the initial infection. A better understanding of virus-mediated carcinogenesis, the networking of pathways involved in transformation and the relevant risk factors, particularly in those cases where tumorigenesis proceeds by way of virus integration, will help to suggest prophylactic and therapeutic strategies to reduce the risk of virus-mediated cancer.

  3. Langerhans Cells Facilitate UVB-induced Epidermal Carcinogenesis

    Science.gov (United States)

    Lewis, Julia M.; Bürgler, Christina D.; Freudzon, Marianna; Golubets, Kseniya; Gibson, Juliet F.; Filler, Renata B.; Girardi, Michael

    2015-01-01

    Ultraviolet B (UVB) light is considered the major environmental inducer of human keratinocyte DNA mutations, including within the tumor-suppressor gene p53, and chronic exposure is associated with cutaneous squamous cell carcinoma (SCC) formation. Langerhans cells (LC) comprise a dendritic network within the suprabasilar epidermis, yet the role of LC in UVB-induced carcinogenesis is largely unknown. Herein, we show that LC-intact epidermis develops UVB-induced tumors more readily than LC-deficient epidermis. While levels of epidermal cyclopyrimidine dimers (CPD) following acute UVB exposure are equivalent in the presence or absence of LC, chronic UVB-induced p53 mutant clonal islands expand more readily in association with LC which remain largely intact and are preferentially found in proximity to the expanding mutant keratinocyte populations. The observed LC facilitation of mutant p53 clonal expansion is completely αβ and γδ T-cell independent, and is associated with increased intraepidermal expression of interleukin (IL)-22 and the presence of group 3 innate lymphoid cells (ILC3). These data demonstrate that LC play a key role in UVB-induced cutaneous carcinogenesis, and suggest that LC locally stimulate keratinocyte proliferation and innate immune cells that provoke tumor outgrowth. PMID:26053049

  4. Transcriptional regulation of cadherins during development and carcinogenesis.

    Science.gov (United States)

    Peinado, Héctor; Portillo, Francisco; Cano, Amparo

    2004-01-01

    The cadherin superfamily of Ca(2+)-dependent homophilic adhesion molecules plays a critical role in regulating cell-to-cell interactions. During development, the expression of different cadherins is highly dynamic, since they are associated with the morphogenesis, establishment and/or maintenance of different tissues. Alterations in cadherin expression or function occur frequently during carcinogenesis, such as the loss of the epithelial cadherin (E-cadherin) and/or the aberrant expression of other cadherins. Indeed, the aberrant expression of cadherins has been detected during carcinoma invasion, a process which is reminiscent of the epithelial-mesenchymal transition (EMT) so important in many critical developmental processes. The functional regulation of cadherins can occur at many different levels, from transcriptional regulation to the control of the strength of the cadherin-mediated cell-cell interaction. In this review, we will focus on the transcriptional control of cadherin expression, both in development and carcinogenesis, paying particular attention to the regulation of E-cadherin given its proposed role as a suppressor of invasion. We will discuss the main genetic and epigenetic mechanisms involved in down-regulating E-cadherin expression, and we will analyse the mechanisms involved in regulating EMT, in an attempt to elucidate which elements are common to this process in both physiological and pathological situations.

  5. Evaluation of techniques used to study vegetation and avifauna in National Petroleum Reserve of Alaska: 1976 NPRA final report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The report covers the evaluation of techniques used to study vegetation and avifauna in National Petroleum Reserve of Alaska. This is the 1976 NPRA final report. The...

  6. Studies of elasticity, sound propagation and attenuation of acoustic modes in granular media: final report

    Energy Technology Data Exchange (ETDEWEB)

    Makse, Hernan A. [City College of New York, NY (United States). Levich Inst., Dept. of Physcis; Johnson, David L. [Schlumberger-Doll Research, Cambridge, MA (United States)

    2014-09-03

    This is the final report describing the results of DOE Grant # DE-FG02-03ER15458 with original termination date of April 31, 2013, which has been extended to April 31, 2014. The goal of this project is to develop a theoretical and experimental understanding of sound propagation, elasticity and dissipation in granular materials. The topic is relevant for the efficient production of hydrocarbon and for identifying and characterizing the underground formation for storage of either CO2 or nuclear waste material. Furthermore, understanding the basic properties of acoustic propagation in granular media is of importance not only to the energy industry, but also to the pharmaceutical, chemical and agricultural industries. We employ a set of experimental, theoretical and computational tools to develop a study of acoustics and dissipation in granular media. These include the concept effective mass of granular media, normal modes analysis, statistical mechanics frameworks and numerical simulations based on Discrete Element Methods. Effective mass measurements allow us to study the mechanisms of the elastic response and attenuation of acoustic modes in granular media. We perform experiments and simulations under varying conditions, including humidity and vacuum, and different interparticle force-laws to develop a fundamental understanding of the mechanisms of damping and acoustic propagation in granular media. A theoretical statistical approach studies the necessary phase space of configurations in pressure, volume fraction to classify granular materials.

  7. Final Report for the Arroyo Las Positas Maintenance Impact Study, Lawrence Livermore National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    van Hattem, M; Paterson, L

    2006-01-12

    In 2000, the Lawrence Livermore National Laboratory's (LLNL) Environmental Protection Department, in coordination with Plant Engineering (PE), began dredging sections of the Arroyo Las Positas (ALP) to alleviate concerns about flooding of sensitive facilities within the mainsite of Lawrence Livermore National Laboratory. In order to reduce potential impacts on the federally threatened California red-legged frog (Rana aurora draytonii), LLNL proposed to dredge sections of the ALP in a ''checkerboard pattern'', resulting in a mosaic of open water habitat and vegetated sections (Figure 1). The Arroyo Las Positas Management Plan (Plan) was coordinated with both state and federal agencies including the U.S. Fish and Wildlife Service (USFWS), California Department of Fish and Game (CDF&G), San Francisco Regional Water Quality Control Board (SFRWQCB), and the Army Corp of Engineers (ACOE). Water Discharge Requirements (WDRs) were issued for this project on December 30, 1999 (Order No. 99-086) by the SFRWQCB. Provision 19 of the WDRs outlined a five-year (2000 through 2004) Maintenance Impact Study (MIS) that LLNL began in coordination with dredging work that was conducted as part of the Arroyo Las Positas Management Plan. Provision 20 of these WDRs requires LLNL to submit a final report of the results of the Maintenance Impact Study for this project to the SFRWQCB. The purpose of this report is to present the results of the Maintenance Impact Study for Arroyo Las Positas and meet the requirements of Provision 20. A description of the annual monitoring included in this Maintenance Impact Study is included in the methods section of this report. Initially the Plan called for dredging the entire length of the Arroyo Las Positas (approximately 6,981 linear feet) over a 5-year period to minimize temporal impacts on the California red-legged frog. Dredging occurred in 2000 ({approx}1,300 ft.), 2001 ({approx}800 ft.), and 2002 ({approx}1,200 ft.), which

  8. Radiation carcinogenesis. Comprehensive final report, 16 May 1979-31 December 1980

    Energy Technology Data Exchange (ETDEWEB)

    Warren, S; Brown, C E; Gates, O

    1981-03-01

    This abstract covers three main areas of investigation: mesothelioma induction by asbestos, radiation tumorigenesis and transplantable tumors. Canadian and Rhodesian asbestos fibers have been administered under anesthesia to rats by intratracheal, intrapleural and intraperitoneal injection. Additional groups were given 3-methylcholanthrene or x-radiation along with asbestos. A large series of mice also treated as above have displayed mesotheliomas. In addition, glass fiber injections and feeding of asbestos were done and have produced negative results to date. The carcinogenic effect of whole-body radiation on hemi-irradiated parabiont partners exposed to a single 1000 R dose of x-ray was evidenced by a significant increase in the incidence of malignant tumors in only six tissues: skin, supporting soft tissue, kidney, bone, pancreatic islets and ovary. In the male adrenal medulla and in the female breast genetic and parabiotic hormonal factors were judged to exert a significant effect. The occurrence of incisional (anastomotic) sarcomas in significant numbers in hemi-irradiated and parabiont control pairs suggests the operation of mechanical factors complicating the healing process, only slightly enhanced by radiation. One of the very valuable but unanticipated developments of the rat radiation program was the isolation of two transplantable endocrine tumors with strong hormonal potentials: an insulinoma of the pancreas and a pheochromocytoma of the adrenal medulla.

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

    Directory of Open Access Journals (Sweden)

    Adil H.H. Bashir

    2011-07-01

    Full Text Available 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.

  10. 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.

  11. Glycemic load, glycemic index, and pancreatic cancer risk in the Netherlands Cohort Study

    NARCIS (Netherlands)

    Heinen, M.M.; Verhage, B.A.J.; Lumey, L.H.; Brants, H.A.M.; Goldbohm, R.A.; Brandt, P.A. van den

    2008-01-01

    Background: Recent studies of pancreatic cancer suggest a role for hyperinsulinemia in carcinogenesis. Because insulin is secreted in response to elevated blood glucose concentrations, dietary factors that increase these concentrations may be important in pancreatic carcinogenesis. Objective: The ob

  12. Study of B-Meson Decays to Final States with a Single Charm Baryon

    Energy Technology Data Exchange (ETDEWEB)

    Majewski, Stephanie A. [Stanford Univ., CA (United States)

    2007-08-01

    A study of B-meson decays to final states with a single charm baryon is presented based on data recorded by the BABAR detector at the Stanford Linear Accelerator Center. Although the B meson is the lightest bottom-flavored meson, it is heavy enough to decay to a baryon made of three quarks and an antibaryon made of three antiquarks. By studying the baryonic weak decays of the B meson, we can investigate baryon production mechanisms in heavy meson decays. In particular, we measure the rates of the decays B- → Λ+c$\\bar{p}$π- and $\\bar{B}$0 → Λ+c$\\bar{p}$. Comparing these rates, we confirm an observed trend in baryonic B decays that the decay with the lower energy release, B- → Λ+c$\\bar{p}$π-, is favored over $\\bar{B}$0 → Λ+c$\\bar{p}$. The dynamics of the baryon-antibaryon (Λ+c$\\bar{p}$) system in the three-body decay also provide insight into baryon-antibaryon production mechanisms. The B- → Λ+c$\\bar{p}$π- system is a laboratory for searches for excited #c baryon states; we observe the resonant decays B- → Σc(2455) 0$\\bar{p}$ and B- → Σc(2800) 0$\\bar{p}$. This is the first observation of the decay B- → Σc(2800) 0$\\bar{p}$; however, the mass of the observed #c(2800)0 state is inconsistent with previous measurements. Finally, we examine the angular distribution of the B- → Σc(2455) 0$\\bar{p}$ decays and measure the spin of the B- → Σc(2455) 0$\\bar{p}$ baryon to be J = 1/2, as predicted by the quark model.

  13. Perceived stress at transition to workplace: a qualitative interview study exploring final-year medical students’ needs

    Directory of Open Access Journals (Sweden)

    Moczko TR

    2016-01-01

    Full Text Available Tobias R Moczko,1,2,* Till J Bugaj,1,* Wolfgang Herzog,1 Christoph Nikendei1 1Department for General Internal and Psychosomatic Medicine, University Hospital of Heidelberg, Heidelberg, 2School of Medicine, Faculty of Health, Witten/Herdecke University, Witten, Germany *These authors contributed equally to this work Objectives: This study was designed to explore final-year medical students’ stressors and coping strategies at the transition to the clinical workplace. Methods: In this qualitative study, semi-standardized interviews with eight final-year medical students (five male, three female; aged 25.9±1.4 years were conducted during their internal medicine rotation. After verbatim transcription, a qualitative content analysis of students’ impressions of stress provoking and easing factors during final-year education was performed. Results: Students’ statements regarding burdens and dealing with stress were classified into four main categories: A perceived stressors and provoking factors, B stress-induced consequences, C personal and external resources for preventing and dealing with stress, and D final-year students’ suggestions for workplace improvement. Conclusion: Final-year medical students perceived different types of stress during their transition to medical wards, and reported both negative consequences and coping resources concerning perceived stress. As supervision, feedback, and coping strategies played an important role in the students’ perception of stress, final-year medical education curricula development should focus on these specifically. Keywords: undergraduate medical education, stress prevention, final-year medical education, workplace learning, qualitative research

  14. Perceptions Regarding Employment Prospects among Final Year Students as Determined by Field of Study, Gender and Race

    Directory of Open Access Journals (Sweden)

    Hillary Tomu

    2013-01-01

    Full Text Available This study investigated university student perceptions regarding their employment prospects and the extent to which differences exist regarding perceptions of employment prospects among beneficiaries and non-beneficiaries of the South African government’s affirmative action policies. A quantitative research design was used in which self administered questionnaires were distributed to respondents. A purposive sampling procedure was utilised. The data was subjected to a number of statistical analyses including one way ANOVA and T-test of independent samples. Results indicated that final Accounting and Pharmacy students reported positive perceptions about their employment prospects than final year sociology students. As hypothesised, female final year students were significantly more confident than male final year students about employment prospects. Also, black final year students were found to be significantly more confident than their white final year counterparts (non-beneficiaries of employment policies about their employment prospects. It is concluded that differences regarding employment prospects among final year students can be accounted for by factors such as gender, field of study, race and whether or not one is a beneficiary of the SA government’s affirmative employment policies.

  15. Final definition and preliminary design study for the initial atmospheric cloud physics laboratory, a Spacelab mission payload

    Science.gov (United States)

    1976-01-01

    The following areas related to the final definition and preliminary design study of the initial atmospheric cloud physics laboratory (ACPL) were covered: (1) proposal organization, personnel, schedule, and project management, (2) proposed configurations, (3) study objectives, (4) ACPL experiment program listing and description, (5) mission/flight flexibility and modularity/commonality, (6) study plan, and (7) description of following tasks: requirement analysis and definition task flow, systems analysis and trade studies, subsystem analysis and trade studies, specifications and interface control documents, preliminary design task flow, work breakdown structure, programmatic analysis and planning, and project costs. Finally, an overview of the scientific requirements was presented.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-07-01

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

  17. Poor final visual outcome after traumatic hyphema: A retrospective study of associated factors

    Directory of Open Access Journals (Sweden)

    Ayda Khalfan Al Ali

    2012-09-01

    Full Text Available OBJECTIVES: To determine the factors associated with a poor final visual outcome following a non-perforating traumatic hyphema. METHODS: The in-patient records of all traumatic hyphema patients admitted to the Department of Ophthalmology of the Hamad Medical Centre (HMC in Doha, Qatar, were retrospectively reviewed for a four-year period from January 2004 to March 2008. One hundred and seventeen patients who did not meet the exclusion criteria were divided into two groups based on their final visual outcome post-treatment. Group 1 (good outcome consisted of 100 patients with a visual acuity (VA of 6/18 or better and group 2 (worse outcome consisted of 17 patients with a VA of less than 6/18. The two groups were compared to determine the factors associated with a poor final visual outcome. RESULTS: Group 2 patients had an 82.3% incidence of complications after a traumatic hyphema compared with a 21% incidence in group 1. Of these complications, secondary glaucoma and rebleeding were significantly associated with a worse final visual outcome. Trauma from projectiles or blows did not differ significantly in their effect on the final visual outcome, although blow injuries had a greater impact on the final visual outcome. Posterior segment injuries were associated with a worse visual outcome. CONCLUSION: It was concluded that secondary glaucoma, rebleeding, and posterior segment injuries are factors associated with a poor final visual outcome.

  18. Final waste forms project: Performance criteria for phase I treatability studies

    Energy Technology Data Exchange (ETDEWEB)

    Gilliam, T.M. [Oak Ridge National Lab., TN (United States); Hutchins, D.A. [Martin Marietta Energy Systems, Inc., Oak Ridge, TN (United States); Chodak, P. III [Massachusetts Institute of Technology (United States)

    1994-06-01

    This document defines the product performance criteria to be used in Phase I of the Final Waste Forms Project. In Phase I, treatability studies will be performed to provide {open_quotes}proof-of-principle{close_quotes} data to establish the viability of stabilization/solidification (S/S) technologies. This information is required by March 1995. In Phase II, further treatability studies, some at the pilot scale, will be performed to provide sufficient data to allow treatment alternatives identified in Phase I to be more fully developed and evaluated, as well as to reduce performance uncertainties for those methods chosen to treat a specific waste. Three main factors influence the development and selection of an optimum waste form formulation and hence affect selection of performance criteria. These factors are regulatory, process-specific, and site-specific waste form standards or requirements. Clearly, the optimum waste form formulation will require consideration of performance criteria constraints from each of the three categories. Phase I will focus only on the regulatory criteria. These criteria may be considered the minimum criteria for an acceptable waste form. In other words, a S/S technology is considered viable only if it meet applicable regulatory criteria. The criteria to be utilized in the Phase I treatability studies were primarily taken from Environmental Protection Agency regulations addressed in 40 CFR 260 through 265 and 268; and Nuclear Regulatory Commission regulations addressed in 10 CFR 61. Thus the majority of the identified criteria are independent of waste form matrix composition (i.e., applicable to cement, glass, organic binders etc.).

