WorldWideScience

Sample records for chemopreventive agent repository

  1. A review of cancer chemopreventive agents.

    Science.gov (United States)

    Levi, M S; Borne, R F; Williamson, J S

    2001-09-01

    In the late 20(th) century, the treatment of cancer began to include its prevention. Today, compounds exist that will lower the risk of developing certain types of cancer. This has been demonstrated in studies where chemically induced tumor growth has been slowed or reversed. Anti-inflammatory compounds having chemopreventive activity are piroxicam, sulindac, aspirin, celecoxib and curcumin. The selective estrogen receptor modulators, tamoxifen and raloxifene, are beneficial in the prevention of estrogen dependent tumors. Retinoids, vitamin A derivatives, such as targretin and fenretinide are useful in the prevention of tumors. Compounds containing sulfur, such as sulforaphane and oltipraz, are even useful as radioprotective agents. The steroid dehydroepiandosterone can inhibit experimental carcinogenesis. All of these chemical classes provide a start for the medicinal chemist to design more effective chemopreventive agents. The biomarkers used to determine the chemopreventive activity of new compounds are quite often activities of enzymes. The identification of those individuals at high risk is still in its infancy and presents a troubling dilemma. PMID:11562271

  2. Beneficial and adverse effects of chemopreventive agents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Byung Mu; Park, Kwang-Kyun

    2003-03-01

    The beneficial and adverse effects of some chemopreventive agents, such as Vitamins A, C, E, beta-carotene, indole-3-carbinol, capsaicin, garlic, and aloe are reviewed. Two large randomized trials with a lung cancer endpoint, the Alpha-Tocopherol, Beta-Carotene (ATBC) Prevention Study and the Beta-Carotene and Retinol Efficacy Trial (CARET), suggested that antioxidants might be harmful in smokers. However, the results of the Linxian study and of the ATBC or the CARET studies were significantly different in this respect, and therefore, the relationship between antioxidant and carcinogenesis remains open to debate. Indole-3-carbinol has cancer promoting activities in the colon, thyroid, pancreas, and liver, whereas capsaicin alters the metabolism of chemical carcinogens and may promote carcinogenesis at high doses. Organosulfur compounds and selenium from garlic have no or a little enhancing effect on cancer promotion stage. Information upon chemopreventive mechanisms that inhibit carcinogenesis is imperfect, although the causes and natures of certain human cancers are known. Therefore, definitive preventive guidelines should be carefully offered for various types of tumors, which properly consider ethnic variations, and the efficacies and the safety of chemopreventive agents.

  3. Beneficial and adverse effects of chemopreventive agents

    International Nuclear Information System (INIS)

    The beneficial and adverse effects of some chemopreventive agents, such as Vitamins A, C, E, beta-carotene, indole-3-carbinol, capsaicin, garlic, and aloe are reviewed. Two large randomized trials with a lung cancer endpoint, the Alpha-Tocopherol, Beta-Carotene (ATBC) Prevention Study and the Beta-Carotene and Retinol Efficacy Trial (CARET), suggested that antioxidants might be harmful in smokers. However, the results of the Linxian study and of the ATBC or the CARET studies were significantly different in this respect, and therefore, the relationship between antioxidant and carcinogenesis remains open to debate. Indole-3-carbinol has cancer promoting activities in the colon, thyroid, pancreas, and liver, whereas capsaicin alters the metabolism of chemical carcinogens and may promote carcinogenesis at high doses. Organosulfur compounds and selenium from garlic have no or a little enhancing effect on cancer promotion stage. Information upon chemopreventive mechanisms that inhibit carcinogenesis is imperfect, although the causes and natures of certain human cancers are known. Therefore, definitive preventive guidelines should be carefully offered for various types of tumors, which properly consider ethnic variations, and the efficacies and the safety of chemopreventive agents

  4. Overview of mechanisms of cancer chemopreventive agents

    International Nuclear Information System (INIS)

    Epidemiological data provide evidence that it is possible to prevent cancer and other chronic diseases, some of which share common pathogenetic mechanisms, such as DNA damage, oxidative stress, and chronic inflammation. An obvious approach is avoidance of exposure to recognized risk factors. As complementary strategies, it is possible to render the organism more resistant to mutagens/carcinogens and/or to inhibit progression of the disease by administering chemopreventive agents. In a primary prevention setting, addressed to apparently healthy individuals, it is possible to inhibit mutation and cancer initiation by triggering protective mechanisms either in the extracellular environment or inside cells, e.g., by modifying transmembrane transport, modulating metabolism, blocking reactive species, inhibiting cell replication, maintaining DNA structure, modulating DNA metabolism and repair, and controlling gene expression. Tumor promotion can be counteracted by inhibiting genotoxic effects, favoring antioxidant and anti-inflammatory activity, inhibiting proteases and cell proliferation, inducing cell differentiation, modulating apoptosis and signal transduction pathways, and protecting intercellular communications. In a secondary prevention setting, when a premalignant lesion has been detected, it is possible to inhibit tumor progression via the same mechanisms, and in addition by affecting the hormonal status and the immune system in various ways, and by inhibiting tumor angiogenesis. Although tertiary prevention, addressed to cancer patients after therapy, is outside the classical definition of chemoprevention, it exploits similar mechanisms. It is also possible to affect cell-adhesion molecules, to activate antimetastasis genes, and to inhibit proteases involved in basement membrane degradation

  5. Beer constituents as potential cancer chemopreventive agents.

    Science.gov (United States)

    Gerhäuser, Clarissa

    2005-09-01

    Beer is a complex alcoholic beverage made from barley (malt), hop, water and yeast. Phenolic constituents of beer are derived from malt (70-80%) and hop (20-30%). Structural classes include simple phenols, benzoic- and cinnamic acid derivatives, coumarins, catechins, di-, tri- and oligomeric proanthocyanidins, (prenylated) chalcones and flavonoids as well as alpha- and iso-alpha-acids derived from hop. Compounds belonging to different structural classes have distinct profiles of biological activity in in vitro test systems, and in combination might lead to enhanced effects. Scientific evidence has accumulated over the past 10 years pointing to the cancer preventive potential of selected hop-derived beer constituents, i.e., prenylflavonoids including xanthohumol and isoxanthohumol, and hop bitter acids. Chemopreventive activities observed with these compounds relevant to inhibition of carcinogenesis at the initiation, promotion and progression phases, as well as results from in vivo studies on metabolism, bioavailability and efficacy are summarised in this review. PMID:15953717

  6. Chain elongation analog of resveratrol as potent cancer chemoprevention agent.

    Science.gov (United States)

    Kang, Yan-Fei; Qiao, Hai-Xia; Xin, Long-Zuo; Ge, Li-Ping

    2016-09-01

    Resveratrol is identified as a natural cancer chemoprevention agent. There has been a lot of interest in designing and developing resveratrol analogs with cancer chemoprevention activity superior to that of parent molecule and exploring their action mechanism in the past several decades. In this study, we have synthesized resveratrol analogs of compounds A-C via conjugated chain elongation based on isoprene unit retention strategy. Remarkably, cytotoxic activity analysis results indicated that compound B possesses the best proliferation inhibition activity for NCI-H460 cells in all the test compounds. Intriguingly, compound B displayed a higher cytotoxicity against human non-small cell lung cancer cells (NCI-H460) compared to normal human embryonic lung fibroblasts (MRC-5). Afterward, flow cytometry analysis showed that compound B would induce cell apoptosis. We further researched the action mechanism. When NCI-H460 cells were incubated by compound B for 6 or 9 h, respectively, the intracellular reactive oxygen species (ROS) level was enhanced obviously. With elevation of intracellular ROS level, flow cytometry measurement verified mitochondrial transmembrane potential collapse, which was accompanied by the up-regulation of Bax and down-regulation of Bcl-2. More interestingly, compound B increased the expression of caspase-9 and caspase-3, which induced cell apoptosis. Moreover, compound B arrested cell cycle in G0/G1 phase. These are all to provide useful information for designing resveratrol-based chemoprevention agent and understanding the action mechanism. PMID:27160168

  7. Terpenoids as potential chemopreventive and therapeutic agents in liver cancer.

    Science.gov (United States)

    Thoppil, Roslin J; Bishayee, Anupam

    2011-09-27

    Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called "isoprenoids") are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed. PMID:21969877

  8. Targeting multiple signal pathways by chemopreventive agents for cancer prevention and therapy

    Institute of Scientific and Technical Information of China (English)

    Fazlul H SARKAR; Yi-wei LI

    2007-01-01

    In recent years, growing interest has been focused on the field of cancer prevention.Cancer prevention by chemopreventive agents offers significant promise for re-ducing the incidence and mortality of cancer. Chemopreventive agents may exert their effects either by blocking or metabolizing carcinogens or by inhibiting tumor cell growth. Another important benefit of chemopreventive agents is their non-toxic nature. Therefore, chemopreventive agents have recently been used for cancer treatment in combination with chemotherapeutics or radiotherapy, uncov-ering a novel strategy for cancer therapy. This strategy opens a new avenue fromcancer prevention to cancer treatment. In vitro and in vivo studies have demon-strated that chemopreventive agents could enhance the antitumor activity of chemotherapeutics, improving the treatment outcome. Growing evidence has shown that chemopreventive agents potentiate the efficacy of chemotherapy and radiotherapy through the regulation of multiple signaling pathways, including Akt, NF-κB, c-Myc, cyclooxygenase-2, apoptosis, and others, suggesting a multitargeted nature of chemopreventive agents. However, further in-depth mecha-nistic studies, in vivo animal experiments, and clinical trials are needed to investi-gate the effects of chemopreventive agents in combination treatment of cancer with conventional cancer therapies. More potent natural and synthetic chemo-preventive agents are also needed to improve the efficacy of mechanism-based and targeted therapeutic strategies against cancer, which are likely to make a significant impact on saving lives. Here, we have briefly reviewed the role of chemopreventive agents in cancer prevention, but most importantly, we have reviewed how they could be useful for cancer therapy in combination with con-ventional therapies.

  9. Aspirin as a chemoprevention agent for colorectal cancer.

    LENUS (Irish Health Repository)

    Lee, Chun Seng

    2012-11-01

    Colorectal cancer (CRC) is one of the leading causes of mortality in the western world. It is widely accepted that neoplasms such as colonic polyps are precursors to CRC formation; with the polyp-adenoma-carcinoma sequences well described in medical literature [1, 2]. It has been shown that Aspirin and other non-steroid anti-inflammatory drugs (NSAID) have a negative effect on polyp and cancer formation. This review aims to describe some of the mechanism behind the chemoprotective properties of aspirin; COX 2 inhibition, regulation of proliferation and apoptosis and effects on the immune system and also the current evidence that supports its use as a chemoprevention agent against CRC. We will also aim to explore the side effects with the use of aspirin and the pitfalls of using aspirin routinely for primary prophylaxis against CRC.

  10. About the Chemopreventive Agent Development Research Group | Division of Cancer Prevention

    Science.gov (United States)

    The Chemopreventive Agent Development Research Group promotes and supports research on early chemopreventive agent development, from preclinical studies to phase I clinical trials. The group’s projects aim to identify and develop prevention agents with the potential to block, reverse, or delay the early stages of cancer. The overarching goal is to determine positive and negative predictive values of preclinical models for clinical development. |

  11. Chemopreventive Agents from Physalis minima Function as Michael Reaction Acceptors

    Science.gov (United States)

    Men, Ruizhi; Li, Ning; Ding, Chihong; Tang, Yingzhan; Xing, Yachao; Ding, Wanjing; Ma, Zhongjun

    2016-01-01

    Background: The fruits of some varieties of genus Physalis have been used as delicious fruits and functional food in the Northeast of China. Materials and Methods: To reveal the functional material basis, we performed bioactivity-guided phytochemical research and chemopreventive effect assay of the constituents from Physalis minima. Results: It was demonstrated that the ethyl acetate extract of P. minima L. (EEPM) had potential quinone reductase (QR) inducing activity with induction ratio (IR, QR induction activity) value of 1.47 ± 0.24, and glutathione binding property as potential Michael reaction acceptors (with an α, β-unsaturated ketone moiety). Furthermore, bioactivity-guided phytochemical research led eight compounds (1–8), which were elucidated as 3-isopropyl-5-acetoxycyclohexene-2-one-1 (1), isophysalin B (2), physalin G (3), physalin D (4), physalin I (5), physordinose B (6), stigmasterol-3-O-β-D-glucopyranoside (7) and 5α-6β-dihydroxyphysalin R (8) on the basis of nuclear magnetic resonance spectroscopy analyses and HRESIMS. Then, isophysalin B (2) and physordinose B (6) showed significant QR inducing activity with IR value of 2.80 ± 0.19 and 2.38 ± 0.46, respectively. SUMMARY An ultra-performance liquid chromatographic method with glutathione as the substrate was used to detect the Michael reaction acceptors in extracts of Physalis minima (EPM)We investigated the chemical constituents of EPM guided by biological activity methodIsophysalin B (1) and physordinose B (6) showed strong quinone reductase inducing activity with induction ratio values of 2.80 ± 0.19 and 2.38 ± 0.46This study generated useful information for consumers and many encourage researchers to utilize edible fruits from Physalis as a source of phytochemicals Abbreviations used: EPM: Extracts of Physalis minima, EEPM: Ethyl acetate extract of Physalis minima L., GSH: Glutathione, MRAs: Michael reaction acceptors, QR: Quinone reductase. PMID:27279713

  12. Natural products as a source of potential cancer chemotherapeutic and chemopreventive agents.

    Science.gov (United States)

    Cassady, J M; Baird, W M; Chang, C J

    1990-01-01

    Recent advances in the chemistry of novel bioactive natural products are reported. This research is directed to the exploration of plants with confirmed activity in bioassays designed to detect potential cancer chemotherapeutic and chemopreventive agents. Structural work and chemical studies are reported for several cytotoxic agents from the plants Annona densicoma, Annona reticulata, Claopodium crispifolium, Polytrichum obioense, and Psorospermum febrifugum. Studies are also reported based on development of a mammalian cell culture benzo[a]pyrene metabolism assay for the detection of potential anticarcinogenic agents from natural products. In this study a number of isoflavonoids and flavonoids with antimutagenic activity have been discovered. PMID:2189947

  13. Phase 0 Trials: Expediting the Development of Chemoprevention Agents

    OpenAIRE

    Kummar, Shivaani; Doroshow, James H.

    2011-01-01

    Phase 0 trials are first-in-human clinical trials performed under the Exploratory IND [investigational new drug] Guidance of the US Food and Drug Administration. Unlike traditional phase I trials, these studies have no therapeutic or diagnostic intent but instead aim to provide only pharmacokinetic and/or pharmacodynamic data to inform the next step in developing an agent. We discuss the role that such trials, including one reported by Reid et al. (beginning on page XXX in this issue of the j...

  14. Cancer chemoprevention by phytochemicals. Expectation for phytochemicals as preventive agents against radiation-induced carcinogenesis

    International Nuclear Information System (INIS)

    There is growing evidence from the studies using animal models that phytochemicals in plants have preventive effect on cancer induction, which is mediated by polyphenol anti-oxidative and anti-inflammatory functions. Some phytochemicals such as curcumin and epigallocatechin gallate have been moved onto clinical trials. These phytochemicals are also expected to reduce the deleterious effect of radiation, and to be a powerful tool for the prevention of radiation carcinogenesis. In this review, we summarized the general concept of cancer chemoprevention and usefulness of phytochemicals as cancer preventive agents, and pointed out their possibilities for prevention of radiation-induced carcinogenesis. (author)

  15. Curcumin as a therapeutic agent in the chemoprevention of inflammatory bowel disease.

    Science.gov (United States)

    Sreedhar, Remya; Arumugam, Somasundaram; Thandavarayan, Rajarajan A; Karuppagounder, Vengadeshprabhu; Watanabe, Kenichi

    2016-05-01

    Inflammatory bowel diseases (IBD), mainly Crohn's disease (CD) and ulcerative colitis (UC) are chronic ailments of the gastrointestinal tract, characterized by recurrent inflammation. Current therapeutic strategies are based on the mitigation of symptoms, including inflammatory remission and healing of mucosal manifestations. Extensive studies have suggested that continuous oxidative damage can lead to the inflammatory signaling cascade in IBD. Curcumin, a potent modulator of cell signaling, is popular for its antioxidant and anti-inflammatory activities, and has already been shown remarkable therapeutic results in IBD. Here, we review and discuss the effects of curcumin as a therapeutic agent in the chemoprevention of IBD. PMID:26995272

  16. Bladder urotoxicity pathophysiology induced by the oxazaphosphorine alkylating agents and its chemoprevention 

    Directory of Open Access Journals (Sweden)

    Łukasz Dobrek

    2012-09-01

    Full Text Available The use of oxazaphosphorines (cyclophosphamide, ifosfamide in the treatment of numerous neoplastic disorders is associated with their essential adverse effect in the form of hemorrhagic cystitis, which considerably limits the safety and efficacy of their pharmacotherapy. HC is a complex inflammatory response, induced by toxic oxazaphosphorines metabolite – acrolein with subsequent immunocompetetive cells activation and release of many proinflammatory agents. However, there are some chemoprotectant agents which help reduce the HC exacerbation.The article briefly discuses the mechanism of action of oxazaphosphorines, the pathophysiology of the hemorrhagic cystitis development and currently accepted chemopreventive agents, applied to the objective of urotoxicity amelioration. Moreover, the rationale for some phytopharmaceuticals administration as novel bladder protective compounds accompanying cyclophosphamide or ifosfamide therapy was also mentioned. 

  17. 5-aminosalicylic acid is an attractive candidate agent for chemoprevention of colon cancer in patients with inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Yang Cheng; Pierre Desreumaux

    2005-01-01

    Inflammatory bowel disease (IBD) is classically subdivided into ulcerative colitis (UC) and Crohn's disease (CD). Patients with IBD have increased risk for colorectal cancer. Because the pathogenesis of colorectal carcinoma has not been entirely defined yet and there is no ideal treatment for colon cancer, cancer prevention has become increasingly important in patients with IBD. The two adopted methods to prevent the development of colon cancer in clinical practice include the prophylactic colectomy and colonoscopic surveillance.But patients and physicians seldom accept colectomy as a routine preventive method and most patients do not undergo appropriate colonoscopic surveillance. Chemoprevention refers to the use of natural or synthetic chemical agents to reverse, suppress, or to delay the process of carcinogenesis.Chemoprevention is a particularly useful method in the management of patients at high risk for the development of specific cancers based on inborn genetic susceptibility, the presence of cancer-associated disease, or other known risk factors. Prevention of colorectal cancer by administration of chemopreventive agents is one of the most promising options for IBD patients who are at increased risks of the disease. The chemopreventive efficacy of nonsteroidal antiinflammatory drugs (NSAIDs) against intestinal tumors has been well established. But with reports that NSAIDs aggravated the symptoms of colitis, their sustained use for the purpose of cancer chemoprevention has been relatively contraindicated in IBD patients. Another hopeful candidate chemoprevention drug for IBD patients is 5-aminosalicylic acid (5-ASA), which is well tolerated by most patients and has limited systemic adverse effects, and no gastrointestinal toxicity. 5-ASA lacks the well-known side effects of longterm NSAIDs use. Retrospective correlative studies have suggested that the long-term use of 5-ASA in IBD patients may significantly reduce the risk of development of colorectal cancer

  18. Tea: age-old beverage as an effective cancer chemopreventive agent

    Directory of Open Access Journals (Sweden)

    Jasmine George

    2011-12-01

    Full Text Available Cancer is the major public health problem, causing approximately 7 million deaths every year worldwide. The existing treatment approaches and surgical techniques have not been able to cope effectively with this dreaded disease. Because of this, the concept of chemoprevention is now considered a valid approach to reduce the incidence of cancer. There is convincing epidemiological and experimental evidence to show that dietary polyphenolic plant-derived compounds have cancer preventive properties. Based on evidence from in vitro, in vivo data and epidemiological studies, tea has received considerable attention over recent years for reducing the risk of several cancers. Much of the cancer preventive effects of tea, and in particular green tea, appear to be mediated by the polyphenols they contain. In addition to inhibiting mutagenesis and proliferation, tea is relatively non-toxic, is low cost, and can be taken orally or as a part of the daily diet. Therefore it is logical that future clinical studies should focus on examining the efficacy of tea and its active constituents, such as epigallocatechin- 3-gallate (EGCG and theaflavins (TFs, in chemoprevention as an alternative to pharmacological agents. In this review, we address the use of tea and its constituents for the prevention and treatment of cancer. Further mechanistic and dose-response studies will help us to understand the effects of tea consumption on human carcinogenesis.

  19. Oriental herbs as a source of novel anti-androgen and prostate cancer chemopreventive agents

    Institute of Scientific and Technical Information of China (English)

    Junxuan L(U); Sung-Hoon KIM; Cheng JIANG; HyoJeong LEE; Junming GUO

    2007-01-01

    Androgen and androgen receptor (AR) signaling are crucial for the genesis of prostate cancer (Pca), which can often develop into androgen-ligand-indepen-dent diseases that are lethal to the patients. Recent studies show that even these hormone-refractory Pca require ligand-independent AR signaling for survival. As current chemotherapy is largely ineffective for Pca and has serious toxic side-effects, we have initiated a collaborative effort to identify and develop novel, safe and naturally occurring agents that target AR signaling from Oriental medicinal herbs for the chemoprevention and treatment of Pca. We highlight our discovery of decursin from an Oriental formula containing Korean Angelica gigas Nakal(Dang Gui) root as a novel anti-androgen/AR agent. We have identified the following mechanisms to account for the specific anti-AR actions: rapid block of AR nuclear translocation, inhibition of binding of 5α-dihydrotestesterone to Arand increased proteasomal degradation of AR protein. Furthermore, decursin lacks the agonist activity of the "pure" anti-androgen bicalutamide and is more potent than bicalutamide in inducing Pca apoptosis. Structure-activity analyses reveal a critical requirement of the side-chain on decursin or its structural isomerdecursinol angelate for anti-AR, cell cycle arrest and proapoptotic activities. This work demonstrates the feasibility of using activity-guided fractionation in cell culture assays combined with mechanistic studies to identify novel anti-andro-gen/AR agents from complex herbal mixtures.

  20. Salvianolic Acid B, a Potential Chemopreventive Agent, for Head and Neck Squamous Cell Cancer

    Directory of Open Access Journals (Sweden)

    Yuan Zhao

    2011-01-01

    Full Text Available Head and neck squamous cell cancer (HNSCC is one of the top ten cancers in the United States. The survival rate of HNSCC has only marginally improved over the last two decades. In addition, African-American men bear a disproportionate burden of this preventable disease. Therefore, a critical challenge of preventive health approaches is warranted. Salvianolic acid B (Sal-B isolated from Salvia miltiorrhiza Bge, which is a well-know Chinese medicines has been safely used to treat and prevent aging diseases for thousand of years. Recently, the anticancer properties of Sal-B have received more attention. Sal-B significantly inhibits or delays the growth of HNSCC in both cultured HNSCC cells and HNSCC xenograft animal models. The following anticancer mechanisms have been proposed: the inhibition of COX-2/PGE-2 pathway, the promotion of apoptosis, and the modulation of angiogenesis. In conclusion, Sal-B is a potential HNSCC chemopreventive agent working through antioxidation and anti-inflammation mechanisms.

  1. Characterization of chemopreventive agents from the dichloromethane extract of Eurycorymbus cavaleriei by liquid chromatography-ion trap mass spectrometry.

    Science.gov (United States)

    Cheng, Lin; Zhang, Xiaoyu; Zhang, Min; Zhang, Peng; Song, Zhihang; Ma, Zhongjun; Cheng, Yiyu; Qu, Haibin

    2009-06-12

    In the present study, we examined the potential chemopreventive activity of dichloromethane extract of Eurycorymbus cavaleriei by investigating the change of constitutions after incubation with glutathione (GSH). The major constitutions in the dichloromethane extract of E. cavaleriei were cumarin compounds and their cleavage pattern was examined by LC-MS-MS and the characteristic product ions at m/z 206 and 207 were helpful to determine the substitutions of coumarinolignoid compounds. The mechanism of conjugations of 5'-demethylaquillochin and its isomer with GSH was discussed and validated through analysis of the conjugations of reference compound 6-hydroxy-7-methoxycoumarin with GSH by LC-MS-MS and NMR spectrum. The relative ability to induce the detoxification enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1) of nine coumarin compounds was tested which also showed 5'-demethylaquillochin exhibited the most potential chemopreventive ability. These observations suggest that 5'-demethylaquillochin and its isomer from the dichloromethane extract of E. cavaleriei have potential as chemopreventive agents through induction of detoxification enzymes. PMID:19439309

  2. Dietary Pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer

    Science.gov (United States)

    Dietary nutrients with ability to reverse adverse epigenetic events have great potential for cancer chemoprevention. Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1-d...

  3. LEARNING REPOSITORY ADAPTABILITY IN AN AGENT-BASED UNIVERSITY ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Vanco Cabukovski

    2016-06-01

    Full Text Available Automated e-Learning Systems (AeLS are fundamental to contemporary educational concepts worldwide.It has become a standard not only in support to the formal curriculum, but containing social platform capabilities, gamification elements and functionalities fostering communities of experts, also for faster knowledge dissemination. Additionally, AeLSs support internal communications and customizable analytics and methodologies to quickly identify learning performance, which in turn can be used as feedback to implement adaptability in tailoring the content management to meet specific individual needs. The volume of fast growing AeLS content of supplement material and exchanged communication combined with the already huge material archived in the university libraries is enormous and needs sophisticated managing through electronic repositories. Such integration of content management systems (CMS present challenges which can be solved optimally with the use of distributed management implemented through agent-based systems. This paper depicts a successful implementation of an Integrated Intelligent Agent Based UniversityInformation System (IABUIS.

  4. In vivo phase II-enzymes inducers, as potential chemopreventive agents, based on the chalcone and furoxan skeletons.

    Science.gov (United States)

    Cabrera, Mauricio; Mastandrea, Ignacio; Otero, Gabriel; Cerecetto, Hugo; González, Mercedes

    2016-04-15

    Cancer chemoprevention involves prevention/delay/reverse of the carcinogenic process through administration of cancer chemopreventive agents (CCA). Compounds which are able to induce detoxification-enzymes, especially monofunctional phase II enzymes, have become in excellent approaches for new CCA. Herein, we report the synthesis of new furoxanyl chalcone-like hybrid compounds as CCA. In vitro studies showed that phenylfuroxanyl derivatives 6 and 9 displayed the best activities being 9 the greatest monofunctional-inducer. Additionally, compounds were non-mutagenic against TA98 Salmonella typhimurium strain (Ames test) and could be used in the prevention of the progression of pre-malignant lesions for their cytotoxic activity against tumoral cells. In vivo proof of concept showed increment on phase II-enzymes activities in liver, colon and mammary gland having derivative 9 the best induction profiles. We probed Nrf2 nuclear translocation is operative for both compounds allowing to exert protective effects via expression of downstream phase-II enzymes. PMID:26970663

  5. Chemoprevention of Lung Cancer

    OpenAIRE

    Keith, Robert L

    2009-01-01

    Lung cancer is the leading cause of cancer death in the United States, and the majority of diagnoses are made in former smokers. While avoidance of tobacco abuse and smoking cessation clearly will have the greatest impact on lung cancer development, effective chemoprevention could prove to be more effective than treatment of established disease. Chemoprevention is the use of dietary or pharmaceutical agents to reverse or inhibit the carcinogenic process and has been successfully applied to co...

  6. Lung Cancer Chemoprevention

    OpenAIRE

    Keith, Robert L

    2012-01-01

    Lung cancer is the leading cause of cancer death in the United States, and the majority of diagnoses are made in former smokers. Although avoidance of tobacco abuse and smoking cessation clearly will have the greatest impact on lung cancer development, effective chemoprevention could prove to be more effective than treatment of established, advanced-stage disease. Chemoprevention is the use of dietary or pharmaceutical agents to reverse or block the carcinogenic process and has been successfu...

  7. α-Santalol, a skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis.

    Science.gov (United States)

    Santha, Sreevidya; Dwivedi, Chandradhar

    2013-01-01

    This study is designed to investigate the chemopreventive effect and molecular mechanisms of α-santalol on UVB-induced skin tumor development in SKH-1 hairless mouse, a widely used model for human photocarcinogenesis. A dose of UVB radiation (30 mJ cm(-2) day(-1)) that is in the range of human sunlight exposure was used for the initiation and promotion of tumor. Topical treatment of mice with α-santalol (10%, wt/vol in acetone) caused reduction in tumor incidence, multiplicity and volume. In our study, the anticarcinogenic action of α-santalol against UVB-induced photocarcinogenesis was found to be associated with inhibition of inflammation and epidermal cell proliferation, cell cycle arrest and induction of apoptosis. α-Santalol pretreatment strongly inhibited UVB-induced epidermal hyperplasia and thickness of the epidermis, expression of proliferation and inflammation markers proliferating cell nuclear antigen (PCNA), Ki-67 and cyclooxygenase 2 (Cox-2). Significant decrease in the expression of cyclins A, B1, D1 and D2 and cyclin-dependent kinases (Cdk)s Cdk1 (Cdc2), Cdk2, Cdk4 and Cdk6 and an upregulated expression of cyclin-dependent kinase (CDK) inhibitor Cip1/p21 were found in α-santalol pretreated group. Furthermore, an elevated level of cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) were observed in α-santalol-treated group. Our data suggested that α-santalol is a safer and promising skin cancer chemopreventive agent with potential to target various pathways involved in photocarcinogenesis. PMID:23480292

  8. Speciation and bioavailability of selenium in yeast-based intervention agents used in cancer chemoprevention studies

    DEFF Research Database (Denmark)

    Larsen, Erik Huusfeldt; Hansen, Marianne; Paulin, H.; Moesgaard, S.; Reid, M.; Rayman, M.

    2004-01-01

    This study investigated the speciation and bioavailability of selenium in yeast-based intervention agents from multiple manufacturers from several time points. Sources of selenized yeast included Nutrition 21 (San Diego, CA), which supplied the Nutritional Prevention of Cancer (NPC) Trial from 1981......-1996; Cypress Systems (Fresno, CA; 1997-1999); and Pharma Nord (Vejle, Denmark; 1999-2000), which supplied the Prevention of Cancer by Intervention by Selenium (PRECISE) Trial pilot studies. The low-molecular-selenium species were liberated from the samples by proteolytic hydrolysis followed by separation by...

  9. N-acetil-l-cysteine and 2-amino-2-thiiazoline N-acetyl-l-cysteinate as a possible cancer chemopreventive agents in murine models.

    Science.gov (United States)

    Simkeviciene, Vitalija; Straukas, J; Uleckiene, Saule

    2002-01-01

    The aim of this study was to investigate N-acetyl-cysteine (NAC) and its 2-amino-2-thiazoline salt (NACAT) as potential chemopreventive agents on experimentally induced lung tumours by urethane (U) in mice. Female BALB/c mice were used. U was given by intraperitoneal injections during 2 weeks (single dose - 10 mg/mouse, total - 50 mg/mouse). Mice were treated daily per os with NAC 1/10 LD50, NACAT 1/10 or 1/100 LD50 starting 2 weeks prior U administration, then during U treatment and thereafter for 2 months. The duration of experiment was 4 months. The results showed that NAC (1000 mg/kg) reduced the lung tumour incidence to 30% that of controls, P < or = 0.05. Most effective of NACAT was 100 mg/kg dose; it reduced an average of lung adenomas per mouse by 26%, P < or = 0.05, but lower dose (10 mg/kg) was less effective. In order to achieve similar chemopreventive effect (approximately 30%) on mice, it is necessary to use 0.38 mM/kg of NACAT or 6.13 mM/kg of NAC. It means that 16 times less of NACAT is required, if calculated by molar concentration. In general, NAC and NACAT have a moderate chemopreventive effect on lung tumorigenesis induced by urethane in mice. PMID:12371608

  10. Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhary, Sandeep C.; Singh, Tripti; Kapur, Puneet; Weng, Zhiping; Arumugam, Aadithya; Elmets, Craig A. [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, 6130 Executive Blvd, Suite 2114, Bethesda, MD 20892 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, 1530 3rd Avenue South, VH509, Birmingham, AL 35294-0019 (United States)

    2013-05-01

    Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs, possess anti-proliferative, pro-apoptotic and anti-cancer activities. Here, we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice. Topical application of NO-sulindac reduced tumor incidence, number (p < 0.05) and volume (p < 0.005) as compared to UVB (alone)-irradiated vehicle-treated mice. An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio. The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced. However, proliferation was identified as the major target of NO-sulindac in this study. A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed. The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway. UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2, p38 and JNK1/2. In this regard, NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2, the direct NFκB transcription target proteins. NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial–mesenchymal transition. A marked decrease in the expression of mesenchymal markers such as Fibronectin, N-cadherin, SNAI, Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors. Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways. - Highlights: ► NO-sulindac is a potent chemopreventive agent for UVB-induced skin cancer. ► NO

  11. Nitric oxide-releasing sulindac is a novel skin cancer chemopreventive agent for UVB-induced photocarcinogenesis

    International Nuclear Information System (INIS)

    Nitric oxide (NO)-releasing non-steroidal anti-inflammatory drugs (NO-NSAIDs) which have been synthesized to reduce gastro-intestinal and cardiovascular toxicities of NSAIDs, possess anti-proliferative, pro-apoptotic and anti-cancer activities. Here, we show that NO-sulindac inhibited UVB-induced skin tumorigenesis in SKH-1 hairless mice. Topical application of NO-sulindac reduced tumor incidence, number (p < 0.05) and volume (p < 0.005) as compared to UVB (alone)-irradiated vehicle-treated mice. An increase in TUNEL-positive cells in skin lesions was accompanied by the enhanced Bax:Bcl-2 ratio. The expression of pro-apoptotic Bax was increased whereas anti-apoptotic Bcl-2 reduced. However, proliferation was identified as the major target of NO-sulindac in this study. A reduced expression of PCNA and cyclin D1 associated with the dampening of cell cycle progression was observed. The mechanism of this inhibition was related to the reduction in UVB-induced Notch signaling pathway. UVB-induced inflammatory responses were diminished by NO-sulindac as observed by a remarkable reduction in the levels of phosphorylated MAP Kinases Erk1/2, p38 and JNK1/2. In this regard, NO-sulindac also inhibited NFκB by enhancing IκBα as evidenced by the reduced expression of iNOS and COX-2, the direct NFκB transcription target proteins. NO-sulindac significantly diminished the progression of benign lesions to invasive carcinomas by suppressing the tumor aggressiveness and retarding epithelial–mesenchymal transition. A marked decrease in the expression of mesenchymal markers such as Fibronectin, N-cadherin, SNAI, Slug and Twist and an increase in epithelial cell polarity marker E-cadherin were noted in NO-sulindac-treated tumors. Our data suggest that NO-sulindac is a potent inhibitor of UVB-induced skin carcinogenesis and acts by targeting proliferation-regulatory pathways. - Highlights: ► NO-sulindac is a potent chemopreventive agent for UVB-induced skin cancer. ► NO

  12. Cancer chemoprevention by natural compounds

    OpenAIRE

    スズキ, マスミ; Masumi, SUZUI

    2007-01-01

    There is growing interest in the use of natural compounds for the treatment and prevention of a wide variety of diseases, including cancer. Several herb-derived components are currently evaluated in preclinical studies as potential cancer chemopreventive agents. We have recently found that several herbal plants in the Ryukyu Islands, or any other natural compound, have a potential chemopreventive effect on biomarkers of colon carcinogenesis and a growth inhibitory effect on human cancer cells...

  13. Chemoprevention of Melanoma

    OpenAIRE

    Madhunapantula, SubbaRao V.; Robertson, Gavin P.

    2012-01-01

    Despite advances in drug discovery programs and molecular approaches for identifying the drug targets, incidence and mortality rates due to melanoma continues to rise at an alarming rate. Existing preventive strategies generally involve mole screening followed by surgical removal of the benign nevi and abnormal moles. However, due to lack of effective programs for screening and disease recurrence after surgical resection there is a need for better chemopreventive agents. Although sunscreens h...

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

    Directory of Open Access Journals (Sweden)

    Chinthalapally V. Rao

    2013-09-01

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

  15. The Model Repository (MREP) of the Models of Infectious Disease Agent Study (MIDAS)

    Science.gov (United States)

    Cooley, Phillip C.; Roberts, D.; Bakalov, V. D.; Bikmal, S.; Cantor, S.; Costandine, T.; Ganapathi, L.; Golla, B. J.; Grubbs, G.; Hollingsworth, C.; Li, S.; Qin, Y.; Savage, B.; Simoni, D.; Solano, E.; Wagener, D.

    2009-01-01

    The model repository (MREP) is a relational database management system (RDBMS) developed under the auspices of the Models of Infectious Disease Agent Study (MIDAS. The purpose of the MREP is to organize and catalog the models, results, and suggestions for using MIDAS and to store them in a way to allow users to run models from an access-controlled disease model repository. The model repository contains source and object code of disease models developed by infectious disease modelers and tested in a production environment. Different versions of models used to describe various aspects of the same disease are housed in the repository. Models are linked to their developers and different versions of the codes are tied to Subversion, a version control tool. An additional element of the MREP will be to house, manage, and control access to a disease model results warehouse, which consists of output generated by the models contained in the MREP. The results tables and files are linked to the version of the model and the input parameters that collectively generated the results. The results tables are warehoused in a relational database that permits them to be easily identified, categorized, and downloaded. PMID:18632331

  16. Growth-inhibitory effects of the chemopreventive agent indole-3-carbinol are increased in combination with the polyamine putrescine in the SW480 colon tumour cell line

    Directory of Open Access Journals (Sweden)

    Gescher Andreas

    2003-01-01

    Full Text Available Abstract Background Many tumours undergo disregulation of polyamine homeostasis and upregulation of ornithine decarboxylase (ODC activity, which can promote carcinogenesis. In animal models of colon carcinogenesis, inhibition of ODC activity by difluoromethylornithine (DFMO has been shown to reduce the number and size of colon adenomas and carcinomas. Indole-3-carbinol (I3C has shown promising chemopreventive activity against a range of human tumour cell types, but little is known about the effect of this agent on colon cell lines. Here, we investigated whether inhibition of ODC by I3C could contribute to a chemopreventive effect in colon cell lines. Methods Cell cycle progression and induction of apoptosis were assessed by flow cytometry. Ornithine decarboxylase activity was determined by liberation of CO2 from 14C-labelled substrate, and polyamine levels were measured by HPLC. Results I3C inhibited proliferation of the human colon tumour cell lines HT29 and SW480, and of the normal tissue-derived HCEC line, and at higher concentrations induced apoptosis in SW480 cells. The agent also caused a decrease in ODC activity in a dose-dependent manner. While administration of exogenous putrescine reversed the growth-inhibitory effect of DFMO, it did not reverse the growth-inhibition following an I3C treatment, and in the case of the SW480 cell line, the effect was actually enhanced. In this cell line, combination treatment caused a slight increase in the proportion of cells in the G2/M phase of the cell cycle, and increased the proportion of cells undergoing necrosis, but did not predispose cells to apoptosis. Indole-3-carbinol also caused an increase in intracellular spermine levels, which was not modulated by putrescine co-administration. Conclusion While indole-3-carbinol decreased ornithine decarboxylase activity in the colon cell lines, it appears unlikely that this constitutes a major mechanism by which the agent exerts its antiproliferative

  17. Chemopreventive Potential of Probiotics and Prebiotics

    OpenAIRE

    Rajitha Sunkata; Josh Herring; Walker, Lloyd T.; Martha Verghese

    2014-01-01

    Utilization of probiotics and prebiotics in food products and in the diet supplemental form continues to gain interest because of their health benefits. Cancer is the leading cause of death and strategies for chemoprevention are important to reduce mortality and morbidity. Probiotics are gaining attention to use as preventive agents. Efficacy of their use as chemopreventive agents was established through research. This review focused on the mechanisms of prebiotics and probiotics action again...

  18. Chemoprevention by WR-2721

    International Nuclear Information System (INIS)

    WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is an effective chemopreventive agent. C57BL x BALB/c F1 female mice, were exposed to a single whole-body dose of 206 cGy from a 60Co photon source. Those groups treated with VATR-2721 (400 mg/kg) were administered the agent i.p. 30 min prior to irradiation. Over 90% of deaths were determined to be due to tumor involvement. WR-2721 afforded significant protection against life shortening due to radiation-induced tumors of connective tissue and epithelial tissue origins. Subsequent survival time in WR-2721-treated and irradiated animals as compared to matched irradiated-only controls was extended up to 59 days. A single exposure of animals to VVR-2721 did not affect the cumulative survival curves for unirradiated mice. WR-2721 possesses chemopreventive properties which can be clinically exploited to reduce the risk to therapy-induced secondary cancers in patients who otherwise would have an excellent prognosis for cure and long-term survival

  19. Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B1

    International Nuclear Information System (INIS)

    Aflatoxin B1 (AFB1) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB1-DNA adducts in AFB1-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB1 and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB1 administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB1-induced hepatotoxicity. At 24 h after AFB1 administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB1-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB1 hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer. - Highlights: • This study revealed sulforaphane (SF)-deregulated gene sets in aflatoxin B1 (AFB1)-treated rat livers. • SF redirects biochemical networks toward lipid biosynthesis in AFB1-dosed rats. • SF enhanced gene sets that would be expected to favor cell repair and regeneration

  20. Localized sequence-specific release of a chemopreventive agent and an anticancer drug in a time-controllable manner to enhance therapeutic efficacy.

    Science.gov (United States)

    Pan, Wen-Yu; Lin, Kun-Ju; Huang, Chieh-Cheng; Chiang, Wei-Lun; Lin, Yu-Jung; Lin, Wei-Chih; Chuang, Er-Yuan; Chang, Yen; Sung, Hsing-Wen

    2016-09-01

    Combination chemotherapy with multiple drugs commonly requires several injections on various schedules, and the probability that the drug molecules reach the diseased tissues at the proper time and effective therapeutic concentrations is very low. This work elucidates an injectable co-delivery system that is based on cationic liposomes that are adsorbed on anionic hollow microspheres (Lipos-HMs) via electrostatic interaction, from which the localized sequence-specific release of a chemopreventive agent (1,25(OH)2D3) and an anticancer drug (doxorubicin; DOX) can be thermally driven in a time-controllable manner by an externally applied high-frequency magnetic field (HFMF). Lipos-HMs can greatly promote the accumulation of reactive oxygen species (ROS) in tumor cells by reducing their cytoplasmic expression of an antioxidant enzyme (superoxide dismutase) by 1,25(OH)2D3, increasing the susceptibility of cancer cells to the cytotoxic action of DOX. In nude mice that bear xenograft tumors, treatment with Lipos-HMs under exposure to HFMF effectively inhibits tumor growth and is the most effective therapeutic intervention among all the investigated. These empirical results demonstrate that the synergistic anticancer effects of sequential release of 1,25(OH)2D3 and DOX from the Lipos-HMs may have potential for maximizing DOX cytotoxicity, supporting more effective cancer treatment. PMID:27294541

  1. Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver

    International Nuclear Information System (INIS)

    Epidemiological and animal studies linking high fruit and vegetable consumption to lower cancer risk have strengthened the belief that long-term administration of isolated naturally occurring dietary constituents could reduce the risk of cancer. In recent years, metabolites derived from phytoalexins, such as glucoraphanin found in broccoli and other cruciferous vegetables (Brassicaceae), have gained much attention as potential cancer chemopreventive agents. The protective effect of these micronutrients is assumed to be due to the inhibition of Phase-I carcinogen-bioactivating enzymes and/or induction of Phase-II detoxifying enzymes, an assumption that still remains uncertain. The protective effect of glucoraphanin is thought to be due to sulforaphane, an isothiocyanate metabolite produced from glucoraphanin by myrosinase. Here we show, in rat liver, that while glucoraphanin slightly induces Phase-II enzymes, it powerfully boosts Phase-I enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), nitrosamines and olefins. Induction of the cytochrome P450 (CYP) isoforms CYP1A1/2, CYP3A1/2 and CYP2E1 was confirmed by Western immunoblotting. CYP induction was paralleled by an increase in the corresponding mRNA levels. Concomitant with this Phase-I induction, we also found that glucoraphanin generated large amount of various reactive radical species, as determined by electron paramagnetic resonance (EPR) spectrometry coupled to a radical-probe technique. This suggests that long-term uncontrolled administration of glucoraphanin could actually pose a potential health hazard

  2. Antineoplastic effect of a novel chemopreventive agent, neokestose, on the Caco-2 cell line via inhibition of expression of nuclear factor-κB and cyclooxygenase-2.

    Science.gov (United States)

    Lee, Shun-Mei; Chang, Jan-Yi; Wu, Jiann-Shing; Sheu, Dey-Chyi

    2015-07-01

    Neokestose is a 6G-fructooligosaccharide (FOS) and an important prebiotic. When FOS are ingested by patients with colorectal cancer, they may come into contact with cancer cells prior to being fermented by bifidobacteria in the colon. In the present study, the effects of neokestose on cell proliferation, cell cycle and apoptosis of the colorectal cancer cell line Caco-2 were investigated to evaluate its anti-cancer effect. An MTT assay showed that neokestose-treated Caco-2 cells exhibited a significant and dose-dependent loss of viability. Flow cytometric analysis indicated that the sub-G1 population of Caco-2 cells was significantly increased following treatment with neokestose, and the percentage of Caco-2 cells in the stage of late apoptosis was also significantly increased in a dose-dependent manner. Western blot analysis showed that the overexpression of nuclear factor-κB, a central molecule responsible for the transition from inflammation to cancer, and cyclooxygenase-2, an important enzyme in colorectal tumorigenesis, in colorectal carcinoma cells was inhibited by neokestose. Accordingly, the present study provided in vitro evidence that neokestose may be used as a dietary chemopreventive agent, whose application is more rational than that of COX-2 inhibitors or aspirin for preventing colorectal cancer. PMID:25815878

  3. Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Perocco, Paolo [Department of Experimental Pathology, Cancerology Section, viale Filopanti 22, I-40126, University of Bologna, Bologna (Italy); Bronzetti, Giorgio [Institute of Biology and Agricultural Biotechnology - CNR Research Area, via Moruzzi, I-56124 Pisa (Italy); Canistro, Donatella; Sapone, Andrea; Affatato, Alessandra; Pozzetti, Laura; Broccoli, Massimiliano [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Valgimigli, Luca [Department of Organic Chemistry ' A. Mangini' , Viale Risorgimento 4, I-40127, Alma-Mater Studiorum, University of Bologna, Bologna (Italy); Pedulli, Gian Franco [Department of Organic Chemistry ' A. Mangini' , Viale Risorgimento 4, I-40127, Alma-Mater Studiorum, University of Bologna, Bologna (Italy); Iori, Renato [C.R.A - Research Institute for Industrial Crops, via di Corticella 133, I-40129 Bologna (Italy); Barillari, Jessica [Institute of Biology and Agricultural Biotechnology - CNR Research Area, via Moruzzi, I-56124 Pisa (Italy)]|[C.R.A - Research Institute for Industrial Crops, via di Corticella 133, I-40129 Bologna (Italy); Sblendorio, Valeriana [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Legator, Marvin S. [Department of Preventive Medicine and Community Health, Division of Environmental Toxicology, The University of Texas Medical Branch at Galveston, 700 Harborside Drive, Galveston, TX 77555-1110 (United States); Paolini, Moreno [Department of Pharmacology, Molecular Toxicology Unit, via Irnerio 48, I-40126, University of Bologna, Bologna (Italy); Abdel-Rahman, Sherif Z. [Department of Preventive Medicine and Community Health, Division of Environmental Toxicology, The University of Texas Medical Branch at Galveston, 700 Harborside Drive, Galveston, TX 77555-1110 (United States)]. E-mail: sabdelra@utmb.edu

    2006-03-20

    Epidemiological and animal studies linking high fruit and vegetable consumption to lower cancer risk have strengthened the belief that long-term administration of isolated naturally occurring dietary constituents could reduce the risk of cancer. In recent years, metabolites derived from phytoalexins, such as glucoraphanin found in broccoli and other cruciferous vegetables (Brassicaceae), have gained much attention as potential cancer chemopreventive agents. The protective effect of these micronutrients is assumed to be due to the inhibition of Phase-I carcinogen-bioactivating enzymes and/or induction of Phase-II detoxifying enzymes, an assumption that still remains uncertain. The protective effect of glucoraphanin is thought to be due to sulforaphane, an isothiocyanate metabolite produced from glucoraphanin by myrosinase. Here we show, in rat liver, that while glucoraphanin slightly induces Phase-II enzymes, it powerfully boosts Phase-I enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), nitrosamines and olefins. Induction of the cytochrome P450 (CYP) isoforms CYP1A1/2, CYP3A1/2 and CYP2E1 was confirmed by Western immunoblotting. CYP induction was paralleled by an increase in the corresponding mRNA levels. Concomitant with this Phase-I induction, we also found that glucoraphanin generated large amount of various reactive radical species, as determined by electron paramagnetic resonance (EPR) spectrometry coupled to a radical-probe technique. This suggests that long-term uncontrolled administration of glucoraphanin could actually pose a potential health hazard.

  4. The Use of Animal Models for Cancer Chemoprevention Drug Development

    OpenAIRE

    Steele, Vernon E.; Lubet, Ronald A.

    2010-01-01

    Animal models currently are used to assess the efficacy of potential chemopreventive agents, including synthetic chemicals, chemical agents obtained from natural products and natural product mixtures. The observations made in these models as well as other data are then used to prioritize agents to determine which are qualified to progress to clinical chemoprevention trials. Organ specific animal models are employed to determine which agents or classes of agents are likely to be the most effec...

  5. Chemoprevention of photocarcinogenesis by selected dietary botanicals.

    OpenAIRE

    Baliga, Manjeshwar S; Santosh K. Katiyar

    2006-01-01

    KEYWORDS - CLASSIFIACATION: adverse effects;Animals;Antineoplastic Agents;Antineoplastic Agents,Phytogenic;Antioxidants;chemistry;Chemoprevention;drug therapy;Dermatology;dietary modulation of cancer & cancer biomarkers;Dietary Supplements;Evaluation;Humans;methods;Neoplasms,Radiation-Induced;prevention & control;Phytotherapy;radiation effects;Research;Skin;Skin Neoplasms;therapeutic use;toxicity;Ultraviolet Rays. Epidemiological, clinical and laboratory studies have implicated solar ultra...

  6. Chemoprevention of bladder cancer.

    Science.gov (United States)

    Kamat, Ashish M; Lamm, Donald L

    2002-02-01

    The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from definitive. Many authorities question the validity of current recommendations for nutritional chemoprevention against bladder cancer. The reason for the wide variations reported in epidemiologic studies lies in the nature of observational studies. Dietary studies are limited in their conclusions because the protection afforded by the consumption of a particular nutrient may be multifactorial, with different components of the food exerting potential chemopreventive effects. Furthermore, measuring levels of nutrients in the food intake of populations is confounded by factors that might affect these levels and also the incidence of cancer. For example, vitamin A can come from animal or vegetarian sources. Because animal fat has been identified as a potential carcinogen in man, depending on the source of the vitamin, varying levels of protection might be deduced. In addition, chemoprevention studies using dietary supplements are expected to have mild effects, and large studies would be required to confirm statistical significance. Even with agents such as intravesical chemotherapy, only half the studies achieve statistical significance [29]. Prospective randomized trials with a large sample size, longer follow-up, and an extended duration of treatment are needed to clarify the association between micronutrients and cancer protection. With these caveats in mind, several recommendations can be made. Simple measures, such as drinking more fluids (especially water), can have a profound impact on the incidence of bladder cancer. Vitamins are being extensively studied in chemopreventive trials for different cancers. There is strong evidence for a chemoprotective effect of vitamin A in bladder cancer. The authors recommend 32,000 IU/day of vitamin A initially, with lower doses (24,000 IU) for persons less than 50 kg. Because liver toxicity is a

  7. Strategy of research for cancer-chemoprevention

    International Nuclear Information System (INIS)

    It has been reported that environmental chemicals are important factors in terms of both development and prevention of human cancer. For prevention of human cancer, detection of early cancer and clinical trials at the early stage have been focused so far. Now, next main project will be investigation for prevention of cancer development itself. Chemoprevention of carcinogenesis, which means prevention of carcinogenesis by some chemical compounds, have been investigated extensively in a variety of organs, but in only one organ. However, from results of our studies, antioxidants such as BHA, responded differently to organs, and whole body investigation, not only one organ carcinogenesis, should be performed to investigate of chemoprevention. Furthermore, the mechanisms of action of chemoprevention and on which step of carcinogenesis does the chemopreventive compound prevent, such as initiation, promotion, progression or whole carcinogenesis steps should be discussed. We have developed a medium term bioassay system and multi-organ carcinogenesis system, which can be used for investigation of cancer chemoprevention. Using these systems, we have investigated dose response inhibitory effects of BHA and α-tocopherol by the medium-term bioassay system, and catechins in the green tea inhibit small intestinal carcinogenesis in the multi-organ carcinogenesis. It is important for prevent human cancer to find other candidates for chemopreventive agents using animal study. (author)

  8. Chemoprevention of familial adenomatous polyposis.

    Science.gov (United States)

    Lynch, Patrick M

    2016-07-01

    Familial adenomatous polyposis (FAP) has always been first and foremost a surgical disease, whose treatment with colectomy has long been known to reduce risk of premature cancer death. The notion of reducing polyp burden and potentially delaying surgical intervention has spawned a host of "chemoprevention" trials. In this paper I selectively review the findings from these studies, highlighting trial design issues and in particular some of the limitations of historical and existing trial endpoint measures. Nonsteroidal anti-inflammatory agents have been the most commonly employed chemopreventive agents. Sulindac, largely by historical accident, has been the most extensively studied, and is widely considered the standard of care when a clinical decision to intervene medically is made. Newer trials are evaluating combinations of agents in order to take advantage of differing mechanisms of action, in the hope of achieving synergy, as no single agent predictably or completely suppresses adenoma growth. Some of these studies and other single-agent interventions are discussed, though an exploration of the various mechanisms of action is beyond the scope of this paper. It is essential that future trials focus on the issue of "clinical benefit", not simply because the US Food and Drug Administration has insisted on it, but because only real evidence-based advances can improve the standard of medical care for FAP patients. Hence my focus on issues of trial design and clinically relevant endpoints. PMID:27083160

  9. Molecular Targeted Therapies Using Botanicals for Prostate Cancer Chemoprevention

    OpenAIRE

    Kumar, Nagi; Chornokur, Ganna

    2012-01-01

    In spite of the large number of botanicals demonstrating promise as potential cancer chemopreventive agents, most have failed to prove effectiveness in clinical trials. Critical requirements for moving botanical agents to recommendation for clinical use include adopting a systematic, molecular-target based approach and utilizing the same ethical and rigorous methods that are used to evaluate other pharmacological agents. Preliminary data on a mechanistic rationale for chemoprevention activity...

  10. Chemoprevention of cancer: current evidence and future prospects [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Vassiliki Benetou

    2015-09-01

    Full Text Available Cancer chemoprevention refers to the use of agents for the inhibition, delay, or reversal of carcinogenesis before invasion. In the present review, agents examined in the context of cancer chemoprevention are classified in four major categories—hormonal, medications, diet-related agents, and vaccines—and the main representatives of each category are presented. Although there are serious constraints in the documentation of effectiveness of chemopreventive agents, mainly stemming from the long latency of the condition they are addressing and the frequent lack of intermediate biomarkers, there is little disagreement about the role of aspirin, whereas a diet rich in vegetables and fruits appears to convey more protection than individual micronutrients. Among categories of cancer chemopreventive agents, hormonal ones and vaccines might hold more promise for the future. Also, the identification of individuals who would benefit most from chemopreventive interventions on the basis of their genetic profiles could open new prospects for cancer chemoprevention.

  11. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    OpenAIRE

    Hesham Fahmy; Ahmed, Safwat A.; Szymanski, Pawel T.; Bhimanna Kuppast; Sherief Khalifa

    2011-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enh...

  12. Breast Cancer Chemoprevention: Old and New Approaches

    Directory of Open Access Journals (Sweden)

    Massimiliano Cazzaniga

    2012-01-01

    Full Text Available In 1976, Sporn has defined chemoprevention as “the use of pharmacologic or natural agents that inhibit the development of invasive breast cancer either by blocking the DNA damage that initiates carcinogenesis, or by arresting or reversing the progression of premalignant cells in which such damage has already occurred.” Although the precise mechanism or mechanisms that promote a breast cancer are not completely established, the success of several recent clinical trials in preventive settings in selected high-risk populations suggests that chemoprevention is a rational and an appealing strategy. Breast cancer chemoprevention has focused heavily on endocrine intervention using selective estrogen receptor modulators (SERMs and aromatase inhibitors (AIs. Achieving much success in this particular setting and new approaches as low-dose administration are actually under investigations in several topics. Unfortunately, these drugs are active in prevention of endocrine responsive lesions only and have no effect in reducing the risk of estrogen-negative breast cancer. Thus, recently new pathways, biomarkers, and agents likely are to be effective in this subgroup of cancers and were put under investigation. Moreover, the identification of new potential molecular targets and the development of agents aimed at these targets within cancer have already had a significant impact on advanced cancer therapy and provide a wealth of opportunities for chemoprevention. This paper will highlight current clinical research in both ER-positive and ER-negative breast cancer chemoprevention, explaining the biologic effect of the various agents on carcinogenesis and precancerous lesions, and finally presenting an excursus on the state-of-the-art about new molecular targets under investigations in breast cancer settings.

  13. Sarcophine-Diol, a Skin Cancer Chemopreventive Agent, Inhibits Proliferation and Stimulates Apoptosis in Mouse Melanoma B16F10 Cell Line

    Directory of Open Access Journals (Sweden)

    Hesham Fahmy

    2011-12-01

    Full Text Available Sarcodiol (SD is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B16F10 cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3 and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4. SD treatment also enhances cellular level of tumor suppressor protein 53 (p53 and stimulates cleavage of the nuclear poly (ADP-ribose polymerase (cleaved-PARP. SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B16F10 tumor cells.

