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Sample records for dcp chemoprevention protocol

  1. DCP Series

    Directory of Open Access Journals (Sweden)

    Philip Stearns

    2011-06-01

    Full Text Available Photo essay. A collection of Images produced by intentionally corrupting the circuitry of a Kodak DC280 2 MP digitalcamera. By rewiring the electronics of a digital camera, glitched images are produced in a manner that parallels chemically processing unexposed film or photographic paper to produce photographic images without exposure to light. The DCP Series of Digital Images are direct visualizations of data generated by a digital camera as it takes a picture. Electronic processes associated with the normal operations of the camera, which are usually taken for granted, are revealed through an act of intervention. The camera is turned inside­out through complexes of short­circuits, selected by the artist, transforming the camera from a picture taking device to a data capturing device that renders raw data (electronic signals as images. In essence, these images are snap­shots of electronic signals dancing through the camera's circuits, manually rerouted, written directly to the on­board memory device. Rather than seeing images of the world through a lens, we catch a glimpse of what the camera sees when it is forced to peer inside its own mind.

  2. Cancer Chemoprevention by Carotenoids

    Directory of Open Access Journals (Sweden)

    Takuji Tanaka

    2012-03-01

    Full Text Available Carotenoids are natural fat-soluble pigments that provide bright coloration to plants and animals. Dietary intake of carotenoids is inversely associated with the risk of a variety of cancers in different tissues. Preclinical studies have shown that some carotenoids have potent antitumor effects both in vitro and in vivo, suggesting potential preventive and/or therapeutic roles for the compounds. Since chemoprevention is one of the most important strategies in the control of cancer development, molecular mechanism-based cancer chemoprevention using carotenoids seems to be an attractive approach. Various carotenoids, such as β-carotene, a-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, fucoxanthin, canthaxanthin and astaxanthin, have been proven to have anti-carcinogenic activity in several tissues, although high doses of β-carotene failed to exhibit chemopreventive activity in clinical trials. In this review, cancer prevention using carotenoids are reviewed and the possible mechanisms of action are described.

  3. Chemoprevention of Lung Cancer

    Science.gov (United States)

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

    2013-01-01

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

  4. [Coffee in Cancer Chemoprevention].

    Science.gov (United States)

    Neuwirthová, J; Gál, B; Smilek, P; Urbánková, P

    Coffee consumption is associated with a reduced risk of several diseases including cancer. Its chemopreventive effect has been studied in vitro, in animal models, and more recently in humans. Several modes of action have been proposed, namely, inhibition of oxidative stress and damage, activation of metabolizing liver enzymes involved in carcinogen detoxification processes, and anti-inflammatory effects. The antioxidant activity of coffee relies partly on its chlorogenic acid content and is increased during the roasting process. Maximum antioxidant activity is observed for medium-roasted coffee. The roasting process leads to the formation of several components, e.g., melanoidins, which have antioxidant and anti-inflammatory properties. Coffee also contains two specific diterpenes, cafestol and kahweol, which have anticarcinogenic properties. Roasted coffee is a complex mixture of various chemicals. Previous studies have reported that the chemopreventive components present in coffee induce apoptosis, inhibit growth and metastasis of tumor cells, and elicit antiangiogenic effects. A meta-analysis of epidemiological studies showed that coffee consumption is associated with a lower risk of developing various malignant tumors. This review summarizes the molecular mechanisms and the experimental and epidemiological evidence supporting the chemopreventive effect of coffee.Key words: coffee - chemoprevention - antioxidative enzyme - detoxification enzyme - anti-inflammatory effect The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 11. 9. 2016Accepted: 24. 11. 2016.

  5. Chemoprevention by WR-2721

    Energy Technology Data Exchange (ETDEWEB)

    Grdina, D.J. [Argonne National Lab., IL (United States)]|[Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology; Carnes, B.A. [Argonne National Lab., IL (United States)

    1993-05-01

    WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is an effective chemopreventive agent. C57BL {times} BALB/c F{sub 1} female mice, were exposed to a single whole-body dose of 206 cGy from a {sup 60}Co 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.

  6. Chemoprevention by WR-2721

    Energy Technology Data Exchange (ETDEWEB)

    Grdina, D.J. (Argonne National Lab., IL (United States) Chicago Univ., IL (United States). Dept. of Radiation and Cellular Oncology); Carnes, B.A. (Argonne National Lab., IL (United States))

    1993-01-01

    WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is an effective chemopreventive agent. C57BL [times] BALB/c F[sub 1] female mice, were exposed to a single whole-body dose of 206 cGy from a [sup 60]Co 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.

  7. Natural chemopreventive alternatives in oral cancer chemoprevention.

    Science.gov (United States)

    Scrobota, I; Bolfa, P; Filip, A G; Catoi, C; Alb, C; Pop, O; Tatomir, C; Baciut, G

    2016-02-01

    We studied the effect of grape seed extract Burgund Mare (BM) on oral carcinogenesis and compared it with that of curcumin (CU). Wistar rats were divided into six groups (n = 10): 4-nitro-quinoline-1-oxide (4NQO) oral carcinogenesis was induced to groups 1 - 5; groups 2 and 3 received BM and CU respectively during initiation and groups 4 and 5 BM and CU during post-initiation of carcinogenesis; group 6 represented the negative control group. Total malondialdehyde (MDA) and reduced glutathione (GSH) were assayed fluorometrically in oral tissue (gingival, jugal, palatal, lingual mucosa) and serum. Histopathological exam was performed and a dysplasia score given to each oral mucosal lesion. Ki67, cyclin D1, p63, Bcl2 and p53 were immunohistochemically evaluated. BM and CU reduced tissue MDA values elevated by 4NQO (P = 0.000). The difference between CU and BM effect was significant in the initiation (P = 0.02) but not in the post-initiation phase of carcinogenesis (P = 0.58). Tissue GSH levels decreased by 4NQO (P < 0.001) were not significantly modified by BM or CU. Serum MDA levels increased by 4NQO (P = 0.000) were significantly lowered by CU (P = 0.04) and BM (P = 0.04) during initiation and by CU during post-initiation of carcinogenesis (P = 0.01). CU was more potent than BM during post-initiation of carcinogenesis (P = 0.01). Serum GSH lowered by 4NQO (P = 0.55) was significantly decreased by BM and CU (P < 0.012), with no significant difference between groups receiving BM or CU. Moderate dysplasia was the most advanced dysplasia induced and gingival localization the most frequent. Both BM and CU lowered dysplasia scores, with BM being the most efficient during post-initiation of carcinogenesis (P = 0.001). Ki67, cyclin D1, p63, Bcl2 and p53 expression increased with dysplasia scores. BM showed chemopreventive properties during initiation and post-initiation of oral carcinogenesis, reducing local and general oxidative stress and the intensity of dysplasia

  8. Chemopreventive properties of curcumin analogues ...

    African Journals Online (AJOL)

    Chemopreventive properties of curcumin analogues, ... These compounds .... using microscope with 400 × magnification. APC ... Figure 3: Microscopic images of rat colorectal tissue stained with APC rabbit polyclonal antibody with different.

  9. Natural Radioactivity In Poultry Rations And DCP For Bovine Nutrition

    International Nuclear Information System (INIS)

    Luz-Filho, Isaias V.; Scheibel, Viviane; Appoloni, Carlos R.

    2011-01-01

    The aim of this study is to determine the level of radioactivity present in samples of poultry rations and dicalcium phosphate (DCP) used for cattle feed. Knowledge of these levels is of fundamental importance, because part of this radioactivity will possibly be transferred to humans. The radiation found in such samples is due to the presence of radioactive series of 238 U and 232 Th and 40 K. Measurements were performed with a 66% HPGe detector at the Laboratory of Applied Nuclear Physics, State University of Londrina. The measured samples were commercialized in Londrina, Brazil, in the second half of 2007. The accommodation recipient of the samples was a 1 L Marinelli beaker. Poultry rations were divided into two types: for young chickens and adult chickens. Among these, the ration for adult chickens showed the highest values for the activities of 226 Ra and 228 Ra, 0.23±0.17 and 0.493±0.091 Bq/kg respectively. But the ration for young chickens showed the highest activity for the 40 K, 304±15 Bq/kg. The DCP sample showed a much higher value for the series of 238 U and 232 Th, 83±26 and 7.79±0.70 Bq/kg, respectively. However, the 40 K activity in this sample was about 5 or 6 times lower than samples for poultry feed, reaching 46.6±2.8 Bq/kg.

  10. Moringa oleifera Lam: Targeting Chemoprevention.

    Science.gov (United States)

    Karim, Nurul Ashikin Abd; Ibrahim, Muhammad Din; Kntayya, Saie Brindha; Rukayadi, Yaya; Hamid, Hazrulizawati Abd; Razis, Ahmad Faizal Abdull

    2016-01-01

    Moringa oleifera Lam, family Moringaceae, is a perennial plant which is called various names, but is locally known in Malaysia as "murungai" or "kelor". Glucomoringin, a glucosinolate with from M. oleifera is a major secondary metabolite compound. The seeds and leaves of the plant are reported to have the highest amount of glucosinolates. M. oleifera is well known for its many uses health and benefits. It is claimed to have nutritional, medicinal and chemopreventive potentials. Chemopreventive effects of M. oleifera are expected due to the existence of glucosinolate which it is reported to have the ability to induce apoptosis in anticancer studies. Furthermore, chemopreventive value of M. oleifera has been demonstrated in studies utilizing its leaf extract to inhibit the growth of human cancer cell lines. This review highlights the advantages of M. oleifera targeting chemoprevention where glucosinolates could help to slow the process of carcinogenesis through several molecular targets. It is also includes inhibition of carcinogen activation and induction of carcinogen detoxification, anti-inflammatory, anti-tumor cell proliferation, induction of apoptosis and inhibition of tumor angiogenesis. Finally, for synergistic effects of M. oleifera with other drugs and safety, essential for chemoprevention, it is important that it safe to be consumed by human body and works well. Although there is promising evidence about M. oleifera in chemoprevention, extensive research needs to be done due to the expected rise of cancer in coming years and to gain more information about the mechanisms involved in M. oleifera influence, which could be a good source to inhibit several major mechanisms involved in cancer development.

  11. Combination Chemoprevention with Grape Antioxidants

    OpenAIRE

    Singh, Chandra K.; Siddiqui, Imtiaz A.; El-Abd, Sabah; Mukhtar, Hasan; Ahmad, Nihal

    2016-01-01

    Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resver...

  12. 75 FR 38802 - DCP Raptor Pipeline, LLC; Notice of Baseline Filing

    Science.gov (United States)

    2010-07-06

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR10-42-000] DCP Raptor Pipeline, LLC; Notice of Baseline Filing June 28, 2010. Take notice that on June 22, 2010, DCP Raptor Pipeline, LLC submitted a baseline filing of its Statement of Operating Conditions for services provided...

  13. 76 FR 79675 - DCP Raptor Pipeline, LLC; Notice of Extension of Time

    Science.gov (United States)

    2011-12-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR09-32-003] DCP Raptor Pipeline, LLC; Notice of Extension of Time On November 30, 2011, DCP Raptor Pipeline, LLC (Raptor) filed a...) of the Commission's regulations.\\1\\ In support of this request, Raptor states that in Order No. 735...

  14. Des-γ-Carboxy Prothrombin (DCP as a Potential Autologous Growth Factor for the Development of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Yu-Sheng Zhang

    2014-08-01

    Full Text Available Des-γ-carboxy prothrombin (DCP is a prothrombin precursor produced in hepatocellular carcinoma (HCC. Because of deficiency of vitamin K or γ-glutamyl carboxylase in HCC cells, the 10 glutamic acid (Glu residues in prothrombin precursor did not completely carboxylate to γ-carboxylated glutamic acid (Gla residues, leaving some Glu residues remained in N-terminal domain. These prothrombin precursors with Glu residues are called DCPs. DCP displays insufficient coagulation activity. Since Liebman reported an elevated plasma DCP in patients with HCC, DCP has been used in the diagnosis of HCC. Recently, its biological malignant potential has been specified to describe DCP as an autologous growth factor to stimulate HCC growth and a paracrine factor to integrate HCC with vascular endothelial cells. DCP was found to stimulate HCC growth through activation of the DCP-Met-JAK1-STAT3 signaling pathway. DCP might increase HCC invasion and metastasis through activation of matrix metalloproteinase (MMPs and the ERK1/2 MAPK signaling pathway. DCP has also been found to play a crucial role in the formation of angiogenesis. DCP could increase the angiogenic factors released from HCC and vascular endothelial cells. These effects of DCP in angiogenesis might be related to activation of the DCP-KDR-PLC-γ-MAPK signaling pathway. In this article, we summarized recent studies on DCP in biological roles related to cancer progression and angiogenesis in HCC.

  15. Resveratrol: Chemoprevention with red wine

    OpenAIRE

    Arısan, Elif Damla; Palavan-Ünsal, Narçin

    2007-01-01

    According to epidemiological studies, western diet has disadvantages because of cancer prevalence more than Mediterranean or Asia people who consume more vegetables and fruits. Resveratrol (trans-3,4,5-trihydroxystilbene) which is highly found in grapes, berries has received attention for its potential chemopreventive and antitumor effects in experimental systems. Because of high resveratrol content, researchers noted that red wine has multidimensional benefits for ...

  16. Combination chemoprevention with grape antioxidants.

    Science.gov (United States)

    Singh, Chandra K; Siddiqui, Imtiaz A; El-Abd, Sabah; Mukhtar, Hasan; Ahmad, Nihal

    2016-06-01

    Antioxidant ingredients present in grape have been extensively investigated for their cancer chemopreventive effects. However, much of the work has been done on individual ingredients, especially focusing on resveratrol and quercetin. Phytochemically, whole grape represents a combination of numerous phytonutrients. Limited research has been done on the possible synergistic/additive/antagonistic interactions among the grape constituents. Among these phytochemical constituents of grapes, resveratrol, quercetin, kaempferol, catechin, epicatechin, and anthocyanins (cyanidin and malvidin) constitute more than 70% of the grape polyphenols. Therefore, these have been relatively well studied for their chemopreventive effects against a variety of cancers. While a wealth of information is available individually on cancer chemopreventive/anti-proliferative effects of resveratrol and quercetin, limited information is available regarding the other major constituents of grape. Studies have also suggested that multiple grape antioxidants, when used in combination, alone or with other agents/drugs show synergistic or additive anti-proliferative response. Based on strong rationale emanating from published studies, it seems probable that a combination of multiple grape ingredients alone or together with other agents could impart 'additive synergism' against cancer. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Evaluation of automated serum des-gamma-carboxyprothrombin (DCP) assays for detecting hepatocellular carcinoma.

    Science.gov (United States)

    Choi, Jonghyeon; Park, Yongjung; Kim, Jeong-Ho; Kim, Hyon-Suk

    2011-12-01

    We evaluated two new autoanalyzers, μTAS and Lumipulse for des-γ-carboxyprothrombin (DCP) assay. Analytical performance was evaluated, and the upper reference limit of the 97.5th percentile for DCP was re-established using sera from 140 healthy individuals. DCP levels were determined by the two autoanalyzers and EIA in a total of 239 sera from HCC patients (n=120) and those without HCC (n=119). Total imprecision of the two automated assays was Lumipulse. There were proportional and constant biases between the results from the autoanalyzers and those from EIA. The two newly developed DCP assays showed high analytical performance, but re-establishment of reference limits would be necessary. The new analyzers could be useful for clinical laboratories because of convenience of operation and wide AMRs. Copyright © 2011 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  18. Cancer chemopreventive property of Bidens pilosa methanolic ...

    African Journals Online (AJOL)

    Cancer chemopreventive property of Bidens pilosa methanolic extract on two stage in vivo skin carcinogenesis model. ... In the forestomach, kidney and lung, glutathione S-transferase and DT-diaphorase levels were significantly reduced. Chemopreventive response was calculated by the mean number of papillomas ...

  19. Analysis of 3-MCPD and 1,3-DCP in Various Foodstuffs Using GC-MS

    Science.gov (United States)

    Kim, Wooseok; Jeong, Yun A; On, Jiwon; Choi, Ari; Lee, Jee-yeon; Lee, Joon Goo; Lee, Kwang-Geun

    2015-01-01

    3-Monochloro-1,2-propanediol (3-MCPD) and 1,3-dichloro-2-propanol (1,3-DCP) are not only produced in the manufacturing process of foodstuffs such as hydrolyzed vegetable proteins and soy sauce but are also formed by heat processing in the presence of fat and low water activity. 3-MCPD exists both in free and ester forms, and the ester form has been also detected in various foods. Free 3-MCPD and 1,3-DCP are classified as Group 2B by the International Agency for Research on Cancer. Although there is no data confirming the toxicity of either compound in humans, their toxicity was evidenced in animal experimentation or in vitro. Although few studies have been conducted, free 3-MCPD has been shown to have neurotoxicity, reproductive toxicity, and carcinogenicity. In contrast, 1,3-DCP only has mutagenic activity. The purpose of this study was to analyze 3-MCPD and 1,3-DCP in various foods using gas chromatography -mass spectrometry. 3-MCPD and 1,3-DCP were analyzed using phenyl boronic acid derivatization and the liquid–liquid extraction method, respectively. The analytical method for 3-MCPD and 1,3-DCP was validated in terms of linearity, limit of detection (LOD), limit of quantitation, accuracy and precision. Consequently, the LODs of 3-MCPD and 1,3-DCP in various matrices were identified to be in the ranges of 4.18~10.56 ng/g and 1.06~3.15 ng/g, respectively. PMID:26483891

  20. 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.

  1. Chemical carcinogenesis and chemoprevention: Scientific priority ...

    African Journals Online (AJOL)

    Occupational cancers are now a serious concern in industrializing developing countries where exposure levels to hazardous chemicals considerably exceed regulatory limits established in industrialized countries. The association between increasing use of chemicals and associated disorders and chemoprevention or ...

  2. Analysis of 3-MCPD and 1,3-DCP in Various Foodstuffs Using GC-MS

    OpenAIRE

    Kim, Wooseok; Jeong, Yun A; On, Jiwon; Choi, Ari; Lee, Jee-yeon; Lee, Joon Goo; Lee, Kwang-Geun; Pyo, Heesoo

    2015-01-01

    3-Monochloro-1,2-propanediol (3-MCPD) and 1,3-dichloro-2-propanol (1,3-DCP) are not only produced in the manufacturing process of foodstuffs such as hydrolyzed vegetable proteins and soy sauce but are also formed by heat processing in the presence of fat and low water activity. 3-MCPD exists both in free and ester forms, and the ester form has been also detected in various foods. Free 3-MCPD and 1,3-DCP are classified as Group 2B by the International Agency for Research on Cancer. Although th...

  3. 76 FR 76711 - DCP Raptor Pipeline, LLC; Notice of Motion for Extension of Rate Case Filing Deadline

    Science.gov (United States)

    2011-12-08

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR09-32-003] DCP Raptor..., 2011, DCP Raptor Pipeline, LLC (Raptor) filed a request for an extension consistent with the Commission... pipelines to extend the cycle for such reviews from three to five years.\\1\\ Therefore, Raptor requests that...

  4. Applying the dynamic cone penetrometer (DCP) design method to low volume roads

    CSIR Research Space (South Africa)

    Paige-Green, P

    2011-07-01

    Full Text Available The Dynamic Cone Penetrometer (DCP) has been in use since the 1950s for various applications in pavement investigation. During the 1980s, Kleyn and Van Zyl described a method for upgrading unsealed roads to light sealed road standard based...

  5. 75 FR 9201 - DCP Raptor Pipeline, LLC; Notice of Compliance Filing

    Science.gov (United States)

    2010-03-01

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. PR09-32-002] DCP Raptor... Raptor Pipeline, LLC (Raptor) filed its Statement of Operating Conditions in compliance with the January 27, 2010 Letter Order (January 27th Letter Order) in Docket Nos. PR09-32-000 and PR09-32-001. Raptor...

  6. Optimum design of sustainable sealed low volume roads using the Dynamic Cone Penetrometer (DCP)

    CSIR Research Space (South Africa)

    Paige-Green, P

    2012-09-01

    Full Text Available in a reduction in the need to import large quantities of virgin material. Appropriate testing with the simple DCP test device can be used to assess the in situ conditions including material quality and moisture regimes along the road alignment...

  7. Effects of 2,4-D and DCP on the DHT-induced androgenic action in human prostate cancer cells.

    Science.gov (United States)

    Kim, Hyun-Jung; Park, Young In; Dong, Mi-Sook

    2005-11-01

    2,4-Dichlorophenoxyacetic acid (2,4-D) and its metabolite 2,4-dichlorophenol (DCP) are used extensively in agriculture as herbicides, and are suspected of potential endocrine disruptor activity. In a previous study, we showed that these compounds exhibited synergistic androgenic effects by co-treatment with testosterone in the Hershberger assay. To elucidate the mechanisms of the synergistic effects of these compounds on the androgenicity of testosterone, the androgenic action of 2,4-D and DCP was characterized using a mammalian detection system in prostate cancer cell lines. In in vitro assay systems, while 2,4-D or DCP alone did not show androgenic activity, 2,4-D or DCP with 5alpha-dihydroxytestosterone (DHT) exhibited synergistic androgenic activities. Co-treatment of 10 nM 2,4-D or DCP with 10 nM DHT was shown to stimulate the cell proliferation by 1.6-fold, compared to 10 nM DHT alone. In addition, in transient transfection assays, androgen-induced transactivation was also increased to a maximum of 32-fold or 1.28-fold by co-treatment of 2,4-D or DCP with DHT, respectively. However, 2,4-D and DCP exerted no effects on either mRNA or protein levels of AR. In a competitive AR binding assay, 2,4-D and DCP inhibited androgen binding to AR, up to 50% at concentrations of approximately 0.5 microM for both compounds. The nuclear translocation of green fluorescent protein-AR fusion protein in the presence of DHT was promoted as the result of the addition of 2,4-D and DCP. Collectively, these results that 2,4-D and DCP enhanced DHT-induced AR transcriptional activity might be attributable, at least in part, to the promotion of AR nuclear translocation.

  8. Ellagitannins in Cancer Chemoprevention and Therapy

    Directory of Open Access Journals (Sweden)

    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.

  9. Targeting NRF2 signaling for cancer chemoprevention

    International Nuclear Information System (INIS)

    Kwak, Mi-Kyoung; Kensler, Thomas W.

    2010-01-01

    Modulation of the metabolism and disposition of carcinogens through induction of cytoprotective enzymes is one of several promising strategies to prevent cancer. Chemopreventive efficacies of inducers such as dithiolethiones and sulforaphane have been extensively studied in animals as well as in humans. The KEAP1-NRF2 system is a key, but not unilateral, molecular target for these chemopreventive agents. The transcription factor NRF2 (NF-E2-related factor 2) is a master regulator of the expression of a subset of genes, which produce proteins responsible for the detoxication of electrophiles and reactive oxygen species as well as the removal or repair of some of their damage products. It is believed that chemopreventive enzyme inducers affect the interaction between KEAP1 and NRF2 through either mediating conformational changes of the KEAP1 protein or activating phosphorylation cascades targeting the KEAP1-NRF2 complex. These events in turn affect NRF2 stability and trafficking. Recent advances elucidating the underlying structural biology of KEAP1-NRF2 signaling and identification of the gene clusters under the transcriptional control of NRF2 are facilitating understanding of the potential pleiotropic effects of NRF2 activators and discovery of novel classes of potent chemopreventive agents such as the triterpenoids. Although there is appropriately a concern regarding a deleterious role of the KEAP1-NRF2 system in cancer cell biology, especially as the pathway affects cell survival and drug resistance, the development and the use of NRF2 activators as chemopreventive agents still holds a great promise for protection of normal cells from a diversity of environmental stresses that contribute to the burden of cancer and other chronic, degenerative diseases.

  10. Cancer chemoprevention through dietary flavonoids: what's limiting?

    Science.gov (United States)

    Amawi, Haneen; Ashby, Charles R; Tiwari, Amit K

    2017-06-19

    Flavonoids are polyphenols that are found in numerous edible plant species. Data obtained from preclinical and clinical studies suggest that specific flavonoids are chemo-preventive and cytotoxic against various cancers via a multitude of mechanisms. However, the clinical use of flavonoids is limited due to challenges associated with their effective use, including (1) the isolation and purification of flavonoids from their natural resources; (2) demonstration of the effects of flavonoids in reducing the risk of certain cancer, in tandem with the cost and time needed for epidemiological studies, and (3) numerous pharmacokinetic challenges (e.g., bioavailability, drug-drug interactions, and metabolic instability). Currently, numerous approaches are being used to surmount some of these challenges, thereby increasing the likelihood of flavonoids being used as chemo-preventive drugs in the clinic. In this review, we summarize the most important challenges and efforts that are being made to surmount these challenges.