  19. Study of charmonia in four-meson final states produced in two-photon collisions

    CERN Document Server

    Uehara, S; Aihara, H; Aulchenko, V; Aushev, T; Bakich, A M; Balagura, V; Barberio, E; Bay, A; Belous, K S; Bitenc, U; Bondar, A; Bozek, A; Bracko, M; Brodzicka, J; Browder, T E; Chang, P; Chao, Y; Chen, A; Chen, K F; Chen, W T; Cheon, B G; Cho, I S; Choi, Y; Choi, Y K; Dalseno, J; Dash, M; Drutskoy, A; Eidelman, S; Epifanov, D; Fratina, S; Gabyshev, N; Gokhroo, G; Golob, B; Ha, H; Haba, J; Hayasaka, K; Hayashii, H; Hazumi, M; Heffernan, D; Hokuue, T; Hoshi, Y; Hou, W S; Hyun, H J; Iijima, T; Ikado, K; Inami, K; Ishikawa, A; Itoh, R; Iwasaki, M; Iwasaki, Y; Kah, D H; Kaji, H; Kang, J H; Kawai, H; Kawasaki, T; Kichimi, H; Kim, H O; Kim, S K; Kim, Y J; Korpar, S; Krizan, P; Krokovny, P; Kumar, R; Kuo, C C; Kuzmin, A; Kwon, Y J; Lee, J S; Lee, M J; Lee, S E; Lesiak, T; Li, J; Limosani, A; Lin, S W; Liu, Y; Liventsev, D; Mandl, F; Matsumoto, T; Matyja, A; McOnie, S; Medvedeva, T; Miyake, H; Miyata, H; Miyazaki, Y; Mizuk, R; Nagasaka, Y; Nakano, E; Nakao, M; Nakazawa, H; Natkaniec, Z; Nishida, S; Nitoh, O; Ogawa, S; Ohshima, T; Okuno, S; Olsen, S L; Onuki, Y; Ozaki, H; Pakhlov, P; Pakhlova, G; Palka, H; Park, C W; Park, H; Peak, L S; Pestotnik, R; Piilonen, L E; Sahoo, H; Sakai, Y; Schneider, O; Seidl, R; Senyo, K; Sevior, M E; Shapkin, M; Shibuya, H; Shiu, J G; Shwartz, B; Singh, J B; Sokolov, A; Somov, A; Soni, N; Stanic, S; Staric, M; Stöck, H; Sumiyoshi, T; Takasaki, F; Tamai, K; Tanaka, M; Taylor, G N; Teramoto, Y; Tian, X C; Tikhomirov, I; Tsuboyama, T; Unno, Y; Uno, S; Urquijo, P; Usov, Yu; Varner, G; Vervink, K; Villa, S; Vinokurova, A; Wang, C H; Wang, P; Watanabe, Y; Won, E; Yabsley, B D; Yamaguchi, A; Yamashita, Y; Yuan, C Z; Zhang, C C; Zhang, Z P; Zhilich, V; Zupanc, A

    2008-01-01

    We report measurements of charmonia produced in two-photon collisions and decaying to four-meson final states, where the meson is either a charged pion or a charged kaon. The analysis is based on a 395fb^{-1} data sample accumulated with the Belle detector at the KEKB electron-positron collider. We observe signals for the three C-even charmonia eta_c(1S), chi_{c0}(1P) and chi_{c2}(1P) in the pi^+pi^-pi^+pi^-, K^+K^-pi^+pi^- and K^+K^-K^+K^- decay modes. No clear signals for eta_c(2S) production are found in these decay modes. We have also studied resonant structures in charmonium decays to two-body intermediate meson resonances. We report the products of the two-photon decay width and the branching fractions, Gamma_{gamma gamma}B, for each of the charmonium decay modes.

  20. Study of the K S0K S0 final state in two-photon collisions

    Science.gov (United States)

    Acciarri, M.; Adam, A.; Adriani, O.; Aguilar-Benitez, M.; Ahlen, S.; Alpat, B.; Alcaraz, J.; Allaby, J.; Aloisio, A.; Alverson, G.; Alviggi, M. G.; Ambrosi, G.; An, Q.; Anderhub, H.; Andreev, V. P.; Angelescu, T.; Antreasyan, D.; Arefiev, A.; Azemoon, T.; Aziz, T.; Baba, P. V. K. S.; Bagnaia, P.; Baksay, L.; Ball, R. C.; Banerjee, S.; Banicz, K.; Barillère, R.; Barone, L.; Bartalini, P.; Baschirotto, A.; Basile, M.; Battiston, R.; Bay, A.; Becattini, F.; Becker, U.; Behner, F.; Bencze, Gy. L.; Berdugo, J.; Berges, P.; Bertucci, B.; Betev, B. L.; Biasini, M.; Biland, A.; Bilei, G. M.; Bizzarri, R.; Blaising, J. J.; Bobbink, G. J.; Bock, R.; Böhm, A.; Borgia, B.; Boucham, A.; Bourilkov, D.; Bourquin, M.; Boutigny, D.; Braccini, S.; Brambilla, E.; Branson, J. G.; Brigljevic, V.; Brock, I. C.; Buijs, A.; Bujak, A.; Burger, J. D.; Burger, W. J.; Burgos, C.; Busenitz, J.; Buytenhuijs, A.; Cai, X. D.; Capell, M.; Cara Romeo, G.; Caria, M.; Carlino, G.; Cartacci, A. M.; Casaus, J.; Castellini, G.; Castello, R.; Cavallari, F.; Cavallo, N.; Cecchi, C.; Cerrada, M.; Cesaroni, F.; Chamizo, M.; Chan, A.; Chang, Y. H.; Chaturvedi, U. K.; Chemarin, M.; Chen, A.; Chen, C.; Chen, G.; Chen, G. M.; Chen, H. F.; Chen, H. S.; Chen, M.; Chiefari, G.; Chien, C. Y.; Choi, M. T.; Cifarelli, L.; Cindolo, F.; Civinini, C.; Clare, I.; Clare, R.; Coan, T. E.; Cohn, H. O.; Coignet, G.; Colijn, A. P.; Colino, N.; Commichau, V.; Costantini, S.; Cotorobai, F.; de la Cruz, B.; Cui, X. T.; Cui, X. Y.; Dai, T. S.; D'Alessandro, R.; de Asmundis, R.; De Boeck, H.; Degré, A.; Deiters, K.; Dénes, E.; Denes, P.; DeNotaristefani, F.; DiBitonto, D.; Diemoz, M.; van Dierendonck, D.; Di Lodovico, F.; Dionisi, C.; Dittmar, M.; Dominguez, A.; Doria, A.; Dorne, I.; Dova, M. T.; Drago, E.; Duchesneau, D.; Duinker, P.; Duran, I.; Dutta, S.; Easo, S.; Efremenko, Yu.; El Mamouni, H.; Engler, A.; Eppling, F. J.; Erné, F. C.; Ernenwein, J. P.; Extermann, P.; Fabbretti, R.; Fabre, M.; Faccini, R.; Falciano, S.; Favara, A.; Fay, J.; Felcini, M.; Ferguson, T.; Fernandez, D.; Fernandez, G.; Ferroni, F.; Fesefeldt, H.; Fiandrini, E.; Field, J. H.; Filthaut, F.; Fisher, P. H.; Forconi, G.; Fredj, L.; Freudenreich, K.; Gailloud, M.; Galaktionov, Yu.; Ganguli, S. N.; Garcia-Abia, P.; Gau, S. S.; Gentile, S.; Gerald, J.; Gheordanescu, N.; Giagu, S.; Goldfarb, S.; Goldstein, J.; Gong, Z. F.; Gonzalez, E.; Gougas, A.; Goujon, D.; Gratta, G.; Gruenewald, M. W.; Gu, C.; Guanziroli, M.; Gupta, V. K.; Gurtu, A.; Gustafson, H. R.; Gutay, L. J.; Hartmann, B.; Hasan, A.; He, J. T.; Hebbeker, T.; Hervé, A.; Hilgers, K.; van Hoek, W. C.; Hofer, H.; Hoorani, H.; Hou, S. R.; Hu, G.; Ilyas, M. M.; Innocente, V.; Janssen, H.; Jin, B. N.; Jones, L. W.; de Jong, P.; Josa-Mutuberria, I.; Kasser, A.; Khan, R. A.; Kamyshkov, Yu.; Kapinos, P.; Kapustinsky, J. S.; Karyotakis, Y.; Kaur, M.; Khokhar, S.; Kienzle-Focacci, M. N.; Kim, D.; Kim, J. K.; Kim, S. C.; Kim, Y. G.; Kinnison, W. W.; Kirkby, A.; Kirkby, D.; Kirkby, J.; Kittel, W.; Klimentov, A.; König, A. C.; Koffeman, E.; Kornadt, O.; Koutsenko, V.; Koulbardis, A.; Kraemer, R. W.; Kramer, T.; Krenz, W.; Kuijten, H.; Kunin, A.; Ladron de Guevara, P.; Landi, G.; Lapoint, C.; Lassila-Perini, K.; Laurikainen, P.; Lebeau, M.; Lebedev, A.; Lebrun, P.; Lecomte, P.; Lecoq, P.; Le Coultre, P.; Lee, J. S.; Lee, K. Y.; Leggett, C.; Le Goff, J. M.; Leiste, R.; Lenti, M.; Leonardi, E.; Levtchenko, P.; Li, C.; Lieb, E.; Lin, W. T.; Linde, F. L.; Lindemann, B.; Lista, L.; Liu, Y.; Liu, Z. A.; Lohmann, W.; Longo, E.; Lu, W.; Lu, Y. S.; Lübelsmeyer, K.; Luci, C.; Luckey, D.; Ludovici, L.; Luminari, L.; Lustermann, W.; Ma, W. G.; Macchiolo, A.; Maity, M.; Malgeri, L.; Malik, R.; Malinin, A.; Maña, C.; Mangla, S.; Maolinbay, M.; Marchesini, P.; Marin, A.; Martin, J. P.; Marzano, F.; Massaro, G. G. G.; Mazumdar, K.; McNally, D.; Mele, S.; Merola, L.; Meschini, M.; Metzger, W. J.; Mi, Y.; Mihul, A.; van Mil, A. J. W.; Mir, Y.; Mirabelli, G.; Mnich, J.; Möller, M.; Monteleoni, B.; Moore, R.; Morand, R.; Morganti, S.; Moulai, N. E.; Mount, R.; Müller, S.; Muheim, F.; Nagy, E.; Nahn, S.; Napolitano, M.; Nessi-Tedaldi, F.; Newman, H.; Niaz, M. A.; Nippe, A.; Nowak, H.; Organtini, G.; Ostonen, R.; Pandoulas, D.; Paoletti, S.; Paolucci, P.; Pascale, G.; Passaleva, G.; Patricelli, S.; Paul, T.; Pauluzzi, M.; Paus, C.; Pauss, F.; Pei, Y. J.; Pensotti, S.; Perret-Gallix, D.; Petrak, S.; Pevsner, A.; Piccolo, D.; Pieri, M.; Pinto, J. C.; Piroué, P. A.; Pistolesi, E.; Plyaskin, V.; Pohl, M.; Pojidaev, V.; Postema, H.; Produit, N.; Qureshi, K. N.; Raghavan, R.; Rahal-Callot, G.; Rancoita, P. G.; Rattaggi, M.; Raven, G.; Razis, P.; Read, K.; Redaelli, M.; Ren, D.; Ren, Z.; Rescigno, M.; Reucroft, S.; Ricker, A.; Riemann, S.; Riemers, B. C.; Riles, K.; Rind, O.; Rizvi, H. A.; Ro, S.; Robohm, A.; Rodin, J.; Rodriguez, F. J.; Roe, B. P.; Röhner, M.; Röhner, S.; Romero, L.; Rosier-Lees, S.; Rosselet, Ph.; van Rossum, W.; Roth, S.; Rubio, J. A.; Rykaczewski, H.; Salicio, J.; Salicio, J. M.; Sanchez, E.; Santocchia, A.; Sarakinos, M. E.; Sarkar, S.; Sartorelli, G.; Sassowsky, M.; Sauvage, G.; Schäfer, C.; Schegelsky, V.; Schmitz, D.; Schmitz, P.; Schneegans, M.; Schoeneich, B.; Scholz, N.; Schopper, H.; Schotanus, D. J.; Schulte, R.; Schultze, K.; Schwenke, J.; Schwering, G.; Sciacca, C.; Sehgal, R.; Seiler, P. G.; Sens, J. C.; Servoli, L.; Shevchenko, S.; Shivarov, N.; Shoutko, V.; Shukla, J.; Shumilov, E.; Son, D.; Sopczak, A.; Soulimov, V.; Smith, B.; Spickermann, T.; Spillantini, P.; Steuer, M.; Stickland, D. P.; Sticozzi, F.; Stone, H.; Stoyanov, B.; Strauch, K.; Sudhakar, K.; Sultanov, G.; Sun, L. Z.; Susinno, G. F.; Suter, H.; Swain, J. D.; Tang, X. W.; Tauscher, L.; Taylor, L.; Timellini, R.; Ting, Samuel C. C.; Ting, S. M.; Toker, O.; Tonisch, F.; Tonutti, M.; Tonwar, S. C.; Tóth, J.; Tsaregorodtsey, A.; Tsipolitis, G.; Tully, C.; Tuchscherer, H.; Ulbricht, J.; Urbán, L.; Uwer, U.; Valente, E.; Van de Walle, R. T.; Vetlitsky, I.; Viertel, G.; Vikas, P.; Vikas, U.; Vivargent, M.; Völkert, R.; Vogel, H.; Vogt, H.; Vorobiev, I.; Vorobyov, A. A.; Vorobyov, An. A.; Vuilleumier, L.; Wadhwa, M.; Wallraff, W.; Wang, J. C.; Wang, X. L.; Wang, Y. F.; Wang, Z. M.; Weber, A.; Weill, R.; Willmott, C.; Wittgenstein, F.; Wu, S. X.; Wynhoff, S.; Xu, J.; Xu, Z. Z.; Yang, B. Z.; Yang, C. G.; Yang, G.; Yao, X. Y.; Ye, C. H.; Ye, J. B.; Ye, Q.; Yeh, S. C.; You, J. M.; Yunus, N.; Zaccardelli, C.; Zalite, An.; Zemp, P.; Zeng, J. Y.; Zeng, M.; Zeng, Y.; Zhang, Z.; Zhang, Z. P.; Zhou, B.; Zhou, G. J.; Zhou, J. F.; Zhou, Y.; Zhu, G. Y.; Zhu, R. Y.; Zichichi, A.; van der Zwaan, B. C. C.; L3 Collaboration

    1995-02-01

    The reaction e +e - → e +e -γ ∗γ ∗ → e +e -K S0K S0 is studied with the L3 detector at LEP and the formation of the f 2‧(1525) resonance is observed. For an integrated luminosity of 114 pb -1, 31±6 f 2‧ events are found. Their angular distribution is consistent with a pure helicity two. The radiative width times the branching ratio is measured to be Γ γγ(f 2‧)×Br(f 2‧ → K overlineK) =(0.093±0.018±0.022) keV. Only three events are found in the f 2(1270)-a 2(1320) mass region, consistent with destructive f 2-a 2 interference in the K S0K S0 final state. The mixing angle of the tensor meson nonet is determined to the θ = (29.4 -1.6+1.4)°.

  1. Final report on the public involvement process phase 1, Monitored Retrievable Storage Facility Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Moore, L.; Shanteau, C.

    1992-12-01

    This report summarizes the pubic involvement component of Phase 1 of the Monitored Retrievable Storage Facility (NM) Feasibility Study in San Juan County, Utah. Part of this summary includes background information on the federal effort to locate a voluntary site for temporary storage of nuclear waste, how San Juan County came to be involved, and a profile of the county. The heart of the report, however, summarizes the activities within the public involvement process, and the issues raised in those various forums. The authors have made every effort to reflect accurately and thoroughly all the concerns and suggestions expressed to us during the five month process. We hope that this report itself is a successful model of partnership with the citizens of the county -- the same kind of partnership the county is seeking to develop with its constituents. Finally, this report offers some suggestions to both county officials and residents alike. These suggestions concern how decision-making about the county's future can be done by a partnership of informed citizens and listening decision-makers. In the Appendix are materials relating to the public involvement process in San Juan County.

  2. Final report on the public involvement process phase 1, Monitored Retrievable Storage Facility Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Moore, L.; Shanteau, C.

    1992-12-01

    This report summarizes the pubic involvement component of Phase 1 of the Monitored Retrievable Storage Facility (NM) Feasibility Study in San Juan County, Utah. Part of this summary includes background information on the federal effort to locate a voluntary site for temporary storage of nuclear waste, how San Juan County came to be involved, and a profile of the county. The heart of the report, however, summarizes the activities within the public involvement process, and the issues raised in those various forums. The authors have made every effort to reflect accurately and thoroughly all the concerns and suggestions expressed to us during the five month process. We hope that this report itself is a successful model of partnership with the citizens of the county -- the same kind of partnership the county is seeking to develop with its constituents. Finally, this report offers some suggestions to both county officials and residents alike. These suggestions concern how decision-making about the county`s future can be done by a partnership of informed citizens and listening decision-makers. In the Appendix are materials relating to the public involvement process in San Juan County.

  3. Oral administration of the anti-proliferative substance taurolidine has no impact on dextran sulfate sodium-induced colitis-associated carcinogenesis in mice

    Directory of Open Access Journals (Sweden)

    Chromik Ansgar

    2010-01-01

    Full Text Available Background: New chemopreventive strategies for ulcerative colitis (UC-associated dysplasia and cancer have to be evaluated. Taurolidine (TRD has anti-inflammatory, anti-proliferative and anti-neoplastic properties with almost absent toxicity. The aim of the study was to determine whether TRD decreases dysplasia in the well-characterized Dextran Sulfate Sodium - Azoxymethane (DSS-AOM animal model for UC-associated carcinogenesis. Material and Methods: The DSS-AOM model of carcinogenesis was induced in female inbred C57BL/6 mice. Half of the mice were treated with TRD, the other served as control. After 100 days macroscopic, histological and immunhistochemical (β-Catenin, E-Cadherin, SOX9, Ki-67, Cyclin-D1 examination of the colon was performed. Results: Incidence, multiplicity, grading and growth pattern of adenomas did not differ significantly between TRD and control group. In all animals, inflammatory changes were absent. Immunhistochemistry revealed increased expression of Ki-67, β-catenin, SOX9 and Cyclin-D1 in adenomas compared to normal mucosa - without significant difference between TRD and control treatment. Conclusion: Oral administration of TRD has no impact on DSS-induced colitis-associated carcinogenesis. However, SOX9 and Cyclin-D1 representing key members of the Wnt pathway have not yet been described in the DSS-AOM model of carcinogenesis - underlining the importance of this oncogenic pathway in this setting.

  4. Factors influencing final/near-final height in 12 boys with central precocious puberty treated with gonadotrophin-releasing hormone agonists. Italian Study Group of Physiopathology of Puberty.