  14. Sarcophine-diol, a skin cancer chemopreventive agent, inhibits proliferation and stimulates apoptosis in mouse melanoma B₁₆F₁₀ cell line.

    Science.gov (United States)

    Szymanski, Pawel T; Kuppast, Bhimanna; Ahmed, Safwat A; Khalifa, Sherief; Fahmy, Hesham

    2012-01-01

    Sarcodiol (SD) is a semi-synthetic derivative of sarcophine, a marine natural product. In our previous work, we reported the significant chemopreventive effects of SD against non-melanoma skin cancer both in vitro and in vivo mouse models. In this investigation, we extended this work to study the effect of sarcodiol on melanoma development, the more deadly form of skin cancer, using the mouse melanoma B₁₆F₁₀ cell line. In this study we report that SD inhibits the de novo DNA synthesis and enhances fragmentation of DNA. We also evaluated the antitumor effect of SD on melanoma cell viability using several biomarkers for cell proliferation and apoptosis. SD inhibits the expression levels of signal transducers and activators of transcription protein (STAT-3) and cyclin D1, an activator of cyclin-dependent kinase 4 (Cdk4). SD treatment also enhances cellular level of tumor suppressor protein 53 (p53) and stimulates cleavage of the nuclear poly (ADP-ribose) polymerase (cleaved-PARP). SD also enhances cellular levels of cleaved Caspase-3, -8, -9 and stimulates enzymatic activities of Caspase-3, -8 and -9. These results, in addition to inhibition of cell viability, suggest that SD inhibits melanoma cell proliferation by arresting the cell-division cycle in a Go quiescent phase and activates programmed cell death (apoptosis) via extrinsic and intrinsic pathways. Finally, these studies demonstrate that SD shows a very promising chemopreventive effect in melanoma B₁₆F₁₀ tumor cells. PMID:22363217

  15. Pancreatic Cancer Chemoprevention Translational Workshop: Meeting Report.

    Science.gov (United States)

    Miller, Mark Steven; Allen, Peter; Brentnall, Teresa A; Goggins, Michael; Hruban, Ralph H; Petersen, Gloria M; Rao, Chinthalapally V; Whitcomb, David C; Brand, Randall E; Chari, Suresh T; Klein, Alison P; Lubman, David M; Rhim, Andrew D; Simeone, Diane M; Wolpin, Brian M; Umar, Asad; Srivastava, Sudhir; Steele, Vernon E; Rinaudo, Jo Ann S

    2016-09-01

    Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a 5-year survival rate of less than 10%. The Division of Cancer Prevention of the National Cancer Institute sponsored the Pancreatic Cancer Chemoprevention Translational Workshop on September 10 to 11, 2015. The goal of the workshop was to obtain information regarding the current state of the science and future scientific areas that should be prioritized for pancreatic cancer prevention research, including early detection and intervention for high-risk precancerous lesions. The workshop addressed the molecular/genetic landscape of pancreatic cancer and precursor lesions, high-risk populations and criteria to identify a high-risk population for potential chemoprevention trials, identification of chemopreventative/immunopreventative agents, and use of potential biomarkers and imaging for assessing short-term efficacy of a preventative agent. The field of chemoprevention for pancreatic cancer is emerging, and this workshop was organized to begin to address these important issues and promote multi-institutional efforts in this area. The meeting participants recommended the development of an National Cancer Institute working group to coordinate efforts, provide a framework, and identify opportunities for chemoprevention of pancreatic cancer. PMID:27518363

  16. Cancer chemoprevention by targeting the epigenome.

    Science.gov (United States)

    Huang, Joseph; Plass, Christoph; Gerhauser, Clarissa

    2011-12-01

    The term "epigenetics" refers to modifications in gene expression caused by heritable, but potentially reversible, changes in DNA methylation and chromatin structure. Given the fact that epigenetic modifications occur early in carcinogenesis and represent potentially initiating events in cancer development, they have been identified as promising new targets for prevention strategies. The present review will give a comprehensive overview of the current literature on chemopreventive agents and their influence on major epigenetic mechanisms, that is DNA methylation, histone acetylation and methylation, and microRNAs, both in vitro and in rodent and human studies, taking into consideration specific mechanisms of action, target sites, concentrations, methods used for analysis, and outcome. Chemopreventive agents with reported mechanisms targeting the epigenome include micronutrients (folate, selenium, retinoic acid, Vit. E), butyrate, polyphenols (from green tea, apples, coffee, and other dietary sources), genistein and soy isoflavones, parthenolide, curcumin, ellagitannin, indol-3-carbinol (I3C) and diindolylmethane (DIM), mahanine, nordihydroguaiaretic acid (NDGA), lycopene, sulfur-containing compounds from Allium and cruciferous vegetables (sulforaphane, phenylethyl isothiocyanate (PEITC), phenylhexyl isothiocyanate (PHI), diallyldisulfide (DADS), allyl mercaptan (AM)), antibiotics (mithramycin A, apicidin), pharmacological agents (celecoxib, DFMO, 5-aza-2'-deoxycytidine and zebularine), compounds affecting sirtuin activity (resveratrol, dihydrocoumarin, cambinol), inhibitors of histone acetyl transferases (anacardic acid, garcinol, ursodeoxycholic acid), and relatively unexplored modulators of histone lysine methylation (chaetocin, polyamine analogues, n-3 polyunsaturated fatty acids). Their effects on global DNA methylation, tumor suppressor genes silenced by promoter methylation, histone modifications, and miRNAs deregulated during carcinogenesis have potential

  17. Exploring the Potential Role of Chemopreventive Agent, Hesperetin Conjugated Pegylated Gold Nanoparticles in Diethylnitrosamine-Induced Hepatocellular Carcinoma in Male Wistar Albino Rats.

    Science.gov (United States)

    Gokuladhas, Krishnan; Jayakumar, Subramaniyan; Rajan, Balan; Elamaran, Ramasamy; Pramila, Chengalvarayan Subramani; Gopikrishnan, Mani; Tamilarasi, Sasivarman; Devaki, Thiruvengadam

    2016-04-01

    Liver cancer is the fifth most common cancer and is still one of the leading causes of death world wide, due to food additives, alcohol, fungal toxins, air, toxic industrial chemicals, and water pollutants. Chemopreventive drugs play a potential role in liver cancer treatment. Obviously in the production of anticancer drugs, the factors like poor solubility, bioavailability, biocompatibility, limited chemical stability, large amount of dose etc., plays a major role. Against this backdrop, the idea of designing the chemopreventive nature of bio flavanoid hesperetin (HP) drug conjugated with pegylated gold nanoparticles to increasing the solubility, improve bioavailability and enhance the targeting capabilities of the drug during diethylnitrosamine (DEN) induced liver cancer in male wistar albino rats. The dose fixation studies and the toxicity of pure HP and HP conjugated gold nanoparticles (Au-mPEG(5000)-S-HP) were analysed. After concluded the dose fixation and toxicity studies the experimental design were segregated in six groups for the anticancer analysis of DEN induced HCC for 16 weeks. After the experimental period the body weight, relative liver weight, number of nodules and size of nodules, the levels of tumor markers like CEA, AFP and the level of lipid peroxidation, lipid hydroperoxides and the activities of antioxidant enzymes were assessed. The administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma glutamyl transpeptidase. The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase, catalase, reduced glutathione, glutathione peroxidise, and glutathione reductase. HP supplementation (20 mg/kg b.wt) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer and the

  18. Comet Assay in Cancer Chemoprevention.

    Science.gov (United States)

    Santoro, Raffaela; Ferraiuolo, Maria; Morgano, Gian Paolo; Muti, Paola; Strano, Sabrina

    2016-01-01

    The comet assay can be useful in monitoring DNA damage in single cells caused by exposure to genotoxic agents, such as those causing air, water, and soil pollution (e.g., pesticides, dioxins, electromagnetic fields) and chemo- and radiotherapy in cancer patients, or in the assessment of genoprotective effects of chemopreventive molecules. Therefore, it has particular importance in the fields of pharmacology and toxicology, and in both environmental and human biomonitoring. It allows the detection of single strand breaks as well as double-strand breaks and can be used in both normal and cancer cells. Here we describe the alkali method for comet assay, which allows to detect both single- and double-strand DNA breaks. PMID:26608293

  19. Breast Cancer Chemoprevention: Old and New Approaches

    OpenAIRE

    Massimiliano Cazzaniga; Bernardo Bonanni

    2012-01-01

    In 1976, Sporn has defined chemoprevention as “the use of pharmacologic or natural agents that inhibit the development of invasive breast cancer either by blocking the DNA damage that initiates carcinogenesis, or by arresting or reversing the progression of premalignant cells in which such damage has already occurred.” Although the precise mechanism or mechanisms that promote a breast cancer are not completely established, the success of several recent clinical trials in preventive settings i...

  20. Preclinical Assays for Identifying Cancer Chemopreventive Phytochemicals

    OpenAIRE

    Oyama, Takeru; Yasui, Yumiko; Sugie, Shigeyuki; Tanaka, Takuji

    2009-01-01

    Dietary factors influence carcinogenesis in a variety of tissues. The consumption of fruits and vegetables is associated with a decreased risk of several types of epithelial malignancies. In addition, there are interrelationships between diet, environmental factors, and genetics that can affect cancer risk. Potential chemopreventive agents against cancer development can be found among nutritive and/or nonnutritive compounds in inedible and edible plants. To identify potential cancer chemoprev...

  1. Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B{sub 1}

    Energy Technology Data Exchange (ETDEWEB)

    Techapiesancharoenkij, Nirachara [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Fiala, Jeannette L.A. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Navasumrit, Panida [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Croy, Robert G.; Wogan, Gerald N. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Groopman, John D. [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 (United States); Ruchirawat, Mathuros [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Essigmann, John M., E-mail: jessig@mit.edu [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2015-01-01

    Aflatoxin B{sub 1} (AFB{sub 1}) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB{sub 1}-DNA adducts in AFB{sub 1}-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB{sub 1} and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB{sub 1} administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB{sub 1}-induced hepatotoxicity. At 24 h after AFB{sub 1} administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB{sub 1}-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB{sub 1} hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer. - Highlights: • This study revealed sulforaphane (SF)-deregulated gene sets in aflatoxin B{sub 1} (AFB{sub 1})-treated rat livers. • SF redirects biochemical networks toward lipid biosynthesis in AFB{sub 1}-dosed rats. • SF enhanced gene sets that would be expected to favor cell repair and regeneration.

  2. Dietary chalcones with chemopreventive and chemotherapeutic potential.

    Science.gov (United States)

    Orlikova, Barbora; Tasdemir, Deniz; Golais, Frantisek; Dicato, Mario; Diederich, Marc

    2011-05-01

    Chalcones are absorbed in the daily diet and appear to be promising cancer chemopreventive agents. Chalcones represent an important group of the polyphenolic family, which includes a large number of naturally occurring molecules. This family possesses an interesting spectrum of biological activities, including antioxidative, antibacterial, anti-inflammatory, anticancer, cytotoxic, and immunosuppressive potential. Compounds of this family have been shown to interfere with each step of carcinogenesis, including initiation, promotion and progression. Moreover, numerous compounds from the family of dietary chalcones appear to show activity against cancer cells, suggesting that these molecules or their derivatives may be considered as potential anticancer drugs. This review will focus primarily on prominent members of the chalcone family with an 1,3-diphenyl-2-propenon core structure. Specifically, the inhibitory effects of these compounds on the different steps of carcinogenesis that reveal interesting chemopreventive and chemotherapeutic potential will be discussed. PMID:21484163

  3. Prostate cancer chemoprevention: Current status and future prospects

    International Nuclear Information System (INIS)

    Chemoprevention is a strategy that aims to reduce the incidence and burden of cancer through the development of agents to prevent, reverse or delay the carcinogenic process. Prostate cancer is a suitable target for prevention because it has a high incidence and prevalence, as well as a long latency and disease-related mortality, and furthermore it is a disease in which lifestyle and environmental factors may play critical roles. The development of chemoprevention strategies against prostate cancer will have a huge impact, both medically and economically. Large-scale clinical trials suggest that some agents such as selenium, lycopene, soy, green tea, vitamins D and E, anti-inflammatory and inhibitors of 5α-reductase are effective in preventing prostate cancer. Although each agent has the potential to affect the natural history of the disease, it is important to develop strategies to strategically proceed for the design and selection of test agents in order to demonstrate clinical benefit with the minimum of adverse effects. Appropriate selection of agent(s), disease stage, trial design and endpoints is critical in selecting the most promising regimens to accomplish these goals. This review highlights the present status of prostate cancer chemoprevention and discusses future prospects for chemopreventive strategies that are safe and clinically beneficial

  4. Chemoprevention of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Esophageal squamous cell carcinoma (SCC) is responsible for approximately one-sixth of all cancer-related mortality worldwide. This malignancy has a multifactorial etiology involving several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. Chemoprevention offers a viable alternative that could well be effective against the disease. Clinical investigations have shown that primary chemoprevention of this disease is feasible if potent inhibitory agents are identified. The Fischer 344 (F-344) rat model of esophageal SCC has been used extensively to investigate the biology of the disease, and to identify chemopreventive agents that could be useful in human trials. Multiple compounds that inhibit tumor initiation by esophageal carcinogens have been identified using this model. These include several isothiocyanates, diallyl sulfide and polyphenolic compounds. These compounds influence the metabolic activation of esophageal carcinogens resulting in reduced genetic (DNA) damage. Recently, a few agents have been shown to inhibit the progression of preneoplastic lesions in the rat esophagus into tumors. These agents include inhibitors of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) and c-Jun [a component of activator protein-1 (AP-1)]. Using a food-based approach to cancer prevention, we have shown that freeze-dried berry preparations inhibit both the initiation and promotion/progression stages of esophageal SCC in F-344 rats. These observations have led to a clinical trial in China to evaluate the ability of freeze-dried strawberries to influence the progression of esophageal dysplasia to SCC

  5. Advanced drug delivery systems of curcumin for cancer chemoprevention.

    Science.gov (United States)

    Bansal, Shyam S; Goel, Mehak; Aqil, Farrukh; Vadhanam, Manicka V; Gupta, Ramesh C

    2011-08-01

    Since ancient times, chemopreventive agents have been used to treat/prevent several diseases including cancer. They are found to elicit a spectrum of potent responses including anti-inflammatory, antioxidant, antiproliferative, anticarcinogenic, and antiangiogenic activity in various cell cultures and some animal studies. Research over the past 4 decades has shown that chemopreventives affect a number of proteins involved in various molecular pathways that regulate inflammatory and carcinogenic responses in a cell. Various enzymes, transcription factors, receptors, and adhesion proteins are also affected by chemopreventives. Although, these natural compounds have shown significant efficacy in cell culture studies, they elicited limited efficacy in various clinical studies. Their introduction into the clinical setting is hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Therefore, to circumvent these limitations and to ease their transition to clinics, alternate strategies should be explored. Drug delivery systems such as nanoparticles, liposomes, microemulsions, and polymeric implantable devices are emerging as one of the viable alternatives that have been shown to deliver therapeutic concentrations of various potent chemopreventives such as curcumin, ellagic acid, green tea polyphenols, and resveratrol into the systemic circulation. In this review article, we have attempted to provide a comprehensive outlook for these delivery approaches, using curcumin as a model agent, and discussed future strategies to enable the introduction of these highly potent chemopreventives into a physician's armamentarium. PMID:21546540

  6. Is There a Future for Chemoprevention of Prostate Cancer?

    Science.gov (United States)

    Bosland, Maarten C

    2016-08-01

    The outcome of the Selenium and Vitamin E Cancer Prevention Trial, demonstrating harm and no preventive activity of selenomethionine and α-tocopherol for prostate cancer, and the lack of approval by the FDA for the use of 5α-reductase inhibitors to prevent prostate cancer have cast doubt about the future of chemoprevention of prostate cancer. This article attempts to critically assess whether the notion that chemoprevention of prostate cancer has no future is warranted. Risk of prostate cancer is modifiable and chemoprevention of prostate cancer, particularly fatal/lethal cancer, is both needed and possible. However, the approach to prostate cancer-chemopreventive agent development has not followed a rational and systematic process. To make progress, the following steps are necessary: (i) identification of intermediate biomarkers predictive of fatal/lethal disease; (ii) development of a rational approach to identification of candidate agents, including high-throughput screening and generation of information on mechanism and biology of candidate agents and potential molecular targets; and (iii) systematic evaluation of the predictive value of preclinical models, phase II trials, and intermediate biomarkers for the outcome of phase III trials. New phase III trials should be based on adequate preclinical and phase II studies. Cancer Prev Res; 9(8); 642-7. ©2016 AACR. PMID:27099271

  7. Chemoprevention of prostate cancer with nutrients and supplements.

    Science.gov (United States)

    Van Poppel, Hendrik; Tombal, Bertrand

    2011-01-01

    As the adult population is increasing, prostate cancer (PCa) will become a considerable health problem in the next millennium. This has raised public interest in potential chemoprevention of this disease. As PCa is extremely common and generally slow to progress it is regarded as an ideal candidate for chemoprevention. At present, the 5 alpha-reductase inhibitors finasteride and dutasteride have been identified as preventive agents. This review describes whether selenium, alpha-tocopherol, isoflavones, lycopene green tea polyphenols, calcium, and resveratrol may be useful for decreasing the risk of PCa in men. Although encouraging results are present, some studies show negative results. Differences in study design, sample size, dose administered, and/or concentrations achieved in the body may be the reason for these inconsistencies. Today, chemopreventive agents may be appropriate for high-risk patients like those with high-grade prostatic intraepithelial neoplasia and other high-risk groups such as patients with elevated prostate specific antigen (PSA) and negative biopsy, rapid PSA velocity, and with a family history of PCa. Although larger randomized controlled studies are needed and epidemiologic evidence should be placed in a clinical context, physicians must be aware of these preventive opportunities in PCa care. Combinations of chemopreventive agents should be carefully investigated because mechanisms of action may be additive or synergistic. PMID:21629831

  8. Keap1 eye on the target: chemoprevention of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Melinda Sue YATES; Thomas Wells KENSLER

    2007-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide,causing nearly 600000 deaths each year. Increased risk of HCC due to chronic infection with hepatitis B virus (HBV) and exposure to dietary aflatoxins is respon-sible for many of these deaths. Prevention strategies targeting HBV infection and aflatoxin exposure could dramatically impact the rates of HCC. Universal HBV vaccination programs have begun in some high-risk areas. Strategies to reduce aflatoxin contamination in food stores have also been implemented. However,complete elimination of aflatoxin contamination might not be possible. For this reason, chemoprevention strategies which alter aflatoxin disposition are a practi-cal strategy to reduce the incidence of HCC in populations with high dietary aflatoxin exposure. The mechanisms of aflatoxin-induced hepatocarcinogenesis are well known. This knowledge provides the basis for evaluation of both expo-sures to aflatoxin, as well as modulation of aflatoxin disposition by chemopreventive agents. Products of aflatoxin DNA damage and toxicity as well as other metabo-lites can be used as biomarkers to evaluate modulation of aflatoxin disposition.Modulation of aflatoxin disposition can be achieved through induction of conju-gating and cytoprotective enzymes. Many of these enzymes are regulated through Kelch ECH-associating protein 1 (Keap 1)-NF-E2-related factor 2(Nrf2)-antioxi-dant response element (ARE) signaling, making this pathway an important mo-lecular target for chemoprevention. Rodent studies have identified several classes of chemopreventive agents which induce cytoprotective genes. These inducers include phenolic antioxidants, dithiolethiones, isothiocyanates, and triterpenoids.Furthermore, clinical interventions have shown that inducers of Keap 1-Nrf2-ARE signaling increase cytoprotective enzyme expression, resulting in modula-tion of aflatoxin disposition. Much work remains to be done in order to take promising chemopreventive

  9. The role of natural dietary compounds in colorectal cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Anna Olejnik

    2010-04-01

    Full Text Available This review discusses the preventive and therapeutic potential of natural dietary compounds against colorectal cancer. The chemopreventive properties of many natural food matrices and purified bioactive compounds have been evaluated. Prominent among the dietary constituents that are the focus of interest in colorectal cancer chemoprevention are dietary fiber, probiotics and prebiotics, methionine and folate, vitamins D and E, calcium and selenium, anthocyanins, procyanidins, phytoestrogens, isothiocyanates, epigallocatechin gallate, curcumin, and resveratrol. Laboratory studies provide strong evidence for the antitumor potential of these dietary agents. The mechanisms of their chemopreventive action are associated with, for example, the modulation of gene expression involved in the regulation of cell proliferation, differentiation, and apoptosis and the suppression of metastasis and angiogenesis. The anti-carcinogenic properties of these food compounds are also related to inhibition of many inflammatory agents, including the expression of cyclooxygenase-2. [i]In vitro[/i] and animal studies showed that most of them can protect against various carcinogens mediating colon cancer and suggest that they can also sensitize tumors to chemotherapy and radiation. Although experimental studies have clearly demonstrated their anticancer activity, not many clinical trials have provided satisfying results, not only because of the lack of efficiency of the chemopreventive agents, but also due to the lack of precise biomarkers monitoring their effects on colon cancer. Despite the lack of strong evidence for the anticancer potential of natural food compounds, clinicians have high hopes for using these factors in colon cancer chemoprevention and decreasing the incidence of this common malignancy in the future.

  10. Chemoprevention of prostate cancer with nutrients and supplements

    Directory of Open Access Journals (Sweden)

    Van Poppel H

    2011-04-01

    Full Text Available Hendrik Van Poppel1, Bertrand Tombal21Department of Urology, University Hospital, KU Leuven, Leuven, Belgium; 2Service d’Urologie, Cliniques Universtaires Saint Luc, Brussels, BelgiumAbstract: As the adult population is increasing, prostate cancer (PCa will become a considerable health problem in the next millennium. This has raised public interest in potential chemoprevention of this disease. As PCa is extremely common and generally slow to progress it is regarded as an ideal candidate for chemoprevention. At present, the 5 alpha-reductase inhibitors finasteride and dutasteride have been identified as preventive agents. This review describes whether selenium, alpha-tocopherol, isoflavones, lycopene green tea polyphenols, calcium, and resveratrol may be useful for decreasing the risk of PCa in men. Although encouraging results are present, some studies show negative results. Differences in study design, sample size, dose administered, and/or concentrations achieved in the body may be the reason for these inconsistencies. Today, chemopreventive agents may be appropriate for high-risk patients like those with high-grade prostatic intraepithelial neoplasia and other high-risk groups such as patients with elevated prostate specific antigen (PSA and negative biopsy, rapid PSA velocity, and with a family history of PCa. Although larger randomized controlled studies are needed and epidemiologic evidence should be placed in a clinical context, physicians must be aware of these preventive opportunities in PCa care. Combinations of chemopreventive agents should be carefully investigated because mechanisms of action may be additive or synergistic.Keywords: alpha-tocopherol, chemoprevention, isoflavones, lycopene, polyphenols, prostate cancer, selenium

  11. Breast cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Ivana Sestak

    2011-12-01

    Full Text Available Trials with tamoxifen have clearly shown that the risk of developing oestrogen receptor positive breast cancer can be reduced by at least 50% with prophylactic agents. The current challenge is to find new agents which achieve this or better efficacy, but with fewer side effects. Recent results indicate that the SERM raloxifene has similar efficacy to tamoxifen, but leads to fewer endometrial cancers, gynecological symptoms, and thromboembolic events. Results for contralateral tumors in adjuvant trials suggest that aromatase inhibitors may be able to prevent up to 70%–80% of ER-positive breast cancers, and this is currently being investigated in two large prevention trials, one using anastrozole (IBIS-II and the other exemestane (MAP.3. New agents are needed for receptor negative breast cancer and several possibilities are currently under investigation.

  12. Discovery and development of sulforaphane as a cancer chemopreventive phytochemical

    Institute of Scientific and Technical Information of China (English)

    Yuesheng ZHANG; Li TANG

    2007-01-01

    Sulforaphane (SF) is a phytochemical that displays both anticarcinogenic and anticancer activity. SF modulates many cancer-related events, including suscep-tibility to carcinogens, cell death, cell cycle, angiogenesis, invasion and metastasis.We review its discovery and development as a cancer chemopreventive agent with the intention of encouraging further research on this important compound and facilitating the identification and development of new phytochemicals for cancer prevention.

  13. Sulforaphane (SFN: An Isothiocyanate in a Cancer Chemoprevention Paradigm

    Directory of Open Access Journals (Sweden)

    Mohammad Fahad Ullah

    2015-07-01

    Full Text Available The International Agency for Research on Cancer (IARC in its latest World Cancer Report (2014 has projected the increase in the global cancer burden from 14 million (2012 to 22 million incidence annually within the next two decades. Such statistics warrant a collaborative engagement of conventional and complementary and alternative therapies to contain and manage cancer. In recent years, there has been a shift in the cancer chemoprevention paradigm with a significant focus turning towards bioactive components of human diets for their anticancer properties. Since diet is an integral part of lifestyle and given that an estimated one third of human cancers are believed to be preventable though appropriate lifestyle modification including dietary habits, the current shift in the conventional paradigm assumes significance. Several epidemiological studies have indicated that consumption of broccoli is associated with a lower risk of cancer incidence including breast, prostate, lung, stomach and colon cancer. The edible plant belonging to the family of cruciferae such as broccoli is a rich source of glucoraphanin, a precursor of isothiocyanate sulforaphane which is considered to be a potent anti-cancer agent. Plant-based dietary agents such as sulforaphane mimic chemotherapeutic drugs such as vorinostat, possessing histone deacetylase inhibition activity. Evidence from epidemiological and experimental studies have emerged, enhancing the clinical plausibility and translational value of sulforaphane in cancer chemoprevention. The present review provides the current understanding of the cancer chemopreventive pharmacology of sulforaphane towards its potential as an anticancer agent.

  14. Natural compounds as anticancer agents: Experimental evidence

    OpenAIRE

    Wang, Jiao; Jiang, Yang-Fu

    2012-01-01

    Cancer prevention research has drawn much attention worldwide. It is believed that some types of cancer can be prevented by following a healthy life style. Cancer chemoprevention by either natural or synthetic agents is a promising route towards lowering cancer incidence. In recent years, the concept of cancer chemoprevention has evolved greatly. Experimental studies in animal models demonstrate that the reversal or suppression of premalignant lesions by chemopreventive agents is achievable. ...

  15. The strategies to control prostate cancer by chemoprevention approaches

    International Nuclear Information System (INIS)

    Prostate cancer (PCA) is the most commonly diagnosed cancer in men in the United States with growing worldwide incidence. Despite intensive investment in improving early detection, PCA often escapes timely detection and mortality remains high; this malignancy being the second highest cancer-associated mortality in American men. Collectively, health care costs of PCA results in an immense financial burden that is only expected to grow. Additionally, even in cases of successful treatment, PCA is associated with long-term and pervasive effects on patients. A proactive alternative to treat PCA is to prevent its occurrence and progression prior to symptomatic malignancy. This may serve to address the issue of burgeoning healthcare costs and increasing number of sufferers. One potential regimen in service of this alternative is PCA chemoprevention. Here, chemical compounds with cancer preventive efficacy are identified on the basis of their potential in a host of categories: their historical medicinal use, correlation with reduced risk in population studies, non-toxicity, their unique chemical properties, or their role in biological systems. PCA chemopreventive agents are drawn from multiple broad classes of chemicals, themselves further subdivided based on source or potential effect, with most derived from natural products. Many such compounds have shown efficacy, varying from inhibiting deregulated PCA cell signaling, proliferation, epithelial to mesenchymal transition (EMT), invasion, metastasis, tumor growth and angiogenesis and inducing apoptosis. Overall, these chemopreventive agents show great promise in PCA pre-clinical models, though additional work remains to be done in effectively translating these findings into clinical use

  16. Estrogen intracrinology: therapy and chemoprevention of breast cancer

    Directory of Open Access Journals (Sweden)

    Barbara Licznerska

    2010-05-01

    Full Text Available Breast cancer affects approximately 1 in 10 women and is the leading cause of death in females between the ages of 40 and 50 years in the Western world. The World Health Organization (WHO classified estrogens as carcinogenic in humans and one of the most important risk factors of breast cancer. One of the main arguments has been that estrogens can not only promote cancers but may also initiate mutations caused by certain estrogen metabolites. Therapeutics and chemopreventive agents (e.g. tamoxifen currently in use for breast cancer generally act through an estrogen receptor (ER mechanism and are thus inappropriate for estrogen-independent disease. In the last decade, numerous studies have searched for new therapeutic and preventive agents acting independently of ER status, hence suitable for cases of estrogen-independent breast cancer. In postmenopausal women, when gonads stop producing estrogens, active hormones are produced locally. These locally produced bioactive estrogens exert their actions in the cells of tissues that have not been considered classical hormone-producing sites (i.e. breast cancer tissue and where synthesis occurs without release into the circulation. This mechanism has been termed “intracrinology”, a phenomenon different from the classical concept of endocrinology. Interference in the local production of estrogens seems to be a good alternative to chemotherapy and chemoprevention of breast carcinoma. In this article, crucial enzymes in estrogen’s biosynthesis in the breast and their potential use in therapy and chemoprevention are discussed.

  17. The strategies to control prostate cancer by chemoprevention approaches

    Energy Technology Data Exchange (ETDEWEB)

    Ting, Harold [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO (United States); Deep, Gagan; Agarwal, Chapla [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado, Aurora, CO (United States); Agarwal, Rajesh, E-mail: Rajesh.Agarwal@UCDenver.edu [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado, Aurora, CO (United States)

    2014-02-15

    Prostate cancer (PCA) is the most commonly diagnosed cancer in men in the United States with growing worldwide incidence. Despite intensive investment in improving early detection, PCA often escapes timely detection and mortality remains high; this malignancy being the second highest cancer-associated mortality in American men. Collectively, health care costs of PCA results in an immense financial burden that is only expected to grow. Additionally, even in cases of successful treatment, PCA is associated with long-term and pervasive effects on patients. A proactive alternative to treat PCA is to prevent its occurrence and progression prior to symptomatic malignancy. This may serve to address the issue of burgeoning healthcare costs and increasing number of sufferers. One potential regimen in service of this alternative is PCA chemoprevention. Here, chemical compounds with cancer preventive efficacy are identified on the basis of their potential in a host of categories: their historical medicinal use, correlation with reduced risk in population studies, non-toxicity, their unique chemical properties, or their role in biological systems. PCA chemopreventive agents are drawn from multiple broad classes of chemicals, themselves further subdivided based on source or potential effect, with most derived from natural products. Many such compounds have shown efficacy, varying from inhibiting deregulated PCA cell signaling, proliferation, epithelial to mesenchymal transition (EMT), invasion, metastasis, tumor growth and angiogenesis and inducing apoptosis. Overall, these chemopreventive agents show great promise in PCA pre-clinical models, though additional work remains to be done in effectively translating these findings into clinical use.

  18. Evidence supporting the conceptual framework of cancer chemoprevention in canines.

    Science.gov (United States)

    Kondratyuk, Tamara P; Adrian, Julie Ann Luiz; Wright, Brian; Park, Eun-Jung; van Breemen, Richard B; Morris, Kenneth R; Pezzuto, John M

    2016-01-01

    As with human beings, dogs suffer from the consequences of cancer. We investigated the potential of a formulation comprised of resveratrol, ellagic acid, genistein, curcumin and quercetin to modulate biomarkers indicative of disease prevention. Dog biscuits were evaluated for palatability and ability to deliver the chemopreventive agents. The extent of endogenous DNA damage in peripheral blood lymphocytes from dogs given the dietary supplement or placebo showed no change. However, H2O2-inducible DNA damage was significantly decreased after consumption of the supplement. The expression of 11 of 84 genes related to oxidative stress was altered. Hematological parameters remained in the reference range. The concept of chemoprevention for the explicit benefit of the canine is compelling since dogs are an important part of our culture. Our results establish a proof-of-principle and provide a framework for improving the health and well-being of "man's best friend". PMID:27216246

  19. Cactus pear: a natural product in cancer chemoprevention

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    Wang Jian

    2005-09-01

    Full Text Available Abstract Background Cancer chemoprevention is a new approach in cancer prevention, in which chemical agents are used to prevent cancer in normal and/or high-risk populations. Although chemoprevention has shown promise in some epithelial cancers, currently available preventive agents are limited and the agents are costly, generally with side effects. Natural products, such as grape seed, green tea, and certain herbs have demonstrated anti-cancer effects. To find a natural product that can be used in chemoprevention of cancer, we tested Arizona cactus fruit solution, the aqueous extracts of cactus pear, for its anti-cancer effects in cultured cells and in an animal model. Method Aqueous extracts of cactus pear were used to treat immortalized ovarian and cervical epithelial cells, as well as ovarian, cervical, and bladder cancer cells. Aqueous extracts of cactus pear were used at six concentrations (0, 0.5, 1, 5, 10 or 25% to treat cells for 1, 3, or 5 days. Growth inhibition, apoptosis induction, and cell cycle changes were analyzed in the cultured cells; the suppression of tumor growth in nude mice was evaluated and compared with the effect of a synthetic retinoid N-(4-hydroxyphernyl retinamide (4-HPR, which is currently used as a chemoprevention agent. Immunohistochemistry staining of tissue samples from animal tumors was performed to examine the gene expression. Results Cells exposed to cactus pear extracts had a significant increase in apoptosis and growth inhibition in both immortalized epithelial cells and cancer cells in a dose- and time-dependent manner. It also affected cell cycle of cancer cells by increasing G1 and decreasing G2 and S phases. Both 4-HPR and cactus pear extracts significantly suppressed tumor growth in nude mice, increased annexin IV expression, and decreased VEGF expression. Conclusion Arizona cactus pear extracts effectively inhibited cell growth in several different immortalized and cancer cell cultures, suppressed

  20. Chemoprevention of lung squamous cell carcinoma by ginseng.

    Science.gov (United States)

    Pan, Jing; Zhang, Qi; Li, Kezhen; Liu, Qian; Wang, Yian; You, Ming

    2013-06-01

    Ginseng has been used as a medicinal herb to maintain physical vitality for thousands of years, and it has also been shown to be a nonorgan-specific cancer preventive agent by several epidemiologic studies. However, the chemopreventive effects of Korea white ginseng (KWG) in lung squamous cell carcinoma (SCC) have not been tested. In this study, we investigated the chemopreventive activity of KWG in a mouse lung SCC model. N-nitroso-trischloroethylurea (NTCU) was used to induce lung tumors in female Swiss mice, and KWG was given orally. KWG significantly reduced the percentage of lung SCCs from 26.5% in the control group to 9.1% in the KWG group and in the meantime, increased the percentage of normal bronchial and hyperplasia. KWG was also found to greatly reduce squamous cell lung tumor area from an average of 9.4% in control group to 1.5% in the KWG group. Treatment with KWG decreased Ki-67 staining, suggesting that the lung tumor inhibitory effects of KWG were partly through inhibition of proliferation. High-performance liquid chromatography/mass spectrometry identified 10 ginsenosides from KWG extracts, Rb1 and Rd being the most abundant as detected in mouse blood and lung tissue. The tumor inhibitory effects of KWG are mediated by inhibition of activator protein (AP-1), as showed by in vitro study conducted on AP-1/NF-κB-dependent mouse non-small cell lung carcinoma cell lines. Western blotting of lung tissues also indicated that NTCU upregulated AP-1 through phosphorylation of c-jun-NH2-kinase, which was downregulated by KWG in concurrence with its chemoprevention function. These results suggest that KWG could be a potential chemopreventive agent for lung SCC. PMID:23550152

  1. Chemoprevention--history and general principles.

    Science.gov (United States)

    Wu, Xiangwei; Patterson, Sherri; Hawk, Ernest

    2011-08-01

    Our current understanding of tumourigenesis suggests that cancer develops as a series of cumulative genetic and epigenetic derangements across time culminating in a clone of cells differing from its population of origin in terms of cellular identity, growth control, and its contextual relationship to its environment. Our increasing knowledge of the timing, sequence, frequency, and specific implications of these changes provides unique opportunities for earlier identification of aberrations and preventive interventions. Here we discuss the fundamentals of cancer prevention including the targets, cohorts, agents, endpoints, mechanistic biomarkers, designs, and strategies employed in preventive drug development. There have been many notable successes in this field such as the identification and development of tamoxifen and raloxifene for breast cancer risk reduction, instillational BCG and valrubicin for treatment of preinvasive bladder cancer, and a variety of topical and systemic agents that effectively treat preinvasive neoplastic lesions of the skin. A variety of null or negative developmental endeavours have occurred as well, including trials of beta-carotene for lung cancer prevention, nutritional modifications for colorectal adenoma prevention, and most recently, selenium and alpha-tocopherol for prostate cancer prevention. A third category of prevention trials can be summarized as investigationally successful, but not achieving regulatory success. The development of finasteride and dutasteride for prostate cancer prevention, and celecoxib for colorectal neoplasia prevention fall into this category. In less than four decades, cancer chemoprevention has transformed from a concept to an achievable reality. PMID:22122762

  2. Chemopreventive Effect of Aerosolized Polyphenon E on Lung Tumorigenesis in A/J Mice

    Directory of Open Access Journals (Sweden)

    Ying Yan

    2007-05-01

    Full Text Available Effective chemoprevention of lung cancer in high-risk patients through the administration of pharmacologic or nutritional agents is urgently needed. Aerosol inhalation can deliver chemopreventive agents directly to the respiratory tract to inhibit the tumorigenic process. In this study, polyphenon E (PolyE and (-epigallocatechin-3-gal late (EGCG were administered by aerosol delivery to A/J mice beginning 2 weeks after carcinogen treatment and continuing daily by inhalation throughout the remainder of the study (20 weeks. PolyE decreased tumor load by ∼ 59%. However, EGCG, both at the same dose and at a higher dose, failed to inhibit lung carcinogenesis. These results indicate that aerosol delivery of PolyE, but not EGCG, may be a useful chemopreventive protocol in subjects at high risk for lung cancer.

  3. Chemoprevention of prostate cancer: Natural compounds, antiandrogens, and antioxidants - In vivo evidence

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    Nur Özten-Kandas

    2011-01-01

    Full Text Available Prostate cancer is the leading non-skin malignancy detected in US males and the second cause of death due to male cancer, in the US. Interventions with drugs or diet supplements that slow down the growth and progression of prostate cancer are potentially very effective in reducing the burden of prostate cancer, particularly if these treatments also prevent the de novo development of new prostatic malignancies. Challenges to identify efficacious agents and develop them for chemopreventive application in men at risk for prostate cancer have included uncertainty about which preclinical models have the ability to predict efficacy in men and lack of consensus about which early phase clinical trial designs are the most appropriate and cost-effective to test promising agents. Efficacy studies in animal models have identified several agents with potential chemopreventive activity against prostate cancer, but few of these findings have been translated into clinical trials. This article identifies some of the major issues associated with prostate cancer chemoprevention research and summarizes the most significant current results from animal efficacy studies and human clinical prevention trials. This summary focuses on: (1 Naturally occurring agents and compounds derived from such agents, including green tea and its constituents, silibinin and milk thistle, and genistein and soy, (2 chemoprevention drugs including agents interfering with androgen action, and (3 antioxidants such as selenium, vitamin E, and lycopene. The general lack of activity of antioxidants is discussed, followed by considerations about translation of preclinical chemoprevention efficacy data, focusing on dose, form, bioavailability, and timing of administration of the agent, as well as discussion of study design of clinical trials and the predictive ability of preclinical models.

  4. Chemoprevention of prostate cancer: current status and future directions.

    Science.gov (United States)

    Lieberman, Ronald

    2002-01-01

    Prostate cancer chemoprevention can be described as the administration of natural products and pharmaceutical agents that inhibit one or more steps in the natural history of prostatic carcinogenesis. The principle components of the chemoprevention strategy are closely connected to this natural history and include: (a) agents and their molecular targets; (b) strategic intermediate endpoint biomarkers (IEBs) and their critical pathways; (c) cohorts identified by genetic and acquired risk factors and (d) efficient designs that combine these elements into a cohesive clinical trial. The primary goal is to find effective noncytotoxic agents that modulate the promotion and progression from normal epithelium to dysplasia to high-grade prostatic intraepithelial neoplasia (HGPIN) to locally invasive cancer and metastatic disease. Another important target for chemoprevention is to modulate progression to clinically aggressive disease and to maintain an androgen-sensitive clinical state and delay the emergence of androgen resistance. There is a rationale for use of antiandrogens as the lead class, e.g., 5 alpha receptor inhibitors (5ARI), for chemoprevention of prostate cancer. Nevertheless, the desire to improve the therapeutic index, achieve synergy (5ARI may have only modest anticancer effects) and prevent the emergence of drug (androgen) resistance provide incentives for developing other effective agents and combinations. The availability of more than a dozen classes of noncytotoxic pharmaceutical and natural products already in clinical development create many opportunities for rational combination therapy. Several agent classes have a pharmacodynamic basis for combination with antiandrogens including antiproliferatives, selective estrogen receptor modulators (SERMs), proapoptotic antioxidant micronutrients and selective cyclo-oxygenase (COX)-2 inhibitors. Many other rational pharmacodynamic combinations without antiandrogens are feasible. It is anticipated that in the

  5. LC-MS-Based Metabolomic Investigation of Chemopreventive Phytochemical-Elicited Metabolic Events.

    Science.gov (United States)

    Wang, Lei; Yao, Dan; Chen, Chi

    2016-01-01

    Phytochemicals are under intensive investigation for their potential use as chemopreventive agents in blocking or suppressing carcinogenesis. Metabolic interactions between phytochemical and biological system play an important role in determining the efficacy and toxicity of chemopreventive phytochemicals. However, complexities of phytochemical biotransformation and intermediary metabolism pose challenges for studying phytochemical-elicited metabolic events. Metabolomics has become a highly effective technical platform to detect subtle changes in a complex metabolic system. Here, using green tea polyphenols as an example, we describe a workflow of LC-MS-based metabolomics study, covering the procedures and techniques in sample collection, preparation, LC-MS analysis, data analysis, and interpretation. PMID:26608291

  6. Genistein chemoprevention of prostate cancer in TRAMP mice

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    Eltoum Isam-Eldin

    2007-01-01

    Full Text Available Abstract Epidemiological studies suggest an inverse association between soy intake and prostate cancer risk. Genistein, the predominant phytoestrogen in soy food, has been proposed as a potential chemopreventive agent due to its anti-estrogen and tyrosine kinase inhibitory effects. To determine the most effective period for genistein chemoprevention, the Transgenic adenocarcinoma mouse prostate (TRAMP model was used. The treatments were 250 mg genistein/kg AIN-76A diet 1 prepubertally only, 2 in adulthood only or 3 through out life. Controls received AIN-76A diet. By 28 weeks of age, 100% TRAMP mice fed control diet developed prostatic intraepithelial neoplasia (PIN or adenocarcinomas with 6%, 16%, 44% and 34% developing high grade PIN, well differentiated, moderately differentiated and poorly differentiated prostatic adenocarcinomas, respectively. Prepubertal only (1–35 days postpartum and adult only genistein treatments (12 – 28 weeks resulted in 6% and 29% decreases in poorly-differentiated cancerous lesions compared with controls, respectively. The most significant effect was seen in the TRAMP mice exposed to genistein throughout life (1–28 weeks with a 50% decrease in poorly-differentiated cancerous lesions. In a separate experiment in castrated TRAMP mice, dietary genistein suppressed the development of advanced prostate cancer by 35% compared with controls. Of the tumors that developed in castrated TRAMP mice, 100% were poorly-differentiated in contrast to the 37% of noncastrated TRAMP mice that developed poorly-differentiated tumors. ICI 182,780 (ICI, genistein and estrogen down-regulated androgen receptor (AR, estrogen receptor alpha (ER-α and progesterone receptor (PR in the prostates of C57BL/6 mice, and act independently of ER. Our data obtained in intact and castrated transgenic mice suggest that genistein may be a promising chemopreventive agent against androgen-dependent and independent prostate cancers.

  7. Hedera nepalensis K. Koch: A Novel Source of Natural Cancer Chemopreventive and Anticancerous Compounds.

    Science.gov (United States)

    Jafri, Laila; Saleem, Samreen; Kondrytuk, Tamara P; Haq, Ihsan-ul; Ullah, Nazif; Pezzuto, John M; Mirza, Bushra

    2016-03-01

    Traditional medicinal plants are often used for both the prevention and the treatment of local diseases. Taking into consideration the medicinal importance of Hedera nepalensis within local Pakistani traditions, the present study was undertaken to analyze the in vitro cancer chemopreventive and cytotoxic properties of the plant. The in vitro cancer chemopreventive testing was performed using nitrite assay, NFκB assay, aromatase assay, and quinone reductase 1 (QR1) assay. The cytotoxic potential was evaluated on three cancer-cell lines: MCF-7, MDA-MB-231, and HeLa using sulforhodamine B (SRB) assay. The results of cancer chemopreventive assays show that n-hexane and ethyl acetate fractions of tested plant have promising cancer chemopreventive potential. Lupeol isolated from n-hexane as well as ethyl acetate fraction showed lowest IC50 (0.20 ± 1.9 μM) in NFκB assay. Crude extract and its fractions inhibited the growth of three cancer cell lines by more than 60%, IC50 value of lupeol varied from 2.32 to 10.2 μM. HPLC-DAD-based quantification of lupeol in different plant tissues demonstrated that leaves of H. nepalensis are a rich source of lupeol (0.196 mg/100 mg dry weight). Our data have shown that H. nepalensis harbors cancer chemopreventive and cytotoxic agents. PMID:26692176

  8. Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

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    Chong-Zhi Wang

    2015-09-01

    Full Text Available Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possesses antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the enteric microbiome before being absorbed. The major metabolites, ginsenoside Rg3 and compound K, showed significant potent anticancer activity compared to that of their parent ginsenosides Rb1, Rc, and Rd. In this review, the molecular mechanisms of ginseng metabolites on cancer chemoprevention, especially apoptosis and angiogenic inhibition, are discussed. Ginseng gut microbiome metabolites showed significant anti-angiogenic effects on pulmonary, gastric and ovarian cancers. This review suggests that in addition to the chemopreventive effects of ginseng compounds, as angiogenic inhibitors, ginsenoside metabolites could be used in combination with other cancer chemotherapeutic agents in cancer management.

  9. Chemoprevention of Radiation Induced Rat Mammary Neoplasms

    Science.gov (United States)

    Huso, David L.

    1999-01-01

    Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable

  10. Pro-oxidant activity of dietary chemopreventive agents: an under-appreciated anti-cancer property [v1; ref status: indexed, http://f1000r.es/15s

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    Asfar S Azmi

    2013-06-01

    Full Text Available “Let food be thy medicine and medicine be thy food” was quoted by Hippocrates more than two thousand years ago and since ancient times the health benefits of different natural agents have been exploited. In modern research, the disease preventive benefits of many such natural agents, particularly dietary compounds and their derivatives, has been attributed to their well recognized activity as the regulators of redox state of the cell. Nevertheless, most of these studies have focused on their antioxidant activity. A large body of evidence indicates that a major fraction of these agents can elicit pro-oxidant (radical generating behavior which has been linked to their anti-cancer effects. This editorial provides an overview of the under-appreciated pro-oxidant activity of natural products, with a special focus on their ability to generate reactive oxygen species in the presence of transition metal ions, and discusses their possible use as cancer chemotherapeutic agents.

  11. Chemopreventive effect of Lagenaria siceraria in two stages DMBA plus croton oil induced skin papillomagenesis.

    Science.gov (United States)

    Kumar, Navneet; Kale, Raosaheb K; Tiku, Ashu B

    2013-01-01

    Cancer chemoprevention is a dietary or therapeutic strategy to prevent, suppress, or delay carcinogenesis either at initiation or progression level with nontoxic agents. Use of natural dietary compounds has been a major chemopreventive approach to modulate tumorigenic pathways. In the present study, we have evaluated Lagenaria siceraria (bottle gourd), a common vegetable of Indian household for its chemomodulatory potential. The fruit has been used in traditional medicine for a very long time for health benefits and to cure pain, ulcers, fever, cough, asthma, and other bronchial disorders. However, despite its reported beneficial effect the chemo modulatory potential of this plant has not been reported. Therefore chemopreventive effect of bottle gourd juice (BGJ) was studied against 7,12-dimethylbenz(a)anthracene (DMBA) plus croton oil induced skin papillomagenesis in Swiss albino mice. The effect was studied both at antiinitiation and antiinitiation/promotion level followed by histopathological study. A dose of 2.5% and 5% given in drinking water showed significant decrease in papilloma number, papilloma incidence, papilloma multiplicity, papilloma latency, papilloma volume, and papilloma size in different size range. Histopathological study showed chemopreventive effect by minimizing loss of stratification, a decrease in number of epithelial layers, reducing dermal infiltration and protection for various cytoplasmic changes. Higher dose of BGJ was found to be more effective than lower dose and the chemopreventive effect was maximum for antiinitiation/promotion treatment. Altogether, this study reports the chemopreventive effect of Lagenaria siceraria on skin papillomagenesis for the first time and suggests that its consumption may help in suppression of skin cancer. PMID:23914728

  12. Ellagitannins in Cancer Chemoprevention and Therapy.

    Science.gov (United States)

    Ismail, Tariq; Calcabrini, Cinzia; Diaz, Anna Rita; Fimognari, Carmela; Turrini, Eleonora; Catanzaro, Elena; Akhtar, Saeed; Sestili, Piero

    2016-01-01

    It is universally accepted that diets rich in fruit and vegetables lead to reduction in the risk of common forms of cancer and are useful in cancer prevention. Indeed edible vegetables and fruits contain a wide variety of phytochemicals with proven antioxidant, anti-carcinogenic, and chemopreventive activity; moreover, some of these phytochemicals also display direct antiproliferative activity towards tumor cells, with the additional advantage of high tolerability and low toxicity. The most important dietary phytochemicals are isothiocyanates, ellagitannins (ET), polyphenols, indoles, flavonoids, retinoids, tocopherols. Among this very wide panel of compounds, ET represent an important class of phytochemicals which are being increasingly investigated for their chemopreventive and anticancer activities. This article reviews the chemistry, the dietary sources, the pharmacokinetics, the evidence on chemopreventive efficacy and the anticancer activity of ET with regard to the most sensitive tumors, as well as the mechanisms underlying their clinically-valuable properties. PMID:27187472

  13. Ellagitannins in Cancer Chemoprevention and Therapy

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    Tariq Ismail

    2016-05-01

    Full Text Available It is universally accepted that diets rich in fruit and vegetables lead to reduction in the risk of common forms of cancer and are useful in cancer prevention. Indeed edible vegetables and fruits contain a wide variety of phytochemicals with proven antioxidant, anti-carcinogenic, and chemopreventive activity; moreover, some of these phytochemicals also display direct antiproliferative activity towards tumor cells, with the additional advantage of high tolerability and low toxicity. The most important dietary phytochemicals are isothiocyanates, ellagitannins (ET, polyphenols, indoles, flavonoids, retinoids, tocopherols. Among this very wide panel of compounds, ET represent an important class of phytochemicals which are being increasingly investigated for their chemopreventive and anticancer activities. This article reviews the chemistry, the dietary sources, the pharmacokinetics, the evidence on chemopreventive efficacy and the anticancer activity of ET with regard to the most sensitive tumors, as well as the mechanisms underlying their clinically-valuable properties.

  14. [Chemoprevention of prostate cancer - a plea].

    Science.gov (United States)

    Schmitz-Dräger, B J; Bismarck, E; Schöffski, O; Fischer, C

    2012-05-01

    The high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make the diagnosis of and therapy for prostate cancer a special challenge for urologists. Effective prevention of the disease may help to improve some of the problems mentioned above. Two randomised, controlled studies have proved that effective chemoprevention of prostate cancer is viable using 5α-reductase inhibitors (finasteride, dutasteride). Furthermore, there is increasing evidence that other compounds, e. g., selective oestrogen receptor modulators (SERMs), NSAIDs and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economical aspects. The authors conclude that the options of chemoprevention should be investigated in an open and unbiased way. PMID:22639024

  15. Advances in prostate cancer chemoprevention: a translational perspective.

    Science.gov (United States)

    Nambiar, Dhanya; Singh, Rana P

    2013-01-01

    Chemopreventive interventions are steadily emerging as an important aspect of cancer management and control. Herein, we have discussed the major epidemiological and clinical studies advocating the role of androgen inhibitors, flavonoids and antioxidants in preventing prostate cancer (PCa). Androgen inhibitors have lately been discussed not only in treatment of PCa, but also as preventive agents especially after trials with Finasteride and Dutasteride. Flavonoids such as silibinin, green tea polyphenols, genistein, curcumin have shown great promise, but avenues to improve their bioavailability are requisite. Agents with antioxidant potentials like lycopene, selenium, and vitamin E have also been explored. Antioxidant trials have yielded mixed results or benefitted only a subgroup of population, although further studies are needed to establish them as preventive agent. Although a majority of the trials resulted in positive outcomes supporting their role as preventive agents; one should be cautious of neutral or negative results as well. For clinical applicability of these agents, we need to identify the ideal target population, time of intervention, appropriate dosage, and extent of intervention required. Incoherency of data with these agents urges for a stringent study design and thorough interpretation to accurately judge the necessity and feasibility of the preventive measures. PMID:23682779

  16. The role of aspirin in colorectal cancer chemoprevention.

    Science.gov (United States)

    Singh Ranger, Gurpreet

    2016-08-01

    Considerable interest has emerged over the last decade regarding the role of aspirin in prevention of colorectal cancer. This disease is one of the commonest cancers in the Western World, therefore, the existence of a simple "everyday" agent, which could have the ability to prevent the disease, represents an invaluable opportunity clinicians may be able to exploit. Evidence from case-control and cohort studies, and recent updates of randomised controlled trials have been very encouraging-indicating benefit from long term use of aspirin at low dose. Possible mechanisms of chemoprevention include inhibition of the cyclooxygenase (COX) pathway, or COX-independent mechanisms, for example, the PIK3CA pathway, or therapy-induced senescence of cancer cells. The most serious side effect of prolonged aspirin treatment is haemorrhage, especially from the GI tract. This is likely to be less of a problem with chemoprevention at lower doses. One also needs to consider the impact if aspirin resistance, an increasingly recognised clinical entity. PMID:27289249

  17. COX-independent mechanisms of cancer chemoprevention by anti-inflammatory drugs

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    Evrim eGurpinar

    2013-07-01

    Full Text Available Epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs, including cyclooxygenase (COX-2 selective inhibitors, reduce the risk of developing cancer. Experimental studies in human cancer cell lines and rodent models of carcinogenesis support these observations by providing strong evidence for the antineoplastic properties of NSAIDs. The involvement of COX-2 in tumorigenesis and its overexpression in various cancer tissues suggest that inhibition of COX-2 is responsible for the chemopreventive efficacy of these agents. However, the precise mechanisms by which NSAIDs exert their antiproliferative effects are still a matter of debate. Numerous other studies have shown that NSAIDs can act through COX-independent mechanisms. This review provides a detailed description of the major COX-independent molecular targets of NSAIDs and discusses how these targets may be involved in their anticancer effects. Toxicities resulting from COX inhibition and the suppression of prostaglandin synthesis preclude the long-term use of NSAIDs for cancer chemoprevention. Furthermore, chemopreventive efficacy is incomplete and treatment often leads to the development of resistance. Identification of alternative NSAID targets and elucidation of the biochemical processes by which they inhibit tumor growth could lead to the development of safer and more efficacious drugs for cancer chemoprevention.

  18. Acteoside-mediates chemoprevention of experimental liver carcinogenesis through STAT-3 regulated oxidative stress and apoptosis.

    Science.gov (United States)

    Peerzada, Kaiser J; Faridi, Aamir H; Sharma, Love; Bhardwaj, Subhash C; Satti, Naresh K; Shashi, Bhushan; Tasduq, Sheikh A

    2016-07-01

    In the absence of an effective therapy against Hepatocellular Carcinoma (HCC), chemoprevention remains an important strategy to circumvent morbidity and mortality. Here, we examined chemopreventive potential of Acteoside (ACT), a plant derived phenylethanoid glycoside against an environmental and dietary carcinogen, diethylnitrosamine (DEN)-induced rat hepatocarcinogenesis. ACT treatment (0.1 and 0.3% supplemented with diet) started 2 weeks before DEN challenge and continued for 18 weeks thereafter, showed a remarkable chemopreventive activity. ACT treatment resulted in reduced HCC nodules. Histopathology showed progressive tissue damage, necrosis (5 weeks), hepatocytic injury (10 weeks), anisonucleosis with presence of prominent nucleoli, sinusidal dilations, and lymphomono nuclear inflammation (18 weeks). Biochemical analysis showed hepatocytic injury (raised ALT, p reactive oxygen species (ROS) levels and prevented mitochondrial membrane potential (MMP) loss. Immunoblotting showed ACT treatment reversed DEN-induced NF-κB, Bax, Cytochrome C, Bcl-2, and Stat-3 levels. We conclude that chemoprotective effect of ACT is mediated by STAT-3 dependent regulation of oxidative stress and apoptosis and ACT has potential to be developed as a chemopreventive agent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 782-798, 2016. PMID:26990576

  19. Repurposing old drugs to chemoprevention: the case of metformin.

    Science.gov (United States)

    Heckman-Stoddard, Brandy M; Gandini, Sara; Puntoni, Matteo; Dunn, Barbara K; DeCensi, Andrea; Szabo, Eva

    2016-02-01

    Multiple epidemiologic studies have documented an association between the anti-diabetic agent metformin and reduced cancer incidence and mortality. However, this effect has not been consistently demonstrated in animal models or more recent epidemiological studies. The purpose of this paper is to examine metformin's chemopreventive potential by reviewing relevant mechanisms of action, preclinical evidence of efficacy, updated epidemiologic evidence after correction for potential biases and confounders, and recently completed and ongoing clinical trials. Although repurposing drugs with well described mechanisms of action and safety profiles is an appealing strategy for cancer prevention, there is no substitute for well executed late phase clinical trials to define efficacy and populations that are most likely to benefit from an intervention. PMID:26970131

  20. Injectable Sustained Release Microparticles of Curcumin: A New Concept for Cancer Chemoprevention

    OpenAIRE

    Shahani, Komal; Swaminathan, Suresh Kumar; Freeman, Diana; Blum, Angela; Ma, Linan; Panyam, Jayanth

    2010-01-01

    Poor oral bioavailability limits the use of curcumin and other dietary polyphenols in the prevention and treatment of cancer. Minimally invasive strategies that can provide effective and sustained tissue concentrations of these agents will be highly valuable tools in the fight against cancer. The objective of this study was to investigate the use of an injectable sustained release microparticle formulation of curcumin as a novel approach to breast cancer chemoprevention. A biodegradable and b...