  11. Pathobiology and Chemoprevention of Bladder Cancer

    Science.gov (United States)

    Tanaka, Takuji; Miyazawa, Katsuhito; Tsukamoto, Tetsuya; Kuno, Toshiya; Suzuki, Koji

    2011-01-01

    Our understanding of the pathogenesis of bladder cancer has improved considerably over the past decade. Translating these novel pathobiological discoveries into therapies, prevention, or strategies to manage patients who are suspected to have or who have been diagnosed with bladder cancer is the ultimate goal. In particular, the chemoprevention of bladder cancer development is important, since urothelial cancer frequently recurs, even if the primary cancer is completely removed. The numerous alterations of both oncogenes and tumor suppressor genes that have been implicated in bladder carcinogenesis represent novel targets for therapy and prevention. In addition, knowledge about these genetic alterations will help provide a better understanding of the biological significance of preneoplastic lesions of bladder cancer. Animal models for investigating bladder cancer development and prevention can also be developed based on these alterations. This paper summarizes the results of recent preclinical and clinical chemoprevention studies and discusses screening for bladder cancer. PMID:21941546

  12. Curcumin in chemoprevention of breast cancer

    Directory of Open Access Journals (Sweden)

    Katarzyna Terlikowska

    2014-01-01

    Full Text Available Breast cancer is the most common malignant cancer among women, both in Poland and worldwide. Due to the constantly increasing number of breast cancer cases, it is vital to develop effective activities in primary and secondary prevention. One of the promising methods of best value, connecting both types of cancer prevention, appears to be chemoprevention. Chemoprevention uses natural or synthetic compounds to inhibit, delay or reverse the process of carcinogenesis. Among ingredients of natural origin, great attention is paid to curcumin – a broad-spectrum anti-cancer polyphenol derivative, extracted from the rhizome of Curcuma longa L. Curcumin has a number of chemopreventive properties such as anti-inflammatory activity, induction of apoptosis, inhibition of angiogenesis as well as tumor metastasis. Numerous in vitro and in vivo studies have demonstrated the mentioned anti-cancer effect in the epithelial breast cell line MCF-10A and in the epithelial breast cell lines MCF-7, BT-474, SK-BR-3-hr and MDA-MB-231. The main problem associated with the use of curcumin as a chemopreventive agent in humans is its low absorption from the gastrointestinal tract, poor solubility in body fluids and low bioavailability. Current studies are underway to increase the bioavailability and effectiveness of curcumin in vivo. Good results in the prevention and the treatment of breast cancer could be ensured by curcumin nanoparticles coated with albumin, known as nanocurcumin. The studies using nanocurcumin, however, are still in the preclinical stage, which is why there is a need to conduct extensive long-term randomized clinical trials to determine its effectiveness.

  13. Beneficial and adverse effects of chemopreventive agents

    International Nuclear Information System (INIS)

    Lee, Byung Mu; Park, Kwang-Kyun

    2003-01-01

    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

  14. 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.

  15. Optimizing therapeutic efficacy of chemopreventive agents: A critical review of delivery strategies in oral cancer chemoprevention clinical trials

    OpenAIRE

    Andrew S Holpuch; Kashappa-Goud H Desai; Steven P Schwendeman; Susan R Mallery

    2011-01-01

    Due to its characterized progression from recognized premalignant oral epithelial changes (i.e., oral epithelial dysplasia) to invasive cancer, oral squamous cell carcinoma represents an optimal disease for chemopreventive intervention prior to malignant transformation. The primary goal of oral cancer chemoprevention is to reverse, suppress, or inhibit the progression of premalignant lesions to cancer. Over the last several decades, numerous oral cancer chemoprevention clinical trials have as...

  16. Prediction of Liquefaction Potential of Dredge Fill Sand by DCP and Dynamic Probing

    International Nuclear Information System (INIS)

    Alam, Md. Jahangir; Azad, Abul Kalam; Rahman, Ziaur

    2008-01-01

    From many research it is proved that liquefaction potential of sand is function of mainly relative density and confining pressure. During routine site investigations, high-quality sampling and laboratory testing of sands are not feasible because of inevitable sample disturbance effects and budgetary constraints. On the other hand quality control of sand fill can be done by determining in situ density of sand in layer by layer which is expensive and time consuming. In this paper TRL DCP (Transportation Research Laboratory Dynamic Cone Penetration) and DPL (Dynamic Probing Light) are calibrated to predict the relative density of sand deposit. For this purpose sand of known relative density is prepared in a calibration chamber which is a mild steel cylinder with diameter 0.5 m and height 1.0 m. Relative density of sand is varied by controlling height of fall and diameter of hole of sand discharge bowl. After filling, every time DPL and DCP tests are performed and for every blow the penetration of cone is recorded. N10 is then calculated from penetration records. Thus a database is compiled where N10 and relative densities are known. A correlation is made between N 10 and relative density for two types of sand. A good correlation of N 10 and relative density is found

  17. Chemopreventive effect of tadalafil in cisplatin-induced ...

    African Journals Online (AJOL)

    Summary: Nephrotoxicity remains a common untoward effect of cisplatin therapy with limited effective chemopreventive options available till date. This study aims to evaluate the possible chemopreventive effect and mechanism(s) of action of 2 mgkg-1 and 5 mgkg-1 of Tadalafil in cisplatin-induced nephrotoxic rats. In this ...

  18. Breast Cancer Profile among Patients with a History of Chemoprevention

    Directory of Open Access Journals (Sweden)

    Freya R. Schnabel

    2016-01-01

    Full Text Available Purpose. This study identifies women with breast cancer who utilized chemoprevention agents prior to diagnosis and describes their patterns of disease. Methods. Our database was queried retrospectively for patients with breast cancer who reported prior use of chemoprevention. Patients were divided into primary (no history of breast cancer and secondary (previous history of breast cancer groups and compared to patients who never took chemoprevention. Results. 135 (6% of 2430 women used chemoprevention. In the primary chemoprevention group (n = 18, 1%, 39% had completed >5 years of treatment, and fully 50% were on treatment at time of diagnosis. These patients were overwhelmingly diagnosed with ER/PR positive cancers (88%/65% and were diagnosed with equal percentages (44% of IDC and DCIS. 117 (87% used secondary chemoprevention. Patients in this group were diagnosed with earlier stage disease and had lower rates of ER/PR-positivity (73%/65% than the nonchemoprevention group (84%/72%. In the secondary group, 24% were on chemoprevention at time of diagnosis; 73% had completed >5 years of treatment. Conclusions. The majority of patients who used primary chemoprevention had not completed treatment prior to diagnosis, suggesting that the timing of initiation and compliance to prevention strategies are important in defining the pattern of disease in these patients.

  19. Chemoprevention of esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Stoner, Gary D.; Wang Lishu; Chen Tong

    2007-01-01

    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

  20. Null activity of selenium and vitamin e as cancer chemopreventive agents in the rat prostate.

    Science.gov (United States)

    McCormick, David L; Rao, K V N; Johnson, William D; Bosland, Maarten C; Lubet, Ronald A; Steele, Vernon E

    2010-03-01

    To evaluate the potential efficacy of selenium and vitamin E as inhibitors of prostate carcinogenesis, four chemoprevention studies using a common protocol were done in a rat model of androgen-dependent prostate cancer. After stimulation of prostate epithelial cell proliferation by a sequential regimen of cyproterone acetate followed by testosterone propionate, male Wistar-Unilever rats received a single i.v. injection of N-methyl-N-nitrosourea (MNU) followed by chronic androgen stimulation via subcutaneous implantation of testosterone pellets. At 1 week post-MNU, groups of carcinogen-treated rats (39-44/group) were fed either a basal diet or a basal diet supplemented with l-selenomethionine (3 or 1.5 mg/kg diet; study 1), dl-alpha-tocopherol (vitamin E, 4,000 or 2,000 mg/kg diet; study 2), l-selenomethionine + vitamin E (3 + 2,000 mg/kg diet or 3 + 500 mg/kg diet; study 3), or selenized yeast (target selenium levels of 9 or 3 mg/kg diet; study 4). Each chemoprevention study was terminated at 13 months post-MNU, and prostate cancer incidence was determined by histopathologic evaluation. No statistically significant reductions in prostate cancer incidence were identified in any group receiving dietary supplementation with selenium and/or vitamin E. These data do not support the hypotheses that selenium and vitamin E are potent cancer chemopreventive agents in the prostate, and when considered with the recent clinical data reported in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), show the predictive nature of this animal model for human prostate cancer chemoprevention.

  1. Overview of mechanisms of cancer chemopreventive agents

    International Nuclear Information System (INIS)

    De Flora, Silvio; Ferguson, Lynnette R.

    2005-01-01

    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

  2. Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer.

    Science.gov (United States)

    Marin, Jose J G; Sanchez de Medina, Fermin; Castaño, Beatriz; Bujanda, Luis; Romero, Marta R; Martinez-Augustin, Olga; Moral-Avila, Rosario Del; Briz, Oscar

    2012-05-01

    Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.

  3. 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.

  4. Phyto-oestrogens and breast cancer chemoprevention

    International Nuclear Information System (INIS)

    Limer, Jane L; Speirs, Valerie

    2004-01-01

    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

  5. 7-methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity.

    Science.gov (United States)

    Wypijewska, Anna; Bojarska, Elzbieta; Lukaszewicz, Maciej; Stepinski, Janusz; Jemielity, Jacek; Davis, Richard E; Darzynkiewicz, Edward

    2012-10-09

    Decapping scavenger (DcpS) enzymes catalyze the cleavage of a residual cap structure following 3' → 5' mRNA decay. Some previous studies suggested that both m(7)GpppG and m(7)GDP were substrates for DcpS hydrolysis. Herein, we show that mononucleoside diphosphates, m(7)GDP (7-methylguanosine diphosphate) and m(3)(2,2,7)GDP (2,2,7-trimethylguanosine diphosphate), resulting from mRNA decapping by the Dcp1/2 complex in the 5' → 3' mRNA decay, are not degraded by recombinant DcpS proteins (human, nematode, and yeast). Furthermore, whereas mononucleoside diphosphates (m(7)GDP and m(3)(2,2,7)GDP) are not hydrolyzed by DcpS, mononucleoside triphosphates (m(7)GTP and m(3)(2,2,7)GTP) are, demonstrating the importance of a triphosphate chain for DcpS hydrolytic activity. m(7)GTP and m(3)(2,2,7)GTP are cleaved at a slower rate than their corresponding dinucleotides (m(7)GpppG and m(3)(2,2,7)GpppG, respectively), indicating an involvement of the second nucleoside for efficient DcpS-mediated digestion. Although DcpS enzymes cannot hydrolyze m(7)GDP, they have a high binding affinity for m(7)GDP and m(7)GDP potently inhibits DcpS hydrolysis of m(7)GpppG, suggesting that m(7)GDP may function as an efficient DcpS inhibitor. Our data have important implications for the regulatory role of m(7)GDP in mRNA metabolic pathways due to its possible interactions with different cap-binding proteins, such as DcpS or eIF4E.

  6. A genetic screen for modifiers of Drosophila caspase Dcp-1 reveals caspase involvement in autophagy and novel caspase-related genes

    Directory of Open Access Journals (Sweden)

    Ahnn Joohong

    2010-01-01

    Full Text Available Abstract Background Caspases are cysteine proteases with essential functions in the apoptotic pathway; their proteolytic activity toward various substrates is associated with the morphological changes of cells. Recent reports have described non-apoptotic functions of caspases, including autophagy. In this report, we searched for novel modifiers of the phenotype of Dcp-1 gain-of-function (GF animals by screening promoter element- inserted Drosophila melanogaster lines (EP lines. Results We screened ~15,000 EP lines and identified 72 Dcp-1-interacting genes that were classified into 10 groups based on their functions and pathways: 4 apoptosis signaling genes, 10 autophagy genes, 5 insulin/IGF and TOR signaling pathway genes, 6 MAP kinase and JNK signaling pathway genes, 4 ecdysone signaling genes, 6 ubiquitination genes, 11 various developmental signaling genes, 12 transcription factors, 3 translation factors, and 11 other unclassified genes including 5 functionally undefined genes. Among them, insulin/IGF and TOR signaling pathway, MAP kinase and JNK signaling pathway, and ecdysone signaling are known to be involved in autophagy. Together with the identification of autophagy genes, the results of our screen suggest that autophagy counteracts Dcp-1-induced apoptosis. Consistent with this idea, we show that expression of eGFP-Atg5 rescued the eye phenotype caused by Dcp-1 GF. Paradoxically, we found that over-expression of full-length Dcp-1 induced autophagy, as Atg8b-GFP, an indicator of autophagy, was increased in the eye imaginal discs and in the S2 cell line. Taken together, these data suggest that autophagy suppresses Dcp-1-mediated apoptotic cell death, whereas Dcp-1 positively regulates autophagy, possibly through feedback regulation. Conclusions We identified a number of Dcp-1 modifiers that genetically interact with Dcp-1-induced cell death. Our results showing that Dcp-1 and autophagy-related genes influence each other will aid future

  7. A Chemopreventive Nanodiamond Platform for Oral Cancer Treatment.

    Science.gov (United States)

    Yen, Albert; Zhang, Kangyi; Daneshgaran, Giulia; Kim, Ho-Joong; Ho, Dean

    2016-02-01

    Standard oral cancer therapy generally includes a combination of surgery with chemotherapy and/or radiotherapy. This treatment paradigm has not changed in some time. In this paper, we propose a chemopreventive nanodiamond platform for the delivery of celecoxib (Celebrex) to oral cancer lesions. This innovative platform allows for sustained drug release under physiological conditions, potentially enhancing chemopreventive efficacy of celecoxib without the physical and toxicological damage associated with conventional means of drug delivery.

  8. Incorporation of 210Pb and 210Po to Poultry through the Addition of Dicalcium Phosphate (DCP) to the Diet

    International Nuclear Information System (INIS)

    Casacuberta, N.; Masque, P.; Garcia-Orellana, J.; Gasa, J.; Anguita, M.

    2008-01-01

    Due to the replacement of calcium by uranium in the phosphorite, sedimentary phosphate rock contains high concentrations of 238 U (i.e. from 1500 Bq·kg -1 in Morocco to 4000 Bq·kg -1 in Tanzania ores). Dicalcium Phosphate (DCP) is produced by the wet acid digestion of the phosphorite, and is used as a source of calcium and phosphorus for livestock feed supplement. If the phosphorite acid digestion is made with hydrochloric acid, DCP may present specific activities of about 10 3 Bq·kg -1 of 238 U and some of its decay chain daughters. In particular, due to its radiological implications, the presence of 210 Pb and 210 Po in DCP is of special relevance. The aim of this work was to investigate the potential incorporation of these radionuclides to poultry through its diet. Three different diets were therefore prepared with different contents of both DCP and 210 Pb and 210 Po. Diet A was used as a blank, and had a 2.5% in weight of monocalcium phosphate (MCP); diet B, with a 5% in weight of DCP; and diet C, with a 2.5% of DCP. Concentrations of 210 Pb were 0.93, 101.4 and 51.2 Bq·kg -1 ; whereas concentrations of 210 Po were 0.92, 74 and 36 Bq·kg -1 of food for diets A, B and C, respectively. Accumulation of 210 Pb and 210 Po was analysed at several times during poultry growth in samples of bone, liver, kidney, muscle, excrements as well as entire animals, with a total of 30 broilers fed with the 3 different diets. Results showed clear enhancements in the accumulation of both 210 Pb and 210 Po in chicken for diets B and C, and in particular in liver and bone. However, total accumulation of radionuclides in chicken, and especially in edible parts, is low compared to its expulsion through excrements. These results are interpreted in terms of the potential dose through consumption of chicken

  9. Fenton-like oxidation of 2,4-DCP in aqueous solution using iron-based nanoparticles as the heterogeneous catalyst.

    Science.gov (United States)

    Li, Renchao; Gao, Ying; Jin, Xiaoying; Chen, Zuliang; Megharaj, Mallavarapu; Naidu, Ravendra

    2015-01-15

    In this report, various iron-based nanoparticles (nZVI, n-Ni/Fe, n-Pd/Fe) were used for both heterogeneous Fenton oxidation of 2,4-dichlorophenol (2,4-DCP) and reductive dechlorination of 2,4-DCP in order to understand their roles in the Fenton oxidation and the reductive degradation of 2,4-DCP. The dechlorination efficiency of 2,4-DCP using nZVI, n-Ni/Fe, n-Fe/Pd and Fe(2)(+) was 6.48%, 6.80%, 15.95%, 5.02%, while Fenton oxidation efficiency of 2,4-DCP was 57.87%, 34.23%, 27.94%, 19.61% after 180 min, respectively. The new findings included a higher dechlorination using n-Fe/Pd due to Pd effective catalysis and the effective heterogeneous Fenton oxidation using nZVI depending on reductive dechlorination and heterogeneous Fenton oxidation occurs simultaneously. However, nZVI as the potential catalyst for heterogeneous Fenton was observed, and SEM, EDS and XRD demonstrate that change on the nZVI surface occurred due to the Fe(2+) leaching, and Total Organic Carbon (TOC) (30.71%) shows that 2,4-DCP was degraded. Furthermore, the experiment indicates that the pH values and concentration of 2,4-DCP significantly impacted on the heterogeneous Fenton oxidation of 2,4-DCP and the data fits well with the pseudo first-order kinetic model, which was a diffusion-controlled reaction. Finally, a possible mechanism for degradation of 2,4-DCP was proposed. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. 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.

  11. Chemoprevention of cancer: an ongoing saga.

    Science.gov (United States)

    Kellen, J A

    1999-01-01

    The trivial adage "an ounce of prevention..." is certainly appropriate in oncology; cancer has and continues to have an enormous impact on morbidity, suffering, socioeconomics and mortality. Curative therapy is elusive--cancer remains a mainly lethal disease, which makes the objective of prevention even more important and attractive. Sober estimates put the potentially avoidable or preventable cancers in the Western World at 80% (1): the effects of smoking and alcohol, being overweight, diet promiscuity and other lifestyle choices are well known, yet at the individual level, corrective measures are disappointingly ignored. Lately, this issue is being further weakened by our acceptance of inherited susceptibility--why change our habits and indulgences, if we can not escape our genetic destiny? However, there is a massive and growing amount of information on chemoprevention which needs to be carefully evaluated, in the hope that someday, we should be able to avoid or at least delay cancer by the use of natural or synthetic compounds which intervene in the early precancerous process.

  12. Endotoxin and cancer chemo-prevention.

    Science.gov (United States)

    Mastrangelo, Giuseppe; Fadda, Emanuela; Cegolon, Luca

    2013-10-01

    Reduced rates of lung cancer have been observed in several occupational groups exposed to high levels of organic dusts contaminated by endotoxin. The underlying anti-neoplastic mechanism of endotoxin may be an increased secretion of endogenous anti-neoplastic mediators and activation of the toll-like receptors (TLR). A detoxified endotoxin derivative, Monophosphoryl Lipid A (MPL(®)) is marketed in Europe since 1999 as part of the adjuvant systems in allergy vaccines for treatment of allergic rhino-conjunctivitis and allergic asthma. Over 200,000 patients have used them to date (nearly 70% in Germany). Since detailed exposure (MPL(®) dose and timing of administration) and individual data are potentially available, an observational follow-up study could be conducted in Germany to investigate the protective effect of MPL(®) against cancer, comparing cancer incidence in two groups of patients with allergic rhinitis: those treated with allergoids plus MPL(®) and those treated with a vaccine including the same allergoids but not MPL(®). The protective effect of MPL(®) could be quantified in ever and never smokers. If this proposed observational study provides evidence of protective effects, MPL(®) could be immediately used as a chemo-preventive agent since it is already in use as adjuvant in human vaccines against cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Plasma emission spectroscopy (DCP) for rare earths determination in waters from Morro do Ferro (MG) Brazil, after chromatographic preconcentration

    International Nuclear Information System (INIS)

    Figueiredo, A.M.R. de.

    1987-01-01

    Rare earth determinations in surface and well waters from Morro do Ferro was studied using chemical preconcentration methods of the group and plasma emission spectroscopy excited by direct current are - DCP. A method that combines retention in alumina is HF medium with ion exchange for the preconcentration of the group was developed in semi micro scale. DCP determination, in the sequencial mode by using mixed standards containing, Y, La, Ce, Nd, Pr, Sm, Eu, Ga, Tb, Dy, Er, Yb and Al, principal concentrate componentes was studied by analysis of the profile of each spectral line. Principal cations, anions, ph and Eh were determined. Semi-micro techniques were developed for anions preconcentration and for determination of sulphate, phosphate and carbonate. (M.J.C.) [pt

  14. Radiation levels in samples of dicalcium phosphate (DCP) and bovine and poultry rations by gamma-ray spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Luz Filho, Isaias Venancio da; Scheibel, Viviane; Appoloni, Carlos Roberto, E-mail: isaiasfilhojr@yahoo.com.b [Universidade Estadual de Londrina (UEL), PR (Brazil). Dept. de Fisica

    2009-07-01

    The objective of the present work is to determine the radiation levels found in bovine rations and in the dicalcium phosphate (DCP) feed supplement. Knowledge of the radiation levels in samples of rations and DCP for cattle is important, because they are directly and indirectly-part of the human diet. In order to obtain this data, gamma-ray spectrometry technique was used, employing a HPGe detector of 66% of relative efficiency, with an energy resolution of 2.03 KeV for the {sup 60}Co 1332.46 KeV line. The radioactive activity of the radionuclides {sup 40}K, {sup 137}Cs, {sup 238}U, {sup 232}Th and its respective decay series was measured. The accommodation recipient of the samples was a Marinelli beaker of 1 L. The {sup 238}U series activities were calculated through {sup 214}Pb and {sup 214}Bi activities, and the {sup 232}Th series' activity was calculated through the {sup 228}Ac, {sup 212}Pb, {sup 212}Bi and {sup 208}Tl values. The DCP samples and the rations measured in this work were produced in Londrina city, Brazil, in the second semester of 2007. Among the rations, the largest {sup 40}K and {sup 228}Ra activities were found in the ration sample for milk cattle, 402 +- 14 and 1.71 +- 0.10 Bq/kg, respectively. The ration for beef cattle yielded the largest activity for {sup 226}Ra, 1.51 + 0.93 Bq/kg. In the DCP sample, the activities for the {sup 238}U, {sup 40}K and {sup 232}Th were respectively 83 +- 26; 46.6 +- 2.8 and 7.79 +- 0.70 Bq/kg. The MDA values for {sup 137}Cs varied from 0.037 to 0.29 Bq/kg. (author)

  15. Radiation levels in samples of dicalcium phosphate (DCP) and bovine and poultry rations by gamma-ray spectrometry

    International Nuclear Information System (INIS)

    Luz Filho, Isaias Venancio da; Scheibel, Viviane; Appoloni, Carlos Roberto

    2009-01-01

    The objective of the present work is to determine the radiation levels found in bovine rations and in the dicalcium phosphate (DCP) feed supplement. Knowledge of the radiation levels in samples of rations and DCP for cattle is important, because they are directly and indirectly-part of the human diet. In order to obtain this data, gamma-ray spectrometry technique was used, employing a HPGe detector of 66% of relative efficiency, with an energy resolution of 2.03 KeV for the 60 Co 1332.46 KeV line. The radioactive activity of the radionuclides 40 K, 137 Cs, 238 U, 232 Th and its respective decay series was measured. The accommodation recipient of the samples was a Marinelli beaker of 1 L. The 238 U series activities were calculated through 214 Pb and 214 Bi activities, and the 232 Th series' activity was calculated through the 228 Ac, 212 Pb, 212 Bi and 208 Tl values. The DCP samples and the rations measured in this work were produced in Londrina city, Brazil, in the second semester of 2007. Among the rations, the largest 40 K and 228 Ra activities were found in the ration sample for milk cattle, 402 ± 14 and 1.71 ± 0.10 Bq/kg, respectively. The ration for beef cattle yielded the largest activity for 226 Ra, 1.51 + 0.93 Bq/kg. In the DCP sample, the activities for the 238 U, 40 K and 232 Th were respectively 83 ± 26; 46.6 ± 2.8 and 7.79 ± 0.70 Bq/kg. The MDA values for 137 Cs varied from 0.037 to 0.29 Bq/kg. (author)

  16. Estimate of dietary intake of chloropropanols (3-MCPD and 1,3-DCP and health risk assessment

    Directory of Open Access Journals (Sweden)

    Adriana Pavesi Arisseto

    2013-02-01

    Full Text Available Chloropropanols, including 3-monochloropropane-1,2-diol (3-MCPD and 1,3-dichloropropan-2-ol (1,3-DCP, comprise a group of chemical contaminants with carcinogenic and genotoxic properties. They have been found in a variety of processed foods and food ingredients, such as hydrolyzed vegetable protein, soy sauce, cereal-based products, malt-derived ingredients, and smoked foods. This study aimed to assess the dietary exposure to 3-MCPD and 1,3-DCP in Brazil and verify whether the presence of these substances in foods could represent health risks. The intake was calculated by combining data on food consumption, provided by the Consumer Expenditure Survey 2008-2009, with the levels of contaminant occurrence determined by gas chromatography-mass spectrometry. The exposure to 3-MCPD ranged from 0.06 to 0.51 µg.kg bw-1.day-1 considering average and high consumers, while the intake of 1,3-DCP was estimated to be 0.0036 µg.kg bw-1.day-1 in the worst case scenario evaluated. Based on these results, it was verified that the Brazilians' exposure to chloropropanols does not present a significant health risk. However, the consumption of specific foods containing high levels of 3-MCPD could exceed the provisional maximum tolerable daily intake of 2 µg.kg bw-1 established for this compound and, therefore, represent a potential concern.

  17. Plant flavonoids in cancer chemoprevention: role in genome stability.

    Science.gov (United States)

    George, Vazhappilly Cijo; Dellaire, Graham; Rupasinghe, H P Vasantha

    2017-07-01

    Carcinogenesis is a multistage process that involves a series of events comprising of genetic and epigenetic changes leading to the initiation, promotion and progression of cancer. Chemoprevention is referred to as the use of nontoxic natural compounds, synthetic chemicals or their combinations to intervene in multistage carcinogenesis. Chemoprevention through diet modification, i.e., increased consumption of plant-based food, has emerged as a most promising and potentially cost-effective approach to reducing the risk of cancer. Flavonoids are naturally occurring polyphenols that are ubiquitous in plant-based food such as fruits, vegetables and teas as well as in most medicinal plants. Over 10,000 flavonoids have been characterized over the last few decades. Flavonoids comprise of several subclasses including flavonols, flavan-3-ols, anthocyanins, flavanones, flavones, isoflavones and proanthocyanidins. This review describes the most efficacious plant flavonoids, including luteolin, epigallocatechin gallate, quercetin, apigenin and chrysin; their hormetic effects; and the molecular basis of how these flavonoids contribute to the chemoprevention with a focus on protection against DNA damage caused by various carcinogenic factors. The present knowledge on the role of flavonoids in chemoprevention can be used in developing effective dietary strategies and natural health products targeted for cancer chemoprevention. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. 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.