    Science.gov (United States)

    Rizzo, V; De Sanctis, V; Corrias, A; Fortini, M; Galluzzi, F; Bertelloni, S; Guarneri, M P; Pozzan, G; Cisternino, M; Pasquino, A M

    2000-07-01

    Gonadotrophin-releasing hormone agonists (GnRHa) have been demonstrated as the therapy of choice for central precocious puberty (CPP). Few studies have provided male patients' adult height data. In our multicenter study we evaluated long-term effects of different GnRHa preparations and final/near-final height (FH) in 12 boys with CPP and analyzed the factors influencing FH. Patients' mean chronological age at the time of diagnosis was 7.6 +/- 0.9 yr. Three patients were treated only with triptorelin at a mean dose of 90 microg/kg i.m. every 28 days. Nine patients initially received buserelin (at a mean initial dose of 53.4 microg/kg/day i.n. divided into 3-6 equal doses) or buserelin (at a mean dose of 36.7 microg/kg/day s.c.) and were subsequently switched to triptorelin. The GnRHa therapy was continued for 4.1 +/- 0.6 yr (range 2.9-5.4). The mean predicted adult height increased from 169.9 +/- 4.2 cm at diagnosis to 180.7 +/- 6.0 cm at the end of treatment. Mean FH was 176.1 +/- 6.1 cm (170.1-190.7), corresponding to mean SDS(CA) 0.4 +/- 0.8 (-0.6/2.5), mean SDSBA 0.2 +/- 0.9 (-0.6/2.4) and mean corrected SDS for target height of 0.4 +/- 0.6 (-0.8/1.2). Multiple regression analysis revealed that FH was mainly influenced by target height and height at discontinuation of GnRHa therapy. The present data indicate that GnRHa therapy significantly improves growth prognosis in boys with CPP and fully restores genetic height potential.

  5. Cherry Valley National Wildlife Refuge Final Feasibility Study and Environmental Assessment

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — In accordance with the National Environmental Policy Act (NEPA), as amended, the Service has developed a Final EA in response to the Cherry Valley National Wildlife...

  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. Significance of CpG methylation for solar UV-induced mutagenesis and carcinogenesis in skin.

    Science.gov (United States)

    Ikehata, Hironobu; Ono, Tetsuya

    2007-01-01

    Mutations detected in the p53 gene in human nonmelanoma skin cancers show a highly UV-specific mutation pattern, a dominance of C --> T base substitutions at dipyrimidine sites plus frequent CC --> TT tandem substitutions, indicating a major involvement of solar UV in the skin carcinogenesis. These mutations also have another important characteristic of frequent occurrences at CpG dinucleotide sites, some of which actually show prominent hotspots in the p53 gene. Although mammalian solar UV-induced mutation spectra were studied intensively in the aprt gene using rodent cultured cells and the UV-specific mutation pattern was confirmed, the second characteristic of the p53 mutations in human skin cancers had not been reproduced. However, studies with transgenic mouse systems developed thereafter for mutation research, which harbor methyl CpG-abundant transgenes as mutation markers, yielded complete reproductions of the situation of the human skin cancer mutations in terms of both the UV-specific pattern and the frequent occurrence at CpG sites. In this review, we evaluate the significance of the CpG methylation for solar UV mutagenesis in the mammalian genome, which would lead to skin carcinogenesis. We propose that the UV-specific mutations at methylated CpG sites, C --> T transitions at methyl CpG-associated dipyrimidine sites, are a solar UV-specific mutation signature, and have estimated the wavelength range effective for the solar-UV-specific mutation as 310-340 nm. We also recommend the use of methyl CpG-enriched sequences as mutational targets for studies on solar-UV genotoxicity for human, rather than conventional mammalian mutational marker genes such as the aprt and hprt genes.

  8. Oxidative stress and cyclooxygenase activity in prostate carcinogenesis: targets for chemopreventive strategies.

    Science.gov (United States)

    Pathak, S K; Sharma, R A; Steward, W P; Mellon, J K; Griffiths, T R L; Gescher, A J

    2005-01-01

    Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. Oxidative stress may be linked to the effects of androgens, anti-oxidant systems and the pre-malignant condition, high-grade prostatic intraepithelial neoplasia. Cyclooxygenase-2 activity has been linked with prostate carcinogenesis. Evidence suggests that oxidative stress and cyclo-oxygenase-2 activity may be mechanistically linked. Agents such as anti-oxidants and cyclo-oxgenase-2 inhibitors may be of value in the chemoprevention of prostate cancer. The feasibility of intervention with such agents will depend on the development and validation of biomarkers for clinical trials, particularly markers of oxidative damage caused by reactive oxygen species (ROS). A greater understanding of the molecular events associated with oxidative stress will enhance the development of such biomarkers and should result in better strategies for the chemoprevention of prostate cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Takuji; Morishita, Yukio; Kawamori, Toshihiko; Suzui, Masumi; Kojima, Toshihiro; Sugie, Shigeyuki; Mori, Hideki (Gifu Univ. (Japan). Faculty of Medicine)

    1993-10-01

    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).

  10. 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.

  11. 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.

  12. 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.

  13. γ-glutamyl tranferase in a model of carcinogenesis in rats

    Directory of Open Access Journals (Sweden)

    S. O. Babij

    2010-07-01

    compounds of rhenium (III with organic ligands and cisplatin (rhenium-platinum system was studied. The increased activity of the membrane bound enzyme and decrease of its cytosolic activity in the red blood cells during development of Guerin’s carcinoma T8 was found. Also the positive impact of the rheniumplatinum system on the enzymatic activity in the erythrocytes was shown, namely: the reduction of membrane bound and increase of cytosolic activity. As a result, the ratio between activity of the membrane bound enzyme and cytosolic one verged towards the correct level. The conclusion was made that the use of membrane bound and soluble γ-glutamyl transferase in the erythrocytes as a diagnostic enzyme of carcinogenesis is reasonable.

  14. Plug-In Hybrid Electric Vehicle Market Introduction Study: Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Sikes, Karen [Sentech, Inc.; Gross, Thomas [Sentech, Inc.; Lin, Zhenhong [ORNL; Sullivan, John [University of Michigan Transportation Research Institute; Cleary, Timothy [Sentech, Inc.; Ward, Jake [U.S. Department of Energy

    2010-02-01

    Oak Ridge National Laboratory (ORNL), Sentech, Inc., Pacific Northwest National Laboratory (PNNL)/University of Michigan Transportation Research Institute (UMTRI), and the U.S. Department of Energy (DOE) have conducted a Plug-in Hybrid Electric Vehicle (PHEV) Market Introduction Study to identify and assess the effect of potential policies, regulations, and temporary incentives as key enablers for a successful market debut. The timeframe over which market-stimulating incentives would be implemented - and the timeframe over which they would be phased out - are suggested. Possible sources of revenue to help fund these mechanisms are also presented. In addition, pinch points likely to emerge during market growth are identified and proposed solutions presented. Finally, modeling results from ORNL's Market Acceptance of Advanced Automotive Technologies (MA3T) Model and UMTRI's Virtual AutoMotive MarketPlace (VAMMP) Model were used to quantify the expected effectiveness of the proposed policies and to recommend a consensus strategy aimed at transitioning what begins as a niche industry into a thriving and sustainable market by 2030. The primary objective of the PHEV Market Introduction Study is to identify the most effective means for accelerating the commercialization of PHEVs in order to support national energy and economic goals. Ideally, these mechanisms would maximize PHEV sales while minimizing federal expenditures. To develop a robust market acceleration program, incentives and policies must be examined in light of: (1) clarity and transparency of the market signals they send to the consumer; (2) expenditures and resources needed to support them; (3) expected impacts on the market for PHEVs; (4) incentives that are compatible and/or supportive of each other; (5) complexity of institutional and regulatory coordination needed; and (6) sources of funding.

  15. Final cost reduction study for the Geysers Recharge Alternative. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-11-01

    The purpose of this study is to determine whether or not cost reduction opportunities exist for the Geysers Recharge Alternative as defined in the Santa Rosa Subregional Long-Term Wastewater Project EIR/EIS. The City of Santa Rosa has been directed to have a plan for reclaimed water disposal in place by 1999 which will meet future capacity needs under all weather conditions. A Draft EIR/EIS released in July 1996 and a Final EIR certified in June 1997 examine four primary alternatives plus the No Action Alternative. Two of the primary alternatives involve agricultural irrigation with reclaimed water, either in western or southern Sonoma County. Another involves increased discharge of reclaimed water into the Russian River. The fourth involves using reclaimed water to replenish the geothermal reservoir at the Geysers. The addition of this water source would enable the Geysers operators to produce more steam from the geothermal area and thereby prolong the life and economic production level of the steamfield and the geothermal power plants supplied by the steamfield. This study provides additional refined cost estimates for new scenarios which utilize an alternative pipeline alignment and a range of reclaimed water flows, which deliver less water to the Geysers than proposed in the EIR/EIS (by distributing flow to other project components). Also, electrical power rates were revised to reflect the recent changes in costs associated with deregulation of the power industry. In addition, this report provides information on sources of potential public and private funding available and future environmental documentation required if the cost reduction scenarios were to be selected by the City as part of their preferred alternative.

  16. Final Report Phase I Study to Characterize the Market Potential for Non-Motorized Travel

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Ho-Ling [ORNL; Reuscher, Tim [Macrosys; Wilson, Daniel W [ORNL; Schmoyer, Richard L [ORNL

    2012-06-01

    availability, population size, and a mix of geographic locations across the nation. Given the similarities in modeling results from walk trips and walk mileages, additional modeling efforts conducted under the later part of this study were focused on walk trips per person. Bike models were limited only with the stepwise logistic models using Census tracts in the selected regions. Due to NHTS sampling limitations, only about 12% of these tracts have bike trips recorded from NHTS sampled households. The modeling with NHTS bike data proved to be more challenging and time consuming than what was anticipated. Along with the late arrival of Nielsen employment data, the project team had to limit the modeling effort to focus on walking. Therefore, the final modeling and discriminant analysis was conducted only for walking trips.

  17. Growth-related alterations during liver carcinogenesis: Effect of promoters

    Energy Technology Data Exchange (ETDEWEB)

    Seglen, P.O.; Gerlyng, P. (Norwegian Radium Hospital, Oslo (Norway))

    1990-08-01

    Bromodeoxyuridine labeling of DNA, binuclearity counting, and flow cytometric analysis of isolated hepatocytes and hepatocyte nuclei has been used to assess heptocellular growth patterns related to liver carcinogenesis. Three growth patterns can be distinguished. Mononucleating growth is observed during liver regeneration and after treatment with the tumor promoter 2-acetylaminofluorene (2-AAF) and its analogue 4-AAF. In this growth mode binucleation does not occur, resulting in a decrease in the fraction of binucleated cells. Binucleating growth is observed during normal liver development and after treatment with compounds such as phenobarbital, characterized by progressive polyploidization and maintenance of a binucleated cell fraction. Diploid growth is the growth pattern of neoplastic liver hepatocytes. Most of the cells in neoplastic lesions (foci, nodules, and carcinomas) are diploid, in contrast to the normal liver. Diploid tumor cells have a much higher proliferative activity than tetraploid tumor cells, suggesting that the latter may posses a limited growth potential that makes abrogation of binucleation proliferatively advantageous.

  18. 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......-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...

  19. [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.

  20. Multi-step pancreatic carcinogenesis and its clinical implications.

    Science.gov (United States)

    Sakorafas, G H; Tsiotou, A G

    1999-12-01

    The poor prognosis of pancreatic cancer relates mainly to its delayed diagnosis. It has been repeatedly shown that earlier diagnosis of pancreatic cancer is associated with a better outcome. Molecular diagnostic methods (mainly detection of K-ras mutations in pure pancreatic or duodenal juice, on specimens obtained by percutaneous fine-needle aspirations or in stool specimens) can achieve earlier diagnosis in selected subgroups of patients, such as patients with chronic pancreatitis (especially hereditary), adults with recent onset of non-insulin-dependent diabetes mellitus and patients with some inherited disorders that predispose to the development of pancreatic cancer. There is increasing evidence that pancreatic carcinogenesis is a multi-step phenomenon. Screening procedures for precursor lesions in these selected subgroups of patients may reduce the incidence and mortality from pancreatic cancer.

  1. 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...

  2. Differential network analysis reveals dysfunctional regulatory networks in gastric carcinogenesis.

    Science.gov (United States)

    Cao, Mu-Shui; Liu, Bing-Ya; Dai, Wen-Tao; Zhou, Wei-Xin; Li, Yi-Xue; Li, Yuan-Yuan

    2015-01-01

    Gastric Carcinoma is one of the most common cancers in the world. A large number of differentially expressed genes have been identified as being associated with gastric cancer progression, however, little is known about the underlying regulatory mechanisms. To address this problem, we developed a differential networking approach that is characterized by including a nascent methodology, differential coexpression analysis (DCEA), and two novel quantitative methods for differential regulation analysis. We first applied DCEA to a gene expression dataset of gastric normal mucosa, adenoma and carcinoma samples to identify gene interconnection changes during cancer progression, based on which we inferred normal, adenoma, and carcinoma-specific gene regulation networks by using linear regression model. It was observed that cancer genes and drug targets were enriched in each network. To investigate the dynamic changes of gene regulation during carcinogenesis, we then designed two quantitative methods to prioritize differentially regulated genes (DRGs) and gene pairs or links (DRLs) between adjacent stages. It was found that known cancer genes and drug targets are significantly higher ranked. The top 4% normal vs. adenoma DRGs (36 genes) and top 6% adenoma vs. carcinoma DRGs (56 genes) proved to be worthy of further investigation to explore their association with gastric cancer. Out of the 16 DRGs involved in two top-10 DRG lists of normal vs. adenoma and adenoma vs. carcinoma comparisons, 15 have been reported to be gastric cancer or cancer related. Based on our inferred differential networking information and known signaling pathways, we generated testable hypotheses on the roles of GATA6, ESRRG and their signaling pathways in gastric carcinogenesis. Compared with established approaches which build genome-scale GRNs, or sub-networks around differentially expressed genes, the present one proved to be better at enriching cancer genes and drug targets, and prioritizing

  3. Perceived stress at transition to workplace: a qualitative interview study exploring final-year medical students’ needs

    Science.gov (United States)

    Moczko, Tobias R; Bugaj, Till J; Herzog, Wolfgang; Nikendei, Christoph

    2016-01-01

    Objectives This study was designed to explore final-year medical students’ stressors and coping strategies at the transition to the clinical workplace. Methods In this qualitative study, semi-standardized interviews with eight final-year medical students (five male, three female; aged 25.9±1.4 years) were conducted during their internal medicine rotation. After verbatim transcription, a qualitative content analysis of students’ impressions of stress provoking and easing factors during final-year education was performed. Results Students’ statements regarding burdens and dealing with stress were classified into four main categories: A) perceived stressors and provoking factors, B) stress-induced consequences, C) personal and external resources for preventing and dealing with stress, and D) final-year students’ suggestions for workplace improvement. Conclusion Final-year medical students perceived different types of stress during their transition to medical wards, and reported both negative consequences and coping resources concerning perceived stress. As supervision, feedback, and coping strategies played an important role in the students’ perception of stress, final-year medical education curricula development should focus on these specifically. PMID:26834503

  4. Pre-feasibility study for final disposal of radioactive waste. Disposal concepts. Main report

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, L.; Skov, C.; Kueter, A.; Schepper, L.; Gottberg Roemer, H.; Refsgaard, A.; Utko, M.; Kristiansen, Torben (COWI A/S, Kgs. Lyngby (Denmark))

    2011-05-15

    This prefeasibility study is part of the overall process related to the decision on placement and design of a repository for the Danish low and medium level radioactive waste primarily from the facilities at Risoe. The prefeasibility study encompasses the preliminary design of a number of repository types based on the overall types set out in the 'Parliamentary decision' together with a preliminary safety assessment of these repository types based on their possible placement in a set of typical Danish geologies. The report consists of three parts. Part I is the descriptive part containing information on the waste to be disposed of, the potential conditioning (packaging) possibilities for the waste before placement in a repository, the suggested preliminary design of the different repository types, and the suggested visual appearance of the repository. Part II is the assessment part. It contains an introduction to the concepts used in the preliminary safety assessment, which encompasses: the assessment of potential long term impact and the assessment of possible accidental incidents. The division of the preliminary safety assessment in to these two categories has several reasons. One is that the criteria to which impact is to be compared are different for the two types of impact, another is that while the possible variation in the long term impact is primarily due to the possible variation in the parameters influencing the impact, the impact from accidental incidents is governed by the probability of the occurrence of these incidents and the potential consequence of the impact, which calls for a different assessment approach. Since the suggestions for packaging of the different waste types is a result of both types of assessments, part II also contains a description of these suggestions based on the preliminary safety assessments. Finally part II contains the costs related to the different types of repositories and the suggested packaging. Part III of the

  5. Impacts of Outer Continental Shelf (OCS) development on recreation and tourism. Volume 2. Final report and case studies

    Energy Technology Data Exchange (ETDEWEB)

    1987-04-01

    The final report for the project is comprised of five volumes. The volume presents the study conclusions, summarizes the methodology used (more detail is found in Volume 3), discusses four case study applications of the model, and contains profiles of coastal communities in an Appendix.

  6. Identification of a long non-coding RNA NR_026689 associated with lung carcinogenesis induced by NNK

    OpenAIRE

    Wu, Jianjun; Li, Xun; Xu, Yiqin; Yang, Ti; Yang, Qiaoyuan; Yang, Chengfeng; Jiang, Yiguo

    2016-01-01

    Long non-coding RNAs (lncRNA) are thought to be important epigenetic regulators involved in the development of a variety of cancers. Alterations in lncRNA expression are associated with exposure to chemical carcinogens. However, it is still unclear whether lncRNA expression during lung carcinogenesis is induced by chemical carcinogens. In this study, using NNK-induced rat lung cancer model established by our previous study, we determined the lncRNA expression profiles, and an alteration in ln...