  1. STAT3 as a chemoprevention target in carcinogen-induced head and neck squamous cell carcinoma.

    OpenAIRE

    Peyser, ND; Wang, L.; Zeng, Y.; Acquafondata, M.; Freilino, ML; Li, H.; M. Sen; Gooding, WE; Satake, M; Wang, Z.; Johnson; Grandis, JR

    2016-01-01

    Head and neck squamous cell carcinoma (HNSCC) is a frequently fatal disease due in large part to a high rate of second primary tumor (SPT) formation. The 4-nitroquinoline 1-oxide (4-NQO) mouse model of oral carcinogenesis provides a robust system in which to study chemopreventive agents in the context of chemically-induced HNSCC tumors. Signal transducer and activator of transcription 3 (STAT3) is a potent oncogene that is hyperactivated by tyrosine phosphorylation early in HNSCC carcinogenes...

  2. Chemoprevention of prostate cancer: Natural compounds, antiandrogens, and antioxidants - In vivo evidence

    OpenAIRE

    Nur Özten-Kandas; Bosland, Maarten C.

    2011-01-01

    Prostate cancer is the leading non-skin malignancy detected in US males and the second cause of death due to male cancer, in the US. Interventions with drugs or diet supplements that slow down the growth and progression of prostate cancer are potentially very effective in reducing the burden of prostate cancer, particularly if these treatments also prevent the de novo development of new prostatic malignancies. Challenges to identify efficacious agents and develop them for chemopreventive appl...

  3. Multitargeted Low-Dose GLAD Combination Chemoprevention: A Novel and Promising Approach to Combat Colon Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Altaf Mohammed

    2013-05-01

    Full Text Available Preclinical studies have shown that gefitinib, licofelone, atorvastatin, and α-difluoromethylornithine (GLAD are promising colon cancer chemopreventive agents. Because low-dose combination regimens can offer potential additive or synergistic effects without toxicity, GLAD combination was tested for toxicity and chemopreventive efficacy for suppression of intestinal tumorigenesis in adenomatous polyposis coli (APCMin/+ mice. Six-week-old wild-type and APCMin/+ mice were fed modified American Institute of Nutrition 76A diets with or without GLAD (25 + 50 + 50 + 500 ppm for 14 weeks. Dietary GLAD caused no signs of toxicity based on organ pathology and liver enzyme profiles. GLAD feeding strongly inhibited (80–83%, P 95% fewer polyps with sizes of >2 mm compared with control mice and showed 75% and 85% inhibition of colonic tumors in males and females, respectively. Molecular analyses of polyps suggested that GLAD exerts efficacy by inhibiting cell proliferation, inducing apoptosis, decreasing β-catenin and caveolin-1 levels, increasing caspase-3 cleavage and p21, and modulating expression profile of inflammatory cytokines. These observations demonstrate that GLAD, a novel cocktail of chemopreventive agents at very low doses, suppresses intestinal tumorigenesis in APCMin/+ mice with no toxicity. This novel strategy to prevent colorectal cancer is an important step in developing agents with high efficacy without unwanted side effects.

  4. Ellagitannins in Cancer Chemoprevention and Therapy

    OpenAIRE

    Tariq Ismail; Cinzia Calcabrini; Anna Rita Diaz; Carmela Fimognari; Eleonora Turrini; Elena Catanzaro; Saeed Akhtar; Piero Sestili

    2016-01-01

    It is universally accepted that diets rich in fruit and vegetables lead to reduction in the risk of common forms of cancer and are useful in cancer prevention. Indeed edible vegetables and fruits contain a wide variety of phytochemicals with proven antioxidant, anti-carcinogenic, and chemopreventive activity; moreover, some of these phytochemicals also display direct antiproliferative activity towards tumor cells, with the additional advantage of high tolerability and low toxicity. The most i...

  5. Learning Object Repositories

    Science.gov (United States)

    Lehman, Rosemary

    2007-01-01

    This chapter looks at the development and nature of learning objects, meta-tagging standards and taxonomies, learning object repositories, learning object repository characteristics, and types of learning object repositories, with type examples. (Contains 1 table.)

  6. Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: implications for chemoprevention

    OpenAIRE

    Jeremy J Johnson; Syed, Deeba N.; Suh, Yewseok; Heren, Chenelle R.; Saleem, Mohammad; Siddiqui, Imtiaz A.; Mukhtar, Hasan

    2010-01-01

    Emerging data is suggesting that estrogens, in addition to androgens, may also be contributing to the development of prostate cancer (PCa). In view of this notion agents that target estrogens, in addition to androgens, may be a novel approach for PCa chemoprevention and treatment. Thus, the identification and development of non-toxic dietary agents capable of disrupting androgen receptor (AR) in addition to estrogen receptor (ER) could be extremely useful in the management of PCa. Through mol...

  7. Capsaicin: A novel chemopreventive molecule and its underlying molecular mechanisms of action

    Directory of Open Access Journals (Sweden)

    A A Oyagbemi

    2010-01-01

    Full Text Available Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide is the a principal pungent ingredient of hot red and chili peppers that belong to the plant genus Capsicum (Solanaceae. Capsaicin is a cancer-suppressing agent. It blocks the translocation of nuclear factor kappa B (NF-kB, activator protein 1 (AP-1, and signal transducer and activator of transcription (STAT3 signaling pathway that are required for carcinogenesis. The anti-inflammatory potential of capsaicin is attributed to its inhibitory effect on inducible COX-2 mRNA expression. Cytochrome P4502E1 mediates the activation of xenobiotics such as vinyl carbamate and dimethyl nitrosamine to their toxic metabolites. This metabolic activation of xenobiotics by Cytochrome P4502E1 has been shown to be inhibited by capsaicin. Capsaicin also generates reactive oxygen species in cells with resultant induction of apoptosis and cell cycle arrest, which is beneficial for cancer chemoprevention. Therefore, the use of capsaicin as a chemopreventive agent is of immense benefit for cancer chemoprevention. The search strategy included printed journals, pubmed, and medline, using the terms ′capsaicin′ and ′anticancer′ citations, relevant to anticancer properties of capsaicin.

  8. Targeting specific cell signaling transduction pathways by dietary and medicinal phytochemicals in cancer chemoprevention

    International Nuclear Information System (INIS)

    Natural phytochemicals derived from dietary sources or medicinal plants have gained significant recognition in the potential management of several human clinical conditions. Much research has also been geared towards the evaluation of plant extracts as effective prophylactic agents since they can act on specific and/or multiple molecular and cellular targets. Plants have been an abundant source of highly effective phytochemicals which offer great potential in the fight against cancer by inhibiting the process of carcinogenesis through the upregulation of cytoprotective genes that encode for carcinogen detoxifying enzymes and antioxidant enzymes. The mechanistic insight into chemoprevention further includes induction of cell cycle arrest and apoptosis or inhibition of signal transduction pathways mainly the mitogen-activated protein kinases (MAPK), protein kinases C (PKC), phosphoinositide 3-kinase (PI3K), glycogen synthase kinase (GSK) which lead to abnormal cyclooxygenase-2 (COX-2), activator protein-1 (AP-1), nuclear factor-kappaB (NF-κB) and c-myc expression. Effectiveness of chemopreventive agents reflects their ability to counteract certain upstream signals that leads to genotoxic damage, redox imbalances and other forms of cellular stress. Targeting malfunctioning molecules along the disrupted signal transduction pathway in cancer represent a rational strategy in chemoprevention. NF-κB and AP-1 provide mechanistic links between inflammation and cancer, and moreover regulate tumor angiogenesis and invasiveness, indicating that signaling pathways that mediate their activation provide attractive targets for new chemotherapeutic approaches. Thus cell signaling cascades and their interacting factors have become important targets of chemoprevention and phenolic phytochemicals and plant extracts seem to be promising in this endeavor.

  9. Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Chen-Yi Liao

    2015-01-01

    Full Text Available We would like to highlight the application of natural products to hepatocellular carcinoma (HCC. We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signaling pathways and serve as antioxidants. In this review, we will discuss seven common flavonoids that exert different biological effects against HCC via different pathways.

  10. Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

    OpenAIRE

    Chen-Yi Liao; Ching-Chang Lee; Chi-chang Tsai; Chao-Wen Hsueh; Chih-Chiang Wang; I-Hung Chen; Ming-Kai Tsai; Mei-Yu Liu; An-Tie Hsieh; Kuan-Jen Su; Hau-Ming Wu; Shih-Chung Huang; Yi-Chen Wang; Chien-Yao Wang; Shu-Fang Huang

    2015-01-01

    We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, ...

  11. Flavonoids as Chemopreventive and Therapeutic Agents Against Lung Cancer

    Directory of Open Access Journals (Sweden)

    Albert Cabrera

    2014-05-01

    Full Text Available The objective of the present review is to study the relationship between flavonoids and lung cancer, proposing that their regular consumption in Western diets could be beneficial for protecting patients against lung cancer. An extensive search of the scientific literature was performed in the following electronic specialized databases (PubMed central (PMC-NBCI, Elsevier Journal, SciELO Spain, Scirus, Science Direct, including studies in animals, cells, and humans, in order to establish the effect of flavonoids in the prevention and development of lung cancer. Although in vitro and animal studies show the potential ability of flavonoids to act against different types of cancers, especially against lung cancers, the diverse results reported within epidemiological studies, together with the lack of experiments in humans, are the major factors in limiting making dietary recommendations based on scientific evidence for the management of patients with lung cancer. Therefore, the authors of the present study recommend following the dietary health practice guidelines which promotes the consumption of food enriched in flavonoids and reflects the current state of knowledge of an effective and appropriate diet in lung cancer patients.Erratum in: Rev Esp Nutr Hum Diet. 2013;17(2:91-92Link: http://www.renhyd.org/index.php/renhyd/article/view/6/17

  12. The influence of organic complexing agents upon the mobilization and migration of radionuclides from ILW contained in cement and bitumen under nearfield conditions for a repository in a salt dome

    International Nuclear Information System (INIS)

    Within the frame of this project the influence of the synthetic organic complexing agents dibutylphosphate, tributylphosphate, ethylenediamine-tetra acetic acid, citrate and oxalate on the solubilities, the migration and sorption behaviour of the elements iodine, cesium, uranium neptunium, plutonium and americium was investigated in electrolyte solutions, representing the conditions of a near field of a waste repository in a salt dome after an intrusion of brines, considered as a hypothetical scenario. The electrolyte solutions were saturated NaCl solution and Q-brine, which were equilibrated with corrosion products of the matrices Portland 35-F cement and bitumen (Shell Mexphalte R 80-100) before starting the experiments, in order to simulate their influence on the chemical behaviour of the solutions used for the experiments. The temperature, at which the experiments were carried out, was 298 K. After determining the relevant pH- and Eh-values, pH was adapted to 12.3 for saturated NaCl solution equilibrated with cement and to 6.4 for Q-brine also being at equilibrium with cement. The electrolyte systems on the other hand containing bitumen were kept at those pH-values, which resulted from saturation with the complexing agents. 120 tabs., 87 figs., 67 refs

  13. Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Shirode AB

    2015-01-01

    Full Text Available Amit B Shirode,1,2,* Dhruba J Bharali,3,* Sameera Nallanthighal,1,2 Justin K Coon,1,2 Shaker A Mousa,3 Ramune Reliene1,2 1Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA; 2Cancer Research Center, University at Albany, Rensselaer, NY, USA; 3Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA *These authors contributed equally to this work Abstract: Pomegranate polyphenols are potent antioxidants and chemopreventive agents but have low bioavailability and a short half-life. For example, punicalagin (PU, the major polyphenol in pomegranates, is not absorbed in its intact form but is hydrolyzed to ellagic acid (EA moieties and rapidly metabolized into short-lived metabolites of EA. We hypothesized that encapsulation of pomegranate polyphenols into biodegradable sustained release nanoparticles (NPs may circumvent these limitations. We describe here the development, characterization, and bioactivity assessment of novel formulations of poly(D,L-lactic-co-glycolic acid–poly(ethylene glycol (PLGA–PEG NPs loaded with pomegranate extract (PE or individual polyphenols such as PU or EA. Monodispersed, spherical 150–200 nm average diameter NPs were prepared by the double emulsion–solvent evaporation method. Uptake of Alexa Fluor-488-labeled NPs was evaluated in MCF-7 breast cancer cells over a 24-hour time course. Confocal fluorescent microscopy revealed that PLGA–PEG NPs were efficiently taken up, and the uptake reached the maximum at 24 hours. In addition, we examined the antiproliferative effects of PE-, PU-, and/or EA-loaded NPs in MCF-7 and Hs578T breast cancer cells. We found that PE, PU, and EA nanoprototypes had a 2- to 12-fold enhanced effect on cell growth inhibition compared to their free counterparts, while void NPs did not affect cell growth. PU-NPs were the most potent nanoprototype of pomegranates. Thus, PU may be the

  14. Anthocyans from fruits and vegetables--does bright colour signal cancer chemopreventive activity?

    Science.gov (United States)

    Cooke, Darren; Steward, William P; Gescher, Andreas J; Marczylo, Tim

    2005-09-01

    Consumption of fruits and berries has been associated with decreased risk of developing cancer. The most abundant flavonoid constituents of fruits and berries are anthocyans (i.e. anthocyanins, glycosides, and their aglycons, anthocyanidins) that cause intense colouration. In this review, we describe epidemiological evidence hinting at the cancer preventive activity of anthocyan-containing foods in humans, results of chemoprevention studies in rodent models with anthocyans or anthocyan-containing fruit/vegetable extracts, and pharmacological properties of anthocyans. Anthocyanidins have been shown to inhibit malignant cell survival and confound many oncogenic signalling events in the 10(-6)-10(-4) M concentration range. Studies of the pharmacokinetics of anthocyanins after their consumption as single agents, anthocyanin mixtures or berry extracts suggest that anthocyanins reach levels of 10(-8)-10(-7) M in human blood. It is unclear whether such concentrations are sufficient to explain anticarcinogenic effects, and whether anthocyanins exert chemopreventive efficacy themselves, or if they need to undergo hydrolysis to their aglyconic counterparts. The currently available literature provides tantalising hints of the potential usefulness of anthocyans or anthocyan mixtures as cancer chemopreventive interventions. Nevertheless further studies are necessary to help adjudge the propitiousness of their clinical development. PMID:16084717

  15. Novel aspects for the application of Curcumin in chemoprevention of various cancers.

    Science.gov (United States)

    Bachmeier, Beatrice E; Killian, Peter; Pfeffer, Ulrich; Nerlich, Andreas G

    2010-01-01

    Chemoprevention of malignant tumor growth is a novel and potentially powerful approach for tumor therapy. Recent in vitro and in vivo investigations provide increasing evidence that naturally occurring substances may exhibit significant chemopreventive activities. To this regard, the spice Curcumin, widely used in Indian cuisine, has been identified to show considerable anti-tumor effects. Most interestingly, numerous studies have not shown toxic side effects of this substance. Curcumin induces tumor cell apoptosis along with a reduction of tumor cell invasion and metastasis. Recent molecular studies provide evidence that Curcumin acts via a control of the NFkappaB pathway exerting most of the various modulating and moderating effects on malignant cells. Along with these in vitro studies, ex vivo and first clinical investigations confirm the anti-tumor effects of Curcumin, either as an isolated chemoprevention substance or in combination with chemotherapeutic agents as supportive measure reducing pharmaceutical resistance of tumor cells to certain chemotherapeutics. Despite our increasing knowledge on this interesting substance there still remain many unknown effects that deserve intense investigation. PMID:20036978

  16. Chemopreventive effect of Quercus infectoria against chemically induced renal toxicity and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Muneeb U Rehman

    2012-06-01

    Full Text Available In this study we have shown that Quercus infectoria attenuates Fe- NTA induced renal oxidative stress, hyperproliferative response and renal carcinogenesis in rats. Fe-NTA promoted DEN (N-diethyl nitrosamine initiated renal carcinogenesis by increasing the percentage incidence of tumors and induces early tumor markers viz. ornithine decarboxylase (ODC level and PCNA expression. Fe- NTA (9 mg Fe/kg body weight, intraperitoneally enhances renal Malondialdehyde, xanthine oxidase and hydrogen peroxide generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolizing enzymes such as glutathione-S-transferase and quinone reductase. It also enhances blood urea nitrogen and serum creatinine. Fe-NTA also lead to increase in levels of some inflammatory markers viz NO and MPO and some proinflammatory cytokines viz PGE-2 and TNF-1. The chemopreventive efficacy of Quercus infectoria was studied in terms of xenobiotic metabolizing enzyme activities, LPO, redox status, serum toxicity markers, inflammatory and proinflammatory markers and cell proliferation in the kidney tissue. Oral administration of Quercus infectoria at doses of 75 and 150 mg/kg b wt effectively suppressed renal oxidative stress, inflammation and tumor incidence. Chemopreventive effects of Quercus infectoria were associated with up-regulation of xenobiotic metabolizing enzyme activities and down regulation of serum toxicity markers. Present study supports Quercus infectoria as a potent chemopreventive agent and suppresses Fe-NTA-induced renal carcinogenesis and oxidative and inflammatory response in Wistar rat.

  17. Phyto-oestrogens and breast cancer chemoprevention

    International Nuclear Information System (INIS)

    Phytoestrogens are polyphenol compounds of plant origin that exhibit a structural similarity to the mammalian steroid hormone 17β-oestradiol. In Asian nations the staple consumption of phyto-oestrogen-rich foodstuffs correlates with a reduced incidence of breast cancer. Human dietary intervention trials have noted a direct relationship between phyto-oestrogen ingestion and a favourable hormonal profile associated with decreased breast cancer risk. However, these studies failed to ascertain the precise effect of dietary phyto-oestrogens on the proliferation of mammary tissue. Epidemiological and rodent studies crucially suggest that breast cancer chemoprevention by dietary phyto-oestrogen compounds is dependent on ingestion before puberty, when the mammary gland is relatively immature. Phyto-oestrogen supplements are commercially marketed for use by postmenopausal women as natural and safe alternatives to hormone replacement therapy. Of current concern is the effect of phyto-oestrogen compounds on the growth of pre-existing breast tumours. Data are contradictory, with cell culture studies reporting both the oestrogenic stimulation of oestrogen receptor-positive breast cancer cell lines and the antagonism of tamoxifen activity at physiological phyto-oestrogen concentrations. Conversely, phyto-oestrogen ingestion by rodents is associated with the development of less aggressive breast tumours with reduced metastatic potential. Despite the present ambiguity, current data do suggest a potential benefit from use of phyto-oestrogens in breast cancer chemoprevention and therapy. These aspects are discussed

  18. Cancer Chemopreventive Ability of Conjugated Linolenic Acids

    Directory of Open Access Journals (Sweden)

    Kazuo Miyashita

    2011-11-01

    Full Text Available Conjugated fatty acids (CFA have received increased interest because of their beneficial effects on human health, including preventing cancer development. Conjugated linoleic acids (CLA are such CFA, and have been reviewed extensively for their multiple biological activities. In contrast to other types of CFAs including CLA that are found at low concentrations (less than 1% in natural products, conjugated linolenic acids (CLN are the only CFAs that occur in higher quantities in natural products. Some plant seeds contain a considerably high concentration of CLN (30 to 70 wt% lipid. Our research group has screened CLN from different plant seed oils to determine their cancer chemopreventive ability. This review describes the physiological functions of CLN isomers that occur in certain plant seeds. CLN are able to induce apoptosis through decrease of Bcl-2 protein in certain human cancer cell lines, increase expression of peroxisome proliferator-activated receptor (PPAR-γ, and up-regulate gene expression of p53. Findings in our preclinical animal studies have indicated that feeding with CLN resulted in inhibition of colorectal tumorigenesis through modulation of apoptosis and expression of PPARγ and p53. In this review, we summarize chemopreventive efficacy of CLN against cancer development, especially colorectal cancer.

  19. Chemoprevention of prostate cancer by isoflavonoids.

    Science.gov (United States)

    Aufderklamm, Stefan; Miller, Florian; Galasso, Anastasia; Stenzl, Arnulf; Gakis, Georgios

    2014-01-01

    In Europe, prostate cancer (PC) is the most common malignancy in males. There are three known risk factors strongly coherent to the development of PC: heredity, ethnical origin, and age. Migration studies have shown that environmental factors may influence the development of PC. In this context, specific nutritional components may exert an influence on the tumorigenesis of PC. Primary prevention of PC is still an important issue due to its high prevalence, treatment-associated morbidities, and long-term complications. Phytoestrogenes as flavonoids seem to play an essential role in the chemoprevention of PC which is possibly due to their hormonal function and antioxidative capability. Flavonoids and their subgroups are naturally existent in traditional asian and vegetarian nutrients as coverings of plants, fruits, and vegetables. Two of the most frequently investigated flavonoids are genistein and quercetin. These nutritional components may have therapeutic potential and may impact the development of PC. Even though these flavonoids show promising results in the chemoprevention of PC, the literature is almost experimental, epidemiological, and retrospective with a missing long-term follow-up. Therefore, randomized clinical trials are urgently needed to evaluate in depth its oncologic effects in PC. PMID:24531783

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

    Directory of Open Access Journals (Sweden)

    William N. Rom

    2013-01-01

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

  1. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms.

    Science.gov (United States)

    Singh, Madhulika; Suman, Shankar; Shukla, Yogeshwer

    2014-01-01

    Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer. PMID:24757666

  2. New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms

    Directory of Open Access Journals (Sweden)

    Madhulika Singh

    2014-01-01

    Full Text Available Skin cancer is still a major cause of morbidity and mortality worldwide. Skin overexposure to ultraviolet irradiations, chemicals, and several viruses has a capability to cause severe skin-related disorders including immunosuppression and skin cancer. These factors act in sequence at various steps of skin carcinogenesis via initiation, promotion, and/or progression. These days cancer chemoprevention is recognized as the most hopeful and novel approach to prevent, inhibit, or reverse the processes of carcinogenesis by intervention with natural products. Phytochemicals have antioxidant, antimutagenic, anticarcinogenic, and carcinogen detoxification capabilities thereby considered as efficient chemopreventive agents. Considerable efforts have been done to identify the phytochemicals which may possibly act on one or several molecular targets that modulate cellular processes such as inflammation, immunity, cell cycle progression, and apoptosis. Till date several phytochemicals in the light of chemoprevention have been studied by using suitable skin carcinogenic in vitro and in vivo models and proven as beneficial for prevention of skin cancer. This revision presents a comprehensive knowledge and the main molecular mechanisms of actions of various phytochemicals in the chemoprevention of skin cancer.

  3. Chemopreventive Effect of Cardamom (Elettaria cardamomum L.) Against Benzo(α)Pyrene-Induced Forestomach Papillomagenesis in Swiss Albino Mice.

    Science.gov (United States)

    Qiblawi, Samir; Dhanarasu, Sasikumar; Faris, Mo'ez Al-Islam

    2015-01-01

    Prevention of cancer through dietary intervention has recently gained significant recognition. Cardamom (Elettaria cardamomum), a dietary phytoproduct, is a popular spice that is regularly used as a flavoring agent in various cuisines, and is much valued for its medicinal properties. In the present study, the cancer chemopreventive potential of cardamom was investigated against benzo(α)pyrene [B(α)P]-induced forestomach papillomagenesis in mice. Results showed that treatment with cardamom [(B(α)P + cardamom] reduced tumor incidence and multiplicity significantly (Pcardamom compared with the control. Furthermore, the nonenzymatic antioxidant glutathione was significantly (Pcardamom-treated group, whereas the lipid peroxidation level along with lactate dehydrogenase activity exhibited a significant (Pcardamom treatment compared to the control. These results suggest that cardamom has the potential to become a pivotal chemopreventive agent against forestomach cancer. PMID:26081028

  4. Mixture of Uncaria and Tabebuia Extracts are Potentially Chemopreventive in CBA/Ca Mice - A Long-term Experiment

    OpenAIRE

    Budán, Ferenc; Szabo, István; Varjas, Timea; Nowrasteh, Ghodratollah; Dávid, Tamás; Gergely, Péter; Varga, Zsuzsa; Molnár, Kornélia; Kádár, Balázs; Orsos, Zsuzsa; Kiss, István; Ember, István

    2010-01-01

    Abstract A long-term experimental animal model was developed by our research group for the evaluation of potential chemopreventive effects. The inhibitory effects of agents on carcinogen (7,12-Dimetilbenz[a]anthracene (DMBA)) induced molecular epidemiological biomarkers, in this case the expression of key onco/suppressor genes were investigated. Expression pattern of c-myc, Ha-ras, Bcl-2, K-ras protoonco and p53 tumoursuppressor genes were studied to elucidate early carcinogenic...

  5. SHERPA and Institutional Repositories

    OpenAIRE

    Hubbard, Bill

    2003-01-01

    The SHERPA project (Securing a Hybrid Environment for Research Preservation and Access) has been set up to encourage change in the scholarly communication process by creating open-access institutional "e-print" repositories for the dissemination of research findings. This article looks at the terminology involved with such repositories and at the issues that such repositories raise for their construction and use. It reviews the advantages of having an institutional basis for a repository and ...

  6. The Emperor's New Repository

    Science.gov (United States)

    Chudnov, Daniel

    2008-01-01

    The author does not know the first thing about building digital repositories. Maybe that is a strange thing to say, given that he works in a repository development group now, worked on the original DSpace project years ago, and worked on a few repository research projects in between. Given how long he has been around people and projects aiming to…

  7. Chemopreventive Herbal Anti-Oxidants: Current Status and Future Perspectives

    OpenAIRE

    Patel, Rachana; Garg, Rachana; Erande, Suvarna; B. Maru, Girish

    2007-01-01

    Cancer chemoprevention is fast becoming a lucrative approach for controlling cancer. Carcinogenesis being a complex multi-step, multi-factorial process, a number of chemopreventive interventions can be employed. These strategies are generally directed against two broad events of carcinogenesis viz., initiation and promotion/progression. Anti-initiation interventions principally involve inhibition of carcinogen activation, scavenging of free radicals and reactive carcinogen metabolites along w...

  8. An agent framework for dynamic agent retraining: Agent academy

    OpenAIRE

    Mitkas, P.; A. Symeonidis; Kechagias, D.; Athanasiadis, I.N.; Laleci, G.; KURT, G.; Kabak, Y.; Acar, A.; Dogac, A.

    2004-01-01

    Agent Academy (AA) aims to develop a multi-agent society that can train new agents for specific or general tasks, while constantly retraining existing agents in a recursive mode. The system is based on collecting information both from the environment and the behaviors of the acting agents and their related successes/failures to generate a body of data, stored in the Agent Use Repository, which is mined by the Data Miner module, in order to generate useful knowledge about the application domai...

  9. Chemopreventive and therapeutic potentials of thymoquinone in HepG2 cells: mechanistic perspectives.

    Science.gov (United States)

    ElKhoely, Abeer; Hafez, Hafez F; Ashmawy, Abeer M; Badary, Osama; Abdelaziz, Ahmed; Mostafa, Adel; Shouman, Samia A

    2015-07-01

    Liver cancer is the fifth commonest malignancy worldwide and the third leading cause of death. Identifying novel curative and preventive therapy may improve its prognosis. In this study, thymoquinone (TQ), the most active biological ingredient of Nigella sativa Linn, was investigated for its antitumor activity. Mechanistic perspectives underlying this antitumor activity were explored by testing its effect on cell cycle, apoptosis, and angiogenesis. In addition, the chemopreventive effect of TQ was carried out by measuring its effect on phase I CYP1A1 and phase II glutathione S-transferase (GST) drug-metabolizing enzymes. The results of the present study revealed the effectiveness of TQ as an antitumor agent against different types of cancer including brain, colon, cervix and liver at both a time- and concentration-dependent manner. In HepG2 cells, it induced G2/M phase cell cycle arrest and a concentration-dependent increase in the percentage of apoptotic cells with an increase in the ratio of Bax/BCL-2. Moreover, the expression of mRNA and protein level of vascular endothelial growth factor decreased as the concentration of TQ increased. Our data showed a significant inhibition of induced phase I CYP1A1 enzyme, and elevation in the content of glutathione and activity of phase II enzyme GST, in HepG2 cells. Our results provide support for the beneficial use of TQ as a therapeutic and chemopreventive agent against liver cancer. PMID:25796541

  10. Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats

    International Nuclear Information System (INIS)

    Highlights: • Dietary administration of an ethanolic extract of aerial parts of T. portulacastrum (TPE) exhibits a striking chemopreventive effect in an experimentally induced classical animal model of breast cancer. • The mammary tumor-inhibitory effect of TPE could be achieved, at least in part, though intervention of key hallmark capabilities of tumor cells, such as abnormal cell proliferation and evasion of apoptosis. • TPE is capable of diminishing activated canonical Wnt/β-catenin signaling to exhibit antiproliferative, proapoptotic and oncostatic effects during this early-stage mammary carcinoma. • These results coupled with a safety profile of T. portulacastrum may encourage further studies to understand the full potential of this dietary plant for chemoprevention of breast cancer. - Abstract: Due to limited treatment options for advanced-stage metastatic breast cancer, a high priority should be given to develop non-toxic chemopreventive drugs. The value of various natural and dietary agents to reduce the risk of developing breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a dietary and medicinal plant, has been found to exert antihepatotoxic and antihepatocarcinogenic properties in rodents. This study was initiated to investigate mechanism-based chemopreventive potential of an ethanolic extract of T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary gland carcinogenesis, an experimental tumor model that closely resembles human breast cancer. Rats had access to a basal diet supplemented with TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden and average tumor weight

  11. Trianthema portulacastrum Linn. exerts chemoprevention of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bishayee, Anupam, E-mail: abishayee@auhs.edu [Department of Pharmaceutical Sciences, School of Pharmacy, American University of Health Sciences, Signal Hill, CA 90755 (United States); Mandal, Animesh [Cancer Therapeutics and Chemoprevention Group, Department of Pharmaceutical Sciences, College of Pharmacy, Northeast Ohio Medical University, Rootstown, OH 44272 (United States)

    2014-10-15

    Highlights: • Dietary administration of an ethanolic extract of aerial parts of T. portulacastrum (TPE) exhibits a striking chemopreventive effect in an experimentally induced classical animal model of breast cancer. • The mammary tumor-inhibitory effect of TPE could be achieved, at least in part, though intervention of key hallmark capabilities of tumor cells, such as abnormal cell proliferation and evasion of apoptosis. • TPE is capable of diminishing activated canonical Wnt/β-catenin signaling to exhibit antiproliferative, proapoptotic and oncostatic effects during this early-stage mammary carcinoma. • These results coupled with a safety profile of T. portulacastrum may encourage further studies to understand the full potential of this dietary plant for chemoprevention of breast cancer. - Abstract: Due to limited treatment options for advanced-stage metastatic breast cancer, a high priority should be given to develop non-toxic chemopreventive drugs. The value of various natural and dietary agents to reduce the risk of developing breast cancer is well established. Trianthema portulacastrum Linn. (Aizoaceae), a dietary and medicinal plant, has been found to exert antihepatotoxic and antihepatocarcinogenic properties in rodents. This study was initiated to investigate mechanism-based chemopreventive potential of an ethanolic extract of T. portulacastrum (TPE) against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary gland carcinogenesis, an experimental tumor model that closely resembles human breast cancer. Rats had access to a basal diet supplemented with TPE to yield three dietary doses of the extract, i.e., 50, 100 and 200 mg/kg body weight. Following two weeks of TPE treatment, mammary tumorigenesis was initiated by oral administration of DMBA (50 mg/kg body weight). At the end of the study (16 weeks after DMBA exposure), TPE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden and average tumor weight

  12. Repositories with Direct Representation

    OpenAIRE

    Allen, Robert Burnell

    2015-01-01

    A new generation of digital repositories could be based on direct representation of the contents with rich semantics and models rather than be collections of documents. The contents of such repositories would be highly structured which should help users to focus on meaningful relationships of the contents. These repositories would implement earlier proposals for model-oriented information organization by extending current work on ontologies to cover state changes, instances, and scenarios. Th...

  13. Measuring Model Repositories

    OpenAIRE

    Vépa, Éric; Bézivin, Jean; Brunelière, Hugo; Jouault, Frédéric

    2006-01-01

    International audience We first present a model repository that has been built as part of the open source Eclipse GMT/AM3 project (Generative Modeling Technology/ATLAS MegaModel Management). Several contributed artifacts present in this repository are organized into sets of models of similar nature called zoos. The structure of the repository will be rapidly described. Its content is very rapidly extending, providing a publicly available source of experimental data to evaluate real life se...

  14. Administrative Data Repository (ADR)

    Data.gov (United States)

    Department of Veterans Affairs — The Administrative Data Repository (ADR) was established to provide support for the administrative data elements relative to multiple categories of a person entity...

  15. Cancer Prevention and Interception: A New Era for Chemopreventive Approaches.

    Science.gov (United States)

    Albini, Adriana; DeCensi, Andrea; Cavalli, Franco; Costa, Alberto

    2016-09-01

    At several recent, internationally attended scientific meetings, including the American Association for Cancer Research (AACR)'s "Shaping the Future of Cancer Prevention: A Roadmap for Integrative Cancer Science and Public Health" summit in Leesburg (VA) and the AACR Annual Meeting in New Orleans, the focus on cancer prevention to reduce cancer-related deaths was extensively discussed with renewed attention and emphasis. Cancer prevention should be actively proposed even to healthy individuals, and not just to individuals with high cancer risk. We discuss evaluation of a high cancer risk versus the relatively low risk for side effects of chemopreventive agents. The concept of cancer interception, which is halting transformed cells from becoming malignant cancers, should be adopted for cancer prevention. Potential prevention/interception actions include adopting healthy life style and avoiding carcinogens, repressing inflammation and pathologic angiogenesis, controlling metabolism, correcting insulin resistance and other metabolic alterations. Current drugs with limited toxicity can be repurposed to reduce cancer incidence. Aspirin is now being recommended for the prevention of colorectal cancer and it prevents other neoplasms as well. Metformin and β-blockers could be valuable for reducing pancreatic and breast cancer onset. On the basis of the evaluation of cancer risk, we here call for personalized approaches for cancer prevention and preventive interception and we envisage a list of measures and potential guidelines for preventive and interceptive strategies to reduce cancer burden. Investment into translational research to bring these approaches into public health policies and in the clinic is urgently needed. Clin Cancer Res; 22(17); 4322-7. ©2016 AACR. PMID:27220959

  16. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer

    Science.gov (United States)

    Malik, Arshi; Afaq, Farrukh; Sarfaraz, Sami; Adhami, Vaqar M.; Syed, Deeba N.; Mukhtar, Hasan

    2005-01-01

    Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among U.S. males, with a similar trend in many Western countries. One approach to control this malignancy is its prevention through the use of agents present in diet consumed by humans. Pomegranate from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting effects in mouse skin. In this study, employing human prostate cancer cells, we evaluated the antiproliferative and proapoptotic properties of PFE. PFE (10-100 μg/ml; 48 h) treatment of highly aggressive human prostate cancer PC3 cells resulted in a dose-dependent inhibition of cell growth/cell viability and induction of apoptosis. Immunoblot analysis revealed that PFE treatment of PC3 cells resulted in (i) induction of Bax and Bak (proapoptotic); (ii) down-regulation of Bcl-XL and Bcl-2 (antiapoptotic); (iii) induction of WAF1/p21 and KIP1/p27; (iv) a decrease in cyclins D1, D2, and E; and (v) a decrease in cyclin-dependent kinase (cdk) 2, cdk4, and cdk6 expression. These data establish the involvement of the cyclin kinase inhibitor-cyclin-cdk network during the antiproliferative effects of PFE. Oral administration of PFE (0.1% and 0.2%, wt/vol) to athymic nude mice implanted with androgen-sensitive CWR22Rν1 cells resulted in a significant inhibition in tumor growth concomitant with a significant decrease in serum prostate-specific antigen levels. We suggest that pomegranate juice may have cancer-chemopreventive as well as cancer-chemotherapeutic effects against prostate cancer in humans. PMID:16192356

  17. Comparing Repository Types - Challenges and barriers for subject-based repositories, research repositories, national repository systems and institutional repositories in serving scholarly communication

    OpenAIRE

    Armbruster, Chris; Romary, Laurent

    2010-01-01

    After two decades of repository development, some conclusions may be drawn as to which type of repository and what kind of service best supports digital scholarly communication, and thus the production of new knowledge. Four types of publication repository may be distinguished, namely the subject-based repository, research repository, national repository system and institutional repository. Two important shifts in the role of repositories may be noted. With regard to content, a well-defined a...

  18. Efficacy of geraniol but not of β-ionone or their combination for the chemoprevention of rat colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    A. Vieira

    2011-06-01

    Full Text Available β-ionone (βI, a cyclic isoprenoid, and geraniol (GO, an acyclic monoterpene, represent a promising class of dietary chemopreventive agents against cancer, whose combination could result in synergistic anticarcinogenic effects. The chemopreventive activities of βI and GO were evaluated individually or in combination during colon carcinogenesis induced by dimethylhydrazine in 48 3-week-old male Wistar rats (12 per group weighing 40-50 g. Animals were treated for 9 consecutive weeks with βI (16 mg/100 g body weight, GO (25 mg/100 g body weight, βI combined with GO or corn oil (control. Number of total aberrant crypt foci (ACF and of ACF ≥4 crypts in the distal colon was significantly lower in the GO group (66 ± 13 and 9 ± 2, respectively compared to control (102 ± 9 and 17 ± 3 and without differences in the βI (91 ± 11 and 14 ± 3 and βI+GO groups (96 ± 5 and 19 ± 2. Apoptosis level, identified by classical apoptosis morphological criteria, in the distal colon was significantly higher in the GO group (1.64 ± 0.06 apoptotic cells/mm² compared to control (0.91 ± 0.07 apoptotic cells/mm². The GO group presented a 0.7-fold reduction in Bcl-2 protein expression (Western blot compared to control. Colonic mucosa concentrations of βI and GO (gas chromatography/mass spectrometry were higher in the βI and GO groups, respectively, compared to the control and βI+GO groups. Therefore, GO, but not βI, represents a potential chemopreventive agent in colon carcinogenesis. Surprisingly, the combination of isoprenoids does not represent an efficient chemopreventive strategy.

  19. In vitro cancer chemopreventive properties of polysaccharide extract from the brown alga, Sargassum latifolium.

    Science.gov (United States)

    Gamal-Eldeen, Amira M; Ahmed, Eman F; Abo-Zeid, Mona A

    2009-06-01

    Polysaccharides of edible algae attracted extensive interest due to their numerous biological activities. Sargassum latifolium (Turner) C. Agardh, belongs to Sargassaceae, is a brown algae in red sea shores in Egypt. This work is a novel attempt to explore the cancer chemopreventive activity of different fractions of water-soluble polysaccharide extract derived from S. latifolium. Estimation of cancer chemopreventive activity, specifically anti-initiation, including the modulation of carcinogen metabolism and the antioxidant capacity, revealed that E1 and E4 were potent anti-initiators, where they lead not only to an inhibition in the carcinogen activator cytochrome P450 1A (IC50 2.54 and 10.30 microg/ml, respectively), but also to an induction in the carcinogen detoxification enzymes glutathione-S-transferases (144% and 225% of the control, respectively). E1 and E4 inhibited 59% and 63% of the induced-DNA damage, as measured by comet assay. Similarly both E1 and E4 possessed potential anti-promoting properties as indicated by their anti-inflammatory activity. E1 and E4 enhanced the macrophage proliferation; however they dramatically inhibited the stimulated NO (30.7% and 59.3%), TNF-alpha (38.2% and 54.9) and COX-2 (20% and 18%), respectively. E3 showed a selective cytotoxicity against lymphoblastic leukemia (1301 cells), while other fraction extracts had no cytotoxic effect against all tested cell lines. E3 led to a major disturbance in cell cycle including arrest in both S-phases in 1301 cells. This disturbance was associated with an induced-cell death due to apoptosis, but not necrosis. In conclusion, E1 and E4 are promising cancer chemopreventive fractions, since they had tumor anti- initiating activity via their protective modulation of carcinogen metabolism, and tumor anti-promoting activity via their anti-inflammatory activity, while E3 can be considered as a promising anti-cancer agent against leukemia. PMID:19306910

  20. Tale of two repositories

    International Nuclear Information System (INIS)

    This paper reviews the history of the West and East proposed siting of the two HLW repositories and of the conflict between USDOE and Congress over the secondary repository (in the east). The author sums up the paper with a call for resignation of the Secretary of Energy

  1. The Lincoln Repository poster

    OpenAIRE

    Prichard, Dave

    2010-01-01

    Poster created by the University of Lincoln's department of Marketing, Recruitment & Communications, to promote the Lincoln Repository to staff. The text on the poster reads: "The Lincoln Repository / Linking your research to the world / Find out more at eprints.lincoln.ac.uk".

  2. Molecular Mechanisms Behind the Chemopreventive Effects of Anthocyanidins

    Directory of Open Access Journals (Sweden)

    De-Xing Hou

    2004-01-01

    Full Text Available Anthocyanins are polyphenolic ring-based flavonoids, and are widespread in fruits and vegetables of red-blue color. Epidemiological investigations and animal experiments have indicated that anthocyanins may contribute to cancer chemoprevention. The studies on the mechanism have been done recently at molecular level. This review summarizes current molecular bases for anthocyanidins on several key steps involved in cancer chemoprevention: (i inhibition of anthocyanidins in cell transformation through targeting mitogen-activated protein kinase (MAPK pathway and activator protein 1 (AP-1 factor; (ii suppression of anthocyanidins in inflammation and carcinogenesis through targeting nuclear factor kappa B (NF-κB pathway and cyclooxygenase 2 (COX-2 gene; (iii apoptotic induction of cancer cells by anthocyanidins through reactive oxygen species (ROS / c-Jun NH2-terminal kinase (JNK-mediated caspase activation. These data provide a first molecular view of anthocyanidins contributing to cancer chemoprevention.

  3. Chemopreventive effects of cardamom (Elettaria cardamomum L.) on chemically induced skin carcinogenesis in Swiss albino mice.

    Science.gov (United States)

    Qiblawi, Samir; Al-Hazimi, Awdah; Al-Mogbel, Mohammed; Hossain, Ashfaque; Bagchi, Debasis

    2012-06-01

    The chemopreventive potential of cardamom was evaluated on 7,12-dimethylbenz[a]anthracene-initiated and croton oil-promoted mouse skin papillomagenesis. A significant reduction in the values of tumor incidence, tumor burden, and tumor yield and the cumulative number of papillomas was observed in mice treated orally with 0.5 mg of cardamom powder in suspension continuously at pre-, peri-, and post-initiational stages of papillomagenesis compared with the control group. The average weight and diameter of tumors recorded were also comparatively lower in the cardamom-treated mouse group. Treatment of cardamom suspension by oral gavage for 15 days resulted in a significant decrease in the lipid peroxidation level of the liver (P < .01). In addition, the reduced glutathione level was significantly elevated in comparison with the control group (P < .05) following cardamom suspension treatment. Taken together, these findings indicate the potential of cardamom as a chemopreventive agent against two-stage skin cancer. PMID:22404574

  4. Acyclic retinoid in chemoprevention of hepatocellular carcinoma: Targeting phosphorylated retinoid X receptor-α for prevention of liver carcinogenesis

    Directory of Open Access Journals (Sweden)

    Masahito Shimizu

    2012-01-01

    Full Text Available One of the key features of hepatocellular carcinoma (HCC is the high rate of intrahepatic recurrence that correlates with poor prognosis. Therefore, in order to improve the clinical outcome for patients with HCC, development of a chemopreventive agent that can decrease or delay the incidence of recurrence is a critical issue for urgent investigation. Acyclic retinoid (ACR, a synthetic retinoid, successfully improves HCC patient survival by preventing recurrence and the formation of secondary tumors. A malfunction of the retinoid X receptor-α (RXRα due to phosphorylation by the Ras-MAPK signaling pathway plays a critical role in liver carcinogenesis, and ACR exerts chemopreventive effects on HCC development by inhibiting RXRα phosphorylation. Here, we review the relationship between retinoid signaling abnormalities and liver disease, the mechanisms of how RXRα phosphorylation contributes to liver carcinogenesis, and the detailed effects of ACR on preventing HCC development, especially based on the results of our basic and clinical research. We also outline the concept of "clonal deletion and inhibition" therapy, which is defined as the removal and inhibition of latent malignant clones from the liver before they expand into clinically detectable HCC, because ACR prevents the development of HCC by implementing this concept. Looking toward the future, we discuss "combination chemoprevention" using ACR as a key drug since it can generate a synergistic effect, and may thus be an effective new strategy for the prevention of HCC.

  5. Gas generation in repositories

    International Nuclear Information System (INIS)

    The nature and quantities of gases likely to be produced by various processes in repositories for low level and intermediate level radioactive wastes are examined in this preliminary study. Many simplifying assumptions are made where published or experimental data is unavailable. The corrosion of the canisters and metallic components in wastes is likely to be the major gas production process in both types of repository. A significant contribution from microbiological activity is expected to occur in low level repositories, predominantly where no cement grouting of the cans has been carried out. A number of areas for further research, required before a more comprehensive study could be carried out, have been identified. (author)

  6. A theoretical study on predicted protein targets of apple polyphenols and possible mechanisms of chemoprevention in colorectal cancer.

    Science.gov (United States)

    Scafuri, Bernardina; Marabotti, Anna; Carbone, Virginia; Minasi, Paola; Dotolo, Serena; Facchiano, Angelo

    2016-01-01

    We investigated the potential role of apple phenolic compounds in human pathologies by integrating chemical characterization of phenolic compounds in three apple varieties, computational approaches to identify potential protein targets of the compounds, bioinformatics analyses on data from public archive of gene expression data, and functional analyses to hypothesize the effects of the selected compounds in molecular pathways. Starting by the analytic characterization of phenolic compounds in three apple varieties, i.e. Annurca, Red Delicious, and Golden Delicious, we used computational approaches to verify by reverse docking the potential protein targets of the identified compounds. Direct docking validation of the potential protein-ligand interactions has generated a short list of human proteins potentially bound by the apple phenolic compounds. By considering the known chemo-preventive role of apple antioxidants' extracts against some human pathologies, we performed a functional analysis by comparison with experimental gene expression data and interaction networks, obtained from public repositories. The results suggest the hypothesis that chemo-preventive effects of apple extracts in human pathologies, in particular for colorectal cancer, may be the interference with the activity of nucleotide metabolism and methylation enzymes, similarly to some classes of anticancer drugs. PMID:27587238

  7. Risk adapted chemoprevention for prostate cancer: an option?

    Science.gov (United States)

    Schmitz-Dräger, Bernd J; Schöffski, Oliver; Marberger, Michael; Sahin, Sevim; Schmid, Hans-Peter

    2014-01-01

    A high disease prevalence, the presentation in older age, a frequently slowly progressing course of disease, and high costs make diagnosis and therapy of prostate cancer a special challenge for urologists. Effective prevention of the disease may help to resolve some of the problems mentioned above. Two randomised, controlled studies prove that effective chemoprevention of prostate cancer is possible using 5-α reductase inhibitors (finasteride, dutasteride) (LoE 1) both in individuals at low and those at high risk developing prostate cancer. Furthermore, there is evidence that other compounds, e.g. selective estrogen receptor modulators (SERMs), non-steroidal anti-inflammatory drugs (NSAIDs) and statins might also be effective. This review investigates potential risks and benefits of chemoprevention including a consideration of health economic aspects. The authors conclude that chemoprevention in a high risk cohort using 5-α reductase inhibitors is a viable option and may even be cost effective. In consequence, the options of chemoprevention in prostate cancer should be further explored in an open and unbiased way. PMID:24531781

  8. Corticotropin, Repository Injection

    Science.gov (United States)

    ... protein in the blood; high levels of certain fats in the blood; and swelling of the arms, hands, feet, and legs). Corticotropin repository injection is in a class of medications called hormones. ...

  9. NIA Aging Cell Repository

    Data.gov (United States)

    Federal Laboratory Consortium — To facilitate aging research on cells in culture, the NIA provides support for the NIA Aging Cell Repository, located at the Coriell Institute for Medical Research...

  10. NIDDK Central Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The NIDDK Central Repository stores biosamples, genetic and other data collected in designated NIDDK-funded clinical studies. The purpose of the NIDDK Central...

  11. NIH Data Sharing Repositories

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of NIH-supported repositories that accept submissions of appropriate scientific research data from biomedical researchers. It includes resources that...

  12. Preserving repository content: practical steps for repository managers

    OpenAIRE

    Pickton, Miggie; Hitchcock, Steve; Coles, Simon; Morris, Debra; Meece, Stephanie

    2010-01-01

    The stated aim of most repositories is to provide permanent open access to the material therein. Why, then, have so few repositories implemented practical action plans for long term preservation of their content? Although a number of preservation tools and services already exist, until now few have addressed the specific needs of repositories; in practical terms they have necessitated action that is additional rather than integral to repository workflow. Repository content is typically highly...

  13. Repositories Unleashing Data: Ideas

    OpenAIRE

    Ward, Pauline Nathalie

    2015-01-01

    Participants at Repositories Fringe (RepoFringe) 2015 were invited to discuss how new audiences (particularly beyond the academic community) and new uses for data from institutional repositories could be identified and reached. A number of questions relating to this goal were discussed in groups. Participants contributed their ideas, questions and comments on post-it notes. The post-it notes have been transcribed.

  14. Redefining the Institutional Repository

    OpenAIRE

    Keene, Chris

    2014-01-01

    Institutional Repositories have grown in importance over the last 10 years to offer a core University and Library service, however, their role is developing faster now than it has ever done. Funder Open Access requirements, internal reporting, research data. Ref2020 and more are increasing the demands on the traditional repository, putting pressure on staff resources and challenging the underlying software. This webinar will outline these issues as well as look at how the needs and use of...

  15. Creating an institutional repository

    OpenAIRE

    Grozdanić, Marija; Macan, Bojan; Vodopijevec, Alen

    2006-01-01

    Institutional repository is a digital collection that capture, mantain, save, index, preserve and redistribute entire output of an institution in digital format. They adhere to open access modell and they are OAI – compliant. Building of insitutional repository is essential to the library whose mission is to provide access to wide range of information sources including open access sources and to promote them, as well. Intellectual output of the Institute might contain: pre-prints, post-...

  16. Trust in Digital Repositories

    OpenAIRE

    Elizabeth Yakel; Faniel, Ixchel M.; Adam Kriesberg; Ayoung Yoon

    2013-01-01

    ISO 16363:2012, Space Data and Information Transfer Systems - Audit and Certification of Trustworthy Digital Repositories (ISO TRAC), outlines actions a repository can take to be considered trustworthy, but research examining whether the repository’s designated community of users associates such actions with trustworthiness has been limited. Drawing from this ISO document and the management and information systems literatures, this paper discusses findings from interviews with 66 archaeologis...

  17. Managing and Evaluating Digital Repositories

    Science.gov (United States)

    Zuccala, Alesia; Oppenheim, Charles; Dhiensa, Rajveen

    2008-01-01

    Introduction: We examine the role of the digital repository manager, discuss the future of repository management and evaluation and suggest that library and information science schools develop new repository management curricula. Method: Face-to-face interviews were carried out with managers of five different types of repositories and a Web-based…

  18. Repository Performance Confirmation - 12119

    International Nuclear Information System (INIS)

    Repository performance confirmation links the technical bases of repository science and societal acceptance. Among the countless aspects of monitoring, performance confirmation holds a special place, involving distinct activities combining technical and social significance in radioactive waste management. Discussion is divided into four themes: 1. A distinction is drawn between performance confirmation monitoring and other testing and monitoring objectives, 2. A case study illustrates confirmation activities integrated within a long-term testing and monitoring strategy for Yucca Mountain, 3. A case study reviews compliance monitoring developed and implemented for the Waste Isolation Pilot Plant, and 4. An approach for developing, evaluating and implementing the next generation of performance confirmation monitoring is presented. International interest in repository monitoring is exhibited by the European Commission Seventh Framework Programme 'Monitoring Developments for Safe Repository Operation and Staged Closure' (MoDeRn) Project. The MoDeRn partners are considering the role of monitoring in a phased approach to the geological disposal of radioactive waste. As repository plans advance in different countries, the need to consider monitoring strategies within a controlled framework has become more apparent. The MoDeRn project pulls together technical and societal experts to assimilate a common understanding of a process that could be followed to develop a monitoring program. Experience from two repository programs in the United States sheds light on how performance confirmation has been executed. Lessons learned can help the next generation of performance confirmation. (author)

  19. Repository seals requirements study

    International Nuclear Information System (INIS)

    The Yucca Mountain Site Characterization Project, managed by the Civilian Radioactive Waste Management System (CRWMS) Management and Operating Contractor (M and O) is conducting investigations to support the Viability Assessment and the License Application for a high-level nuclear waste repository at Yucca Mountain, Nevada. The sealing subsystem is part of the Yucca Mountain Waste Isolation System. The Yucca Mountain Site Characterization Project is currently evaluating the role of the sealing subsystem (shaft, ramp and exploratory borehole seals) in achieving the overall performance objectives for the Waste Isolation System. This report documents the results of those evaluations. This report presents the results of a repository sealing requirements study. Sealing is defined as the permanent closure of the shafts, ramps, and exploratory boreholes. Sealing includes those components that would reduce potential inflows above the repository, or that would divert flow near the repository horizon to allow vertical infiltration to below the repository. Sealing of such features as emplacement drifts was not done in this study because the current capability to calculate fracture flow into the drifts is not sufficiently mature. The objective of the study is to provide water or air flow performance based requirements for shafts, ramps, and exploratory boreholes located near the repository. Recommendations, as appropriate, are provided for developing plans, seals component testing, and other studies relating to sealing

  20. Repository seals requirements study

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-11-03

    The Yucca Mountain Site Characterization Project, managed by the Civilian Radioactive Waste Management System (CRWMS) Management and Operating Contractor (M and O) is conducting investigations to support the Viability Assessment and the License Application for a high-level nuclear waste repository at Yucca Mountain, Nevada. The sealing subsystem is part of the Yucca Mountain Waste Isolation System. The Yucca Mountain Site Characterization Project is currently evaluating the role of the sealing subsystem (shaft, ramp and exploratory borehole seals) in achieving the overall performance objectives for the Waste Isolation System. This report documents the results of those evaluations. This report presents the results of a repository sealing requirements study. Sealing is defined as the permanent closure of the shafts, ramps, and exploratory boreholes. Sealing includes those components that would reduce potential inflows above the repository, or that would divert flow near the repository horizon to allow vertical infiltration to below the repository. Sealing of such features as emplacement drifts was not done in this study because the current capability to calculate fracture flow into the drifts is not sufficiently mature. The objective of the study is to provide water or air flow performance based requirements for shafts, ramps, and exploratory boreholes located near the repository. Recommendations, as appropriate, are provided for developing plans, seals component testing, and other studies relating to sealing.

  1. Breast Cancer Metabolism and Mitochondrial Activity: The Possibility of Chemoprevention with Metformin

    Directory of Open Access Journals (Sweden)

    Massimiliano Cazzaniga

    2015-01-01

    Full Text Available Metabolic reprogramming refers to the ability of cancer cells to alter their metabolism in order to support the increased energy request due to continuous growth, rapid proliferation, and other characteristics typical of neoplastic cells. It has long been believed that the increase of metabolic request was independent of the mitochondrial action but recently we know that mitochondrial activity together with metabolism plays a pivotal role in the regulation of the energy needed for tumor cell growth and proliferation. For these reasons the mitochondria pathways could be a new target for therapeutic and chemopreventive intervention. Metformin in particular is actually considered a promising agent against mitochondrial activity thanks to its ability to inhibit the mitochondrial complex I.

  2. Breast Cancer Metabolism and Mitochondrial Activity: The Possibility of Chemoprevention with Metformin.

    Science.gov (United States)

    Cazzaniga, Massimiliano; Bonanni, Bernardo

    2015-01-01

    Metabolic reprogramming refers to the ability of cancer cells to alter their metabolism in order to support the increased energy request due to continuous growth, rapid proliferation, and other characteristics typical of neoplastic cells. It has long been believed that the increase of metabolic request was independent of the mitochondrial action but recently we know that mitochondrial activity together with metabolism plays a pivotal role in the regulation of the energy needed for tumor cell growth and proliferation. For these reasons the mitochondria pathways could be a new target for therapeutic and chemopreventive intervention. Metformin in particular is actually considered a promising agent against mitochondrial activity thanks to its ability to inhibit the mitochondrial complex I. PMID:26605341

  3. Growth of Indian Institutional Repositories

    OpenAIRE

    Sawant, S. S.

    2010-01-01

    The present study estimated the number and the rate of growth of digital documents of Indian institutional repositories. Total 16 institutional repositories were identified using various sources of information such as: Literature; Search by search engines especially Google; Directories of archives / repositories; Blogs etc. It was observed that the IISc repository contained highest number of digital documents (6305) was the first institutional repository available to users for submission and ...