    2011-01-01

    From 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, anti-oxidant, anti-proliferative, anti-carcinogenic, and anti-angiogenic activity in various cell culture and some animal studies. Research over the past four 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 demonstrated 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

  19. Molecular medicine and the development of cancer chemopreventive agents.

    Science.gov (United States)

    Izzotti, Alberto

    2012-07-01

    Chemoprevention is effective in inhibiting the onset of cancer in experimental animal models, but the transferability of similar results to humans is questionable. Therefore, reliable intermediate molecular biomarkers are needed to evaluate the efficacy of chemopreventive agents before the onset of cancer. The use of genomic biomarkers is limited by their poor predictive value. Although post-genomic biomarkers (i.e., gene-expression analyses) are useful for evaluating the safety, efficacy, and mechanistic basis of chemopreventive agents, the biomarkers are often poorly related to the phenotype, due to posttranscriptional regulation. Proteome analyses can evaluate preclinical phenotype alterations, but only at low protein counts. MicroRNA alterations, which are essential for the development of cancer, may be modulated by chemopreventive agents. Furthermore, microRNA delivery may be used to counteract carcinogenesis. Exposure to cigarette smoke induces microRNA let-7 downregulation and cell proliferation that can be converted to cell growth arrest and apoptosis upon let-7a transfection. Therefore, microRNAs are reliable biomarkers for evaluating chemoprevention efficacy and may be used to counteract carcinogenesis. © 2012 New York Academy of Sciences.

  20. 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.

  1. Stalagmite carbon isotopes and dead carbon proportion (DCP) in a near-closed-system situation: An interplay between sulphuric and carbonic acid dissolution

    Science.gov (United States)

    Bajo, Petra; Borsato, Andrea; Drysdale, Russell; Hua, Quan; Frisia, Silvia; Zanchetta, Giovanni; Hellstrom, John; Woodhead, Jon

    2017-08-01

    In this study, the 'dead carbon proportion' (DCP) calculated from combined U-Th and radiocarbon analyses was used to explore the carbon isotope systematics in Corchia Cave (Italy) speleothems, using the example of stalagmite CC26 which grew during the last ∼12 ka. The DCP values in CC26 are among the highest ever recorded in a stalagmite, spanning the range 44.8-68.8%. A combination of almost closed-system conditions and sulphuric acid dissolution (SAD) are proposed as major drivers in producing such a high DCP with minor contribution from old organic matter from the deep vadose zone. The long-term decrease in both DCP and δ13C most likely reflects post-glacial soil recovery above the cave, with a progressive increase of soil CO2 contribution to the total dissolved inorganic carbon (DIC). Pronounced millennial-scale shifts in DCP and relatively small coeval but antipathetic changes in δ13C are modulated by the effects of hydrological variability on open and closed-system dissolution, SAD and prior calcite precipitation. Hence, the DCP in Corchia Cave speleothems represents an additional proxy for rainfall amount.

  2. Prostate cancer chemoprevention: Current status and future prospects

    International Nuclear Information System (INIS)

    Gupta, Sanjay

    2007-01-01

    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

  3. Colon Cancer Chemoprevention by Flavonoid Silibinin | Division of Cancer Prevention

    Science.gov (United States)

    DESCRIPTION (provided by applicant): Cancer stem cells (CSC) are now recognized as the main cause for initiation, promotion and progression of most of the cancers, including colorectal cancer (CRC). Despite this fact, efficacy of chemopreventive agents towards CSC generation leading to cancer initiation and tumorigenesis has not yet been well- defined. |

  4. Aspirin Metabolomics in Colorectal Cancer Chemoprevention | Division of Cancer Prevention

    Science.gov (United States)

    Substantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well-established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in humans, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which

  5. Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin.

    Science.gov (United States)

    Raju, Jayadev; Mehta, Rekha

    2009-01-01

    Cancer chemoprevention is a strategy taken to retard, regress, or resist the multistep process of carcinogenesis, including the blockage of its vital morphogenetic milestones viz. normal-preneoplasia-neoplasia-metastasis. For several reasons, including safety, minimal (or no) toxicity and side-effects, and better availability, alternatives such as naturally occurring phytochemicals that are found in foods are becoming increasingly popular over synthetic drugs. Food saponins have been used in complimentary and traditional medicine against a variety of diseases including several cancers. Diosgenin, a naturally occurring steroid saponin found abundantly in legumes and yams, is a well-known precursor of various synthetic steroidal drugs that are extensively used in the pharmaceutical industry. Over the past decade, a series of preclinical and mechanistic studies have been conducted to understand the role of diosgenin as a chemopreventive/therapeutic agent against several cancers. This review highlights the biological activity of diosgenin that contributes to cancer chemoprevention and control. The anticancer mode of action of diosgenin has been demonstrated via modulation of multiple cell signaling events involving critical molecular candidates associated with growth, differentiation, apoptosis, and oncogenesis. Altogether, these preclinical and mechanistic findings strongly implicate the use of diosgenin as a novel, multitarget-based chemopreventive or therapeutic agent against several cancer types. Future research in this field will help to establish not only whether diosgenin is safe and efficacious as a chemopreventive agent against several human cancers, but also to develop and evaluate standards of evidence for health claims for diosgenin-containing foods as they become increasingly popular and enter the marketplace labeled as functional foods and nutraceuticals.

  6. 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

    2016-05-24

    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".

  7. 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...

  8. Use of nonsteroidal antiinflamatory drugs for chemoprevention of colon cancer

    Directory of Open Access Journals (Sweden)

    Milić Aleksandra

    2013-01-01

    Full Text Available Colorectal cancer is in the third most frequent cancer among malignant tumors of both sexes in developed countries. It is predominantly a disease of older persons and occurs mostly after the age of 60. Although the etiology of colon cancer is unknown, it is assumed to arise as a result of unclear and complex interactions between genetic and environmental factors. The main element in the etiology of colorectal cancer is the process of genetic changes in epithelial cells of colon mucosa. It is believed that specific epidemiological factors such as stress, hypoxia, reduced intake of glucose and other nutrients, a hereditary predisposition to mutagenic effects, the meat in the diet, bile acids, reduced intake of minerals and vitamins as well as changes in pH of feces lead to initiation of the process of carcinogenesis in mucosa of the colon. Cancer chemoprevention is defined as the use of chemical agents in order to block, prevent or delay the reversal development or progress of cancer. It is believed that chemoprevention is a key component of cancer control, and numerous studies indicate potential role of NSAIDs in chemoprevention of colon cancer.

  9. 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.

  10. Arsenic and skin cancer – Case report with chemoprevention

    Directory of Open Access Journals (Sweden)

    Uwe Wollina

    2016-04-01

    Full Text Available ABSTRACT Introduction: Arsenic is a potentially hazardous metalloid that can cause skin cancer. We want to demonstrate a case of chronic arsenicosis and the potential of chemoprevention with retinoids. Case Report: This is a case report of a 72-year-old male patient who was exposed to arsenics by dust and direct skin contact over 3 years in a chemical plant in the late fourties. He developed multiple arsenic keratosis clincialll resembling actinic keratoses, Bowen’s disease and palmar minute keratoses. To prevent a transformation into invasive cancer and to lower the burden of precancerous and in situ cancer lesions, he was treated orally with acitretin 20 mg/day. During 9 months of chemopreventive retinoid therapy a partial response of pre-existent skin lesions was noted. Treatment was well tolerated. During follow-up of 5 years no invasive malignancy developed. Conclusions: Intense exposure to arsenics during a relatively short period of 3 years bears a life-long health hazard with the delayed development of multiple in situ carcinomas and precancerous lesions. Chemoprevention with retinoids can induce a partial response.

  11. The strategies to control prostate cancer by chemoprevention approaches

    International Nuclear Information System (INIS)

    Ting, Harold; Deep, Gagan; Agarwal, Chapla; Agarwal, Rajesh

    2014-01-01

    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

  12. Colorectal cancer chemoprevention: the potential of a selective approach.

    Science.gov (United States)

    Ben-Amotz, Oded; Arber, Nadir; Kraus, Sarah

    2010-10-01

    Colorectal cancer (CRC) is a leading cause of cancer death, and therefore demands special attention. Novel recent approaches for the chemoprevention of CRC focus on selective targeting of key pathways. We review the study by Zhang and colleagues, evaluating a selective approach targeting APC-deficient premalignant cells using retinoid-based therapy and TNF-related apoptosis-inducing ligand (TRAIL). This study demonstrates that induction of TRAIL-mediated death signaling contributes to the chemopreventive value of all-trans-retinyl acetate (RAc) by sensitizing premalignant adenoma cells for apoptosis without affecting normal cells. We discuss these important findings, raise few points that deserve consideration, and may further contribute to the development of RAc-based combination therapies with improved efficacy. The authors clearly demonstrate a synergistic interaction between TRAIL, RAc and APC, which leads to the specific cell death of premalignant target cells. The study adds to the growing body of literature related to CRC chemoprevention, and provides solid data supporting a potentially selective approach for preventing CRC using RAc and TRAIL.

  13. Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum

    Directory of Open Access Journals (Sweden)

    Aymeric Monteillier

    2018-03-01

    Full Text Available Lung cancer is the most lethal form of cancer in the world. Its development often involves an overactivation of the nuclear factor kappa B (NF-κB pathway, leading to increased cell proliferation, survival, mobility, and a decrease in apoptosis. Therefore, NF-κB inhibitors are actively sought after for both cancer chemoprevention and therapy, and fungi represent an interesting unexplored reservoir for such molecules. The aim of the present work was to find naturally occurring lung cancer chemopreventive compounds by investigating the metabolites of Penicillium vulpinum, a fungus that grows naturally on dung. Penicillium vulpinum was cultivated in Potato Dextrose Broth and extracted with ethyl acetate. Bioassay-guided fractionation of this extract was performed by measuring NF-κB activity using a HEK293 cell line transfected with an NF-κB-driven luciferase reporter gene. The mycotoxin patulin was identified as a nanomolar inhibitor of TNF-α-induced NF-κB activity. Immunocytochemistry and Western blot analyses revealed that its mechanism of action involved an inhibition of p65 nuclear translocation and was independent from the NF-κB inhibitor α (IκBα degradation process. Enhancing its interest in lung cancer chemoprevention, patulin also exhibited antiproliferative, proapoptotic, and antimigration effects on human lung adenocarcinoma cells through inhibition of the Wnt pathway.

  14. Computerized decision support, task delegation and feedback on performance in type 2 diabetes care : the diabetes care protocol

    NARCIS (Netherlands)

    Cleveringa, F.G.W.

    2010-01-01

    The increasing number of type 2 diabetes patient and the strict targets for glycemic and cardiovascular control demand a good practice organisation and task delegation. The Diabetes Care Protocol (DCP) may improve diabetes management. It consists of a diabetes consultation hour run by a practice

  15. 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.

  16. Assessing barriers to a rational chemoprevention trial design in young patients with familial adenomatous polyposis.

    Science.gov (United States)

    Wood, Joanna P; Howells, Lynne M; Brown, Karen; Thomas, Anne L

    2017-07-01

    Familial adenomatous polyposis coli (FAP) is an autosomal dominant condition caused by a germline mutation in the adenomatous polyposis coli gene. Colonic adenomas form and almost all patients will develop colorectal cancer if they are not managed at an early stage. The safest preventive strategy is surgical resection of the colon, most commonly performed in late teenage years. There is a paucity of trials investigating the use of primary chemoprevention to delay polyp formation in paediatric FAP. There are extensive preclinical and early clinical data demonstrating that curcumin may be a safe and effective chemotherapeutic agent in reducing the polyp burden in this disease. We ultimately proposed to design and conduct a clinical study to assess whether curcumin treatment delays the need for surgery and/or prevents cancer in young patients with FAP. Research into clinical trial protocols has demonstrated that assessing patients' perceptions at the initial stage leads to better outcomes. We therefore conducted a questionnaire study of patients and parents of children affected by FAP to gain information to aid the protocol design. Results demonstrated that there are some FAP patients for whom this study is relevant and desirable. Those with a personal history of curcumin use reported that it was well tolerated. However, the response rate was poor (25%), indicating that there are potential difficulties ensuring adequate recruitment to the proposed trial. This report draws on lessons learnt from prior trials and the findings from the questionnaire to outline the challenges faced in designing such a study.

  17. Deployment Strategies and Clustering Protocols Efficiency

    Directory of Open Access Journals (Sweden)

    Chérif Diallo

    2017-06-01

    Full Text Available Wireless sensor networks face significant design challenges due to limited computing and storage capacities and, most importantly, dependence on limited battery power. Energy is a critical resource and is often an important issue to the deployment of sensor applications that claim to be omnipresent in the world of future. Thus optimizing the deployment of sensors becomes a major constraint in the design and implementation of a WSN in order to ensure better network operations. In wireless networking, clustering techniques add scalability, reduce the computation complexity of routing protocols, allow data aggregation and then enhance the network performance. The well-known MaxMin clustering algorithm was previously generalized, corrected and validated. Then, in a previous work we have improved MaxMin by proposing a Single- node Cluster Reduction (SNCR mechanism which eliminates single-node clusters and then improve energy efficiency. In this paper, we show that MaxMin, because of its original pathological case, does not support the grid deployment topology, which is frequently used in WSN architectures. The unreliability feature of the wireless links could have negative impacts on Link Quality Indicator (LQI based clustering protocols. So, in the second part of this paper we show how our distributed Link Quality based d- Clustering Protocol (LQI-DCP has good performance in both stable and high unreliable link environments. Finally, performance evaluation results also show that LQI-DCP fully supports the grid deployment topology and is more energy efficient than MaxMin.

  18. Update on the chemopreventive effects of ginger and its phytochemicals.

    Science.gov (United States)

    Baliga, Manjeshwar Shrinath; Haniadka, Raghavendra; Pereira, Manisha Maria; D'Souza, Jason Jerome; Pallaty, Princy Louis; Bhat, Harshith P; Popuri, Sandhya

    2011-07-01

    The rhizomes of Zingiber officinale Roscoe (Zingiberaceae), commonly known as ginger, is one of the most widely used spice and condiment. It is also an integral part of many traditional medicines and has been extensively used in Chinese, Ayurvedic, Tibb-Unani, Srilankan, Arabic, and African traditional medicines, since antiquity, for many unrelated human ailments including common colds, fever, sore throats, vomiting, motion sickness, gastrointestinal complications, indigestion, constipation, arthritis, rheumatism, sprains, muscular aches, pains, cramps, hypertension, dementia, fever, infectious diseases, and helminthiasis. The putative active compounds are nonvolatile pungent principles, namely gingerols, shogaols, paradols, and zingerone. These compounds are some of the extensively studied phytochemicals and account for the antioxidant, anti-inflammatory, antiemetic, and gastroprotective activities. A number of preclinical investigations with a wide variety of assay systems and carcinogens have shown that ginger and its compounds possess chemopreventive and antineoplastic effects. A number of mechanisms have been observed to be involved in the chemopreventive effects of ginger. The cancer preventive activities of ginger are supposed to be mainly due to free radical scavenging, antioxidant pathways, alteration of gene expressions, and induction of apoptosis, all of which contribute towards decrease in tumor initiation, promotion, and progression. This review provides concise information from preclinical studies with both cell culture models and relevant animal studies by focusing on the mechanisms responsible for the chemopreventive action. The conclusion describes directions for future research to establish its activity and utility as a human cancer preventive and therapeutic drug. The above-mentioned mechanisms of ginger seem to be promising for cancer prevention; however, further clinical studies are warranted to assess the efficacy and safety of ginger.

  19. Grapefruit and its biomedical, antigenotoxic and chemopreventive properties.

    Science.gov (United States)

    Cristóbal-Luna, José Melesio; Álvarez-González, Isela; Madrigal-Bujaidar, Eduardo; Chamorro-Cevallos, Germán

    2018-02-01

    Grapefruit (Citrus paradisi Mcfad) is a perenifolium tree 5-6 m high with a fruit of about 15 cm in diameter, protected by the peel we can find about 11-14 segments (carpels), each of which is surrounded by a membrane and each containing the juice sacs, as well as the seeds. The fruit is made up of numerous compounds, and is known to have nutritive value because of the presence of various vitamins and minerals, among other chemicals. The fruit is also used in the field of gastronomy. Information has been accumulated regarding the participation of the fruit structures in a variety of biomedical, antigenotoxic and chemopreventive effects, surely related with the presence of the numerous chemicals that have been determined to constitute the fruit. Such studies have been carried out in different in vitro and in vivo experimental models, and in a few human assays. The information published so far has shown interesting results, therefore, the aims of the present review are to initially examine the main characteristics of the fruit, followed by systematization of the acquired knowledge concerning the biomedical, antigenotoxic and chemopreventive effects produced by the three main structures of the fruit: peel, seed, and pulp. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Intrinsic fluorescence biomarkers in cells treated with chemopreventive drugs

    Science.gov (United States)

    Kirkpatrick, Nathaniel D.; Brands, William R.; Zou, Changping; Brewer, Molly A.; Utzinger, Urs

    2005-03-01

    Non-invasive monitoring of cellular metabolism offers promising insights into areas ranging from biomarkers for drug activity to cancer diagnosis. Fluorescence spectroscopy can be utilized in order to exploit endogenous fluorophores, typically metabolic co-factors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), and estimate the redox status of the sample. Fluorescence spectroscopy was applied to follow metabolic changes in epithelial ovarian cells as well as bladder epithelial cancer cells during treatment with a chemopreventive drug that initiates cellular quiescence. Fluorescence signals consistent with NADH, FAD, and tryptophan were measured to monitor cellular activity, redox status, and protein content. Cells were treated with varying concentrations of N-4-(hydroxyphenyl) retinamide (4-HPR) and measured in a stable environment with a sensitive fluorescence spectrometer. A subset of measurements was completed on a low concentration of cells to demonstrate feasibility for medical application such as in bladder or ovary washes. Results suggest that all of the cells responded with similar dose dependence but started at different estimated redox ratio baseline levels correlating with cell cycle, growth inhibition, and apoptosis assays. NADH and tryptophan related fluorescence changed significantly while FAD related fluorescence remained unaltered. Fluorescence data collected from approximately 1000 - 2000 cells, comparable to a bladder or ovary wash, was measurable and useful for future experiments. This study suggests that future intrinsic biomarker measurements may need to be most sensitive to changes in NADH and tryptophan related fluorescence while using FAD related fluorescence to help estimate the baseline redox ratio and predict response to chemopreventive agents.

  1. Transcutaneous electrical nerve stimulation (TENS) improves the diabetic cytopathy (DCP) via up-regulation of CGRP and cAMP.

    Science.gov (United States)

    Ding, Liucheng; Song, Tao; Yi, Chaoran; Huang, Yi; Yu, Wen; Ling, Lin; Dai, Yutian; Wei, Zhongqing

    2013-01-01

    The objective of this study was to investigate the effects and mechanism of Transcutaneous Electrical Nerve Stimulation (TENS) on the diabetic cytopathy (DCP) in the diabetic bladder. A total of 45 rats were randomly divided into diabetes mellitus (DM)/TENS group (n=15), DM group (n=15) and control group (n=15). The rats in the DM/TENS and TENS groups were electronically stimulated (stimulating parameters: intensity-31 V, frequency-31 Hz, and duration of stimulation of 15 min) for three weeks. Bladder histology, urodynamics and contractile responses to field stimulation and carbachol were determined. The expression of calcitonin gene-related peptide (CGRP) was analyzed by RT-PCR and Western blotting. The results showed that contractile responses of the DM rats were ameliorated after 3 weeks of TENS. Furthermore, TENS significantly increased bladder wet weight, volume threshold for micturition and reduced PVR, V% and cAMP content of the bladder. The mRNA and protein levels of CGRP in dorsal root ganglion (DRG) in the DM/TENS group were higher than those in the DM group. TENS also significantly up-regulated the cAMP content in the bladder body and base compared with diabetic rats. We conclude that TENS can significantly improve the urine contractility and ameliorate the feeling of bladder fullness in DM rats possibly via up-regulation of cAMP and CGRP in DRG.

  2. Acceptance and adherence to chemoprevention among women at increased risk of breast cancer.

    Science.gov (United States)

    Roetzheim, Richard G; Lee, Ji-Hyun; Fulp, William; Matos Gomez, Elizabeth; Clayton, Elissa; Tollin, Sharon; Khakpour, Nazanin; Laronga, Christine; Lee, Marie Catherine; Kiluk, John V

    2015-02-01

    Chemoprevention is an option for women who are at increased risk of breast cancer (five year risk ≥1.7%). It is uncertain, however, how often women accept and complete five years of therapy and whether clinical or demographic factors predict completion. Medical records were abstracted for 219 women whose five year risk of breast cancer was ≥1.7% and who were offered chemoprevention while attending a high risk breast clinic at the Moffitt Cancer Center. We examined the likelihood of accepting chemoprevention and completing five years of therapy, and potential clinical and demographic predictors of these outcomes, using multivariable logistic regression and survival analysis models. There were 118/219 women (54.4%) who accepted a recommendation for chemoprevention and began therapy. The likelihood of accepting chemoprevention was associated with lifetime breast cancer risk and was higher for women with specific high risk conditions (lobular carcinoma in situ and atypical ductal hyperplasia). Women with osteoporosis and those that consumed alcohol were also more likely to accept medication. There were 58/118 (49.2%) women who stopped medication at least temporarily after starting therapy. Based on survival curves, an estimated 60% of women who begin chemoprevention will complete five years of therapy. A substantial percentage of women at increased risk of breast cancer will decline chemoprevention and among those that accept therapy, approximately 40% will not be able to complete five years of therapy because of side effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. COMPARATIVE STUDY BETWEEN TITANIUM ELASTIC NAILING (TENS AND DYNAMIC COMPRESSION PLATING (DCP IN THE TREATMENT OF FEMORAL DIAPHYSEAL FRACTURES IN CHILDREN

    Directory of Open Access Journals (Sweden)

    Ramasubba Reddy

    2015-08-01

    Full Text Available BACKGROUND : Orthopaedic surgeons have long maintained that all children who have sustained a diaphyseal fracture of femur recover with c onservative treatment, given the excellent remodeling ability of immature bone in children. Angulations, shortenings and malrotations are not always corrected by conservative treatment. Of many surgical options, titanium elastic nailing has been the newer implant which is being used regularly. Although good results have been reported with elastic intramedullary nails, plate fixation continues to be a viable alternative in surgical treatment of femoral shaft fractures. However there are not many studies comp aring the efficiency of titanium elastic nailing and plating for femoral diaphyseal fractures in pediatric age group. AIM : The present study aims to compare the surgical management of diaphyseal fractures of femur in children with Dynamic Compression Plati ng versus Titanium Elastic Nailing. DESIGN : This is a prospective study . MATERIALS AND METHODS : This prospective study was conducted in a tertiary hospital. Patients who presented to the out - patient department and casualty of the hospital with femoral diap hyseal fractures during April 2012 to June 2014 were considered for the study. Subjects fulfilling the predetermined inclusion and exclusion criteria were included in the study. STATISTICAL METHODS : Fisher Exact test, Chi - Square Test, Student t test (Two t ailed, independent . RESULTS : Patients in the age group of 6 - 14 years were considered for the study, Patients were divided into two groups and treated with DCP/TENS. The duration of surgery, hospital stay, and, amount of blood loss was minimal in TENS grou p. Callus was seen early in TENS group. Radiological union was early in TENS group by 2 - 3 weeks. Outcome was better in patients treated with TENS (Excellent - 70%; Satisfactory – 30%; Poor - 0% in comparison to DCP (Excellent - 70%; Satisfactory - 25%; Poor - 5%. CO NCLUSION : TENS

  4. Simultaneous Analysis of 3-MCPD and 1,3-DCP in Asian Style Sauces Using QuEChERS Extraction and Gas Chromatography–Triple Quadrupole Mass Spectrometry

    Science.gov (United States)

    Genualdi, Susan; Nyman, Patricia; DeJager, Lowri

    2017-01-01

    Acid hydrolyzed vegetable protein (aHVP) is used for flavoring a wide variety of foods and also in the production of nonfermented soy sauce. During the production of aHVP, chloropropanols including 3-monochloropropane-1,2-diol (3-MCPD) and 1,3 dichloropropane-2-ol (1,3-DCP) can be formed through the reaction of the hydrochloric acid catalyst and residual fat and the reaction of 3-MCPD with acetic acid, respectively. 3-MCPD is a carcinogen, and 1,3-DCP has been classified as a genotoxic carcinogen. The European Union (EU) has set a maximum concentration of 0.02 mg/kg of 3-MCPD in aHVP, and the Food and Drug Administration (FDA) set a guidance limit of 1 mg/kg of 3-MCPD in aHVP. 1,3-DCP is not an approved food additive, and the Joint FAO/WHO Expert Committee on Food Additives (JEFCA) has set a limit at 0.005 mg/kg, which is close to the estimated method detection limit. Currently there are few analytical methods for the simultaneous determination of 3-MCPD and 1,3-DCP without derivatization due to differences in their physical chemical properties and reactivity. A new method was developed using QuEChERS (quick, easy, cheap, effective, rugged, and safe) with direct analysis of the extract without derivatization using gas chromatography–triple quadrupole mass spectrometry (GC-QQQ). Additionally, a market sampling of 60 soy sauce samples was performed in 2015 to determine if concentrations have changed since the FDA limit was set in 2008. The sampling results were compared between the new QuEChERS method and a method using phenylboronic acid (PBA) as a derivatizing agent for 3-MCPD analysis. The concentrations of 3-MCPD detected in soy sauce samples collected in 2015 (3-MCPD below current regulatory limits PMID:28064506

  5. Simultaneous Analysis of 3-MCPD and 1,3-DCP in Asian Style Sauces Using QuEChERS Extraction and Gas Chromatography-Triple Quadrupole Mass Spectrometry.