  7. Expression of some tumor associated factors in human carcinogenesis and development of gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming-Dong Zhao; Xue-Mei Hu; Dian-Jing Sun; Qun Zhang; Yu-Hao Zhang; Wei Meng

    2005-01-01

    AIM: To study the effect of IGF-1/IGF-1R and gastrin/ CCK-BR on carcinogenesis and development of human gastric carcinoma and to explore its mechanism and provide a credible theoretical foundation for early diagnosis and molecular therapy of gastric carcinoma. METHODS: mRNA expression levels of IGF-1/IGF-1R and gastrin/CCK-BR were assessed by RT-PCR method in gastric cancer tissues, adjacent mucosa, and tumor-free tissues from 56 patients with gastric carcinoma and normal gastric mucosae from 56 healthy controls. Tissue specimens were obtained by biopsy and confirmed by histological evaluation.RESULTS: The mRNA levels of IGF-1/IGF-1R were increased in gastric cancer tissues compared with normal tissues from healthy controls and successively increased in tumor-free tissues, adjacent mucosa, and gastric cancer tissues. The mRNA levels of gastrin/CCK-BR were increased in gastric cancer tissues compared with normal tissues from healthy controls. There was a significant difference between gastric cancer tissues and adjacent mucosa and tumor-free tissues, but the mRNA levels of gastrin were not significantly increased in adjacent mucosa and gastric cancer tissues compared with tumorfree tissues. The mRNA levels of CCK-BR were increased in gastric cancer tissues and adjacent mucosa compared with tumor-free tissues, but not significantly increased in adjacent mucosa and gastric cancer tissues compared with gastric cancer tissues. CONCLUSION: Overexpression of IGF-1/IGF-1R and gastrin/CCK-BR promotes the disorderly proliferation of gastric mucosa epithelia and it is of great significance in the carcinogenesis and development of gastric carcinoma.

  8. 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. .

  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. Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Breast Carcinogenesis.

    Science.gov (United States)

    Margan, Madalin Marius; Jitariu, Andreea Adriana; Cimpean, Anca Maria; Nica, Cristian; Raica, Marius

    2016-06-01

    Normal human breast tissue consists of epithelial and nonepithelial cells with different molecular profiles and differentiation grades. This molecular heterogeneity is known to yield abnormal clones that may contribute to the development of breast carcinomas. Stem cells that are found in developing and mature breast tissue are either positive or negative for cytokeratin 19 depending on their subtype. These cells are able to generate carcinogenesis along with mature cells. However, scientific data remains controversial regarding the monoclonal or polyclonal origin of breast carcinomas. The majority of breast carcinomas originate from epithelial cells that normally express BRCA1. The consecutive loss of the BRCA1 gene leads to various abnormalities in epithelial cells. Normal breast epithelial cells also express hypoxia inducible factor (HIF) 1α and HIF-2α that are associated with a high metastatic rate and a poor prognosis for malignant lesions. The nuclear expression of estrogen receptor (ER) and progesterone receptor (PR) in normal human breast tissue is maintained in malignant tissue as well. Several controversies regarding the ability of ER and PR status to predict breast cancer outcome remain. Both ER and PR act as modulators of cell activity in normal human breast tissue. Ki-67 positivity is strongly correlated with tumor grade although its specific role in applied therapy requires further studies. Human epidermal growth factor receptor 2 (HER2) oncoprotein is less expressed in normal human breast specimens but is highly expressed in certain malignant lesions of the breast. Unlike HER2, epidermal growth factor receptor expression is similar in both normal and malignant tissues. Molecular heterogeneity is not only found in breast carcinomas but also in normal breast tissue. Therefore, the molecular mapping of normal human breast tissue might represent a key research area to fully elucidate the mechanisms of breast carcinogenesis.

  11. 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.

  12. Role of microsatellites instability in carcinogenesis of postcricoid carcinoma on top of plummer-vinson syndrome.

    Science.gov (United States)

    Badawy, Badawy Shahat; Ahmad, Mohamed Abdel-Kader; Sayed, Ramadan Hashem; Habib, Tito Naeem

    2010-10-01

    To develop a molecular pattern that might help in understanding carcinogenesis of postcricoid carcinoma (PCC) on top of Plummer-Vinson syndrome (PVS) in a prospective controlled study. Twenty-four patients with PVS were diagnosed and followed up over a 4 year period, during which eight of them showed malignant change to PCC. Twenty volunteers free of neoplastic diseases were included as a control group. In the two groups, DNA extraction from mononuclear peripheral blood cells, and analysis of loss of heterozygosity (LOH) and microsatellite instability (MSI) using six paired simple tandem repeats (STRs) primers were done. The molecular weight of each STRs locus was scored and statistical correlations were performed. LOH occurred in 55.6 and 72.9% of PVS and PCC cases compared to 25% of control group. At loci D17S695, D9S753 and D9S171, LOH occurred in 54.2, 66.7, and 70.8% of PVS cases; and in 62.5% of PCC cases for each locus compared to 15, 25 and 45% of control cases. D3S1286 and CFS1-R displayed the highest frequency of LOH in PCC (100% for each) while recorded in 58.3 and 33.3% in PVS compared to 30 and 0% in control cases. Certain genetic events tend to occur as early and late events in malignant change of PVS to PCC. Detection of these events may help in understanding carcinogenesis and in early detection of malignancy. CFS1-R is the most informative marker of tumor progression.

  13. 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.

  14. Epithelial nuclear factor-κB signaling promotes lung carcinogenesis via recruitment of regulatory T lymphocytes.

    Science.gov (United States)

    Zaynagetdinov, R; Stathopoulos, G T; Sherrill, T P; Cheng, D-S; McLoed, A G; Ausborn, J A; Polosukhin, V V; Connelly, L; Zhou, W; Fingleton, B; Peebles, R S; Prince, L S; Yull, F E; Blackwell, T S

    2012-06-28

    The mechanisms by which chronic inflammatory lung diseases, particularly chronic obstructive pulmonary disease, confer enhanced risk for lung cancer are not well-defined. To investigate whether nuclear factor (NF)-κB, a key mediator of immune and inflammatory responses, provides an interface between persistent lung inflammation and carcinogenesis, we utilized tetracycline-inducible transgenic mice expressing constitutively active IκB kinase β in airway epithelium (IKTA (IKKβ trans-activated) mice). Intraperitoneal injection of ethyl carbamate (urethane), or 3-methylcholanthrene (MCA) and butylated hydroxytoluene (BHT) was used to induce lung tumorigenesis. Doxycycline-treated IKTA mice developed chronic airway inflammation and markedly increased numbers of lung tumors in response to urethane, even when transgene expression (and therefore epithelial NF-κB activation) was begun after exposure to carcinogen. Studies using a separate tumor initiator/promoter model (MCA+BHT) indicated that NF-κB functions as an independent tumor promoter. Enhanced tumor formation in IKTA mice was preceded by increased proliferation and reduced apoptosis of alveolar epithelium, resulting in increased formation of premalignant lesions. Investigation of inflammatory cells in lungs of IKTA mice revealed a substantial increase in macrophages and lymphocytes, including functional CD4+/CD25+/FoxP3+ regulatory T lymphocytes (Tregs). Importantly, Treg depletion using repetitive injections of anti-CD25 antibodies limited excessive tumor formation in IKTA mice. At 6 weeks following urethane injection, antibody-mediated Treg depletion in IKTA mice reduced the number of premalignant lesions in the lungs in association with an increase in CD8 lymphocytes. Thus, persistent NF-κB signaling in airway epithelium facilitates carcinogenesis by sculpting the immune/inflammatory environment in the lungs.

  15. Methylation-mediated transcriptional repression of microRNAs during cervical carcinogenesis

    Science.gov (United States)

    Wilting, Saskia M.; Verlaat, Wina; Jaspers, Annelieke; Makazaji, Nour A.; Agami, Reuven; Meijer, Chris J.L.M.; Snijders, Peter J.F.

    2013-01-01

    Deregulated expression of microRNAs (miRNAs) is common and biologically relevant in cervical carcinogenesis and appears only partly related to chromosomal changes. We recently identified 32 miRNAs showing decreased expression in high-grade cervical intraepithelial neoplasia (CIN) and carcinomas not associated with a chromosomal loss, 6 of which were located within a CpG island. This study aimed to investigate to what extent these miRNAs are subject to DNA methylation-mediated transcriptional repression in cervical carcinogenesis.   Methylation-specific PCR (MSP) analysis on a cell line panel representing different stages of human papillomavirus (HPV) induced transformation revealed an increase in methylation of hsa-miR-149, -203 and -375 with progression to malignancy, whereas expression of these miRNAs was restored upon treatment with a demethylating agent. All three miRNAs showed significantly increased levels of methylation in cervical carcinomas, whereas methylation levels of hsa-miR-203 and -375 were also significantly increased in high-grade CIN. A pilot analysis showed that increased hsa-miR-203 methylation was also detectable in HPV-positive cervical scrapes of women with high-grade CIN compared with controls. Similar to recent findings on hsa-miR-375, ectopic expression of hsa-miR-203 in cervical cancer cells decreased both the proliferation rate and anchorage independent growth. We found evidence for methylation-mediated transcriptional repression of hsa-miR-149, -203 and -375 in cervical cancer. Methylation of the latter two was already apparent in precancerous lesions and represent functionally relevant events in HPV-mediated transformation. Increased hsa-miR-203 methylation was detectable in scrapes of women with high-grade CIN, indicating that methylated miRNAs may provide putative markers to assess the presence of (pre)cancerous lesions. PMID:23324622

  16. Boolean Network Model for Cancer Pathways: Predicting Carcinogenesis and Targeted Therapy Outcomes

    Science.gov (United States)

    Fumiã, Herman F.; Martins, Marcelo L.

    2013-01-01

    A Boolean dynamical system integrating the main signaling pathways involved in cancer is constructed based on the currently known protein-protein interaction network. This system exhibits stationary protein activation patterns – attractors – dependent on the cell's microenvironment. These dynamical attractors were determined through simulations and their stabilities against mutations were tested. In a higher hierarchical level, it was possible to group the network attractors into distinct cell phenotypes and determine driver mutations that promote phenotypic transitions. We find that driver nodes are not necessarily central in the network topology, but at least they are direct regulators of central components towards which converge or through which crosstalk distinct cancer signaling pathways. The predicted drivers are in agreement with those pointed out by diverse census of cancer genes recently performed for several human cancers. Furthermore, our results demonstrate that cell phenotypes can evolve towards full malignancy through distinct sequences of accumulated mutations. In particular, the network model supports routes of carcinogenesis known for some tumor types. Finally, the Boolean network model is employed to evaluate the outcome of molecularly targeted cancer therapies. The major find is that monotherapies were additive in their effects and that the association of targeted drugs is necessary for cancer eradication. PMID:23922675

  17. Final Report May 1, 2012 to May 31, 2015: "Theoretical Studies in Elementary Particle Physics"

    Energy Technology Data Exchange (ETDEWEB)

    Collins, John C. [Pennsylvania State Univ., State College, PA (United States); Roiban, Radu [Pennsylvania State Univ., State College, PA (United States)

    2015-08-19

    This final report summarizes work at Penn State University from May 1, 2012 to May 31, 2015. The work was in theoretical elementary particle physics. Many new results in perturbative QCD, in string theory, and in related areas were obtained, with a substantial impact on the experimental program.

  18. Economic Studies and Out-of-School Education Program Evaluation for the Ivory Coast. Final Report.

    Science.gov (United States)

    Grant, Stephen; And Others

    This report is a final one in a series of 17 reports concerned with costs analysis/projections of the instructional television program and the Out of School Television (OSTV) project in the Ivory Coast. It includes an introduction to the OSTV project after its first five years of existence, a description of the main elements of the in-school…

  19. Study of hadronic final states from double tagged $gammagamma$ events at LEP

    CERN Document Server

    Heister, A; Antonelli, A; Antonelli, M; Armstrong, S R; Awunor, O; Azzurri, P; Badaud, F; Bagliesi, G; Barate, R; Barklow, Timothy L; Bencivenni, G; Berkelman, K; Beuselinck, R; Blair, G A; Bloch-Devaux, B; Blondel, A; Blumenschein, U; Boccali, T; Bonissent, A; Booth, C N; Borean, C; Bossi, F; Boucrot, J; Bouhova-Thacker, E; Boumediene, D E; Bowdery, C K; Brandt, S; Bravo, S; Brient, J C; Brunelière, R; Buchmüller, O L; Böhrer, A; Callot, O; Cameron, W; Capon, G; Cartwright, S; Casado, M P; Cattaneo, M; Cavanaugh, R J; Cerutti, F; Chiarella, V; Chmeissani, M; Ciulli, V; Clarke, D P; Clerbaux, B; Clifft, R W; Colaleo, A; Colas, P; Combley, F; Cowan, G; Coyle, P; Cranmer, K; Creanza, D; Crespo, J M; Curtil, C; David, A; Davier, M; Davies, G; De Bonis, I; De Filippis, N; De Palma, M; Delaere, C; Dessagne, S; Dhamotharan, S; Dietl, H; Dissertori, G; Dornan, P J; Drevermann, H; Duflot, L; Décamp, D; Ealet, A; Edgecock, T R; Ellis, G; Fabbro, B; Falvard, A; Fayolle, D; Ferguson, D P S; Fernández-Bosman, M; Fernández, E; Finch, A J; Focardi, E; Forty, R W; Foster, F; Fouchez, D; Foà, L; Frank, M; Ganis, G; Gao, Y; García-Bellido, A; Garrido, L; Gay, P; Geweniger, C; Ghete, V M; Giammanco, A; Giannini, G; Gianotti, F; Giassi, A; Girone, M; Girtler, P; González, S; Goy, C; Green, M G; Grivaz, J F; Grupen, C; Hanke, P; Hansen, J B; Hansen, J D; Hansen, J R; Hansen, P H; Harvey, J; Hayes, O J; He, H; Hepp, V; Hess, J; Heusse, P; Hill, R D; Hodgson, P N; Hu, H; Huang, X; Hughes, G; Hutchcroft, D E; Hölldorfer, F; Hüttmann, K; Iaselli, G; Jacholkowska, A; Jakobs, K; Janot, P; Jin, S; Jones, L T; Jones, R W L; Jost, B; Jousset, J; Jézéquel, S; Kado, M; Kayser, F; Kennedy, J; Kile, J; Kleinknecht, K; Kluge, E E; Kneringer, E; Konstantinidis, N P; Kraan, A C; Kuhn, D; Kyriakis, A; Lançon, E; Laurelli, P; Lees, J P; Lehto, M H; Leibenguth, G; Lemaire, M C; Lemaître, V; Ligabue, F; Lin, J; Litke, A M; Locci, E; Lynch, J G; Lütjens, G; Machefert, F P; Maggi, G; Maggi, M; Mannocchi, G; Marinelli, N; Markou, C; Martin, F; Martínez, M; Mato, P; McNamara, P A; Medcalf, T; Merle, E; Messineo, A; Michel, B; Minard, M N; Misiejuk, A; Monteil, S; Moser, H G; Moutoussi, A; Murtas, G P; Männer, W; Müller, A S; Negus, P; Ngac, A; Nielsen, J; Nilsson, B S; Norton, P R; Nowell, J; Nuzzo, S; O'Shea, V; Ouyang, Q; Pacheco, A; Palla, Fabrizio; Pallin, D; Pan, Y B; Parrini, G; Pascolo, J M; Passalacqua, L; Payre, P; Pearson, M R; Perret, P; Pietrzyk, B; Prange, G; Putzer, A; Pérez, P; Pütz, J; Ragusa, F; Rander, J; Ranieri, A; Ranjard, F; Raso, G; Renk, B; Robertson, N A; Rolandi, Luigi; Rothberg, J E; Rougé, A; Rudolph, G; Ruggieri, F; Ruiz, H; Rutherford, S A; Sander, H G; Sanguinetti, G; Schael, S; Schlatter, W D; Schmeling, S; Sciabà, A; Sedgbeer, J K; Selvaggi, G; Serin, L; Settles, Ronald; Sguazzoni, G; Silvestris, L; Simopoulou, Errietta; Smizanska, M; Spagnolo, P; Stenzel, H; Strong, J A; Swynghedauw, M; Tanaka, R; Taylor, G; Teixeira-Dias, P; Tejessy, W; Tempesta, P; Tenchini, R; Teubert, F; Thompson, A S; Thompson, J C; Thompson, L F; Tilquin, A; Tittel, K; Tomalin, I R; Tricomi, A; Trocmé, B; Tuchming, B; Valassi, Andrea; Vallage, B; Vayaki, Anna; Veillet, J J; Venturi, A; Verdini, P G; Videau, H L; Videau, I; Villegas, M; Von Wimmersperg-Töller, J H; Wachsmuth, H W; Wang, T; Ward, J J; Wasserbaech, S R; White, R; Wiedenmann, W; Wolf, G; Wu, J; Wu Sau Lan; Wu, X; Wunsch, M; Xie, Y; Xu, R; Xue, S; Zachariadou, K; Zeitnitz, C; Zhang, J; Zhang, L; Zhao, W; Ziegler, T; Zito, G; Zobernig, G; van der Aa, O

    2003-01-01

    The interaction of virtual photons is investigated using double tagged gammagamma events with hadronic final states recorded by the ALEPH experiment at e^+e^- centre-of-mass energies between 188 and 209 GeV. The measured cross section is compared to Monte Carlo models, and to next-to-leading-order QCD and BFKL calculations.

  20. Climate system studies: final report to the U.S. Department of Energy

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, Raymond S.; Diaz, Henry F.

    2000-03-01

    In this final report, we summarize research on climate variability and forcing mechanisms responsible for these changes. We report on research related to high elevation climate change, changes in the hydrological cycle and the seasonality of precipitation and on changes in climatic extremes. A comprehensive bibliography of research articles and books arising from this grant is included as an appendix.

  1. An Aggregate Data Archive for the Russian Area Studies Center, Louisiana State University. Final Report.

    Science.gov (United States)

    Zwick, Peter R.

    This final report announces the completion of a project, the purpose of which was to develop in coded machine retrievable form, a biographical data archive on the Soviet political elite, and in addition, to gather data on socio-economic and political factors in the Soviet Union and Eastern Europe. The computer processed data is intended to help…

  2. Early diagnosis of colorectal cancer in rats with DMH induced carcinogenesis by means of urine autofluorescence analysis.