  4. Cancer chemoprevention and nutriepigenetics: state of the art and future challenges.

    Science.gov (United States)

    Gerhauser, Clarissa

    2013-01-01

    The term "epigenetics" refers to modifications in gene expression caused by heritable, but potentially reversible, changes in DNA methylation and chromatin structure. Epigenetic alterations have been identified as promising new targets for cancer prevention strategies as they occur early during carcinogenesis and represent potentially initiating events for cancer development. Over the past few years, nutriepigenetics - the influence of dietary components on mechanisms influencing the epigenome - has emerged as an exciting new field in current epigenetic research. During carcinogenesis, major cellular functions and pathways, including drug metabolism, cell cycle regulation, potential to repair DNA damage or to induce apoptosis, response to inflammatory stimuli, cell signalling, and cell growth control and differentiation become deregulated. Recent evidence now indicates that epigenetic alterations contribute to these cellular defects, for example epigenetic silencing of detoxifying enzymes, tumor suppressor genes, cell cycle regulators, apoptosis-inducing and DNA repair genes, nuclear receptors, signal transducers and transcription factors by promoter methylation, and modifications of histones and non-histone proteins such as p53, NF-κB, and the chaperone HSP90 by acetylation or methylation.The present review will summarize the potential of natural chemopreventive agents to counteract these cancer-related epigenetic alterations by influencing the activity or expression of DNA methyltransferases and histone modifying enzymes. Chemopreventive agents that target the epigenome include micronutrients (folate, retinoic acid, and selenium compounds), butyrate, polyphenols from green tea, apples, coffee, black raspberries, and other dietary sources, genistein and soy isoflavones, curcumin, resveratrol, dihydrocoumarin, nordihydroguaiaretic acid (NDGA), lycopene, anacardic acid, garcinol, constituents of Allium species and cruciferous vegetables, including indol-3-carbinol

  5. Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced Hamster Cheek Pouch Carcinogenesis by a 5-Lipoxygenase Inhibitor, Garcinol

    OpenAIRE

    Chen, Xin; Zhang, Xinyan; Lu, Ye; Shim, Joong-Youn; Sang, Shengmin; Sun, Zheng; Chen, Xiaoxin

    2012-01-01

    Our previous studies have shown that aberrant arachidonic acid metabolism, especially the 5-lipoxygenase (5-Lox) pathway, is involved in oral carcinogenesis, and can be targeted for cancer prevention. In order to develop potent topical agents for oral cancer chemoprevention, five known 5-Lox inhibitors from dietary and synthetic sources, Zileuton, ABT-761, Licofelone, Curcumin and Garcinol, were evaluated in silico for their potential efficacy. Garcinol, a polyisoprenylated benzophenone from ...

  6. Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity

    International Nuclear Information System (INIS)

    1-Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is an anti-inflammatory agent with a propenone moiety and chemically synthesized recently. In this study, we examined the chemopreventive effect of FPP-3 on 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in MCF-7 cells. FPP-3 reduced the formation of the DMBA-DNA adduct. DMBA-induced CYP1A1 and CYP1B1 gene expression and enzyme activity were inhibited by FPP-3. It inhibited DMBA-induced aryl hydrocarbon receptor (AhR) transactivation and DMBA-inducible nuclear localization of the AhR. Induction of detoxifying phase II genes by chemopreventive agents represents a coordinated protective response against oxidative stress and neoplastic effects of carcinogens. Transcription factor NF-E2 related factor 2 (Nrf2) regulates antioxidant response element (ARE) of phase II detoxifying and antioxidant enzymes, such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase (QR). FPP-3 increased the expression and enzymatic activity of GST and QR. Moreover, FPP-3 increased transcriptional activity of GST and QR. GST and QR induction and Nrf2 translocation by FPP-3 were blocked by the PKC inhibitor Goe6983, and the p38 inhibitor SB203580. These results reflected a partial role of PKCδ and p38 signaling in FPP-3-mediated GSTA and QR induction through nuclear translocation of Nrf2. Classically, chemopreventive agents either inhibit CYP metabolizing enzyme or induce phase II detoxifying enzymes. These results suggest that FPP-3 has a potent protective effect against DMBA-induced genotoxicity through modulating phase I and II enzymes and that it has potential as a chemopreventive agent

  7. Trust in Digital Repositories

    Directory of Open Access Journals (Sweden)

    Elizabeth Yakel

    2013-06-01

    Full Text Available ISO 16363:2012, Space Data and Information Transfer Systems - Audit and Certification of Trustworthy Digital Repositories (ISO TRAC, outlines actions a repository can take to be considered trustworthy, but research examining whether the repository’s designated community of users associates such actions with trustworthiness has been limited. Drawing from this ISO document and the management and information systems literatures, this paper discusses findings from interviews with 66 archaeologists and quantitative social scientists. We found similarities and differences across the disciplines and among the social scientists. Both disciplinary communities associated trust with a repository’s transparency. However, archaeologists mentioned guarantees of preservation and sustainability more frequently than the social scientists, who talked about institutional reputation. Repository processes were also linked to trust, with archaeologists more frequently citing metadata issues and social scientists discussing data selection and cleaning processes. Among the social scientists, novices mentioned the influence of colleagues on their trust in repositories almost twice as much as the experts. We discuss the implications our findings have for identifying trustworthy repositories and how they extend the models presented in the management and information systems literatures.

  8. Comparing Repository Types - Challenges and barriers for subject-based repositories, research repositories, national repository systems and institutional repositories in serving scholarly communication

    CERN Document Server

    Armbruster, Chris

    2010-01-01

    After two decades of repository development, some conclusions may be drawn as to which type of repository and what kind of service best supports digital scholarly communication, and thus the production of new knowledge. Four types of publication repository may be distinguished, namely the subject-based repository, research repository, national repository system and institutional repository. Two important shifts in the role of repositories may be noted. With regard to content, a well-defined and high quality corpus is essential. This implies that repository services are likely to be most successful when constructed with the user and reader uppermost in mind. With regard to service, high value to specific scholarly communities is essential. This implies that repositories are likely to be most useful to scholars when they offer dedicated services supporting the production of new knowledge. Along these lines, challenges and barriers to repository development may be identified in three key dimensions: a) identific...

  9. Chemoprevention of HBV-related hepatocellular carcinoma by the combined product of resveratrol and silymarin in transgenic mice

    Directory of Open Access Journals (Sweden)

    Wen-Chuan Hsieh

    2013-09-01

    Full Text Available ABSTRACTBackground: Patients with chronic hepatitis B virus (HBV infection are at a high risk to develop hepatocellular carcinoma (HCC. Recently, metabolic syndrome has been found to carry a risk for HCC development. Considering the limitation of chemotherapeutic drugs for HCCs, the development of chemopreventive agents for high risk chronic HBV carriers is urgently demanded. In this study, we used combined silymarin and resveratrol extract which have been shown to exhibit biologic effects on activating peroxisome proliferator activated receptors (PPAR and inhibiting mTOR signaling in a transgenic mice model harboring HBV viral oncoproteins.Methods: The transgenic mice model harboring HBx and pre-S2 mutant constructs which develop HCC was adopted. First, we in vitro tested the ideal combination dosages of the silymarin and resveratrol product, and then we fed the natural product to the transgenic mice.The chemopreventive effects on preventing the development of HCC were evaluated.Results: MTT assay showed an enhanced effect of the combined silymarin and resveratrol product on the reduction of cell proliferation in two hepatoma cell lines, Huh-7 and Hep G2. In vitro reporter assay and Western blot analyses revealed that the combined product couldactivate PPAR/PGC-1 signaling and inhibit mTOR expression. In vivo, the combined products could significantly ameliorate fatty liver and reduce HCCs in transgenic miceharboring HBV oncoproteins.Conclusions: The combined silymarin and resveratrol product exhibits a synergistic effect on the reduction of HCC development in transgenic mice model and may represent a potential agent for the prevention of HCC in high risk chronic HBV carriers.Key words: HBV, HCC, Transgenic mice, Chemoprevention

  10. The Mechanism in Gastric Cancer Chemoprevention by Allicin.

    Science.gov (United States)

    Luo, Runlan; Fang, Dengyang; Hang, Hongdong; Tang, Zeyao

    2016-01-01

    Gastric cancer remains high prevalence and fatality rates in China even though its morbidity has been decreased drastically. Allicin, which is from an assistance food-garlic (Allium Sativum L), was found to be effective in gastric cancer treatment. It is a defensive substance with a board biological properties: inhibition of bacteria, fungus, virus, controlled hypertension, diabetes, and chemoprevention of several cancers, etc. Experiments have shown that allicin can be chemopreventive to gastric cancer by inhibiting the growth of cancer cells, arresting cell cycle at G2/M phase, endoplasmic reticulum (ER) stress, and mitochondria-mediated apoptosis, which includes the caspase-dependent/-independent pathways and death receptor pathway. Those mechanisms probably involve in modulating enzymatic activity, restraining DNA formation, scavenging free radicals, and affecting cell proliferation and even tumor growth. Therefore, this review is focus on the mechanism of allicin in gastric cancer. PMID:26555611

  11. Polyphenols: Key Issues Involved in Chemoprevention of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Sebastiano Cimino

    2012-01-01

    Full Text Available Prostate cancer is is the most common solid neoplasm and it is now recognized as one of the most important medical problems facing the male population. Due to its long latency and its identifiable preneoplastic lesions, prostate cancer is an ideal target tumor for chemoprevention. Different compounds are available and certainly polyphenols represent those with efficacy against prostate cancer. This review take a look at activity and properties of major polyphenolic substances, such as epigallocatechin-3-gallate, curcumin, resveratrol and the flavonoids quercetin and genistein. Although the current studies are limited, mechanisms of action of polyphenols added with the lack of side effects show a a start for future strategies in prostate chemoprevention.

  12. Shrimp Lipids: A Source of Cancer Chemopreventive Compounds

    Directory of Open Access Journals (Sweden)

    Armando Burgos-Hernández

    2013-10-01

    Full Text Available Shrimp is one of the most popular seafoods worldwide, and its lipids have been studied for biological activity in both, muscle and exoskeleton. Free fatty acids, triglycerides, carotenoids, and other lipids integrate this fraction, and some of these compounds have been reported with cancer chemopreventive activities. Carotenoids and polyunsaturated fatty acids have been extensively studied for chemopreventive properties, in both in vivo and in vitro studies. Their mechanisms of action depend on the lipid chemical structure and include antioxidant, anti-proliferative, anti-mutagenic, and anti-inflammatory activities, among others. The purpose of this review is to lay groundwork for future research about the properties of the lipid fraction of shrimp.

  13. Crocus sativus L. (saffron) for cancer chemoprevention: A mini review

    OpenAIRE

    Prasan R Bhandari

    2015-01-01

    Cancer is one of the most feared diseases globally and there has been a sustained rise in its incidence in both developing and developed countries. Despite the growing therapeutic options for patients with cancer, their efficacy is time-limited and non-curative. Hence to overcome these drawbacks, an incessant screening for superior and safer drugs has been ongoing for numerous decades, resulting in the detection of anti-cancer properties of several phytochemicals. Chemoprevention using readil...

  14. Chemopreventive effect of apple and berry fruits against colon cancer

    OpenAIRE

    Jaganathan, Saravana Kumar; Vellayappan, Muthu Vignesh; Narasimhan, Gayathri; Supriyanto, Eko; Octorina Dewi, Dyah Ekashanti; Narayanan, Aqilah Leela T; Balaji, Arunpandian; Subramanian, Aruna Priyadarshini; Yusof, Mustafa

    2014-01-01

    Colon cancer arises due to the conversion of precancerous polyps (benign) found in the inner lining of the colon. Prevention is better than cure, and this is very true with respect to colon cancer. Various epidemiologic studies have linked colorectal cancer with food intake. Apple and berry juices are widely consumed among various ethnicities because of their nutritious values. In this review article, chemopreventive effects of these fruit juices against colon cancer are discussed. Studies de...

  15. Colon cancer chemoprevention with ginseng and other botanicals.

    OpenAIRE

    Wargovich, M J

    2001-01-01

    Colorectal cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer deaths in the United States. Efforts to prevent colon cancer have targeted early detection through screening and chemoprevention. For the last ten years our laboratory has utilized an in vivo screening assay for the testing of potential cancer preventives for colon cancer. We have conducted investigations on over 150 compounds including many with botanical or herbal origin...

  16. Chemoprevention of Breast Cancer: The Paradox of Evidence versus Advocacy Inaction

    Directory of Open Access Journals (Sweden)

    Rakhshanda Layeequr Rahman

    2012-10-01

    Full Text Available Women who are at high risk of breast cancer can be offered chemoprevention. Chemoprevention strategies have expanded over the past decade and include selective receptor modulator inhibitors and aromatase inhibitors. Physicians are expected to provide individualized risk assessments to identify high risk women who may be eligible for chemoprevention. It is prudent that physicians utilize a shared decision approach when counseling high risk women about their preventive options. Barriers and misperceptions however exist with patient and physician acceptance of chemoprevention and continue to impede uptake of chemoprevention as a strategy to reduce breast cancer risk. Programs to increase awareness and elucidate the barriers are critical for women to engage in cancer prevention and promote chemoprevention adherence.

  17. Cancer chemoprevention: Evidence of a nonlinear dose response for the protective effects of resveratrol in humans and mice.

    Science.gov (United States)

    Cai, Hong; Scott, Edwina; Kholghi, Abeer; Andreadi, Catherine; Rufini, Alessandro; Karmokar, Ankur; Britton, Robert G; Horner-Glister, Emma; Greaves, Peter; Jawad, Dhafer; James, Mark; Howells, Lynne; Ognibene, Ted; Malfatti, Michael; Goldring, Christopher; Kitteringham, Neil; Walsh, Joanne; Viskaduraki, Maria; West, Kevin; Miller, Andrew; Hemingway, David; Steward, William P; Gescher, Andreas J; Brown, Karen

    2015-07-29

    Resveratrol is widely promoted as a potential cancer chemopreventive agent, but a lack of information on the optimal dose prohibits rationally designed trials to assess efficacy. To challenge the assumption that "more is better," we compared the pharmacokinetics and activity of a dietary dose with an intake 200 times higher. The dose-response relationship for concentrations generated and the metabolite profile of [(14)C]-resveratrol in colorectal tissue of cancer patients helped us to define clinically achievable levels. In Apc(Min) mice (a model of colorectal carcinogenesis) that received a high-fat diet, the low resveratrol dose suppressed intestinal adenoma development more potently than did the higher dose. Efficacy correlated with activation of adenosine monophosphate-activated protein kinase (AMPK) and increased expression of the senescence marker p21. Nonlinear dose responses were observed for AMPK and mechanistic target of rapamycin (mTOR) signaling in mouse adenoma cells, culminating in autophagy and senescence. In human colorectal tissues exposed to low dietary concentrations of resveratrol ex vivo, we measured enhanced AMPK phosphorylation and autophagy. The expression of the cytoprotective NAD(P)H dehydrogenase, quinone 1 (NQO1) enzyme was also increased in tissues from cancer patients participating in our [(14)C]-resveratrol trial. These findings warrant a revision of developmental strategies for diet-derived agents designed to achieve cancer chemoprevention. PMID:26223300

  18. The Computational Materials Repository

    DEFF Research Database (Denmark)

    Landis, David D.; Hummelshøj, Jens S.; Nestorov, Svetlozar;

    2012-01-01

    The possibilities for designing new materials based on quantum physics calculations are rapidly growing, but these design efforts lead to a significant increase in the amount of computational data created. The Computational Materials Repository (CMR) addresses this data challenge and provides a...

  19. Salt repository design approach

    International Nuclear Information System (INIS)

    This paper presents a summary discussion of the approaches that have been and will be taken in design of repository facilities for use with disposal of radioactive wastes in salt formations. Since specific sites have yet to be identified, the discussion is at a general level, supplemented with illustrative examples where appropriate. 5 references, 1 figure

  20. Inhibition of akt enhances the chemopreventive effects of topical rapamycin in mouse skin

    Science.gov (United States)

    Dickinson, Sally E; Janda, Jaroslav; Criswell, Jane; Blohm-Mangone, Karen; Olson, Erik R.; Liu, Zhonglin; Barber, Christie; Rusche, Jadrian J.; Petricoin, Emmanuel, III; Calvert, Valerie; Einspahr, Janine G.; Dickinson, Jesse; Stratton, Steven P.; Curiel-Lewandrowski, Clara; Saboda, Kathylynn; Hu, Chengcheng; Bode, Ann M.; Dong, Zigang; Alberts, David S.; Bowden, G. Timothy

    2016-01-01

    The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced non-melanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin, (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared to those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here we explored the use of topical rapamycin as a chemopreventive agent in the context of solar simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared to controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared to vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.

  1. Chemopreventive effect of sinapic acid on 1,2-dimethylhydrazine-induced experimental rat colon carcinogenesis.

    Science.gov (United States)

    Balaji, C; Muthukumaran, J; Nalini, N

    2014-12-01

    Sinapic acid (SA) is a naturally occurring phenolic acid found in various herbal plants which is attributed with numerous pharmacological properties. This study was aimed to investigate the chemopreventive effect of SA on 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Rats were treated with DMH injections (20 mg kg(-1) bodyweight (b.w.) subcutaneously once a week for the first 4 consecutive weeks and SA (20, 40 and 80 mg kg(-1) b.w.) post orally for 16 weeks. At the end of the 16-week experimental period, all the rats were killed, and the tissues were evaluated biochemically. Our results reveal that DMH alone treatment decreased the levels/activities of lipid peroxidation by-products such as thiobarbituric acid reactive substances, conjugated dienes and antioxidants such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and reduced glutathione in the intestine and colonic tissues which were reversed on supplementation with SA. Moreover, the activities of drug-metabolizing enzymes of phase I (cytochrome P450 and P4502E1) were enhanced and those of phase II (glutathione-S-transferase, DT-diaphorase and uridine diphosphate glucuronosyl transferase) were diminished in the liver and colonic mucosa of DMH alone-treated rats and were reversed on supplementation with SA. All the above changes were supported by the histopathological observations of the rat liver and colon. These findings suggest that SA at the dose of 40 mg kg(-1) b.w. was the most effective dose against DMH-induced colon carcinogenesis, and thus, SA could be used as a potential chemopreventive agent. PMID:24532707

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  3. Australian clinicians and chemoprevention for women at high familial risk for breast cancer

    Directory of Open Access Journals (Sweden)

    Keogh Louise A

    2009-05-01

    Full Text Available Abstract Objectives Effective chemoprevention strategies exist for women at high risk for breast cancer, yet uptake is low. Physician recommendation is an important determinant of uptake, but little is known about clinicians' attitudes to chemoprevention. Methods Focus groups were conducted with clinicians at five Family Cancer Centers in three Australian states. Discussions were recorded, transcribed and analyzed thematically. Results Twenty three clinicians, including genetic counselors, clinical geneticists, medical oncologists, breast surgeons and gynaecologic oncologists, participated in six focus groups in 2007. The identified barriers to the discussion of the use of tamoxifen and raloxifene for chemoprevention pertained to issues of evidence (evidence for efficacy not strong enough, side-effects outweigh benefits, oophorectomy superior for mutation carriers, practice (drugs not approved for chemoprevention by regulatory authorities and not government subsidized, chemoprevention not endorsed in national guidelines and not many women ask about it, and perception (clinicians not knowledgeable about chemoprevention and women thought to be opposed to hormonal treatments. Conclusion The study demonstrated limited enthusiasm for discussing breast cancer chemoprevention as a management option for women at high familial risk. Several options for increasing the likelihood of clinicians discussing chemoprevention were identified; maintaining up to date national guidelines on management of these women and education of clinicians about the drugs themselves, the legality of "off-label" prescribing, and the actual costs of chemopreventive medications.

  4. Institutional Repository Bibliography, Version 1

    OpenAIRE

    Bailey, Jr., Charles W.

    2009-01-01

    The Institutional Repository Bibliography (IRB) presents selected English-language articles, books, and other scholarly textual sources that are useful in understanding institutional repositories. Although institutional repositories intersect with a number of open access and scholarly communication topics, this bibliography only includes works that are primarily about institutional repositories. For example, an article dealing with the NIH open access policy would not be included, but one dea...

  5. Developing a sustainable institutional repository

    OpenAIRE

    White, Wendy

    2008-01-01

    This paper will provide an assessment of the factors involved in the development of sustainable platforms and processes for institutional repositories, drawing on the experience of the team at the University of Southampton and from project initiatives in the UK. It will look at the fundamental integration of repositories into the cultural, financial and technical structures of institutions to promote healthy repository growth. How do we effectively link repository development to institutional...

  6. Facets of Software Component Repository

    OpenAIRE

    Vaneet Kaur; Shivani Goel

    2011-01-01

    The software repository is used for storing, managing, and retrieving large numbers of software components. Repositories should be designed to meet the growing and changing needs of the software development organizations. Storage and representation of reusable software components in software repositories to assist retrieval is a key concern area. In this paper we have discussed various assets of thecomponent repository like component searching mechanisms and classifications such as Free Text,...

  7. Chemopreventive effect of 18β-glycyrrhetinic acid via modulation of inflammatory markers and induction of apoptosis in human hepatoma cell line (HepG2).

    Science.gov (United States)

    Hasan, Syed Kazim; Siddiqi, Aisha; Nafees, Sana; Ali, Nemat; Rashid, Summya; Ali, Rashid; Shahid, Ayaz; Sultana, Sarwat

    2016-05-01

    Hepatocellular carcinoma is one of the most common lethal diseases worldwide and there is no effective treatment till date. Natural products derived from the plants play an important role in chemoprevention and act as therapeutic antitumor agents. Licorice is a plant that has been used in food and medicine for the treatment of various diseases. 18β-Glycyrrhetinic acid (18β-GA), a pentacyclic triterpenoid obtained from the roots of licorice plant, is reported to possess various pharmacological properties such as antitumor and antiinflammatory activities. The present study was designed to elucidate the chemopreventive effect of 18β-GA through antiinflammation, antiproliferation, and induction of apoptosis in human hepatoma cell line HepG2. 18β-GA significantly inhibits the proliferation of HepG2 cell without affecting the normal liver cell line (Chang's). In the present study, 18β-GA increased the formation of reactive oxygen species, nitric oxide production, and loss of mitochondrial membrane potential, suggesting the involvement of 18β-GA in apoptosis which was also confirmed by assessing the markers involved in apoptosis like caspase-3, caspase-9, Bax:Bcl-2 ratio, and cleaved PARP. 18β-GA also downregulated the expression of inflammatory proteins such as NF-κB, iNOS, and COX-2. Keeping these data into consideration, our results suggest that 18β-GA may be used as a chemopreventive agent in liver cancer. PMID:27116616

  8. Repository program licensing approach

    International Nuclear Information System (INIS)

    Yucca Mountain, Nevada is currently being studied by the US Department of Energy (DOE) as a potential site for a mined geologic repository for high-level nuclear waste. DOE has the responsibility to determine the suitability of the site and to develop a license application (LA) for authorization to construct the potential repository. If the site is suitable, the license application would be submitted to the US Nuclear Regulatory Commission (NRC). The repository program licensing approach is focused on the timely acquisition of information needed in licensing and the resolution of potential licensing issues with the NRC staff. Licensing involves an iterative process requiring refinements as data are acquired, analyzed, and evaluated. The repository licensing approach presented in this paper ensures that the information is available when needed to facilitate the licensing process. Identifying the information needed to evaluate compliance with the performance objectives in 10 CFR 60, monitoring the acquisition of such information, and developing a successful license application are integral elements of DOE's repository program licensing approach. Activities to characterize the site are being systematically conducted as planned in the Site Characterization Plan (SCP). In addition, DOE is implementing the issue resolution initiative, the license application annotated outline (LAAO) process, and interim licensability evaluations to update the early planning in the SCP and to focus site characterization, design, and performance assessment activities on the acquisition of information needed for a site suitability determination and licensing. Collectively, the issue resolution initiative, LAAO process, and interim licensability evaluations are key elements of a transition to the iterative process to answer the question: open-quotes When do we have enough data to support licensing?close quotes

  9. Publishers and repositories

    CERN Document Server

    CERN. Geneva

    2007-01-01

    The impact of self-archiving on journals and publishers is an important topic for all those involved in scholarly communication. There is some evidence that the physics arXiv has had no impact on physics journals, while 'economic common sense' suggests that some impact is inevitable. I shall review recent studies of librarian attitudes towards repositories and journals, and place this in the context of IOP Publishing's experiences with arXiv. I shall offer some possible reasons for the mis-match between these perspectives and then discuss how IOP has linked with arXiv and experimented with OA publishing. As well as launching OA journals we have co-operated with Cornell and the arXiv on Eprintweb.org, a platform that offers new features to repository users. View Andrew Wray's biography

  10. Repository seals requirement study

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-11-03

    The Yucca Mountain Site Characterization Project, managed by the Civilian Radioactive Waste Management System (CRWMS) Management and Operating Contractor (M and O) is conducting investigations to support the Viability Assessment and the License Application for a high-level nuclear waste repository at Yucca Mountain, Nevada. The sealing subsystem is part of the Yucca Mountain Waste Isolation System. The Yucca Mountain Site Characterization Project is currently evaluating the role of the sealing subsystem (shaft, ramp and exploratory borehole seals) in achieving the overall performance objectives for the Waste Isolation System. This report documents the results of those evaluations. The objective of the study is to provide water or air flow performance based requirements for shafts, ramps, and exploratory boreholes located near the repository. Recommendations, as appropriate, are provided for developing plans, seals component testing, and other studies relating to sealing.

  11. Czech Republic. Dukovany repository

    International Nuclear Information System (INIS)

    Full text: The repository at the Dukovany site is a structure located above the land surface. It consists of two double-rows of reinforced concrete vaults. Each double-row has dimensions 38x160x6 meters and contains 2x28 vaults. The internal dimensions of each vault are 18x6x5.4 meters. The repository serves for reactor wastes from the Dukovany and Temelin nuclear power plants (NPPs). Its capacity is 55,000 m3 or 130,000 drums. The repository is a fully engineered facility with multiple barriers. The first engineered barrier is the waste form (in the case of waste from the Dukovany NPP, the waste form is mainly bitumen, but concrete and glass are also considered as suitable solidification products). The second barrier is the container (a 200 litre steel drum or a HIC container), whereas the third consists of cut-off reinforced concrete walls with asphalt-based hydro-insulation. The fourth barrier is a cap which should protect the vaults against infiltration of rainwater and should serve also as an intrusion and erosion barrier. The fifth barrier is a drainage system around the repository which is composed of layers of gravel and sand. The void space in drums around the waste is filled with specially composed grout. Such waste packages are emplaced into the disposal vault, which is covered by pre-fabricated panels. Thereafter, joints between the panels are sealed and a provisional coverage added; the final cover, however, will be constructed only over the whole row of 28 vaults, until all vaults are filled with waste. The final cover will encompass the following components: reinforced concrete pre-fabricated panels (500 mm); cement overcoat (30 mm); insulation foil; concrete layer for cap levelling (5-150 mm); layer of asphalto-propylene concrete (150 mm); soil (450 mm); geotextile foil with topsoil (top surface vegetation). (author)

  12. Chemoprevention or mastectomy for women at high risk of developing breast cancer.

    Science.gov (United States)

    Sismondi, Piero; D'Alonzo, Marta; Pecchio, Silvia; Bounous, Valentina Elisabetta; Robba, Elisabetta; Biglia, Nicoletta

    2015-11-01

    Breast cancer (BC) is the most commonly diagnosed invasive cancer among women; in developed countries, BC occurs in one out of eight women during her lifetime. Many factors, both genetic and non-genetic, determine a woman's risk of breast cancer and several mathematical models have been proposed that determine the risk. It is important to identify those at high risk, as there are now effective preventive strategies, such as chemoprevention therapy and risk-reduction surgery. Risk-reduction agents are recommended for women aged 35 years or more who are at high risk of breast cancer. Tamoxifen is presently deemed to be the agent of choice. However, raloxifene may be preferable, at least for some postmenopausal women, because of its lack of effect on the endometrium and the reduced incidence of venous thromboembolic events compared with tamoxifen. Prophylactic surgery has been widely investigated. Bilateral mastectomy decreases the risk of developing breast cancer by approximately 90% in women at moderate or high risk and in known BRCA1/2 mutation carriers. This review summarizes the recent advances in the identification of women at high risk of developing breast cancer and reports on the strategies used to prevent breast cancer; the risk-benefit balance of such preventive choices is also briefly analyzed. PMID:26276104

  13. The chemopreventive flavonoid apigenin confers radiosensitizing effect in human tumor cells grown as monolayers and spheroids

    International Nuclear Information System (INIS)

    Apigenin, a common dietary flavonoid present in many fruits and vegetables, is a nonmutagenic chemopreventive agent. In the present study, we investigated the effect of apigenin on the radiosensitivity of SQ-5 cells, which are derived from a human lung carcinoma. Actively growing cells were incubated for 16 h at 37 deg C in medium containing 40 μM apigenin. The cells were then irradiated with X-rays and incubated with apigenin for a further 8 h. Radiosensitivity was assessed using a clonogenic assay. Apoptosis and necrosis were assessed using acridine orange/ethidium bromide double staining. Cells incubated with apigenin exhibited significantly greater radiosensitivity and apoptosis levels than cells not incubated with apigenin. Protein levels were measured by Western blotting. Incubation with apigenin increased protein expression of WAF1/p21 and decreased protein expression of Bcl-2. Furthermore, apigenin sensitized SQ-5 spheroids (cell aggregates growing in a three-dimensional structure that simulate the growth and microenvironmental conditions of in vivo tumors) to radiation. Thus, apigenin appears to be a promising radiosensitizing agent for use against human carcinomas. (author)

  14. Nitroxides as antioxidants – possibilities of their application in chemoprevention and radioprotection

    Directory of Open Access Journals (Sweden)

    Sabina Tabaczar

    2011-01-01

    Full Text Available Nitroxides as stabile organic radicals were used initially as spin labels in spectroscopy of electron paramagnetic resonance (EPR with respect to parameters such as pH of an intercellular environment, oxygenation of cells and tissues, fluidity of biological membranes, conformational state and topography of proteins. Nitroxides have also been used in biology and medicine as contrast agents in magnetic resonance imaging (MRI. When their antioxidant activities were discovered, an era of research on the potential utility of these agents began. Nitroxides can modulate the redox state of the cell by participation in oxidation/reduction reactions. Therefore, they are extensively examined in various models of oxidative stress. The antioxidant effect of nitroxides is a result of their ability to catalyze dismutation of superoxide radical (superoxide dismutase-like activity, inhibit lipid peroxidation, prevent Fenton and Haber-Weiss reactions by oxidation of transition metal ions to a higher oxidative state, and confer catalase-like activity on heme proteins. In the present paper the antioxidative mechanisms of nitroxides are presented. The relation between structure, function and the rate of nitroxide reduction inside cells and tissues is also presented. The application of nitroxides in chemoprevention and radioprotection is discussed.

  15. Implications for chemoprevention of prostate cancer with intake of cruciferous vegetables

    Institute of Scientific and Technical Information of China (English)

    Jeanny B Aragon-Ching

    2011-01-01

    @@ Efforts on chemoprevention have been an attractive target of investigation for prostate cancer.Since prostate cancer is the most common non-cutaneous malignancy among American men, efforts for chemopreventative strategies make sense.However, such undertaking has been wrought with problems and wide-scale efforts to launch drug chemoprevention have been dampened by mixed results.

  16. Staged Repository Development Programmes

    Energy Technology Data Exchange (ETDEWEB)

    Isaacs, T

    2003-10-01

    Programs to manage and ultimately dispose of high-level radioactive wastes are unique from scientific and technological as well as socio-political aspects. From a scientific and technological perspective, high-level radioactive wastes remain potentially hazardous for geological time periods-many millennia-and scientific and technological programs must be put in place that result in a system that provides high confidence that the wastes will be isolated from the accessible environment for these many thousands of years. Of course, ''proof'' in the classical sense is not possible at the outset, since the performance of the system can only be known with assurance, if ever, after the waste has been emplaced for those geological time periods. Adding to this challenge, many uncertainties exist in both the natural and engineered systems that are intended to isolate the wastes, and some of the uncertainties will remain regardless of the time and expense in attempting to characterize the system and assess its performance. What was perhaps underappreciated in the early days of waste management and repository program development were the unique and intense reactions that the institutional, political, and public bodies would have to repository program development, particularly in programs attempting to identify and then select sites for characterization, design, licensing, and ultimate development. Reactions in most nations were strong, focused, unrelenting, and often successful in hindering, derailing, and even stopping national repository programs. The reasons for such reactions and the measures to successfully respond to them are still evolving and continue to be the focus of many national program and political leaders. Adaptive Staging suggests an approach to repository program development that reflects the unique challenges associated with the disposal of high-level radioactive waste. The step-wise, incremental, learn-as-you-go approach is intended to

  17. Staged Repository Development Programmes

    International Nuclear Information System (INIS)

    Programs to manage and ultimately dispose of high-level radioactive wastes are unique from scientific and technological as well as socio-political aspects. From a scientific and technological perspective, high-level radioactive wastes remain potentially hazardous for geological time periods-many millennia-and scientific and technological programs must be put in place that result in a system that provides high confidence that the wastes will be isolated from the accessible environment for these many thousands of years. Of course, ''proof'' in the classical sense is not possible at the outset, since the performance of the system can only be known with assurance, if ever, after the waste has been emplaced for those geological time periods. Adding to this challenge, many uncertainties exist in both the natural and engineered systems that are intended to isolate the wastes, and some of the uncertainties will remain regardless of the time and expense in attempting to characterize the system and assess its performance. What was perhaps underappreciated in the early days of waste management and repository program development were the unique and intense reactions that the institutional, political, and public bodies would have to repository program development, particularly in programs attempting to identify and then select sites for characterization, design, licensing, and ultimate development. Reactions in most nations were strong, focused, unrelenting, and often successful in hindering, derailing, and even stopping national repository programs. The reasons for such reactions and the measures to successfully respond to them are still evolving and continue to be the focus of many national program and political leaders. Adaptive Staging suggests an approach to repository program development that reflects the unique challenges associated with the disposal of high-level radioactive waste. The step-wise, incremental, learn-as-you-go approach is intended to maximize the

  18. Repository performance confirmation

    International Nuclear Information System (INIS)

    Repository performance confirmation links the technical bases of repository science and societal acceptance. This paper explores the myriad aspects of what has been labeled performance confirmation in U.S. programs, which involves monitoring as a collection of distinct activities combining technical and social significance in radioactive waste management. This paper is divided into four parts: (1) A distinction is drawn between performance confirmation monitoring and other testing and monitoring objectives; (2) A case study illustrates confirmation activities integrated within a long-term testing and monitoring strategy for Yucca Mountain; (3) A case study reviews compliance monitoring developed and implemented for the Waste Isolation Pilot Plant; and (4) An approach for developing, evaluating and implementing the next generation of performance confirmation monitoring is presented. International interest in repository monitoring is exhibited by the European Commission Seventh Framework Programme 'Monitoring Developments for Safe Repository Operation and Staged Closure' (MoDeRn) Project. The MoDeRn partners are considering the role of monitoring in a phased approach to the geological disposal of radioactive waste. As repository plans advance in different countries, the need to consider monitoring strategies within a controlled framework has become more apparent. The MoDeRn project pulls together technical and societal experts to assimilate a common understanding of a process that could be followed to develop a monitoring program. A fundamental consideration is the differentiation of confirmation monitoring from the many other testing and monitoring activities. Recently, the license application for Yucca Mountain provided a case study including a technical process for meeting regulatory requirements to confirm repository performance as well as considerations related to the preservation of retrievability. The performance confirmation plan developed as part of the

  19. Repository performance confirmation.

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Francis D.

    2011-09-01

    Repository performance confirmation links the technical bases of repository science and societal acceptance. This paper explores the myriad aspects of what has been labeled performance confirmation in U.S. programs, which involves monitoring as a collection of distinct activities combining technical and social significance in radioactive waste management. This paper is divided into four parts: (1) A distinction is drawn between performance confirmation monitoring and other testing and monitoring objectives; (2) A case study illustrates confirmation activities integrated within a long-term testing and monitoring strategy for Yucca Mountain; (3) A case study reviews compliance monitoring developed and implemented for the Waste Isolation Pilot Plant; and (4) An approach for developing, evaluating and implementing the next generation of performance confirmation monitoring is presented. International interest in repository monitoring is exhibited by the European Commission Seventh Framework Programme 'Monitoring Developments for Safe Repository Operation and Staged Closure' (MoDeRn) Project. The MoDeRn partners are considering the role of monitoring in a phased approach to the geological disposal of radioactive waste. As repository plans advance in different countries, the need to consider monitoring strategies within a controlled framework has become more apparent. The MoDeRn project pulls together technical and societal experts to assimilate a common understanding of a process that could be followed to develop a monitoring program. A fundamental consideration is the differentiation of confirmation monitoring from the many other testing and monitoring activities. Recently, the license application for Yucca Mountain provided a case study including a technical process for meeting regulatory requirements to confirm repository performance as well as considerations related to the preservation of retrievability. The performance confirmation plan developed as part

  20. Towards Interoperable Preservation Repositories: TIPR

    Directory of Open Access Journals (Sweden)

    Priscilla Caplan

    2010-07-01

    Full Text Available Towards Interoperable Preservation Repositories (TIPR is a project funded by the Institute of Museum and Library Services to create and test a Repository eXchange Package (RXP. The package will make it possible to transfer complex digital objects between dissimilar preservation repositories.  For reasons of redundancy, succession planning and software migration, repositories must be able to exchange copies of archival information packages with each other. Every different repository application, however, describes and structures its archival packages differently. Therefore each system produces dissemination packages that are rarely understandable or usable as submission packages by other repositories. The RXP is an answer to that mismatch. Other solutions for transferring packages between repositories focus either on transfers between repositories of the same type, such as DSpace-to-DSpace transfers, or on processes that rely on central translation services.  Rather than build translators between many dissimilar repository types, the TIPR project has defined a standards-based package of metadata files that can act as an intermediary information package, the RXP, a lingua franca all repositories can read and write.

  1. Repository simulation model: Final report

    International Nuclear Information System (INIS)

    This report documents the application of computer simulation for the design analysis of the nuclear waste repository's waste handling and packaging operations. The Salt Repository Simulation Model was used to evaluate design alternatives during the conceptual design phase of the Salt Repository Project. Code development and verification was performed by the Office of Nuclear Waste Isolation (ONWL). The focus of this report is to relate the experience gained during the development and application of the Salt Repository Simulation Model to future repository design phases. Design of the repository's waste handling and packaging systems will require sophisticated analysis tools to evaluate complex operational and logistical design alternatives. Selection of these design alternatives in the Advanced Conceptual Design (ACD) and License Application Design (LAD) phases must be supported by analysis to demonstrate that the repository design will cost effectively meet DOE's mandated emplacement schedule and that uncertainties in the performance of the repository's systems have been objectively evaluated. Computer simulation of repository operations will provide future repository designers with data and insights that no other analytical form of analysis can provide. 6 refs., 10 figs

  2. Antioxidative and Chemopreventive Properties of Vernonia amygdalina and Garcinia biflavonoid

    Directory of Open Access Journals (Sweden)

    Olatunde Owoeye

    2011-06-01

    Full Text Available Recently, considerable attention has been focused on dietary and medicinal phytochemicals that inhibit, reverse or retard diseases caused by oxidative and inflammatory processes. Vernonia amygdalina is a perennial herb belonging to the Asteraceae family. Extracts of the plant have been used in various folk medicines as remedies against helminthic, protozoal and bacterial infections with scientific support for these claims. Phytochemicals such as saponins and alkaloids, terpenes, steroids, coumarins, flavonoids, phenolic acids, lignans, xanthones, anthraquinones, edotides and sesquiterpenes have been extracted and isolated from Vernonia amygdalina. These compounds elicit various biological effects including cancer chemoprevention. Garcinia kola (Guttiferae seed, known as “bitter kola”, plays an important role in African ethnomedicine and traditional hospitality. It is used locally to treat illnesses like colds, bronchitis, bacterial and viral infections and liver diseases. A number of useful phytochemicals have been isolated from the seed and the most prominent of them is the Garcinia bioflavonoids mixture called kolaviron. It has well-defined structure and an array of biological activities including antioxidant, antidiabetic, antigenotoxic and hepatoprotective properties. The chemopreventive properties of Vernonia amygdalina and Garcinia biflavonoids have been attributed to their abilities to scavenge free radicals, induce detoxification, inhibit stress response proteins and interfere with DNA binding activities of some transcription factors.

  3. Tea beverage in chemoprevention and chemotherapy of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Imtiaz A SIDDIQUI; Mohammad SALEEM; Vaqar M ADHAMI; Mohammad ASIM; Hasan MUKHTAR

    2007-01-01

    Prostate cancer (Pca) is the most frequently diagnosed malignancy and the sec-ond leading cause of cancer-related deaths in American males with similar trends in many western countries. The existing treatment approaches and surgical inter-vention have not been able to effectively cope with this dreaded disease. For these reasons, it is necessary to intensify our efforts for a better understanding of the disease process and for the development of novel approaches for its preven-tion and treatment. Based on considerable evidence from in vivo and in vitro data and epidemiological studies, in recent years the beverage tea has gained consid-erable attention for reducing the risk of several cancers. Much of the cancerpreventive effects of tea, especially green tea appear to be mediated by the polyphe-nols present therein. Geographical evidence suggests that the incidence and occurrence of Pca is lower in populations that consume tea regularly. This evi-dence suggests that tea polyphenols could be extrapolated to optimize their chemopreventive properties against Pca. Pca represents an excellent candidate disease for chemoprevention because it is typically diagnosed in men over 50 years of age and therefore, even a modest delay in neoplastic development achieved through pharmacological or nutritional intervention could result in a substantial reduction in the incidence of clinically detectable disease. In this review we address the issue of possible use of tea, especially green tea, for the prevention aswell as treatment of Pca.

  4. NASA Biological Specimen Repository

    Science.gov (United States)

    McMonigal, K. A.; Pietrzyk, R. A.; Sams, C. F.; Johnson, M. A.

    2010-01-01

    The NASA Biological Specimen Repository (NBSR) was established in 2006 to collect, process, preserve and distribute spaceflight-related biological specimens from long duration ISS astronauts. This repository provides unique opportunities to study longitudinal changes in human physiology spanning may missions. The NBSR collects blood and urine samples from all participating ISS crewmembers who have provided informed consent. These biological samples are collected once before flight, during flight scheduled on flight days 15, 30, 60, 120 and within 2 weeks of landing. Postflight sessions are conducted 3 and 30 days after landing. The number of in-flight sessions is dependent on the duration of the mission. Specimens are maintained under optimal storage conditions in a manner that will maximize their integrity and viability for future research The repository operates under the authority of the NASA/JSC Committee for the Protection of Human Subjects to support scientific discovery that contributes to our fundamental knowledge in the area of human physiological changes and adaptation to a microgravity environment. The NBSR will institute guidelines for the solicitation, review and sample distribution process through establishment of the NBSR Advisory Board. The Advisory Board will be composed of representatives of all participating space agencies to evaluate each request from investigators for use of the samples. This process will be consistent with ethical principles, protection of crewmember confidentiality, prevailing laws and regulations, intellectual property policies, and consent form language. Operations supporting the NBSR are scheduled to continue until the end of U.S. presence on the ISS. Sample distribution is proposed to begin with selections on investigations beginning in 2017. The availability of the NBSR will contribute to the body of knowledge about the diverse factors of spaceflight on human physiology.

  5. On Duplication in Mathematical Repositories

    OpenAIRE

    Grabowski, Adam; Schwarzweller, Christoph

    2010-01-01

    Building a repository of proof-checked mathematical knowledge is without any doubt a lot of work, and besides the actual formalization process there also is the task of maintaining the repository. Thus it seems obvious to keep a repsoitory as small as possible, in particular each piece of mathematical knowledge should be formalized only once. In this paper, however, we claim that it might be reasonable or even necessary to duplicate knowledge in a mathematical repository. We analyze different...

  6. The institutional repository

    CERN Document Server

    Jones, Richard; MacColl, John

    2006-01-01

    Providing a thorough review of the concept of the Institutional Repository (IR) the book examines how they can be set up, maintained and embedded into general institutional working practice. Specific reference is made to capturing certain types of research material such as E-Theses and E-Prints and what the issues are with regard to obtaining the material, ensuring that all legal grounds are covered and then storing the material in perpetuity. General workflow and administrative processes that may come up during the implementation and maintenance of an IR are discussed.

  7. Granite-repository - geochemical environment

    International Nuclear Information System (INIS)

    Some geochemical data of importance for a radioactive waste repository in hard rock are reviewed. The ground water composition at depth is assessed. The ground water chemistry in the vicinity of uranium ores is discussed. The redox system in Swedish bedrock is described. Influences of extreme climatic changes and of repository mining and construction are also evaluated

  8. The business of digital repositories

    OpenAIRE

    Swan, Alma

    2008-01-01

    This chapter is aimed at those who are involved in planning, setting up and running a digital repository for an institution or community. It covers making a business case, costs, staffing requirements, managing growth and change and other sustainability issues. A number of repository case studies across Europe were used to derive data to inform the study.

  9. ACCELERATION PHYSICS CODE WEB REPOSITORY.

    Energy Technology Data Exchange (ETDEWEB)

    WEI, J.

    2006-06-26

    In the framework of the CARE HHH European Network, we have developed a web-based dynamic accelerator-physics code repository. We describe the design, structure and contents of this repository, illustrate its usage, and discuss our future plans, with emphasis on code benchmarking.

  10. Institutional Repositories, Tout de Suite

    OpenAIRE

    Bailey, Jr., Charles W.

    2008-01-01

    Institutional Repositories, Tout de Suite is designed to give the reader a very quick introduction to key aspects of institutional repositories and to foster further exploration of this topic through liberal use of relevant references to online documents and links to pertinent websites.

  11. Safety analysis in subsurface repositories

    International Nuclear Information System (INIS)

    The development of mathematical models to represent the repository-geosphere-biosphere system, and the development of a structure for data acquisition, processing, and use to analyse the safety of subsurface repositories, are presented. To study the behavior of radionuclides in geosphere a laboratory to determine the hydrodynamic dispersion coefficient was constructed. (M.C.K.)

  12. BEI Resource Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — BEI Resources provides reagents, tools and information for studying Category A, B, and C priority pathogens, emerging infectious disease agents, non-pathogenic...

  13. Influence analysis of Github repositories.

    Science.gov (United States)

    Hu, Yan; Zhang, Jun; Bai, Xiaomei; Yu, Shuo; Yang, Zhuo

    2016-01-01

    With the support of cloud computing techniques, social coding platforms have changed the style of software development. Github is now the most popular social coding platform and project hosting service. Software developers of various levels keep entering Github, and use Github to save their public and private software projects. The large amounts of software developers and software repositories on Github are posing new challenges to the world of software engineering. This paper tries to tackle one of the important problems: analyzing the importance and influence of Github repositories. We proposed a HITS based influence analysis on graphs that represent the star relationship between Github users and repositories. A weighted version of HITS is applied to the overall star graph, and generates a different set of top influential repositories other than the results from standard version of HITS algorithm. We also conduct the influential analysis on per-month star graph, and study the monthly influence ranking of top repositories. PMID:27540501

  14. Women victims of sexual violence: adherence to chemoprevention of HIV.

    Science.gov (United States)

    Diniz, Normélia Maria Freire; de Almeida, Lílian Conceição Guimarães; dos S Ribeiro, Bárbara Cristina; de Macêdo, Valéria Góes

    2007-01-01

    This study aimed to investigate the adherence of women victims of sexual violence, to AIDS chemoprevention treatment. A quantitative study was carried out at a care service to victims of sexual violence in Salvador (Bahia, Brazil). Study participants were 172 women. Data were collected through interviews with forms and consultation of patient files. The results showed that 45.4% of the abused women were teenagers and 40.7% of the attended women were raped. Only 54% of the women were advised to use antiretrovirals to prevent HIV. Adherence to treatment occurred in 57.4% of cases and discontinuity corresponded to 42.6%. Non-adherence to treatment was attributed to psychological or emotional disorders and non-understanding of the established treatment. Therefore, it is important that professionals pay careful attention in order to perceive the conditions that might increase women's vulnerability to the infection. PMID:17375226

  15. Analysis of the development of Ukrainian repositories

    OpenAIRE

    Tarasov, Dmytro; Andrukhiv, Andriy; Тарасов, Д.; Андрухів, А.

    2012-01-01

    The article presents analysis of the development of Ukrainian repositories and contribution of Lviv Polytechnic National University Institutional Repository in the development of Open Access in Ukraine.

  16. Chemopreventive drugs: Mechanisms via inhibition of cancer stem cells in colorectal cancer

    OpenAIRE

    Kim, Tae Il

    2014-01-01

    Recent epidemiological studies, basic research and clinical trials on colorectal cancer (CRC) prevention have helped identify candidates for effective chemopreventive drugs. However, because of the conflicting results of clinical trials or side effects, the effective use of chemopreventive drugs has not been generalized, except for patients with a high-risk for developing hereditary CRC. Advances in genetic and molecular technologies have highlighted the greater complexity of carcinogenesis, ...

  17. Chemoprevention of chemical-induced skin cancer by Panax ginseng root extract

    OpenAIRE

    Sharma, Jyoti; Pradeep K. Goyal

    2015-01-01

    Background Cancer has emerged as a major health problem globally as a consequence to the increased longevity of the population, changing the environment and life style. Chemoprevention is a new and promising strategy for reducing cancer burden. Recently, some natural products have been identified for their chemopreventive activity to reduce the cancer incidence. Ginseng is known for its potential to treat various ailments in human beings. The present study was designed to explore the anticanc...

  18. Biomarker and animal models for assessment of retinoid efficacy in cancer chemoprevention

    Institute of Scientific and Technical Information of China (English)

    Richard M NILES

    2007-01-01

    Vitamin A is essential for normal growth and development. Epidemiology and laboratory studies suggest that decreased vitamin A levels and defective metabo-lisrn/action may contribute to the genesis of certain cancers. Based on this information, natural and synthetic derivatives of vitamin A (retinoids) have been used for chemoprevention of cancer. Retinoids have had some success in the chemoprevention of leukoplakia and in the decreased incidence of second prima-ties in head and neck cancer. There is little information on biomarkers that can be used to assess the efficacy of the chemopreventive activity of retinoids. The ability of retinoids to induce RARb has been consistently shown to correlate with the response of cells and tissues to retinoic acid, but few other biomarkers have been certified as indicators of retinoid activity. In light of the failure of the ATBC and CARET clinical intervention trials for chemoprevention of lung cancer, greater use of animal models for chemoprevention studies is necessary. The potential combination of phytochemicals that inhibit DNA methyltransferase activity with retinoids holds promise for more effective chemoprevention of retinoid-unrespon-sive premalignant lesions.

  19. Phytoconstituents as apoptosis inducing agents: strategy to combat cancer.

    Science.gov (United States)

    Kumar, Manish; Kaur, Varinder; Kumar, Subodh; Kaur, Satwinderjeet

    2016-08-01

    Advancement in the field of cancer molecular biology has aided researchers to develop various new chemopreventive agents which can target cancer cells exclusively. Cancer chemopreventive agents have proficiency to inhibit, reverse and delay process of carcinogenesis during its early and later course. Chemopreventive agents can act as antioxidative, antimutagenic/antigenotoxic, anti-inflammatory agents or via aiming various molecular targets in a cell to induce cell death. Apoptosis is a kind of cell death which shows various cellular morphological alterations such as cell shrinkage, blebbing of membrane, chromatin condensation, DNA fragmentation, formation of apoptotic bodies etc. Nowadays, apoptosis is being one of the new approaches for the identification and development of novel anticancer therapies. For centuries, plants are known to play part in daily routine from providing food to management of human health. In the last two decades, diverse phytochemicals and various botanical formulations have been characterized as agents that possess potential to execute cancer cells via inducing apoptosis. Data obtained from the research carried out globally pointed out that natural products are the potential candidates which have capability to combat cancer. In the present review, we surveyed literature on natural products which throws light on the mechanism through which these phytochemicals induce apoptosis in cancer cells. PMID:26239338

  20. Biospecimen repositories and cytopathology.

    Science.gov (United States)

    Krishnamurthy, Savitri

    2015-03-01

    Biospecimen repositories are important for the advancement of biomedical research. Literature on the potential for biobanking of fine-needle aspiration, gynecologic, and nongynecologic cytology specimens is very limited. The potential for biobanking of these specimens as valuable additional resources to surgically excised tissues appears to be excellent. The cervicovaginal specimens that can be used for biobanking include Papanicolaou-stained monolayer preparations and residual material from liquid-based cytology preparations. Different types of specimen preparations of fine-needle aspiration and nongynecologic specimens, including Papanicolaou-stained and Diff-Quik-stained smears, cell blocks. and dedicated passes/residual material from fine-needle aspiration stored frozen in a variety of solutions, can be used for biobanking. Because of several gaps in knowledge regarding the standard of operative procedures for the procurement, storage, and quality assessment of cytology specimens, further studies as well as national conferences and workshops are needed not only to create awareness but also to facilitate the use of cytopathology specimens for biobanking. PMID:25524469

  1. VHA Data Sharing Agreement Repository

    Data.gov (United States)

    Department of Veterans Affairs — The VHA Data Sharing Agreement Repository serves as a centralized location to collect and report on agreements that share VHA data with entities outside of VA. It...

  2. Book Review: The Institutional Repository

    Directory of Open Access Journals (Sweden)

    Isabel Galina

    2007-03-01

    Full Text Available At a time when the future nature of scholarly communication and publishing are being debated this book serves as a useful reference guide for one of the key aspects- the institutional repository. Institutional repositories are a popular recent development for distributing and communicating research. They are a useful academic tool for administrating and publishing electronic resources produced by university members in order to increase access to these, both at an institutional and global level. However, there is still no general concensus about the characteristics of an institutional repository. What types of material are deposited? Who is responsible for building and maintaing a repository, how will copyright be managed, who will cover installation and maintenance costs? How will quality, integrity and preservation of the materials be assured?

  3. Privacy Impact Assessment (PIA) Repository

    Data.gov (United States)

    Department of Veterans Affairs — This repository contains Privacy Impact Assessments (PIA) that have been vetted/approved. Section 208 of the Electronic Government Act of 2002 (E-Gov Act) requires...

  4. NIH Common Data Elements Repository

    Data.gov (United States)

    U.S. Department of Health & Human Services — The NIH Common Data Elements (CDE) Repository has been designed to provide access to structured human and machine-readable definitions of data elements that have...

  5. Business models for digital repositories

    CERN Document Server

    CERN. Geneva; Bjørnshauge, Lars

    2007-01-01

    Those setting up, or planning to set up, a digital repository may be interested to know more about what has gone before them. What is involved, what is the cost, how many people are needed, how have others made the case to their institution, and how do you get anything into it once it is built? I have recently undertaken a study of European repository business models for the DRIVER project and will present an overview of the findings.

  6. Institutional Repository Movement in Turkey

    OpenAIRE

    Akbayrak, Emre Hasan; Bayram, Özlem; Coşkun, Cem; Holt, İlkay; Karasözen, Bülent; Tonta, Yaşar

    2006-01-01

    ANKOS (The Anatolian University Libraries Consortium) established Open Access and the Institutional Repositories Working Group (OAIRWG) in order to raise awareness on Open Access (OA) and Institutional Repositories (IRs) among information professionals in Turkey. Ankara University is one of the first open access initiatives in Turkey. It has been involved in ANKOS since 2001, expressing a strong interest from the beginning. Over seven hundred and fifty scientific papers produced by faculty...

  7. Management of Indian Institutional Repositories

    OpenAIRE

    Sawant, S. S.

    2010-01-01

    The study investigates various issues concerning the management of institutional repositories (IRs) developed in India. Data collection done using a web based questionnaire, created using software provided by surveymonkey.com. The entire population i.e. all IRs identified in India were surveyed. It was observed that in 42.86% (6) of Institutional Repositories implementation programmes were headed by librarians. No special staff was appointed by any institution for carrying out different jobs...

  8. Distributed Repositories for Educational Content

    OpenAIRE

    Klebl, Michael; Bernd J. Krämer

    2010-01-01

    As education providers increasingly integrate digital learning media into their education processes, the need for the systematic management of learning materials and learning arrangements becomes clearer. Digital repositories, often called Learning Object Repositories (LOR), promise to provide an answer to this challenge. This article is composed of two parts. In this part, we derive technological and pedagogical requirements for LORs from a concretization of information quality criteria for ...

  9. Distributed Repositories for Educational Content

    OpenAIRE

    Klebl, Michael; Bernd J. Krämer; Zobel, Annett; Hupfer, Matthias; Lukaschik, Christian

    2010-01-01

    In Part 1 of this article we discussed the need for information quality and the systematic management of learning materials and learning arrangements. Digital repositories, often called Learning Object Repositories (LOR), were introduced as a promising answer to this challenge. We also derived technological and pedagogical requirements for LORs from a concretization of information quality criteria for e-learning technology. This second part presents technical solutions that particularly addre...

  10. Evaluation of Nuclide Release Scenarios for a Hypothetical LILW Repository

    International Nuclear Information System (INIS)

    A program for the safety assessment and performance evaluation of a low- and intermediate-level radioactive waste (LILW) repository system has been developed. Utilizing GoldSim (GoldSim, 2006), the program evaluates nuclide release and transport into the geosphere and biosphere under various disruptive natural and manmade events and scenarios that can occur after a waste package failure. We envisaged and illustrated these events and scenarios as occurring after the closure of a hypothetical LILW repository, and they included the degradation of various manmade barriers, pumping well drilling, and natural disruptions such as the sudden formation of a preferential flow pathway in the far-field area of the repository. Possible enhancement of nuclide transport facilitated by colloids or chelating agents is also dealt with. We used the newly-developed GoldSim template program, which is capable of various nuclide release scenarios and is greatly suited for simulating a potential repository given the geological circumstances in Korea, to create the detailed source term and near-field release scheme, various nuclide transport modes in the far-field geosphere area, and the biosphere transfer. Even though all parameter values applied to the hypothetical repository were assumed, the illustrative results, particularly the probabilistic calculations and sensitivity studies, may be informative under various scenarios

  11. Chemoprevention of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster cheek pouch carcinogenesis by a 5-lipoxygenase inhibitor, garcinol.