    Science.gov (United States)

    Genualdi, Susan; Nyman, Patricia; DeJager, Lowri

    2017-02-01

    Acid hydrolyzed vegetable protein (aHVP) is used for flavoring a wide variety of foods and also in the production of nonfermented soy sauce. During the production of aHVP, chloropropanols including 3-monochloropropane-1,2-diol (3-MCPD) and 1,3 dichloropropane-2-ol (1,3-DCP) can be formed through the reaction of the hydrochloric acid catalyst and residual fat and the reaction of 3-MCPD with acetic acid, respectively. 3-MCPD is a carcinogen, and 1,3-DCP has been classified as a genotoxic carcinogen. The European Union (EU) has set a maximum concentration of 0.02 mg/kg of 3-MCPD in aHVP, and the Food and Drug Administration (FDA) set a guidance limit of 1 mg/kg of 3-MCPD in aHVP. 1,3-DCP is not an approved food additive, and the Joint FAO/WHO Expert Committee on Food Additives (JEFCA) has set a limit at 0.005 mg/kg, which is close to the estimated method detection limit. Currently there are few analytical methods for the simultaneous determination of 3-MCPD and 1,3-DCP without derivatization due to differences in their physical chemical properties and reactivity. A new method was developed using QuEChERS (quick, easy, cheap, effective, rugged, and safe) with direct analysis of the extract without derivatization using gas chromatography-triple quadrupole mass spectrometry (GC-QQQ). Additionally, a market sampling of 60 soy sauce samples was performed in 2015 to determine if concentrations have changed since the FDA limit was set in 2008. The sampling results were compared between the new QuEChERS method and a method using phenylboronic acid (PBA) as a derivatizing agent for 3-MCPD analysis. The concentrations of 3-MCPD detected in soy sauce samples collected in 2015 (3-MCPD below current regulatory limits.

  6. Aspirin as a Chemopreventive Agent for Cancer: a New Hope?

    Directory of Open Access Journals (Sweden)

    Isnatin Miladiyah

    2016-01-01

    Full Text Available Introduction: inflammation has been shown to play a major role in the pathogenesis of cancer. Inflammatory process activates the immune system through pro-inflammatory mediators and subsequent triggers transformation into malignant cells. Some tumors or cancers has been associated with chronic infections, such as hepatitis B and C viruses (hepatocellular carcinoma, human papilloma virus (cervical cancer, Helicobacter pylori (gastric cancer and lymphoma, and prostatitis (prostate cancer. A considerable study have investigated the benefits of aspirin for the prevention and treatment of cancer or tumors. Objectives: This paper aims to describe the relationship between inflammation and cancer incidence, so that use of aspirin as an anti-inflammatory agent is a rational choice in the treatment and prevention of cancer. Conclusion: Aspirin potential for chemoprevention of various types of cancer. Considering the high risk of side effects of aspirin, aspirin is not intended as a routine therapy to prevent the occurrence of cancer.

  7. Trial endpoints for drug approval in oncology: Chemoprevention.

    Science.gov (United States)

    Beitz, J

    2001-04-01

    As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug.

  8. Oleuropein and Cancer Chemoprevention: The Link is Hot

    Directory of Open Access Journals (Sweden)

    Ammad Ahmad Farooqi

    2017-04-01

    Full Text Available Cancer comprises a collection of related diseases characterized by the existence of altered cellular pathways resulting in an abnormal tendency for uncontrolled growth. A broad spectrum, coordinated, and personalized approach focused on targeting diverse oncogenic pathways with low toxicity and economic natural compounds can provide a real benefit as a chemopreventive and/or treatment of this complex disease. Oleuropein, a bioactive phenolic compound mainly present in olive oil and other natural sources, has been reported to modulate several oncogenic signalling pathways. This review presents and critically discusses the available literature about the anticancer and onco-suppressive activity of oleuropein and the underlying molecular mechanisms implicated in the anticarcinogenic and therapeutic effects. The existence of limitations and the promising perspectives of research on this phenolic compound are also critically analyzed and discussed.

  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. ent-Rosane and abietane diterpenoids as cancer chemopreventive agents.

    Science.gov (United States)

    Núñez, Marvin J; Reyes, Carolina P; Jiménez, Ignacio A; Hayashi, Hirotaka; Tokuda, Harukuni; Bazzocchi, Isabel L

    2011-04-01

    Two ent-rosane- (cuzcol, 1 and 6-dehydroxycuzcol, 2) and a abietatriene- (salvadoriol, 3) type diterpenoids have been isolated from Maytenus cuzcoina and Crossopetalum uragoga, respectively, along with five known diterpene compounds (4-8). Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, and computational data. The absolute configuration of cuzcol was determined by application of Riguera ester procedure. This is the first instance of isolation of ent-rosane diterpenoids from species of the Celastraceae. The isolated diterpenes were found to be potent anti-tumour-promoter agents, and carnosol (7) also showed a remarkable chemopreventive effect in an in vivo two-stage carcinogenesis model. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Carcinogenicity of chromium and chemoprevention: a brief update

    Directory of Open Access Journals (Sweden)

    Wang Y

    2017-08-01

    Full Text Available Yafei Wang,1,* Hong Su,1,* Yuanliang Gu,1 Xin Song,1 Jinshun Zhao1,2 1Department of Preventative Medicine, Zhejiang Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, People’s Republic of China; 2Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, USA *These authors contributed equally to this work Abstract: Chromium has two main valence states: hexavalent chromium (Cr[VI] and trivalent chromium (Cr[III]. Cr(VI, a well-established human carcinogen, can enter cells by way of a sulfate/phosphate anion-transport system, and then be reduced to lower-valence intermediates consisting of pentavalent chromium (Cr[V], tetravalent chromium (Cr[IV] or Cr(III via cellular reductants. These intermediates may directly or indirectly result in DNA damage or DNA–protein cross-links. Although Cr(III complexes cannot pass easily through cell membranes, they have the ability to accumulate around cells to induce cell-surface morphological alteration and result in cell-membrane lipid injuries via disruption of cellular functions and integrity, and finally to cause DNA damage. In recent years, more research, including in vitro, in vivo, and epidemiological studies, has been conducted to evaluate the genotoxicity/carcinogenicity induced by Cr(VI and/or Cr(III compounds. At the same time, various therapeutic agents, especially antioxidants, have been explored through in vitro and in vivo studies for preventing chromium-induced genotoxicity/carcinogenesis. This review aims to provide a brief update on the carcinogenicity of Cr(VI and Cr(III and chemoprevention with different antioxidants. Keywords: hexavalent chromium, Cr(VI, trivalent chromium, Cr(III, genotoxicity, carcinogenicity, chemoprevention, antioxidant 

  12. Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention.

    Science.gov (United States)

    Shirode, Amit B; Bharali, Dhruba J; Nallanthighal, Sameera; Coon, Justin K; Mousa, Shaker A; Reliene, Ramune

    2015-01-01

    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 polyphenol of choice for further chemoprevention studies with pomegranate nanoprototypes. These data demonstrate that nanotechnology-enabled delivery of pomegranate polyphenols enhances their anticancer effects in breast cancer cells. Thus, pomegranate polyphenols are promising agents for nanochemoprevention of breast cancer.

  13. Can transcriptomics provide insight into the underlying chemopreventive mechanisms of complex mixtures of phytochemicals in humans?

    NARCIS (Netherlands)

    Breda, van S.G.; Wilms, L.C.; Gaj, S.; Briedé, J.J.; Helsper, J.P.F.G.; Kleinjans, J.C.; Kok, de T.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

  14. Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to Respond

    OpenAIRE

    Stockbrugger, Reinhold W.

    2010-01-01

    In the past four decades, chemoprevention of colorectal cancer (CRC) has been the subject of many epidemiologic and intervention trials of naturally occurring or pharmacologic agents. Recently, the positioning of cyclooxygenase 2 inhibitors as a viable option in this context was a major breakthrough; however, it was hampered by adverse cardiovascular events. This review questions whether chemopreventive measures for CRC are ready to be used in mass or individual applications, standing alone o...

  15. Study on the interaction of chemopreventive compounds and food born carcinogens with cytochrome P450 enzymes

    OpenAIRE

    Brabencová, Eliška

    2013-01-01

    The use of food supplements containing natural chemopreventive compounds increased in recent years. Some of the most popular chemopreventive compounds are flavonoids. Due to their natural origin, flavonoids are generally accepted as safe compounds. They exert antioxidant, anti-cancer and anti-inflammatory properties. However, flavonoids should be considered as foreign compounds (xenobiotics). Flavonoids interact with many enzymes, among the most important belong cytochromes P450 (CYPs), key e...

  16. The GDP-switched GAF domain of DcpA modulates the concerted synthesis/hydrolysis of c-di-GMP in Mycobacterium smegmatis.

    Science.gov (United States)

    Chen, Hui-Jie; Li, Na; Luo, Ye; Jiang, Yong-Liang; Zhou, Cong-Zhao; Chen, Yuxing; Li, Qiong

    2018-04-09

    The second messenger c-di-GMP [bis-(3'-5')-cyclic dimeric guanosine monophosphate] plays a key role in bacterial growth, survival and pathogenesis, and thus its intracellular homeostasis should be finely maintained. Mycobacterium smegmatis encodes a GAF (mammalian c G MP-regulated phosphodiesterases, Anabaena a denylyl cyclases and Escherichia coli transcription activator F hlA) domain containing bifunctional enzyme DcpA ( d iguanylate c yclase and p hosphodiesterase A ) that catalyzes the synthesis and hydrolysis of c-di-GMP . Here, we found that M. smegmatis DcpA catalyzes the hydrolysis of c-di-GMP at a higher velocity, compared with synthetic activity, resulting in a sum reaction from the ultimate substrate GTP to the final product pGpG [5'-phosphoguanylyl-(3'-5')-guanosine]. Fusion with the N-terminal GAF domain enables the GGDEF (Gly-Gly-Asp-Glu-Phe) domain of DcpA to dimerize and accordingly gain synthetic activity. Screening of putative metabolites revealed that GDP is the ligand of the GAF domain. Binding of GDP to the GAF domain down-regulates synthetic activity, but up-regulates hydrolytic activity, which, in consequence, might enable a timely response to the transient accumulation of c-di-GMP at the stationary phase or under stresses. Combined with the crystal structure of the EAL (Glu-Ala-Leu) domain and the small-angle X-ray scattering data, we propose a putative regulatory model of the GAF domain finely tuned by the intracellular GTP/GDP ratio. These findings help us to better understand the concerted control of the synthesis and hydrolysis of c-di-GMP in M. smegmatis in various microenvironments. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  17. 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....

  18. Dynamic compression plate (DCP) fixation of propagating medial condylar fractures of the third metacarpal/metatarsal bone in 30 racehorses: retrospective analysis (1990-2005).

    Science.gov (United States)

    Goodrich, L R; Nixon, A J; Conway, J D; Morley, P S; Bladon, B M; Hogan, P M

    2014-11-01

    An in-depth review of dynamic compression plate (DCP) fixation of propagating medial condyle fractures of the third metacarpus or metatarsus has not been previously reported. To describe the technique, evaluate short-term outcome and long-term race performance of racehorses that underwent DCP fixation for repair of propagating or spiralling medial condylar fractures of the third metacarpal (McIII) or metatarsal (MtIII) bone. Retrospective case series. The surgical case records of 30 horses with propagating fractures of the medial condyle of McIII or MtIII were reviewed. Medical information included: age, breed, sex, presentation, how injury occurred (racing or training), surgical treatment and post operative complications. Racing information included: starts, top 3 placing and career earnings. Long propagating fractures of the medial condyle of Mc/tIII were identified in 23 Thoroughbred (TB) and 7 Standardbred (STB) racehorses. The fracture spiralled proximally in 22 of 30 cases (73%). Standardbreds had a higher propensity for hindlimb involvement (71%), whereas TBs tended to have more front limb involvement (61%). Twelve of 30 (40%) horses raced post surgery. Career earnings were significantly lower for TB horses with medial condylar fractures; $34,916 when compared with the national average of $60,841 (P≤0.03). Overall, horses having DCP fixation for medial condylar fractures had less starts post surgery (3.1 TBs and 5.8 STBs) compared with the national average (7 TBs and 17.3 STBs) and decreased lifetime starts 13.4 (TBs) compared with 17.3 nationally. Propagating medial condyle fractures can be repaired with plate fixation to potentially lessen the risk of catastrophic fracture destabilisation and return to racing can be expected in 40% of horses. Further prospective studies are warranted comparing lag screw fixation with DCP fixation for repair of severe medial condylar fractures of the metacarpus/metatarsus. © 2013 The Authors. Equine Veterinary Journal

  19. Black tea: Phytochemicals, cancer chemoprevention, and clinical studies.

    Science.gov (United States)

    Singh, Brahma N; Rawat, A K S; Bhagat, R M; Singh, B R

    2017-05-03

    Tea (Camellia sinensis L.) is the most popular, flavored, functional, and therapeutic non-alcoholic drink consumed by two-thirds of the world's population. Black tea leaves are reported to contain thousands of bioactive constituents such as polyphenols, amino acids, volatile compounds, and alkaloids that exhibit a range of promising pharmacological properties. Due to strong antioxidant property, black tea inhibits the development of various cancers by regulating oxidative damage of biomolecules, endogenous antioxidants, and pathways of mutagen and transcription of antioxidant gene pool. Regular drinking of phytochemicals-rich black tea is linked to regulate several molecular targets, including COX-2, 5-LOX, AP-1, JNK, STAT, EGFR, AKT, Bcl2, NF-κB, Bcl-xL, caspases, p53, FOXO1, TNFα, PARP, and MAPK, which may be the basis of how dose of black tea prevents and cures cancer. In vitro and preclinical studies support the anti-cancer activity of black tea; however, its effect in human trails is uncertain, although more clinical experiments are needed at molecular levels to understand its anti-cancer property. This review discusses the current knowledge on phytochemistry, chemopreventive activity, and clinical applications of black tea to reveal its anti-cancer effect.

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

    Directory of Open Access Journals (Sweden)

    Prasan R. Bhandari

    2015-04-01

    Full Text Available 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 readily available natural substances from vegetables, fruits, herbs and spices is one of the significantly important approaches for cancer prevention in the present era. Among the spices, Crocus sativus L. (saffron; 番紅花 fān hóng huā has generated interest because pharmacological experiments have established numerous beneficial properties including radical scavenging, anti-mutagenic and immuno-modulating effects. The more powerful components of saffron are crocin, crocetin and safranal. Studies in animal models and with cultured human malignant cell lines have demonstrated antitumor and cancer preventive activities of saffron and its main ingredients. This review provides a brief insight into the anticancer properties of saffron and its components.

  1. The Role of Nutraceuticals in Chemoprevention and Chemotherapy and Their Clinical Outcomes

    Directory of Open Access Journals (Sweden)

    Sabita N. Saldanha

    2012-01-01

    Full Text Available The genesis of cancer is often a slow process and the risk of developing cancer increases with age. Altering a diet that includes consumption of beneficial phytochemicals can influence the balance and availability of dietary chemopreventive agents. In chemopreventive approaches, foods containing chemicals that have anticancer properties can be supplemented in diets to prevent precancerous lesions from occurring. This necessitates further understanding of how phytochemicals can potently maintain healthy cells. Fortunately there is a plethora of plant-based phytochemicals although few of them are well studied in terms of their application as cancer chemopreventive and therapeutic agents. In this analysis we will examine phytochemicals that have strong chemopreventive and therapeutic properties in vitro as well as the design and modification of these bioactive compounds for preclinical and clinical applications. The increasing potential of combinational approaches using more than one bioactive dietary compound in chemoprevention or cancer therapy will also be evaluated. Many novel approaches to cancer prevention are on the horizon, several of which are showing great promise in saving lives in a cost-effective manner.

  2. Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

    Science.gov (United States)

    Chan, Andrew T.; Arber, Nadir; Burn, John; Chia, John Whay-Kuang; Elwood, Peter; Hull, Mark A.; Logan, Richard F.; Rothwell, Peter M.; Schrör, Karsten; Baron, John A.

    2011-01-01

    Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term post-trial follow-up of nearly 14,000 patients from 4 randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about 5 years was associated with a 34% reduction in 20-year CRC mortality. A separate meta-analysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in 4 randomized adenoma prevention trials demonstrated that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least 2 years, there was a ≥ 50% reduction in the risk of CRC commencing 5 years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin’s anticancer effect require further investigation. PMID:22084361

  3. Chemopreventive and Anticancer Activities of Allium victorialis var. platyphyllum Extracts.

    Science.gov (United States)

    Kim, Hyun-Jeong; Park, Min Jeong; Park, Hee-Juhn; Chung, Won-Yoon; Kim, Ki-Rim; Park, Kwang-Kyun

    2014-09-01

    Allium victorialis var. platyphyllum is an edible perennial herb and has been used as a vegetable or as a Korean traditional medicine. Allium species have received much attention owing to their diverse pharmacological properties, including antioxidative, anti-inflammatory, and anticancer activities. However, A. victorialis var. platyphyllum needs more study. The chemopreventive potential of A. victorialis var. platyphyllum methanol extracts was examined by measuring 12-O-tetra-decanoylphorbol 13-acetate (TPA)-induced superoxide anion production in the differentiated HL-60 cells, TPA-induced mouse ear edema, and Ames/Salmonella mutagenicity. The apoptosis-inducing capabilities of the extracts were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, 4',6-diamidino-2-phenylindole staining, and the DNA fragmentation assay in human colon cancer HT-29 cells. Antimetastatic activities of the extracts were also investigated in an experimental mouse lung metastasis model. The methanol extracts of A. victorialis var. platyphyllum rhizome (AVP-R) and A. victorialis var. platyphyllum stem (AVP-S) dose-dependently inhibited the TPA-induced generation of superoxide anion in HL-60 cells and TPA-induced ear edema in mice, as well as 7,12-dimethylbenz[a]anthracene (DMBA) and tert-butyl hydroperoxide (t-BOOH) -induced bacterial mutagenesis. AVP-R and AVP-S reduced cell viability in a dose-related manner and induced apoptotic morphological changes and internucleosomal DNA fragmentation in HT-29 cells. In the experimental mouse lung metastasis model, the formation of tumor nodules in lung tissue was significantly inhibited by the treatment of the extracts. AVP-R and AVP-S possess antioxidative, anti-inflammatory, antimutagenic, proapoptotic, and antimetastatic activities. Therefore, these extracts can serve as a beneficial supplement for the prevention and treatment of cancer.

  4. Epigenetic Regulation by Sulforaphane: Opportunities for Breast and Prostate Cancer Chemoprevention.

    Science.gov (United States)

    Atwell, Lauren L; Beaver, Laura M; Shannon, Jackilen; Williams, David E; Dashwood, Roderick H; Ho, Emily

    2015-04-01

    Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that has multiple molecular targets and anti-cancer properties. Researchers have demonstrated several chemopreventive benefits of SFN consumption, such as reductions in tumor growth, increases in cancer cell apoptosis, and disruption of signaling within tumor microenvironments both in vitro and in vivo . Emerging evidence indicates that SFN exerts several of its chemopreventive effects by altering epigenetic mechanisms. This review summarizes evidence of the impact of SFN on epigenetic events and how they relate to the chemopreventive effects of SFN observed in preclinical and clinical studies of breast and prostate cancers. Specific areas of focus include the role of SFN in the regulation of cell cycle, apoptosis, inflammation, antioxidant defense, and cancer cell signaling and their relationships to epigenetic mechanisms. Finally, remaining challenges and research needs for translating mechanistic work with SFN into human studies and clinical intervention trials are discussed.

  5. The chemopreventive properties and therapeutic modulation of green tea polyphenols in oral squamous cell carcinoma.

    Science.gov (United States)

    Lee, Ui-Lyong; Choi, Sung-Weon

    2011-01-01

    Chemoprevention is a relatively novel and promising approach for controlling cancer that uses specific natural products or synthetic agents to suppress, reverse, or prevent premalignancy before transformation into invasive cancer. Oral cavity squamous cell carcinoma (OCSCC) represents a large, worldwide health burden with approximately 274,000 cases diagnosed annually worldwide. Smoking and alcohol consumption are major inducers of OCSCC. Recently, the human papilloma virus was also shown to potentially be an etiologic factor. Due to its easily identifiable risk factors and the presence of premalignant regions, oral cancer makes a good candidate for chemoprevention. Green tea is the most widely consumed beverage in the world, and it has received considerable attention because of its abundant, scientifically proven, beneficial effects on human health. In this review, we discuss the role of green tea in oral cancer chemoprevention with regard to the multiple molecular mechanisms proposed in various in vitro, in vivo, and clinical trials.

  6. 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...

  7. Targeting Chemoprevention of Colorectal Cancer to Those Who Are Likely to Respond.

    Science.gov (United States)

    Stockbrugger, Reinhold W

    2010-01-01

    In the past four decades, chemoprevention of colorectal cancer (CRC) has been the subject of many epidemiologic and intervention trials of naturally occurring or pharmacologic agents. Recently, the positioning of cyclooxygenase 2 inhibitors as a viable option in this context was a major breakthrough; however, it was hampered by adverse cardiovascular events. This review questions whether chemopreventive measures for CRC are ready to be used in mass or individual applications, standing alone or in combination with other CRC-preventive measures. It also discusses steps that may be undertaken to explore this field further.

  8. Simultaneous Analysis of 3-MCPD and 1,3-DCP in Asian Style Sauces Using QuEChERS Extraction and Gas Chromatography���Triple Quadrupole Mass Spectrometry

    OpenAIRE

    Genualdi, Susan; Nyman, Patricia; DeJager, Lowri

    2017-01-01

    Acid hydrolyzed vegetable protein (aHVP) is used for flavoring a wide variety of foods and also in the production of nonfermented soy sauce. During the production of aHVP, chloropropanols including 3-monochloropropane-1,2-diol (3-MCPD) and 1,3 dichloropropane-2-ol (1,3-DCP) can be formed through the reaction of the hydrochloric acid catalyst and residual fat and the reaction of 3-MCPD with acetic acid, respectively. 3-MCPD is a carcinogen, and 1,3-DCP has been classified as a genotoxic carcin...

  9. Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices

    Directory of Open Access Journals (Sweden)

    Farrukh Aqil

    2017-02-01

    Full Text Available Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish rat model. Female ACI rats were given either control diet (AIN 93M or diet supplemented with 7.5% (w/w of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2. Diet intake and body weight were recorded weekly, and animals were euthanized after 3 and 12 weeks. E2-treatment showed significantly (2.1- and 3.4-fold enhanced growth of pituitary gland at 3 and 12 weeks, respectively. All test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as three weeks. Immunohistochemical analysis for proliferative cell nuclear antigen (PCNA in mammary tissues showed significant reduction in E2-mediated mammary cell proliferation. Test spices reduced the circulating levels of both E2 and prolactin at three weeks. This protection was more pronounced at 12 weeks, with celery eliciting the highest effect. RT-PCR and western blot analysis were performed to determine the potential molecular targets of the spices. Anise and caraway diets significantly offset estrogen-mediated overexpression of both cyclin D1 and estrogen receptor α (ERα. The effect of anise was modest. Likewise, expression of CYP1B1 and CYP1A1 was inhibited by all test spices. Based on short-term molecular markers, caraway was selected over other spices based on its enhanced effect on estrogen-associated pathway. Therefore, a tumor-end point study in ACI rats was conducted with dietary caraway. Tumor palpation from 12 weeks onwards revealed tumor latency of 29 days in caraway-treated animals compared with first tumor appearance at 92

  10. Chemoprevention of Rat Mammary Carcinogenesis by Apiaceae Spices.

    Science.gov (United States)

    Aqil, Farrukh; Jeyabalan, Jeyaprakash; Munagala, Radha; Ravoori, Srivani; Vadhanam, Manicka V; Schultz, David J; Gupta, Ramesh C

    2017-02-16

    Scientific evidence suggests that many herbs and spices have medicinal properties that alleviate symptoms or prevent disease. In this study, we examined the chemopreventive effects of the Apiaceae spices, anise, caraway, and celery seeds against 17β-estrogen (E2)-mediated mammary tumorigenesis in an ACI (August-Copenhagen Irish) rat model. Female ACI rats were given either control diet (AIN 93M) or diet supplemented with 7.5% ( w / w ) of anise, caraway, or celery seed powder. Two weeks later, one half of the animals in each group received subcutaneous silastic implants of E2. Diet intake and body weight were recorded weekly, and animals were euthanized after 3 and 12 weeks. E2-treatment showed significantly (2.1- and 3.4-fold) enhanced growth of pituitary gland at 3 and 12 weeks, respectively. All test spices significantly offset the pituitary growth by 12 weeks, except celery which was effective as early as three weeks. Immunohistochemical analysis for proliferative cell nuclear antigen (PCNA) in mammary tissues showed significant reduction in E2-mediated mammary cell proliferation. Test spices reduced the circulating levels of both E2 and prolactin at three weeks. This protection was more pronounced at 12 weeks, with celery eliciting the highest effect. RT-PCR and western blot analysis were performed to determine the potential molecular targets of the spices. Anise and caraway diets significantly offset estrogen-mediated overexpression of both cyclin D1 and estrogen receptor α (ERα). The effect of anise was modest. Likewise, expression of CYP1B1 and CYP1A1 was inhibited by all test spices. Based on short-term molecular markers, caraway was selected over other spices based on its enhanced effect on estrogen-associated pathway. Therefore, a tumor-end point study in ACI rats was conducted with dietary caraway. Tumor palpation from 12 weeks onwards revealed tumor latency of 29 days in caraway-treated animals compared with first tumor appearance at 92 days in

  11. Bioremediation protocols

    National Research Council Canada - National Science Library

    Sheehan, David

    1997-01-01

    ..., .. . . . . .. ,. . . .. . . . . . . . .. . . . . .. . . .. . .. 3 2 Granular Nina Sludge Christiansen, Consortia lndra for Bioremediation, M. Mathrani, and Birgitte K. Ahring . 23 PART II PROTOCOLS...