    Science.gov (United States)

    Šteffeková, Zuzana; Birková, Anna; Bomba, Alojz; Mareková, Mária

    2014-01-01

    Cancer is one of the most highlighted topics of current research. Early detection of this disease allows more effective therapy, hence higher chance of cure. Application of fluorescence spectral techniques into oncological diagnostic is one of the potential alternatives. Chemically induced carcinogenesis in rats is widely used model for exploration of various aspects of colorectal cancer. This study shows value of discriminate analysis of urine fluorescent fingerprint between healthy control group of rats and those with dimethylhydrazine induced early lesions of colorectal cancer. Using fluorescence spectroscopy, significant difference (P < 0.05) between both of group was achieved.

  3. 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.

  4. Relationship between Helicobacter pylori infection and gastric carcinogenesis in elderly patients

    Institute of Scientific and Technical Information of China (English)

    李文新

    2013-01-01

    Objective To explore the relationship between Helicobacter pylori (HP) infection and gastric carcinogenesis,and to investigate its mechanism.Methods Totally 333elderly patients with different degrees of gastric mucosal lesions in our hospital were selected.Patients were

  5. 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 pub

  6. The role of B-vitamins - gene interactions in colorectal carcinogenesis: A molecular epidemiological approach

    NARCIS (Netherlands)

    Donk, van den M.

    2005-01-01

    Folate deficiency can affect DNA methylation and DNA synthesis. Both factors may be operative in colorectal carcinogenesis. Many enzymes, like methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS), methionine synthase (MTR), and serine hydroxymethyltransferase (SHMT), are needed for

  7. The Multi-Disciplinary Graduate Program in Educational Research. Final Report, Part V; The Frame of Reference Study.

    Science.gov (United States)

    Lazarsfeld, Paul F., Ed.

    This "Frame of Reference Study" consists of the fifth section of the final report of the Multi-Disciplinary Graduate Program in Educational Research of the University of Pittsburgh. The term, "frames of reference," is used to mean the context of assumptions, procedures, rules, cognitive models, and conceptions of the nature of…

  8. Master plan study - District heating Kohtla-Jaerve and Johvi municipalities. Estonia. Final report. Appendices for chapter 9

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The appendices to chapter nine of the final report of the master plan study on district heating in the municipalities of Kohtla-Jarve and Johvi municipalities (Estonia) present extensive data relating to economic, financial and environmental calculations, fuel consumption, energy balance and prices. (ARW)

  9. ERDA summer study of heavy ions for inertial fusion, Oakland/Berkeley, California, July 19--30, 1976. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Bangerter, R.O.; Herrmannsfeldt, W.B.; Judd, D.L.; Smith, L.

    1976-12-01

    Technical summaries are given for the following areas: (1) target and reactor design, (2) ion sources, (3) low-velocity acceleration, (4) atomic and molecular physics, (5) accelerator parameters, (6) beam manipulations, (7) induction linac, (8) final focusing and transmission to the target, (9) systems and cost studies, and (10) alternatives. Several groups of appendices are given that relate to these technical summaries. (MOW)

  10. Master plan study - District heating Kohtla-Jaerve and Johvi municipalities. Estonia. Final report. Appendices for chapter 8

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    The appendices to chapter 8 of the final report on the master plan study on district heating in the municipalities of Kohtla-Jarve and Johvi (Estonia) presents technical data with the emphasis on district heating pipes, heat losses, prices, retrofitting, economics, costs and heat load duration. (ARW)

  11. High resolution study of the LAMBDAp final state interaction in the reaction p+p->K{sup +}+(LAMBDAp)

    Energy Technology Data Exchange (ETDEWEB)

    Budzanowski, A. [Institute of Nuclear Physics, Polish Academy of Sciences, Krakow (Poland); Chatterjee, A. [Nuclear Physics Division, BARC, Mumbai (India); Clement, H.; Dorochkevitch, E. [Physikalisches Institut, Universitaet Tuebingen (Germany); Hawranek, P. [Institute of Physics, Jagellonian University, Krakow (Poland); Hinterberger, F., E-mail: fh@hiskp.uni-bonn.d [Helmholtz-Institut fuer Strahlen- und Kernphysik, Universitaet Bonn, Bonn (Germany); Jahn, R.; Joosten, R. [Helmholtz-Institut fuer Strahlen- und Kernphysik, Universitaet Bonn, Bonn (Germany); Kilian, K. [Institut fuer Kernphysik, Forschungszentrum Juelich, Juelich (Germany); Juelich Centre for Hadron Physics, Forschungszentrum Juelich, Juelich (Germany); Kliczewski, S. [Institute of Nuclear Physics, Polish Academy of Sciences, Krakow (Poland); Kirillov, Da. [Institut fuer Kernphysik, Forschungszentrum Juelich, Juelich (Germany); Juelich Centre for Hadron Physics, Forschungszentrum Juelich, Juelich (Germany); Fachbereich Physik, Universitaet Duisburg-Essen, Duisburg (Germany); Kirillov, Di. [Laboratory for High Energies, JINR Dubna (Russian Federation); Kolev, D. [Physics Faculty, University of Sofia, Sofia (Bulgaria); Kravcikova, M. [Technical University Kosice, Kosice (Slovakia); Lesiak, M. [Institute of Physics, Jagellonian University, Krakow (Poland); Institut fuer Kernphysik, Forschungszentrum Juelich, Juelich (Germany); Juelich Centre for Hadron Physics, Forschungszentrum Juelich, Juelich (Germany); Machner, H. [Institut fuer Kernphysik, Forschungszentrum Juelich, Juelich (Germany); Juelich Centre for Hadron Physics, Forschungszentrum Juelich, Juelich (Germany); Fachbereich Physik, Universitaet Duisburg-Essen, Duisburg (Germany); Magiera, A. [Institute of Physics, Jagellonian University, Krakow (Poland); Martinska, G. [P.J. Safarik University, Kosice (Slovakia); Piskunov, N. [Laboratory for High Energies, JINR Dubna (Russian Federation)

    2010-04-05

    The reaction pp->K{sup +}+(LAMBDAp) was measured at T{sub p}=1.953 GeV and THETA=0{sup o} with a high missing mass resolution in order to study the LAMBDAp final state interaction. The large final state enhancement near the LAMBDAp threshold can be described using the standard Jost-function approach. The singlet and triplet scattering lengths and effective ranges are deduced by fitting simultaneously the LAMBDAp invariant mass spectrum and the total cross section data of the free LAMBDAp scattering.

  12. High resolution study of the Lambda p final state interaction in the reaction p + p -> K+ + (Lambda p)

    CERN Document Server

    Budzanowski, A; Clement, H; Dorochkevitch, E; Hawranek, P; Hinterberger, F; Jahn, R; Joosten, R; Kilian, K; Kliczewski, S; Kirillov, Da; Kirillov, Di; Kolev, D; Kravcikova, M; Lesiak, M; Machner, H; Magiera, A; Martinska, G; Piskunov, N; Ritman, J; von Rossen, P; Roy, B J; Sibirtsev, A; Sitnik, I; Siudak, R; Tsenov, R; Ulbrich, K; Urban, J; Wagner, G J

    2010-01-01

    The reaction pp -> K+ + (Lambda p) was measured at Tp=1.953 GeV and Theta = 0 deg with a high missing mass resolution in order to study the Lambda p final state interaction. The large final state enhancement near the Lambda p threshold can be described using the standard Jost-function approach. The singlet and triplet scattering lengths and effective ranges are deduced by fitting simultaneously the Lambda p invariant mass spectrum and the total cross section data of the free Lambda p scattering.

  13. Modifier-concept of colorectal carcinogenesis: Lipidomics as a technical tool in pathway analysis

    Institute of Scientific and Technical Information of China (English)

    Nikolaus; Gassler; Christina; Klaus; Elke; Kaemmerer; Andrea; Reinartz

    2010-01-01

    In the modifier concept of intestinal carcinogenesis, lipids have been established as important variables and one focus is given to long-chain fatty acids. Increased consumption of long-chain fatty acids is in discussion to modify the development of colorectal carcinoma in humans. Saturated long-chain fatty acids, in particular, are assumed to promote carcinogenesis, whereas poly-unsaturated forms are likely to act in the opposite way. At present, the molecular mechanisms behind these effects are not well u...

  14. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats

    Science.gov (United States)

    Kakehashi, Anna; Yoshida, Midori; Tago, Yoshiyuki; Ishii, Naomi; Okuno, Takahiro; Gi, Min; Wanibuchi, Hideki

    2016-01-01

    Pueraria mirifica (PM), a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA) initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w.)/day) PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG), respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3%, and more pronouncedly, at 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA. PMID:27827907

  15. Insights into the field carcinogenesis of ovarian cancer based on the nanocytology of endocervical and endometrial epithelial cells.

    Science.gov (United States)

    Damania, Dhwanil; Roy, Hemant K; Kunte, Dhananja; Hurteau, Jean A; Subramanian, Hariharan; Cherkezyan, Lusik; Krosnjar, Nela; Shah, Maitri; Backman, Vadim

    2013-09-01

    Ovarian cancer ranks fifth in cancer fatalities among American women. Although curable at early stages with surgery, most women are diagnosed with symptoms of late-stage metastatic disease. Moreover, none of the current diagnostic techniques are clinically recommended for at-risk women as they preferentially target low-grade tumors (which do not affect longevity) and fail to capture early signatures of more lethal serous tumors which originate in the fimbrae region of the fallopian tubes. Hence, the early detection of ovarian cancer is challenging given the current strategy. Recently, our group has developed a novel optical imaging technique, partial wave spectroscopic (PWS) microscopy, that can quantify the nanoscale macromolecular density fluctuations within biological cells via a biomarker, disorder strength (Ld ). Using the concept of field carcinogenesis, we propose a method of detecting ovarian cancer by PWS assessment of endometrial and endocervical columnar cells. The study includes 26 patients (controls = 15, cancer = 11) for endometrium and 23 (controls = 13, cancer = 10) for endocervix. Our results highlight a significant increase in Ld (% fold-increase > 50%, p-value < 0.05) for columnar epithelial cells obtained from cancer patients compared to controls for both endocervix and endometrium. Overall, the quantification of field carcinogenic events in the endometrium and the novel observation of its extension to the cervix are unique findings in the understanding of ovarian field carcinogenesis. We further show independent validation of the presence of cervical field carcinogenesis with micro-RNA expression data.

  16. A novel mouse model for colitis-associated colon carcinogenesis induced by 1,2-dimethylhydrazine and dextran sulfate sodium

    Institute of Scientific and Technical Information of China (English)

    Jian-Guo Wang; Dong-Fei Wang; Bing-Jian Lv; Jian-Min Si

    2004-01-01

    AIM: To develop an efficient animal colitis-associated carcinogenesis model and to detect the expression of β-catenin and p53 in this new model.METHODS: Dysplasia and cancer were investigated in mice pretreated with a single intraperitoneal injection of 20 mg/kg body mass of 1,2-dimethylhydrazine prior to three repetitive oral administrations of 30 g/L dextran sulfate sodium to give conditions similar to the clinically observed active and remission phases. Immunohistochemical staining of β-catenin and p53 was performed on paraffin-imbedded specimens of animals with cancer and/or dysplasia, those without dysplasia and the normal control animals.RESULTS: At wk 11, four early-invasive adenocarcinomas and 36 dysplasia were found in 10 (90.9%) of the 11 mice that underwent 1,2-dimethylhydrazine-pretreatment with 3 cycles of 30 g/L dextran sulfate sodium-exposure. Dysplasia and/or cancer occurred as flat lesions or as dysplasia-associated lesion or mass (DALM) as observed in humans. Colorectal carcinogenesis occurred primarily on the distal portion of the large intestine. No dysplasia and/or cancer lesion was observed in the control groups with 1,2-dimethylhydrazine pretreatment or 3 cycles of 30 g/L dextran sulfate sodium exposure alone. Immunohistochemical investigation revealed that β-catenin was translocated from cell membrane to cytoplasm and/or nucleus in 100% of cases with dysplasia and neoplasm, while normal membrane staining was observed in cases without dysplasia and the normal control animals. Nuclear expression of p53 was not detected in specimens.CONCLUSION: A single dose of procarcinogen followed by induction of chronic ulcerative colitis results in a high incidence of colorectal dysplasia and cancer. Abnormal expression of β-catenin occurs frequently in dysplasia and cancer. This novel mouse model may provide an excellent vehicle for studying colitis-related colon carcinogenesis.

  17. Pueraria mirifica Exerts Estrogenic Effects in the Mammary Gland and Uterus and Promotes Mammary Carcinogenesis in Donryu Rats

    Directory of Open Access Journals (Sweden)

    Anna Kakehashi

    2016-11-01

    Full Text Available Pueraria mirifica (PM, a plant whose dried and powdered tuberous roots are now widely used in rejuvenating preparations to promote youthfulness in both men and women, may have major estrogenic influence. In this study, we investigated modifying effects of PM at various doses on mammary and endometrial carcinogenesis in female Donryu rats. Firstly, PM administered to ovariectomized animals at doses of 0.03%, 0.3%, and 3% in a phytoestrogen-low diet for 2 weeks caused significant increase in uterus weight. Secondly, a 4 week PM application to non-operated rats at a dose of 3% after 7,12-dimethylbenz[a]anthracene (DMBA initiation resulted in significant elevation of cell proliferation in the mammary glands. In a third experiment, postpubertal administration of 0.3% (200 mg/kg body weight (b.w./day PM to 5-week-old non-operated animals for 36 weeks following initiation of mammary and endometrial carcinogenesis with DMBA and N-ethyl-N′-nitro-N-nitrosoguanidine (ENNG, respectively, resulted in significant increase of mammary adenocarcinoma incidence. A significant increase of endometrial atypical hyperplasia multiplicity was also observed. Furthermore, PM at doses of 0.3%, and more pronouncedly, at 1% induced dilatation, hemorrhage and inflammation of the uterine wall. In conclusion, postpubertal long-term PM administration to Donryu rats exerts estrogenic effects in the mammary gland and uterus, and at a dose of 200 mg/kg b.w./day was found to promote mammary carcinogenesis initiated by DMBA.

  18. Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Vasile Ostafe

    2011-08-01

    Full Text Available Given the modeling and predictive abilities of quantitative structure activity relationships (QSARs for genotoxic carcinogens or mutagens that directly affect DNA, the present research investigates structural alert (SA intermediate-predicted correlations ASA of electrophilic molecular structures with observed carcinogenic potencies in rats (observed activity, A = Log[1/TD50], i.e., ASA=f(X1SA,X2SA,.... The present method includes calculation of the recently developed residual correlation of the structural alert models, i.e., ARASA=f(A-ASA,X1SA,X2SA,... . We propose a specific electrophilic ligand-receptor mechanism that combines electronegativity with chemical hardness-associated frontier principles, equality of ligand-reagent electronegativities and ligand maximum chemical hardness for highly diverse toxic molecules against specific receptors in rats. The observed carcinogenic activity is influenced by the induced SA-mutagenic intermediate effect, alongside Hansch indices such as hydrophobicity (LogP, polarizability (POL and total energy (Etot, which account for molecular membrane diffusion, ionic deformation, and stericity, respectively. A possible QSAR mechanistic interpretation of mutagenicity as the first step in genotoxic carcinogenesis development is discussed using the structural alert chemoinformation and in full accordance with the Organization for Economic Co-operation and Development QSAR guidance principles.

  19. Alert-QSAR. Implications for Electrophilic Theory of Chemical Carcinogenesis

    Science.gov (United States)

    Putz, Mihai V.; Ionaşcu, Cosmin; Putz, Ana-Maria; Ostafe, Vasile

    2011-01-01

    Given the modeling and predictive abilities of quantitative structure activity relationships (QSARs) for genotoxic carcinogens or mutagens that directly affect DNA, the present research investigates structural alert (SA) intermediate-predicted correlations ASA of electrophilic molecular structures with observed carcinogenic potencies in rats (observed activity, A = Log[1/TD50], i.e., ASA=f(X1SA,X2SA,…)). The present method includes calculation of the recently developed residual correlation of the structural alert models, i.e., ARASA=f(A−ASA,X1SA,X2SA,…). We propose a specific electrophilic ligand-receptor mechanism that combines electronegativity with chemical hardness-associated frontier principles, equality of ligand-reagent electronegativities and ligand maximum chemical hardness for highly diverse toxic molecules against specific receptors in rats. The observed carcinogenic activity is influenced by the induced SA-mutagenic intermediate effect, alongside Hansch indices such as hydrophobicity (LogP), polarizability (POL) and total energy (Etot), which account for molecular membrane diffusion, ionic deformation, and stericity, respectively. A possible QSAR mechanistic interpretation of mutagenicity as the first step in genotoxic carcinogenesis development is discussed using the structural alert chemoinformation and in full accordance with the Organization for Economic Co-operation and Development QSAR guidance principles. PMID:21954348

  20. 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.

  1. Cocarcinogenic and tumor-promoting agents in tobacco carcinogenesis.

    Science.gov (United States)

    Van Duuren, B L; Goldschmidt, B M

    1976-06-01

    A series of 21 tobacco smoke components and related compounds werere applied to mouse skin (50 female ICR/Ha Swiss mice/group) three times weekly with a low dose (5 mug/application) of benzo[a]pyrene (B[a]P). The test compounds were of five classes: aliphatic hydrocarbons, aromatic hydrocarbons, phenols, and long-chain acids and alcohols. The following compounds enhanced remarkably the carcinogenicity of B[a]P: catechol, pyrogallol, decane, undecane, pyrene, benzo[e]pyrene, and fluoranthene. The following compounds inhibited B[a]P carcinogenicity completely: esculin, quercetin, squalene, and oleic acid. Phenol, eugenol, resorcinol, hydroquinone, hexadecane, and limonene partially inhibited B[a]P carcinogenicity. Six of the 21 compounds were also tested as tumor promoters im two-stage carcinogenesis. No direct correlation existed between tumor-promoting activity and cocarcinogenic activity. The cocarcinogens pyrogallol and catechol did not show tumor-promoting activity. Decane, tetradecane, anthralin, and phorbol myristate acetate showed both types of activity. Structure-activity relationships and possible modes of action were described.

  2. Emerging role of bacteria in oral carcinogenesis: a review with special reference to perio-pathogenic bacteria

    Science.gov (United States)

    Perera, Manosha; Al-hebshi, Nezar Noor; Speicher, David J.; Perera, Irosha; Johnson, Newell W.