    Science.gov (United States)

    Chen, Xin; Zhang, Xinyan; Lu, Ye; Shim, Joong-Youn; Sang, Shengmin; Sun, Zheng; Chen, Xiaoxin

    2012-01-01

    Our previous studies have shown that aberrant arachidonic acid metabolism, especially the 5-lipoxygenase (5-Lox) pathway, is involved in oral carcinogenesis and can be targeted for cancer prevention. To develop potent topical agents for oral cancer chemoprevention, 5 known 5-Lox inhibitors from dietary and synthetic sources (Zileuton, ABT-761, licofelone, curcumin, and garcinol) were evaluated in silico for their potential efficacy. Garcinol, a polyisoprenylated benzophenone from the fruit rind of Garcinia spp., was found to be a promising agent based on the calculation of a theoretical activity index. Computer modeling showed that garcinol well fit the active site of 5-Lox, and potentially inhibited enzyme activity through interactions between the phenolic hydroxyl groups and the non-heme catalytic iron. In a short-term study on 7,12-dimethylbenz[a]anthracene (DMBA)-treated hamster cheek pouch, topical garcinol suppressed leukotriene B4 (LTB4) biosynthesis and inhibited inflammation and cell proliferation in the oral epithelium. In a long-term carcinogenesis study, topical garcinol significantly reduced the size of visible tumors, the number of cancer lesions, cell proliferation, and LTB4 biosynthesis. These results demonstrated that topical application of a 5-Lox inhibitor, garcinol, had chemopreventive effect on DMBA-induced hamster cheek pouch carcinogenesis. PMID:23137051

  12. Demystifying the institutional repository for success

    CERN Document Server

    Buehler, Marianne

    2013-01-01

    Institutional repositories remain key to data storage on campus, fulfilling the academic needs of various stakeholders. Demystifying the Institutional Repository for Success is a practical guide to creating and sustaining an institutional repository through marketing, partnering, and understanding the academic needs of all stakeholders on campus. This title is divided into seven chapters, covering: traditional scholarly communication and open access publishing; the academic shift towards open access; what the successful institutional repository looks like; institutional repository collaboratio

  13. Experimental DML over digital repositories in Japan

    OpenAIRE

    Namiki, Takao; Kuroda, Hiraku; Naruse, Shunsuke

    2009-01-01

    In this paper the authors show an overview of Virtual Digital Mathematics Library in Japan (DML-JP), contents of which consist of metadata harvested from institutional repositories in Japan and digital repositories in the world. DML-JP is, in a sense, a subject specific repository which collaborate with various digital repositories. Beyond portal website, DML-JP provides subject-specific metadata through OAI-ORE. By the schema it is enabled that digital repositories can load the rich metadata...

  14. Radioactive waste repository of high ecological safety

    International Nuclear Information System (INIS)

    With the purpose to construct a radioactive waste repository of high ecological safety and reliable containment, MosNPO 'Radon' specialists have developed an advanced type repository - large diameter well (LBD) one. A project is started for the development of a technology for LDW repository construction and pilot operation of the new repository for 25-30 years. The 2 LDW repositories constructed at the 'Radon' site and the developed monitoring system are described

  15. Evaluation of the chemopreventive response of naringenin-loaded nanoparticles in experimental oral carcinogenesis using laser-induced autofluorescence spectroscopy

    International Nuclear Information System (INIS)

    The aim of the present study is to investigate the chemopreventive effects of prepared naringenin-loaded nanoparticles (NARNPs) relative to the efficacy of free naringenin (NAR) in modifying the carcinogenic process and to study the changes in the endogenous fluorophores during DMBA-induced hamster buccal pouch (HBP) carcinogenesis by laser-induced autofluorescence (LIAF) spectroscopy. LIAF emission spectra from the hamster buccal mucosa of the control and experimental groups of animals were recorded in the 350–700 nm spectral range on a miniature fiber optic spectrometer from different anatomical sites of each group, with excitation at 404 nm from a diode laser. 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. DMBA-painted animals revealed morphological changes, hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. LIAF emission spectra showed significant difference between the control and tumor tissues. The tumor tissues are characterized by an increase in the emission of porphyrins and a decrease in the emission of nicotinamide adenine dinucleotide hydrogenase (NADH) and flavin adenine nucleotide (FAD) when compared to the control tissues. Furthermore, oral administration of NAR and its nanoparticulates restored the status of endogenous fluorophores in the buccal mucosa of DMBA-painted animals. On a comparative basis, the treatment of nanoparticulate naringenin was found to be more effective than free naringenin in completely preventing the formation of squamous cell carcinoma and in improving the status of endogenous porphyrins to a normal range in DMBA-induced hamster buccal pouch carcinogenesis. The result of the present study further suggests that LIAF spectroscopy may be a very valuable tool for rapid and sensitive detection of endogenous fluorophore changes in response to chemopreventive agents. (paper)

  16. Evaluation of the chemopreventive response of naringenin-loaded nanoparticles in experimental oral carcinogenesis using laser-induced autofluorescence spectroscopy

    Science.gov (United States)

    Sulfikkarali, N. K.; Krishnakumar, N.

    2013-04-01

    The aim of the present study is to investigate the chemopreventive effects of prepared naringenin-loaded nanoparticles (NARNPs) relative to the efficacy of free naringenin (NAR) in modifying the carcinogenic process and to study the changes in the endogenous fluorophores during DMBA-induced hamster buccal pouch (HBP) carcinogenesis by laser-induced autofluorescence (LIAF) spectroscopy. LIAF emission spectra from the hamster buccal mucosa of the control and experimental groups of animals were recorded in the 350-700 nm spectral range on a miniature fiber optic spectrometer from different anatomical sites of each group, with excitation at 404 nm from a diode laser. 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. DMBA-painted animals revealed morphological changes, hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. LIAF emission spectra showed significant difference between the control and tumor tissues. The tumor tissues are characterized by an increase in the emission of porphyrins and a decrease in the emission of nicotinamide adenine dinucleotide hydrogenase (NADH) and flavin adenine nucleotide (FAD) when compared to the control tissues. Furthermore, oral administration of NAR and its nanoparticulates restored the status of endogenous fluorophores in the buccal mucosa of DMBA-painted animals. On a comparative basis, the treatment of nanoparticulate naringenin was found to be more effective than free naringenin in completely preventing the formation of squamous cell carcinoma and in improving the status of endogenous porphyrins to a normal range in DMBA-induced hamster buccal pouch carcinogenesis. The result of the present study further suggests that LIAF spectroscopy may be a very valuable tool for rapid and sensitive detection of endogenous fluorophore changes in response to chemopreventive agents.

  17. Organ-specific exposure and response to sulforaphane, a key chemopreventive ingredient in broccoli: implications for cancer prevention.

    Science.gov (United States)

    Veeranki, Omkara L; Bhattacharya, Arup; Marshall, James R; Zhang, Yuesheng

    2013-01-14

    Naturally occurring sulforaphane (SF) has been extensively studied for cancer prevention. However, little is known as to which organs may be most affected by this agent, which impedes its further development. In the present study, SF was administered to rats orally either in a single dose or once daily for 7 d. Tissue distribution of SF was measured by a HPLC-based method. Glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), two well-known cytoprotective phase 2 enzymes, were measured using biochemical assays to assess tissue response to SF. SF was delivered to different organs in vastly different concentrations. Tissue uptake of SF was the greatest in the stomach, declining rapidly in the descending gastro-intestinal tract. SF was rapidly eliminated through urinary excretion, and urinary concentrations of SF equivalents were 2-4 orders of magnitude higher than those of plasma. Indeed, tissue uptake level of SF in the bladder was second only to that in the stomach. Tissue levels of SF in the colon, prostate and several other organs were very low, compared to those in the bladder and stomach. Moreover, induction levels of GST and NQO1 varied by 3- to 6-fold among the organs of SF-treated rats, though not strictly correlated with tissue exposure to SF. Thus, there is profound organ specificity in tissue exposure and response to dietary SF, suggesting that the potential chemopreventive benefit of dietary SF may differ significantly among organs. These findings may provide a basis for prioritising organs for further chemopreventive study of SF. PMID:22464629

  18. Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells.

    Science.gov (United States)

    Wang, Piwen; Wang, Bin; Chung, Seyung; Wu, Yanyuan; Henning, Susanne M; Vadgama, Jaydutt V

    2014-08-01

    The low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds that share molecular anti-carcinogenic targets may enhance the effect on these targets at low concentrations of individual compound, thereby overcoming the limitations of reduced bioavailability. We therefore investigated whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds of Arctium lappa, green tea polyphenol (-)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency of individual compounds. LNCaP prostate cancer and MCF-7 breast cancer cells were treated with 2-4 mg/L (about 5-10μM) Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG synergistically increased the antiproliferative effect. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of Cur. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest of Cur at G0/G1 phase. The strongest effects on cell cycle arrest and apoptosis were achieved by combining all three compounds in both cell lines. The combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatment. These results warrant in vivo studies to confirm the efficacy of this novel regimen by combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer. PMID:25243063

  19. Combination chemoprevention with diclofenac, calcipotriol and difluoromethylornithine inhibits development of non-melanoma skin cancer in mice

    DEFF Research Database (Denmark)

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

    2013-01-01

    Background/Aim: With increasing incidence of non-melanoma skin cancer (NMSC), focus on chemoprevention of this disease is growing. The aim of this study was to evaluate topical combination therapies as chemoprevention of UV radiation-induced tumors in a mouse model.......Background/Aim: With increasing incidence of non-melanoma skin cancer (NMSC), focus on chemoprevention of this disease is growing. The aim of this study was to evaluate topical combination therapies as chemoprevention of UV radiation-induced tumors in a mouse model....

  20. Novel Marine Phenazines as Potential Cancer Chemopreventive and Anti-Inflammatory Agents

    OpenAIRE

    Rui Yu; van Breemen, Richard B.; Asolkar, Ratnakar N.; Murphy, Brian T.; William Fenical; Kondratyuk, Tamara P.; Pezzuto, John M.; Eun-Jung Park

    2012-01-01

    Two new (1 and 2) and one known phenazine derivative (lavanducyanin, 3) were isolated and identified from the fermentation broth of a marine-derived Streptomyces sp. (strain CNS284). In mammalian cell culture studies, compounds 1, 2 and 3 inhibited TNF-α-induced NFκB activity (IC50 values of 4.1, 24.2, and 16.3 μM, respectively) and LPS-induced nitric oxide production (IC50 values of >48.6, 15.1, and 8.0 μM, respectively). PGE2 production was blocked with greater efficacy (IC50 values of 7...

  1. Light-Induced Toxic Effects of Tamoxifen: A Chemotherapeutic and Chemopreventive Agent

    OpenAIRE

    Wang, Lei; Wang, Shuguang; Yin, Jun-Jie; Peter P. Fu; Yu, Hongtao

    2009-01-01

    Tamoxifen is a powerful drug used to treat breast cancer patients, and more than 500,000 women in the U. S. are being treated with this drug. In our study, tamoxifen is found to be photomutagenic in Salmonella typhimurium TA102 at concentrations as low as 0.08 μM and reaches maximum photomutagenicity at 0.4 μM under a light dose equivalent to 20 min sunlight. These concentrations are comparable to the plasma tamoxifen concentration of 0.4 to 3 μM for patients undergoing tamoxifen therapy. The...

  2. Phytochemical Modulators of Mitochondria: The Search for Chemopreventive Agents and Supportive Therapeutics

    Directory of Open Access Journals (Sweden)

    Maja M. Grabacka

    2014-09-01

    Full Text Available Mitochondria are crucially important for maintaining not only the energy homeostasis, but the proper cellular functions in a general sense. Impairment of mitochondrial functions is observed in a broad variety of pathological states such as neoplastic transformations and cancer, neurodegenerative diseases, metabolic disorders and chronic inflammation. Currently, in parallel to the classical drug design approaches, there is an increasing interest in the screening for natural bioactive substances, mainly phytochemicals, in order to develop new therapeutic solutions for the mentioned pathologies. Dietary phytochemicals such as resveratrol, curcumin and sulforaphane are very well tolerated and can effectively complement classical pharmacological therapeutic regimens. In this paper we disscuss the effect of the chosen phytochemicals (e.g., resveratrol, curcumin, sulforaphane on various aspects of mitochondrial biology, namely mitochondrial biogenesis, membrane potential and reactive oxygen species production, signaling to and from the nucleus and unfolded protein response.

  3. UV-induced immune suppression and photocarcinogenesis: Chemoprevention by dietary botanical agents

    OpenAIRE

    Santosh K. Katiyar

    2007-01-01

    Studies of immune-suppressed transplant recipients and patients with biopsy-proven skin cancer have confirmed that ultraviolet (UV) radiation-induced immune suppression is a risk factor for the development of skin cancer in humans. UV radiation suppresses the immune system in several ways. The UVB spectrum inhibits antigen presentation, induces the release of immunosuppressive cytokines, and elicits DNA damage that is a molecular trigger of UV-mediated immunosuppression. It is therefore impor...

  4. Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator

    OpenAIRE

    Jiao, Yan; Wilkinson, John; Di, Xiumin; Wang, Wei; Hatcher, Heather; Kock, Nancy D.; D'Agostino, Ralph; Knovich, Mary Ann; Torti, Frank M; Suzy V Torti

    2009-01-01

    Curcumin is a natural product currently in human clinical trials for a variety of neoplastic, preneoplastic, and inflammatory conditions. We previously observed that, in cultured cells, curcumin exhibits properties of an iron chelator. To test whether the chelator activity of curcumin is sufficient to induce iron deficiency in vivo, mice were placed on diets containing graded concentrations of both iron and curcumin for 26 weeks. Mice receiving the lowest level of dietary iron exhibited borde...

  5. Spicing up a vegetarian diet: chemopreventive effects of phytochemicals.

    Science.gov (United States)

    Lampe, Johanna W

    2003-09-01

    Thousands of chemical structures have been identified in plant foods. Many are found in spices. Typically, spices are the dried aromatic parts of plants-generally the seeds, berries, roots, pods, and sometimes leaves-that mainly, but not invariably, grow in hot countries. Given the wide range of botanical species and plant parts from which spices are derived, they can contribute significant variety and complexity to the human diet. In the past, the medicinal uses of spices and herbs were often indistinguishable from their culinary uses, and for good reason: people have recognized for centuries both the inherent value, as well as the potential toxicity, of phytochemicals in relation to human health. Plants have the capacity to synthesize a diverse array of chemicals, and understanding how phytochemicals function in plants may further our understanding of the mechanisms by which they benefit humans. In plants, these compounds function to attract beneficial and repel harmful organisms, serve as photoprotectants, and respond to environmental changes. In humans, they can have complementary and overlapping actions, including antioxidant effects, modulation of detoxification enzymes, stimulation of the immune system, reduction of inflammation, modulation of steroid metabolism, and antibacterial and antiviral effects. Embracing a cuisine rich in spice, as well as in fruit and vegetables, may further enhance the chemopreventive capacity of one's diet. PMID:12936952

  6. Cancer chemopreventive and therapeutic activities of red ginseng.

    Science.gov (United States)

    Xiaoguang, C; Hongyan, L; Xiaohong, L; Zhaodi, F; Yan, L; Lihua, T; Rui, H

    1998-02-01

    Red ginseng extract A and B are the active components of Panax ginseng. Red ginseng is a classical traditional Chinese medicine. Among Chinese herbs, red ginseng has been considered as one of the tonics. Many studies indicated that red ginseng could enhance immune function of the human body. The effects of red ginseng extracts on transplantable tumors, proliferation of lymphocyte, two-stage model and rat liver lipid peroxidation were studied. In a two-stage model, red ginseng extracts had a significant cancer chemoprevention. At 50-400 mg/kg, they could inhibit DMBA/Croton oil-induced skin papilloma in mice, decrease the incidence of papilloma, prolong the latent period of tumor occurrence and reduce tumor number per mouse in a dose-dependent manner. Red ginseng extract B could effectively inhibit the Fe2+/cysteine-induced lipid peroxidation of rat liver microsome, suggesting that red ginseng extract B has a stronger antioxidative effect than that of extract A. The results indicated that red ginseng extracts (50 approximately 400 mg/kg) could significantly inhibit the growth of transplantable mouse sarcoma S180 and melanoma B16. Red ginseng extracts A (0.5 mg/ml) and B (0.1 and 0.25 mg/ml) might effectively promote the transformation of T lymphocyte, but there was no influence on lymphocyte proliferation stimulated by concanavalin A. This suggests that red ginseng extracts have potent tumor therapeutic activity and improve the cell immune system. PMID:9533434

  7. Molecular targets of cancer chemoprevention by garlic-derived organosulfides

    Institute of Scientific and Technical Information of China (English)

    Anna HERMAN-ANTOSIEWICZ; Anna A POWOLNY; Shivendra V SINGH

    2007-01-01

    The medicinal benefits of Allium vegetables, especially garlic, have been noted throughout recorded history. The known health benefits of Allium vegetables and their constituents include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, radioprotection, improvement of memory loss, protection against microbial, viral and fungal infections, as well as anticancer effects. Population-based case control studies have suggested an inverse correlation between dietary intake of Allium vegetables and the risk of different types of cancers. The anticarcinogenic effect of Allium vegetables in-eluding garlic is attributed to organosulfur compounds (OSC), which are highly effective in affording protection against cancer in animal models induced by a variety of chemical carcinogens. More recent studies have shown that certain naturally occurring OSC analogues can suppress proliferation of cancer cells in culture and in vivo. The OSC-induced changes in the proliferation of cancer Cellsare frequently associated with perturbations in cell cycle progression and induc-tion of G2/M phase arrest. The OSC have also been demonstrated to induce apoptosis via the intrinsic pathway by altering the ratio of the Bc1-2 family of proteins both in cell culture and in in vivo models. Anti-angiogenic activity for garlic-derived OSC has also been documented. This article summarizes current knowledge on molecular targets of cancer chemoprevention by OSC.

  8. The chemopreventive activity of the histone deacetylase inhibitor tributyrin in colon carcinogenesis involves the induction of apoptosis and reduction of DNA damage

    International Nuclear Information System (INIS)

    The chemopreventive activity of the histone deacetylase inhibitor (HDACi) tributyrin (TB), a prodrug of butyric acid (BA), was evaluated in a rat model of colon carcinogenesis. The animals were treated with TB (TB group: 200 mg/100 g of body weight, b.w.) or maltodextrin (MD isocaloric control group: 300 mg/100 g b.w.) daily for 9 consecutive weeks. In the 3rd and 4th weeks of treatment, the rats in the TB and MD groups were given DMH (40 mg/kg b.w.) twice a week. After 9 weeks, the animals were euthanized, and the distal colon was examined. Compared with the control group (MD group), TB treatment reduced the total number of aberrant crypt foci (ACF; p < 0.05) as well as the ACF with ≥ 4 crypts (p < 0.05), which are considered more aggressive, but not inhibited the formation of DMH-induced O6-methyldeoxyguanosine DNA adducts. The TB group also showed a higher apoptotic index (p < 0.05) and reduced DNA damage (p < 0.05) compared with MD group. TB acted as a HDACi, as rats treated with the prodrug of BA had higher levels of histone H3K9 acetylation compared with the MD group (p < 0.05). TB administration resulted in increased colonic tissue concentrations of BA (p < 0.05) compared with the control animals. These results suggest that TB can be considered a promising chemopreventive agent for colon carcinogenesis because it reduced the number of ACF, including those that were more aggressive. Induction of apoptosis and reduction of DNA damage are cellular mechanisms that appear to be involved in the chemopreventive activity of TB. - Highlights: • Tributyrin is a chemopreventive agent for rat colon aberrant crypt foci. • Tributyrin increased apoptosis in an experimental rat colon carcinogenesis model. • Tributyrin treatment in a rat colon carcinogenesis model decreased DNA damage. • Tributyrin treatment induced H3K9 acetylation in a rat colon carcinogenesis model

  9. The chemopreventive activity of the histone deacetylase inhibitor tributyrin in colon carcinogenesis involves the induction of apoptosis and reduction of DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Heidor, Renato [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Advanced Research Center in Food Science and Nutrition (NAPAN) and Food Research Center (FoRC), Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Furtado, Kelly Silva; Ortega, Juliana Festa [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Oliveira, Tiago Franco de [Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Tavares, Paulo Eduardo Latorre Martins; Vieira, Alessandra; Miranda, Mayara Lilian Paulino [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Purgatto, Eduardo [Laboratory of Food Chemistry and Biochemistry, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Advanced Research Center in Food Science and Nutrition (NAPAN) and Food Research Center (FoRC), Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Moreno, Fernando Salvador, E-mail: rmoreno@usp.br [Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil); Advanced Research Center in Food Science and Nutrition (NAPAN) and Food Research Center (FoRC), Faculty of Pharmaceutical Sciences, University of São Paulo (Brazil)

    2014-04-15

    The chemopreventive activity of the histone deacetylase inhibitor (HDACi) tributyrin (TB), a prodrug of butyric acid (BA), was evaluated in a rat model of colon carcinogenesis. The animals were treated with TB (TB group: 200 mg/100 g of body weight, b.w.) or maltodextrin (MD isocaloric control group: 300 mg/100 g b.w.) daily for 9 consecutive weeks. In the 3rd and 4th weeks of treatment, the rats in the TB and MD groups were given DMH (40 mg/kg b.w.) twice a week. After 9 weeks, the animals were euthanized, and the distal colon was examined. Compared with the control group (MD group), TB treatment reduced the total number of aberrant crypt foci (ACF; p < 0.05) as well as the ACF with ≥ 4 crypts (p < 0.05), which are considered more aggressive, but not inhibited the formation of DMH-induced O6-methyldeoxyguanosine DNA adducts. The TB group also showed a higher apoptotic index (p < 0.05) and reduced DNA damage (p < 0.05) compared with MD group. TB acted as a HDACi, as rats treated with the prodrug of BA had higher levels of histone H3K9 acetylation compared with the MD group (p < 0.05). TB administration resulted in increased colonic tissue concentrations of BA (p < 0.05) compared with the control animals. These results suggest that TB can be considered a promising chemopreventive agent for colon carcinogenesis because it reduced the number of ACF, including those that were more aggressive. Induction of apoptosis and reduction of DNA damage are cellular mechanisms that appear to be involved in the chemopreventive activity of TB. - Highlights: • Tributyrin is a chemopreventive agent for rat colon aberrant crypt foci. • Tributyrin increased apoptosis in an experimental rat colon carcinogenesis model. • Tributyrin treatment in a rat colon carcinogenesis model decreased DNA damage. • Tributyrin treatment induced H3K9 acetylation in a rat colon carcinogenesis model.

  10. Dietary factors and cancer chemoprevention: An overview of obesity-related malignancies

    Directory of Open Access Journals (Sweden)

    Murthy N

    2009-01-01

    Full Text Available Obesity is a growing health problem in developed nations and in countries that are in the process of westernization like India. Obesity is linked with several health disorders such as hypertension and cardiovascular diseases, Type 2 diabetes, dyslipidemia and certain cancers. Currently, obesity-related malignancies, e.g., cancers of the breast, prostate and colon are the leading cancers in the industrialized societies. An increased amount of fat or adipose tissue in an overweight or obese person probably influences the development of cancer by releasing several hormone-like factors or adipokines. The majority of adipokines are pro-inflammatory, which promote pathological conditions like insulin resistance and cancer. On the other hand, many recent studies have shown that adiponectin, an anti-inflammatory adipokine, has anti-cancer and insulin-sensitizing effects. Adiponectin exerts its physiological functions chiefly by activation of AMP kinase via adiponectin receptors. Interestingly, several fruits and vegetables may contain adiponectin-like molecules or may increase the biosynthesis of adiponectin in our body. Studies on adiponectin analogues or adiponectin receptor agonists are a promising area of cancer chemoprevention research. In general, fruits and vegetables contain various dietary substances such as vitamins, minerals (like calcium and selenium, fiber and phytochemicals or phenolic compounds (like flavonoids and vanilloids, which may act as anti-cancer agents. Similarly, several dietary constituents including phytochemicals may have anti-obesity effects. Consumption of such dietary compounds along with caloric restriction and physical activity may be helpful in preventing obesity-related cancers. For this review article, we searched PubMed primarily to get the relevant literature.

  11. Folic acid supplementation inhibits recurrence of colorectal adenomas: A randomized chemoprevention trial

    Institute of Scientific and Technical Information of China (English)

    Richard Jaszewski; Adhip PN Majumdar; Sabeena Misra; Martin Tobi; Nadeem Ullah; Jo Ann Naumoff; Omer Kucuk; Edi Levi; Bradley N Axelrod; Bhaumik B Patel

    2008-01-01

    AIM: To determine whether folic acid supplementation will reduce the recurrence of colorectal adenomas,the precursors of colorectal cancer, we performed a double-blind placebo-controlled trial in patients with adenomatous polyps.METHODS: In the current double-blind, placebo-controlled trial at this VA Medical Center, patients with colorectal adenomas were randomly assigned to receive either a daily 5 mg dose of folic acid or a matched identical placebo for 3 years. All polyps were removed at baseline colonoscopy and each patient had a follow up colonoscopy at 3 years. The primary endpoint was a reduction in the number of recurrent adenomas at 3 years.RESULTS: Of 137 subjects, who were eligible after confirmation of polyp histology and run-in period to conform compliance, 94 completed the study; 49 in folic acid group and 45 in placebo group. Recurrence of adenomas at 3-year was compared between the two groups. The mean number of recurrent polyps at 3-year was 0.36 (SD, 0.69) for folic acid treated patients compared to 0.82 (SD, 1.17) for placebo treated subjects, resulting in a 3-fold increase in polyp recurrence in the placebo group. Patients below 70 years of age and those with left-sided colonic adenomas or advanced adenomas responded better to folic acid supplementation.CONCLUSION: High dose folic acid supplementation is associated with a significant reduction in the recurrence of colonic adenomas suggesting that folic acid may be an effective chemopreventive agent for colorectal neoplasia.

  12. CANCER CHEMOPREVENTIVE ACTIVITIES OF S-3-1,A SYNTHETIC DERIVATIVE OF DANSHINONE

    Institute of Scientific and Technical Information of China (English)

    XIAO-GUANG CHEN; YAN LI; CHUN-HONG YAN; LIAN-NIANG LI; RUI HAN

    2001-01-01

    Salvia miltiorrhiza is a traditional Chinese medicine which has been well documented for its anti-cancer effects. Based on the structure of danshinone, one of the active compounds derived from Salvia miltiorrhiza, we synthesized a simplified phenolic analog, S-3-1, and tried to explore its possible actions in preventing the development of cancer. With the Ames test, S-3-1 was found to efficiently suppress the mutagenicity of benzo[a]pyrene. This result is consistent with the inhibitory effect of S-3-1 on the activation of benzo[α]pyrene by hepatic microsomal enzymes. Besides the anti-initiation effects, S-3-1 could significantly inhibit the croton oil induced increase of mouse skin epithermal ornithine decarboxylase activity. Moreover, S-3-1 quenched both superoxide and hydroxyl free radicals whereas it inhibited lipid peroxidation in the in vitro model. These results suggest that S-3-1 might act as anti-initiation and anti-promo tion agents through reversing the biochemical alterations induced by carcinogen during carcino genesis. Therefore, we further investigated the effects of S-3-1 on carcinogenesis. In vitro, S-3-1inhibited the benzo[a]pyrene-induced transformation of V79 Chinese hamster lung fibroblasts.At 10-40 mg/kg, S-3-1 was found to inhibit the development of DM BA/croton oil-induced skin papilloma in mice through decreasing the incidence of papilloma, prolonging the latent period of tumor occurrence and reducing tumor number per mouse in a dose-dependent manner. We concluded from this study that S-3-1 might be developed as a new chemopreventive drug.

  13. Repository Subsurface Preliminary Fire Hazard Analysis

    International Nuclear Information System (INIS)

    This fire hazard analysis identifies preliminary design and operations features, fire, and explosion hazards, and provides a reasonable basis to establish the design requirements of fire protection systems during development and emplacement phases of the subsurface repository. This document follows the Technical Work Plan (TWP) (CRWMS M and O 2001c) which was prepared in accordance with AP-2.21Q, ''Quality Determinations and Planning for Scientific, Engineering, and Regulatory Compliance Activities''; Attachment 4 of AP-ESH-008, ''Hazards Analysis System''; and AP-3.11Q, ''Technical Reports''. The objective of this report is to establish the requirements that provide for facility nuclear safety and a proper level of personnel safety and property protection from the effects of fire and the adverse effects of fire-extinguishing agents

  14. Thermomechanical interactions in repository design

    International Nuclear Information System (INIS)

    The design goal for radioactive waste repository design is a configuration that will last a very long time and restrict radionuclide migration. Because experiments and prototype observations cannot be relied upon to ascertain fully the long-term behavior of the repository, numerical modeling has been employed in attempts to predict the future repository conditions. Unfortunately, the variability of geologic media defies accurate modeling. Models may be verified for numerical accuracy but may not be validated by actual observations of the phenomena to the degree desired. Hence, there is a need to establish a strategy for design and performance assessment that does not fully rely on the validation of models. A strategy proposed here relies on an identification of plausible and possible failure modes rather than on a reliable prediction of aspects of repository behavior. Once failure modes have been identified, efforts can be concentrated on dealing with them, either by assessing their (low) probability of occurrence, or by preventing these failure modes by appropriate repository design. (orig.)

  15. In vitro and In vivo Studies on Stilbene Analogs as Potential Treatment Agents for Colon Cancer

    Science.gov (United States)

    Based upon the potential of resveratrol as a cancer chemopreventive agent, 27 stilbenes analogs were synthesized and tested against colon cancer cell line HT-29. Among these compounds, amino derivative (Z)-4-(3,5-dimethoxystyryl) aniline (4), (Z)-methyl 4-(3,5-dimethoxystyryl) benzoate (6) and (Z)-1...

  16. Cost-effectiveness of prostate cancer chemoprevention among high-risk men.

    Science.gov (United States)

    Zeliadt, Steven B; Ramsey, Scott D

    2010-10-01

    EVALUATION OF: Earnshaw SR, McDade CL, Black LK, Bell CF, Kattan MW. Cost effectiveness of 5-α reductase inhibitors for the prevention of prostate cancer in multiple patient populations. Pharmacoeconomics 28(6), 489-505 (2010). Chemoprevention with 5-α reductase inhibitors (5ARIs) has been shown in clinical trials to reduce the incidence of prostate cancer. Although avoiding or delaying a diagnosis of prostate cancer through chemoprevention is attractive, it is unknown whether 5ARI chemoprevention reduces the number of prostate cancer deaths. Prior cost-effectiveness studies have found the adoption of 5ARIs in the general population to not be cost effective owing to the high costs of 5ARIs and multiple years of treatment required before gains are realized. The current study examines the cost-effectiveness of 5ARIs for men with multiple risk factors, including an elevated prostate-specific antigen and a prior negative biopsy. The analysis consistently observes under multiple assumptions that chemoprevention in the subgroup of high-risk men is cost effective and represents a good value for money, while chemoprevention among men from the general population appears to not be cost effective. PMID:20950065

  17. Chemopreventive potential of Triphala (a composite Indian drug) on Benzo(a)pyrene induced forestomach tumorigenesis in murine tumor model system

    International Nuclear Information System (INIS)

    The present work is probably the first report on cancer chemopreventive potential of Triphala, a combination of fruit powder of three different plants namely Terminalia chebula, Terminalia belerica and Emblica officinalis. Triphala is a popular formulation of the Ayurvedic system of medicine. Our findings have shown that Triphala in diet has significantly reduced the benzo(a)pyrene [B(a)P] induced forestomach papillomagenesis in mice. In the short term treatment groups, the tumor incidences were lowered to 77.77% by both doses of Triphala mixed diet. In the case of long-term treatment the tumor incidences were reduced to 66.66% and 62.50% respectively by 2.5% and 5% triphala containing diet. Tumor burden was 7.27±1.16 in the B(a)P treated control group, whereas it reduced to 3.00±0.82 (p<0.005) by 2.5% dose and 2.33 +/- 1.03 (p<0.001) by 5% dose of Triphala. In long-term studies the tumor burden was reduced to 2.17±0.75 (p<0.001) and 2.00±0.71 (p<0.001) by 2.5% and 5% diet of Triphala, respectively. It was important to observe that Triphala was more effective in reducing tumor incidences compared to its individual constituents. Triphala also significantly increased the antioxidant status of animals which might have contributed to the chemoprevention. It was inferred that the concomitant use of multiple agents seemed to have a high degree of chemoprevention potential

  18. Oral chemoprevention with acetyl salicylic Acid, vitamin d and calcium reduces the risk of tobacco carcinogen-induced bladder tumors in mice

    DEFF Research Database (Denmark)

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

    2013-01-01

    , and diet with chemoprevention (acetyl salicylic acid, 1-alpha 25(0H)2-vitamin D3 and calcium). There were significantly fewer tumors (0 (0-0) vs. 0 (0-2), p = .045) and fewer animals with tumors (0/20 vs. 5/20, p = .045) in the chemoprevention group compared with controls. Thus, chemoprevention diet...

  19. Institutional Repositories in BRICS Countries : A Study

    Directory of Open Access Journals (Sweden)

    S. Dhanavandan

    2015-06-01

    Full Text Available An institutional repository includes digital assets generated by academics, such as administrative documents, course notes, learning objects, or conference proceedings. It will provide a window that gives open access to improve the sponsoring institution’s visibility and status. This paper discusses the growth and development of Institutional Repositories available in BRICS Countries. The relevant data was collected from the directory of OpenDOAR. Based on the data in OpenDOAR, 242 repositories are represented from BRICS countries. Among the 242, 84 (34.71% repositories are from Brazil, 39 (16.12% from China, 68 (28.10% repositories from India, 22 (9.109% repositories from Russia, and 29(11.98% repositories from South Africa. Brazil has the largest number of records (11, 17,688 among BRICS Countries repositories.

  20. Gaining independence through institutional repositories

    OpenAIRE

    Buckholtz, Alison

    2002-01-01

    The author presents SPARC's Initiative about open archives and its relationship with the OAI. Institutional repositories are institutionally defined as a content generated by institutional community, have a scholarly content: preprints and working papers, published articles, enduring teaching materials, student theses, etc. And also are cumulative and perpetual (preserve ongoing access to material) and interoperable and open access: free, online, global.

  1. Semantic repository and ontology mapping

    NARCIS (Netherlands)

    J. Gracia; M. Trna; E. Lozano; T.T. Nguyen; A. Gómez-Pérez; C. Montaña; J. Liem

    2010-01-01

    This document discusses the core Semantic Technologies in DynaLearn: i) The semantic repository, which supports the online storage and access of qualitative reasoning models, ii) the grounding process, which establishes semantic equivalences between the concepts in the models and the concepts in a b

  2. Repository operational criteria comparative analysis

    Energy Technology Data Exchange (ETDEWEB)

    Hageman, J.P.; Chowdhury, A.H. [Southwest Research Inst., San Antonio, TX (United States). Center for Nuclear Waste Regulatory Analyses

    1994-06-01

    The objective of the ``Repository Operational Criteria (ROC) Feasibility Studies`` (or ROC task) was to conduct comprehensive and integrated analyses of repository design, construction, and operations criteria in 10 CFR Part 60 regulations considering the interfaces among the components of the regulations and impacts of any potential changes to those regulations. The ROC task addresses regulatory criteria and uncertainties related to the preclosure aspects of the geologic repository. Those parts of 10 CFR Part 60 that require routine guidance or minor changes to the rule were addressed in Hageman and Chowdhury, 1992. The ROC task shows a possible need for further regulatory clarity, by major changes to the rule, related to the design bases and siting of a geologic repository operations area and radiological emergency planning in order to assure defense-in-depth. The analyses, presented in this report, resulted in the development and refinement of regulatory concepts and their supporting rationale for recommendations for potential major changes to 10 CFR Pan 0 regulations.

  3. Effect of gallic acid on xenobiotic metabolizing enzymes in 1,2-dimethyl hydrazine induced colon carcinogenesis in Wistar rats--a chemopreventive approach.

    Science.gov (United States)

    Giftson Senapathy, J; Jayanthi, S; Viswanathan, P; Umadevi, P; Nalini, N

    2011-04-01

    Colon cancer risk may be influenced by phase I and II xenobiotic-metabolizing enzyme systems. The chemopreventive agent gallic acid (GA), a plant polyphenol, is found in various natural products. Our aim was to evaluate the potential role of GA on drug-metabolizing enzymes in 1,2-dimethyl hydrazine (DMH) induced rat colon carcinogenesis. The total experimental duration was 30 weeks. The effect of GA (50 mg/kg b.w.) on the activities of phase I enzymes (cytochrome P450 and cytochrome b5) and phase II enzymes (glutathione S-transferase, DT-diaphorase and gamma glutamyl transpeptidase) were assessed in the liver and colonic mucosa and the colons were also examined visually. In DMH induced rats, there was a decrease in the activities of phase II enzymes and an increase in the activities of phase I enzymes. On GA supplementation, there was a significant increase in the activities of phase II enzymes and a significant decrease in the activities of phase I enzymes, in addition to the decreased tumor incidence. Histopathological changes also confirm this. Thus, the marked potential of GA in modulating the phase I and II xenobiotic-metabolizing enzymes suggests that GA may have a major impact on colon cancer chemoprevention. PMID:21172399

  4. Faulty assumptions for repository requirements

    International Nuclear Information System (INIS)

    Long term performance requirements for a geologic repository for spent nuclear fuel and high-level waste are based on assumptions concerning water use and subsequent deaths from cancer due to ingesting water contaminated with radio isotopes ten thousand years in the future. This paper argues that the assumptions underlying these requirements are faulty for a number of reasons. First, in light of the inevitable technological progress, including efficient desalination of water, over the next ten thousand years, it is inconceivable that a future society would drill for water near a repository. Second, even today we would not use water without testing its purity. Third, today many types of cancer are curable, and with the rapid progress in medical technology in general, and the prevention and treatment of cancer in particular, it is improbable that cancer caused by ingesting contaminated water will be a significant killer in the far future. This paper reviews the performance requirements for geological repositories and comments on the difficulties in proving compliance in the face of inherent uncertainties. The already tiny long-term risk posed by a geologic repository is presented and contrasted with contemporary every day risks. A number of examples of technological progress, including cancer treatments, are advanced. The real and significant costs resulting from the overly conservative requirements are then assessed. Examples are given of how money (and political capital) could be put to much better use to save lives today and in the future. It is concluded that although a repository represents essentially no long-term risk, monitored retrievable dry storage (above or below ground) is the current best alternative for spent fuel and high-level nuclear waste

  5. Digital Preservation Initiatives in Ontario: Trusted Digital Repositories and Research Data Repositories

    Directory of Open Access Journals (Sweden)

    Wayne Johnston

    2012-12-01

    Full Text Available The first in a series of two articles dealing with digital preservation, this article discusses repositories, more specifically Trusted Digital Repositories (TDR and Research Data Repositories. The focus will be on the TDRs at Scholars Portal and Library and Archives Canada (LAC, and the data repository at the University of Guelph.

  6. Digital Preservation Initiatives in Ontario: Trusted Digital Repositories and Research Data Repositories

    OpenAIRE

    Wayne Johnston

    2012-01-01

    The first in a series of two articles dealing with digital preservation, this article discusses repositories, more specifically Trusted Digital Repositories (TDR) and Research Data Repositories. The focus will be on the TDRs at Scholars Portal and Library and Archives Canada (LAC), and the data repository at the University of Guelph.

  7. Exploiting and improving institutional repositories for bibliometrics

    OpenAIRE

    Iriarte, Pablo; de Kaenel, Isabele; Krause, Jan Brice; Magnenat, Nathalie

    2011-01-01

    Institutional repositories have a dual role, being both open archives, disseminating without barriers research results financed by public funds, and a directory of institutional scientific publications. Today, a new kind of functionality may be added to these repositories : they allow to evaluate University's scientific production through bibliometric analysis. Indeed, two special types of metadata are included into institutional repositories: bibliographic and administrative information (att...

  8. Urban Radioactive Waste Repositories in China

    International Nuclear Information System (INIS)

    In order to strengthen the storage and management of radioactive waste and disused radioactive sources, the Chinese Government decided in 2005 to construct urban radioactive waste repositories to achieve “one province, one repository”. This project constructed and renovated 31 urban repositories as well as one national repository. Through several years of unremitting efforts, all the repositories have been completed and put into use. The paper introduces the situation of this project and details information by taking the Jiangsu repository as an example, and analyses challenges and problems of disused sources in recovery, conditioning and disposal in China. (author)

  9. Online educational repositories for promoting agricultural knowledge

    Directory of Open Access Journals (Sweden)

    C.I. Costopoulou

    2010-11-01

    Full Text Available Towards promoting sustainable agriculture and economic growth, the development of the agricultural workforce and set up of innovative agricultural systems are required. Agricultural educational repositories are systems used for storing, reusing and sharing agricultural learning resources. They contribute to agricultural education at different educational levels and target groups. Thus, this paper firstly provides an overview of Institutional repositories (IRs and Open Access Archives (OAAs in Greece and agricultural repositories worldwide. Also, it describes the agricultural repositories that provide access to educational content in Greek and presents experiences from the establishment of Agricultural University of Athens’ (AUA repository.

  10. Experimental DML over digital repositories in Japan

    CERN Document Server

    Namiki, Takao; Naruse, Shunsuke

    2009-01-01

    In this paper the authors show an overview of Virtual Digital Mathematics Library in Japan (DML-JP), contents of which consist of metadata harvested from institutional repositories in Japan and digital repositories in the world. DML-JP is, in a sense, a subject specific repository which collaborate with various digital repositories. Beyond portal website, DML-JP provides subject-specific metadata through OAI-ORE. By the schema it is enabled that digital repositories can load the rich metadata which were added by mathematicians.

  11. Azoxymethane-induced rat aberrant crypt foci: Relevance in studying chemoprevention of colon cancer

    Institute of Scientific and Technical Information of China (English)

    Jayadev Raju

    2008-01-01

    The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries.Aberrant crypt foci (ACF) represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans.ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis.For over two decades,since its first discovery,azoxymethane(AOM)-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens.Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system.There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up,and extensive research in this field is currently in progress.In chemoprevention studies,AOM-induced rat ACF have been very successful as biomarkers,and have provided several standardized analyses of data.There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome,however,and hence there has been an ambiguity about their role as biomarkers.The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies.The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.

  12. Disruption of androgen and estrogen receptor activity in prostate cancer by a novel dietary diterpene carnosol: implications for chemoprevention

    Science.gov (United States)

    Johnson, Jeremy J.; Syed, Deeba N.; Suh, Yewseok; Heren, Chenelle R.; Saleem, Mohammad; Siddiqui, Imtiaz A.; Mukhtar, Hasan

    2010-01-01

    Emerging data is suggesting that estrogens, in addition to androgens, may also be contributing to the development of prostate cancer (PCa). In view of this notion agents that target estrogens, in addition to androgens, may be a novel approach for PCa chemoprevention and treatment. Thus, the identification and development of non-toxic dietary agents capable of disrupting androgen receptor (AR) in addition to estrogen receptor (ER) could be extremely useful in the management of PCa. Through molecular modeling we found carnosol, a dietary diterpene fits within the ligand binding domain of both AR and ER-α. Using a TR-FRET assay we found that carnosol interacts with both AR and ER-α and additional experiments confirmed that it functions as a receptor antagonist with no agonist effects. LNCaP, 22Rv1, and MCF7 cells treated with carnosol (20–40 µM) showed decreased protein expression of AR and ER-α. Oral administration of carnosol at 30 mg/kg five days weekly for 28 days to 22Rv1 PCa xenografted mice suppressed tumor growth by 36% (p = 0.028) and was associated with a decrease in serum PSA by 26% (p=0.0042). These properties make carnosol unique to any known anti-androgen or anti-estrogen investigated so far for the simultaneous disruption of AR and ER-α. We suggest that carnosol may be developed or chemically modified through more rigorous structure activity relationship studies for a new class of investigational agents - a dual AR/ER modulator. PMID:20736335

  13. Coupled processes in repository sealing

    International Nuclear Information System (INIS)

    The significance of coupled processes in repository sealing is evaluated. In most repository designs, shaft seals will be located in areas of relatively low temperature perturbation, in which case the coupling of temperature with stress and permeability may be less significant than the coupling between stress and permeability that occurs during excavation. Constitutive relationships between stress and permeability are reviewed for crystal-line rock and rocksalt. These provide a basis for predicting the development of disturbed zones near excavations. Field case histories of the degree of disturbance are presented for two contrasting types-Stripa granite and Southeastern New Mexico rocksalt. The results of field investigations in both rock types confirm that hydraulic conductivity or permeability is stress dependent, and that shaft seal performance may be related to the degree that stresses are perturbed and restored near the seal

  14. Evaluating the NTUA institutional repository

    OpenAIRE

    Koulouris, Alexandros; Kokkinos, Dionysios; Anagnostopoulos, Angelos; Zidropoulos, Spilios

    2008-01-01

    The National Technical University of Athens (NTUA), through its Central Library, offers an Institutional Repository (IR) and ETD submission service, currently operating in a pilot testing period. The main objectives of this paper can be summarized into three major points. Primarily, to evaluate the IR service pilot period, focusing on the ETD submission process. Secondarily, to refine and improve the above mentioned process and, finally, to promote the concept of self-archiving and open acces...

  15. Thermomechanical response of WIPP repositories

    International Nuclear Information System (INIS)

    Coarsely zoned STEALTH 2D calculations were used to investigate two candidate WIPP repositories. The grid was designed for one hundred thousand years of response with modest computing costs. As a result, the early time mechanical response was compromised by non-real oscillations that could not be damped completely before a few thousand years. In spite of these oscillations, it was possible to see that the dominant effects of stress and strain peaked between one and two thousand years, at the time of maximum heat in the site. This time corresponded to the condition that the surface heat loss rate balanced the heat generation rate. Though the creep strains were quite small, a large volume of salt was involved and the effects were significant. The peak surface uplift of 75HLW was increased by about 25% due to creep. However, the deviatoric stress relaxation due to creep produced large changes in the stress fields. The Rustler layer survived reasonable failure criterion for the 75HLW case with creep, and failed both in tension and shear, according to these same criterion, when the calculation was repeated without creep. The deviatoric stress fields, with and without salt creep, concentrated near the repository as expected and also in the Rustler layer due to its relatively high Young's modulus compared to the neighboring layers. Since the time of interest is so much smaller than the 100,000 years this calculation was designed to examine, it is possible to model the WIPP stratigraphy in much more detail and still be able to calculate the response for the time of interest. A finer zoned calculation of the response of the WIPP stratigraphy to a repository similar to the 75 K watt/acre repository is modeled in this report. In this calculation the Rustler formation is modeled as a five layered formation using material properties derived from data taken at the Nome site

  16. APLIKASI ONLINE MOBILE REPOSITORY SYSTEM

    OpenAIRE

    Michael Yoseph Ricky

    2011-01-01

    In order to support the decision-making process effectively and efficiently, a lot of companies invest in information technology for data management and storage. The information technology is emphasized in data storage of daily transactions in large numbers in a medium, so that data can be easily processed. Online Mobile Repository System is a system that uses a temporary storage system which is practical and can be accessed online. Thus, the system simplifies data access and organization ...

  17. Underground repository for radioactive wastes

    International Nuclear Information System (INIS)

    In the feasibility study for an underground repository in Argentina, the conceptual basis for the final disposal of high activity nuclear waste was set, as well as the biosphere isolation, according to the multiple barrier concept or to the engineering barrier system. As design limit, the container shall act as an engineering barrier, granting the isolation of the radionuclides for approximately 1000 years. The container for reprocessed and vitrified wastes shall have three metallic layers: a stainless steel inner layer, an external one of a metal to be selected and a thick intermediate lead layer preselected due to its good radiological protection and corrosion resistance. Therefore, the study of the lead corrosion behaviour in simulated media of an underground repository becomes necessary. Relevant parameters of the repository system such as temperature, pressure, water flux, variation in salt concentrations and oxidants supply shall be considered. At the same time, a study is necessary on the galvanic effect of lead coupled with different candidate metals for external layer of the container in the same experimental conditions. Also temporal evaluation about the engineering barrier system efficiency is presented in this thesis. It was considered the extrapolated results of corrosion rates and literature data about the other engineering barriers. Taking into account that corrosion is of a generalized type, the integrity of the lead shall be maintained for more than 1000 years and according to temporal evaluation, the multiple barrier concept shall retard the radionuclide dispersion to the biosphere for a period of time between 104 and 106 years. (Author)

  18. Geotechnical instrumentation for repository shafts

    International Nuclear Information System (INIS)

    The US Congress passed the Nuclear Waste Policy Act in 1980, which required that three distinctly different geologic media be investigated as potential candidate sites for the permanent disposal of high-level nuclear waste. The three media that were selected for study were basalt (WA), salt (TX, LA, MS, UT), and tuff (NV). Preliminary Exploratory Shaft Facilities (ESF) designs were prepared for seven candidate salt sites, including bedded and domal salt environments. A bedded-salt site was selected in Deaf Smith County, TX for detailed site characterization studies and ESF Final Design. Although Congress terminated the Salt Repository Program in 1988, Final Design for the Deaf Smith ESF was completed, and much of the design rationale can be applied to subsequent deep repository shafts. This paper presents the rationale for the geotechnical instrumentation that was designed for construction and operational performance monitoring of the deep shafts of the in-situ test facility. The instrumentation design described herein can be used as a general framework in designing subsequent instrumentation programs for future high-level nuclear waste repository shafts

  19. Repository development status in Spain

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Beceiro, Alvaro; Zuloaga, Pablo [ENRESA (Spain)

    2009-06-15

    The paper describes the status of repository development for the different waste categories. Low and Intermediate Waste Disposal facility of El Cabril was commissioned in 1992 and is in normal operation. The major modifications and activities during the last years are the adaptation to waste streams not initially foreseen such as some decommissioning waste or waste from steel industry, and the improvement of its performance assessment, supported by a R and D and refined models. As part of this facility, a new disposal facility specifically intended for very low activity waste has been constructed and commissioned in July 2008. Its design is based on the European Directive for hazardous waste disposal. National policy for Nuclear Spent Fuel and High-Level waste is focused on the development of a centralized storage facility of the vault type, whose site location would be selected through a volunteering process. Meanwhile, with the aim of solving specific problems, three individual storage facilities are in different status at reactor sites. Research on final solution, including some repository aspects as well as separation and transmutation are being carried out in accordance to ENRESA's R and D program. ENRESA has developed conceptual designs for non site specific repositories, both in granite and clay, and has carried out their corresponding performance assessment exercises. (authors)

  20. Preclinical renal cancer chemopreventive efficacy of geraniol by modulation of multiple molecular pathways

    International Nuclear Information System (INIS)

    Graphical abstract: Diagrammatic presentation of the hypothesis of the article in a concise manner. It reveals the chemopreventive efficacy of GOH possibly through the modulation of multiple molecular targets. GOH inhibits ROS generation, NFκB and PCNA expression thereby abrogating inflammation and proliferation of tubular cells of kidney. Whereas, GOH induces effector caspase-3 expression both through mitochondrial signalling pathway and death receptor signalling pathway. Highlights: → Geraniol modulates renal carcinogenesis in Wistar rats. → It abrogates Fe-NTA induced oxidative stress, inflammation and hyperproliferation. → Promotes apoptosis via induction of both mitochondrial and death receptor pathway. → Thus, inhibits renal carcinogenesis by modulating multiple molecular targets. -- Abstract: In the present study, we have evaluated the chemopreventive potential of geraniol (GOH), an acyclic monoterpene alcohol against ferric nitrilotriacetate (Fe-NTA) induced renal oxidative stress and carcinogenesis in Wistar rats. Chronic treatment of Fe-NTA induced oxidative stress, inflammation and cellular proliferation in Wistar rats. The chemopreventive efficacy of GOH was studied in terms of xenobiotic metabolizing enzyme activities, LPO, redox status, serum toxicity markers and the expression of putative nephrotoxicity biomarker Kim-1, tumor suppressor gene P53, inflammation, cell proliferation and apoptosis related genes in the kidney tissue. Oral administration of GOH at doses of 100 and 200 mg/kg b wt effectively suppressed renal oxidative stress and tumor incidence. Chemopreventive effects of GOH were associated with upregulation of xenobiotic metabolizing enzyme activities and down regulation of serum toxicity markers. GOH was able to down regulate expression of Kim-1, NFκB, PCNA, P53 along with induction of apoptosis. However, higher dose of GOH was more effective in modulating these multiple molecular targets both at transcriptional and protein

  1. Familial adenomatous polyposis in pediatrics: natural history, emerging surveillance and management protocols, chemopreventive strategies, and areas of ongoing debate.

    Science.gov (United States)

    Septer, Seth; Lawson, Caitlin E; Anant, Shrikant; Attard, Thomas

    2016-07-01

    Familial adenomatous polyposis (FAP) is a hereditary condition with a near 100 % lifetime risk of colorectal cancer without prophylactic colectomy. Most patients with FAP have a mutation in the adenomatous polyposis coli gene on chromosome 5q22. This condition frequently presents in children with polyps developing most frequently in the second decade of life and surveillance colonoscopy is required starting at age ten. Polyps are found not only in the colon, but in the stomach and duodenum. Knowledge of the natural history of FAP is important as there are several extra-colonic sequelae which also require surveillance. In infants and toddlers, there is an increased risk of hepatoblastoma, while in teenagers and adults duodenal carcinomas, desmoid tumors, thyroid cancer and medulloblastoma are more common in FAP than in the general population. Current chemopreventive strategies include several medications and natural products, although to this point there is no consensus on the most efficacious and safe agent. Genetic counseling is an important part of the diagnostic process for FAP. Appropriate use and interpretation of genetic testing is best accomplished with genetic counselor involvement as many families also have concerns regarding future insurability or discrimination when faced with genetic testing. PMID:27056662

  2. People's perception of LILW repository

    International Nuclear Information System (INIS)

    Full text: Social acceptability of the radioactive waste repository presents a great problem in every country with such a waste. Even if people agree with the need for its construction, the chosen location should be far from their homes (NIMBY). The reasons for such attitudes were attributed to different causes: uneducated public, differences in understanding of radioactivity and risk by experts and lay public, risk communication problems, lack of credibility and social trust, etc. While in earlier days public was blamed for its irrationality, and need for education and information was emphasized, today it is realized that public trust is extremely important if effective risk communication is to be achieved. It is also recognized that it is not so much the content of the risk message itself, as the lack of trust to those responsible for provision of information that is behind this opposition. Perhaps we could apply here Petty and Caciopo's elaboration likelihood model of persuasion, with credibility as a factor in peripheral route of persuasion. Nevertheless also general lowering of social trust should explain social non-agreement. This lack of trust in experts and political institutions is perhaps caused by outwitting public in earlier years, its bad experiences with responsible officials, dangerous accidents (e.g. TMI, Chernobyl), increased influence that professions have over people's welfare, a greater value placed on equality and better educated public, etc. In 1996 the ARAO re-initiated the search for a LILW repository location with a new, so-called combined approach to the site selection, where the technical, geologically led process is combined with participation of local community. In order to get information on people's perception of the LILW repository construction, their willingness to accept it and factors that influence the acceptability, several surveys have been conducted. Groups of experts and lay persons answered the questionnaires. The results of

  3. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer

    OpenAIRE

    Malik, Arshi; Afaq, Farrukh; Sarfaraz, Sami; Adhami, Vaqar M.; Syed, Deeba N.; Mukhtar, Hasan

    2005-01-01

    Prostate cancer is the most common invasive malignancy and the second leading cause of cancer-related deaths among U.S. males, with a similar trend in many Western countries. One approach to control this malignancy is its prevention through the use of agents present in diet consumed by humans. Pomegranate from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. We recently showed that pomegranate fruit extract (PFE) possesses remarkable antitumor-promoting e...

  4. Ginseng Metabolites on Cancer Chemoprevention: An Angiogenesis Link?

    OpenAIRE

    Chong-Zhi Wang; Yi Cai; Samantha Anderson; Chun-Su Yuan

    2015-01-01

    Cancer is a leading cause of death in the United States. Angiogenesis inhibitors have been introduced for the treatment of cancer. Based on the fact that many anticancer agents have been developed from botanical sources, there is a significant untapped resource to be found in natural products. American ginseng is a commonly used herbal medicine in the U.S., which possesses antioxidant properties. After oral ingestion, natural ginseng saponins are biotransformed to their metabolites by the ent...

  5. Pancreatic Cancer Chemoprevention Translational Workshop | Division of Cancer Prevention

    Science.gov (United States)

    Thursday, September 10th (6:00 to 9:30 PM) Welcome Barnett Kramer, MD, MPH (6:00 to 6:10 PM) Director of the Division of Cancer Prevention, NCI Introduction – Goals of the Workshop: ABCs of Cancer Prevention (Agents, Biomarkers, Cohorts) Mark Miller, PhD (6:10 to 6:25 PM) Program Director Division of Cancer Prevention, NCI |

  6. Knowledge repositories for multiple uses

    Science.gov (United States)

    Williamson, Keith; Riddle, Patricia

    1991-01-01

    In the life cycle of a complex physical device or part, for example, the docking bay door of the Space Station, there are many uses for knowledge about the device or part. The same piece of knowledge might serve several uses. Given the quantity and complexity of the knowledge that must be stored, it is critical to maintain the knowledge in one repository, in one form. At the same time, because of quantity and complexity of knowledge that must be used in life cycle applications such as cost estimation, re-design, and diagnosis, it is critical to automate such knowledge uses. For each specific use, a knowledge base must be available and must be in a from that promotes the efficient performance of that knowledge base. However, without a single source knowledge repository, the cost of maintaining consistent knowledge between multiple knowledge bases increases dramatically; as facts and descriptions change, they must be updated in each individual knowledge base. A use-neutral representation of a hydraulic system for the F-111 aircraft was developed. The ability to derive portions of four different knowledge bases is demonstrated from this use-neutral representation: one knowledge base is for re-design of the device using a model-based reasoning problem solver; two knowledge bases, at different levels of abstraction, are for diagnosis using a model-based reasoning solver; and one knowledge base is for diagnosis using an associational reasoning problem solver. It was shown how updates issued against the single source use-neutral knowledge repository can be propagated to the underlying knowledge bases.

  7. Quality Classifiers for Open Source Software Repositories

    OpenAIRE

    Tsatsaronis, George; Halkidi, Maria; Giakoumakis, Emmanouel A.

    2009-01-01

    Open Source Software (OSS) often relies on large repositories, like SourceForge, for initial incubation. The OSS repositories offer a large variety of meta-data providing interesting information about projects and their success. In this paper we propose a data mining approach for training classifiers on the OSS meta-data provided by such data repositories. The classifiers learn to predict the successful continuation of an OSS project. The `successfulness' of projects is defined in terms of th...