  12. Estimate of dietary intake of chloropropanols (3-MCPD and 1,3-DCP and health risk assessment Estimativa da ingestão de cloropropanóis (3-MCPD e 1,3-DCP e avaliação do risco à saúde

    Directory of Open Access Journals (Sweden)

    Adriana Pavesi Arisseto

    2013-02-01

    Full Text Available Chloropropanols, including 3-monochloropropane-1,2-diol (3-MCPD and 1,3-dichloropropan-2-ol (1,3-DCP, comprise a group of chemical contaminants with carcinogenic and genotoxic properties. They have been found in a variety of processed foods and food ingredients, such as hydrolyzed vegetable protein, soy sauce, cereal-based products, malt-derived ingredients, and smoked foods. This study aimed to assess the dietary exposure to 3-MCPD and 1,3-DCP in Brazil and verify whether the presence of these substances in foods could represent health risks. The intake was calculated by combining data on food consumption, provided by the Consumer Expenditure Survey 2008-2009, with the levels of contaminant occurrence determined by gas chromatography-mass spectrometry. The exposure to 3-MCPD ranged from 0.06 to 0.51 µg.kg bw-1.day-1 considering average and high consumers, while the intake of 1,3-DCP was estimated to be 0.0036 µg.kg bw-1.day-1 in the worst case scenario evaluated. Based on these results, it was verified that the Brazilians' exposure to chloropropanols does not present a significant health risk. However, the consumption of specific foods containing high levels of 3-MCPD could exceed the provisional maximum tolerable daily intake of 2 µg.kg bw-1 established for this compound and, therefore, represent a potential concern.Os cloropropanóis, entre eles o 3-monocloropropano-1,2-diol (3-MCPD e o 1,3-dicloropropan-2-ol (1,3-DCP, compreendem um grupo de contaminantes químicos com propriedades carcinogênicas e genotóxicas, encontrados em diversos alimentos processados e ingredientes alimentícios, como proteína vegetal hidrolisada, molho de soja, produtos à base de cereais, ingredientes derivados de malte e alimentos defumados. Este trabalho teve como objetivo avaliar a exposição ao 3-MCPD e 1,3-DCP pela dieta no Brasil e verificar se a presença destes compostos em alimentos pode representar um risco à saúde da população. A ingestão foi

  13. Identification of Serratia marcescens SE1 and determination of its Herbicide 2,2-dichloropropionate (2,2-DCP Degradation Potential

    Directory of Open Access Journals (Sweden)

    Abel, E.

    2012-01-01

    Full Text Available Aims: The goal of the study is to isolate species of bacteria that capable of utilizing 2,2-dichloropropionic acid (2,2-DCP as sole carbon source from soil sample collected from surrounding lake water located in Universiti Teknologi Malaysia, Skudai, Johor. Methodology and Results: Genomic DNA from bacterium SE1 was extracted and PCR amplification was carried out using universal primers, Fd1 (5’ - AGA GTT TGA TCC TGGCTC AG - 3’ and rP1 (5’- ACG GTC ATA CCT TGT TAC GAC TT - 3’ before sending for sequencing. The 16S rDNA nucleotide sequences were compared with Basic Local Alignment Search Tool nucleotide (BLASTn and further analyzed using phylogenetic tree of Neighbour-Joining method (MEGA 5. Phylogenetic analysis indicated that SE1 strain clearly shared 97% homology to the genus of Serratia marcescens and therefore designated as Serratia marcescens sp. SE1. SE1 exhibited the ability to utilize 2,2-DCP as sole carbon source at 20 mM concentration with cell doubling time of 5 h and maximum chloride ion release of 38 μmolCl-/mL. This result suggests that the dehalogenase enzyme present in the bacteria has high affinity towards the substrate. Based on morphological and partial biochemical characteristics, strain SE1 was a non-motile Gram negative bacterium with red colonies, that gave a catalase positive reaction. Conclusion, significance and impact of study: A better understanding of dehalogenases enzyme produce by this S. marcescens sp. SE1 in general will be useful to be used as bioremediation tools for environmental management. This is the first reported case that Serratia sp. has the ability to degrade halogenated compound.

  14. Mejoramiento de las propiedades de tensión en WPC de LDPE: HIPS/fibra natural mediante entrecruzamiento con DCP

    Directory of Open Access Journals (Sweden)

    Arnoldo Emilio Delgado Tobón

    2014-06-01

    Full Text Available Fibra de Retamo Liso (telinemonspessulana fue mezclada en una matriz polimérica formada por: polietileno de baja densidad (LDPE y poliestireno de alto impacto (HIPS en relación 70:30 respectivamente. La fibra natural fue sometida a reducción de tamaño entre 1700 y 850 µm; se le realizó tratamiento superficial de mercerización; el contenido de humedad fue 0,17%. El análisis termo gravimétrico (TGA muestra que la fibra tratada tiene estabilidad de 200,53 °C. La elaboración del compuesto se realizó en mezclador interno y la técnica de obtención de las probetas fue mediante moldeo por compresión. Se evaluó el efecto del agente entrecruzante peróxido de dicumilo (DCP en compuestos con varios porcentajes de fibra: 0; 10; 25; 50 phr. La adición de DCP (1 phr en los compuestos, mejora significativamente las propiedades de tensión con respecto a similares concentraciones de fibra; sin embargo, esta diferencia en los valores de las propiedades disminuye progresivamente cuando la cantidad de fibra se aproxima a 50 phr. El aumento en la concentración de fibra afecta negativamente las propiedades de tensión, con excepción del Módulo de Elasticidad y la Resistencia a la Fluencia. La causa principal es originada por la baja adhesión interfacial fibra natural-matriz polimérica, claramente evidenciada en las imágenes SEM.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Chemopreventive agents attenuate rapid inhibition of gap junctional intercellular communication induced by environmental toxicants

    Czech Academy of Sciences Publication Activity Database

    Babica, Pavel; Čtveráčková, Lucie; Lenčešová, Zuzana; Trosko, J. E.; Upham, B. L.

    2016-01-01

    Roč. 68, č. 5 (2016), s. 827-837 ISSN 0163-5581 R&D Projects: GA MŠk LH12034 Institutional support: RVO:67985939 Keywords : gap junctional intercellular communication * chemopreventive agents * environmental toxicants Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.447, year: 2016

  17. A Review of Promising Natural Chemopreventive Agents for Head and Neck Cancer.

    Science.gov (United States)

    Crooker, Kyle; Aliani, Rana; Ananth, Megha; Arnold, Levi; Anant, Shrikant; Thomas, Sufi Mary

    2018-03-30

    Head and neck squamous cell carcinoma (HNSCC) accounts for 300,000 deaths per year worldwide and overall survival rates have shown little improvement over the past three decades. Current treatment methods including surgery, chemotherapy, and radiotherapy leave patients with secondary morbidities. Thus, treatment of HNSCC may benefit from exploration of natural compounds as chemopreventive agents. With excellent safety profiles, reduced toxicities, antioxidant properties, and general acceptance for use as dietary supplements, natural compounds are viewed as a desirable area of investigation for chemoprevention. Though most of the field is early in development, numerous studies display the potential utility of natural compounds against HNSCC. These compounds face additional challenges such as low bioavailability for systemic delivery, potential toxicities when consumed in pharmacological doses, and acquired resistance. However, novel delivery vehicles and synthetic analogs have shown overcome some of these challenges. This review covers eleven promising natural compounds in the chemoprevention of HNSCC including vitamin A, curcumin, isothiocyanate, green tea, luteolin, resveratrol, genistein, lycopene, bitter melon, withaferin A, and guggulsterone. The review discusses the therapeutic potential and associated challenges of these agents in the chemopreventive efforts against HNSCC. Copyright ©2018, American Association for Cancer Research.

  18. Effect of a vegan diet on biomarkers of chemoprevention in females

    NARCIS (Netherlands)

    Verhagen, H.; Rauma, A.L.; Törrönen, R.; Vogel, N. de; Bruijntjes-Rozier, G.C.D.M.; Dreve, M.A.; Bogaards, J.J.P.; Mykkänen, H.

    1996-01-01

    1. In order to study the potential beneficial effects of a vegan diet, a cross-sectional study was performed and several biomarkers of chemoprevention were measured in a population of female 'living food' eaters ('vegans'; n = 20) vs matched omnivorous controls (n = 20). 2. White blood cells

  19. Chemoprevention of hormone-dependent prostate cancer in the Wistar-Unilever rat.

    Science.gov (United States)

    McCormick, D L; Rao, K V

    1999-01-01

    The high incidence and long latent period of prostate cancer make it an ideal target for chemoprevention. We have evaluated a series of agents for chemopreventive efficacy using a model in which hormone-dependent prostate cancers are induced in the Wistar-Unilever (WU) rat by sequential treatment with antiandrogen (cyproterone acetate), androgen (testosterone propionate), and direct-acting chemical carcinogen (N-methyl-N-nitrosourea), followed by chronic androgen stimulation (testosterone). This regimen reproducibly induces prostate cancers in high incidence, with no gross toxicity and a low incidence of neoplasia in the seminal vesicle and other non-target tissues. Dehydroepiandrosterone (DHEA) and 9-cis-retinoic acid (9-cis-RA) are the most active agents identified to date. DHEA inhibits prostate cancer induction both when chronic administration is begun prior to carcinogen exposure, and when administration is delayed until preneoplastic prostate lesions are present. 9-cis-RA is the most potent inhibitor of prostate carcinogenesis identified; a study to determine the efficacy of delayed administration of 9-cis-RA is in progress. Liarozole fumarate confers modest protection against prostate carcinogenesis, while N-(4-hydroxyphenyl)retinamide (fenretinide), alpha-difluoromethylornithine, oltipraz, DL-alpha-tocopherol acetate (vitamin E), and L-selenomethionine are inactive. Chemoprevention efficacy evaluations in the WU rat will support the identification of agents that merit study for prostate cancer chemoprevention in humans.

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

    International Nuclear Information System (INIS)

    Ahmad, Shiekh Tanveer; Arjumand, Wani; Seth, Amlesh; Nafees, Sana; Rashid, Summya; Ali, Nemat; Sultana, Sarwat

    2011-01-01

    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. Using Breast Cancer Risk Associated Polymorphisms to Identify Women for Breast Cancer Chemoprevention.

    Directory of Open Access Journals (Sweden)

    Elad Ziv

    Full Text Available Breast cancer can be prevented with selective estrogen receptor modifiers (SERMs and aromatase inhibitors (AIs. The US Preventive Services Task Force recommends that women with a 5-year breast cancer risk ≥3% consider chemoprevention for breast cancer. More than 70 single nucleotide polymorphisms (SNPs have been associated with breast cancer. We sought to determine how to best integrate risk information from SNPs with other risk factors to risk stratify women for chemoprevention.We used the risk distribution among women ages 35-69 estimated by the Breast Cancer Surveillance Consortium (BCSC risk model. We modeled the effect of adding 70 SNPs to the BCSC model and examined how this would affect how many women are reclassified above and below the threshold for chemoprevention.We found that most of the benefit of SNP testing a population is achieved by testing a modest fraction of the population. For example, if women with a 5-year BCSC risk of >2.0% are tested (~21% of all women, ~75% of the benefit of testing all women (shifting women above or below 3% 5-year risk would be derived. If women with a 5-year risk of >1.5% are tested (~36% of all women, ~90% of the benefit of testing all women would be derived.SNP testing is effective for reclassification of women for chemoprevention, but is unlikely to reclassify women with <1.5% 5-year risk. These results can be used to implement an efficient two-step testing approach to identify high risk women who may benefit from chemoprevention.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Breast cancer chemopreventive and chemotherapeutic effects of Camellia Sinensis (green tea): an updated review.

    Science.gov (United States)

    Rafieian-Kopaei, Mahmoud; Movahedi, Mino

    2017-02-01

    Camellia sinensis belongs to the plant family of Theaceae, native to East Asia, the Indian Subcontinent and Southeast Asia, but naturalized in many parts of the world. The aim of this study was to overview its anti-breast cancer chemopreventive and chemotherapeutic effects. This review article is aimed to overview breast cancer chemopreventive and chemotherapeutic effects of Camellia sinensis (green tea). This review article was carried out by searching studies in PubMed, Medline, Web of Science, and IranMedex databases. The initial search strategy identified around 108 references. In this study, 68 studies were accepted for further screening, and met all our inclusion criteria [in English, full text, chemopreventive and chemotherapeutic effects of Camellia sinensis and dated mainly from the year 1999 to 2016. The search terms were Camellia sinensis, chemopreventive, chemotherapeutic properties, pharmacological effects. The result of this study suggested that the catechin available in Camellia sinensis has properties which can prevent and treat breast cancer. It has also been shown to inhibit proliferation of breast cancer cells and to block carcinogenesis. It was found that increased Camellia sinensis consumption may lower the risk of breast cancer. Camellia sinensis intake was shown to reduce the risk of breast cancer incidence. In addition, potential breast cancer chemopreventive effect of Camellia sinensis both in vivo and in vitro was highly confirmed. However, the evidence of low effect and no effect was observed. More clinical trial studies are needed to prove its anti-breast cancer activity decisively. Camellia sinensis is broadly utilized as a part of customary medication since antiquated time because of its cost adequacy, and fewer reaction properties. The studies demonstrated anti-breast cancer activity of Camellia sinensis and its component by adjusting cell signaling pathways such as angiogenesis, apoptosis, and transcription factor. Furthermore

  4. Plasmonic Ag-pillared rectorite as catalyst for degradation of 2,4-DCP in the H{sub 2}O{sub 2}-containing system under visible light irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yunfang [School of Chemistry and Environment, South China Normal University, Guangzhou 510006, Guangdong (China); Fang, Jianzhang, E-mail: fangjzh@scnu.edu.cn [School of Chemistry and Environment, South China Normal University, Guangzhou 510006, Guangdong (China); Guangdong Technology Research Center for Ecological Management and Remediation of Urban Water System, Guangzhou 510006 (China); Lu, Shaoyou [Shenzhen Center for Disease Control and Prevention, Shenzhen 518055 (China); Wu, Yan; Chen, Dazhi; Huang, Liyan [Institute of Engineering Technology of Guangdong Province, Key Laboratory of Water Environmental Pollution Control of Guangdong Province, Guangzhou 510440 (China); Cheng, Cong; Ren, Lu; Zhu, Ximiao [School of Chemistry and Environment, South China Normal University, Guangzhou 510006, Guangdong (China); Fang, Zhanqiang [School of Chemistry and Environment, South China Normal University, Guangzhou 510006, Guangdong (China); Guangdong Technology Research Center for Ecological Management and Remediation of Urban Water System, Guangzhou 510006 (China)

    2015-10-30

    Highlights: • The Ag-R catalyst was synthesized via a novel thermal decomposition method. • Ag-R catalyst possessed the synergistic effects of SPR and adsorption capacity. • The degradation of 2,4-DCP was evaluated in Ag-R/H{sub 2}O{sub 2}/visible light system. - Abstract: This study aims at photocatalytic degradation of 2,4-DCP with the assistance of H{sub 2}O{sub 2} in aqueous solution by a composite catalyst of Ag-rectorite. The catalysts were prepared via a novel thermal decomposition method followed after the cation-exchange process. The synthesized nano-materials were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Brunauer–Emmett–Teller (BET) surface analyzer, Ultraviolet–visible light (UV–vis) absorption spectra, field-emission scanning electron microscope (FE-SEM) and transmission electron microscope (TEM). The different mechanisms of degradation process with or without visible light irradiation were discussed, respectively. Moreover, the degradation efficiency of 2,4-DCP wastewater under Ag-rectorite/H{sub 2}O{sub 2}/visible light system was investigated by series of experiments, concerning on effects of major operation factors, such as H{sub 2}O{sub 2} dosage and the initial pH value. The highest degradation rate was observed when adding 0.18 mL H{sub 2}O{sub 2} into 50 mL 2,4-DCP solution, and the optimal pH value was 4 for the reaction. Afterwards, total organic carbon (TOC) experiments were carried out to evaluate the mineralization ratio of 2,4-DCP.

  5. A Chemopreventive Trial to Study the Effects of High Tea Consumption on Smoking-Related Oxidative Stress

    National Research Council Canada - National Science Library

    Hakim, Iman

    2004-01-01

    .... We are conducting a 6-month randomized, controlled, double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

  6. A Chemopreventive Trial to Study the Effects of High Tea Consumption on Smoking-Related Oxidative Stress

    National Research Council Canada - National Science Library

    Hakim, Iman A

    2006-01-01

    .... We are conducting a 6-month randomized, controlled, double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

  7. A Chemoprevention Trial to Study the Effects of High Tea Consumption on Smoking-Related Oxidative Stress

    National Research Council Canada - National Science Library

    Hakim, Iman A

    2005-01-01

    .... We are conducting a 6-month randomized, controlled, double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

  8. A Chemoprevention Trial to Study the Effects of High Tea Consumption on Smoking-Related Oxidative Stress

    National Research Council Canada - National Science Library

    Hakim, Iman A

    2008-01-01

    .... We are conducting a 6-month randomized controlled double-blinded chemopreventive trial in a group of COPD subjects who are being randomized to green or black tea preparations or a control intervention (matching placebo...

  9. El indicador sintético DCP como instrumento de medición de la sostenibilidad turística

    Directory of Open Access Journals (Sweden)

    Guerrero Casas, Flor Mª

    2009-01-01

    Full Text Available RESUMEN Actualmente, los procesos de planificación turística están orientados para que sean los agentes locales quienes formulen las actuaciones necesarias en cada destino. Sin embargo, en la práctica estos agentes no cuentan con la información suficiente para realizar esta tarea. Necesitan de herramientas que les permitan evaluar el actual grado de sostenibilidad de la actividad turística y determinar las medidas necesarias para mejorarlo. En este trabajo proponemos como instrumento de medición un sistema de indicadores de turismo sostenible. Para facilitar el uso de la información del mismo, obtenemos indicadores sintéticos que proporcionan una visión de conjunto mediante un procedimiento que combina el Análisis en Componentes Principales y la distancia a un punto de referencia, de forma que el indicador sintético obtenido, que denominamos DCP, tenga una menor subjetividad asociada. Finalmente, analizamos la sostenibilidad de los destinos costeros en Andalucía para ilustrar la forma en la que se aplica la metodología propuesta y se interpretan los resultados obtenidos.ABSTRACT Nowadays, local agents formulate the necessary public measures in the processes of tourism planning of each destination. However, in the practice these agents do not have enough information to carry out this task. They need tools to assess the current level of sustainability of tourism activity and identify the necessary measures to improve it. In this paper we propose a system of sustainable tourism indicators as a measuring tool. In order to facilitate the use of information system, we also develop synthetic indicators that provide an overview. They are obtained with a methodology that combines Principal Components Analysis and the distance to a reference point, so that this synthetic indicator, called DCP indicator, have a smaller associate subjectivity. Finally, we apply the proposed methodology to Andalusian coastal destinations and we illustrate how

  10. Prostate cancer chemoprevention in men of African descent: current state of the art and opportunities for future research.

    Science.gov (United States)

    Chornokur, Ganna; Kumar, Nagi B

    2013-08-01

    Prostate cancer is the most frequently diagnosed malignancy in men. However, African American/Black men are 60 % more likely to be diagnosed with and 2.4 times more likely to die from prostate cancer, compared to Non-Hispanic White men. Despite the increased burden of this malignancy, no evidence-based recommendation regarding prostate cancer screening exists for the high-risk population. Moreover, in addition to screening and detection, African American men may constitute a prime population for chemoprevention. Early detection and chemoprevention may thus represent an integral part of prostate cancer control in this population. Importantly, recent research has elucidated biological differences in the prostate tumors of African American compared to European American men. The latter may enable a more favorable response in African American men to specific chemopreventive agents that target relevant signal transduction pathways. Based on this evolving evidence, the aims of this review are threefold. First, we aim to summarize the biological differences that were reported in the prostate tumors of African American and European American men. Second, we will review the single- and multi-target chemopreventive agents placing specific emphasis on the pathways implicated in prostate carcinogenesis. And lastly, we will discuss the most promising nutraceutical chemopreventive compounds. Our review underscores the promise of chemoprevention in prostate cancer control, as well as provides justification for further investment in this filed to ultimately reduce prostate cancer morbidity and mortality in this high-risk population of African American men.

  11. Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention.

    Science.gov (United States)

    Ornelas, Argentina; Zacharias-Millward, Niki; Menter, David G; Davis, Jennifer S; Lichtenberger, Lenard; Hawke, David; Hawk, Ernest; Vilar, Eduardo; Bhattacharya, Pratip; Millward, Steven

    2017-06-01

    After more than a century, aspirin remains one of the most commonly used drugs in western medicine. Although mainly used for its anti-thrombotic, anti-pyretic, and analgesic properties, a multitude of clinical studies have provided convincing evidence that regular, low-dose aspirin use dramatically lowers the risk of cancer. These observations coincide with recent studies showing a functional relationship between platelets and tumors, suggesting that aspirin's chemopreventive properties may result, in part, from direct modulation of platelet biology and biochemistry. Here, we present a review of the biochemistry and pharmacology of aspirin with particular emphasis on its cyclooxygenase-dependent and cyclooxygenase-independent effects in platelets. We also correlate the results of proteomic-based studies of aspirin acetylation in eukaryotic cells with recent developments in platelet proteomics to identify non-cyclooxygenase targets of aspirin-mediated acetylation in platelets that may play a role in its chemopreventive mechanism.

  12. Chemopreventive Potential of Flavonoids in Oral Squamous Cell Carcinoma in Human Studies

    Directory of Open Access Journals (Sweden)

    Elena Maria Varoni

    2013-07-01

    Full Text Available Evidence available from nutritional epidemiology has indicated an inverse association between regular consumption of fruits and vegetables and the risk of developing certain types of cancer. In turn, preclinical studies have attributed the health-promoting effects of plant foods to some groups of phytochemicals, by virtue of their many biological activities. In this survey, we briefly examine the chemopreventive potential of flavonoids and flavonoid-rich foods in human oral carcinogenesis. Despite the paucity of data from clinical trials and epidemiological studies, in comparison to in vitro/in vivo investigations, a high level of evidence has been reported for epigallocatechin gallate (EGCG and anthocyanins. These flavonoids, abundant in green tea and black raspberries, respectively, represent promising chemopreventive agents in human oral cancer.

  13. Pomegranate-mediated chemoprevention of experimental hepatocarcinogenesis involves Nrf2-regulated antioxidant mechanisms

    Science.gov (United States)

    Bishayee, Anupam; Bhatia, Deepak; Thoppil, Roslin J.; Darvesh, Altaf S.; Nevo, Eviatar; Lansky, Ephraim P.

    2011-01-01

    Hepatocellular carcinoma (HCC), one of the most prevalent and lethal cancers, has shown an alarming rise in the USA. Without effective therapy for HCC, novel chemopreventive strategies may effectively circumvent the current morbidity and mortality. Oxidative stress predisposes to hepatocarcinogenesis and is the major driving force of HCC. Pomegranate, an ancient fruit, is gaining tremendous attention due to its powerful antioxidant properties. Here, we examined mechanism-based chemopreventive potential of a pomegranate emulsion (PE) against dietary carcinogen diethylnitrosamine (DENA)-induced rat hepatocarcinogenesis that mimics human HCC. PE treatment (1 or 10 g/kg), started 4 weeks prior to the DENA challenge and continued for 18 weeks thereafter, showed striking chemopreventive activity demonstrated by reduced incidence, number, multiplicity, size and volume of hepatic nodules, precursors of HCC. Both doses of PE significantly attenuated the number and area of γ-glutamyl transpeptidase-positive hepatic foci compared with the DENA control. PE also attenuated DENA-induced hepatic lipid peroxidation and protein oxidation. Mechanistic studies revealed that PE elevated gene expression of an array of hepatic antioxidant and carcinogen detoxifying enzymes in DENA-exposed animals. PE elevated protein and messenger RNA expression of the hepatic nuclear factor E2-related factor 2 (Nrf2). Our results provide substantial evidence, for the first time, that pomegranate constituents afford chemoprevention of hepatocarcinogenesis possibly through potent antioxidant activity achieved by upregulation of several housekeeping genes under the control of Nrf2 without toxicity. The outcome of this study strongly supports the development of pomegranate-derived products in the prevention and treatment of human HCC, which remains a devastating disease. PMID:21389260

  14. 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.

  15. Chemoprevention of Colorectal Cancer by Artocarpin, a Dietary Phytochemical from Artocarpus heterophyllus.

    Science.gov (United States)

    Sun, Guochuan; Zheng, Zongping; Lee, Mee-Hyun; Xu, Yijuan; Kang, Soouk; Dong, Zigang; Wang, Mingfu; Gu, Zhennan; Li, Haitao; Chen, Wei

    2017-05-03

    Artocarpus heterophyllus is an evergreen tree distributed in tropical regions, and its fruit (jackfruit) is well-known as the world's largest tree-borne fruit. Although A. heterophyllus has been widely used in folk medicines against inflammation, its potential in cancer chemoprevention remains unclear. Herein we identified artocarpin from A. heterophyllus as a promising colorectal cancer chemopreventive agent by targeting Akt kinase. Phenotypically, artocarpin exhibited selective cytotoxicity against human colon cancer cells. Artocarpin impaired the anchorage-independent growth capability, suppressed colon cancer cell growth, and induced a G1 phase cell cycle arrest which was followed by apoptotic as well as autophagic cell death. Mechanistic studies revealed that artocarpin directly targeted Akt 1 and 2 kinase activity evidenced by in vitro kinase assay, ex vivo binding assay as well as Akt downstream cellular signal transduction. Importantly, oral administration of artocarpin attenuated colitis-associated colorectal tumorigenesis in mice. Taken together, artocarpin, a bioactive component of A. heterophyllus, might merit investigation as a potential colorectal cancer chemopreventive agent.