    2016-01-01

    Oral cancer, primarily oral squamous cell carcinoma (OSCC), continues to be a major global health problem with high incidence and low survival rates. While the major risk factors for this malignancy, mostly lifestyle related, have been identified, around 15% of oral cancer cases remain unexplained. In light of evidence implicating bacteria in the aetiology of some cancer types, several epidemiological studies have been conducted in the last decade, employing methodologies ranging from traditional culture techniques to 16S rRNA metagenomics, to assess the possible role of bacteria in OSCC. While these studies have demonstrated differences in microbial composition between cancerous and healthy tissues, they have failed to agree on specific bacteria or patterns of oral microbial dysbiosis to implicate in OSCC. On the contrary, some oral taxa, particularly Porphyromonas gingivalis and Fusobacterium nucleatum, show strong oral carcinogenic potential in vitro and in animal studies. Bacteria are thought to contribute to oral carcinogenesis via inhibition of apoptosis, activation of cell proliferation, promotion of cellular invasion, induction of chronic inflammation, and production of carcinogens. This narrative review provides a critical analysis of and an update on the association between bacteria and oral carcinogenesis and the possible mechanisms underlying it. PMID:27677454

  3. Emerging role of bacteria in oral carcinogenesis: a review with special reference to perio-pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Manosha Perera

    2016-09-01

    Full Text Available Oral cancer, primarily oral squamous cell carcinoma (OSCC, continues to be a major global health problem with high incidence and low survival rates. While the major risk factors for this malignancy, mostly lifestyle related, have been identified, around 15% of oral cancer cases remain unexplained. In light of evidence implicating bacteria in the aetiology of some cancer types, several epidemiological studies have been conducted in the last decade, employing methodologies ranging from traditional culture techniques to 16S rRNA metagenomics, to assess the possible role of bacteria in OSCC. While these studies have demonstrated differences in microbial composition between cancerous and healthy tissues, they have failed to agree on specific bacteria or patterns of oral microbial dysbiosis to implicate in OSCC. On the contrary, some oral taxa, particularly Porphyromonas gingivalis and Fusobacterium nucleatum, show strong oral carcinogenic potential in vitro and in animal studies. Bacteria are thought to contribute to oral carcinogenesis via inhibition of apoptosis, activation of cell proliferation, promotion of cellular invasion, induction of chronic inflammation, and production of carcinogens. This narrative review provides a critical analysis of and an update on the association between bacteria and oral carcinogenesis and the possible mechanisms underlying it.

  4. Effect of the electronic and physicochemical parameters on the carcinogenesis activity of some sulfa drugs using QSAR analysis based on genetic-MLR and genetic-PLS.

    Science.gov (United States)

    Deeb, Omar; Hemmateenejad, Bahram; Jaber, Amal; Garduno-Juarez, R; Miri, Ramin

    2007-05-01

    A quantitative structure activity relationship study has been applied to a data set of 18 sulfa drugs with carcinogenesis activity. Semi-empirical quantum chemical calculation (AM1 method) was used to find the optimum 3D geometry of the studied molecules. Two types of molecular descriptors including chemical and electronic was used to derive a quantitative relation between the carcinogenesis activity and structural properties. Two multi-parametric equations with good statistical qualities were obtained using genetic algorithms multiple linear regression (GA-MLR) methods. In addition, genetic algorithm-partial least squares (GA-PLS) regression was used to model the structure-activity relationships, more accurately. The results confirmed the superiority of the results obtained by GA-PLS relative to GA-MLR. The significant effect of the HOMO energy on the carcinogenic activity was explained in the context of the shape of this orbital.

  5. Study of Charmless Hadronic B Meson Decays to Pseudoscalar-Vector Final States

    CERN Document Server

    Jessop, C P; Perl, Martin Lewis; Savinov, V; Ugolini, D W; Zhou, X; Coan, T E; Fadeev, V; Maravin, Y; Narsky, I; Stroynowski, R; Ye, J; Wlodek, T; Artuso, M; Ayad, R; Boulahouache, C; Bukin, K; Dambasuren, E; Karamov, S; Majumder, G; Moneti, G C; Mountain, R; Schuh, S; Skwarnicki, T; Stone, S; Viehhauser, G; Wang, J C; Wolf, A; Wu, J; Kopp, S E; Csorna, S E; Danko, I; McLean, K W; Marka, S; Xu, Z; Godang, R; Kinoshita, K; Lai, I C; Schrenk, S; Bonvicini, G; Cinabro, D; McGee, S; Perera, L P; Zhou, G J; Lipeles, E; Schmidtler, M; Shapiro, A; Sun, W M; Weinstein, A J; Würthwein, F; Jaffe, D E; Masek, G E; Paar, H P; Potter, E M; Prell, S; Sharma, V; Asner, D M; Eppich, A; Hill, T S; Morrison, R J; Nelson, H N; Briere, R A; Behrens, B H; Ford, W T; Gritsan, A; Roy, J D; Smith, J G; Alexander, J P; Baker, R; Bebek, C; Berger, B E; Berkelman, K; Blanc, F; Boisvert, V; Cassel, David G; Dickson, M; Drell, P S; Ecklund, K M; Ehrlich, R; Foland, A D; Gaidarev, P B; Gibbons, L K; Gittelman, B; Gray, S W; Hartill, D L; Heltsley, B K; Hopman, P I; Jones, C D; Kreinick, D L; Lohner, M; Magerkurth, A; Meyer, T O; Mistry, N B; Nordberg, E; Patterson, J R; Peterson, D; Riley, D; Thayer, J G; Thies, P G; Valant-Spaight, B L; Warburton, A; Avery, P; Prescott, C; Rubiera, A I; Yelton, J; Zheng, J; Brandenburg, G; Ershov, A; Gao, Y S; Kim, D Y J; Wilson, R; Browder, T E; Li, Y; Rodríguez, J L; Yamamoto, H; Bergfeld, T; Eisenstein, B I; Ernst, J; Gladding, G E; Gollin, G D; Hans, R M; Johnson, E; Karliner, I; Marsh, M A; Palmer, M; Plager, C; Sedlack, C; Selen, M; Thaler, J J; Williams, J; Edwards, K W; Janicek, R; Patel, P M; Sadoff, A J; Ammar, R; Bean, A; Besson, D; Davis, R; Kwak, N; Zhao, X; Anderson, S; Frolov, V V; Kubota, Y; Lee, S J; Mahapatra, R; O'Neill, J J; Poling, R A; Riehle, T; Smith, A; Urheim, J; Ahmed, S; Alam, M S; Athar, S B; Jian, L; Ling, L; Mahmood, A H; Saleem, M; Timm, S; Wappler, F; Anastassov, A; Duboscq, J E; Gan, K K; Gwon, C; Hart, T; Honscheid, K; Hufnagel, D; Kagan, H; Kass, R; Pedlar, T K; Schwarthoff, H; Thayer, J B; Von Törne, E; Zoeller, M M; Richichi, S J; Severini, H; Skubic, P L; Undrus, A; Chen, S; Fast, J; Hinson, J W; Lee, J; Menon, N; Miller, D H; Shibata, E I; Shipsey, I P J; Pavlunin, V; Cronin-Hennessy, D; Kwon, Y; Lyon, A L; Thorndike, E H

    2000-01-01

    We report results of searches for charmless hadronic B meson decays to pseudoscalar ($\\pi^{\\pm}$, $K^{\\pm}$ or $\\pi^{0}$) -vector($\\rho$, $K^{*}$ or $\\omega$) final states. Using 9.7 million $B\\bar{B}$ pairs collected with the CLEO detector, we report first observation of $B^{-}\\to\\pi^{-}\\rho^{0}$, $B^{0}\\to\\pi^{\\pm}\\rho^{\\mp}$ and $B^{-}\\to\\pi^{-}\\omega$, which are expected to be dominated by hadronic b to u transitions. The measured branching fractions are (10.4 +3.3-3.4 +- 2.1) x 10$^{-6}$, (27.6 +8.4-7.4 +- 4.2) x 10$^{-6}$ and (11.3 +3.3-2.9 +- 1.4) x 10$^{-6}$, respectively. Branching fraction upper limits are set for all the other decay modes investigated.

  6. Study of di-lepton final state with missing transverse momentum with ATLAS detector

    CERN Document Server

    Basalaev, Artem; The ATLAS collaboration

    2016-01-01

    Common analysis techniques are reviewed for di-lepton searches with large missing transverse momentum in proton-proton collisions at the ATLAS detector. Background estimates and corresponding systematic uncertainties are shown. The presented analyses are the search for an additional heavy Higgs boson with a mass in the range between 300 and 1000 GeV decaying to Z boson pairs with two leptons and two neutrinos in the final state, the search for invisible-particle decay modes of a Higgs boson with a mass of ~125 GeV produced in association with a Z boson, and the search for dark matter particle candidates produced in association with a Z boson. Results are presented for 8 TeV proton-proton collisions, except for the search for heavy Higgs bosons, for which 13 TeV results are shown.

  7. A complete kinematics approach to study multi-particle final state reactions

    Energy Technology Data Exchange (ETDEWEB)

    Alcorta, M. [Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, Madrid E-28006 (Spain)], E-mail: alcorta@iem.cfmac.csic.es; Kirsebom, O. [Department of Physics and Astronomy, University of Aarhus, DK-8000 Aarhus C (Denmark); Borge, M.J.G. [Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, Madrid E-28006 (Spain); Fynbo, H.O.U.; Riisager, K. [Department of Physics and Astronomy, University of Aarhus, DK-8000 Aarhus C (Denmark); Tengblad, O. [Instituto de Estructura de la Materia, CSIC, Serrano 113 bis, Madrid E-28006 (Spain)

    2009-07-01

    Detection in complete kinematics using highly segmented detectors can provide detailed information on the structure of excited nuclear states and their decay mechanisms. The detection of final states consisting of several particles gives rise to many challenges. We present here new techniques that allow for the extraction of physics from the many open channels. In particular this complete kinematic analysis technique has been applied to data from low-energy, high Q-value, light-ion reactions {sup 10}B({sup 3}He,p{alpha}{alpha}{alpha}), {sup 11}B({sup 3}He,d{alpha}{alpha}{alpha}), and {sup 7}Li({sup 3}He,p{alpha}{alpha})n, all of them performed at the CMAM tandem accelerator in Madrid.

  8. Study of the di-lepton final state with missing transverse momentum with the ATLAS detector

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00399337; The ATLAS collaboration

    2016-01-01

    Common analysis techniques are reviewed for di-lepton searches with large missing transverse momentum in proton-proton collisions in ATLAS detector at the LHC. Background estimates and corresponding systematic uncertainties are shown. The presented analyses are the search for an additional heavy Higgs boson with a mass in the range between 300 and 1000 GeV decaying to Z boson pairs with two leptons and two neutrinos in the final state, the search for invisible-particle decay modes of a Higgs boson with a mass of 125 GeV produced in association with a Z boson, and the search for dark matter particle candidates produced in association with a Z boson. Results are presented for 8 TeV proton-proton collisions, except for the search for heavy Higgs bosons, for which 13 TeV results are shown.

  9. LUPEOL PROTECTS ABNORMALITIES IN CELL SURFACE MOITIES DURING 7, 12-DIMETHYLBENZ[A]ANTHRACENE INDUCED HAMSTER BUCCAL POUCH CARCINOGENESIS

    Directory of Open Access Journals (Sweden)

    D. Palanimuthu and S. Manoharan*

    2012-05-01

    Full Text Available Lupeol, a pentacyclic triterpene, possesses diverse pharmacological and biochemical activities including anticancer and antioxidant effects. Abnormalities in the status of glycoconjugates and lipids in the cell results in malignant transformation. The aim of the present study was to investigate the protective effect of lupeol on cell surface glycoconjugates and lipids abnormalities during 7,12-dimethylbenz[a]anthracene (DMBA-induced hamster buccal pouch carcinogenesis. Oral squamous cell carcinoma was developed in the buccal pouches of golden Syrian hamsters by treating with 0.5% DMBA in liquid paraffin, three times a week, for 14 weeks. The status of glycoconjugates and lipids were measured using specific colorimetric methods. We observed 100% tumor formation with marked abnormalities in the status of glycoconjugates and lipids in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50mg/kg bw, completely prevented the formation of tumors and restored the status of glycoconjugates and lipids in hamsters treated with DMBA. The results of the present study thus suggest that lupeol has the potential to protect cell surface abnormalities during DMBA-induced hamster buccal pouch carcinogenesis.

  10. Folic acid, polymorphism of methyl-group metabolism genes, and DNA methylation in relation to GI carcinogenesis.

    Science.gov (United States)

    Fang, Jing Yuan; Xiao, Shu Dong

    2003-01-01

    DNA methylation is the main epigenetic modification after replication in humans. DNA (cytosine-5)-methyltransferase (DNMT) catalyzes the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to C5 of cytosine within CpG dinucleotide sequences in the genomic DNA of higher eukaryotes. There is considerable evidence that aberrant DNA methylation plays an integral role in carcinogenesis. Folic acid or folate is crucial for normal DNA synthesis and can regulate DNA methylation, and through this, it affects cellular SAM levels. Folate deficiency results in DNA hypomethylation. Epidemiological studies have indicated that folic acid protects against gastrointestinal (GI) cancers. Methylene-tetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are the enzymes involved in folate metabolism and are thought to influence DNA methylation. MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level. Two common MTHFR polymorphisms, 677CT (or 677TT) and A1298C, and an MS polymorphism, A-->G at 2756, have been identified. Most studies support an inverse association between folate status and the rate of colorectal adenomas and carcinomas. During human GI carcinogenesis, MTHFR is highly polymorphic, and the variant genotypes result in decreased MTHFR enzyme activity and lower plasma folate level, as well as aberrant methylation.

  11. A novel sulindac derivative lacking cyclooxygenase-inhibitory activities suppresses carcinogenesis in the transgenic adenocarcinoma of mouse prostate model.

    Science.gov (United States)

    Zhang, Yong; Zhang, Jinhui; Wang, Lei; Quealy, Emily; Gary, Bernard D; Reynolds, Robert C; Piazza, Gary A; Lü, Junxuan

    2010-07-01

    Nonsteroidal anti-inflammatory drugs including sulindac are well documented to be highly effective for cancer chemoprevention. However, their cyclooxygenase (COX)-inhibitory activities cause severe gastrointestinal, renal, and cardiovascular toxicities, limiting their chronic use. Recent studies suggest that COX-independent mechanisms may be responsible for the chemopreventive benefits of nonsteroidal anti-inflammatory drugs and support the potential for the development of a novel generation of sulindac derivatives lacking COX inhibition for cancer chemoprevention. A prototypic sulindac derivative with a N,N-dimethylammonium substitution called sulindac sulfide amide (SSA) was recently identified to be devoid of COX-inhibitory activity yet displays much more potent tumor cell growth-inhibitory activity in vitro compared with sulindac sulfide. In this study, we investigated the androgen receptor (AR) signaling pathway as a potential target for its COX-independent antineoplastic mechanism and evaluated its chemopreventive efficacy against prostate carcinogenesis using the transgenic adenocarcinoma of mouse prostate model. The results showed that SSA significantly suppressed the growth of human and mouse prostate cancer cells expressing AR in strong association with G(1) arrest, and decreased AR level and AR-dependent transactivation. Dietary SSA consumption dramatically attenuated prostatic growth and suppressed AR-dependent glandular epithelial lesion progression through repressing cell proliferation in the transgenic adenocarcinoma of mouse prostate mice, whereas it did not significantly affect neuroendocrine carcinoma growth. Overall, the results suggest that SSA may be a chemopreventive candidate against prostate glandular epithelial carcinogenesis.

  12. Anticarcinogenic efficacy of phytic acid extracted from rice bran on azoxymethane-induced colon carcinogenesis in rats.

    Science.gov (United States)

    Norazalina, S; Norhaizan, M E; Hairuszah, I; Norashareena, M S

    2010-05-01

    This study is carried out to determine the potential of phytic acid extracted from rice bran in the suppression of colon carcinogenesis induced by azoxymethane (AOM) in rats. Seventy-two male Sprague-Dawley rats were divided into 6 groups with 12 rats in each group. The intended rats for cancer treatment received two intraperitoneal injections of AOM in saline (15mg/kg bodyweight) over a 2-week period. The treatments of phytic acid were given in two concentrations: 0.2% (w/v) and 0.5% (w/v) during the post-initiation phase of carcinogenesis phase via drinking water. The colons of the animals were analyzed for detection and quantification of aberrant crypt foci (ACF) after 8 weeks of treatment. The finding showed treatment with 0.2% (w/v) extract phytic acid (EPA) gave the greatest reduction in the formation of ACF. In addition, phytic acid significantly suppressed the number of ACF in the distal, middle and proximal colon as compared to AOM alone (pphytic acid (CPA) had the highest percentage (71%) of non-dysplastic ACF followed by treatment with 0.2% (w/v) EPA (61%). Administration of phytic acid also reduced the incidence and multiplicity of total tumors even though there were no significant differences between groups. In conclusion, this study found the potential value of phytic acid extracted from rice bran in reducing colon cancer risk in rats.

  13. Common cancer in a wild animal: the California sea lion (Zalophus californianus) as an emerging model for carcinogenesis.

    Science.gov (United States)

    Browning, Helen M; Gulland, Frances M D; Hammond, John A; Colegrove, Kathleen M; Hall, Ailsa J

    2015-07-19

    Naturally occurring cancers in non-laboratory species have great potential in helping to decipher the often complex causes of neoplasia. Wild animal models could add substantially to our understanding of carcinogenesis, particularly of genetic and environmental interactions, but they are currently underutilized. Studying neoplasia in wild animals is difficult and especially challenging in marine mammals owing to their inaccessibility, lack of exposure history, and ethical, logistical and legal limits on experimentation. Despite this, California sea lions (Zalophus californianus) offer an opportunity to investigate risk factors for neoplasia development that have implications for terrestrial mammals and humans who share much of their environment and diet. A relatively accessible California sea lion population on the west coast of the USA has a high prevalence of urogenital carcinoma and is regularly sampled during veterinary care in wildlife rehabilitation centres. Collaborative studies have revealed that genotype, persistent organic pollutants and a herpesvirus are all associated with this cancer. This paper reviews research to date on the epidemiology and pathogenesis of urogenital carcinoma in this species, and presents the California sea lion as an important and currently underexploited wild animal model of carcinogenesis.