  8. Journals and repositories: an evolving relationship?

    OpenAIRE

    Pinfield, Stephen

    2009-01-01

    It is now widely accepted that there are two routes to open access (OA): OA repositories and OA journals. It is often assumed these are distinct alternative parallel tracks. However, it has recently become clear that there is potential for repositories and journals to interact with each other on an ongoing basis and between them to form a coherent OA scholarly communication system. This paper puts forward three possible models of interaction between repositories and journals; services such as...

  9. Digital Repositories: All hype and no substance

    OpenAIRE

    Swanepoel, Marinus

    2005-01-01

    The development of digital repositories has been a recent one, starting in late 2000 when the UK's University of Southampton released a software package called E-Prints. Since that time, the establishment of digital repositories has gained momentum. Factors such as the falling costs for online storage, the increase of broadband and gigabit networking technologies, as well as the development of metadata standards to describe repository content, all contributed to their current popularity. Q...

  10. Institutional Repositories in BRICS Countries : A Study

    OpenAIRE

    Dhanavandan, S.; M. Tamizhchelvan

    2015-01-01

    An institutional repository includes digital assets generated by academics, such as administrative documents, course notes, learning objects, or conference proceedings. It will provide a window that gives open access to improve the sponsoring institution’s visibility and status. This paper discusses the growth and development of Institutional Repositories available in BRICS Countries. The relevant data was collected from the directory of OpenDOAR. Based on the data in OpenDOAR, 242 repositori...

  11. DINI Institutional Repository Certification and Beyond

    OpenAIRE

    Dobratz, Susanne

    2006-01-01

    Overview on certification of institutional repositories as a means to support Open Access in Germany and description of the DINI Certificate 2006 developed by DINI, the German Initiative for Networked Information. The DINI Certificate for Document and Publication Repositories shows potential users and authors of digital documents that a certain level of quality in operating the repository is guaranteed and that this distinguishes it from common institutional web servers. The Certificate ca...

  12. Nationwide Census of Institutional Repositories: Preliminary Findings

    OpenAIRE

    Markey, Karen; St. Jean, Beth; Rieh, Soo Young; Yakel, Elizabeth; Kim, Jihyun; Kim, Yong-Mi

    2007-01-01

    The MIRACLE (Making Institutional Repositories A Collaborative Learning Environment) Project is a multi-phased research project that is investigating the development of institutional repositories (IRs) in U. S. colleges and universities to identify models and best practices in the administration, technical infrastructure, access to, and preservation of repository collections. This paper features preliminary findings from the project’s first phase, a nationwide census that will reveal the exte...

  13. Starting, Strengthening, and Managing Institutional Repositories

    OpenAIRE

    Therese F. Triumph

    2011-01-01

    Over the past decade, the U.S. has experienced an explosion in the number of institutional repositories (IRs), from just more than 20 in 2002 to approximately 400 active repositories as of August, 2011. For any institution seeking to implement a repository, Jonathan Nabe has written an informative and practical manual, divided into two parts. Part I provides guidelines for starting and managing an IR, while Part II shares seven cases of actual IR implementations. Nabe starts with the premise ...

  14. PAPER REGISTRATION TO REPOSITORY FROM RESEARCHER DATABASE

    OpenAIRE

    Kensuke Baba; Masao Mori

    2012-01-01

    This paper introduces a system that realizes a simultaneous registration of scholarly papers for both a researcher database and a repository. An institutional repository is a method to realize free access to research outputs. However, the number of scholarly papers archived in institutional repositories is extremely small compared to the papers practically produced by researchers. The authors considered that an obstacle to increase the number is the efforts of researchers to register their pa...

  15. Institutional Repositories, Open Source Options, and Libraries

    OpenAIRE

    Amaral, Megan E.

    2008-01-01

    This paper examines the purposes of institutional digital repositories and the development options that are available via open source software. Preservation of an institution's digital output is valuable to the submitting authors and the institution. There are digital repository products available as open source software that may be extremely helpful to an organization establishing an institutional repository. The role of libraries and librarians in this process is discussed.

  16. Author Identifiers in Scholarly Repositories

    CERN Document Server

    Warner, Simeon

    2010-01-01

    Bibliometric and usage-based analyses and tools highlight the value of information about scholarship contained within the network of authors, articles and usage data. Less progress has been made on populating and using the author side of this network than the article side, in part because of the difficulty of unambiguously identifying authors. I briefly review a sample of author identifier schemes, and consider use in scholarly repositories. I then describe preliminary work at arXiv to implement public author identifiers, services based on them, and plans to make this information useful beyond the boundaries of arXiv.

  17. Method for minimizing technetium-99 migration from a geologic repository

    Science.gov (United States)

    Demartino, Virlynda

    2000-10-01

    A method for minimizing technetium-99 (99Tc) migration in groundwater by using reducing agents was investigated. This information could be used to tailor the spent nuclear fuel waste packages or near-field environment at a geologic repository to prevent 99Tc migration should water infiltration occur. The proposed geologic repository at Yucca Mountain will likely remain dry for several hundred years because (1) it will be located in the unsaturated zone above the water table, and (2) it will have significant radioactive decay heat. As time passes, the decay heat generated will lessen. The repository will then cool below the boiling point of water, and then water could contact spent fuel in any breached waste package. At that time, the soluble radionuclides, such as 99Tc, may possibly dissolve and migrate from the repository into the environment. This research also could be applied to technetium-soil decontamination by adding the reducing agent to the soil and disposing of the soil as hazardous mixed waste. A computational analysis (EQ3/6 software package) and an experimental approach were used during this investigation. Both approaches investigated the effect of reducing agents on technetium(VII) solutions. Theoretically, the 99Tc would precipitate as lower valent oxides or technetium metal because of the reducing environment, and its migration would be minimized. Copper, iron, stannous chloride, and tin were used as reducing agents in both approaches. Experimentally, iron reduced the technetium concentration to below detectable limits; copper, tin, and stannous chloride only temporarily reduced the technetium concentration. The experimental results were consistent with the computer simulations for iron and one of the stannous chloride experiments. The other stannous chloride experiment temporarily reduced the technetium concentration, but not to the values indicated by the codes. Experimentally, copper and tin developed passivation layers, and therefore, the

  18. The European Repository Landscape 2008 Inventory of Digital Repositories for Research Output

    CERN Document Server

    Van der Graaf, Maurits

    2009-01-01

    It is widely acknowledged that a common knowledge base for European research is necessary. Research repositories are an important innovation to the scientific information infrastructure. In 2006, digital repositories in the 27 countries of the European we

  19. The influence of organic materials on the near field of an intermediate level radioactive waste repository

    International Nuclear Information System (INIS)

    The influence of organic materials which are present in some intermediate level wastes on the chemistry of the near field of a radioactive waste repository is discussed. Particular attention is given to the possible formation of water soluble complexing agents as a result of the radiation field and chemical conditions. The present state of the research is reviewed. (author)

  20. Center for Leadership Development (CLD) Repository

    Data.gov (United States)

    Office of Personnel Management — The Center for Leadership Development Repository stores various data including policies, procedures, governance, guidance, security, and financial documents of the...

  1. Nuclear waste repository simulation experiments

    International Nuclear Information System (INIS)

    This document is the third joint annual report on the Cooperative German-American 'Brine Migration Tests' that are in progress at the Asse salt mine in the Federal Republic of Germany (FRG). This Government supported mine serves as an underground test facility for research and development (R and D)-work in the field of nuclear waste repository research and simulation experiments. The tests are designed to simulate a nuclear waste repository to measure the effects of heat and gamma radiation on brine migration, salt decrepitation, disassociation of brine, and gases collected. The thermal mechanical behavior of salt, such as room closure, stresses and changes of the properties of salt are measured and compared with predicted behavior. This document covers the following sections: Issues and test objectives: This section presents issues that are investigated by the Brine Migration Test, and the test objectives derived from these issues; test site: This section describes the test site location and geology in the Asse mine; test description: A description of the test configuration, procedures, equipment, and instrumentation is given in this section; actual test chronology: The actual history of the test, in terms of the dates at which major activities occured, is presented in this section. Test results: This section presents the test results observed to data and the planned future work that is needed to complete the test; conclusions and recommendations: This section summarizes the conclusions derived to date regarding the Brine Migration Test. Additional work that would be useful to resolve the issues is discussed. (orig.)

  2. Radioactive Waste Repositories Administration - SURAO

    International Nuclear Information System (INIS)

    The Atomic Act specifies, among other things, responsibilities of the government in the field of safe disposal of radioactive wastes. To satisfy this responsibility, the Ministry of Industry and Trade has established the Radioactive Waste Repositories Administration (SURAO). SURAO's major responsibilities include: (a) the preparation, construction, commissioning, operation, and decommissioning of radioactive waste repositories and the monitoring of their environmental impacts; (b) radioactive waste management; (c) spent or irradiated nuclear fuel processing into a form suitable for storage/disposal or reuse; (d) record-keeping of received radioactive wastes and their producers; (e) administration of fund transfers as stipulated by the Atomic Act, Article 27; (f) development of proposals for specification of fees to be paid to the Nuclear Account; (g) responsibility for and coordination of research and development in the field of radioactive waste handling and management; (h) supervision of licensees' margin earmarked for the decommissioning of their facilities; (i) providing services in radioactive waste handling and management; (j) handling and management of radioactive wastes that have been transferred to the Czech Republic from abroad and cannot be sent back; (k) interim administration of radioactive wastes that have become state property. The Statute of the Administration is reproduced in full. (P.A.)

  3. INIS: Nuclear Grey Literature Repository

    International Nuclear Information System (INIS)

    As one of the world's largest collections of published information on the peaceful uses of nuclear science and technology, INIS represents an extraordinary example of world cooperation. Currently, as INIS members, 130 countries and 24 international organizations share and allow access to their valuable nuclear information resources, preserving them for future generations and offering a freely available nuclear knowledge repository. Since its creation in 1970, INIS has collected and provided access to more than 3.8 million bibliographic references to publications, documents, technical reports, non-copyrighted documentation, and other grey literature, as well as over a million full texts. Public interest throughout the years in accessing the INIS Collection has been remarkable. This paper deals with the challenges faced by INIS in its endeavour to increase the use, accessibility, usability and expandability of its on-line repository. It also describes document collection, the features and characteristics of implementing a new search engine, as well as the lessons learned. (author)

  4. Molecular mechanisms underlying chemopreventive potential of curcumin: Current challenges and future perspectives.

    Science.gov (United States)

    Kumar, Gaurav; Mittal, Sonam; Sak, Katrin; Tuli, Hardeep Singh

    2016-03-01

    In recent years, natural compounds have received considerable attention in preventing and curing most dreadful diseases including cancer. The reason behind the use of natural compounds in chemoprevention is associated with fewer numbers of side effects than conventional chemotherapeutics. Curcumin (diferuloylmethane, PubMed CID: 969516), a naturally occurring polyphenol, is derived from turmeric, which is used as a common Indian spice. It governs numerous intracellular targets, including proteins involved in antioxidant response, immune response, apoptosis, cell cycle regulation and tumor progression. A huge mass of available studies strongly supports the use of Curcumin as a chemopreventive drug. However, the main challenge encountered is the low bioavailability of Curcumin. This extensive review covers various therapeutic interactions of Curcumin with its recognized cellular targets involved in cancer treatment, strategies to overcome the bioavailability issue and adverse effects associated with Curcumin consumption. PMID:26876915

  5. Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway.

    Science.gov (United States)

    Hasan, Shirin; Suhail, Nida; Bilal, Nayeem; Ashraf, Ghulam Md; Zaidi, Syed Kashif; AlNohair, Sultan; Banu, Naheed

    2016-05-01

    Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention. PMID:26596837

  6. Chemopreventive Effects of RXR-Selective Rexinoid Bexarotene on Intestinal Neoplasia of ApcMin/+ Mice

    OpenAIRE

    Janakiram, Naveena B; Altaf Mohammed; Li Qian; Chang-In Choi; Steele, Vernon E.; Rao, Chinthalapally V.

    2012-01-01

    Retinoid X receptor (RXR) has been implicated in several neoplastic diseases. Previously, we have shown that RXR-α is downregulated in human and rodent colonic tumors, suggesting a potential target for colon cancer prevention (http://www.cancer.org/Cancer/ColonandRectumCancer/DetailedGuide/colorectal-cancer-key-statistics). Experiments were designed to assess the chemopreventive efficacy of the selective RXR agonist bexarotene for the suppression of intestinal tumorigenesis in ApcMin/+ mice. ...

  7. Participation of Asian-American Women in Cancer Chemoprevention Research: Physician Perspectives

    OpenAIRE

    Nguyen, Tung T.; Somkin, Carol P.; Ma, Yifei

    2005-01-01

    To the authors’ knowledge, little is known regarding the participation of Asian Americans in cancer prevention research. In 2002, the authors mailed surveys to primary care physicians in Northern California to assess their knowledge, attitudes, behaviors, and barriers concerning the participation of Asian-American women in breast cancer chemoprevention research. The response rate was 52.3% (n = 306 physicians). For physician barriers, most respondents selected lack of study knowledge (73%) an...

  8. CHEMOPREVENTIVE POTENTIAL OF CARALLUMA ADSCENDENS (ROXB.) AGAINST 1,2 DIMETHYL HYDRAZINE INDUCED COLON CARCINOGENESIS

    OpenAIRE

    Gowri S; Chinnaswamy, P.; Suganthi. V.

    2013-01-01

    Colorectal cancer is increasingly common nowadays in Asian countries and still remains the second leading cause of cancer death in the United States. The chemopreventive and hypolipidemic effect of Caralluma adscendens (Roxb.), an edible succulent, was studied in 1,2-dimethylhydrazine (DMH)-induced colon cancer. Rats were given a weekly subcutaneous injection of DMH (20 mg/kg body weight), a known colon carcinogen, in the groin for 16 weeks. Caralluma adscendens (Roxb.) (50 & 100 mg/kg body w...

  9. Can Transcriptomics Provide Insight into the Chemopreventive Mechanisms of Complex Mixtures of Phytochemicals in Humans?

    OpenAIRE

    van Breda, Simone G.J.; Wilms, Lonneke C.; Gaj, Stan; Jennen, Danyel G.J.; Briedé, Jacob J.; Helsper, Johannes P.; Kleinjans, Jos C.S.; de Kok, Theo M.C.M.

    2014-01-01

    Blueberries contain relatively large amounts of different phytochemicals, which are suggested to have chemopreventive properties, but little information is available on the underlying molecular modes of action. This study investigates whole genome gene expression changes in lymphocytes of 143 humans after a 4-week blueberry-apple juice dietary intervention. Differentially expressed genes and genes correlating with the extent of antioxidant protection were identified in four subgroups. The mag...

  10. Co-chemoprevention of Mouse Lung Tumors by SAHA and Atorvastatin

    OpenAIRE

    Pereira, Michael A.; Warner, Blake M.; Knobloch, Thomas J.; Weghorst, Christopher M.; Lubet, Ronald A.; Steele, Vernon E; Casto, Bruce C.

    2012-01-01

    Atorvastatin and SAHA were evaluated for co-chemoprevention of mouse lung tumors. In Experiment 1, lung tumors were induced by vinyl carbamate in strain A/J mice followed by 500 mg/kg SAHA, 60 or 180 mg/kg Atorvastatin, and combinations containing SAHA and Atorvastatin administered in their diet. SAHA and both combinations, but not Atorvastatin, decreased the multiplicity of lung tumors, including large adenomas and adenocarcinomas with the combinations demonstrating the greatest efficacy. In...

  11. Evaluation of anti-inflammatory, immunomodulatory, chemopreventive and wound healing potentials from Schinus terebinthifolius methanolic extract

    OpenAIRE

    Lis E.S. Fedel-Miyasato; Cândida A.L. Kassuya; Sarah A. Auharek; Anelise S. N. Formagio; Cardoso, Claudia A. L.; Mariana O. Mauro; Andréa L. Cunha-Laura; Antônio C.D. Monreal; MARIA C. VIEIRA; Rodrigo J. Oliveira

    2014-01-01

    Inflammatory and genetic alterations are related to the development of chronic diseases such as cancer. Schinus terebinthifolius Raddi, Anacardiaceae, is used in folk medicine to treat inflammation, wounds and tumors. This study evaluated the anti-inflammatory, immunomodulatory, chemopreventive, and wound healing potentials of the methanolic extract from the leaves of Schinus terebinthifolius. The chemical composition of the extract was characterized using preliminary analytical LC methods. T...

  12. Chemopreventive Effects of Oplopantriol A, a Novel Compound Isolated from Oplopanax horridus, on Colorectal Cancer

    OpenAIRE

    Zhiyu Zhang; Chunhao Yu; Chun-Feng Zhang; Xiao-Hui Wu; Xiao-Dong Wen; Samantha Anderson; Wei Du; Wei-Hua Huang; Shao-Ping Li; Chong-Zhi Wang; Chun-Su Yuan

    2014-01-01

    Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A) is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects (p < 0.01). Next, we characterized the co...

  13. Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer

    OpenAIRE

    Ting, Harold; Deep, Gagan; Agarwal, Rajesh

    2013-01-01

    Despite advances in early detection, prostate cancer remains the second highest cancer mortality in American men, and even successful interventions are associated with enormous health care costs as well as prolonged deleterious effects on quality of patient life. Prostate cancer chemoprevention is one potential avenue to alleviate these burdens. It is a regime whereby long-term treatments are intended to prevent or arrest cancer development, in contrast to more direct intervention upon diseas...

  14. Going Green: The Role of the Green Tea Component EGCG in Chemoprevention

    OpenAIRE

    Schramm, Laura

    2013-01-01

    Tea is one of the most consumed beverages worldwide, and green tea is the least processed from the buds of the Camellia sinensis plant. The most abundant component of green tea is (−)-epigallocatechin-3-gallate (EGCG), which has been the focus of many cell culture, animal and clinical trials, revealing that EGCG possesses antiproliferative, antimutagenic, antioxidant, antibacterial, antiviral and chemopreventive effects. In this review we briefly summarize the mechanism of action(s) of the gr...

  15. Notes from the Field: “Green” Chemoprevention as Frugal Medicine

    OpenAIRE

    Fahey, Jed W.; Talalay, Paul; Kensler, Thomas W.

    2012-01-01

    Prevention trials of whole foods or simple extracts offer prospects for reducing an expanding global burden of cancer effectively and, in contrast to promising isolated phytochemicals or pharmaceuticals, frugally. We use the term “green chemoprevention” to differentiate a food-centered approach that is sustainable in underserved populations. It can be applied to personalized medicine just as well as can a pharmaceutical approach, but only green chemoprevention can be applied in both rich and ...

  16. Polyamines as mediators of APC-dependent intestinal carcinogenesis and cancer chemoprevention

    OpenAIRE

    Rial, Nathaniel S; Meyskens, Frank L.; Gerner, Eugene W.

    2009-01-01

    Combination chemoprevention for cancer was proposed a quarter of a century ago, but has not been implemented in standard medical practice owing to limited efficacy and toxicity. Recent trials have targeted inflammation and polyamine biosynthesis, both of which are increased in carcinogenesis. Preclinical studies have demonstrated that DFMO (difluoromethylornithine), an irreversible inhibitor of ODC (ornithine decarboxylase) which is the first enzyme in polyamine biosynthesis, combined with NS...

  17. Quimioprevenção do câncer de mama Current status of breast cancer chemoprevention

    Directory of Open Access Journals (Sweden)

    Vilmar Marques de Oliveira

    2006-12-01

    Full Text Available Quimioprevenção é definida como o uso de agentes químicos naturais ou sintéticos para reverter, suprimir ou prevenir a progressão carcinogênica para carcinoma invasor. Os fármacos que agem como agentes quimiopreventivos contra o câncer de mama são divididos em dois grupos principais: os que previnem cânceres de mama receptor de estrogênio (RE positivos, como os moduladores seletivos do receptor de estrogênio (SERM, inibidores de aromatase, agonistas de GnRH e fitoestrogênios; e os fármacos que previnem os cânceres RE-negativos, como os inibidores da ciclooxigenase-2 (COX-2, retinóides, as estatinas, os inibidores do receptor tirosina quinase, o anticorpo monoclonal contra HER-2 e os inbidores da telomerase. Resultados do estudo conduzido pelo NSABP que comparou o tamoxifeno com o raloxifeno (STAR, avaliando a eficácia na redução de risco, assim como a toxicidade desses dois SERMs em uma população similar e de alto risco para câncer de mama, demonstrou que o raloxifeno é tão efetivo quanto o tamoxifeno na redução de risco de câncer de mama invasor (p=0,83 e apresentou menor risco de eventos tromboembólicos e catarata; todavia, exibiu maior risco de carcinoma não invasor, porém sem significância estatística. Baseado nos dados promissores que revelaram diminuição de risco de câncer de mama contralateral em estudos de adjuvância, alguns inibidores de aromatase, incluindo o letrozol, anastrazol e exemestane, estão sendo incorporados em investigações para avaliar sua eficácia como agentes preventivos de alto risco em mulheres. Os inibidores de COX-2 demonstraram sua eficácia na prevenção do câncer de mama em estudos caso-controle e coorte, sendo necessários estudos aleatórios para atestar sua eficácia. O resultado positivo de alguns ensaios clínicos na prevenção do câncer de mama em populações de alto risco sugere que a quimioprevenção é uma estratégia racional e atraente.Chemoprevention is

  18. Distributed enterprise search using software agents

    OpenAIRE

    Gunadi, Erwin; Meder, Michael; Plumbaum, Till; Hopfgartner, Frank; Albayrak, Sahin

    2014-01-01

    In this paper we introduce a distributed information retrieval system using agent-based technology. In this multiagent system, each agent has its own specific task and can be used to handle a specific document repository. The system is designed to automatically comply with access restriction rules that are normally enforced in companies. It is used in the administration offices of the German capital city Berlin where it serves as a testbed for further research on aggre...

  19. Reference repository design concept for bedded salt

    International Nuclear Information System (INIS)

    A reference design concept is presented for the subsurface portions of a nuclear waste repository in bedded salt. General geologic, geotechnical, hydrologic and geochemical data as well as descriptions of the physical systems are provided for use on generic analyses of the pre- and post-sealing performance of repositories in this geologic medium. The geology of bedded salt deposits and the regional and repository horizon stratigraphy are discussed. Structural features of salt beds including discontinuities and dissolution features are presented and their effect on repository performance is discussed. Seismic hazards and the potential effects of earthquakes on underground repositories are presented. The effect on structural stability and worker safety during construction from hydrocarbon and inorganic gases is described. Geohydrologic considerations including regional hydrology, repository scale hydrology and several hydrological failure modes are presented in detail as well as the hydrological considerations that effect repository design. Operational phase performance is discussed with respect to operations, ventilation system, shaft conveyances, waste handling and retrieval systems and receival rates of nuclear waste. Performance analysis of the post sealing period of a nuclear repository is discussed, and parameters to be used in such an analysis are presented along with regulatory constraints. Some judgements are made regarding hydrologic failure scenarios. Finally, the design and licensing process, consistent with the current licensing procedure is described in a format that can be easily understood

  20. Reference repository design concept for bedded salt

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, D.W.; Martin, R.W.

    1980-10-08

    A reference design concept is presented for the subsurface portions of a nuclear waste repository in bedded salt. General geologic, geotechnical, hydrologic and geochemical data as well as descriptions of the physical systems are provided for use on generic analyses of the pre- and post-sealing performance of repositories in this geologic medium. The geology of bedded salt deposits and the regional and repository horizon stratigraphy are discussed. Structural features of salt beds including discontinuities and dissolution features are presented and their effect on repository performance is discussed. Seismic hazards and the potential effects of earthquakes on underground repositories are presented. The effect on structural stability and worker safety during construction from hydrocarbon and inorganic gases is described. Geohydrologic considerations including regional hydrology, repository scale hydrology and several hydrological failure modes are presented in detail as well as the hydrological considerations that effect repository design. Operational phase performance is discussed with respect to operations, ventilation system, shaft conveyances, waste handling and retrieval systems and receival rates of nuclear waste. Performance analysis of the post sealing period of a nuclear repository is discussed, and parameters to be used in such an analysis are presented along with regulatory constraints. Some judgements are made regarding hydrologic failure scenarios. Finally, the design and licensing process, consistent with the current licensing procedure is described in a format that can be easily understood.

  1. Types of Online Hierarchical Repository Structures

    Science.gov (United States)

    Hershkovitz, Arnon; Azran, Ronit; Hardof-Jaffe, Sharon; Nachmias, Rafi

    2011-01-01

    This study presents an empirical investigation of online hierarchical repositories of items presented to university students in Web-supported course websites, using Web mining methods. To this end, data from 1747 courses were collected, and the use of online repositories of content items in these courses was examined. At a later stage, courses…

  2. Online educational repositories for promoting agricultural knowledge

    OpenAIRE

    C.I. Costopoulou; M.S. Ntaliani; M.T. Maliappis; R. Georgiades; A.B. Sideridis

    2010-01-01

    Towards promoting sustainable agriculture and economic growth, the development of the agricultural workforce and set up of innovative agricultural systems are required. Agricultural educational repositories are systems used for storing, reusing and sharing agricultural learning resources. They contribute to agricultural education at different educational levels and target groups. Thus, this paper firstly provides an overview of Institutional repositories (IRs) and Open Access Archives (OAAs) ...

  3. Culture Heritage Digital Repositories. Research Questions

    OpenAIRE

    Stanchev, Peter

    2010-01-01

    This discussion is about innovative solutions for assembling multimedia digital repositories for collaborative use in specific contexts and communities and enhancing scholarly understanding and experiences of digital cultural heritage. Several aspects are stress such as the dynamic aggregation of cross-media resources across existing institutional digital libraries and repositories. Research questions about the scalability, interoperability and distributed architectures, aggregation, an...

  4. A Survey of Software Reuse Repositories

    OpenAIRE

    Guo, Jiang; Luqi

    2000-01-01

    Reuse libraries are organizations of personnel, procedures, tools, and software components directed toward facilitating software component reuse to meet specific cost-effectiveness and productivity goals. The paper gives a survey of the major software reusable component repositories. This survey will be a base to develop future efficiently searchable, user-friendly, useful, and well-organized repositories.

  5. ORBi – Open Repository and Bibliography

    Czech Academy of Sciences Publication Activity Database

    Burešová, Iva; Doleželová, Jana; Lhoták, Martin

    -, 1-2 (2011). E-ISSN 1805-2800 Institutional research plan: CEZ:AV0Z70830501 Keywords : repository * open access * ORBi * University of Liege http://www.lib.cas.cz/casopis-informace/orbi-%E2%80%93- open -repository- and -bibliography/

  6. Modelling saline intrusion for repository performance assessment

    International Nuclear Information System (INIS)

    UK Nirex Ltd are currently considering the possibility of disposal of radioactive waste by burial in deep underground repositories. The natural pathway for radionuclides from such a repository to return to Man's immediate environment (the biosphere) is via groundwater. Thus analyses of the groundwater flow in the neighbourhood of a possible repository, and consequent radionuclide transport form an important part of a performance assessment for a repository. Some of the areas in the UK that might be considered as possible locations for a repository are near the coast. If a repository is located in a coastal region seawater may intrude into the groundwater flow system. As seawater is denser than fresh water buoyancy forces acting on the intruding saline water may have significant effects on the groundwater flow system, and consequently on the time for radionuclides to return to the biosphere. Further, the chemistry of the repository near-field may be strongly influenced by the salinity of the groundwater. It is therefore important for Nirex to have a capability for reliably modelling saline intrusion to an appropriate degree of accuracy in order to make performance assessments for a repository in a coastal region. This report describes work undertaken in the Nirex Research programme to provide such a capability. (author)

  7. Chemopreventive effects of the polyunsaturated fatty acids omega-3 on the carcinogenesis process of the upper aerodigestive tract induced by 4-nitroquinoline-1-oxide in Swiss mice

    OpenAIRE

    Gama, Ricardo Ribeiro; Allan GIOVANINI; de Rosa, Fernanda Scarmato; Ogata, Daniel Cury; de Oliveira, André Luiz Vettore; Cardoso Costa, Ana Flávia; Talini, Carolina; Feniman, Denise; Kamei, Douglas; Júnior, Celso Felipe; Coco, Allan; Carvalho, André Lopes

    2014-01-01

    Objective: To study the potential chemopreventive effects of polyunsaturated fatty acids omega-3 in Swiss mice submitted to oral and oesophageal carcinogenesis induction by 4-nitroquinoline-1-oxide (4-NQO). Study design: The animals underwent carcinogenesis induction with 50 µg/mL 4-NQO for eight weeks. The animals were divided into groups: Group I—4-NQO induction without chemoprevention, Group II—chemoprevention with the addition of 5% fish oil (FO) in their diet after 4-NQO carcinogenesis i...

  8. Final repository Morsleben. Operational safety and radiation protection

    International Nuclear Information System (INIS)

    The Information booklet on the final repository Morsleben prepared by BfS includes information on the following issues: stability of the repository, water in repository, operational radiation protection, discharge of radioactive materials, environmental monitoring.

  9. PAPER REGISTRATION TO REPOSITORY FROM RESEARCHER DATABASE

    Directory of Open Access Journals (Sweden)

    Kensuke Baba

    2012-01-01

    Full Text Available This paper introduces a system that realizes a simultaneous registration of scholarly papers for both a researcher database and a repository. An institutional repository is a method to realize free access to research outputs. However, the number of scholarly papers archived in institutional repositories is extremely small compared to the papers practically produced by researchers. The authors considered that an obstacle to increase the number is the efforts of researchers to register their papers to institutional repositories, and they developed a system that realizes a simultaneous registration of papers to the researcher database and the institutional repository in their university. This paper introduces the main idea and the details of the implementation of the system.

  10. Expected repository environments in granite: thermal environment

    International Nuclear Information System (INIS)

    This report was prepared for the Reference Repository Conditions - Interface Working Group and will be used to formulate a standardized description of repository conditions for use by the Civilian Radioactive Waste Management Program. A baseline repository in granite is defined and three waste types are considered: unreprocessed spent fuel, commercial high-level waste, and defense high-level waste. Three different scales of repository environment are described - the very-near field (near the waste canister), the near field (the room and pillar), and the far field (the entire repository and surroundings). Information was compiled from the literature and, in addition, a number of calculations were performed. The major emphasis is on describing the thermal environment although the ground-water flow and chemical and radiation environments are also described. 61 figures, 24 tables

  11. EEI/UWASTE oversight of the DOE Repository Program by the Repository Information Exchange Team

    International Nuclear Information System (INIS)

    The Utility Nuclear Waste and Transportation Program of the Edison Electric Institute (EEI/UWASTE) has conducted reviews of the US DOE's repository program through its Repository Information Exchange Team (RIET or Team). Eight such reviews have been conducted since 1985 covering topics that include repository program management and control; repository schedule; repository budget; quality assurance; site characterization; repository licensing; environmental issues; and institutional and public information activities. The utility industry has used these repository program reviews as a forum for providing DOE's Office of Civilian Radioactive Waste Management (OCRWM) with comments on the direction of the repository program, advice for future actions regarding quality assurance activities and repository licensing, and suggestions for management and control of the Repository Program. The most significant recommendations made by the utility industry through the RIET are discussed along with any subsequent action by OCRWM in response to or subsequent to utility industry recommendations. The process used by the RIET to develop its recommendations to OCRWM regarding the repository program is also discussed

  12. Hydrologic issues in repository siting

    International Nuclear Information System (INIS)

    Extrapolation of Darcy's law to the transport of water an solutes in unfractured poorly permeable rocks being studied for nuclear waste disposal is questioned. The hydrologic literature includes numerous references to both non-Darcian flow in dense materials devoid of macrofractures and microfractures and to threshold gradients below which no flow occurs. For such situations to occur, the pore-size range must be small enough so that all pore water is sufficiently close to mineral surfaces to be affected by the surficial forces. Then the flow will be non-Newtonian and non-Darcian, and solute transport will be by molecular diffusion. If fluid transport in very dense unfractured rocks is non-Darcian, useful methods of testing candidate host rocks become apparent. In situ nondestructive pressure testing of canister waste emplacement boreholes in a mined repository can verify the absence of both fracture flow and Darcian flow. 18 references

  13. Monitored Geologic Repository Requirements Document

    International Nuclear Information System (INIS)

    The objective of this document is to define the performance and system requirements for the development of the Monitored Geologic Repository (MGR), including the Waste Handling System, Waste Isolation System, and the Operational Support System consistent with the Civilian Radioactive Waste Management System Requirements Document (CRD). These requirements apply to design, construction, operation, and decommissioning. The document also presents an overall description of the MGR, its functions and its systems as described in Section 2.3. In addition, the MGR interfaces are identified. Development of the MGR must be consistent with the requirements of the this document. While the MGR may evolve and change through the design process, changes must occur in a controlled manner. This document and, as necessary, the CRD, will be revised to capture the changes. Also, changes in the CRD will be captured in revisions to this document as necessary

  14. Characteristics of potential repository wastes

    International Nuclear Information System (INIS)

    This report presents the results of a fully documented peer review of DOE/RW-0184, Rev. 1, ''Characteristics of Potential Repository Wastes''. The peer review was chaired and administered by oak Ridge National Laboratory (ORNL) for the Department of Energy (DOE), Office of Civilian Radioactive Waste Management (OCRWM) and was conducted in accordance with OCRWM QA procedure QAAP 3.3 ''Peer Review'' for the purpose of quailing the document for use in OCRWM quality-affecting work. The peer reviewers selected represent a wide range of experience and knowledge particularly suitable for evaluating the subject matter. A total of 596 formal comments were documented by the seven peer review panels, and all were successfully resolved. The peers reached the conclusion that DOE/RW-0184, Rev. 1, is quality determined and suitable for use in quality-affecting work

  15. Embedding Repositories: A Guide and Self-Assessment Tool

    OpenAIRE

    Wyngard, Michele I

    2012-01-01

    As the number of institutional repositories continues to grow, the conversation is evolving from how to establish a repository to how to make a repository integral to the operations of an institution. In an effort to create a coherent synthesis of previous studies, literature, and best practices on the topic of embedded repositories, the Joint Information Systems Committee’s Repositories Support Project has developed a free online service called Embedding Repositories: A Guide and Self-Assess...

  16. In vitro chemo-preventive activities of hydroxytyrosol: the main phenolic compound present in extra-virgin olive oil.

    Science.gov (United States)

    Rosignoli, Patrizia; Fuccelli, Raffaela; Sepporta, Maria Vittoria; Fabiani, Roberto

    2016-01-01

    The co-incubation in the culture medium with hydroxytyrosol [3,4-dihydroxyphenyl ethanol (3,4-DHPEA)], the main phenolic compound present in extra-virgin olive oil, and H2O2 reduces the oxidative DNA damage in peripheral blood mononuclear cells (PBMC). In this study we investigate, by the comet assay, the ability of 3,4-DHPEA to inhibit the H2O2 induced DNA damage when pre-incubated with PBMC and then removed before the exposure of cells to H2O2. Low doses of 3,4-DHPEA (10-100 μM) pre-incubated for 30 min with PBMC reduced the DNA damage induced by the treatment with H2O2 200 μM for 5 min at 4 °C. Prolonging the exposure time up to 6 h completely prevented the DNA damage. Furthermore we extensively analysed, by the MTT assay, the anti-proliferative activities of 3,4-DHPEA on breast (MDA and MCF-7), prostate (LNCap and PC3) and colon (SW480 and HCT116) cancer cell lines and correlated these effects with the H2O2 accumulation. The concentration of H2O2 in the culture medium was measured by the ferrous ion oxidation-xylenol orange method. The proliferation of all the cell lines was inhibited but at different levels: the prostate cancer cells were more resistant to the growth inhibition with respect to breast and colon cancer cells. The ability of the different cell lines to remove H2O2 from the culture medium was inversely correlated with their sensitivity to the anti-proliferative effect of 3,4-DHPEA. Therefore, 3,4-DHPEA may act as a chemopreventive agent acting on both initiation and promotion/progression phases of carcinogenesis. PMID:26469183

  17. Effects of chemopreventive natural products on non-homologous end-joining DNA double-strand break repair.

    Science.gov (United States)

    Charles, Catherine; Nachtergael, Amandine; Ouedraogo, Moustapha; Belayew, Alexandra; Duez, Pierre

    2014-07-01

    Double-strand breaks (DSBs) may result from endogenous (e.g., reactive oxygen species, variable (diversity) joining, meiotic exchanges, collapsed replication forks, nucleases) or exogenous (e.g., ionizing radiation, chemotherapeutic agents, radiomimetic compounds) events. DSBs disrupt the integrity of DNA and failed or improper DSBs repair may lead to genomic instability and, eventually, mutations, cancer, or cell death. Non-homologous end-joining (NHEJ) is the major pathway used by higher eukaryotic cells to repair these lesions. Given the complexity of NHEJ and the number of proteins and cofactors involved, secondary metabolites from medicinal or food plants might interfere with the process, activating or inhibiting repair. Twelve natural products, arbutin, curcumin, indole-3-carbinol, and nine flavonoids (apigenin, baicalein, chalcone, epicatechin, genistein, myricetin, naringenin, quercetin, sakuranetin) were chosen for their postulated roles in cancer chemoprevention and/or treatment. The effects of these compounds on NHEJ were investigated with an in vitro protocol based on plasmid substrates. Plasmids were linearized by a restriction enzyme, generating cohesive ends, or by a combination of enzymes, generating incompatible ends; plasmids were then incubated with a nuclear extract prepared from normal human small-intestinal cells (FHS 74 Int), either treated with these natural products or untreated (controls). The NHEJ repair complex from nuclear extracts ligates linearized plasmids, resulting in plasmid oligomers that can be separated and quantified by on-chip microelectrophoresis. Some compounds (chalcone, epicatechin, myricetin, sakuranetin and arbutin) clearly activated NHEJ, whereas others (apigenin, baicalein and curcumin) significantly reduced the repair rate of both types of plasmid substrates. Although this in vitro protocol is only partly representative of the in vivo situation, the natural products appear to interfere with NHEJ repair and warrant

  18. How many geologic repositories will be needed

    International Nuclear Information System (INIS)

    DOE's postponement of site-specific work on the second repository program had rekindled debate over the number of geologic repositories needed for disposal of high level radioactive waste. The multiple repository approach grew out of the March, 1979 IRG report, which recommended co-disposal of civilian and defense HLW in a system of regional repositories. The multiple repository approach was adopted by DOE, and incorporated in the Nuclear Waste Policy Act passed by Congress in December, 1982. Since the late 1970's, the slower than anticipated growth of the nuclear power industry has substantially reduced earlier estimates of the amount of civilian spent fuel which will require geologic disposal. Reactors currently in operation (78.5 GWe) and reactors in the construction pipeline (28 GWe) are expected to discharge about 103,200 MTU of spent fuel by the year 2036, assuming no increase in fuel burnup rate. By the year 2020, defense high level radioactive wastes equivalent to as much as 27,000 MTU could require geologic disposal. Small amounts of high level waste from other sources will also require geologic disposal. Total disposal requirements appear to be less than 140,000 MTU. The five sites nominated for the first repository, as well as hypothetical sites in granite, the host rock under primary consideration for the second repository, all appear capable of accommodating up to 140,000 MTU

  19. Gas generation in deep geological repositories

    International Nuclear Information System (INIS)

    Deep geological disposal repositories are expected to achieve adequate long-term safety for long-lived radioactive waste without reliance on continuing institutional controls. While geological repositories will continue to evolve over time, in order to effectively contain and isolate emplaced radioactive waste from the environment, most will use backfill materials (bentonite, crushed rocks or cement) as engineered barriers against groundwater infiltration and radionuclide transport. Gases generated within the repository will not pose any major concern during the operational phase. However, after closure, geological repositories are prone to potential gas build up, which may result in the loss of integrity of the engineered barrier system (EBS) and the disposal system. This article, based on a more detailed position paper recently issued (2015) by the NEA Integration Group for the Safety Case (IGSC), examines the significant issues of concern in relation to gas generation and migration from radioactive waste disposal repositories: gases generated in the repository, anaerobic metal corrosion and radiolysis, microbial degradation of organic waste, radioactive gases released from waste and radioactive decay, gas transport and migration in deep geological repositories, gas transport in clay, in crystalline rocks and in rock salt

  20. Repository site characterization - Comparing international experience - 16082

    International Nuclear Information System (INIS)

    An important part of the work described here was a study of existing international experience in investigating deep geological repository sites. The objective of this study was to derive a basis for planning the content and extent of investigations which might be carried out in Germany in the future. Such investigations would be required in the course of a site selection process for a repository for HLW (high level radioactive waste). For this purpose information on suitable sites was gathered, mainly from literature sources. Suitable in this context meant two things. Firstly, the investigated site should be in rock similar to four being considered in Germany (salt, clay, crystalline and other hard rock under a clay cover). Secondly, the investigations carried out could reasonably be considered as being intended to lead to the use of the site as a repository. The investigation processes were presented, analysed and compared. The comparison was based on the quality and the intensity of the methods employed to obtain the information necessary for deciding between candidate repository sites in terms of safety and the feasibility of construction. In the final stage of the work the analysis and presentation method developed for the international sites was applied to the investigations already carried out at three German sites (Gorleben - a prospective HLW repository, Morsleben - an existing but now not operational repository for radioactive waste and Konrad - a repository currently under construction). The reported investigatory work was compared with the ideal investigations developed on the basis of the existing international experience. (authors)

  1. Citizen participation in nuclear waste repository siting

    International Nuclear Information System (INIS)

    Citizen participation, which is both legally and morally mandated, must be an essential part of the nuclear waste repository siting process. The experience from siting other large-scale development projects suggests that a repository is unlikely to be sited without an effective citizen participation program to illustrate how the program can be based upon past lessons and principles derived from appropriate social science theory. To be effective, it must be based on open and mutally respectful communication between repository developers and local citizens and be guided by a trained and experienced community development professional

  2. Architecture and Workflow of Medical Knowledge Repository

    Science.gov (United States)

    Choi, Hyunsook; Kim, Jeong Ah; Cho, Insook

    Recently, clinical field builds various forms of computerized medical knowledge and tries to use it efficiently. In general, to build and reuse knowledge easily, it is needed to build a knowledge repository. Especially, the credibility of knowledge is important in clinical domain. This paper proposes methods for supporting it. To perform it systematically, we propose the method of the knowledge management processes. The methods for knowledge management can serve equal quality, usability and credibility of knowledge. Knowledge management methods consist of 2 methods. They are the knowledge management processes and the specification of the management targets. And this paper proposes the requirement of a knowledge repository and the architecture of the knowledge repository.

  3. Repository for radioactive waste from petroleum operations

    International Nuclear Information System (INIS)

    In March 2008, the Norwegian Radiation Protection Authority (NRPA) gave the first authorisation to a new repository for radioactive waste from the petroleum industry on the Norwegian continental shelf. The authorisation is for four years initially. The repository will be the final storage destination for radioactive waste which contains enhanced levels of naturally occurring radioactive substances from petroleum extraction operations. Thus, it gives a safe and final storage facility for radioactive waste temporarily stored in facilities along the Norwegian coast. The repository is the first of its kind in Norway and is situated at Stangeneset Industrial Site in Gulen, Sogn og Fjordane County

  4. Learning frameworks as an alternative to repositories

    DEFF Research Database (Denmark)

    Dalsgaard, Christian

    2005-01-01

    This paper presents the concept of ‘learning frameworks’. The purpose of the paper is to discuss and question collections of digital learning objects in large repositories and to argue for large learning frameworks which organise a number of thematically related digital learning materials. Whereas...... a learning object repository contains all kinds of materials, a learning framework consists of an organisation of materials related to a common theme. Further, a repository consists of single, self-contained objects, whereas a learning framework is an open-ended environment which presents a number...

  5. Repository as a service (RaaS)

    OpenAIRE

    Lewis, Stuart; Shepherd, Kim; Latt, Yin Yin; Schweer, Andrea; Field, Adam

    2012-01-01

    In his oft-quoted seminal paper ‘Institutional Repositories: Essential Infrastructure For Scholarship In The Digital Age’ Clifford Lynch (2003) described the Institutional Repository as “a set of services that a university offers to the members of its community for the management and dissemination of digital materials created by the institution and its community members.” This paper seeks instead to define the repository service at a more primitive level, without the specialism of being an ‘I...

  6. The Cigeo industrial geological repository project - 59265

    International Nuclear Information System (INIS)

    The Planning Act of 28 June 2006 prescribed that a reversible repository in a deep geological formation be chosen as the reference solution for the long-term management of high-level and intermediate-level long-lived radioactive waste. It also entrusted the responsibility of further studies and investigations on the siting and design of the new repository upon the French Radioactive Waste Management Agency (Agence nationale pour la gestion des dechets radioactifs - Andra), in order for the review of the creation-licence application to start in 2015 and, subject to its approval, the commissioning of the new repository in 2025. In late 2009, Andra submitted to the French government proposals concerning the implementation and the design of Cigeo (Centre industriel de stockage geologique). A significant step of the project was completed with the delineation of an interest zone for the construction of the repository's underground facilities in 2010. This year, Andra has launched a new dialogue phase with local actors in order to clarify the implementation scenarios on the surface. The selected site will be validated after the public debate that is now scheduled for the first half of 2013. This debate will be organized by the National Public Debate Committee (Commission nationale du debat public). In parallel, the State is leading the preparation of an territorial development scheme, which will be presented during the public debate. The 2009 milestone also constitutes a new step in the progressive design process of the repository. After the 1998, 2001 and 2005 iterations, which focused mainly on the long-term safety of the repository, the Dossier 2009 highlighted its operational safety, with due account of the non-typical characteristics of an underground nuclear facility. It incorporates the first results of the repository-optimisation studies, which started in 2006 and will continue in the future. The reversibility options for the repository constitute proposals in

  7. Agent engineering

    CERN Document Server

    Liu, Jiming; Zhong, Ning; Wang, Patrick S P

    2001-01-01

    Agent engineering concerns the development of autonomous computational or physical entities capable of perceiving, reasoning, adapting, learning, cooperating and delegating in a dynamic environment. It is one of the most promising areas of research and development in information technology, computer science and engineering. This book addresses some of the key issues in agent engineering: What is meant by "autonomous agents"? How can we build agents with autonomy? What are the desirable capabilities of agents with respect to surviving (they will not die) and living (they will furthermore enjoy

  8. Repository Closure and Sealing Approach

    International Nuclear Information System (INIS)

    The scope of this analysis will be to develop the conceptual design of the closure seals and their locations in the Subsurface Facilities. The design will be based on the recently established program requirements for transitioning to the Site Recommendation (SR) design as outlined by ''Approach to Implementing the Site Recommendation Baseline'' (Stroupe 2000) and the ''Monitored Geologic Repository Project Description Document'' (CRWMS M andO 1999b). The objective of this analysis will be to assist in providing a description for the Subsurface Facilities System Description Document, Section 2 and finally to document any conclusions reached in order to contribute and provide support to the SR. This analysis is at a conceptual level and is considered adequate to support the SR design. The final closure barriers and seals for the ventilation shafts, and the north and south ramps will require these openings to be permanently sealed to limit excessive air and water inflows and prevent human intrusion. The major tasks identified with closure in this analysis are: (1) Developing the overall subsurface seal layout and identifying design and operational interfaces for the Subsurface Facilities. (2) Summarizing the general site conditions and general rock characteristic with respect to seal location and describing the seal selected. (3) Identify seal construction materials, methodology of construction and strategic locations including design of the seal and plugs. (4) Discussing methods to prevent human intrusion

  9. Economics of mined geologic repositories

    International Nuclear Information System (INIS)

    During 1982, Congress considered legislation to provide for the development of repositories for the disposal of high-level radioactive waste and spent nuclear fuel. The result of this legislative effort was the Nuclear Waste Policy Act of 1982 (NWPA), PL 97-425, signed into law January 7, 1983. An important part of the NWPA was the establishment of special funds in the US Treasury for Waste Disposal and Interim Storage to be financed by user fees to pay for all costs of the program. An initial fee of 1.0 mill per kilowatt-hour was specified. The Secretary was asked to annually review the amount of the fees established... to evaluate whether collection of the fee will provide sufficient revenues to offset the costs... In the event of a prospective fee cost mismatch, the Secretary was asked to propose an adjustment to the fee to insure full cost recovery. A series of studies were sponsored by DOE in 1982 to estimate program costs, to calculate the necessary fees to assure cost recovery, and to address uncertainties that could affect future program costs and consequent fee schedules. A brief summary of the 1982 cost estimates is presented. Sources of key cost uncertainties are discussed and the bases for the cost recovery fee calculations are summarized. 17 references, 2 figures, 3 tables

  10. Andra's geologic repository monitoring strategy

    International Nuclear Information System (INIS)

    Document available in extended abstract form only. After having concluded a feasibility study of deep geological disposal for high-level and long-lived radioactive waste in 2005, Andra was charged by the Planning Act no. 2006-739 to design and create an industrial site for geological disposal called Cigeo which must be reversible for at least a century-long period. The French Safety Guide recommends that Andra develop a monitoring program to be implemented at repository construction and conducted until closure, and possibly after closure, with the aim to confirming prior expectations and enhancing knowledge of relevant processes. This abstract focuses on underground structure monitoring. The monitoring system is based on a combination of in-situ instrumentation and nondestructive methods to obtain the required level of reliable performance. To optimize the device distribution, we take into account both the repetitive design of disposal cells and the homogeneity of the rock properties. This resulted in distinguishing pilot disposal cells that are highly instrumented and standard disposal cells where the instrumentation density could be reduced; monitoring will rely mostly on robotic nondestructive evaluations. If monitoring technologies do not comply with all monitoring objectives, real withdrawal tests of high level wastes in some pilot disposal cells are also planned to provide the possibility of carrying out visual inspection, destructive analyses and samplings on construction materials. Such cells are planned to be dismantled because of the potential disturbance of their component performances from the testing process. Based on this overall strategy, Andra has analyzed the technical requirements that must be met by its monitoring equipment. First, these must be able to provide information on key THMCR (Thermal- Hydraulic-Mechanical-Chemical and Radiological) processes, to provide a three-dimensional image of a disposal component's behavior and thus to understand

  11. Building the repositories to serve

    International Nuclear Information System (INIS)

    The project to design and build the Superconducting Super Collider (SSC) Laboratory also includes the exciting opportunity to implement client/server information systems. Lab technologists were eager to take advantage of the cost savings inherent in the open systems and a distributed, client server environment and, at the same time, conscious of the need to provide secure repositories for sensitive data as well as a schedule sensitive acquisition strategy for mission critical software. During the first year of project activity, micro-based project management and business support systems were acquired and implemented to support a small study project of less than 400 people allocating contracts of less than $1 million. The transition to modern business systems capable of supporting more than 10,000 participants (world wide) who would be researching and developing the new technologies that would support the world's largest scientific instrument, a 42 Tevatron, superconducting, super collider became a mission critical event. This paper will present the SSC Laboratory's strategy to balance its commitment to open systems, structured query language (SQL) standards and its success with acquiring commercial off the shelf software to support immediate goals. Included will be an outline of the vital roles played by other labs (Livermore, CERN, Brookhaven, Fermi and others) and a discussion of future collaboration potentials to leverage the information activities of all Department of Energy funded labs

  12. Sorption on inactive repository components

    International Nuclear Information System (INIS)

    The near-field of an intermediate level/low level radioactive waste repository will contain significant quantities of iron and steel, Magnox and Zircaloy. Their corrosion products may possess significant sorption capacity for radioelements. The sorption of americium and plutonium onto magnesium hydroxide, zirconium hydroxide, colloidal magnetite and colloidal haematite has been studied under conditions typical of the porewater of a cementitious near-field. RD values ≥ 105 ml g-1 were measured for both actinides on the oxides and hydroxides. These values are at least as great at those measured on crushed 3:1 Blast Furnace Slag/Ordinary Portland Cement. Competitive sorption experiments have shown that sorption onto the corrosion products does not take place in preference to that on the cement or the converse. Magnetite and haematite colloids are positively charged in cement-equilibrated water whilst zirconium hydroxide is negatively charged. Crushed cement was found to be positively charged. Simple experiments show that only a small proportion of haematite colloids is potentially mobile through a column of crushed cement. (author)

  13. Characteristics of potential repository wastes

    International Nuclear Information System (INIS)

    The LWR spent fuels discussed in Volume 1 of this report comprise about 99% of all domestic non-reprocessed spent fuel. In this report we discuss other types of spent fuels which, although small in relative quantity, consist of a number of diverse types, sizes, and compositions. Many of these fuels are candidates for repository disposal. Some non-LWR spent fuels are currently reprocessed or are scheduled for reprocessing in DOE facilities at the Savannah River Site, Hanford Site, and the Idaho National Engineering Laboratory. It appears likely that the reprocessing of fuels that have been reprocessed in the past will continue and that the resulting high-level wastes will become part of defense HLW. However, it is not entirely clear in some cases whether a given fuel will be reprocessed, especially in cases where pretreatment may be needed before reprocessing, or where the enrichment is not high enough to make reprocessing attractive. Some fuels may be canistered, while others may require special means of disposal. The major categories covered in this chapter include HTGR spent fuel from the Fort St. Vrain and Peach Bottom-1 reactors, research and test reactor fuels, and miscellaneous fuels, and wastes generated from the decommissioning of facilities

  14. REPOSITORY RADIATION SHIELDING DESIGN GUIDE

    International Nuclear Information System (INIS)

    The scope of this document includes radiation safety considerations used in the design of facilities for the Yucca Mountain Site Characterization Project (YMP). The purpose of the Repository Radiation Shielding Design Guide is to document the approach used in the radiological design of the Mined Geologic Disposal System (MGDS) surface and subsurface facilities for the protection of workers, the public, and the environment. This document is intended to ensure that a common methodology is used by all groups that may be involved with Radiological Design. This document will also assist in ensuring the long term survivability of the information basis used for radiological safety design and will assist in satisfying the documentation requirements of the licensing body, the Nuclear Regulatory Commission (NRC). This design guide provides referenceable information that is current and maintained under the YMP Quality Assurance (QA) Program. Furthermore, this approach is consistent with maintaining continuity in spite of a changing design environment. This approach also serves to ensure common inter-disciplinary interpretation and application of data

  15. Building the repositories to serve

    International Nuclear Information System (INIS)

    The project to design and build the Superconducting Super Collider (SSC) Laboratory also includes the exciting opportunity to implement client/server information systems. Lab technologists were eager to take advantage of the cost savings inherent in the open systems and a distributed, client server environment and, at the same time, conscious of the need to provide secure repositories for sensitive data as well as a schedule sensitive acquisition strategy for mission critical software. During the first year of project activity, micro-based project management and business support systems were acquired and implemented to support a small study project of less than 400 people allocating contracts of less than $1 million. The transition to modern business systems capable of supporting more than 10,000 participants (world wide) who would be researching and developing the new technologies that would support the world's largest scientific instrument, a 42 Tevatron, superconducting, super collider became a mission critical event. This paper will present the SSC Laboratory's strategy to balance our commitment to open systems, structured query language (SQL) standards and our success with acquiring commercial off the shelf software (COTS) to support our immediate goals. Included will be an outline of the vital roles played by other labs (Livermore, CERN, Brookhaven, Fermi and others) and a discussion of future collaboration potentials to leverage the information activities of all Department of Energy (DOE) funded labs

  16. The European Repository Landscape 2008 : Inventory of Digital Repositories for Research Output

    OpenAIRE

    Van der Graaf, Maurits

    2009-01-01

    It is widely acknowledged that a common knowledge base for European research is necessary. The DRIVER project aims towards this. European practices may be harmonised and the development of stateof-the-art technology facilitated. As a first step, a clear picture of the state-of-the-art of the European repositories is needed. To get this picture, digital repositories in the 27 countries of the European were surveyed in 2006, covering 114 repositories from 17 European countries. Basically, this ...

  17. Engineered and geologic barriers in repository storage

    International Nuclear Information System (INIS)

    Together with several partners the Karlsruhe Research Center (FZK) conducted a comparison of repository concepts in salt and in hard rock (Geisha). The study was based on the concept of direct disposal of spent fuel elements. This allows a generalization to high-level waste from reprocessing to be made. Both geologic formations allow the protective goal associated with repository storage to be attained. The decision in favor of salt, taken in Germany at an early stage, seems to be reasonable. Knowledge about this type of storage in Germany is clearly better than about hard rock. The cost of a repository in hard rock is higher than in rock salt. Additional costs of repositories in hard rock arise, inter alia, from the more expensive excavation techniques. (orig.)

  18. Biospecimen Repository Access and Data Sharing (BRADS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — BRADS is a repository for data and biospecimens from population health research initiatives and clinical or interventional trials designed and implemented by...

  19. Abadia de Goias repository: design conception

    International Nuclear Information System (INIS)

    In this paper have been presented the criteria, the methodologies and the parameters that were utilized for the design of Abadia de Goias Repository. Hereby the purpose is to show in a succinct way the know how that has been acquired for the design of a LLW and ILW repository. This paper presents information and details concerning to the various phases of the design, beginning with the data collecting activity, the safety analysis elaboration up to the definition of the final concept of the repository and of the required infrastructure work. The safety analysis, based on the Cs-137 migration through the groundwater, made possible at first to determine the places of the repository site where the population is not allowed to drill wells. The analysis allowed also the institutional control period calculation based on the maximum concentration of Cs-137 in the aquifer as well as in the intrusion models. (author). 16 refs., 3 figs., 1 tab

  20. Decision theory applied to radioactive repository construction

    International Nuclear Information System (INIS)

    The objective of this article is to present, through the presentation of an example, the applicability of the decision theory on the selection and construction of a repository for low and intermediate radioactive waste. (author)

  1. NIMH Repository and Genomics Resources (RGR)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The NIMH Repository and Genomics Resource (RGR) stores biosamples, genetic, pedigree and clinical data collected in designated NIMH-funded human subject studies....