  16. Chemoprevention utility of silibinin and Cdk4 pathway inhibition in Apc−/+ mice

    International Nuclear Information System (INIS)

    Karim, Baktiar O; Rhee, Ki-Jong; Liu, Guosheng; Zheng, Dongfeng; Huso, David L

    2013-01-01

    Colorectal cancer (CRC) is the second leading cause of death from cancer in the United States. Colorectal cancers have a prolonged latency following initiation that may span decades providing ample time for implementing a chemoprevention strategy that could block or reverse the progression to CRC. Cdk4 pathway alterations have been linked to a number of cancers including CRC. In these experiments we focused on the Cdk4 pathway and its role in intestinal tumorigenesis as a possible target in chemoprevention strategies. We evaluated the effect of Cdk4 blockade on the prevention of intestinal tumor formation by crossing Cdk4 −/− mice to Apc −/+ mice. In addition, we tested the effect of the dietary compound silibinin on the Cdk4 pathway in Apc −/+ mice and HT-29 colon cancer cells in culture. Cdk4 −/− mice backcrossed to Apc −/+ mice reduced intestinal adenoma formation compared to Apc −/+ controls. Silibinin effectively targeted the Cdk4 pathway causing hypophosphorylation of the retinoblastoma protein, inhibited cell growth, and induced apoptosis. As a result silibinin blocked the development of intestinal adenomas by 52% in this genetic model (Apc −/+ mice) of early events in colorectal cancer formation. No toxic abnormalities were detected in mice which received silibinin. Modification of the Cdk4 pathway using a natural plant-derived compound such as silibinin may be a useful chemopreventive strategy for colorectal carcinomas

  17. Nutraceuticals for prostate cancer chemoprevention: from molecular mechanisms to clinical application.

    Science.gov (United States)

    Wang, Zhijun; Fan, Jeffery; Liu, Mandy; Yeung, Steven; Chang, Andy; Chow, Moses S S; Pon, Doreen; Huang, Ying

    2013-12-01

    Nutraceutical is a food, or part of a food, used for the prevention and/or treatment of diseases. A number of nutraceuticals serve as candidates for development of prostate cancer chemopreventive agents because of promising epidemiological, preclinical and pilot clinical findings. Their mechanisms of action may involve an ability to target multiple molecular pathways in carcinogenesis without eliciting toxic side effects. This review provides an overview of several nutraceuticals, including green tea polyphenol, omega-3 fatty acids, vitamin D, lycopene, genistein, quercetin, resveratrol and sulforaphane, for the clinical relevance to chemoprevention of prostate cancer. Their mechanisms of action on regulating key processes of carcinogenesis are also discussed. For each of these agents, a brief summary of completed or currently ongoing clinical trials related to the chemopreventive efficacy on prostate cancer is given. Even though a few clinical trials have been conducted, review of these results indicate that further studies are required to confirm the clinical efficacy and safety, and to provide a guidance on how to use nutraceuticals for optimal effect. Future cancer prevention clinical trials for the nutraceuticals should recruit men with an increased risk of prostate cancer.

  18. Colon Cancer Chemoprevention by Sage Tea Drinking: Decreased DNA Damage and Cell Proliferation.

    Science.gov (United States)

    Pedro, Dalila F N; Ramos, Alice A; Lima, Cristovao F; Baltazar, Fatima; Pereira-Wilson, Cristina

    2016-02-01

    Salvia officinalis and some of its isolated compounds have been found to be preventive of DNA damage and increased proliferation in vitro in colon cells. In the present study, we used the azoxymethane model to test effects of S. officinalis on colon cancer prevention in vivo. The results showed that sage treatment reduced the number of ACF formed only if administered before azoxymethane injection, demonstrating that sage tea drinking has a chemopreventive effect on colorectal cancer. A decrease in the proliferation marker Ki67 and in H2 O2 -induced and azoxymethane-induced DNA damage to colonocytes and lymphocytes were found with sage treatment. This confirms in vivo the chemopreventive effects of S. officinalis. Taken together, our results show that sage treatment prevented initiation phases of colon carcinogenesis, an effect due, at least in part, to DNA protection, and reduced proliferation rates of colon epithelial cell that prevent mutations and their fixation through cell replication. These chemopreventive effects of S. officinalis on colon cancer add to the many health benefits attributed to sage and encourage its consumption. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Chemoprevention of skin cancer by the flavonoid fraction of Saraca asoka.

    Science.gov (United States)

    Cibin, T R; Devi, D Gayathri; Abraham, Annie

    2010-05-01

    Saraca asoka (Family - Caesalpiniaceae) has been widely used in the Ayurvedic (traditional Indian) system of medicine especially due to its wound healing property. The present study investigated the chemopreventive property of flavonoids from the flowers of Saraca asoka on 7,12 dimethyl benz(a)anthracene (DMBA) induced skin cancer in mice models. A single topical application of DMBA (100 microg/50 microL of acetone) followed after 2 weeks by three times a week treatment with croton oil (1% in acetone), for 20 weeks resulted in tumor induction. The topical application of the flavonoid fraction of S. asoka (FF S. asoka), 30 min prior to the application of croton oil thrice weekly for 20 weeks, caused a significant reduction in the number of tumors per mouse and the percentage of tumor-bearing mice. Also the latency period for the appearance of the first tumor was delayed by S. asoka pretreatment. In the flavonoid fraction (5 mg and 10 mg/kg body weight) treated animals, the levels of biochemical markers - rhodanese, myeloperoxidase, beta-D-glucuronidase, sialic acid, hexokinase and caspase 3 were significantly restored to near normal levels. These findings suggest the chemopreventive activity of flavonoids from S. asoka on two stage skin carcinogenesis. Histological data also support the chemopreventive potential of S. asoka. Copyright (c) 2009 John Wiley & Sons, Ltd.

  20. Application of response surface methodology (RSM) for optimisation of COD, NH3-N and 2,4-DCP removal from recycled paper wastewater in a pilot-scale granular activated carbon sequencing batch biofilm reactor (GAC-SBBR).

    Science.gov (United States)

    Muhamad, Mohd Hafizuddin; Sheikh Abdullah, Siti Rozaimah; Mohamad, Abu Bakar; Abdul Rahman, Rakmi; Hasan Kadhum, Abdul Amir

    2013-05-30

    In this study, the potential of a pilot-scale granular activated carbon sequencing batch biofilm reactor (GAC-SBBR) for removing chemical oxygen demand (COD), ammoniacal nitrogen (NH3-N) and 2,4-dichlorophenol (2,4-DCP) from recycled paper wastewater was assessed. For this purpose, the response surface methodology (RSM) was employed, using a central composite face-centred design (CCFD), to optimise three of the most important operating variables, i.e., hydraulic retention time (HRT), aeration rate (AR) and influent feed concentration (IFC), in the pilot-scale GAC-SBBR process for recycled paper wastewater treatment. Quadratic models were developed for the response variables, i.e., COD, NH3-N and 2,4-DCP removal, based on the high value (>0.9) of the coefficient of determination (R(2)) obtained from the analysis of variance (ANOVA). The optimal conditions were established at 750 mg COD/L IFC, 3.2 m(3)/min AR and 1 day HRT, corresponding to predicted COD, NH3-N and 2,4-DCP removal percentages of 94.8, 100 and 80.9%, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Cryptographic Protocols:

    DEFF Research Database (Denmark)

    Geisler, Martin Joakim Bittel

    cryptography was thus concerned with message confidentiality and integrity. Modern cryptography cover a much wider range of subjects including the area of secure multiparty computation, which will be the main topic of this dissertation. Our first contribution is a new protocol for secure comparison, presented...... implemented the comparison protocol in Java and benchmarks show that is it highly competitive and practical. The biggest contribution of this dissertation is a general framework for secure multiparty computation. Instead of making new ad hoc implementations for each protocol, we want a single and extensible...... in Chapter 2. Comparisons play a key role in many systems such as online auctions and benchmarks — it is not unreasonable to say that when parties come together for a multiparty computation, it is because they want to make decisions that depend on private information. Decisions depend on comparisons. We have...

  2. Phase 0 Clinical Chemoprevention Trial of the AKT Inhibitor SR13668

    Science.gov (United States)

    Reid, Joel M.; Walden, Chad; Qin, Rui; Allen Ziegler, Katie L.; Haslam, John L.; Rajewski, Roger A.; Warndahl, Roger; Fitting, Cindy L.; Boring, Daniel; Szabo, Eva; Crowell, James; Perloff, Marjorie; Jong, Ling; Mandrekar, Sumithra J.; Ames, Matthew M.; Limburg, Paul J.

    2011-01-01

    Purpose SR13668, an orally active AKT pathway inhibitor, has demonstrated cancer chemopreventive potential in preclinical studies. To accelerate the clinical development of this promising agent, we designed and conducted the first-ever phase 0 chemoprevention trial to evaluate and compare the effects of food and formulation on SR13668 bioavailability. Patients and Methods Healthy adult volunteers were randomly assigned to receive a single, 38 mg oral dose of SR13668 in one of five different formulations, with or without food. Based on existing animal data, SR13668 in a PEG400/Labrasol® oral solution was defined as the reference formulation. Blood samples were obtained pre- and post-agent administration for pharmacokinetic analyses. Area under the plasma concentration-time curve (AUC0-∞) was defined as the primary endpoint. Data were analyzed and compared using established statistical methods for phase 0 trials with a limited sample size. Results Participants (N=20) were rapidly accrued over a 5-month period. Complete pharmacokinetic data were available for 18 randomized participants. AUC0-∞ values were highest in the fed state (range = 122–439 ng/mL × hours) and were statistically significantly different across formulations (p = 0.007), with Solutol® HS15 providing the highest bioavailability. SR13668 time to peak plasma concentration (3 hours; range, 2 – 6 hours) and half-life were (11.2 ± 3.1 hours) were not formulation dependent. Conclusions Using a novel, highly efficient study design, we rapidly identified a lead formulation of SR13668 for further clinical testing. Our findings support application of the phase 0 trial paradigm to accelerate chemoprevention agent development. PMID:21372034

  3. PPARγ Ligand as a Promising Candidate for Colorectal Cancer Chemoprevention: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Hirokazu Takahashi

    2010-01-01

    Full Text Available Activating synthetic ligands for peroxisome proliferator-activated receptor gamma (PPARγ, such as pioglitazone, are commonly used to treat persons with diabetes mellitus with improvement of insulin resistance. Several reports have clearly demonstrated that PPARγ ligands could inhibit colorectal cancer cell growth and induce apoptosis. Meanwhile, aberrant crypt foci (ACF have come to be established as a biomarker of the risk of CRC in azoxymethane-treated mice and rats. In humans, ACF can be detected using magnifying colonoscopy. Previously, CRC and adenoma were used as a target for chemopreventive agents, but it needs a long time to evaluate, however, ACF can be a surrogate marker of CRC even for a brief period. In this clinical study, we investigated the chemopreventive effect of pioglitazone on the development of human ACF as a surrogate marker of CRC. Twenty-nine patients were divided into two groups, 20 were in the endoscopically normal control group and 9 were in the pioglitazone (15 mg/day group, and ACF and adenoma were examined before and after 1-month treatment. The number of ACF was significantly decreased (5.8±1.1 to 3.3±2.3 after 1 month of pioglitazone treatment, however, there was no significant change in the number of crypts/ACF or in the number and size of adenomas. Pioglitazone may have a clinical application as a cancer-preventive drug. This investigation is just a pilot study, therefore, further clinical studies are needed to show that the PPARγ ligand may be a promising candidate as a chemopreventive agent for colorectal carcinogenesis.

  4. Kaiware Daikon (Raphanus sativus L.) extract: a naturally multipotent chemopreventive agent.

    Science.gov (United States)

    Barillari, Jessica; Iori, Renato; Papi, Alessio; Orlandi, Marina; Bartolini, Giovanna; Gabbanini, Simone; Pedulli, Gian Franco; Valgimigli, Luca

    2008-09-10

    Brassica vegetables are attracting major attention as healthy foods because of their content of glucosinolates (GLs) that release the corresponding isothiocyanates (ITCs) upon myrosinase hydrolysis. A number of studies have so far documented the chemopreventive properties of some ITCs. On the other hand, single nutrients detached from the food itself risk being somewhat "reductive", since plants contain several classes of compounds endowed with a polyhedral mechanism of action. Our recent finding that 4-methylthio-3-butenyl isothiocyanate (GRH-ITC) and 4-methylsulfinyl-3-butenyl isothiocyanate (GRE-ITC), released by the GLs purified from Japanese (Kaiware) Daikon (Raphanus sativus L.) seeds and sprouts, had selective cytotoxic/apoptotic activity on three human colon carcinoma cell lines prompted further research on the potential chemopreventive role of a standardized Kaiware Daikon extract (KDE), containing 10.5% w/w GRH and 3.8% w/w GRE, compared to its isolated components. KDE administered in combination with myrosinase at doses corresponding to 50 microM GRH-ITC plus 15 microM GRE-ITC (50 microM KDE-ITC) to three human cancer cell lines (LoVo, HCT-116 and HT-29) significantly reduced cell growth by 94-96% of control in six days (p oxygen consumption rate), as monitored by Clark-type microelectrode oxygen-uptake kinetics, and induced very fast quenching of DPPH. radical in methanol with t(1/2) (s) = (1.47 +/- 0.25) x 10(-2)/[KDE; (g/L)], measured by stopped-flow UV-vis kinetics at 298 K. The potential chemopreventive role of KDE is discussed.

  5. Immunochemical protocols

    National Research Council Canada - National Science Library

    Pound, John D

    1998-01-01

    ... easy and important refinements often are not published. This much anticipated 2nd edition of Immunochemzcal Protocols therefore aims to provide a user-friendly up-to-date handbook of reliable techniques selected to suit the needs of molecular biologists. It covers the full breadth of the relevant established immunochemical methods, from protein blotting and immunoa...

  6. 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.

  7. Chemopreventive effects of embelin and curcumin against N-nitrosodiethylamine/phenobarbital-induced hepatocarcinogenesis in Wistar rats.

    Science.gov (United States)

    Sreepriya, M; Bali, Geetha

    2005-09-01

    The effects of embelin (50 mg/kg/day), a benzoquinone derivative of Embelia ribes, and the effects of curcumin (100 mg/kg/day), the active principle of Curcuma longa, against N-nitrosodiethylamine (DENA)-initiated and phenobarbital (PB)-promoted hepatocarcinogenesis were studied in Wistar rats. They were able to prevent the induction of hepatic hyper plastic nodules, body weight loss, increase in the levels of hepatic diagnostic markers, and hypoproteinemia induced by DENA/PB treatment. Hence, results of our study suggest the possible chemopreventive effects of embelin (EMB) and curcumin (CUR) against DENA/PB-induced hepatocarcinogenesis in Wistar rats.

  8. Cancer Chemoprevention by Resveratrol: The p53 Tumor Suppressor Protein as a Promising Molecular Target

    Directory of Open Access Journals (Sweden)

    Danielly C. Ferraz da Costa

    2017-06-01

    Full Text Available Increasing epidemiological and experimental evidence has demonstrated an inverse relationship between the consumption of plant foods and the incidence of chronic diseases, including cancer. Microcomponents that are naturally present in such foods, especially polyphenols, are responsible for the benefits to human health. Resveratrol is a diet-derived cancer chemopreventive agent with high therapeutic potential, as demonstrated by different authors. The aim of this review is to collect and present recent evidence from the literature regarding resveratrol and its effects on cancer prevention, molecular signaling (especially regarding the involvement of p53 protein, and therapeutic perspectives with an emphasis on clinical trial results to date.

  9. MRI to assess chemoprevention in transgenic adenocarcinoma of mouse prostate (TRAMP)

    International Nuclear Information System (INIS)

    Arbab, Ali S; Shankar, Adarsh; Varma, Nadimpalli RS; Deeb, Dorrah; Gao, Xiaohua; Iskander, ASM; Janic, Branislava; Ali, Meser M; Gautam, Subhash C

    2011-01-01

    The current method to determine the efficacy of chemoprevention in TRAMP mouse model of carcinoma of prostate (CaP) is by extracting and weighing the prostate at different time points or by immunohistochemistry analysis. Non-invasive determination of volumes of prostate glands and seminal vesicles before, during and after treatment would be valuable in investigating the efficacy of newer chemopreventive agents in CaP. The purpose of this study was to determine whether in vivo magnetic resonance imaging (MRI) using a 3 tesla clinical MRI system can be used to follow the effect of chemoprevention in TRAMP model of mouse CaP. Mice were randomized into control and treated groups. The animals in treated group received 10 µmol/kg of CDDO, 5 days a week for 20 weeks. Animals underwent in vivo MRI of prostate gland and seminal vesicles by a clinical 3 Tesla MRI system just before (at 5 weeks), during and at the end of treatment, at 25 weeks. T1-weighted and fat saturation (FATSAT) multiecho fast spin echo T2- weighted images (T2WI) were acquired. Volume of the prostate glands and seminal vesicles was determined from MR images. T2 signal intensity changes in the seminal vesicles were determined by subtracting higher echo time (TE) from lower TE T2WI. Following treatments all animals were sacrificed, prostate and seminal vesicles collected, and the tissues prepared for histological staining. All data were expressed as mean ± 1 standard deviation. Two-way or multivariate analysis of variance followed by post-hoc test was applied to determine the significant differences. A p-value of <0.05 was considered significant. Histological analysis indicated tumor in 100% of control mice, whereas 10% of the treated mice showed tumor in prostate gland. Both MRI and measured prostate weights showed higher volume/weight in control mouse group. MRI showed significantly higher volume of seminal vesicles in control animals and T2 signal intensity changes in seminal vesicles of control mice

  10. Chemopreventive Activities of Sulforaphane and Its Metabolites in Human Hepatoma HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Peng Liu

    2018-05-01

    Full Text Available Sulforaphane (SFN exhibits chemopreventive effects through various mechanisms. However, few studies have focused on the bioactivities of its metabolites. Here, three metabolites derived from SFN were studied, known as sulforaphane glutathione, sulforaphane cysteine and sulforaphane-N-acetylcysteine. Their effects on cell viability, DNA damage, tumorigenicity, cell migration and adhesion were measured in human hepatoma HepG2 cells, and their anti-angiogenetic effects were determined in a 3D co-culture model of human umbilical vein endothelial cells (HUVECs and pericytes. Results indicated that these metabolites at high doses decreased cancer cell viability, induced DNA damage and inhibited motility, and impaired endothelial cell migration and tube formation. Additionally, pre-treatment with low doses of SFN metabolites protected against H2O2 challenge. The activation of the nuclear factor E2-related factor 2 (Nrf2-antioxidant response element (ARE pathway and the induction of intracellular glutathione (GSH played an important role in the cytoprotective effects of SFN metabolites. In conclusion, SFN metabolites exhibited similar cytotoxic and cytoprotective effects to SFN, which proves the necessity to study the mechanisms of action of not only SFN but also of its metabolites. Based on the different tissue distribution profiles of these metabolites, the most relevant chemical forms can be selected for targeted chemoprevention.

  11. Clinical cancer chemoprevention: From the hepatitis B virus (HBV vaccine to the human papillomavirus (HPV vaccine

    Directory of Open Access Journals (Sweden)

    Horng-Jyh Tsai

    2015-04-01

    Full Text Available Approximately 2 million new cancer cases are attributed to infectious agents each year worldwide. Vaccines for the hepatitis B virus (HBV, a risk factor of hepatocellular cancer, and human papillomavirus (HPV, a risk factor of cervical cancer, are considered major successes in clinical chemoprevention of cancer. In Taiwan, the first evidence of cancer prevention through vaccinations was provided by HBV vaccination data in infants. The Taiwanese HBV vaccination program has since become a model immunization schedule for newborns worldwide. Persistent infection with high-risk HPV is generally accepted as prerequisite for cervical cancer diagnosis; however, cervical cancer is a rare complication of HPV infections. This is due to the fact that such infections tend to be transient. The safety and efficacy of both available HPV quadrivalent vaccine and bivalent vaccine are not in doubt at the present time. Until a human cytomegalovirus (CMV vaccine becomes available, simple hygienic practices, such as hand washing, can prevent CMV infection both before and during pregnancy. Each country should establish her official guidelines regarding which vaccines should be used to treat various conditions, the target population (i.e., universal or limited to a selected population, and the immunization schedules. After a vaccine is recommended, decisions regarding reimbursement by the public health care fund are evaluated. The guidelines become part of the immunization schedule, which is updated annually and published in the official bulletin. In conclusion, both HBV and HPV vaccines are considered major successes in the chemoprevention of cancer.

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

    Directory of Open Access Journals (Sweden)

    Sazal Patyar

    2017-01-01

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

  13. 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.

  14. Chemopreventive effects of in vitro digested and fermented bread in human colon cells.

    Science.gov (United States)

    Schlörmann, Wiebke; Hiller, Beate; Jahns, Franziska; Zöger, Romy; Hennemeier, Isabell; Wilhelm, Anne; Lindhauer, Meinolf G; Glei, Michael

    2012-10-01

    Bread as a staple food product represents an important source for dietary fibre consumption. Effects of wheat bread, wholemeal wheat bread and wholemeal rye bread on mechanisms which could have impact on chemoprevention were analysed in colon cells after in vitro fermentation. Effects of fermented bread samples on gene expression, glutathione S-transferase activity and glutathione content, differentiation, growth and apoptosis were investigated using the human colon adenoma cell line LT97. Additionally, apoptosis was studied in normal and tumour colon tissue by determination of caspase activities. The expression of 76 genes (biotransformation, differentiation, apoptosis) was significantly upregulated (1.5-fold) in LT97 cells. The fermented bread samples were able to significantly increase glutathione S-transferase activity (1.8-fold) and glutathione content (1.4-fold) of the cells. Alkaline phosphatase activity as a marker of differentiation was also significantly enhanced (1.7-fold). The fermented bread samples significantly inhibited LT97 cell growth and increased the level of apoptotic cells (1.8-fold). Only marginal effects on apoptosis in tumour compared to normal tissue were observed. This is the first study which presents chemopreventive effects of different breads after in vitro fermentation. In spite of differences in composition, the results were comparable between the bread types. Nevertheless, they indicate a potential involvement of this staple food product regarding the prevention of colon cancer.

  15. Curcumin and Other Polyphenolic Compounds in Head and Neck Cancer Chemoprevention

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    Philipp Baumeister

    2012-01-01

    Full Text Available Despite clear results of observational studies linking a diet rich in fruits and vegetables to a decreased cancer risk, large interventional trials evaluating the impact of dietary micronutrient supplementation, mostly vitamins, could not show any beneficial effects. Today it has become clear that a single micronutrient, given in supernutritional doses, cannot match cancer preventive effects of whole fruits and vegetables. In this regard polyphenols came into focus, not only because of their antioxidant potential but also because of their ability to interact with molecular targets within the cells. Because polyphenols occur in many foods and beverages in high concentration and evidence for their anticancer activity is best for tissues they can come into direct contact with, field cancerization predestines upper aerodigestive tract epithelium for cancer chemoprevention by polyphenols. In this paper, we summarize cancer chemopreventive attempts with emphasis on head and neck carcinogenesis and discuss some methodological issues. We present data regarding antimutagenic effects of curcumin and epigallocatechin-3-gallate in human oropharyngeal mucosa cultures exposed to cigarette smoke condensate.

  16. Drug delivery strategies for chemoprevention of UVB-induced skin cancer: A review.

    Science.gov (United States)

    Bagde, Arvind; Mondal, Arindam; Singh, Mandip

    2018-01-01

    Annually, more skin cancer cases are diagnosed than the collective incidence of the colon, lung, breast, and prostate cancer. Persistent contact with sunlight is a primary cause for all the skin malignancies. UVB radiation induces reactive oxygen species (ROS) production in the skin which eventually leads to DNA damage and mutation. Various delivery approaches for the skin cancer treatment/prevention have been evolving and are directed toward improvements in terms of delivery modes, therapeutic agents, and site-specificity of therapeutics delivery. The effective chemoprevention activity achieved is based on the efficiency of the delivery system used and the amount of the therapeutic molecule deposited in the skin. In this article, we have discussed different studies performed specifically for the chemoprevention of UVB-induced skin cancer. Ultra-flexible nanocarriers, transethosomes nanocarriers, silica nanoparticles, silver nanoparticles, nanocapsule suspensions, microemulsion, nanoemulsion, and polymeric nanoparticles which have been used so far to deliver the desired drug molecule for preventing the UVB-induced skin cancer. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. 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.

  18. Curcumin and metformin-mediated chemoprevention of oral cancer is associated with inhibition of cancer stem cells.

    Science.gov (United States)

    Siddappa, Gangotri; Kulsum, Safeena; Ravindra, Doddathimmasandra Ramanjanappa; Kumar, Vinay V; Raju, Nalini; Raghavan, Nisheena; Sudheendra, Holalugunda Vittalamurthy; Sharma, Anupam; Sunny, Sumsum P; Jacob, Tina; Kuruvilla, Binu T; Benny, Merina; Antony, Benny; Seshadri, Mukund; Lakshminarayan, Padma; Hicks, Wesley; Suresh, Amritha; Kuriakose, Moni A

    2017-11-01

    Effective chemoprevention is critical for improving outcomes of oral cancer. As single agents, curcumin and metformin are reported to exhibit chemopreventive properties, in vitro as well as in patients with oral cancer. In this study, the chemopreventive efficacy of this drug combination was tested in a 4-nitro quinoline-1-oxide (4NQO) induced mice oral carcinogenesis model. Molecular analysis revealed a cancer stem cell (CSC)-driven oral carcinogenic progression in this model, wherein a progressive increase in the expression of CSC-specific markers (CD44 and CD133) was observed from 8th to 25th week, at transcript (40-100-fold) and protein levels (P ≤ 0.0001). Chemopreventive treatment of the animals at 17th week with curcumin and metformin indicated that the combination regimen decreased tumor volume when compared to the control arm (0.69+0.03 vs 6.66+2.4 mm 3 ; P = 0.04) and improved overall survival of the animals (P = 0.03). Assessment of the molecular status showed an overall downregulation of CSC markers in the treatment arms as compared to the untreated control. Further, in vitro assessment of the treatment on the primary cells generated from progressive stages of 4NQO-induced mice tissue showed a concordant and consistent downregulation of the CSC markers following combination treatment (P oral squamous cell carcinoma through a CSC-associated mechanism. © 2017 Wiley Periodicals, Inc.

  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

    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.