  14. Safrole-DNA adducts in tissues from esophageal cancer patients: clues to areca-related esophageal carcinogenesis.

    Science.gov (United States)

    Lee, Jang-Ming; Liu, Tsung-Yung; Wu, Deng-Chyang; Tang, Hseau-Chung; Leh, Julie; Wu, Ming-Tsang; Hsu, Hsao-Hsun; Huang, Pei-Ming; Chen, Jin-Shing; Lee, Chun-Jean; Lee, Yung-Chie

    2005-01-01

    Epidemiological studies have demonstrated that areca quid chewing can be an independent risk factor for developing esophageal cancer. However, no studies are available to elucidate the mechanisms of how areca induces carcinogenesis in the esophagus. Since the areca nut in Taiwan contains a high concentration of safrole, a well-known carcinogenic agent, we analyzed safrole-DNA adducts by the 32P-postlabelling method in tissue specimens from esophageal cancer patients. In total, we evaluated 47 patients with esophageal cancer (16 areca chewers and 31 non-chewers) who underwent esophagectomy at the National Taiwan University Hospital between 1996 and 2002. Of the individuals with a history of habitual areca chewing (14 cigarette smokers and two non-smokers), one of the tumor tissue samples and five of the normal esophageal mucosa samples were positive for safrole-DNA adducts. All patients positive for safrole-DNA adducts were also cigarette smokers. Such adducts could not be found in patients who did not chew areca, irrespective of their habits of alcohol consumption or cigarette smoking (psafrole was also tested in vitro in three esophageal cell lines and four cultures of primary esophageal keratinocytes. In two of the esophageal keratinocyte cultures, adduct formation was increased by treatment with safrole after induction of cytochrome P450 by 3-methyl-cholanthrene. This paper provides the first observation of how areca induces esophageal carcinogenesis, i.e., through the genotoxicity of safrole, a component of the areca juice.

  15. Raman spectroscopic investigation of the chemopreventive response of naringenin and its nanoparticles in DMBA-induced oral carcinogenesis

    Science.gov (United States)

    Krishnakumar, N.; Sulfikkarali, N. K.; Manoharan, S.; Venkatachalam, P.

    2013-11-01

    Raman spectroscopy is a vibrational spectroscopic technique that can be used to optically probe the biomolecular changes associated with tumor progression. The aim of the present study is to investigate the biomolecular changes in chemopreventive response of prepared naringenin-loaded nanoparticles (NARNPs) relative to efficacy of free naringenin (NAR) during 7,12-dimethyl benz(a)anthracene (DMBA)-induced oral carcinogenesis by Fourier Transform Raman (FT-Raman) spectroscopy. Oral squamous cell carcinoma (OSCC) was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Raman spectra differed significantly between the control and tumor tissues, with tumors showing higher percentage signals for nucleic acids, phenylalanine and tryptophan and a lower in the percentage of phospholipids. Moreover, oral administration of free NAR and NARNPs significantly increased phospholipids and decreased the levels of tryptophan, phenylalanine and nucleic acid contents. On a comparative basis, NARNPs was found to have a more potent antitumor effect than free NAR in completely preventing the formation of squamous cell carcinoma and in improving the biochemical status to a normal range in DMBA-induced oral carcinogenesis. The present study further suggest that Raman spectroscopy could be a valuable tool for rapid and sensitive detection of specific biomolecular changes in response to chemopreventive agents.

  16. Role of infectious agents in the carcinogenesis of brain and head and neck cancers

    Directory of Open Access Journals (Sweden)

    Alibek Kenneth

    2013-02-01

    Full Text Available Abstract This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV in distinct types of brain tumour, namely glioblastoma multiforme (GBM and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV and nasopharyngeal carcinoma (NPC. Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV and head and neck squamous cell carcinoma (HNSCC; specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90% and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of

  17. Magnetic Fustion Reactor Design Studies Program final report, 1 July 1986--30 September 1986

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1986-09-30

    This report presents progress reported during the period, 7/1/86 - 9/30/86 for the Technical Support Services (TSS) for the Magnetic Fusion Reactor Design Studies Program. Tasks reported include: systems studies work plan, normalization of reactor design studies, interpretation of design study activities, research and development plan, conference support, and reports generated.

  18. Predictive value of clinical risk indicators in child development: final results of a study based on psychoanalytic theory

    OpenAIRE

    Maria Cristina Machado Kupfer; Alfredo Nestor Jerusalinsky; Leda Mariza Fischer Bernardino; Daniele Wanderley; Paulina Schmidtbauer Barbosa Rocha; Silvia Eugenia Molina; Léa Martins Sales; Regina Stellin; M. Eugênia Pesaro; Rogerio Lerner

    2010-01-01

    We present the final results of a study using the IRDI (Clinical Risk Indicators in Child Development). Based on a psychoanalytic approach, 31 risk signs for child development were constructed and applied to 726 children between the ages of 0 and 18 months. One sub-sample was evaluated at the age of three. The results showed a predictive capacity of IRDIs to indicate developmental problems; 15 indicators for the IRDI were also highlighted that predict psychic risk for the constitution of the ...

  19. Chemopreventive Effects of Azadirachta indica on Cancer Marker Indices and Ultrastructural Changes During 1,2-Dimethylhydrazine-Induced Colon Carcinogenesis in Rats.

    Science.gov (United States)

    Liu, Ning; Sun, Bo; Wu, Peiwei; Wei, Xi

    2015-09-01

    The present study elucidated the prospective of Azadirachta indica supplementation, if any, in affording chemoprevention by modulating the altered cancer markers and ultrastructural changes in DMH-induced colorectal carcinogenesis in rats. The rats were segregated into four groups viz., normal control, DMH treated, A. indica treated, and DMH+AI treated. Initiation and induction of colon carcinogenesis were achieved through weekly subcutaneous injections of DMH (30 mg/kg body weight) for both 10 and 20 weeks. A. indica extract was supplemented to rats at a dose rate of 100 mg/kg body weight of animals thrice a week on alternative days, ad libitum for two different time durations of 10 and 20 weeks. The study observed a significant increase in the number of aberrant crypt foci in colons of DMH-treated rats at both the time intervals which were decreased significantly upon AI supplementation. Also, a significant increase was seen in the enzyme activity of alkaline phosphatase, which, however, was moderated upon AI administration to DMH-treated rats. Changes in the ultrastructural architecture of colonic cells were apparent following both the treatment schedules of DMH; however, the changes were prominent following 20 weeks of DMH treatment. The most obvious changes were seen in the form of altered nuclear shape and disruption of cellular integrity, which were appreciably improved upon AI supplementation. In conclusion, the study shows the chemopreventive abilities of AI against DMH-induced colorectal carcinogenesis in rats.

  20. Air pollution, UV irradiation and skin carcinogenesis: what we know, where we stand and what is likely to happen in the future?

    Science.gov (United States)

    Zegarska, Barbara; Zegarski, Wojciech; Bolibok, Paulina; Wiśniewski, Marek; Roszek, Katarzyna; Czarnecka, Joanna; Nowacki, Maciej

    2017-01-01

    The link between air pollution, UV irradiation and skin carcinogenesis has been demonstrated within a large number of epidemiological studies. Many have shown the detrimental effect that UV irradiation can have on human health as well as the long-term damage which can result from air pollution, the European ESCAPE project being a notable example. In total, at present around 2800 different chemical substances are systematically released into the air. This paper looks at the hazardous impact of air pollution and UV and discusses: 1) what we know; 2) where we stand; and 3) what is likely to happen in the future. Thereafter, we will argue that there is still insufficient evidence of how great direct air pollution and UV irradiation are as factors in the development of skin carcinogenesis. However, future prospects of progress are bright due to a number of encouraging diagnostic and preventive projects in progress at the moment.

  1. 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.

  2. Atomistic studies of grain boundaries and heterophase interfaces in alloys and compounds. Final report, July 1987-August 1998

    Energy Technology Data Exchange (ETDEWEB)

    Vitek, Vaclav

    1998-08-01

    The overarching goal of the research supported by this grant was investigation of the structure and properties of interfaces in multicomponent systems by atomistic modeling. Initially, the research was devoted to studies of segregation to grain boundaries in binary disordered alloys. The next step was then studies of the structure and properties of grain boundaries in ordered compounds, specifically Ni3Al and NiAl, and grain boundary segregation in these compounds in the case of off-stoichiometry. Finally, the structure of Nb/sapphire interfaces, in particular the core configurations of the misfit dislocations, was studied.

  3. Organic tanks safety program waste aging studies. Final report, Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Camaioni, D.M.; Samuels, W.D.; Linehan, J.C. [and others

    1998-09-01

    Uranium and plutonium production at the Hanford Site produced large quantities of radioactive byproducts and contaminated process chemicals that are stored in underground tanks awaiting treatment and disposal. Having been made strongly alkaline and then subjected to successive water evaporation campaigns to increase storage capacity, the wastes now exist in the physical forms of saltcakes, metal oxide sludges, and aqueous brine solutions. Tanks that contain organic process chemicals mixed with nitrate/nitrite salt wastes might be at risk for fuel-nitrate combustion accidents. This project started in fiscal year 1993 to provide information on the chemical fate of stored organic wastes. While historical records had identified the organic compounds originally purchased and potentially present in wastes, aging experiments were needed to identify the probable degradation products and evaluate the current hazard. The determination of the rates and pathways of degradation have facilitated prediction of how the hazard changes with time and altered storage conditions. Also, the work with aged simulated waste contributed to the development of analytical methods for characterizing actual wastes. Finally, the results for simulants provide a baseline for comparing and interpreting tank characterization data.

  4. Studies of charmed strange baryons in the $\\Lambda D$ final state at Belle

    CERN Document Server

    Kato, Y; Adachi, I; Aihara, H; Asner, D M; Aulchenko, V; Ayad, R; Badhrees, I; Bakich, A M; Barberio, E; Behera, P; Bhardwaj, V; Bhuyan, B; Biswal, J; Bobrov, A; Bondar, A; Bonvicini, G; Bozek, A; Bračko, M; Browder, T E; Červenkov, D; Chekelian, V; Chilikin, K; Chistov, R; Cho, K; Chobanova, V; Choi, S -K; Choi, Y; Cinabro, D; Dalseno, J; Danilov, M; Dash, N; Di Carlo, S; Doležal, Z; Drásal, Z; Dutta, D; Eidelman, S; Epifanov, D; Farhat, H; Fast, J E; Ferber, T; Fulsom, B G; Gaur, V; Gabyshev, N; Garmash, A; Gillard, R; Glattauer, R; Goldenzweig, P; Grzymkowska, O; Haba, J; Hayasaka, K; Hayashii, H; Hirose, S; Hou, W -S; Inguglia, G; Ishikawa, A; Itoh, R; Iwasaki, Y; Jaegle, I; Joo, K K; Julius, T; Kato, E; Kiesling, C; Kim, D Y; Kim, J B; Kim, K T; Kim, S H; Kim, Y J; Kinoshita, K; Kodyš, P; Korpar, S; Kotchetkov, D; Križan, P; Krokovny, P; Kuhr, T; Kuzmin, A; Kwon, Y -J; Lange, J S; Li, C H; Li, H; Li, L; Li, Y; Gioi, L Li; Libby, J; Liventsev, D; Lubej, M; Luo, T; Masuda, M; Matsuda, T; Matvienko, D; Miyata, H; Mizuk, R; Mohanty, G B; Mohanty, S; Moll, A; Moon, H K; Mussa, R; Nakao, M; Nanut, T; Nath, K J; Natkaniec, Z; Nayak, M; Niiyama, M; Nishida, S; Ogawa, S; Okuno, S; Olsen, S L; Pakhlov, P; Pakhlova, G; Pal, B; Park, C -S; Park, H; Pestotnik, R; Petrič, M; Piilonen, L E; Pulvermacher, C; Rauch, J; Ritter, M; Rostomyan, A; Sakai, Y; Sandilya, S; Santelj, L; Sanuki, T; Savinov, V; Schlüter, T; Schneider, O; Schnell, G; Schwanda, C; Seino, Y; Semmler, D; Senyo, K; Seon, O; Seong, I S; Sevior, M E; Shen, C P; Shibata, T -A; Shiu, J -G; Sokolov, A; Solovieva, E; Starič, M; Sumihama, M; Sumiyoshi, T; Takizawa, M; Tanida, K; Tenchini, F; Trabelsi, K; Uchida, M; Uehara, S; Uglov, T; Unno, Y; Uno, S; Urquijo, P; Usov, Y; Varner, G; Varvell, K E; Vorobyev, V; Wang, C H; Wang, P; Watanabe, M; Watanabe, Y; Wehle, S; Williams, K M; Won, E; Yamaoka, J; Yamashita, Y; Yashchenko, S; Ye, H; Yelton, J; Yook, Y; Yuan, C Z; Zhang, Z P; Zhilich, V; Zhukova, V; Zhulanov, V; Zupanc, A

    2016-01-01

    We report the discovery of $\\Xi_{c}(3055)^{0}$, observed by its decay into the final state $\\Lambda D^{0}$, and present the first observation and evidence of the decays of $\\Xi_c(3055)^{+}$ and $\\Xi_c(3080)^{+}$ into $\\Lambda D^{+}$. We also perform a combined analysis of the $\\Lambda D^{+}$ with the $\\Sigma_{c}^{++}K^{-}$ and $\\Sigma_{c}^{\\ast ++}K^{-}$ decay modes to measure the ratios of branching fractions, masses and widths with improved accuracy. We measure the ratios of branching fractions ${\\cal B}(\\Xi_{c}(3055)^{+} \\to \\Lambda D^{+})/{\\cal B}(\\Xi_{c}(3055)^{+} \\to \\Sigma_{c}^{++}K^{-})=5.09\\pm1.01\\pm0.76$, ${\\cal B}(\\Xi_{c}(3080)^{+} \\to \\Lambda D^{+})/{\\cal B}(\\Xi_{c}(3080)^{+} \\to \\Sigma_{c}^{++}K^{-})=1.29\\pm0.30\\pm0.15$, and ${\\cal B}(\\Xi_{c}(3080)^{+} \\to \\Sigma_{c}^{\\ast ++}K^{-})/{\\cal B}(\\Xi_{c}(3080)^{+} \\to \\Sigma_{c}^{++}K^{-})=1.07\\pm0.27\\pm0.01$, where the uncertainties are statistical and systematic. The analysis is performed using a 980 fb$^{-1}$ data sample collected with the Belle de...

  5. Study of GMSB models with photon final states using the ATLAS detector

    Energy Technology Data Exchange (ETDEWEB)

    Terwort, Mark

    2009-11-30

    Models with gauge mediated supersymmetry breaking (GMSB) provide a possible mechanism to mediate supersymmetry breaking to the electroweak scale. In these models the lightest-supersymmetric particle is the gravitino, while the next-to-lightest supersymmetric particle is either the lightest neutralino or a slepton. In the former case final states with large missing transverse energy from the gravitinos, multiple jets and two hard photons are expected in pp-collisions at the LHC. Depending on the lifetime of the neutralino the photons might not point back to the interaction vertex, which requires dedicated search strategies. Additionally, this feature can be used to measure the neutralino lifetime using either the timing information from the electromagnetic calorimeter or the reconstructed photon direction. Together with the measurements of kinematic endpoints in invariant mass distributions, the lifetime can be used as input for fits of the GMSB model and for the determination of the underlying parameters. The signal selection and the discovery potential for GMSB models with photons in the nal state are discussed using simulated data of the ATLAS detector. In addition, the measurement of supersymmetric particle masses and of the neutralino lifetime as well as the results of the global GMSB fits are presented. (orig.)

  6. Planning of an Integrated Acidification Study and Survey on Acid Rain Impacts in China. Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Lydersen, Espen; Angell, Valter; Eilertsen, Odd; Muniz, Ivar P. [Norsk Inst. for Naturforskning, Trondheim (Norway); Larssen, Thorbjoern; Seip, Hans Martin; Aagaard, Per; Vogt, Rolf D. [Oslo Univ. (Norway); Mulder, Jan

    1997-12-31

    This is the final report from the PIAC project, which was a multidisciplinary survey on acid rain in China. One goal was to document effects of airborne acidifying compounds on vegetation, soil, soil- and surface-water and aquatic biota. Other goals were to exchange knowledge between Chinese and Norwegian scientists, and to visit research sites in highly polluted areas in China and evaluate their need of support in a future collaborative monitoring and research programme. Samples have been collected from over 20 sites in three areas. Negative effects of air pollution are found on all ecosystem levels investigated. The concentration of sulfur in the air in urban and near-urban areas is very high. The concentration of volatile organic compounds is generally high, which means that increased NOx emissions in coming years may increase the ozone problems. Reduced photosynthesis activities were found in some plants and acidification observed in soil and surface water. Aquatic biota also reflect the acidification status of the surface waters investigated. However, it is difficult to assess the degree of damage in these regions because the survey includes too few sites. Surface water acidification is currently not a major environmental problem in China and is unlikely to be one during the next decades. The report includes a status report on acidification in China and a proposed framework for a monitoring programme based on Norwegian experiences. 139 refs., 16 figs., 45 tabs.

  7. Theoretical studies in nuclear structure. Final progress report, June 1, 1991--July 31, 1996

    Energy Technology Data Exchange (ETDEWEB)

    Marshalek, E.R.

    1997-06-01

    The general purview of the project is the theory of collective motion in atomic nuclei. The chief aim is to elucidate the phenomena of (1) anharmonic multiphonon excitations, and (2) collective tilted rotation, both of which are topics of considerable current interest. In the primary stage of an investigation it is often necessary to develop appropriate mathematical tools, as was the case here. In the next stage, the formalism must be tested on simple soluble models. The work described here is mainly concerned with these two stages. The final stage of realistic applications will require more time, manpower and, of course, the necessary funding. Some planning for this last stage has been carried out and anticipated problems axe briefly discussed. As it turns out, both of the above topics can be approached within the unified framework of a theorem that I developed, called the Cranking Bifurcation Theorem (CBT) to be described below. The CBT can be regarded as an outgrowth of the boson expansion method, which provides a general, and, in principal, exact formalism for treating collective excitations. We begin with a brief discussion of the CBT and then continue on to the applications.