  2. State-of-the-art for evaluating the potential effects of erosion and deposition on a radioactive waste repository. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1980-07-16

    The potential impact of future geologic processes on the integrity of a deep, high-level radioactive-waste repository is evaluated. The following study identifies the potential consequences of surface erosion and deposition on sub-surface repository containment characteristics and assesses the ability to measure and predict quantitatively the rates and corresponding extent of these processes in the long term. Numerous studies of the magnitudes and rates of surficial erosion and deposition that have been used to determine the minimum allowable depth for a geologic repository (300 m - NRC Code of Federal Regulations, Part 60.122, Draft 10) are cited in this report. Measurement and interpretation of potential rates and extent of surficial processes in these studies involved considerable uncertainty, and the implications of this uncertainty on presently proposed repository siting criteria are addressed herein. Important concepts that should be considered when developing siting criteria to protect against deleterious effects arising from future erosion or deposition are highlighted. Erosion agents that could affect deep repositories are distinguished in this report so that their individual and combined impacts may be examined. This approach is recommended when evaluating potential repository sites in diverse environments that are susceptible to different agents of erosion. In contrast, agents of sedimentation are not differentiated in this report because of their relatively minor impact on a deep repository.

  3. State-of-the-art for evaluating the potential effects of erosion and deposition on a radioactive waste repository. Final report

    International Nuclear Information System (INIS)

    The potential impact of future geologic processes on the integrity of a deep, high-level radioactive-waste repository is evaluated. The following study identifies the potential consequences of surface erosion and deposition on sub-surface repository containment characteristics and assesses the ability to measure and predict quantitatively the rates and corresponding extent of these processes in the long term. Numerous studies of the magnitudes and rates of surficial erosion and deposition that have been used to determine the minimum allowable depth for a geologic repository (300 m - NRC Code of Federal Regulations, Part 60.122, Draft 10) are cited in this report. Measurement and interpretation of potential rates and extent of surficial processes in these studies involved considerable uncertainty, and the implications of this uncertainty on presently proposed repository siting criteria are addressed herein. Important concepts that should be considered when developing siting criteria to protect against deleterious effects arising from future erosion or deposition are highlighted. Erosion agents that could affect deep repositories are distinguished in this report so that their individual and combined impacts may be examined. This approach is recommended when evaluating potential repository sites in diverse environments that are susceptible to different agents of erosion. In contrast, agents of sedimentation are not differentiated in this report because of their relatively minor impact on a deep repository

  4. Recruitment strategies for a lung cancer chemoprevention trial involving ex-smokers.

    Science.gov (United States)

    Kye, Steve H; Tashkin, Donald P; Roth, Michael D; Adams, Bradley; Nie, Wen-Xian; Mao, Jenny T

    2009-09-01

    The ability to recruit qualified subjects who are willing to adhere to the study protocol in clinical trials is an essential component of translational research. Such tasks can be particularly challenging for chemoprevention studies when the targeted study population is healthy, at risk individuals who do not have signs or symptoms of the disease, and the study participation involves complex scheduling and invasive procedures such as bronchoscopy. In this report, we describe the recruitment process and evaluated the effectiveness of various recruitment strategies utilized in our National Cancer Institute sponsored lung cancer chemoprevention study with celecoxib. Heavy ex-smokers were recruited into the study through various methods such as radio advertisements, print media, mass mailings, flyers, internet postings and others. The number of inquiries, on-site screenees and randomization generated by each method determined the efficacy of that recruitment strategy. We prescreened 4470 individuals, invited 323 people for on-site screening and randomized 137 subjects. Radio advertisements (ads) generated the most inquiries (71.1%), followed by internet posting (11.8%), print media (6.0%), posted and racked flyers (4.4%), mass mailings (2.7%) and other strategies such as referrals from friends or family members or health care providers (2.3%). Radio ads, although costly, yielded the most subjects for on-site screening and randomization. Moreover, among the various types of radio stations, news radio stations were by far the most successful. Our results suggest that advertising on news radio is a highly effective recruitment method for successful accrual of ex-smokers into lung cancer chemoprevention trials. PMID:19508900

  5. Antiproliferative and cancer-chemopreventive properties of sulfated glycosylated extract derived from Leucaena leucocephala

    Directory of Open Access Journals (Sweden)

    Gamal-Eldeen Amira

    2007-01-01

    Full Text Available This work aimed to prove that simple chemical modification could provide new cancer chemopreventive and/or anticancer properties to the inactive extracted polysaccharide derived from Leucaena leucocephala . Polysaccharides were extracted from Leucaena leucocephala seeds and its 2,4-pentanedione-treated derivative (glycosylated form was prepared, which is further sulphated to give sulphated glycosylated form. Estimation of their anti-initiation activity, modulation of carcinogen metabolism, was indicated by the inhibition cytochrome P450 1A (CYP1A and the induction of glutathione-S-transferases (GSTs. Anti-proliferation activity was investigated by MTT assay against human hepatocarcinoma (HepG2, breast carcinoma (MCF-7 and lymphoblastic leukemia (1301. Apoptosis/necrosis and cell cycle were analyzed by flow cytometry. The results revealed that glycosylated form inhibited both CYP1A and GSTs, while sulphated glycosylated form not only inhibited CYP1A, but also induced the GSTs. Unlike GE, sulphated glycosylated form possessed a significant anti-proliferative activity against different cell lines. Analysis of HepG2 cell cycle phases demonstrated that glycosylated form led to a delay of G2/M-phase, while sulphated glycosylated form led to a concomitant arrest in S- and G2/M-phases. Investigation of apoptosis/necrosis ratio demonstrated that both of glycosylated form and sulphated glycosylated form induced HepG2 cell death by necrosis, but not apoptosis. Unmodified crude extract was neither active as cancer chemopreventive nor as anti-proliferative. In conclusion, chemical modification of Leucaena gum induced its cancer chemopreventive and anti-proliferative activities.

  6. The Geant4 physics validation repository

    Science.gov (United States)

    Wenzel, H.; Yarba, J.; Dotti, A.

    2015-12-01

    The Geant4 collaboration regularly performs validation and regression tests. The results are stored in a central repository and can be easily accessed via a web application. In this article we describe the Geant4 physics validation repository which consists of a relational database storing experimental data and Geant4 test results, a java API and a web application. The functionality of these components and the technology choices we made are also described.

  7. The CTU Prague Relational Learning Repository

    OpenAIRE

    Motl, Jan; Schulte, Oliver

    2015-01-01

    The aim of the CTU Prague Relational Learning Repository is to support machine learning research with multi-relational data. The repository currently contains 50 SQL databases hosted on a public MySQL server located at relational.fit.cvut.cz. A searchable meta-database provides metadata (e.g., the number of tables in the database, the number of rows and columns in the tables, the number of foreign key constraints between tables).

  8. Impact of retrievability of repository design

    International Nuclear Information System (INIS)

    In this paper the impact of the retrievability on the design of the repository will be handled. Retrievability of radioactive waste from a repository in geological formations has received increasing attention during recent years. It is obvious that this retrievability will have consequences in terms of mining engineering, safety and cost. The purpose of the present study is to evaluate cost consequences by comparing two extreme options for retrievable storage. (author). 6 refs., 3 figs

  9. Memory provisions for the Manche Surface Repository

    International Nuclear Information System (INIS)

    The French La Manche repository site received its last radioactive waste package in 1994. In 2003, the official surveillance phase of the closed repository started under the supervision of Andra (the national industrial operator), the French Nuclear Safety Authority (ASN) and society (e.g. the local municipalities). Florence Espiet explained that information on the existence of the repository, its content, how it was operated and how it works needs to be preserved. It also is planned to review the information periodically for a minimum of 300 years. She described the creation of two documents on memory (a detailed and a summary one), both on permanent paper, and the preservation of the land registration. The latter constitutes 'passive' provisions for preserving memory. In addition, a number of 'active' provisions are and will be put in place: guided visits, exhibitions, partnerships with organisations dealing with memory preservation, and the creation of a think tank. The latter consists of local citizens and politicians, retired employees from Andra and artists that meet several times a year and reflect on memory preservation from the perspective of, for instance, local history, education, arts and rituals. Finally, two types of markers will be used to preserve the repository's memory: i) three herbaria cataloguing the plants growing on the site of the repository, including a very short description of the repository, will be stored at different sites in France; ii) a stele indicating the main characteristics of the repository, potentially linked to an art work, will be erected at the repository

  10. Learning Object Annotation for Agricultural Learning Repositories

    OpenAIRE

    Ebner, Hannes; Manouselis, Nikos; Palmér, Matthias; Enoksson, Fredrik; Palavitsinis, Nikos; Kastrantas, Kostas; Naeve, Ambjörn

    2009-01-01

    This paper introduces a Web-based tool that has been developed to facilitate learning object annotation in agricultural learning repositories with IEEE LOM-compliant metadata. More specifically, it presents how an application profile of the IEEE LOM standard has been developed for the description of learning objects on organic agriculture and agroecology. Then, it describes the design and prototype development of the Organic.Edunet repository tool: a Web-based for annotating learning objects ...

  11. Quantitative analysis of learning object repositories

    OpenAIRE

    Ochoa, Xavier; Duval, Erik

    2008-01-01

    This paper conducts the first detailed quantitative study of the process of publication of learning objects in repositories. This process has been often discussed theoretically, but never empirically evaluated. Several question related to basic characteristics of the publication process are raised at the beginning of the paper and answered through quantitative analysis. To provide a wide view of the publication process, this paper analyzes four types of repositories: Learning Object Repositor...

  12. Quantitative analysis of learning object repositories

    OpenAIRE

    Ochoa X.; Duval E.

    2009-01-01

    This paper conducts the first detailed quantitative study of the process of publication of learning objects in repositories. This process has been often discussed theoretically, but never empirically evaluated. Several question related to basic characteristics of the publication process are raised at the beginning of the paper and answered through quantitative analysis. To provide a wide view of the publication process, this paper analyzes four types of repositories: Learning Object Repositor...

  13. Repositories: What's the target? An ARROW Perspective

    OpenAIRE

    Whitehead, Derek

    2005-01-01

    The key observation about institutional research repositories is that they are under-used. This paper looks at why take-up has been slow, and what might encourage researchers to use these facilities. This paper surveys the evolution of practice and rationale for the institutional research repository, looks at existing use studies and opinion surveys of users, and examines ways in which university libraries, the main proponents, have changed their approaches in response to their experience...

  14. Metadata, repository and methodology in learning objects

    OpenAIRE

    Fernández Diego, Marta; Gordo Monzó, María Luz; Boza García, Andrés; Cuenca, L.; Ruiz Font, Leonor; Alemany Díaz, María Del Mar; Alarcón Valero, Faustino

    2015-01-01

    Many universities in different countries are redesigning their degree and master programmes on the basis of new academic and professional profiles incorporating a number of competences. One competence can be acquired through several learning objects. A wide variety of learning repositories that provide resources for education in the form of learning objects can be found. These resources are normally stored in learning object repositories where they are catalogued with metadata fac...

  15. The Geant4 Physics Validation Repository

    Energy Technology Data Exchange (ETDEWEB)

    Wenzel, H. [Fermilab; Yarba, J. [Fermilab; Dotti, A. [SLAC

    2015-12-23

    The Geant4 collaboration regularly performs validation and regression tests. The results are stored in a central repository and can be easily accessed via a web application. In this article we describe the Geant4 physics validation repository which consists of a relational database storing experimental data and Geant4 test results, a java API and a web application. The functionality of these components and the technology choices we made are also described

  16. Learning object repositories as knowledge management systems

    OpenAIRE

    Sampson, Demetrios G.; Panagiotis Zervas

    2013-01-01

    Over the past years, a number of international initiatives that recognize the importance of sharing and reusing digital educational resources among educational communities through the use of Learning Object Repositories (LORs) have emerged. Typically, these initiatives focus on collecting digital educational resources that are offered by their creators for open access and potential reuse. Nevertheless, most of the existing LORs are designed more as digital repositories, rather than as Knowled...

  17. Numerical modeling of magma-repository interactions

    OpenAIRE

    Bokhove, O.

    2001-01-01

    This report explains the numerical programs behind a comprehensive modeling effort of magma-repository interactions. Magma-repository interactions occur when a magma dike with high-volatile content magma ascends through surrounding rock and encounters a tunnel or drift filled with either a magmatic gas or air at atmospheric pressure. The simplified mathematical model to describe these flow phenomena consists of compressible flow equations of one- or two-dimensional flow in a flow tube with a ...

  18. Cyclooxygenase as a target for chemoprevention in colorectal cancer: lost cause or a concept coming of age?

    LENUS (Irish Health Repository)

    Doherty, Glen A

    2009-02-01

    COX-2 is upregulated at an early stage in colorectal carcinogenesis and generates prostaglandins, which promote cancer cell proliferation, impair apoptosis and enhance angiogenesis, promoting tumour growth and metastasis. There are ample data from animal models and human studies to demonstrate enhanced tumour progression associated with COX-2 activity in cancer cells. Conversely, NSAIDs including aspirin inhibit COX-2 and, therefore, have anti-neoplastic properties. There has been sustained interest in COX-2 as a chemopreventive target in colorectal cancer (CRC) and although both aspirin and COX-2 selective NSAIDs have demonstrated efficacy, adverse effects have limited their widespread adoption. In particular, evidence of the cardiovascular effects of COX-2 selective inhibitors has led to questioning of the suitability of COX-2 as a target for chemoprevention. This review examines the basis for targeting COX-2 in CRC chemoprevention, evaluates the efficacy and safety of the approach and examines future strategies in this area.

  19. Chemoprevention of Lung Squamous Cell Carcinoma in Mice by a Mixture of Chinese Herbs

    OpenAIRE

    Wang, Yian; Zhang, Zhongqiu; Garbow, Joel R.; Rowland, Doug J.; Ronald A Lubet; Sit, Daniel; Law, Frances; You, Ming

    2009-01-01

    Anti-tumor B (ATB) is a Chinese herbal mixture of six plants. Previous studies have shown significant chemopreventive efficacy of ATB against human esophageal and lung cancers. We have recently developed a new mouse model for lung squamous cell carcinomas (SCC). In this study, lung SCC mouse model was characterized using small-animal imaging techniques (MRI and CT). ATB decreased lung SCC significantly (3.1 fold, p < 0.05) and increased lung hyperplastic lesions by 2.4 fold (p < 0.05). This o...

  20. Steroidal pyrazolines evaluated as aromatase and quinone reductase-2 inhibitors for chemoprevention of cancer.

    Science.gov (United States)

    Abdalla, Mohamed M; Al-Omar, Mohamed A; Bhat, Mashooq A; Amr, Abdel-Galil E; Al-Mohizea, Abdullah M

    2012-05-01

    The aromatase and quinone reductase-2 inhibition of synthesized heterocyclic pyrazole derivatives fused with steroidal structure for chemoprevention of cancer is reported herein. All compounds were interestingly less toxic than the reference drug (Cyproterone(®)). The aromatase inhibitory activities of these compounds were much more potent than the lead compound resveratrol, which has an IC(50) of 80 μM. In addition, all the compounds displayed potent quinone reductase-2 inhibition. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). The aromatase and quinone reductase-2 inhibitors resulting from this study have potential value in the treatment and prevention of cancer. PMID:22361454

  1. The United States Geologic Repository Program

    International Nuclear Information System (INIS)

    The Nuclear Waste Policy Act of 1982 established activities and schedules that must be followed to develop a geological repository for safe disposal of high level radioactive waste and spent nuclear fuel. The status of the Geologic Repository Program is described in terms of five programme phases that will lead to the issuance of a licence to receive and emplace wastes in a geological repository by 1998. These phases are: (1) recommendation of sites for characterization, (2) characterization of sites, (3) selection and approval of one site for development as a geological repository, (4) licensing and construction authorization for the approved site, and (5) construction and performance confirmation testing for the geological repository. Programmatic activities have been concentrated in Phase 1. Following the publication of Siting Guidelines that established performance requirements for a geological repository system, the qualifications for potential sites and how the site selection process should be carried out, the Department of Energy issued draft environmental assessments that nominated five sites as suitable for site characterization and recommended three of these for characterization. After review of public comments and revision of the drafts, the environmental assessments will be submitted to the President for approval. With this approval, critical path activities can be undertaken to implement later phases of the programme. (author)

  2. Implementation of the Brazilian national repository

    Energy Technology Data Exchange (ETDEWEB)

    Tello, Cledola Cassia Oliveira de, E-mail: tellocc@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2013-07-01

    Ionizing radiation in Brazil is used in electricity generation, medicine, industry, agriculture and for research and development purposes. All these activities can generate radioactive waste. At this point, in Brazil, the use of nuclear energy and radioisotopes justifies the construction of a national repository for radioactive wastes of low and intermediate-level. According to Federal Law No. 10308, Brazilian National Commission for Nuclear Energy (CNEN) is responsible for designing and constructing the intermediate and final storages for radioactive wastes. Additionally, a restriction on the construction of Angra 3 is that the repository is under construction until its operation start, attaining some requirements of the Brazilian Environmental Regulator (IBAMA). The RBMN Project (Repository for Low and Intermediate-Level Radioactive Wastes) aims at the implantation of a National Repository for disposal of low and intermediate-level of radiation wastes. This Project has some aspects that are unique in the Brazilian context, especially referring to the time between its construction and the end of its institutional period. This time is about 360 years, when the area will be released for unrestricted uses. It means that the Repository must be safe and secure for more than three hundred years, which is longer than half of the whole of Brazilian history. This aspect is very new for the Brazilian people, bringing a new dimension to public acceptance. Another point is this will be the first repository in South America, bringing a real challenge for the continent. The current status of the Project is summarized. (author)

  3. The development of safeguards for geological repositories

    International Nuclear Information System (INIS)

    Traditionally, research and development on geological repositories for High Level Waste (HLW) focuses on the short- and long-term safety aspects of the repository. If the repository will also be used for the disposal of spent fuel, safeguards aspects have to be taken into account. Safety and safeguards requirements may be contradictory; the safety of a geological repository is based on the non-intrusion of the geological containment, while safeguards require regular inspections of position and amount of the spent fuel. Examples to reconcile these contradictory requirements are the use of information required for the safety assessment of the geological repository for safeguards purposes and the adaptation of the safeguards approach to use non-intrusive inspection techniques. The principles of an inspection approach for a geological repository are now generally accepted within the IAEA. The practical applicability of the envisaged inspection techniques is still subject to investigation. It is specifically important for the Belgian situation that an inspection technique can be used in clay, the geological medium in which Belgium intends to dispose its HLW and spent fuel. The work reported in this chapter is the result of an international cooperation in the framework of the IAEA, in which SCK-CEN participates

  4. Durability of cemented waste in repository and under simulated conditions

    International Nuclear Information System (INIS)

    simulated disposal conditions for reference samples; - emplacement of reference samples in Baita Bihor Repository for real disposal characterization. All samples were positioned in five locations of Baita-Bihor repository where they will be kept for 1, 3, 5 and 10 years before mechanical and structural characterization. These locations have different humidity values, decreasing from location 1 to 5. The results will be compared with those obtained for the same type of samples kept in laboratory conditions. The mechanical performances of the matrix with cement-mineral additives are not influenced if bentonite or volcanic tuff concentration is is lower than 10%. The very good mechanical behaviour of the samples, drives at the conclusion that the additive cement-mineral mixture could be used in the disposal procedure, with good results, if the future structure characterization would prove the role as engineered barrier. Complexing reagents reduce drastically the mechanical performances. The chemical nature of the complexing agent plays an important role, the damaging effect being more pregnant for tartaric and citric acid than for oxalic acid. In any case there is a maximum limit of concentration which is acceptable from mechanical point of view. The mechanical resistance observed in all samples, after one year disposal, are within the accepted limits for the matrix durability. Thus, disposal conditions has not influence the mechanical properties of the cement matrix after one year disposal. The presented results, showed that bentonite seems to have a positive influence on the quality of the examined matrices . These results are preliminary. The data obtained so far will be completed with those to be obtained after three year disposal. XRD initial investigation of waste samples showed complex changes in the structure and components. To understand the systems, series of different compositions need to be characterized. In the next years the durability of samples kept for times

  5. Wetting of bituminized ion-exchangers under simulated repository conditions

    International Nuclear Information System (INIS)

    According to the present plans the spent nuclear fuel from four Finnish nuclear power units will be transferred after interim storage to the final disposal site where it will be encapsulated and disposed of in a final repository constructed into the bedrock at a depth of 500 meters. Low and medium level waste generated at nuclear power plants will be finally disposed of in caverns constructed in the bedrock at the power plant site. The safety of the final disposal is based on a multibarrier concept and the degree of safety is estimated by using predictive models. The properties of the waste form are taken into account in the design of the repository construction. Bitumen has been chosen as an immobilisation agent for the wet wastes at Olkiluoto Power Plant, where two BWR units, TVO 1 and TVO 2, have separate bituminization facilities designed by Asea-Atom. Properties of bituminized spent ion-exchange resins from Olkiluoto power plant have been studied by VTT Chemical Technology since the late 70's. These studies have concentrated mainly on determining the long-term behaviour of the bituminization product under the repository conditions. Current interest lies on wetted product as a diffusion barrier. For this purpose a microscopic method for the visualisation of the structure of the wetted product has been developed. The equilibration of the samples in simulated concrete groundwater is currently going on at a temperature of 5-8 deg. C. Preliminary results are presented in this paper. Diffusion experiments have been planned for the further characterising of the wetted product as a release barrier for radionuclides including modelling. (author)

  6. Qualifying concrete for a low-level waste repository

    International Nuclear Information System (INIS)

    A waste repository for the belowground disposal of low-level radioactive waste, labelled IRUS (Intrusion Resistant Underground Structure), is planned at Chalk River Nuclear Laboratories. It relies greatly on the durability of concrete for a minimum of 500 years of service life. A research program based on laboratory testing to design a durable concrete and predict its useful engineered service life is in progress. Durability of concrete depends on its resistance of deterioration from both internal and external causes. Since the rate of degradation depends to a major extent on the rate of ingress of aggressive ions into concrete, laboratory testing is in progress to establish the diffusion rates of ions, especially chlorides, sulphate and carbonate ions. A total of 1000 concrete specimens and 500 paste specimens are being exposed at 22 and 45 degrees C to twenty-five different combinations of corrosive agents, including CO2. Procedures to measure the ionic profile and to determine the factors controlling diffusion of ions in the various concretes have been developed. The paper presents the initial results from the research program and the longevity predictions to qualify concretes for the IRUS waste repository, based on twelve months of diffusion testing on laboratory specimens

  7. Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population.

    Science.gov (United States)

    Luk, Sze-Ue; Lee, Terence Kin-Wah; Liu, Ji; Lee, Davy Tak-Wing; Chiu, Yung-Tuen; Ma, Stephanie; Ng, Irene Oi-Lin; Wong, Yong-Chuan; Chan, Franky Leung; Ling, Ming-Tat

    2011-01-01

    Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer. PMID:21603625

  8. Updates and Controversies in the Rapidly Evolving Field of Lung Cancer Screening, Early Detection, and Chemoprevention

    Directory of Open Access Journals (Sweden)

    Hasmeena Kathuria

    2014-05-01

    Full Text Available Lung cancer remains the leading cause of cancer-related death in the United States. Cigarette smoking is a well-recognized risk factor for lung cancer, and a sustained elevation of lung cancer risk persists even after smoking cessation. Despite identifiable risk factors, there has been minimal improvement in mortality for patients with lung cancer primarily stemming from diagnosis at a late stage when there are few effective therapeutic options. Early detection of lung cancer and effective screening of high-risk individuals may help improve lung cancer mortality. While low dose computerized tomography (LDCT screening of high risk smokers has been shown to reduce lung cancer mortality, the high rates of false positives and potential for over-diagnosis have raised questions on how to best implement lung cancer screening. The rapidly evolving field of lung cancer screening and early-detection biomarkers may ultimately improve the ability to diagnose lung cancer in its early stages, identify smokers at highest-risk for this disease, and target chemoprevention strategies. This review aims to provide an overview of the opportunities and challenges related to lung cancer screening, the field of biomarker development for early lung cancer detection, and the future of lung cancer chemoprevention.

  9. Antibiotic Agents

    Science.gov (United States)

    ... either as public health or as non-public health antimicrobial agents. What is the difference between bacteriostats, sanitizers, disinfectants ... bacteria, however, there is considerable controversy surrounding their health benefits. The ... producing agents (Table of Antibacterials) have been used for many ...

  10. SUBSURFACE REPOSITORY INTEGRATED CONTROL SYSTEM DESIGN

    Energy Technology Data Exchange (ETDEWEB)

    D.C. Randle

    2000-01-07

    The primary purpose of this document is to develop a preliminary high-level functional and physical control system architecture for the potential repository at Yucca Mountain. This document outlines an overall control system concept that encompasses and integrates the many diverse process and communication systems being developed for the subsurface repository design. This document presents integrated design concepts for monitoring and controlling the diverse set of subsurface operations. The Subsurface Repository Integrated Control System design will be composed of a series of diverse process systems and communication networks. The subsurface repository design contains many systems related to instrumentation and control (I&C) for both repository development and waste emplacement operations. These systems include waste emplacement, waste retrieval, ventilation, radiological and air monitoring, rail transportation, construction development, utility systems (electrical, lighting, water, compressed air, etc.), fire protection, backfill emplacement, and performance confirmation. Each of these systems involves some level of I&C and will typically be integrated over a data communications network throughout the subsurface facility. The subsurface I&C systems will also interface with multiple surface-based systems such as site operations, rail transportation, security and safeguards, and electrical/piped utilities. In addition to the I&C systems, the subsurface repository design also contains systems related to voice and video communications. The components for each of these systems will be distributed and linked over voice and video communication networks throughout the subsurface facility. The scope and primary objectives of this design analysis are to: (1) Identify preliminary system-level functions and interfaces (Section 6.2). (2) Examine the overall system complexity and determine how and on what levels the engineered process systems will be monitored, controlled, and

  11. SUBSURFACE REPOSITORY INTEGRATED CONTROL SYSTEM DESIGN

    International Nuclear Information System (INIS)

    The primary purpose of this document is to develop a preliminary high-level functional and physical control system architecture for the potential repository at Yucca Mountain. This document outlines an overall control system concept that encompasses and integrates the many diverse process and communication systems being developed for the subsurface repository design. This document presents integrated design concepts for monitoring and controlling the diverse set of subsurface operations. The Subsurface Repository Integrated Control System design will be composed of a series of diverse process systems and communication networks. The subsurface repository design contains many systems related to instrumentation and control (I andC) for both repository development and waste emplacement operations. These systems include waste emplacement, waste retrieval, ventilation, radiological and air monitoring, rail transportation, construction development, utility systems (electrical, lighting, water, compressed air, etc.), fire protection, backfill emplacement, and performance confirmation. Each of these systems involves some level of I andC and will typically be integrated over a data communications network throughout the subsurface facility. The subsurface I andC systems will also interface with multiple surface-based systems such as site operations, rail transportation, security and safeguards, and electrical/piped utilities. In addition to the I andC systems, the subsurface repository design also contains systems related to voice and video communications. The components for each of these systems will be distributed and linked over voice and video communication networks throughout the subsurface facility. The scope and primary objectives of this design analysis are to: (1) Identify preliminary system-level functions and interfaces (Section 6.2). (2) Examine the overall system complexity and determine how and on what levels the engineered process systems will be monitored

  12. Honokiol, a chemopreventive agent against skin cancer, induces cell cycle arrest and apoptosis in human epidermoid A431 cells.

    Science.gov (United States)

    Chilampalli, Chandeshwari; Guillermo, Ruth; Kaushik, Radhey S; Young, Alan; Chandrasekher, Gudiseva; Fahmy, Hesham; Dwivedi, Chandradhar

    2011-11-01

    Honokiol is a plant lignan isolated from bark and seed cones of Magnolia officinalis. Recent studies from our laboratory indicated that honokiol pretreatment decreased ultraviolet B-induced skin cancer development in SKH-1 mice. The aim of the present investigation was to study the effects of honokiol on human epidermoid squamous carcinoma A431 cells and to elucidate possible mechanisms involved in preventing skin cancer. A431 cells were pretreated with different concentrations of honokiol for a specific time period and investigated for effects on apoptosis and cell cycle analysis. Treatment with honokiol significantly decreased cell viability and cell proliferation in a concentration- and time-dependent manner. Honokiol pretreatment at 50 μmol/L concentration induced G0/G1 cell cycle arrest significantly (P Cdk4 and Cdk6 proteins and up-regulated the expression of Cdk's inhibitor proteins p21 and p27. Pretreatment of A431 cells with honokiol leads to induction of apoptosis and DNA fragmentation. These findings indicate that honokiol provides its effects in squamous carcinoma cells by inducing cell cycle arrest at G0/G1 phase and apoptosis. PMID:21908486

  13. Fons antic i repositoris universitaris a Espanya

    Directory of Open Access Journals (Sweden)

    Herrera Morillas, José Luis

    2015-12-01

    Full Text Available Es mostra la presència de col·leccions de fons antic en els repositoris de les biblioteques universitàries espanyoles després d'analitzar tots els repositoris. Per a aquesta anàlisi, com a part de la metodologia emprada, s'ha elaborat un model o llista que consta d'onze elements. Del conjunt de les universitats espanyoles, seixanta tenen repositoris, vint-i-vuit dels quals (16,8 % disposen de col·leccions de fons antic. Com que del concepte de repositori institucional no sembla desprendre's que tingui com a finalitat incloure aquest tipus de col·leccions, es reflexiona sobre la peculiaritat que una part dels repositoris universitaris espanyols inclogui col·leccions d'aquestes característiques.Se muestra la presencia de colecciones de fondo antiguo en los repositorios de las bibliotecas universitarias españolas después de analizar todos los repositorios. Para este análisis, como parte de la metodología empleada, se ha elaborado un modelo o lista que consta de once elementos. Del conjunto de las universidades españolas, sesenta cuentan con repositorios y, de estos, veintiocho (16,8 % disponen de colecciones de fondo antiguo. Debido a que del concepto de repositorio institucional no parece desprenderse que tenga como finalidad albergar este tipo de colecciones, se hace una reflexión sobre la peculiaridad de que parte de los repositorios universitarios españoles incluya colecciones de estas características.This paper uses an analysis of the repositories of Spanish universities to identify which institutions contain rare book and manuscript collections. The method used in this analysis involved examining each university on the basis of a list comprising eleven elements. A total of 60 universities were found to have repositories but only 28 (16.8 % of these contained rare book and manuscript collections. In the light of these figures, which suggest that Spanish university repositories do not generally consider the preservation of rare

  14. Enriching the content provided by cultural catalogues with data from institutional repositories

    OpenAIRE

    Á. Rodríguez Miranda; J. M. Valle Melón; M. C. Porcal-Gonzalo

    2013-01-01

    [EN] Institutional repositories play a key role in universities and research centers for the preservation and dissemination of the knowledge generated or collected by these agents. Part of the information contained is related with Cultural Heritage and, therefore, it could be taken into account by thematic catalogues such as Europeana. In this paper, the opportunities and limitations of this connection are considered and presented by means of an ongoing case at the University of the Basque...

  15. Coupling fuel cycles with repositories: how repository institutional choices may impact fuel cycle design

    Energy Technology Data Exchange (ETDEWEB)

    Forsberg, C. [Massachusetts Institute of Technology, 77 Massachusetts Ave., Room 24-207A Cambridge, MA 02139 (United States); Miller, W.F. [Texas A.M. University System, MS 3133 College Station, TX 77843-3133 (United States)

    2013-07-01

    The historical repository siting strategy in the United States has been a top-down approach driven by federal government decision making but it has been a failure. This policy has led to dispatching fuel cycle facilities in different states. The U.S. government is now considering an alternative repository siting strategy based on voluntary agreements with state governments. If that occurs, state governments become key decision makers. They have different priorities. Those priorities may change the characteristics of the repository and the fuel cycle. State government priorities, when considering hosting a repository, are safety, financial incentives and jobs. It follows that states will demand that a repository be the center of the back end of the fuel cycle as a condition of hosting it. For example, states will push for collocation of transportation services, safeguards training, and navy/private SNF (Spent Nuclear Fuel) inspection at the repository site. Such activities would more than double local employment relative to what was planned for the Yucca Mountain-type repository. States may demand (1) the right to take future title of the SNF so if recycle became economic the reprocessing plant would be built at the repository site and (2) the right of a certain fraction of the repository capacity for foreign SNF. That would open the future option of leasing of fuel to foreign utilities with disposal of the SNF in the repository but with the state-government condition that the front-end fuel-cycle enrichment and fuel fabrication facilities be located in that state.

  16. Coupling fuel cycles with repositories: how repository institutional choices may impact fuel cycle design

    International Nuclear Information System (INIS)

    The historical repository siting strategy in the United States has been a top-down approach driven by federal government decision making but it has been a failure. This policy has led to dispatching fuel cycle facilities in different states. The U.S. government is now considering an alternative repository siting strategy based on voluntary agreements with state governments. If that occurs, state governments become key decision makers. They have different priorities. Those priorities may change the characteristics of the repository and the fuel cycle. State government priorities, when considering hosting a repository, are safety, financial incentives and jobs. It follows that states will demand that a repository be the center of the back end of the fuel cycle as a condition of hosting it. For example, states will push for collocation of transportation services, safeguards training, and navy/private SNF (Spent Nuclear Fuel) inspection at the repository site. Such activities would more than double local employment relative to what was planned for the Yucca Mountain-type repository. States may demand (1) the right to take future title of the SNF so if recycle became economic the reprocessing plant would be built at the repository site and (2) the right of a certain fraction of the repository capacity for foreign SNF. That would open the future option of leasing of fuel to foreign utilities with disposal of the SNF in the repository but with the state-government condition that the front-end fuel-cycle enrichment and fuel fabrication facilities be located in that state

  17. The influence of organic materials on the near field of an intermediate level waste radioactive waste repository

    International Nuclear Information System (INIS)

    The influence of organic materials, which are present in some intermediate level wastes, on the chemistry of the near field of a radioactive waste repository is discussed. Particular attention is given to the possible formation of water soluble complexing agents formed as a result of the radiation field and chemical conditions. The present state of the research is reviewed. (author)

  18. Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis.

    Science.gov (United States)

    Bishayee, Anupam; Mandal, Animesh; Bhattacharyya, Piyali; Bhatia, Deepak

    2016-01-01

    Breast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2-5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer. PMID:26699876

  19. Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis

    Science.gov (United States)

    Bishayee, Anupam; Mandal, Animesh; Bhattacharyya, Piyali; Bhatia, Deepak

    2016-01-01

    abstract Breast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2–5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer. PMID:26699876

  20. Acceptability by community health workers in Senegal of combining community case management of malaria and seasonal malaria chemoprevention

    DEFF Research Database (Denmark)

    Tine, Roger Ck; Ndiaye, Pascal; Ndour, Cheikh T;

    2013-01-01

    Community case management of malaria (CCMm) and seasonal malaria chemoprevention (SMC) are anti-malarial interventions that can lead to substantial reduction in malaria burden acting in synergy. However, little is known about the social acceptability of these interventions. A study was undertaken...... to assess whether combining the interventions would be an acceptable approach to malaria control for community health workers (CHWs)....

  1. Modelling gas generation in radioactive waste repositories

    International Nuclear Information System (INIS)

    In a repository containing low- and intermediate-level waste, gas generation will occur principally by the coupled processes of metal corrosion and microbial degradation of cellulosic waste. This Paper describes a mathematical model design to address gas generation by these mechanisms. The metal corrosion model incorporates a three-stage process encompassing both aerobic and anaerobic corrosion regimes; the microbial degradation model simulates the activities of eight different microbial populations, which are maintained as functions both of pH and of the concentrations of particular chemical species. Gas concentrations have been measured over a period of three years in large-scale drum experiments designed to simulate repository conditions. Model predictions are confirmed against the experimental measurements, and a prediction is then made of gas concentrations and generation rates over an assessment period of one million years in a radioactive waste repository. (author)

  2. Modelling gas generation in radioactive waste repositories

    International Nuclear Information System (INIS)

    In a repository containing low- and intermediate-level waste, gas generation will occur principally by the coupled processes of metal corrosion and microbial degradation of cellulosic waste. This paper describes a mathematical model designed to address gas generation by these mechanisms. The metal corrosion model incorporates a three-stage process encompassing both aerobic and anaerobic corrosion regimes; the microbial degradation model simulates the activities of eight different microbial populations, which are maintained as functions both of pH and of the concentrations of particular chemical species. Gas concentrations have been measured over a period of three years in large-scale drum experiments designed to simulate repository conditions. Model predictions are confirmed against the experimental measurements, and a prediction is then made of gas concentrations and generation rates over an assessment period of one million years in a radioactive waste repository. (Author)

  3. Web-based tribology design repository system

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Tribology design is one of the most important parts of mechanical product design as thestrength design. Unfortunately, because tribology design knowledge is often m ulti-disciplinary,complicated and piecemeal, it is therefore difficult for a mechanical designer to capture the neededtribology design knowledge. The concept of tribology design repository is proposed in this paper totry to address this problem. This paper presents an object-oriented knowledge representation lan-guage based on the modeling of tribology design component and it makes the complicated tribol-ogy knowledge represented has such advantages as inheritance, encapsulation, and consistency.A web-based triblogy design repository is then established and it enables the edition, retrieve,sharing and reuse of corporate tribology design knowledge in the repository from the Internet.

  4. Investigative study of standards for digital repositories and related services

    CERN Document Server

    Foulonneau, Muriel; Badolato, Anne-Marie

    2008-01-01

    This study is meant for institutional repository managers, service providers, repository software developers and generally, all players taking an active part in the creation of the digital repository infrastructure for e-research and e-learning. It reviews the current standards, protocols and applications in the domain of digital repositories. Special attention is being paid to the interoperability of repositories to enhance the exchange of data in repositories. It aims to stimulate discussion about these topics and supports initiatives for the integration of and, where needed, development of

  5. Citizen participation in nuclear waste repository siting

    International Nuclear Information System (INIS)

    The following study presents a proposed strategy for citizen participation during the planning stages of nuclear waste repository siting. It discusses the issue from the general perspective of citizen participation in controversial issues and in community development. Second, rural institutions and attitudes toward energy development as the context for developing a citizen participation program are examined. Third, major citizen participation techniques and the advantages and disadvantages of each approach for resolving public policy issues are evaluated. Fourth, principles of successful citizen participation are presented. Finally, a proposal for stimulating and sustaining effective responsible citizen participation in nuclear waste repository siting and management is developed

  6. Citizen participation in nuclear waste repository siting

    Energy Technology Data Exchange (ETDEWEB)

    Howell, R.E.; Olsen, D.

    1982-12-01

    The following study presents a proposed strategy for citizen participation during the planning stages of nuclear waste repository siting. It discusses the issue from the general perspective of citizen participation in controversial issues and in community development. Second, rural institutions and attitudes toward energy development as the context for developing a citizen participation program are examined. Third, major citizen participation techniques and the advantages and disadvantages of each approach for resolving public policy issues are evaluated. Fourth, principles of successful citizen participation are presented. Finally, a proposal for stimulating and sustaining effective responsible citizen participation in nuclear waste repository siting and management is developed.

  7. Actinide behavior under final repository relevant conditions

    International Nuclear Information System (INIS)

    Experiments on the solubility behavior and the redox chemistry of actinides and long-living fission products under different geochemical boundary conditions, here on the Np(V) solubility in alkaline CaCl2 systems, provide basic information on processes that can occur in a nuclear final repository in case of water ingress. The thermodynamic constants derived from these experiments allow the geochemical modeling of these processes and a rough estimation of radionuclide solubility limits for different scenarios. Scientific research projects on this issue will reduce the uncertainties of long-term safety analyses for final repositories for high-level radioactive wastes significantly.

  8. Safety analyses for the planned Konrad repository

    International Nuclear Information System (INIS)

    The safety analyses for the planned federal repository Konrad are described which serve to check and prove observance of the protection goals. The safety analyses lead to the definition of requirements for the plant and the radioactive waste. As a large number of papers dealing with the safety analyses for the repository's operation phase have already been published, the present report concentrates on the investigations into the post-operational phase which were carried out, among others, by the Bundesanstalt fur Geowissenschaften und Rohstoffe (Federal Institute for Geosciences and Natural Resources), Hanover, and the Gesellschaft fur Strahlen- and Umweltforschung (Radiological and Environmental Research Corporation), Braunschweig and Munich, on behalf of the PTB

  9. GreyGuide Forum and Repository

    OpenAIRE

    Biagioni, Stefania; Farace, Dominic

    2014-01-01

    We present the GreyGuide: an online forum and repository of good practice in the field of grey literature. The launch of the GreyGuide Repository took place in December 2013 at the Fifteenth International Conference on Grey Literature. Since then, the acquisition of both proposed and published good practices are underway. The GreyGuide as an online forum is currently in a developmental stage and is influenced by the changes that have taken place in GreyNet's new infrastructure commencing in J...

  10. Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances.

    Science.gov (United States)

    Surh, Y

    1999-07-16

    Recently, considerable attention has been focused on identifying naturally occurring chemopreventive substances capable of inhibiting, retarding, or reversing the multi-stage carcinogenesis. A wide array of phenolic substances, particularly those present in dietary and medicinal plants, have been reported to possess substantial anticarcinogenic and antimutagenic activities. The majority of these naturally occurring phenolics retain antioxidative and anti-inflammatory properties which appear to contribute to their chemopreventive or chemoprotective activity. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide), a pungent ingredient of hot chili pepper, protects against experimentally-induced mutagenesis and tumorigenesis. It also induces apoptosis in various immortalized or malignant cell lines. Plants of ginger family (Zingiberaceae) have been frequently and widely used as spices and also, in traditional oriental medicine. Curcumin, a yellow ingredient from turmeric (Curcuma longa L., Zingiberaceae), has been extensively investigated for its cancer chemopreventive potential. Yakuchinone A [1-(4'-hydroxy-3'-methoxyphenyl)-7-phenyl-3-heptanone] and yakuchinone B [1-(4'-hydroxy-3'-methoxyphenyl)-7-phenylhept-1-en-3-one] present in Alpinia oxyphylla Miquel (Zingiberaceae) have inhibitory effects on phorbol ester-induced inflammation and skin carcinogenesis in mice, and oxidative stress in vitro. These diarylheptanoids suppress phorbol ester-induced activation of ornithine decarboxylase and production of tumor necrosis factor-alpha or interleukin-1alpha and their mRNA expression. They also nullified the phorbol ester-stimulated induction of activator protein 1 (AP-1) in cultured human promyelocytic leukemia (HL-60) cells. In addition, both yakuchinone A and B induced apoptotic death in HL-60 cells. Ginger (Zingiber officinale Roscoe, Zingiberaceae) contains such pungent ingredients as [6]-gingerol and [6]-paradol, which also have anti-tumor promotional and

  11. Statins in the chemoprevention of colorectal cancer in established animal models of sporadic and colitis-associated cancer.

    Science.gov (United States)

    Pikoulis, Emmanouil; Margonis, Georgios A; Angelou, Anastasios; Zografos, George C; Antoniou, Efstathios

    2016-03-01

    Despite the availability of effective surveillance for colorectal cancer with colonoscopy, chemoprevention might be an acceptable alternative. Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins have been found to be beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. This systematic review aimed to gather information on the possible chemopreventive role of statins in preventing carcinogenesis and tumor promotion by a diverse array of mechanisms in both sporadic and colitis-associated cancer in animal models. The MEDLINE database was thoroughly searched using the following keywords: 'statin, HMG-CoA reductase inhibitor, colon cancer, mice, rats, chemoprevention, colitis-associated cancer'. Additional articles were gathered and evaluated. There are a lot of clinical studies and meta-analyses, as well as a plethora of basic research studies implementing cancer cell lines and animal models, on the chemopreventive role of statins in colorectal cancer (CRC). However, data derived from clinical studies are inconclusive, yet they show a tendency toward a beneficial role of statins against CRC pathogenesis. Thus, more research on the molecular pathways of CRC tumorigenesis as related to statins is warranted to uncover new mechanisms and compare the effect of statins on both sporadic and colitis-associated cancer in animal models. Basic science results could fuel exclusive colitis-associated cancer clinical trials to study the chemopreventive effects of statins and to differentiate between their effects on the two types of CRCs in humans. PMID:25768976

  12. Biomedical Properties of a Natural Dietary Plant Metabolite, Zerumbone, in Cancer Therapy and Chemoprevention Trials

    Directory of Open Access Journals (Sweden)

    Heshu Sulaiman Rahman

    2014-01-01

    Full Text Available Zerumbone (ZER is a naturally occurring dietary compound, present in many natural foods consumed today. The compound derived from several plant species of the Zingiberaceae family that has been found to possess multiple biomedical properties, such as antiproliferative, antioxidant, anti-inflammatory, and anticancer activities. However, evidence of efficacy is sparse, pointing to the need for a more systematic review for assessing scientific evidence to support therapeutic claims made for ZER and to identify future research needs. This review provides an updated overview of in vitro and in vivo investigations of ZER, its cancer chemopreventive properties, and mechanisms of action. Therapeutic effects of ZER were found to be scientifically plausible and could be explained partially by in vivo and in vitro pharmacological activities. Much of the research outlined in this paper will serve as a foundation to explain ZER anticancer bioactivity, which will open the door for the development of strategies in the treatment of malignancies using ZER.

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2012-07-01

    Full Text Available 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-16

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

  16. The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling

    Science.gov (United States)

    Weigl, Julia; De Nicola, Gina Rosalinda; Canistro, Donatella; Paolini, Moreno; Iori, Renato; Rascle, Anne

    2016-01-01

    Sulforaphane (SFN) and moringin (GMG-ITC) are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-κB. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFNα-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders. PMID:27304884

  17. The Chemopreventive Effect of Tamoxifen Combined with Celecoxib on DMBA chemically-Induced Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Xiaoxu Liu; Huafeng Kang; Xijing Wang; Zhijun Dai; Fengjie Xue; Xinghuan Xue

    2007-01-01

    Objective: To investigate the chemopreventive effect of tamoxifen combined with a COX-2 selective inhibitor, celecoxib, on breast cancer in rats chemically induced by 7,12-dimethylben (a)anthracene (DMBA). Methods:DMBA was irrigated into the stomaches of SD female rats to build breast cancer model. A total of 120 rats were divided into four groups: control group, tamoxifen group, celecoxib group and combined group. The incidence rate, latent period, number and volume of breast cancer were detected and analyzed. Results:The tumor incidence rate of tamoxifen group (48.15%, 13/27) and celecoxib group (50.00%,14/28) were lower than that of control group (85.71%, 24/28), but higher than that of combined group (21.43%, 6/28). The tumor's latent period of tamoxifen group (97.54±1.85 d) and celecoxib group (96.79±2.89 d) were longer than that of control group (89.50±5.99 d), but shorter than that of combined group (103.67±3.39 d). The average tumor number of tamoxifen group (1.77±0.73) and celecoxib group (1.71±0.61) were less than that of control group (3.50±1.62), but more than that of combined group ( 1.17±0.42 ). The average tumor volume of tamoxifen group (1.78±0.71 cm3) and celecoxib group (2.05±1.04 cm3) were smaller than that of control group (6.42±3.96 cm3), but bigger than that of combined group (0.71±0.96 cm3) (P < 0.05 respectively).Conclusion:Celecoxib and tamoxifen are effective drugs in preventing the occurrence of rat breast cancer chemically induced by DMBA. Furthermore, combination of them has better chemopreventive effect.

  18. Chemoprevention of aberrant crypt foci in the colon of rats by dietary onion.

    Science.gov (United States)

    Taché, Sylviane; Ladam, Aélis; Corpet, Denis E

    2007-01-01

    Onion intake might reduce the risk of colorectal cancer, according to epidemiology. However, Femia showed in 2003 that diets with a 20% onion intake increase carcinogenesis in rats. We speculated this dose was too high. Prevention of initiation was thus tested in 60 rats given a 5% dried onion diet or AIN76 diet, and initiated 12 days later with azoxymethane (AOM, 1x20 mg/kg i.p.), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ, 2x200 mg/kg p.o.), or N-nitroso-N-methylurea (2x50 mg/kg p.o.). Prevention of promotion was tested in 38 rats given AOM, then randomised to: AIN76 diet; 5% onion diet; phytochemicals diet (supplemented with propyl-disulfide, quercetine-glycosides and oligofructose); 1% pluronic F68 diet (a potent chemopreventive PEG-like block-polymer, used as a positive control). Aberrant crypt foci (ACF) were scored 30 days (initiation) or 100 days (promotion) after carcinogen injection. The onion diet given during initiation reduced the number of AOM-induced ACF (60 versus 86, p=0.03), and the size of IQ-induced ACF (1.33 versus 1.97, p=0.02). Given post-initiation, the onion diet reduced the number of ACF (34 versus 59, p=0.008) and of large ACF (6 versus 15, p=0.02). Phytochemicals diet and pluronic diet reduced ACF growth similarly. Data show that a 5% onion diet reduced carcinogenesis during initiation and promotion stages, and suggest this chemoprevention is due to known phytochemicals. PMID:17188859

  19. The Chemopreventive Phytochemical Moringin Isolated from Moringa oleifera Seeds Inhibits JAK/STAT Signaling.

    Science.gov (United States)

    Michl, Carina; Vivarelli, Fabio; Weigl, Julia; De Nicola, Gina Rosalinda; Canistro, Donatella; Paolini, Moreno; Iori, Renato; Rascle, Anne

    2016-01-01

    Sulforaphane (SFN) and moringin (GMG-ITC) are edible isothiocyanates present as glucosinolate precursors in cruciferous vegetables and in the plant Moringa oleifera respectively, and recognized for their chemopreventive and medicinal properties. In contrast to the well-studied SFN, little is known about the molecular pathways targeted by GMG-ITC. We investigated the ability of GMG-ITC to inhibit essential signaling pathways that are frequently upregulated in cancer and immune disorders, such as JAK/STAT and NF-κB. We report for the first time that, similarly to SFN, GMG-ITC in the nanomolar range suppresses IL-3-induced expression of STAT5 target genes. GMG-ITC, like SFN, does not inhibit STAT5 phosphorylation, suggesting a downstream inhibitory event. Interestingly, treatment with GMG-ITC or SFN had a limited inhibitory effect on IFNα-induced STAT1 and STAT2 activity, indicating that both isothiocyanates differentially target JAK/STAT signaling pathways. Furthermore, we showed that GMG-ITC in the micromolar range is a more potent inhibitor of TNF-induced NF-κB activity than SFN. Finally, using a cellular system mimicking constitutive active STAT5-induced cell transformation, we demonstrated that SFN can reverse the survival and growth advantage mediated by oncogenic STAT5 and triggers cell death, therefore providing experimental evidence of a cancer chemopreventive activity of SFN. This work thus identified STAT5, and to a lesser extent STAT1/STAT2, as novel targets of moringin. It also contributes to a better understanding of the biological activities of the dietary isothiocyanates GMG-ITC and SFN and further supports their apparent beneficial role in the prevention of chronic illnesses such as cancer, inflammatory diseases and immune disorders. PMID:27304884

  20. Visual querying and analysis of large software repositories

    NARCIS (Netherlands)

    Voinea, Lucian; Telea, Alexandru

    2009-01-01

    We present a software framework for mining software repositories. Our extensible framework enables the integration of data extraction from repositories with data analysis and interactive visualization. We demonstrate the applicability of the framework by presenting several case studies performed on

  1. DEBATE: Institutional repository success is dependent upon mandates

    OpenAIRE

    Harnad, Stevan

    2009-01-01

    Without universal institutional deposit mandates, institutional open-access repositories will continue to languish near-empty, as most them are now. Hence Institutional repository success is dependent upon mandates.

  2. Repository Planning, Design, and Engineering: Part I--Infrastructure.

    Science.gov (United States)

    Baird, Philip M; Gunter, Elaine W

    2016-04-01

    This is a two-part review describing the planning, engineering, and design considerations for building a new repository for biological and environmental samples. Part I addresses the physical infrastructure requirements for a repository; Part II will cover equipment and costing. Planning for construction of a new repository is a complex process requiring comprehensive preplanning and adherence to many regulatory and safety requirements. Guidance and a planning timeline are provided for many of the physical aspects and large capital acquisition costs for the expansion of an existing repository, or the creation of a new repository facility, using an available unoccupied building such as a former warehouse. This article provides a comprehensive set of information about every aspect of repository construction and operation to be considered in the planning process, and also addresses all aspects of designing and constructing a new repository in an existing structure. The engineering and design parameters for the repository are discussed in detail. PMID:26886580

  3. Geohydrological simulation of a deep coastal repository

    International Nuclear Information System (INIS)

    This conceptual-numerical study treats the dewatering and resaturation phases associated with the construction, use and closure of a coastal nuclear waste repository located at depth in sparsely fractured Baltic Shield rocks. The main objective is to simulate the extent and duration of saline intrusion for a reasonable set of geohydrological assumptions. Long-term changes in the chemical environment associated with saline intrusion may affect the properties of the buffer zone material (bentonite). The first part of the study deals with history matching of a simple model geometry and the second part treats the dewatering and resaturation phases of the simulated repository. The history matching supports the standpoint that the occurrence of saline ground water reflects an ongoing but incomplete Holocene flushing of the Baltic Shield. The drawdown after fifty years of dewatering is highly dependent on the permeability of the excavated damaged zone. If the permeability close the repository is unaltered the entire region between the top side of the model and the repository is more or less partially saturated at the end of the simulation period. The simulations of a fifty year long recovery period suggest that the distribution between fresh and saline ground waters may be quite close to the conditions prior to the dewatering phase already after fifty years of closure despite an incomplete pressure recovery, which is an interesting result considering the objective of the study. 12 refs

  4. The Sellafield repository project information programme

    International Nuclear Information System (INIS)

    The Sellafield Repository Project Information programme has been guided by formal research and by feedback through members of the team. Progress has been made and a significant majority of local people support the project and feel it will benefit the area. (author)

  5. Importance measures for nuclear waste repositories

    International Nuclear Information System (INIS)

    Several importance measures are identified for possible use in the performance assessment of a high-level nuclear waste repository. These importance measures are based on concepts of importance used in system reliability analysis, but the concepts are modified and adapted to the special characteristics of the repository and similar passive systems. In particular, the importance measures proposed here are based on risk (in comparison to traditional importance measures which are based on frequency of failure) and are intended to be more suitable to systems comprised of components whose behavior is most easily and naturally represented as continuous, rather than binary. These importance measures appear to be able to evaluate systems comprised of both continuous-behavior and binary-behavior components. Three separate examples are provided to illustrate the concepts and behavior of these importance measures. The first example demonstrates various formulations for the importance measures and their implementation for a simple radiation safety system comprised of a radiation source and three shields. The second example demonstrates use of these importance measures for a system comprised of components modeled with binary behavior and components modeled with continuous behavior. The third example investigates the use of these importance measures for a proposed repository system, using a total system model and code currently under development. Currently, these concepts and formulations of importance are undergoing further evaluation for a repository system to determine to what degree they provide useful insights and to determine which formulations are most useful

  6. Unifying Learning Object Repositories in MACE

    OpenAIRE

    Prause, Christian; Ternier, Stefaan; De Jong, Tim; Apelt, Stefan; Scholten, Marius; Wolpers, Martin; Eisenhauer, Markus; Vandeputte, Bram; Specht, Marcus; Duval, Erik

    2007-01-01

    Prause, C., Ternier, S., De Jong, T., Apelt, S., Scholten, M., Wolpers, M., et al. (2007). Unifying Learning Object Repositories in MACE. In D. Massart, J.-N. Colin & F. V. Assche (Eds.). Proceedings of the First International Workshop on Learning Object Discovery & Exchange (LODE'07). September, 18, 2007, Crete, Grece.

  7. Repository Services for Outcome-based Learning

    NARCIS (Netherlands)

    Totschnig, Michael; Derntl, Michael; Gutiérrez, Israel; Najjar, Jad; Klemke, Roland; Klerkx, Joris; Duval, Erik; Müller, Franz

    2010-01-01

    Totschnig, M., Derntl, M., Gutiérrez, I., Najjar, J., Klemke, R., Klerkx, J., Duval, E., & Müller, F. (2010). Repository Services for Outcome-based Learning. Fourth International Workshop on Search and Exchange of e-le@rning Materials (SE@M’10). September, 27-28, 2010, Barcelona, Spain.

  8. Gas generation and migration in waste repositories

    International Nuclear Information System (INIS)

    Recent estimates of gas generation in repositories suggest that substantial volumes of gas will be produced on long time-scales. Metals such as steel corrode very slowly and produce hydrogen. Microbiological degradation of organic materials in the waste may produce substantial volumes of carbon dioxide and methane in the anaerobic conditions expected in the repository. Radiolysis of water in cement and organic materials is estimated to produce substantially less gas than corrosion or microbiological degradation. Finally, some long-lived nuclides (238U, 232Th, 235U) have radioactive gaseous daughters (222Rn, 220Rn, 219Rn), which could escape with other gases, together with minor amounts of other active and toxic gases. In this paper, we review (i) the gases that could possibly be produced in a repository, (ii) the volumes and rates of generation of the main inactive gases, and (iii) the volumes and rates of generation of their main active derivatives. Then we discuss the ways these gases move through the repository materials and into the surrounding geology

  9. Grey Guide Repository: presentation and demo

    OpenAIRE

    Biagioni, Stefania; Carlesi, Carlo; Schopfel, Joachim; Farace, Dominic; Frantzen, Jerry

    2013-01-01

    The goal of this project is to develop an open source repository of good practices in the field of grey literature. That which originated in monographic form will now open and expand to include content from the global grey literature community. Such practices will range from the production and processing of grey literature through to its distribution, uses, and preservation.

  10. ProvStore: a public provenance repository

    OpenAIRE

    Huynh, Trung Dong; Moreau, Luc

    2014-01-01

    ProvStore is the first online public provenance repository supporting the new PROV standards by W3C. It allows users and applications to store and (optionally) publish the provenance of their data on the Web. Provenance documents can be transformed, visualized, and shared in various serializations, with all the functionality also available to automated applications via a RESTful API (OAuth supported).

  11. Siting Patterns of Nuclear Waste Repositories.

    Science.gov (United States)

    Solomon, Barry D.; Shelley, Fred M.