  20. Chemopreventive Activity of Honokiol against 7, 12 - Dimethylbenz[a]anthracene-Induced Mammary Cancer in Female Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Zhenyu Wang

    2017-05-01

    Full Text Available Breast cancer is a predominant cause of death in women across the globe. Chemoprevention by using natural, dietary or synthetic products has been appearing to be a fascinating approach to combat the growing burden of breast cancer. In the current study, we intended to explore the mechanisms of chemopreventive action of honokiol against 7, 12 - dimethylbenz[a]anthracene (DMBA-induced mammary cancer in female Sprague Dawlely (SD rats. We induced mammary cancer in SD rats by administering single dose of DMBA (80 mg/kg through intra gastric route. Chemopreventive effects of honokiol (80 mg/kg, i.p. were confirmed from its ameliorating effect on the DMBA-induced anomalies such as liver marker enzymes, Phases I and II metabolizing enzymes and oxidative stress markers. Further, honokiol reversed the DMBA-induced abnormalities in inflammatory cytokines levels and serum tumor markers. Additionally, histopathological examination of mammary tissue and protein expression analysis of NF-κB revealed that honokiol is effective against DMBA-induced mammary cancer. In summary, the results of our study support the chemopreventive feature of honokiol in mammary cancer.

  1. 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)....

  2. 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.

  3. 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.

  4. Study protocol

    DEFF Research Database (Denmark)

    Smith, Benjamin E; Hendrick, Paul; Bateman, Marcus

    2017-01-01

    avoidance behaviours, catastrophising, self-efficacy, sport and leisure activity participation, and general quality of life. Follow-up will be 3 and 6 months. The analysis will focus on descriptive statistics and confidence intervals. The qualitative components will follow a thematic analysis approach....... DISCUSSION: This study will evaluate the feasibility of running a definitive large-scale trial on patients with patellofemoral pain, within the NHS in the UK. We will identify strengths and weaknesses of the proposed protocol and the utility and characteristics of the outcome measures. The results from...... this study will inform the design of a multicentre trial. TRIAL REGISTRATION: ISRCTN35272486....

  5. Reverse screening methods to search for the protein targets of chemopreventive compounds

    Science.gov (United States)

    Huang, Hongbin; Zhang, Guigui; Zhou, Yuquan; Lin, Chenru; Chen, Suling; Lin, Yutong; Mai, Shangkang; Huang, Zunnan

    2018-05-01

    This article is a systematic review of reverse screening methods used to search for the protein targets of chemopreventive compounds or drugs. Typical chemopreventive compounds include components of traditional Chinese medicine, natural compounds and Food and Drug Administration (FDA)-approved drugs. Such compounds are somewhat selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to conventional virtual screening, which identifies the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or unintended targets of a given compound from a large number of receptors by examining their known ligands or crystal structures. This method, also known as in silico or computational target fishing, is highly valuable for discovering the target receptors of query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. Reverse screening can be divided into three major groups: shape screening, pharmacophore screening and reverse docking. Several large software packages, such as Schrödinger and Discovery Studio; typical software/network services such as ChemMapper, PharmMapper, idTarget and INVDOCK; and practical databases of known target ligands and receptor crystal structures, such as ChEMBL, BindingDB and the Protein Data Bank (PDB), are available for use in these computational methods. Different programs, online services and databases have different applications and constraints. Here, we conducted a systematic analysis and multilevel classification of the computational programs, online services and compound libraries available for shape screening, pharmacophore screening and reverse docking to enable non-specialist users to quickly learn and

  6. Evaluation of chemopreventive potential of Strobilanthes crispus against colon cancer formation in vitro and in vivo.

    Science.gov (United States)

    Al-Henhena, Nawal; Khalifa, Shaden A M; Ying, Rozaida Poh Yuen; Ismail, Salmah; Hamadi, Riad; Shawter, Abdrabu N; Idris, Azila Mohd; Azizan, Ainnul; Al-Wajeeh, Nahla Saeed; Abdulla, Mahmood Ameen; El-Seedi, Hesham R

    2015-11-25

    With cancer being one of the major causes of death around the world, studies are ongoing to find new chemotherapeutic leads. There are common mechanisms for colorectal cancer (CRC) formation. Several are connected with oxidative stress-induced cell apoptosis and others are related to imbalanced homeostasis or intake of drugs/toxins. Plants that have been used for decades in folk and traditional medicine have been accepted as one of the commonest sources of discovered natural agents of cancer chemotherapy and chemoprevention. The aim was to study the antioxidant and chemopreventive effects of Strobilanthes crispus on colorectal cancer formation. Five groups of rats were injected subcutaneously with AOM, 15 mg/kg body weight, each once weekly for 2 weeks. The cancer group was continued on 10 % Tween-20 feeding for 8 weeks. The standard drug group was continued on 35 mg/kg 5-fluorouracil intraperitoneal injection twice a week for 8 weeks, and the experimental groups were continued on 250 and 500 mg/kg S. crispus extract oral feeding for 8 weeks, respectively. The normal group was injected subcutaneously with normal saline once a week for 2 weeks, followed by oral administration of 10 % Tween-20 for 8 weeks. All the rats were sacrificed after 10 weeks. The colons were evaluated grossly and histopathologically for aberrant crypt foci (ACF). Gene expression was performed for Bax, Bcl2, Defa24, Slc24a3, and APC genes by real-time PCR. S. crispus and its fractions were evaluated for their chemopreventive effects against human colorectal adenocarcinoma cell line HT29 and cytotoxicity for normal human colon epithelial cell line CCD 841, and the active fraction was assessed for its components. We observed significant decrease in total colonic ACF formation, malonaldehyde (MDA) and lactate dehydrogenase (LDH), increase in superoxide dismutase (SOD), up-regulation of APC, Bax and Slc24a3, and down-regulation of Defa24 and Bcl-2 in rats treated with Strobilanthes

  7. Beyond protocols

    DEFF Research Database (Denmark)

    Vanderhoeven, Sonia; Branquart, Etienne; Casaer, Jim

    2017-01-01

    Risk assessment tools for listing invasive alien species need to incorporate all available evidence and expertise. Beyond the wealth of protocols developed to date, we argue that the current way of performing risk analysis has several shortcomings. In particular, lack of data on ecological impact...... information on risk and the exploration of improved methods for decision making on biodiversity management. This is crucial for efficient conservation resource allocation and uptake by stakeholders and the public......., transparency and repeatability of assessments as well as the incorporation of uncertainty should all be explicitly considered. We recommend improved quality control of risk assessments through formalized peer review with clear feedback between assessors and reviewers. Alternatively, a consensus building...

  8. 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. 

  9. 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.

  10. Fresh garlic extract inhibits Staphylococcus aureus biofilm formation under chemopreventive and chemotherapeutic conditions

    Directory of Open Access Journals (Sweden)

    Panan Ratthawongjirakul

    2016-08-01

    Full Text Available Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA are the leading aetiological pathogens of nosocomial infections worldwide. These bacteria form biofilms on both biotic and abiotic surfaces causing biofilm-associated infections. Within the biofilm, these bacteria might develop persistent and antimicrobial resistant characteristics resulting in chronic infections and treatment failures. Garlic exhibits broad pharmaceutical properties and inhibitory activities against S. aureus. We investigated the effects of aqueous fresh garlic extract on biofilm formation in S. aureus ATCC25923 and MRSA strains under chemopreventive and chemotherapeutic conditions. The viable bacteria and biofilm levels were quantified through colony count and crystal violet staining, respectively. The use of fresh garlic extract under both conditions significantly inhibited biofilm formation in S. aureus strains ATCC25923 and MRSA. Garlic could be developed as either a prophylactic or therapeutic agent to manage S. aureus biofilm-associated infections.

  11. Cancer Chemoprevention Effects of Ginger and its Active Constituents: Potential for New Drug Discovery.

    Science.gov (United States)

    Wang, Chong-Zhi; Qi, Lian-Wen; Yuan, Chun-Su

    2015-01-01

    Ginger is a commonly used spice and herbal medicine worldwide. Besides its extensive use as a condiment, ginger has been used in traditional Chinese medicine for the management of various medical conditions. In recent years, ginger has received wide attention due to its observed antiemetic and anticancer activities. This paper reviews the potential role of ginger and its active constituents in cancer chemoprevention. The phytochemistry, bioactivity, and molecular targets of ginger constituents, especially 6-shogaol, are discussed. The content of 6-shogaol is very low in fresh ginger, but significantly higher after steaming. With reported anti-cancer activities, 6-shogaol can be served as a lead compound for new drug discovery. The lead compound derivative synthesis, bioactivity evaluation, and computational docking provide a promising opportunity to identify novel anticancer compounds originating from ginger.

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

    Directory of Open Access Journals (Sweden)

    Carina Michl

    Full Text Available 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.

  13. Chemopreventive Effect of Aster glehni on Inflammation-Induced Colorectal Carcinogenesis in Mice

    Directory of Open Access Journals (Sweden)

    Kyung-Sook Chung

    2018-02-01

    Full Text Available Although Aster glehni is a common dietary herb that has various bioactivities, including anti-diabetic, anti-adipogenic, and anti-inflammatory effects, A. glehni has not been studied in colon cancer. Therefore, we hypothesized the chemopreventive effects of an ethanol extract of A. glehni (AG on azoxymethane/dextran sulfate sodium (AOM/DSS-induced colitis-associated cancer (CAC in mice. In this study, we found that treatment with AG significantly attenuated the AOM/DSS-induced enlargement of the spleen and shortening of the colon. In addition, colonic tumor formation, colonic damage, and increased muscle thickness were significantly reduced in AOM/DSS-induced mice fed AG. Treatment with AG also reduced intestinal interleukin (IL-1β, IL-6, and tumor necrosis factor (TNF-α production and decreased inducible nitric oxide synthase (iNOS and cyclooxygenase (COX-2 protein expression in mice with AOM/DSS-induced CAC. Furthermore, AG reduced nuclear factor (NF-κB activation via phosphorylation and degradation of inhibitor of kappa Bα (IκBα, leading to inhibition of NF-κB p65 nuclear translocation. It also downregulated the expression of NF-κB-related proteins, including the B-cell lymphoma 2 (Bcl-2 family and inhibitors of apoptosis proteins (IAPs, in mice with AOM/DSS-induced CAC. Taken together, these findings suggest that the treatment with AG inhibited colitis-associated colon carcinogenesis in mice, and this chemopreventive effect was strongly mediated by suppression of the NF-κB signaling pathway, indicating that AG could be a promising protective agent against CAC.

  14. Chemopreventive Effects of Magnesium Chloride Supplementation on Hormone Independent Prostate Cancer Cells

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    Elsa Quiroz

    2016-01-01

    Full Text Available Background: Lifestyle significantly impacts the risk factors associated with prostate cancer, out of which diet appears to be the most influential. An emerging chemopreventive approach, which involves the adequate intake of dietary constituents, has shown great potential in preventing the occurrence or progression of cancer. Magnesium is known to be an essential cofactor for more than 300 enzymatic processes, and is responsible for the regulation of various cellular reactions in the body. A plethora of studies have shown evidence that changes in the intracellular levels of magnesium could contribute to cell proliferation and apoptosis in some normal and malignant cells. The aim of the study was to investigate the effects of magnesium chloride (MgCl2 in DU-145 prostate cancer cells. Methodology: Cultured DU-145 cells were subjected to graded concentrations or doses (50-500 µM of MgCl2 for 48 hours. The cell viability was assessed using MTT and Resazurin reduction assays. NBT assay was also used to assess the treatment-induced intracellular ROS levels. Acridine Orange/Ethidium Bromide (AcrO/EtBr and Rh123/EtBr fluorescent stains were used to assess the cell death type and mitochondrial membrane potential (Δψm respectively. Results: The results revealed a dose-dependent decrease (P < 0.05 in cell viability in treated DU-145 cells after 48 hours. The NBT assay also revealed a dose dependent biphasic response (P < 0.05 in intracellular levels of ROS. There was a drop (P < 0.05 in ROS levels in all groups except at 100 µM, where ROS level was higher than the control. Apoptosis was the primary mode of cell death as observed in the fluorescence analysis. Conclusion: Our finding suggests that MgCl2 may be potentially chemopreventive for prostate cancer. This justifies further studies into its mechanism of action in DU-145 and other prostate cancer cell types.

  15. Occult progression by Apc-deficient intestinal crypts as a target for chemoprevention

    Science.gov (United States)

    Liskay, R.Michael

    2014-01-01

    Although Apc mutation is widely considered an initiating event in colorectal cancer, little is known about the earliest stages of tumorigenesis following sporadic Apc loss. Therefore, we have utilized a novel mouse model that facilitates the sporadic inactivation of Apc via frameshift reversion of Cre in single, isolated cells and subsequently tracks the fates of Apc-deficient intestinal cells. Our results suggest that consistent with Apc being a ‘gatekeeper’, loss of Apc early in life during intestinal growth leads to adenomas or increased crypt fission, manifested by fields of mutant but otherwise normal-appearing crypts. In contrast, Apc loss occurring later in life has minimal consequences, with mutant crypts being less prone to either increased crypt fission or adenoma formation. Using the stem cell-specific Lgr5-CreER mouse, we generated different sized fields of Apc-deficient crypts via independent recombination events and found that field size correlates with progression to adenoma. To evaluate this early stage prior to adenoma formation as a therapeutic target, we examined the chemopreventive effects of sulindac on Apc-deficient occult crypt fission. We found that sulindac treatment started early in life inhibits the morphologically occult spread of Apc-deficient crypts and thus reduces adenoma numbers. Taken together these results suggest that: (i) earlier Apc loss promotes increased crypt fission, (ii) a field of Apc-deficient crypts, which can form via occult crypt fission or independent neighboring events, is an important intermediate between loss of Apc and adenoma formation and (iii) normal-appearing Apc-deficient crypts are potential unappreciated targets for cancer screening and chemoprevention. PMID:23996931

  16. 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; 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.

  17. 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

  18. Selenium Supranutrition: Are the Potential Benefits of Chemoprevention Outweighed by the Promotion of Diabetes and Insulin Resistance?

    Science.gov (United States)

    Rocourt, Caroline R. B.; Cheng, Wen-Hsing

    2013-01-01

    Selenium was considered a toxin until 1957, when this mineral was shown to be essential in the prevention of necrotic liver damage in rats. The hypothesis of selenium chemoprevention is principally formulated by the observations that cancer incidence is inversely associated with selenium status. However, recent clinical and epidemiological studies demonstrate a role for some selenoproteins in exacerbating or promoting other disease states, specifically type 2 diabetes, although other data support a role of selenium in stimulating insulin sensitivity. Therefore, it is clear that our understanding in the role of selenium in glucose metabolism and chemoprevention is inadequate and incomplete. Research exploring the role of selenium in individual healthcare is of upmost importance and possibly will help explain how selenium is a double-edged sword in the pathologies of chronic diseases. PMID:23603996

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

    Science.gov (United States)

    Albert-Baskar, Arul; Ignacimuthu, Savarimuthu

    2010-07-01

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

  20. In vitro chemopreventive properties of peptides released from quinoa (Chenopodium quinoa Willd.) protein under simulated gastrointestinal digestion.

    Science.gov (United States)

    Vilcacundo, Rubén; Miralles, Beatriz; Carrillo, Wilman; Hernández-Ledesma, Blanca

    2018-03-01

    Because of the continuous and direct interaction between the digestive tract and foods, dietary compounds represent an interesting source of chemopreventive agents for gastrointestinal health. In this study, the influence of a standardized static in vitro gastrointestinal digestion model on the release of peptides with chemopreventive potential from quinoa protein was investigated. Gastroduodenal digests and fractions collected by ultrafiltration were evaluated for their in plate oxygen radical absorbance capacity and in vitro colon cancer cell viability inhibitory activity. Highest effects were observed in the digests obtained during the intestinal phase, with fraction containing peptides 5kDa showing the greatest anti-cancer effects. Seventeen potential bioactive peptides derived from quinoa proteins have been identified. These proteins might be utilized as new ingredients in the development of functional foods or nutraceuticals with the aim of reducing oxidative stress-associated diseases, including cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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    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.

  2. Salicylic acid metabolites and derivatives inhibit CDK activity: Novel insights into aspirin's chemopreventive effects against colorectal cancer

    Science.gov (United States)

    Dachineni, Rakesh; Kumar, D. Ramesh; Callegari, Eduardo; Kesharwani, Siddharth S.; Sankaranarayanan, Ranjini; Seefeldt, Teresa; Tummala, Hemachand; Bhat, G. Jayarama

    2017-01-01

    Aspirin's potential as a drug continues to be evaluated for the prevention of colorectal cancer (CRC). Although multiple targets for aspirin and its metabolite, salicylic acid, have been identified, no unifying mechanism has been proposed to clearly explain its chemopreventive effects. Our goal here was to investigate the ability of salicylic acid metabolites, known to be generated through cytochrome P450 (CYP450) enzymes, and its derivatives as cyclin dependent kinase (CDK) inhibitors to gain new insights into aspirin's chemopreventive actions. Using in vitro kinase assays, for the first time, we demonstrate that salicylic acid metabolites, 2,3-dihydroxy-benzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA), as well as derivatives 2,4-dihydroxybenzoic acid (2,4-DHBA), 2,6-dihydroxybenzoic acid (2,6-DHBA), inhibited CDK1 enzyme activity. 2,3-DHBA and 2,6-DHBA did not inhibit CDK2 and 4; however, both inhibited CDK-6 activity. Interestingly, another derivative, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) was highly effective in inhibiting CDK1, 2, 4 and 6 activity. Molecular docking studies showed that these compounds potentially interact with CDK1. Immunoblotting experiments showed that aspirin acetylated CDK1, and pre-incubation with salicylic acid and its derivatives prevented aspirin-mediated CDK1 acetylation, which supported the data obtained from molecular docking studies. We suggest that intracellularly generated salicylic acid metabolites through CYP450 enzymes within the colonic epithelial cells, or the salicylic acid metabolites generated by gut microflora may significantly contribute to the preferential chemopreventive effect of aspirin against CRC through inhibition of CDKs. This novel hypothesis and mechanism of action in aspirin's chemopreventive effects opens a new area for future research. In addition, structural modification to salicylic acid derivatives may prove useful in the development of novel CDK inhibitors in cancer prevention and

  3. Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic.

    Science.gov (United States)

    Meyskens, Frank L; Curt, Gregory A; Brenner, Dean E; Gordon, Gary; Herberman, Ronald B; Finn, Olivera; Kelloff, Gary J; Khleif, Samir N; Sigman, Caroline C; Szabo, Eva

    2011-03-01

    This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high(er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs.

  4. Antimutagenic constituents of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) with potential cancer chemopreventive activity.

    Science.gov (United States)

    Chen, Huang-Hui; Chiang, Wenchang; Chang, Jang-Yang; Chien, Ya-Lin; Lee, Ching-Kuo; Liu, Ko-Jiunn; Cheng, Yen-Ting; Chen, Ting-Fang; Kuo, Yueh-Hsiung; Kuo, Ching-Chuan

    2011-06-22

    Adlay has long been used in traditional Chinese medicine and as a nourishing food. The acetone extract of adlay hull had previously been demonstrated to possess potent antimutagenic activity. The aims of this study were to identify the antimutagenic constituents from adlay hull by using Ames antimutagenic activity-guide isolation procedures and to investigate their chemopreventive efficacies in cultured cells. The results demonstrated that six compounds showing great antimutagenic activity were identified by spectroscopic methods and by comparison with authentic samples to be p-hydroxybenzaldehyde, vanillin, syringaldehyde, trans-coniferylaldehyde, sinapaldehyde, and coixol. Two of them, trans-coniferylaldehyde and sinapaldehyde, exhibit relatively potent scavenging of DPPH radicals, inhibit TPA stimulated superoxide anion generation in neutrophil-like leukocytes, and induce Nrf2/ARE-driven luciferase activity in HSC-3 cells. Moreover, trans-coniferylaldehyde possesses cytoprotective efficacy against tert-butyl hydroperoxide-induced DNA double-strand breaks in cultured cells, and the chemopreventive potency induced by trans-coniferylaldehyde may be through the activation of kinase signals, including p38, ERK1/2, JNK, MEK1/2, and MSK1/2. In summary, we first identified six antimutagenic constituents from adlay hull. Among them, trans-coniferylaldehyde would be a highly promising agent for cancer chemoprevention and merits further investigation.

  5. 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.

  6. 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

  7. The 4Ps of Breast Cancer Chemoprevention: Putting Proven Principles into Practice.

    Science.gov (United States)

    Jordan, V Craig

    2017-04-01

    The pioneering Royal Marsden Tamoxifen Prevention Trial recruited 2,471 eligible high-risk women to be randomized to either placebo or tamoxifen (20 mg daily) for 8 years. Breast cancer incidence was evaluated at a median of 18.4 years from the start of the study. There was a 32% reduction in estrogen/progesterone receptor (ER/PR)-positive breast cancers after tamoxifen treatment finished. Translational research, to study "the good, the bad, and the ugly of tamoxifen" in the 1980s, subsequently ensured women's safety from possible increases in osteoperosis, coronary heart disease, and endometrial cancer. Other tamoxifen chemoprevention trials followed. The result of laboratory research was the unanticipated discovery of raloxifene to prevent osteoporosis and breast cancer at the same time. A new group of medicines, now known as selective ER modulators, was established. Indeed, the ability to prevent or delay multiple diseases with a single cheap medicine has the potential to alleviate pressure on health care systems that are overwhelmed. It is a priority to educate physicians appropriately to apply recommended proven medicines as preventives. Cancer Prev Res; 10(4); 219-22. ©2017 AACR See related article by Detre, et al., Cancer Prev Res 2017;10(3):171-6 . ©2017 American Association for Cancer Research.

  8. 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...

  9. Chemopreventive Potential of Powdered Red Wine Pomace Seasonings against Colorectal Cancer in HT-29 Cells.

    Science.gov (United States)

    Del Pino-García, Raquel; Rivero-Pérez, María D; González-SanJosé, María L; Ortega-Heras, Miriam; García Lomillo, Javier; Muñiz, Pilar

    2017-01-11

    This study evaluates the antiproliferative and antigenotoxic actions of powdered red wine pomace seasonings (Sk-S, seedless; W-S, whole; Sd-S, seeds). In vitro gastrointestinal digested and colonic fermented fractions of the seasonings were used as cell treatments. Phenolic acids from Sk-S showed the highest bioaccessibility in the small intestine, whereas polyphenols contained in Sd-S might be the most fermentable in the colon. Dietary fiber from Sk-S was the best substrate for short chain fatty acids production by gut microbiota. Colon cancerous (HT-29) cell viability was inhibited by 50% (IC 50 values) at treatment concentrations ranging from 845 (Sk-S) to 1085 (Sd-S) μg/mL prior digestion, but all digested fractions exhibited similar antiproliferative activities (mean IC 50 = 814 μg/mL). Oxidative DNA damage in cells was also attenuated by the treatments (200 μg/mL, 24 h preincubation), with all colonic fermented fractions displaying similar genoprotective action. These results suggest the potential of red wine pomace seasonings as chemopreventive agents in colorectal cancer.

  10. Development of in vitro models for cellular and molecular studies in toxicology and chemoprevention

    Energy Technology Data Exchange (ETDEWEB)

    Mace, K.; Offord, E.A.; Harris, C.C.; Pfeifer, A.M.A. [Nestle Research Center, Lausanne (Switzerland)

    1998-12-31

    Many natural dietary phytochemicals found compounds found in fruits, vegetables, spices and tea have been shown in recent years to be protective against cancer in various animal models. In the light of the potential impact of these compounds on human health it is important to elucidate the mechanisms involved. We therefore developed and characterized relevant in vitro models using immortalized human epithelial cell lines derived from target tissues in carcinogenesis, such as lung, liver and colon. Assays were established, allowing the evaluation of the cytotoxic and genotoxic effects of various procarcinogens, including nitrosamines, mycotoxins and heterocyclic amines on these metabolically-competent human epithelial cell lines. These cellular models appeared to be a useful tool to study the capacity of certain food components to block the initiation stage of carcinogenesis. The ability of carnosol and carnosic acid from rosemary as well as the synthetic dithiolethione, oltipraz, to block the formation of DNA adducts, and their effects on the expression of phase I and phase II enzymes was investigated. We have observed that both rosemary extracts and oltiprax inhibited benzo(a)pyrene- or aflatoxin B{sub 1}-induced DNA adduct formation by strongly inhibiting CYP{sub 450} activities and inducing the expression of glutathione S-transferase. These results in human cell models give some insight into the different mechanisms involved in the chemopreventive action of both natural and synthetic compounds in relation to phase I and phase II enzymes. (orig.)

  11. Anti-inflammatory, antiproliferative, and cytoprotective activity of NO chimera nitrates of use in cancer chemoprevention.

    Science.gov (United States)

    Hagos, Ghenet K; Abdul-Hay, Samer O; Sohn, Johann; Edirisinghe, Praneeth D; Chandrasena, R Esala P; Wang, Zhiqiang; Li, Qian; Thatcher, Gregory R J

    2008-11-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown promise in colorectal cancer (CRC), but they are compromised by gastrotoxicity. NO-NSAIDs are hybrid nitrates conjugated to an NSAID designed to exploit the gastroprotective properties of NO bioactivity. The NO chimera ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094), a novel nitrate containing an NSAID and disulfide pharmacophores, is effective in vivo in rat models of CRC and is a lead compound for design of agents of use in CRC. Preferred chemopreventive agents possess 1) antiproliferative and 2) anti-inflammatory actions and 3) the ability to induce cytoprotective phase 2 enzymes. To determine the contribution of each pharmacophore to the biological activity of GT-094, these three biological activities were studied in vitro in compounds that deconstructed the structural elements of the lead GT-094. The anti-inflammatory and antiproliferative actions of GT-094 in vivo were recapitulated in vitro, and GT-094 was seen to induce phase 2 enzymes via the antioxidant responsive element. In the variety of colon, macrophage-like, and liver cell lines studied, the evidence from structure-activity relationships was that the disulfide structural element of GT-094 is the dominant contributor in vitro to the anti-inflammatory activity, antiproliferation, and enzyme induction. The results provide a direction for lead compound refinement. The evidence for a contribution from the NO mimetic activity of nitrates in vitro was equivocal, and combinations of nitrates with acetylsalicylic acid were inactive.