  8. Developmental research study of coal-fines agglomeration for fixed-bed gasification. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Elmquist, S.A.; Girimont, J.A.; Korosi, F.A.; Kuby, O.A.; Nelson, S.G.; Paulin, M.O.; Peterson, C.A.; Baker, R.L.; Saller, E.

    1983-05-31

    This report presents the results of an intensive program to develop and evaluate agglomerates made from coal fines for use in a fixed-bed gasifier. There were several tasks completed earlier and their results published prior to this final report. These included: Task 1-A, a literature survey of coal agglomeration, binders and techniques used in coal agglomeration, coal and binder treatments and the results of work done by others; Task 1-B, an examination of performance of lump coals in coal gasification, testing and evaluation of the properties of these coals, and evaluation of mine site coal upgrading methods; and Task 1-C/D, a laboratory investigation of coal agglomerates, including wafers, briquettes and pellets, in which the agglomerated coal fines were formed and tested, and the performance of various coal/binder combinations was recorded and evaluated, and factors affecting commercial scale coal agglomeration and gasification were evaluated. These three prior tasks are presented in this report in condensed form.

  9. Inhibitory effects of Zengshengping fractions on DMBA-induced buccal pouch carcinogenesis in hamsters

    Institute of Scientific and Technical Information of China (English)

    GUAN Xiao-bing; SUN Zheng; CHEN Xiao-xin; WU Hong-ru; ZHANG Xin-yan

    2012-01-01

    Background Zengshengping (ZSP) tablets had inhibitory effects on oral precancerous lesions by reducing the incidence of oral cancer.However,the severe liver toxicity caused by systemic administration of ZSP limits the long-term use of this anti-cancer drug.The purpose of this study was to evaluate the tumor inhibitory effects due to the topical application of extracts from ZSP,a Chinese herbal drug,on 7,12-dimethlbenz(a)anthracene (DMBA) induced oral tumors in hamsters.The study also investigated the anti-cancer mechanisms of the ZSP extracts on oral carcinogenesis.Methods DMBA (0.5%) was applied topically to the buccal pouches of Syrian golden hamsters (6-8 weeks old) three times per week for six weeks in order to induce the development of oral tumors.Different fractions of ZSP were either applied topically to the oral tumor lesions or fed orally at varying dosages to animals with oral tumors for 18 weeks.Tumor volume was measured by histopathological examination.Tumor cell proliferation was evaluated by counting BrdU labeled cells and by Western blotting for mitogen-activated protein kinase (MAPK) protein levels.The protein levels of apoptosis marker Caspase-3 and regulator Bcl-2 protein were also measured by Western blotting.Results Topical application of DMBA to the left pouch of hamsters induced oral tumor formation.Animals treated with DMBA showed a loss in body weight while animals treated with ZSP maintained normal body weights.Both the ZSP n-butanol fraction and water fraction significantly reduced tumor volume by 32.6% (P <0.01) and 22.9% (P <0.01)respectively.Topical application of ZSP also markedly decreased the BrdU-positive cell numbers in oral tumor lesions and reduced the expression level of MAPK.In addition,ZSP promoted tumor cell apoptosis by increasing Caspase-3 expression but decreasing Bcl-2 protein production.Conclusion The n-butanol and water fractions of ZSP are effective at inhibiting tumor cell proliferation and stimulating

  10. Potential effect of hepatitis C Virus non-structural protein 4B on liver carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Xia Chen; Changping Li; Zhongqiong Wang; Guanghong DU

    2006-01-01

    Objective: To investigate the effect of hepatitis C virus non-structural protein 4B(HCV NS4B) on c-Myc, P53,ras gene expression' and apoptosis in hepatic cells and study the possible role that NS4B played in the carcinogenesis of hepatoma. Methods: The recombinant plasmid(PCXN2-NS4B, PCXN2-P53) and the empty vector were transfected or co-transfected into Chang liver cells with liposome. Screening was performed with G418. Plasmid mRNA was detected by RT-PCR. The pro tein expressions of c-Myc and ras genes were analyzed by immunocytochemistry. The expressions of wild-type P53 (wtp53) gene were detected by in situ hybridization. TUNEL(flow cytometry) was used for assessing the rate of apoptosis. Results :No expression of c-Myc gene was found in PCXN2 group. The expression of c-Myc gene in NS4B group was 21.3% ± 1.2%. The ex pression of ras gene in PCXN2 group was lower than that in NS4B group. Compared with PCXN2 group, the expression of P53mRNA was not promoted or inhibited in NS4B group. But the expression of P53 mRNA in NS4B-P53 group was lower than that in P53 group. In PCXN2, NS4B, P53 and NS4B-P53 group, the rates of apoptosis were 17.02% ± 1.24%, 11.94% ± 2.24%,25.84% ± 3.49% and 18.34% ± 1.55% respectively. Conclusion:HCV NS4B induces the expression of c-Myc and ras gene. HCV NS4B may play a role in the inhibition of cell death through P53-dependent manner. Results from this study suggested that HCV NS4B might conuibute to the viral carcinogenesis.

  11. Role of EZH2 protein expression in gastric carcinogenesis among Asians: a meta-analysis.

    Science.gov (United States)

    Guo, Lin; Yang, Teng-Fei; Liang, Shi-Chao; Guo, Ji-Xiang; Wang, Qiang

    2014-07-01

    The present meta-analysis aggregated the results of relevant studies to identify the role of zeste homolog 2 (EZH2) expression in gastric carcinogenesis among Asians. Related articles were found by searching the following electronic databases without language restrictions: PubMed, SpringerLink, Karger Medical and Scientific Publishers, Chinese Biomedical Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Google Scholar. Meta-analysis was performed using STATA statistical software. Crude odds ratios (ORs) or hazard ratios (HRs) with their corresponding 95 % confidence interval (95 % CI) were calculated. Ten relevant studies, which enrolled a total of 872 gastric cancer patients, were selected for statistical analysis. The most important findings of our meta-analysis was that cancer tissues exhibited higher expression levels of EZH2 protein than normal, adjacent and benign tissues (cancer tissues vs normal tissues: OR = 32.15, 95 % CI 22.58 ~ 45.79, P < 0.001; cancer tissues vs adjacent tissues: OR = 16.10, 95 % CI 11.35 ~ 22.84, P < 0.001; cancer tissues vs benign tissues: OR = 2.66, 95 % CI 1.89 ~ 3.75, P < 0.001; respectively). Furthermore, we observed positive correlations between EZH2 expression and the TNM stage (OR = 2.86, 95 % CI 1.72 ~ 4.75, P < 0.001) as well as lymph node metastasis (OR = 3.02, 95 % CI 2.01 ~ 4.53, P < 0.001) of patients with gastric carcinoma. The correlation between EZH2 expression and gastric cancer prognosis was also evaluated in the meta-analysis. Statistical analysis demonstrated that the overall survival (OS) of EZH2-negative patients was shorter than that of patients with positive expressions of EZH2 (HR = 0.54, 95 % CI = 0.05 ~ 1.03, P = 0.032). Our meta-analysis confirmed the view that EZH2 expression might participate in the development of gastric carcinogenesis. Thus, EZH2 protein may be a valuable biomarker for the diagnosis and prognosis of gastric cancer.

  12. Human colon carcinogenesis is associated with increased interleukin-17-driven inflammatory responses

    Directory of Open Access Journals (Sweden)

    Xie Z

    2015-03-01

    Full Text Available Zhaohui Xie,1 Yine Qu,2 Yanli Leng,2 Wenxiu Sun,2 Siqi Ma,2 Jingbo Wei,2 Jiangong Hu,3 Xiaolan Zhang1 1Department of Gastroenterology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Histology and Embryology, Hebei United University School of Basic Medicine, Tangshan, Hebei, People’s Republic of China; 3Department of Pathology, the Second Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China Abstract: Inflammation is known to contribute to carcinogenesis in human colorectal cancer. Proinflammatory cytokine interleukin-17 (IL-17 or IL-17A has been shown to play a critical role in colon carcinogenesis in mouse models. However, few studies have investigated IL-17A in human colon tissues. In the present study, we assessed IL-17-driven inflammatory responses in 17 cases of human colon adenocarcinomas, 16 cases of human normal colon tissues adjacent to the resected colon adenocarcinomas, ten cases of human ulcerative colitis tissues from biopsies, and eight cases of human colon polyps diagnosed as benign adenomas. We found that human colon adenocarcinomas contained the highest levels of IL-17A cytokine, which was significantly higher than the IL-17A levels in the adenomas, ulcerative colitis, and normal colon tissues (P<0.01. The levels of IL-17 receptor A (IL-17RA were also the highest in human colon adenocarcinomas, followed by adenomas and ulcerative colitis. The increased levels of IL-17A and IL-17RA were accompanied with increased IL-17-driven inflammatory responses, including activation of extracellular signal-regulated kinase (ERK1/2 and c-Jun N-terminal kinase (JNK pathways, increase in expression of matrix metalloproteinase (MMP9, MMP7, MMP2, B-cell lymphoma (Bcl-2, and cyclin D1, decrease in Bcl-2-associated X protein (BAX expression, and increase in vascular endothelial growth factor (VEGF and VEGF receptor (VEGFR expression that

  13. Waterbird populations and wetland habitats at study site: 1978 final report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This report covers the waterbird populations and wetland habitats as Teshekpik Lake study site during 1978. The methods, study area and results are discussed.

  14. Investigations of avian populations and wetland habitats at Square Lake study site: 1978 final report

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This document covers the investigations of avian populations and wetland habitats at Square Lake study site. Study sites, methods, physical conditions, wetland...

  15. Doxycycline Promotes Carcinogenesis & Metastasis via Chronic Inflammatory Pathway: An In Vivo Approach.

    Directory of Open Access Journals (Sweden)

    Neha Nanda

    Full Text Available Doxycycline (DOX exhibits anti-inflammatory, anti-tumor, and pro-apoptotic activity and is being tested in clinical trials as a chemotherapeutic agent for several cancers, including colon cancer.In the current study, the chemotherapeutic activity of doxycycline was tested in a rat model of colon carcinogenesis, induced by colon specific cancer promoter, 1,2, dimethylhydrazine (DMH as well as study the effect of DOX-alone on a separate group of rats.Doxycycline administration in DMH-treated rats (DMH-DOX unexpectedly increased tumor multiplicity, stimulated progression of colonic tumor growth from adenomas to carcinomas and revealed metastasis in small intestine as determined by macroscopic and histopathological analysis. DOX-alone treatment showed markedly enhanced chronic inflammation and reactive hyperplasia, which was dependent upon the dose of doxycycline administered. Moreover, immunohistochemical analysis revealed evidence of inflammation and anti-apoptotic action of DOX by deregulation of various biomarkers.These results suggest that doxycycline caused chronic inflammation in colon, small intestine injury, enhanced the efficacy of DMH in tumor progression and provided a mechanistic link between doxycycline-induced chronic inflammation and tumorigenesis. Ongoing studies thus may need to focus on the molecular mechanisms of doxycycline action, which lead to its inflammatory and tumorigenic effects.

  16. Metabolism of phenylhydroquinone by prostaglandin (H) synthase: possible implications in o-phenylphenol carcinogenesis.

    Science.gov (United States)

    Kolachana, P; Subrahmanyam, V V; Eastmond, D A; Smith, M T

    1991-01-01

    o-Phenylphenol (OPP) and its sodium salt sodium ortho-phenylphenate (NaOPP) are broad spectrum fungicides and antibacterial agents. Both are urinary bladder and renal carcinogens in the Fischer 344 rat. OPP is converted by mixed-function oxidases in the liver to phenylhydroquinone (PHQ). Since appreciable amounts of prostaglandin (H) synthase (PGS) are found in rat bladder and kidney-medullary papilla, the target sites of OPP- and NaOPP-induced tumors, we hypothesized that a secondary PGS-mediated activation of PHQ to phenylbenzoquinone (PBQ) may occur in the bladder and kidney. We have studied the metabolism of PHQ by PGS in the presence of arachidonic acid and hydrogen peroxide as co-factors. These studies showed that PHQ is indeed metabolized to a product having identical spectral and electrochemical properties to PBQ. The disappearance of PHQ with time was stoichiometric to the formation of PBQ. Less than 10% of PHQ was converted to PBQ in the absence of enzyme, indicating that auto-oxidation may play only a minor role in the conversion of PHQ to PBQ. Similar results were obtained when PGS was replaced with either myeloperoxidase or horseradish peroxidase and hydrogen peroxide as co-factor. These studies suggest that the peroxidative metabolism of PHQ by PGS to the reactive PBQ could play an important role in OPP-induced urinary bladder and kidney carcinogenesis in rats.

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

    Directory of Open Access Journals (Sweden)

    Peramaiyan Rajendran

    2014-01-01

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

  18. Genomic lesions and colorectal carcinogenesis: the effects of protein-calorie restriction and inulin supplementation on deficiency statuses.

    Science.gov (United States)

    Cantero, W B; Takahachi, N A; Mauro, M O; Pesarini, J R; Rabacow, A P M; Antoniolli, A C M B; Oliveira, R J

    2015-03-27

    The present study investigated the effects of restricting protein and calories and supplementation of inulin, a fiber comprising a linear type of polydisperse carbohydrates composed primarily of fructil-fructose bonds (β-(2→1), on the deficiency statuses of animals in which genomic lesion development and colorectal carcinogenesis had been induced. This experiment involved adult male Swiss mice (N = 11/group). The experimental groups were as follows: Negative Control (vehicle), Positive Control, 1,2-dimethylhydrazine (DMH), Inulin, and Associate. DMH, which promoted colorectal cancer, was administered intraperitoneally in 4 20-mg/kg body weight (bw) doses during a 2-week period; inulin was administered orally at a daily dose of 50 mg/kg bw. Each group was bifurcated; half of each group was fed a normal protein diet and the other half was fed a low-protein diet. The results indicated that a correlation existed between malnutrition and an increased frequency of genomic lesions but that malnutrition did not predispose animals to colorectal cancer development. Inulin exhibited genotoxic activity, which requires further investigation, and low anti-genotoxic activity. Moreover, inulin reduced the levels of intestinal carcinogenesis biomarkers in both malnourished and healthy animals. These data suggest that inulin holds therapeutic potential and is a strong candidate for inclusion among the functional foods used for cancer prevention in both properly nourished and malnourished individuals.

  19. Molecular analysis of tumor-promoting CD8+ T cells in two-stage cutaneous chemical carcinogenesis.

    Science.gov (United States)

    Kwong, Bernice Y; Roberts, Scott J; Silberzahn, Tobias; Filler, Renata B; Neustadter, Jason H; Galan, Anjela; Reddy, Swapna; Lin, William M; Ellis, Peter D; Langford, Cordelia F; Hayday, Adrian C; Girardi, Michael

    2010-06-01

    T-pro are tumor-infiltrating TCRalphabeta(+)CD8(+) cells of reduced cytotoxic potential that promote experimental two-stage chemical cutaneous carcinogenesis. Toward understanding their mechanism of action, this study uses whole-genome expression analysis to compare T-pro with systemic CD8(+) T cells from multiple groups of tumor-bearing mice. T-pro show an overt T helper 17-like profile (high retinoic acid-related orphan receptor-(ROR)gammat, IL-17A, IL-17F; low T-bet and eomesodermin), regulatory potential (high FoxP3, IL-10, Tim-3), and transcripts encoding epithelial growth factors (amphiregulin, Gro-1, Gro-2). Tricolor flow cytometry subsequently confirmed the presence of TCRbeta(+) CD8(+) IL-17(+) T cells among tumor-infiltrating lymphocytes (TILs). Moreover, a time-course analysis of independent TIL isolates from papillomas versus carcinomas exposed a clear association of the "T-pro phenotype" with malignant progression. This molecular characterization of T-pro builds a foundation for elucidating the contributions of inflammation to cutaneous carcinogenesis, and may provide useful biomarkers for cancer immunotherapy in which the widely advocated use of tumor-specific CD8(+) cytolytic T cells should perhaps accommodate the cells' potential corruption toward the T-pro phenotype. The data are also likely germane to psoriasis, in which the epidermis may be infiltrated by CD8(+) IL-17-producing T cells.

  20. Oxidative DNA damage is a preliminary step during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide.

    Science.gov (United States)

    Miranda, Sandra Regina; Noguti, Juliana; Carvalho, Juliana Gonçalves; Oshima, Celina Tijuko Fujiyama; Ribeiro, Daniel Araki

    2011-04-01

    The aim of this study was to investigate oxidative DNA damage during 4-nitroquinoline 1-oxide (4NQO)-induced rat tongue carcinogenesis. For this purpose, male Wistar rats were distributed into three groups of 10 animals each and treated with 50 ppm 4NQO solution through their drinking water for 4, 12, and 20 weeks. Ten animals were used as negative control. The alkaline Comet assay modified with lesion-specific enzymes was used to detect single and double strand breaks, labile sites (SBs), and oxidised purines and pyrimidines. Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure, oxidative DNA damage was detected in the 'normal' oral epithelium. In pre-neoplastic lesions and squamous cell carcinomas induced after 12 and 20 weeks following carcinogen exposure, respectively, oxidative DNA damage was also increased (P < 0.05) when compared to negative control. In conclusion, our results suggest that oxidative DNA damage is an early event during multistep carcinogenesis assay induced by 4NQO. This kind of approach should be considered to persons with high risk of oral cancer, such as in smokers or alcohol consumers.

  1. Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging.

    Directory of Open Access Journals (Sweden)

    Tetsuya Kadonosono

    Full Text Available An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1 is a transcription factor that regulates oxygen homeostasis and plays key roles in a number of diseases, including cancer. Here, we established transgenic (Tg mice that carry HRE/ODD-luciferase (HOL gene, which generates bioluminescence in an HIF-1-dependent manner and was successfully used in this study to monitor HIF-1 activity in ischemic tissues. To monitor carcinogenesis in vivo, we mated HOL mice with rasH2 Tg mice, which are highly sensitive to carcinogens and are used for short-term carcinogenicity assessments. After rasH2-HOL Tg mice were treated with N-methyl-N-nitrosourea, bioluminescence was detected