    1988-01-01

    Provides an inventory of international radioactive waste-management policies and repository siting decisions for North America, Central and South America, Europe, Asia, and Africa. This discussion stresses the important role of demographic, geologic, and political factors in siting decisions. (Author/BSR)

  12. Estimated water inflow into the repository

    International Nuclear Information System (INIS)

    ONKALO is underground bedrock research facility for the repository of spent nuclear fuel. Posiva is the builder and ONKALO is being constructed to Olkiluoto in Eurajoki. Construction of ONKALO began at 2004 and it is planned to be completed in the year 2014. After this starts construction of the repository. This work is based on groundwater research, which is done in the drillholes at the area of ONKALO and repository. The purpose of this work is to predict the amount of groundwater flow into ONKALO's lowest part and deep repository with different suppositions. At the same time this work helps to estimate the need of grouting. In this water inflow estimation ONKALO has been examined from the depth -300 meters downwards, which includes the repository. The most important starting points of the inflow estimation are the hydrogeological model (Ahokas et al. 2007) and the layouts of ONKALO and repository (Chapter 2 and Appendix 1). The hydrogeological model (Chapter 4) describes essential water conductive structures of the Olkiluoto area and their properties. The hydrozones HZ20A, HZ20B, HZ20Balt, HZ20AE, HZ21, HZ21B, BFZ099, HZ001 and HZ004 intersects the layouts of ONKALO and repository based on the model. These structures are significant for the inflow estimation. Vaittinen et al. (2007) have estimated the expected occurrence frequency of the water conductive fractures at the depth range of -300 - -600 m. This statistic has been used in advantage in this inflow estimation. Groundwater inflow to the tunnels caused by hydrogeological zones and separate fractures outside of the zones is studied in this inflow estimation with analytical methods. Connecting these, the estimation can be presented to the different layouts and suppositions of the properties of the zones and fractures, and for example different amounts of open spaces in the case of repository. For every zone, in the case of water conductive zones, was calculated minimum, maximum and mean flow using minimum

  13. Final repository symposium 2014. Elaboration and consequences of final repository exploration

    International Nuclear Information System (INIS)

    June 23 - 25 the second Symposium for Final Repository took place in Duesseldorf, having been organised by Aachen Institute for Nuclear Training (AiNT). Around 90 participants, national and international, were given the opportunity to discuss contents and consequences of the site location for final repository of thermal active resp. highly radioactive waste. The Symposium introduces the dialogue of implementing the site selection law (StandAG). Through 18 lectures within 4 topics as well as 2 panel discussions an appealing and many-faceted elaboration of the topic ''Repository Exploration'' was given. Concepts of final repository from abroad and as well the juridical controversial interrogations of StandAG were regarded. Consensus of the session: for site selection there needs to be a negotiation process of safety, duration and participation. Through Prof. Dr. Armin Grunwald and Prof. Dr. Bruno Thomauske two members of the commission appointed by the German Bundestag and the Federal Assembly were participating as speakers.

  14. The repository ecology: an approach to understanding repository and service interactions

    CERN Document Server

    CERN. Geneva

    2007-01-01

    An increasing number of university institutions and other organisations are deciding to deploy repositories and a growing number of formal and informal distributed services are supporting or capitalising on the information these repositories provide. Despite reasonably well understood technical architectures, early majority adopters may struggle to articulate their place within the actualities of a wider information environment. The idea of a repository ecology provides developers and administrators with a useful way of articulating and analysing their place in the information environment, and the technical and organisational interactions they have, or are developing, with other parts of such an environment. This presentation will provide an overview of the concept of a repository ecology and examine some examples from the domains of scholarly communications and elearning. View John Robertson's biography

  15. The repository ecology an approach to understanding repository and service interactions

    CERN Document Server

    CERN. Geneva; Hagemann, Melissa

    2007-01-01

    An increasing number of university institutions and other organisations are deciding to deploy repositories and a growing number of formal and informal distributed services are supporting or capitalising on the information these repositories provide. Despite reasonably well understood technical architectures, early majority adopters may struggle to articulate their place within the actualities of a wider information environment. The idea of a repository ecology provides developers and administrators with a useful way of articulating and analysing their place in the information environment, and the technical and organisational interactions they have, or are developing, with other parts of such an environment. This presentation will provide an overview of the concept of a repository ecology and examine some examples from the domains of scholarly communications and elearning.

  16. Incorporating IRUS-UK statistics into an EPrints repository

    OpenAIRE

    Stiles, Alan

    2015-01-01

    Researchers are taking repository download statistics more seriously than ever before, and are citing them in funding bids as evidence of previous impact. The repository staff are receiving more enquiries relating to download statistics as time goes on, so having the most accurate and reliable statistics available is becoming clear. Having them available in a way that requires the least intervention of repository staff would allow for more efficient dealings with other repository tasks, such ...

  17. A Protocol for Building Consensual and Consistent Repositories

    OpenAIRE

    Euzenat, Jérôme

    1997-01-01

    Distributed collaborative construction of a repository (e.g. knowledge base, document, design description) requires tools enforcing the consistency of the repository and the agreement of all the collaborators on the content of the repository. The CO4 protocol presented herein manages the communication between collaborators in order to maintain these properties on a hierarchy of repositories. It mimics the submission of articles to peer-reviewed journals (except that each change must be accept...

  18. New Roles, New Responsibilities: Examining Training Needs of Repository Staff

    OpenAIRE

    Natasha Simons; Joanna Richardson

    2012-01-01

    INTRODUCTION Institutional repositories play a critical role in the research lifecycle. Funding agencies are increasingly seeking an improved return on their investment in research. Repositories facilitate this process by providing storage of, and access to, institutional research outputs and, more recently, research data. While repositories are generally managed within the academic library, repository staff require different skills and knowledge compared with traditional library roles. This ...

  19. Institutional repository as an important part of scholarly communication

    OpenAIRE

    Koler-Povh, Teja; Turk, Goran; Mikoš, Matjaž

    2015-01-01

    Institutional repositories have been established as a good practice for quite some time. The European Commission requires archiving of research articles in institutional repositories in order to grant international project funding. Therefore, the interest in institutional repositories should increase in Slovenia as well. In 2011 the institutional repository DRUGG was built at the Faculty of Civil and Geodetic Engineering of the University of Ljubljana. By the end of 2012 more than...

  20. Repository site selection - Informing the public

    International Nuclear Information System (INIS)

    Full text: The Agency for Radioactive Management started a new site selection procedure in 1996. Tis is a complex technical process which needs strong communication support; but the major problem is in gaining public acceptability. According to the expert recommendation a so called combined or mixed mode approach to the site selection was chosen. This mode incorporates negotiations with the host area/community, which guarantee high public involvement. Only if the negotiations are successful, and the further steps are agreed with the local community, than the desk investigations be followed by more detailed research including field investigations to assess the suitability of the potential location. Communication with the local municipalities is established by inviting them to participate in the site selection process through an independent mediator who conducts the negotiations between the community and the investor. In this demanding phase the mediator, who has to have sufficient public credibility and adequate authorization for negotiations, has to reestablish relations with local communities and also present to them the technical approach for the construction of the repository. In order to provide the mediator with suitable material for the first information on repository design the RAO Agency started to prepare comprehensive communication tools. In addition to design documentation for the generic near-surface LILW repository - in which two different disposal options were considered - different public relation materials were also prepared. Information on the approach to repository design was given in leaflets, special posters, with presentations and on the Internet. As a part of communication service a special video film about the basic engineering design of the repository and its layout has been produced, and will also be presented at the conference. (author)

  1. Repositories for Research: Southampton's Evolving Role in the Knowledge Cycle

    Science.gov (United States)

    Simpson, Pauline; Hey, Jessie

    2006-01-01

    Purpose: To provide an overview of how open access (OA) repositories have grown to take a premier place in the e-research knowledge cycle and offer Southampton's route from project to sustainable institutional repository. Design/methodology/approach: The evolution of institutional repositories and OA is outlined raising questions of multiplicity…

  2. Institutional Repositories in Indian Universities and Research Institutes: A Study

    Science.gov (United States)

    Krishnamurthy, M.; Kemparaju, T. D.

    2011-01-01

    Purpose: The purpose of this paper is to report on a study of the institutional repositories (IRs) in use in Indian universities and research institutes. Design/methodology/approach: Repositories in various institutions in India were accessed and described in a standardised way. Findings: The 20 repositories studied covered collections of diverse…

  3. Prestudy Oskarshamn. Tourism in Oskarshamn with or without a repository

    International Nuclear Information System (INIS)

    Consequences for the tourism at Oskarshamn from siting a spent fuel repository in the community are studied. Four questionnaire/interview enquires were performed, and the analysis of the results show that no noticeable effects are expected. Still, an uncertainty about the impact of a repository is felt by the public, and more thorough information about the repository and its components is needed

  4. Botanical Agents for the Treatment of Nonmelanoma Skin Cancer

    Directory of Open Access Journals (Sweden)

    Jillian W. Millsop

    2013-01-01

    Full Text Available Nonmelanoma skin cancers, including basal cell carcinoma and squamous cell carcinoma, are common neoplasms worldwide and are the most common cancers in the United States. Standard therapy for cutaneous neoplasms typically involves surgical removal. However, there is increasing interest in the use of topical alternatives for the prevention and treatment of nonmelanoma skin cancer, particularly superficial variants. Botanicals are compounds derived from herbs, spices, stems, roots, and other substances of plant origin and may be used in the form of dried or fresh plants, extracted plant material, or specific plant-derived chemicals. They possess multiple properties including antioxidant, anti-inflammatory, and immunomodulatory properties and are, therefore, believed to be possible chemopreventive agents or substances that may suppress or reverse the process of carcinogenesis. Here, we provide a review of botanical agents studied for the treatment and prevention of nonmelanoma skin cancers.

  5. Durable concrete for a waste repository - Measurement of ionic ingress

    International Nuclear Information System (INIS)

    A waste repository for the below ground disposal of low level radioactive waste is planned at Chalk River Nuclear Laboratories. It relies greatly on the durability of concrete for the required 500 year service life. A research program to design durable concrete and predict its service life is in progress. The degradation of the concrete depends to a large extent on the rate of ingress of corrosive agents. Penetration of chloride and sulfate ions are particularly relevant. Twenty mix formulations were developed to create various types and qualities of concrete, and to study their behavior in different site environmental conditions. A total of 1,000 concrete specimens are being exposed at 20C and 45C to 25 different combinations of the corrosive agents including CO2. Procedures to measure the ionic profiles and to determine the factors controlling diffusion of the ions in the various concretes have been developed. Results of selected concrete systems exposed to chloride and sulfate solutions for 1 year are presented and discussed in terms of pore structure and permeability parameters of the concrete

  6. Agent, autonomous

    OpenAIRE

    Luciani, Annie

    2007-01-01

    The expression autonomous agents, widely used in virtual reality, computer graphics, artificial intelligence and artificial life, corresponds to the simulation of autonomous creatures, virtual (i.e. totally computed by a program), or embodied in a physical envelope, as done in autonomous robots.

  7. Chemistry of transuranium elements in salt-base repository

    International Nuclear Information System (INIS)

    The mobility and potential release of actinides into the accessible environment continues to be the key performance assessment concern of nuclear repositories. Actinide, in particular plutonium speciation under the wide range of conditions that can exist in the subsurface is complex and depends strongly on the coupled effects of redox conditions, inorganic/organic complexation, and the extent/nature of aggregation. Understanding the key factors that define the potential for actinide migration is, in this context, an essential and critical part of making and sustaining a licensing case for a nuclear repository. Herein we report on recent progress in a concurrent modeling and experimental study to determine the speciation of plutonium, uranium and americium in high ionic strength Na-CI-Mg brines. This is being done as part of the ongomg recertification effort m the Waste Isolation Pilot Plant (WIPP). The oxidation-state specific solubility of actinides were established in brine as function of pCH+, brine composition and the presence and absence of organic chelating agents and carbonate. An oxidation-state invariant analog approach using Nd3+ and Th4+ was used for An3+ and An4+ respectively. These results show that organic ligands and hydrolysis are key factors for An(III) solubility, hydrolysis at pCH+ above 8 is predominate for An(IV) and carbonates are the key factor for U(VI) solubility. The effect of high ionic strength and brine components measured in absence of carbonates leads to measurable increased in overall solubility over analogous low ionic strength groundwater. Less is known about the bioreduction of actinides by halo-tolerant microorganisms, but there is now evidence that bioreduction does occur and is analogous, in many ways, to what occurs with soil bacteria. Results of solubility studies that focus on Pitzer parameter corrections, new species (e.g. borate complexation), and the thermodynamic parameters for modeling are discussed.

  8. Safety analysis of the VLJ repository

    International Nuclear Information System (INIS)

    The VLJ repository is an underground disposal facility for the low and medium level waste generated at the Olkiluoto nuclear power plant. The repository is located within 1 km from TVO I and TVO II (2 x 710 MWe) BWR's on the Olkiluoto island at the west coast of Finland. It contains two rock silos excavated at the depth of 60...100 meters in the bedrock. Low level waste will be disposed of in a shotcreted rock silo. For bituminized medium level waste, a separate silo of reinforced concrete has been built inside the shotcreted rock silo. The post-closure safety analysis has been done for the Final Safety Analysis Report (FSAR) of the VLJ repository. In addition to the normal evolution scenario, several disturbed evolution and accident scenarios have been analysed. In the reference scenario, radio-nuclides are assumed to be released from the bituminized waste within 500 years, the concrete silo is assumed to gradually disintegrate and finally to collapse at 5 000 years, all concrete in the silo is assumed to be also chemically depleted within 6 000 years, and all the seals of the repository are assumed to deteriorate within 12 000 years. The ability of alone natural barriers to restrict the release of radionuclides into the biosphere has been evaluated by means of scenarios where the degradation of engineered barriers has been assumed to take place at a still faster rate. In one of the disturbed evolution scenarios it has been assumed that the concrete silo for medium level waste is severely impaired immediately after sealing of the repository. Effects of gas generation and consequences of human intrusion have been evaluated, too. The results of the safety analysis show that radiation doses of any significance are caused only if a well is bored in the vicinity of the repository or if the groundwater discharge spot is inhabited and used for cultivation. In the reference scenario the maximum expectation value of the individual dose rate is 0.3 mSv/a

  9. The Characteristic from Repository Radioactive Waste in Shallow Land

    International Nuclear Information System (INIS)

    The characteristic repository material to storage low level radioactive waste in shallow land has been investigated. The repository waste has to strength to defend of all effects from inner and outer repository. From investigation was found repository material which was made in concrete with his composition from water, cement, sand, Ca-bentonite cylinder form 1 cm optimum by thick wall repository. Sr(NO3)2 simulation liquid waste solution with 3.01x10-4 μCi/ml was put into repository. Then repository was done leaching rate to every thick repository and large of mesh size which was varied. The result leaching rate was found the best mesh size of Ca-bentonite which used for every thickener repository. From this test was found the mesh size of 60 mesh Ca-bentonite had strength the best to adsorb radionuclide. Repository leaching rate was 3.7x10-6 g cm-2 day-1. The other leaching rate was done also compressive strength by Paul Webber tester and was found the best compressive strength result at repository with 60 mesh Ca-bentonite namely 249.251 kg/cm2. (author)

  10. Digital Repository of Research Institutes – RCIN

    Directory of Open Access Journals (Sweden)

    Kamila Kaczyńska

    2014-03-01

    Full Text Available The paper describes the project of Digital Repository of Scientific Institutes RCIN and presents opportunities for promoting science by digitization and sharing them on the Internet. The Repository has been created by the 16 Scientific Institutes in Warsaw, Krakow and Bialowieza to modernize the science-research and IT infrastructure, to increase digital resources of mathematical, technical, natural and medical sciences, and to popularize and promote of Polish science. That dissemination and popularization of science affects its development and competitiveness in the international arena and it allows transfer of research results to the economy. In addition, Institutes of RCIN providing contemporary and archival materials of science, support the intellectual capital of Polish science and raise awareness of professional literature of search on the Internet. Project RCIN is implemented in the years 2010–2014 and financing is provided by the funds of the European Fund of Regional Development.

  11. Bedded-salt repository analysis. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Guiffre, M.S.; Kaplan, M.F.; Ensminger, D.A.; Oston, S.G.; Nalbandian, J.Y.

    1980-03-31

    This report contains a description of an analysis of generic nuclear waste repository in bedded salt. This analysis was performed by TASC for inclusion in a major Lawrence Livermore Laboratory report to NRC; this report therefore should be viewed as providing more complete and detailed information about this analysis than was possible to include in the LLL report. The analysis is performed with the NUTRAN computer codes which are described in the report. The model to be analyzed is defined, and the results of a series of possible waste migration scenarios are presented. Several of these scenarios are used as the basis for a sensitivity analysis, and an uncertainty analysis utilizing Monte Carlo techniques is also performed. A new method for defining the consequences to users of a well drilled near the repository is also described, and results are presented based on two of the waste migration scenarios.

  12. Spent fuel disposal in deep geological repositories

    International Nuclear Information System (INIS)

    The technical reasons warranting a postponement of spent fuel disposal are explained, and the time schedule is given of activities associated with the design, construction, and start-up of a deep geological repository, stretching as far as 2070. The status of preparatory activities implemented so far in relation to the repository is summarized. The design is under development but its future is dependent on the Atomic Act which is being prepared by the Czech Government. The problem of liabilities associated with the fuel cycle back end is discussed. A brief overview of deep geological disposal plans in Finland, France, Germany and Sweden is presented. The estimated cost of ultimate radioactive waste disposal is given. (J.B.). 3 tabs., 1 fig

  13. Use of modeling in repository licensing

    International Nuclear Information System (INIS)

    A review of the regulatory history of the Nuclear Regulatory Commission (NRC) regulations applicable to the licensing of a geologic repository, as well as a review of NRC administrative (licensing) decisions and federal case law, support the NRC's use of simplified models, in appropriate circumstances, which provide well-documented and reasonably conservative bounding assumptions, together with the use of expert judgement, natural analogues, and other aids to supplement available information, in reaching its reasonable assurance determination whether the public health and safety will be adequately protected if the Yucca Mountain, Nevada site should be licensed for development as a geologic repository. Specific examples are provided to assist the reader to better understand how such qualitative concepts as open-quote reasonable assurance close-quote, open-quote reasonably conservative close-quote, and open-quote adequate close-quote protection are used in an administrative context to resolve technical issues

  14. Managing an Institutional Repository with CDS Invenio

    CERN Document Server

    Robinson, N; Simko, T

    2007-01-01

    CERN has long been committed to the free dissemination of scientific research results and theories. Towards this end, CERN's own institutional repository, the CERN Document Server (CDS) offers access to CERN works and to all related scholarly literature in the HEP domain. Hosting over 500 document collections containing more than 900,000 records, CDS provides access to anything from preprints and articles, to multimedia information such as photographs, movies, posters and brochures. The software that powers this service, CDS Invenio, is distributed freely under the GNU GPL and is currently used in approximately 15 institutions worldwide. In this paper, we discuss the use of CDS Invenio to manage a repository of scientific literature. We outline some of the issues faced during the lifecycle of a document from acquisition, processing and indexing to dissemination. In particular, we focus on the features and technology developed to meet the complexities of managing scientific information in the LHC era of large ...

  15. Numerical modeling capabilities to predict repository performance

    Energy Technology Data Exchange (ETDEWEB)

    1979-09-01

    This report presents a summary of current numerical modeling capabilities that are applicable to the design and performance evaluation of underground repositories for the storage of nuclear waste. The report includes codes that are available in-house, within Golder Associates and Lawrence Livermore Laboratories; as well as those that are generally available within the industry and universities. The first listing of programs are in-house codes in the subject areas of hydrology, solute transport, thermal and mechanical stress analysis, and structural geology. The second listing of programs are divided by subject into the following categories: site selection, structural geology, mine structural design, mine ventilation, hydrology, and mine design/construction/operation. These programs are not specifically designed for use in the design and evaluation of an underground repository for nuclear waste; but several or most of them may be so used.

  16. Numerical modeling capabilities to predict repository performance

    International Nuclear Information System (INIS)

    This report presents a summary of current numerical modeling capabilities that are applicable to the design and performance evaluation of underground repositories for the storage of nuclear waste. The report includes codes that are available in-house, within Golder Associates and Lawrence Livermore Laboratories; as well as those that are generally available within the industry and universities. The first listing of programs are in-house codes in the subject areas of hydrology, solute transport, thermal and mechanical stress analysis, and structural geology. The second listing of programs are divided by subject into the following categories: site selection, structural geology, mine structural design, mine ventilation, hydrology, and mine design/construction/operation. These programs are not specifically designed for use in the design and evaluation of an underground repository for nuclear waste; but several or most of them may be so used

  17. Bedded-salt repository analysis. Final report

    International Nuclear Information System (INIS)

    This report contains a description of an analysis of generic nuclear waste repository in bedded salt. This analysis was performed by TASC for inclusion in a major Lawrence Livermore Laboratory report to NRC; this report therefore should be viewed as providing more complete and detailed information about this analysis than was possible to include in the LLL report. The analysis is performed with the NUTRAN computer codes which are described in the report. The model to be analyzed is defined, and the results of a series of possible waste migration scenarios are presented. Several of these scenarios are used as the basis for a sensitivity analysis, and an uncertainty analysis utilizing Monte Carlo techniques is also performed. A new method for defining the consequences to users of a well drilled near the repository is also described, and results are presented based on two of the waste migration scenarios

  18. Enriching the Content Provided by Cultural Catalogues with Data from Institutional Repositories

    Science.gov (United States)

    Rodríguez Miranda, Á.; Valle Melón, J. M.; Porcal-Gonzalo, M. C.

    2013-07-01

    Institutional repositories play a key role in universities and research centers for the preservation and dissemination of the knowledge generated or collected by these agents. Part of the information contained is related with Cultural Heritage and, therefore, it could be taken into account by thematic catalogues such as Europeana. In this paper, the opportunities and limitations of this connection are considered and presented by means of an ongoing case at the University of the Basque Country's institutional repository. In particular, we will deal with the information gathered about San Prudencio's Monastery (Clavijo, Spain), which includes a wide range of data from original datasets (photographs, pointclouds, coordinates, sketches and so on) up to finals results (reports, plans, 3D models, papers and so on).

  19. Genotoxicity of the cancer chemopreventive drug candidates CP-31398, SHetA2, and phospho-ibuprofen

    OpenAIRE

    Doppalapudi, Rupa S.; Riccio, Edward S.; Davis, Zoe; Menda, Sean; Wang, Abraham; Du, Nicholas; Green, Carol; Kopelovich, Levy; Rao, Chinthalapally V.; Benbrook, Doris M.; Kapetanovic, Izet M.

    2012-01-01

    The genotoxic activities of three cancer chemopreventive drug candidates, CP-31398 (a cell permeable styrylquinazoline p53 modulator, SHetA2 (a flexible heteroarotinoid), and phospho-ibuprofen (PI, a derivative of ibuprofen) were tested. None of the compounds were mutagenic in the Salmonella/Escherichia coli/microsome plate incorporation test. CP-31398 and SHetA2 did not induce chromosomal aberrations (CA) in Chinese hamster ovary (CHO) cells, either in the presence or absence of rat hepatic ...

  20. Chemopreventive Effects of RXR-Selective Rexinoid Bexarotene on Intestinal Neoplasia of ApcMin/+ Mice1

    OpenAIRE

    Janakiram, Naveena B; Mohammed, Altaf; Qian, Li; Choi, Chang-In; Steele, Vernon E.; Rao, Chinthalapally V.

    2012-01-01

    Retinoid X receptor (RXR) has been implicated in several neoplastic diseases. Previously, we have shown that RXR-α is downregulated in human and rodent colonic tumors, suggesting a potential target for colon cancer prevention (http://www.cancer.org/Cancer/ColonandRectumCancer/DetailedGuide/colorectal-cancer-key-statistics). Experiments were designed to assess the chemopreventive efficacy of the selective RXR agonist bexarotene for the suppression of intestinal tumorigenesis in ApcMin/+ mice. ...

  1. Modulation of polyamine metabolism as a chemopreventive strategy of phytochemicals in a cell culture model of colorectal cancers

    OpenAIRE

    Ulrich, Sandra

    2007-01-01

    Resveratrol a natural occuring polyphenol present in red wine, peanuts and grapes, has been reported to exhibit a wide range of biological and pharmacological properties. In addition to cardioprotective and antiinflammatory effects, potent chemopreventive activities of resveratrol and its analogs in various carcinogenesis models are described and there has been a great deal of experimental effort directed toward defining these effects. We and others could previously demonstrate that resveratr...

  2. Credentialing Data Scientists: A Domain Repository Perspective

    Science.gov (United States)

    Lehnert, K. A.; Furukawa, H.

    2015-12-01

    A career in data science can have many paths: data curation, data analysis, metadata modeling - all of these in different commercial or scientific applications. Can a certification as 'data scientist' provide the guarantee that an applicant or candidate for a data science position has just the right skills? How valuable is a 'generic' certification as data scientist for an employer looking to fill a data science position? Credentials that are more specific and discipline-oriented may be more valuable to both the employer and the job candidate. One employment sector for data scientists are the data repositories that provide discipline-specific data services for science communities. Data science positions within domain repositories include a wide range of responsibilities in support of the full data life cycle - from data preservation and curation to development of data models, ontologies, and user interfaces, to development of data analysis and visualization tools to community education and outreach, and require a substantial degree of discipline-specific knowledge of scientific data acquisition and analysis workflows, data quality measures, and data cultures. Can there be certification programs for domain-specific data scientists that help build the urgently needed workforce for the repositories? The American Geophysical Union has recently started an initiative to develop a program for data science continuing education and data science professional certification for the Earth and space sciences. An Editorial Board has been charged to identify and develop curricula and content for these programs and to provide input and feedback in the implementation of the program. This presentation will report on the progress of this initiative and evaluate its utility for the needs of domain repositories in the Earth and space sciences.

  3. SemanticWeb enabled digital repositories

    OpenAIRE

    Παπαθεοδώρου, Θεόδωρος; Κουτσομητρόπουλος, Δημήτριος Α.; Σολωμού, Γεωργία Δ.; Αλεξόπουλος, Ανδρέας Δ.

    2009-01-01

    Digital repositories and digital libraries are today among the most common tools for managing and disseminating digital object collections of cultural, educational, and other kinds of content over the Web. However, it is often the case that descriptive information about these assets, known as metadata, are usually semi-structured from a semantics point of view; implicit knowledge about this content may exist that cannot always be represented in metadata implementations and thus is not always ...

  4. Refactoring Process Models in Large Process Repositories.

    OpenAIRE

    Weber, B.; Reichert, M.U.

    2008-01-01

    With the increasing adoption of process-aware information systems (PAIS), large process model repositories have emerged. Over time respective models have to be re-aligned to the real-world business processes through customization or adaptation. This bears the risk that model redundancies are introduced and complexity is increased. If no continuous investment is made in keeping models simple, changes are becoming increasingly costly and error-prone. Though refactoring techniques are widely use...

  5. Funding models for Open Access Repositories

    OpenAIRE

    Kitchin, Rob; Collins, S.; Frost, D

    2015-01-01

    Across jurisdictions and domains (academia, government, business) there has been much recent attention paid to open forms of knowledge production (e.g., open-source software, open data/metadata, open infrastructures) and the creation of open digital repositories for the unrestricted sharing of data, publications and other resources. This report focuses on the latter, documenting and critically examining 14 different funding streams, grouped into six classes (institutional...

  6. Institutional Repositories: The Untapped Academic Goldmine

    OpenAIRE

    Utulu, Samuel C. Avemaria; Akadri, Adebayo Aliu

    2010-01-01

    This paper looked at the influence of the Internet on scholarly communication and the emergence of various access-to knowledge initiatives, with stronger emphasis on institutional repositories (IRs). It highlighted the benefits of IRs and the efforts made by Redeemer's University (RUN) towards the implementation of RUNIR. It concluded that Nigerian universities stand to benefit tremendously from IR if they take up the challenges of understanding its features and implementing it.

  7. Digital Repository as Instrument for Knowledge Management

    OpenAIRE

    Hakopov, Zaven

    2016-01-01

    Abstract. In the modern technologically advanced world, implicit knowledge, but also certain manifestations of tacit knowledge, is accumulated primarily in digital form, increasing the dependence of Knowledge Management (KM) on tools and specifically on digital content management platforms and repositories. The latter, powered by subject classification system such as a thesaurus or an ontology, can form a complete Knowledge Organization System (KOS). The purpose of this paper is to describe a...

  8. Repositories and Research Publications: Policies and Politics

    OpenAIRE

    Prosser, D

    2007-01-01

    Scholarly communications are increasingly being influenced by public policy issues. The desire of Governments world-wide to develop 'knowledge economies', ensure value for money, enrich education, and promote e-research all impact on scholarly communications and explain the interest at a political level in open access and institutional repositories. This presentation will explore some of the public policy drivers and describe the most significant of the open access policies, both in developme...

  9. Purdue University Research Repository: A Dataset Solution

    OpenAIRE

    Matthews, Courtney E

    2012-01-01

    The Purdue University Research Repository (PURR) is the free, online research data collaboration platform and data management service solution for Purdue researchers made possible through a partnership of the Purdue University Libraries, the Office of Vice-President Research, and Information Technology at Purdue. PURR provides researchers with a virtual project collaboration space, the ability to issue dataset publications with unique Digital Object Identifiers (DOIs), while meeting the chall...

  10. Dissertations Repository System Using Context Module

    CERN Document Server

    Hmood, Ali K; Alanazi, Hamdan O; Alnaqeib, Rami; Al-Nabhani, Yahya

    2010-01-01

    Without a doubt, the electronic learning makes education quite flexible. Nowadays, all organizations and institutions are trying to avoid Monotony and the delay and inertia. As well the universities should be improving their systems continually to achieve success. Whereas, the students need to access the dissertations in the library. In this paper we will present Dissertations Repository System Using Context Module to allow the students to benefit the dissertations which is in the library flexibly.

  11. Italy update on academic institutional repositories

    OpenAIRE

    Mornati, Susanna

    2005-01-01

    At the CNI-JISC-SURF conference “Making the strategic case for institutional repositories” (http://www.surf.nl/en/bijeenkomsten/index2.php?oid=6), an invitational leadership meeting held in Amsterdam on the 10-11th May 2005, 13 countries presented their updates. This is the Italy update, which reports on the Italian situation of institutional repositories through a questionnaire that was compiled by several contributors.

  12. Introduction to Institutional Data Repositories Workshop

    OpenAIRE

    Witt, Michael; Cragin, Melissa

    2008-01-01

    The course materials from a full-day, continuing education workshop given for the Chicago Metropolitan Library System that covered an introduction to institutional repositories, a rationale for sharing and archiving research data, an introduction to data curation, and related roles, resources, and approaches for librarians. Participants engaged in lab activities where they submitted sample datasets to two popular data-sharing websites, investigated and evaluated research data collections, an...

  13. The institutional repository in the digital library

    OpenAIRE

    MacColl, John; Jones, Richard D.; Andrew, Theo

    2006-01-01

    We begin by looking at the concept of institutional repositories within the broader context of digital libraries. ‘Digital libraries’ can mean many things, but we consider them to be libraries first and foremost, and built upon the enduring principles of information management which have lain at the heart of the practice of librarianship for hundreds of years. We look also at the significance of the qualification which defines the scope of this book – the institutional repos...

  14. Traits and types of health data repositories

    OpenAIRE

    Wade, Ted D.

    2014-01-01

    We review traits of reusable clinical data and offer a typology of clinical repositories with a range of known examples. Sources of clinical data suitable for research can be classified into types reflecting the data’s institutional origin, original purpose, level of integration and governance. Primary data nearly always come from research studies and electronic medical records. Registries collect data on focused populations primarily to track outcomes, often using observational research meth...

  15. Top 300 Institutional Repositories - January 2009

    OpenAIRE

    Consejo Superior de Investigaciones Scientificas; Cybermetrics Lab; Jürgen, Claudia

    2009-01-01

    The number of repositories is growing fast worldwide but still many of them does not have their own domain or subdomain, and for this reason it is not possible to add them in our analysis. Some institutions maintain several databases with completely different URLs which penalize the global visibility they have. We are still unable to add usage/download statics but there are many initiatives already working on standardization of the collecting methods, so we expect that global data could be av...

  16. The once & future repository, HKU's Scholars Hub

    OpenAIRE

    Palmer, DT; Castro, P.; Bollini, A; Mennielli, M

    2015-01-01

    The HKU Scholars Hub (the Hub) began service as a traditional institutional repository of The University of Hong Kong (HKU). However this format was not compelling to HKU researchers. Fortunately a subsequent reformation of the HKU statement on university mission and vision infused new life and purpose into the project. Over the next five years, in partnership with the Italian University Consortium, Cineca, the HKU Libraries transformed the Hub from an IR to a Current Research Information ...

  17. Analyzing software repositories to understand software evolution

    OpenAIRE

    D'Ambros, M; Gall, H.C.; Lanza, M; Pinzger, M.

    2008-01-01

    Software repositories such as versioning systems, defect tracking systems, and archived communication between project personnel are used to help manage the progress of software projects. Software practitioners and researchers increasingly recognize the potential benefit of mining this information to support the maintenance of software systems, improve software design or reuse, and empirically validate novel ideas and techniques. Research is now proceeding to uncover ways in which mining th...

  18. Towards an Open Repository of Teaching Resources

    OpenAIRE

    Millard, David; Howard, Yvonne; Wills, Gary; Watson, Julie; Arrebola, Miguel

    2008-01-01

    In this paper we describe our work to create a set of usability tools for CLARE, an EPrints installation storing Learning Objects. These tools include Web 2.0 style presentation and comments, and a concept map browser. Although the evaluation of our tools was broadly positive, through workshops with the language teaching community we discovered that a Learning Object repository is too heavyweight to be used as an everyday tool for sharing learning resources. In this paper we present the new r...

  19. NCI Repository News – Last Call —

    Science.gov (United States)

    The following strains will be maintained as live colonies until the end of January 2014. After this date, they will be supplied as cryopreserved embryos. If you foresee using one of these strains in the near future, order now! Please be aware that all necessary paperwork (order form, MTA, etc.) needs to be completed and received by the Repository before January 31, 2014 in order to receive live mice.

  20. Hydrothermal evolution of repository groundwaters in basalt

    International Nuclear Information System (INIS)

    Groundwaters in the near field of a radioactive waste repository in basalt will change their chemical composition in response to reactions with the basalt. These reactions will be promoted by the heat generated by the decaying waste. It is important to predict both the rate and the extent of these reactions, and the secondary minerals produced, because the alteration process controls the chemical environment affecting the corrosion of the canister, the solubility and complexation of migrating radionuclides, the reactivity of the alteration products to radionuclides sorption, and the porosity and permeability of the host rock. A comprehensive review of the literature leads to the preliminary finding that hydrothermally altering basalts in geothermal regions such as Iceland lead to a secondary mineralogy and groundwater composition similar to that expected to surround a repository. Furthermore, laboratory experiments replicating the alteration conditions approximate those observed in the field and expected in a repository. Preliminary estimates were made of the rate of hydration and devitrification of basaltic glass and the zero-order dissolution rate of basaltic materials. The rates were compared with those for rhyolitic glasses and silicate minerals. Preliminary calculations made of mixed process alteration kinetics, involving pore diffusion and surface reaction suggest that at temperatures greater than 1500C, alteration proceeds so rapidly as to become pervasive in normally fractured basalt exposed to higher temperatures in the field. 70 references

  1. The performance of Synroc under repository conditions

    International Nuclear Information System (INIS)

    The program at ANSTO on 'the performance of Synroc under repository conditions' is aimed at determining the ability of this waste form to incorporate high-level waste under varying ground water conditions. Important aspects of this study are the verification of the successful inclusion of active elements into the Synroc matrix, the collection of leaching data, description of the mechanisms by which ground water/Synroc and ground water/Synroc/repository host rock interaction proceeds and the use of all of this information as the basis for modelling the performance of Synroc in waste repository environments. Studies, described in this report are focused on long-term leach rates of actinide elements in deionized water, silicate, brine and carbonate leachants, the effect of Boom Clay and granitic materials on actinide releases and in-situ testing carried out for 3.5 years in the underground laboratory at Mol, Belgium. Studies also included comparison between results from experimental studies and findings obtained from naturally occurring zirconolite samples, which have been shown to be good natural analogues for the zirconolite phase in Synroc. (author)

  2. Metadata Management and Semantics in Microarray Repositories

    Science.gov (United States)

    Kocabaş, F; Can, T; Baykal, N

    2011-01-01

    The number of microarray and other high-throughput experiments on primary repositories keeps increasing as do the size and complexity of the results in response to biomedical investigations. Initiatives have been started on standardization of content, object model, exchange format and ontology. However, there are backlogs and inability to exchange data between microarray repositories, which indicate that there is a great need for a standard format and data management. We have introduced a metadata framework that includes a metadata card and semantic nets that make experimental results visible, understandable and usable. These are encoded in syntax encoding schemes and represented in RDF (Resource Description Frame-word), can be integrated with other metadata cards and semantic nets, and can be exchanged, shared and queried. We demonstrated the performance and potential benefits through a case study on a selected microarray repository. We concluded that the backlogs can be reduced and that exchange of information and asking of knowledge discovery questions can become possible with the use of this metadata framework. PMID:24052712

  3. Mining Software Repositories for Automatic Interface Recommendation

    Directory of Open Access Journals (Sweden)

    Xiaobing Sun

    2016-01-01

    Full Text Available There are a large number of open source projects in software repositories for developers to reuse. During software development and maintenance, developers can leverage good interfaces in these open source projects and establish the framework of the new project quickly when reusing interfaces in these open source projects. However, if developers want to reuse them, they need to read a lot of code files and learn which interfaces can be reused. To help developers better take advantage of the available interfaces used in software repositories, we previously proposed an approach to automatically recommend interfaces by mining existing open source projects in the software repositories. We mainly used the LDA (Latent Dirichlet Allocation topic model to construct the Feature-Interface Graph for each software project and recommended the interfaces based on the Feature-Interface Graph. In this paper, we improve our previous approach by clustering the recommending interfaces on the Feature-Interface Graph, which can recommend more accurate interfaces for developers to reuse. We evaluate the effectiveness of the improved approach and the results show that the improved approach can be more efficient to recommend more accurate interfaces for reuse over our previous work.

  4. Reference Design Description for a Geologic Repository

    International Nuclear Information System (INIS)

    One of the current major national environmental problems is the safe disposal of large quantities of spent nuclear fuel and high-level radioactive waste materials, which are rapidly accumulating throughout the country. These radioactive byproducts are generated as the result of national defense activities and from the generation of electricity by commercial nuclear power plants. At present, spent nuclear fuel is accumulating at over 70 power plant sites distributed throughout 33 states. The safe disposal of these high-level radioactive materials at a central disposal facility is a high national priority. This Reference Design Description explains the current design for a potential geologic repository that may be located at Yucca Mountain in Nevada for the disposal of spent nuclear fuel and high-level radioactive waste materials. This document describes a possible design for the three fundamental parts of a repository: a surface facility, subsurface repository, and waste packaging. It also presents the current conceptual design of the key engineering systems for the final four phases of repository processes: operations, monitoring, closure, and postclosure. In accordance with current law, this design does not include an interim storage option. In addition, this Reference Design Description reviews the expected long-term performance of the potential repository. It describes the natural barrier system which, together with the engineered systems, achieves the repository objectives. This design will protect the public and the environment by allowing the safe disposal of radioactive waste received from government-owned custodial spent fuel sites, high-level radioactive waste sites, and commercial power reactor sites. All design elements meet or exceed applicable regulations governing the disposal of high-level radioactive waste. The design will provide safe disposal of waste materials for at least a 10,000 year period. During this time interval, natural radioactive decay

  5. Salt repository project closeout status report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1988-06-01

    This report provides an overview of the scope and status of the US Department of Energy (DOE`s) Salt Repository Project (SRP) at the time when the project was terminated by the Nuclear Waste Policy Amendments Act of 1987. The report reviews the 10-year program of siting a geologic repository for high-level nuclear waste in rock salt formations. Its purpose is to aid persons interested in the information developed during the course of this effort. Each area is briefly described and the major items of information are noted. This report, the three salt Environmental Assessments, and the Site Characterization Plan are the suggested starting points for any search of the literature and information developed by the program participants. Prior to termination, DOE was preparing to characterize three candidate sites for the first mined geologic repository for the permanent disposal of high-level nuclear waste. The sites were in Nevada, a site in volcanic tuff; Texas, a site in bedded salt (halite); and Washington, a site in basalt. These sites, identified by the screening process described in Chapter 3, were selected from the nine potentially acceptable sites shown on Figure I-1. These sites were identified in accordance with provisions of the Nuclear Waste Policy Act of 1982. 196 refs., 21 figs., 11 tabs.

  6. Salt repository project closeout status report

    International Nuclear Information System (INIS)

    This report provides an overview of the scope and status of the US Department of Energy (DOE's) Salt Repository Project (SRP) at the time when the project was terminated by the Nuclear Waste Policy Amendments Act of 1987. The report reviews the 10-year program of siting a geologic repository for high-level nuclear waste in rock salt formations. Its purpose is to aid persons interested in the information developed during the course of this effort. Each area is briefly described and the major items of information are noted. This report, the three salt Environmental Assessments, and the Site Characterization Plan are the suggested starting points for any search of the literature and information developed by the program participants. Prior to termination, DOE was preparing to characterize three candidate sites for the first mined geologic repository for the permanent disposal of high-level nuclear waste. The sites were in Nevada, a site in volcanic tuff; Texas, a site in bedded salt (halite); and Washington, a site in basalt. These sites, identified by the screening process described in Chapter 3, were selected from the nine potentially acceptable sites shown on Figure I-1. These sites were identified in accordance with provisions of the Nuclear Waste Policy Act of 1982. 196 refs., 21 figs., 11 tabs

  7. Transient thermal response in nuclear waste repositories

    International Nuclear Information System (INIS)

    In this paper, it is shown that a previously reported non-linear, one-dimensional, theoretical approximation simplifies - from a computational point of view - the calculation of the time-decay temperature field in nuclear waste repositories (NWR). This conclusion has been reached after solving, by using the control volume numerical method, the full three dimensional, transient, non-linear heat diffusion equation. The transient thermal field in a rock salt repository, is analytically solved and numerically predicted, along 100 years, after the disposal of a high-level waste (HLW). The nuclear waste, with a half-life of 32.9 years, releases an exponentially time dependent heat flux with 12 W m-2 as the initial thermal load. Two cases are studied, in the first one it is assumed that the conductivity (k) and the volumetric heat capacity ρcp of the host rock (diffusion domain) remain constant (linear case), whereas in the second one, a more realistic situation is analysed. In this last case, the conductivity of the rock salt varies as a function of the temperature field and the product ρ x cp remains constant (non-linear case). In order to observe the effect of the salt conductivity (constant or variable) on the repository temperature distribution, a comparison of both cases is performed. It is concluded, that the theoretical model, which provides an analytical solution of the thermal fields may be a powerful low cost method for design purposes. (orig.)

  8. Chemopreventive and renal protective effects for docosahexaenoic acid (DHA: implications of CRP and lipid peroxides

    Directory of Open Access Journals (Sweden)

    Darweish MM

    2009-04-01

    Full Text Available Abstract Background The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA, claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP, lipid peroxidation (measured as malondialdehyde; MDA and leukocytic count (LC. Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein. Results EAC-bearing mice exhibited markedly elevated LC (2-fold, CRP (11-fold and MDA levels (2.7-fold. DHA (125, 250 mg/kg elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively, as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg. Interestingly, DHA (125 mg/kg markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85 and leukocytosis (r = 0.89, thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold, a rise in serum creatinine/urea levels (2–5-fold after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81, TNF-α r = 0.92 and GSH (r = -0

  9. Mechanisms of butylated hydroxytoluene chemoprevention of aflatoxicosis-inhibition of aflatoxin B1 metabolism

    International Nuclear Information System (INIS)

    Chemoprevention of toxicoses and/or cancer through the use of nutrients or pharmacologic compounds is the subject of intense study. Among the many compounds examined, food additives such as antioxidants are being considered due to their ability to reduce disease formation by either induction or inhibition of key enzyme systems. One such compound, butylated hydroxytoluene (BHT), has been found to protect against cancer formation caused by exposure to aflatoxin B1 (AFB1) in rodents. We have shown that dietary BHT protects against clinical signs of aflatoxicosis in turkeys, a species that is very susceptible to this mycotoxin. In this study, the effect of BHT on AFB1 metabolism and other cytochrome P450 (CYP)-related enzyme activities in turkey liver microsomes was examined to discern possible mechanisms of BHT-mediated protection against aflatoxicosis. Ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), prototype activities for CYP1A1 and 1A2, respectively, were decreased in the BHT fed (4000 ppm) animals, while oxidation of nifedipine, a prototype activity for CYP3A4, was increased. However, BHT added to microsomal incubations inhibited these CYP activities in a concentration-related manner. Importantly, BHT inhibited conversion of AFB1 to the reactive intermediate AFB1-8,-9-epoxide (AFBO), exhibiting Michaelis-Menton competitive inhibition kinetics (Ki = 0.81 μM). Likewise, microsomes prepared from turkeys fed BHT were significantly less active in AFBO formation compared to those from control birds. When turkeys were fed BHT for up to 40 days, residual BHT was present in liver, breast meat, thigh meat and abdominal fat in concentrations substantially below U.S. FDA guidelines for this antioxidant, but in concentrations greater than the Ki, likely sufficient to inhibit bioactivation of AFB1in vivo. BHT-induced hydropic degeneration in the livers of BHT fed animals was significantly greater in birds that remained on BHT treatment for up to 30

  10. SUBSURFACE REPOSITORY INTEGRATED CONTROL SYSTEM DESIGN

    International Nuclear Information System (INIS)

    The purpose of this document is to develop preliminary high-level functional and physical control system architectures for the proposed subsurface repository at Yucca Mountain. This document outlines overall control system concepts that encompass and integrate the many diverse systems being considered for use within the subsurface repository. This document presents integrated design concepts for monitoring and controlling the diverse set of subsurface operations. The subsurface repository design will be composed of a series of diverse systems that will be integrated to accomplish a set of overall functions and objectives. The subsurface repository contains several Instrumentation and Control (I andC) related systems including: waste emplacement systems, ventilation systems, communication systems, radiation monitoring systems, rail transportation systems, ground control monitoring systems, utility monitoring systems (electrical, lighting, water, compressed air, etc.), fire detection and protection systems, retrieval systems, and performance confirmation systems. Each of these systems involve some level of I andC and will typically be integrated over a data communication network. The subsurface I andC systems will also integrate with multiple surface-based site-wide systems such as emergency response, health physics, security and safeguards, communications, utilities and others. The scope and primary objectives of this analysis are to: (1) Identify preliminary system level functions and interface needs (Presented in the functional diagrams in Section 7.2). (2) Examine the overall system complexity and determine how and on what levels these control systems will be controlled and integrated (Presented in Section 7.2). (3) Develop a preliminary subsurface facility-wide design for an overall control system architecture, and depict this design by a series of control system functional block diagrams (Presented in Section 7.2). (4) Develop a series of physical architectures

  11. A proposal for national deep geological repository

    International Nuclear Information System (INIS)

    In almost all the countries which operate or have nuclear power plants under construction, management programs for spent fuel or long lived high radioactive waste (HLW) are conducted. The optimal solutions adopted within these programs regarding the main steps of the spent fuel cycle back-end, the disposal being the main target, are unclassified. The general current tendency is that the countries that develop the R and D Programs, organize in a responsible way, a final repository on their own territory. However, construction of a deep geological repository is a very demanding and costly task. As compared with other states Romania, represents a rather small territory, with high population density, wherein the the number of geological formation regions with radioactive waste storage potential are rather limited and restricted not only from the point of view of the selection criteria due to the rocks natural characteristics, but also from the point of view of their social and economical implications. Within of the R and D Programs in the frame of the National Program for Environmental, Energy and Resources, a complex analysis of the host geological formations available for the disposal and relating implications of the construction of a Spent Fuel Repository in Romania was accomplished. By now, the countries that operate CANDU reactors, have not processed the spent fuel passing through the interim storage as a preliminary step towards the final disposal within the nuclear fuel cycle backend. In the framework of the national R and D Programs, series of 'map investigations' have been carried out regarding the selection and preliminary characterization of the host geological formation for the Spent Fuel Deep Geological Repository. The fact that Romania has many deposits of natural gas and oil, minerals and geothermal water, while the soil is intensively utilized and is also very treed, makes some of the seemingly acceptable sites to be rejected to a the thoroughly

  12. Environmental issues of repository licensing: an evaluation of a hypothetical high-level radioactive waste repository

    International Nuclear Information System (INIS)

    This paper presents results of an environmental assessment conducted under the direction of the Office of Nuclear Waste Isolation as part of the National Waste Terminal Storage program. The study defined a range of potential environmental effects of constructing, operating, decommissioning, and long-term isolation of a nuclear waste repository. The analytical methodology used to determine potential environmental effects required definition of a hypothetical environmental setting and repository. Potentially applicable regulatory requirements were identified and were used as guidelines to evaluate permitting feasibility. The environmental effects of repository development were analyzed for the two major time periods of concern: short term (the period of construction, operation, and decommissioning) and long term (the isolation period after decommissioning). As a result of this analysis, major environmental uncertainties and issues were identified. 11 references, 5 figures

  13. New Roles, New Responsibilities: Examining Training Needs of Repository Staff

    Directory of Open Access Journals (Sweden)

    Natasha Simons

    2012-05-01

    Full Text Available INTRODUCTION Institutional repositories play a critical role in the research lifecycle. Funding agencies are increasingly seeking an improved return on their investment in research. Repositories facilitate this process by providing storage of, and access to, institutional research outputs and, more recently, research data. While repositories are generally managed within the academic library, repository staff require different skills and knowledge compared with traditional library roles. This study reports on a survey of Australasian institutional repository staff to identify skills and knowledge sets. METHODS Institutional repository staff working at universities in Australia and New Zealand were invited to participate in an online survey which incorporated both open and closed-ended question types. RESULTS The survey found significant gaps in the current provision of formal training and coursework related to institutional repositories, which echoed findings in the United Kingdom, Italy, and the United States. DISCUSSION There is clearly a need for more and varied training opportunities for repository professionals. Repository work requires a specific set of skills that can be difficult to find and institutions will benefit from investing in training and ongoing development opportunities for repository staff. CONCLUSION The data from this study could be used to facilitate staff recruitment, development, training, and retention strategies.

  14. Radiosensitivity of microorganisms isolated from radioactive waste repository

    International Nuclear Information System (INIS)

    established. The gases produced by the gasforming isolates were CO2 and H2 (anaerobic isolates). About 20% of the aerobic isolates produced siderophores. The highest proportions of organic acid producers in the aerobic and anaerobic isolates from the air samples were 63 % and 54 %, respectively. The radiosensitivity of the aerobic isolates was also determined, the D10 values of the spore-formers ranges between 0.8-2.44 kGy. Our results indicate that the sulfate-reducing bacteria and production of complexing agents may contribute to the mobilization of radionuclides in underground repository. Although our findings contribute to an understanding of the impact of microbial activity on radioactive waste repository, we do not as yet have enough information to develop a model which will predict the consequences of these processes. Future investigation will focus on specific questions such as the effect of biofilms on radionuclide migration and the uptake and accumulation of cations by the isolated bacteria. These processes should be evaluated for the long term safe disposal. (author)

  15. Antifungal agents.

    Science.gov (United States)

    Ryder, N S

    1999-12-01

    At this year's ICAAC Meeting, new data on approximately 20 different antifungal agents were presented, while no new agents were disclosed. Drugs in late development include the triazoles, voriconazole (Pfizer Ltd) and Sch-56592 (Schering-Plough Corp), and the echinocandins, caspofungin (Merck & Co Inc) and FK-463 (Fujisawa Pharmaceutical Co Ltd). In contrast to previous years, presentations on these and earlier developmental compounds were relatively modest in scope, with few significant new data. Little new information appeared on the most recent novel class of agents, the sordarins (Glaxo Wellcome plc). Early clinical results were presented for FK-463, showing acceptable tolerability and dose-dependent efficacy in AIDS-associated esophageal candidiasis. A new liposomal formulation of nystatin (Nyotran; Aronex Pharmaceuticals Inc) was shown to be equivalent to conventional amphotericin B in empiric therapy of presumed fungal infection in neutropenic patients, but with reduced toxicity. Intravenous itraconazole (Janssen Pharmaceutica NV) was an effective prophylactic therapy in invasive pulmonary aspergillosis, while oral itraconazole was discussed as a treatment for fungal infection in heart and liver transplant patients. The allylamine compound, terbinafine (Novartis AG), showed good clinical efficacy against fungal mycetoma, a serious tropical infection. A major highlight was the first presentation of inhibitors of fungal efflux pumps as a strategy for overcoming resistance. MC-510027 (milbemycin alpha-9; Microcide Pharmaceuticals Inc) and its derivatives, potentiated the antifungal activity of triazoles and terbinafine in a number of Candida spp. Another pump inhibitor, MC-005172 (Microcide Pharmaceuticals Inc) showed in vivo potentiation of fluconazole in a mouse kidney infection model. Microcide Pharmaceuticals Inc also presented inhibitors of bacterial efflux pumps. PMID:16113946

  16. Chemopreventive properties of indole-3-carbinol, diindolylmethane and other constituents of cardamom against carcinogenesis.

    Science.gov (United States)

    Acharya, Asha; Das, Ila; Singh, Sushmita; Saha, Tapas

    2010-06-01

    Oxidative stress results from an imbalance in the production of reactive oxygen species (ROS) and cell's own antioxidant defenses that in part lead to numerous carcinogenesis. Several phytochemicals, derived from vegetables, fruits, herbs and spices, have demonstrated excellent chemopreventive properties against carcinogenesis by regulating the redox status of the cells during oxidative stress. I3C (indole-3-carbinol) and DIM (diindolylmethane) are the phytochemicals that are found in all types of cruciferous vegetables and demonstrated exceptional anti-cancer effects against hormone responsive cancers like breast, prostate and ovarian cancers. Novel analogs of I3C were designed to enhance the overall efficacy, particularly with respect to the therapeutic activity and oral bioavailability and that results in several patent applications on symptoms associated with endometriosis, vaginal neoplasia, cervical dysplasia and mastalgia. Likewise, DIM and its derivatives are patented for treatment and prevention of leiomyomas, HPV infection, respiratory syncytial virus, angiogenesis, atherosclerosis and anti-proliferative actions. On the other hand, phytochemicals in cardamom have not been explored in great details but limonene and cineole demonstrate promising effects against carcinogenesis. Thus studies with selected phytochemicals of cardamom and bioavailability research might lead to many patent applications. This review is focused on the patents generated on the effects of I3C, DIM and selected phytochemicals of cardamom on carcinogenesis. PMID:20653562

  17. Chemopreventive activity of sesquiterpene lactones (SLs) from yacon against TPA-induced Raji cells deformation.

    Science.gov (United States)

    Siriwan, D; Miyawaki, C; Miyamoto, T; Naruse, T; Okazaki, K; Tamura, H

    2011-05-15

    Yacon is a medicinal plant used as a traditional medicine by the natives in South America. In Japan, it becomes popular as a health food. Sesquiterpene Lactones (SLs) from yacon leaves were investigated and the active SLs such as enhydrin, uvedalin and sonchifolin, bearing alpha-methylene-gamma-lactone and epoxides as the active functional groups, were identified by 1H-6000 MHz-NMR. Chemopreventive and cytotoxic activities were determined using different primary screening methods. In this study, all tested SLs strongly inhibited TPA-induced deformed of Raji cells. The IC50 values of yacon SLs from anti-deforming assay were 0.04-0.4 microM. Interestingly, yacon SLs showed more potential of chemo preventive activity than both curcumin and parthenolide. However, the cytotoxicity on Raji cells was observed at high concentration of yacon SLs. The degree of anti-deformation was ranked in order: enhydrin >uvedalin >sonchifolin >parthenolide >curcumin. As according to structure-activity relationship, the high activities of enhydrin, uvedalin and sonchifolin may be due to the 2-methyl-2-butenoate and its epoxide moiety. PMID:22097098

  18. Chemopreventive Effects of Oplopantriol A, a Novel Compound Isolated from Oplopanax horridus, on Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Zhiyu Zhang

    2014-07-01

    Full Text Available Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects (p < 0.01. Next, we characterized the compound’s growth inhibitory effects in human colorectal cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells were significantly inhibited in both a concentration- and time-dependent manner (both p < 0.01. The IC50 was approximately 5 µM for HCT-116 and 7 µM for SW-480 cells. OPT A significantly induced apoptosis and arrested the cell cycle at the G2/M phase. From further mechanism explorations, our data showed that OPT A significantly upregulated the expression of a cluster of genes, especially the tumor necrosis factor receptor family and caspase family, suggesting that the tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced apoptosis.

  19. A review of the content of the putative chemopreventive phytoalexin resveratrol in red wine

    DEFF Research Database (Denmark)

    Stervbo, Ulrik; Vang, Ole; Bonnesen, Christine

    2007-01-01

    Resveratrol, a naturally occurring compound of various fruits such as grapes, is thought to possess chemopreventive properties. The levels of resveratrol in grapes and grape products including wine, varies from region to region and from one year to another. This paper reviews the resveratrol...... content in red wine based on relevant published data. Red wine contains an average of 1.9 ± 1.7 mg trans-resveratrol/ l (8.2 ± 7.5 lM), ranging from non-detectable levels to 14.3 mg/l (62.7 lM) trans-resveratrol. In general, wines made from grapes of the Pinot Noir and St. Laurent varieties showed the...... highest level of trans-resveratrol. No region can be said to produce wines with significantly higher level of trans-resveratrol than all other regions. Levels of cis-resveratrol follow the same trend as trans-resveratrol. The average level of trans-resveratrol-glucoside (trans-piceid) in a red wine may be...

  20. Trading Agents

    CERN Document Server

    Wellman, Michael

    2011-01-01

    Automated trading in electronic markets is one of the most common and consequential applications of autonomous software agents. Design of effective trading strategies requires thorough understanding of how market mechanisms operate, and appreciation of strategic issues that commonly manifest in trading scenarios. Drawing on research in auction theory and artificial intelligence, this book presents core principles of strategic reasoning that apply to market situations. The author illustrates trading strategy choices through examples of concrete market environments, such as eBay, as well as abst