  12. Chemoprevention of esophageal adenocarcinoma in a rat model by ursodeoxycholic acid.

    Science.gov (United States)

    Ojima, Eisuke; Fujimura, Takashi; Oyama, Katsunobu; Tsukada, Tomoya; Kinoshita, Jun; Miyashita, Tomoharu; Tajima, Hidehiro; Fushida, Sachio; Harada, Shin-ichi; Mukaisho, Ken-ichi; Hattori, Takanori; Ohta, Tetsuo

    2015-08-01

    Reflux of bile acid into the esophagus induces esophagitis, inflammation-stimulated hyperplasia, metaplasia such as Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC). Caudal-type homeobox 2 (Cdx2) via nuclear factor (NF)-κB induced by bile acid is an important factor in the development of BE and EAC. In colorectal cancer, experimental data suggest a chemopreventive effect of ursodeoxycholic acid (UDCA). We hypothesized that UDCA may protect against the esophageal inflammation-metaplasia-carcinoma sequence by decreasing the overall proportion of the toxic bile acids. Wistar male rats that underwent a duodenoesophageal reflux procedure were divided into two groups. One group was given commercial chow (control group), and the other was given experimental chow containing UDCA (UDCA group). The animals were killed at 40 weeks after surgery, and their bile and esophagus were examined. In the UDCA group, the esophagitis was milder and the incidence of BE was significantly lower (p acid, UDCA was markedly increased in the UDCA group compared with the control group (32.7 ± 11.4 vs. 0.82 ± 0.33 mmol/L, p acid was decreased (32.7 ± 4.05 vs. 60.9 ± 8.26 mmol/L, p acid composition.

  13. 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.

  14. 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.

  15. A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention

    Science.gov (United States)

    Chen, Allen Y.; Chen, Yi Charlie

    2013-01-01

    Kaempferol is a polyphenol antioxidant found in fruits and vegetables. Many studies have described the beneficial effects of dietary kaempferol in reducing the risk of chronic diseases, especially cancer. Epidemiological studies have shown an inverse relationship between kaempferol intake and cancer. Kaempferol may help by augmenting the body’s antioxidant defense against free radicals, which promote the development of cancer. At the molecular level, kaempferol has been reported to modulate a number of key elements in cellular signal transduction pathways linked to apoptosis, angiogenesis, inflammation, and metastasis. Significantly, kaempferol inhibits cancer cell growth and angiognesis and induces cancer cell apoptosis, but on the other hand, kaempferol appears to preserve normal cell viability, in some cases exerting a protective effect. The aim of this review is to synthesize information concerning the extraction of kaempferol, as well as to provide insights into the molecular basis of its potential chemo-preventative activities, with an emphasis on its ability to control intracellular signaling cascades that regulate the aforementioned processes. Chemoprevention using nanotechnology to improve the bioavailability of kaempferol is also discussed. PMID:23497863

  16. "I will miss the study, God bless you all": participation in a nutritional chemoprevention trial.

    Science.gov (United States)

    Moreno-Black, Geraldine; Shor-Posner, Gail; Miguez, Maria-Jose; Burbano, Ximena; O'Mellan, Sandra; Yovanoff, P

    2004-01-01

    Randomized controlled clinical trials are often considered to be the "gold standard" for health research. Consequently, understanding the reasons people participate in these trials, especially minority groups who are often under-represented in clinical trials, or populations who have chronic illnesses or abuse drugs, is salient for successful recruitment, retention, and project design. This paper describes the results of a study that was designed to examine some of the ways in which participants in a randomized double blind clinical trial perceived their participation in the clinical trial, and the reasons they gave for continuing in the study. All of the participants were individuals who were using drugs and were infected with the HIV-1 virus, and had participated in a chemoprevention trial. The data from an exit interview were analyzed thematically in order to reveal units of meaning concerning participation and continuation in the clinical trial. The analysis revealed 3 higher-level concepts, or themes, that guided participation: increased health awareness, personal enhancement, and sociability. The data clearly indicated that involvement and retention in the trial were directly related to the ways in which the participants interpreted the study, perceived the benefits they derived from participating, and imbued their participation with value so that it was important and relevant to their own perceptions of health, as well as personal and social well being.

  17. In Vitro and Ex Vivo Chemopreventive Action of Mauritia flexuosa Products

    Directory of Open Access Journals (Sweden)

    Joilane Alves Pereira-Freire

    2018-01-01

    Full Text Available Mauritia flexuosa (Arecaceae, known as “Buriti,” is a Brazilian palm tree with high economic potential for local communities. Herein, we investigated the phytochemistry profile and antioxidant potential of M. flexuosa fruits and determined the bioaccessibility of phenolic compounds. Peels revealed upper values for phenols, flavonoids, carotenoids, tannins, and ascorbic acid when compared to the pulps and endocarps. All samples showed capacity to scavenger free radicals (0.5, 1.0, 2.0, 4.0, and 8.0 mg/mL but peels presented higher scavenger action in all methods explored. Phenolic compounds identified by HPLC displayed reduced bioaccessibility after in vitro simulated gastrointestinal digestion for pulp (38.7%, peel (18.7%, and endocarp (22.3% extracts (P<0.05. Buriti fruits also protected rat blood cells against lysis induced by peroxyl radicals. We demonstrated the promising chemopreventive potentialities of M. flexuosa fruits and their by-products and peels with higher quantities of bioactive compounds and phenolic substances before and after in vitro bioaccessibility investigation. In Brazil, these parts are discarded or underused, mainly as feed for ruminant animals. Consequently, it is extremely important to explore nutritional characteristics of these by-products for human/livestock foods and to install biofriendly techniques and sustainable biotechnology handling of natural resources.

  18. Chemopreventive and therapeutic activity of dietary blueberry against estrogen-mediated breast cancer.

    Science.gov (United States)

    Jeyabalan, Jeyaprakash; Aqil, Farrukh; Munagala, Radha; Annamalai, Lakshmanan; Vadhanam, Manicka V; Gupta, Ramesh C

    2014-05-07

    Berries are gaining increasing importance lately for their chemopreventive and therapeutic potential against several cancers. In earlier studies, a blueberry-supplemented diet has shown protection against 17β-estradiol (E2)-mediated mammary tumorigenesis. This study tested both preventive and therapeutic activities of diet supplemented with whole blueberry powder (50:50 blend of Tifblue and Rubel). Animals received 5% blueberry diet, either 2 weeks prior to or 12 weeks after E2 treatment in preventive and therapeutic groups, respectively. Both interventions delayed the tumor latency for palpable mammary tumors by 28 and 37 days, respectively. Tumor volume and multiplicity were also reduced significantly in both modes. The effect on mammary tumorigenesis was largely due to down-regulation of CYP 1A1 and ER-α gene expression and also favorable modulation of microRNA (miR-18a and miR-34c) levels. These data suggest that the blueberry blend tested is effective in inhibiting E2-mediated mammary tumorigenesis in both preventive and therapeutic modes.

  19. Sirt1 Is Required for Resveratrol-Mediated Chemopreventive Effects in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Constanze Buhrmann

    2016-03-01

    Full Text Available Sirt1 is a NAD+-dependent protein-modifying enzyme involved in regulating gene expression, DNA damage repair, metabolism and survival, as well as acts as an important subcellular target of resveratrol. The complex mechanisms underlying Sirt1 signaling during carcinogenesis remain controversial, as it can serve both as a tumor promoter and suppressor. Whether resveratrol-mediated chemopreventive effects are mediated via Sirt1 in CRC growth and metastasis remains unclear; which was the subject of this study. We found that resveratrol suppressed proliferation and invasion of two different human CRC cells in a dose-dependent manner, and interestingly, this was accompanied with a significant decrease in Ki-67 expression. By transient transfection of CRC cells with Sirt1-ASO, we demonstrated that the anti-tumor effects of resveratrol on cells was abolished, suggesting the essential role of this enzyme in the resveratrol signaling pathway. Moreover, resveratrol downregulated nuclear localization of NF-κB, NF-κB phosphorylation and its acetylation, causing attenuation of NF-κB-regulated gene products (MMP-9, CXCR4 involved in tumor-invasion and metastasis. Finally, Sirt1 was found to interact directly with NF-κB, and resveratrol did not suppress Sirt1-ASO-induced NF-κB phosphorylation, acetylation and NF-κB-regulated gene products. Overall, our results demonstrate that resveratrol can suppress tumorigenesis, at least in part by targeting Sirt1 and suppression of NF-κB activation.

  20. Nanoemulsions of cancer chemopreventive agent benzyl isothiocyanate display enhanced solubility, dissolution, and permeability.

    Science.gov (United States)

    Qhattal, Hussaini Syed Sha; Wang, Shu; Salihima, Tri; Srivastava, Sanjay K; Liu, Xinli

    2011-12-14

    Benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, is an effective chemopreventive agent. The objective of this study was to develop nanoemulsion formulations for the oral delivery of BITC. Optimized oil-in-water BITC nanoemulsions were prepared by a spontaneous self-nanoemulsification method and a homogenization-sonication method. Both nanoemulsions entrapped high amounts of BITC (15-17 mg/mL), with low polydispersity and good colloidal stability. The BITC nanoemulsions showed enhanced solubility and dissolution compared to pure BITC. These formulations markedly increased the apical to basolateral transport of BITC in Caco-2 cell monolayers. The apparent permeability values were 3.6 × 10(-6) cm/s for pure BITC and (1.1-1.3) × 10(-5) cm/s for BITC nanoemulsions. The nanoemulsions were easily taken up by human cancer cells A549 and SKOV-3 and inhibited tumor growth in vitro. This work shows for the first time that BITC can be formulated into nanoemulsions and may show promise in enhancing absorption and bioavailability.

  1. Vertical Protocol Composition

    DEFF Research Database (Denmark)

    Groß, Thomas; Mödersheim, Sebastian Alexander

    2011-01-01

    The security of key exchange and secure channel protocols, such as TLS, has been studied intensively. However, only few works have considered what happens when the established keys are actually used—to run some protocol securely over the established “channel”. We call this a vertical protocol.......e., that the combination cannot introduce attacks that the individual protocols in isolation do not have. In this work, we prove a composability result in the symbolic model that allows for arbitrary vertical composition (including self-composition). It holds for protocols from any suite of channel and application...

  2. Polyethylene Glycol Mediated Colorectal Cancer Chemoprevention: Roles of Epidermal Growth Factor Receptor and Snail

    Science.gov (United States)

    Wali, Ramesh K.; Kunte, Dhananjay P.; Koetsier, Jennifer L.; Bissonnette, Marc; Roy, Hemant K.

    2008-01-01

    Polyethylene glycol (PEG) is a clinically widely used agent with profound chemopreventive properties in experimental colon carcinogenesis. We previously reported that Snail/β-catenin signaling may mediate the suppression of epithelial proliferation by PEG, although the upstream events remain unclear. We report herein the role of epidermal growth factor receptor (EGFR), a known mediator of Snail and overepressed in ~80% of human colorectal cancers (CRC), on PEG-mediated anti-proliferative and hence anti-neoplastic effects in azoxymethane (AOM)-rats and HT-29 colon cancer cells. AOM-rats were randomized to either standard diet or one with 10% PEG 3350 and euthanized 8 weeks later. The colonic samples were subjected to immunohistochemical or Western blot analyses. PEG decreased mucosal EGFR by 60% (pPEG effects were obtained in HT-29 cells. PEG suppressed EGFR protein via lysosmal degradation with no change in mRNA levels. To show that EGFR antagonism per se was responsible for the antiproliferative effect, we inhibited EGFR by either pre-treating cells with gefitinib or stably transfecting with EGFR-shRNA and measured the effect of PEG on proliferation. In either case PEG effect was blunted suggesting a vital role of EGFR. Flow cytometric analysis revealed that EGFR-shRNA cells, besides having reduced membrane EGFR also expressed low Snail levels (40%), corroborating a strong association. Furthermore, in EGFR silenced cells PEG effect on EGFR or Snail was muted, similar to that on proliferation. In conclusion, we show that EGFR is the proximate membrane signaling molecule through which PEG initiates antiproliferative activity with Snail/β-catenin pathway playing the central intermediary function. PMID:18790788

  3. Polyethylene glycol-mediated colorectal cancer chemoprevention: roles of epidermal growth factor receptor and Snail.

    Science.gov (United States)

    Wali, Ramesh K; Kunte, Dhananjay P; Koetsier, Jennifer L; Bissonnette, Marc; Roy, Hemant K

    2008-09-01

    Polyethylene glycol (PEG) is a clinically widely used agent with profound chemopreventive properties in experimental colon carcinogenesis. We reported previously that Snail/beta-catenin signaling may mediate the suppression of epithelial proliferation by PEG, although the upstream events remain unclear. We report herein the role of epidermal growth factor receptor (EGFR), a known mediator of Snail and overexpressed in approximately 80% of human colorectal cancers, on PEG-mediated antiproliferative and hence antineoplastic effects in azoxymethane (AOM) rats and HT-29 colon cancer cells. AOM rats were randomized to either standard diet or one with 10% PEG-3350 and euthanized 8 weeks later. The colonic samples were subjected to immunohistochemical or Western blot analyses. PEG decreased mucosal EGFR by 60% (P PEG effects were obtained in HT-29 cells. PEG suppressed EGFR protein via lysosmal degradation with no change in mRNA levels. To show that EGFR antagonism per se was responsible for the antiproliferative effect, we inhibited EGFR by either pretreating cells with gefitinib or stably transfecting with EGFR-short hairpin RNA and measured the effect of PEG on proliferation. In either case, PEG effect was blunted, suggesting a vital role of EGFR. Flow cytometric analysis revealed that EGFR-short hairpin RNA cells, besides having reduced membrane EGFR, also expressed low Snail levels (40%), corroborating a strong association. Furthermore, in EGFR silenced cells, PEG effect on EGFR or Snail was muted, similar to that on proliferation. In conclusion, we show that EGFR is the proximate membrane signaling molecule through which PEG initiates antiproliferative activity with Snail/beta-catenin pathway playing the central intermediary function.

  4. Potential chemoprevention of diethylnitrosamine-induced hepatocarcinogenesis in rats: myrrh (Commiphora molmol) vs. turmeric (Curcuma longa).

    Science.gov (United States)

    El-Shahat, Mohamed; El-Abd, Sabah; Alkafafy, Mohamed; El-Khatib, Gamal

    2012-09-01

    The aim of the present study was to assess the potential chemopreventive effects of myrrh (Commiphora molmol) vs. turmeric (Curcuma longa) in hepatocarcinogenic rats induced by a single intraperitoneal injection of diethylnitrosamine (DENA) (200 mg/kg body weight). Ninety male Wistar rats used in this study were randomly divided into six equal groups (n=15). Group 1 rats served as negative controls; group 2 received a single i.p. injection of DENA and served as positive controls. Rats in both groups were fed on basal diet. Group 3 rats were fed a diet containing 5% turmeric, whereas group 4 rats were fed a diet containing 2% myrrh. Rats in groups 5 and 6 received a single i.p. injection of DENA and were fed diets containing 5% turmeric and 2% myrrh, respectively. The study demonstrated that DENA caused a significant increase in serum indices of liver enzymes and also severe histological and immunohistochemical changes in hepatic tissues. These included disorganized hepatic parenchyma, appearance of pseudoacinar and trabecular arrays of hepatocytes and alterations in CD10-immunoreactivity. Dietary supplementation of turmeric relatively improved the biochemical parameters to values approximating those of the negative controls and delayed the initiation of carcinogenesis. In contrast, myrrh did not improve the biochemical parameters or delay the hepatocarcinogenesis. Both turmeric and myrrh induced significant biochemical and histological changes in non-treated rats. In conclusion, DENA significantly changes the biological enzymatic activities in serum and the integrity of hepatic tissues. Phytochemicals with potential hepatoprotective effects must be applied cautiously owing to their potential hepatotoxicity. Copyright © 2011 Elsevier GmbH. All rights reserved.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Naveena B. Janakiram

    2012-02-01

    Full Text Available 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. Before the efficacy studies, we determined that the maximal tolerated dose in C57BL/6J mice was less than 400 ppm. For the efficacy study, 6-week-old male and female C57BL/6J-ApcMin/+ mice (nine mice per group were fed diets containing 0, 30, and 60 ppm of bexarotene or 200 ppm of bexarotene for 80 days before intestinal tumors were evaluated. Dietary administration of 30 and 60 ppm of bexarotene suppressed the intestinal polyp formation by 38% (P < .015 and 60% (P < .0001 in males, respectively, and by 8.5% and 37% (P < .007 in females, respectively. Also, significant inhibition (50%–100% of colonic tumor formation was observed in both male and female mice with bexarotene treatment. Administration of 200 ppm of bexarotene showed significant suppression of tumor formation (66%, P < .0001; however, it had significant toxicity. Intestinal tumors of bexarotene-fed mice showed significantly reduced expression of proliferating cell nuclear antigen (60%, P < .0001, cyclin D1, and cyclooxygenase 2 and increased RXR-α messenger RNA and uptake of oleate (34%, P < .01. Also, bexarotene-fed mice showed dose-dependent suppression of serum triglycerides (25%–72%, P < .0001 and inflammatory cytokines.

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

    Science.gov (United States)

    Setia, Shruti; Sanyal, Sankar N

    2012-01-01

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

  8. Intrinsic mitochondrial membrane potential change and associated events mediate apoptosis in chemopreventive effect of diclofenac in colon cancer.

    Science.gov (United States)

    Kaur, Jasmeet; Sanyal, S N

    2010-01-01

    The present study explored the role of intrinsic mitochondrial membrane potential (delta psi M) in NSAID-induced apoptosis in the early stages of colon cancer. 1,2-Dimethylhydrazine dihydrochloride (DMH) was used to induce colon cancer and its chemoprevention was studied by diclofenac in a rat model. After 6 weeks of treatment with DMH (early stage), morphological analysis revealed a marked occurrence of preneoplastic features [i.e., mucosal plaque lesions (MPLs) in the colonic tissue]. Coadministration of diclofenac with DMH resulted in a significant reduction of these lesions, thereby proving the chemopreventive efficacy of diclofenac at the chosen anti-inflammatory dose. DMH treatment also led to a significant increase in delta psi M in the isolated colonocytes as assessed by JC-1 fluorescent staining, measured both by fluorescence microscopy and spectrofluorometerically. Further, there was seen a reduction in the number of cells showing low delta psi M, and hence monomer intensity of JC-1 by DMH treatment. To study the mechanism of these alterations in delta psi M in the present work, we studied the protein expression of important proapoptotic proteins, cytochrome c and Bax, by Western blot analysis and immunohistochemistry. DMH treatment reduced the mitochondrial translocation of Bax whereas cytochrome c was found to be located prominently in the mitochondria. Protein expression of antiapoptotic Bcl-2 was also studied in the colonic mucosa, which was expectedly found to be overexpressed after DMH treatment. Diclofenac treatment ameliorated the elevated delta psi M and its associated events to exert its chemopreventive action against early stages of colon cancer.

  9. Chemoprevention of DMH-induced rat colon carcinoma initiation by combination administration of piroxicam and C-phycocyanin.

    Science.gov (United States)

    Saini, Manpreet Kaur; Vaiphei, Kim; Sanyal, Sankar Nath

    2012-02-01

    Cancer research illustrated that combinatorial studies can provide significant improvement in safety and effectiveness over the monotherapy regimens. A combination of two drugs may restrain precancerous colon polyps, opening a new possible opportunity for chemoprevention of colon cancer. In this context, chemopreventive efficacy of a combination regimen of C-phycocyanin, a biliprotein present in Spirulina platensis, a cyanobacterium, which is a selective cycloxygenase-2 (COX-2) inhibitor and piroxicam, a traditional non-steroidal anti-inflammatory drug was considered in 1,2 dimethylhyadrazine (DMH)-induced colon carcinogenesis in rats. Western blotting, immunohistochemistry, DNA fragmentation, fluorescent staining, PGE(2) enzyme immunoassay, and carrageenan-induced paw edema test were performed along with morphological and histological analysis. DMH treatment showed a rich presence of preneoplastic lesions such as multiple plaque lesions, aberrant crypt foci, and well-characterized dysplasia. These features were reduced with piroxicam and C-phycocyanin administration. The number of apoptotic cells was featured prominently in all the groups compared with DMH. DMH treatment revealed intact high molecular weight genomic DNA with no signs of laddering/DNA fragmentation while it was noticeable significantly in control and DMH + piroxicam + C-phycocyanin. DMH group showed highest COX-2 expression and PGE(2) level in comparison with other groups. Doses of piroxicam and C-phycocyanin used in the present study were established at an anti-inflammatory range. A combination regimen of piroxicam and C-phycocyanin, rather than individually has the much greater potential for reduction of DMH-induced colon cancer development and COX-2 being the prime possible target in such chemoprevention.

  10. Evaluating the potential cancer chemopreventive efficacy of two different solvent extracts of Seriphidium herba-alba in vitro

    Directory of Open Access Journals (Sweden)

    Mahmoud Mohamed Mokhtar

    2017-06-01

    Full Text Available Cancer is the second leading cause of death world-wide. One of the most important medical practices of the 21st century is the chemoprevention of cancer. For a long history, it has been accepted that plants could prevent and exert suitable anti-carcinogenic effects for multiple types of cancers. Seriphidium herba-alba family Asteraceae has been used in the folk medicine by many cultures for treatment of various ailments since ancient times. In the current research we were aimed to evaluate the cancer chemopreventive activity of two crude extracts of S. herba-alba, methylene chloride extract and methanol extract on two cell lines: Human breast cancer cells (MCF-7 and human hepatocellular carcinoma cells (Hep-G2. Assessment of cytotoxicity using methyl thiazole tetrazolium (MTT assay indicated that both extracts exhibit poor cytotoxicity with half maximal inhibitory concentration (IC50 >20 µg/mL. Assessment of glutathione-S-transferases (GSTs activity (spectrophotometrically showed statistically significant enhancement of enzyme activity after treatment with three different doses of methylene chloride extract and glutathione (GSH concentrations were decreased. Analysis of cell mode of death by Ethidium bromide/Acridine orange (EB/AO staining revealed that the dominant mode of death in MCF-7 cells was apoptosis. Assessment of vascular endothelial growth factor (VEGF and platelets derived growth factor (PDGFBB using ELISA showed that VEGF and PDGFBB levels were statistically significant decreased. In Conclusion: both extracts may be cancer chemopreventive agents since they had tumor anti-initiating, and anti-promoting activity.

  11. The French dosimetry protocol

    International Nuclear Information System (INIS)

    Dutreix, A.

    1985-01-01

    After a general introduction the protocol is divided in five sections dealing with: determination of the quality of X-ray, γ-ray and electron beams; the measuring instrument; calibration of the reference instrument; determination of the reference absorbed dose in the user's beams; determination of the absorbed dose in water at other points, in other conditions. The French protocol is not essentially different from the Nordic protocol and it is based on the experience gained in using both the American and the Nordic protocols. Therefore, only the main difference with the published protocols are discussed. (Auth.)

  12. Protocol Implementation Generator

    DEFF Research Database (Denmark)

    Carvalho Quaresma, Jose Nuno; Probst, Christian W.

    2010-01-01

    Users expect communication systems to guarantee, amongst others, privacy and integrity of their data. These can be ensured by using well-established protocols; the best protocol, however, is useless if not all parties involved in a communication have a correct implementation of the protocol and a...... Generator framework based on the LySatool and a translator from the LySa language into C or Java....... necessary tools. In this paper, we present the Protocol Implementation Generator (PiG), a framework that can be used to add protocol generation to protocol negotiation, or to easily share and implement new protocols throughout a network. PiG enables the sharing, verification, and translation...

  13. Chemopreventive effects of free and bound phenolics associated to steep waters (nejayote) obtained after nixtamalization of different maize types.

    Science.gov (United States)

    Rojas-García, Carlos; García-Lara, Silverio; Serna-Saldivar, Sergio O; Gutiérrez-Uribe, Janet A

    2012-03-01

    Free and bound phenolics extracts from nejayote solids were obtained after optimally lime-cooking blue, normal white, red, normal yellow, high-carotenoid and quality protein maize types. The extraction yield ranged from 4.47 to 10.05%. Bound phenolics extracts had higher content of total phenolics, antioxidant activity and ferulic acid compared to the free phenolics extracts. In general, free phenolics extracts were less cytotoxic than the bound phenolics counterparts. Bound phenolics extracts had higher induction of quinone reductase (QR) and particularly the normal yellow nejayote exerted the highest chemopreventive index tested in Hepa1c1c7 cells. When tested for monofunctional phase 2 induction capacity in BPrc1 cells, the bound phenolics extracts of blue, normal white and quality protein nejayotes were better inducers than the normal yellow counterpart. Particularly, the free phenolics extract of the white maize nejayote induced BPrc1 cells QR and exerted a higher chemopreventive index compared to the bound phenolics extract. Therefore, the nejayote of the normal white maize was the best source of monofunctional phase 2 enzyme inducers.

  14. Health Promoting Effects of Brassica-Derived Phytochemicals: From Chemopreventive and Anti-Inflammatory Activities to Epigenetic Regulation

    Directory of Open Access Journals (Sweden)

    Anika Eva Wagner

    2013-01-01

    Full Text Available A high intake of brassica vegetables may be associated with a decreased chronic disease risk. Health promoting effects of Brassicaceae have been partly attributed to glucosinolates and in particular to their hydrolyzation products including isothiocyanates. In vitro and in vivo studies suggest a chemopreventive activity of isothiocyanates through the redox-sensitive transcription factor Nrf2. Furthermore, studies in cultured cells, in laboratory rodents, and also in humans support an anti-inflammatory effect of brassica-derived phytochemicals. However, the underlying mechanisms of how these compounds mediate their health promoting effects are yet not fully understood. Recent findings suggest that brassica-derived compounds are regulators of epigenetic mechanisms. It has been shown that isothiocyanates may inhibit histone deacetylase transferases and DNA-methyltransferases in cultured cells. Only a few papers have dealt with the effect of brassica-derived compounds on epigenetic mechanisms in laboratory animals, whereas data in humans are currently lacking. The present review aims to summarize the current knowledge regarding the biological activities of brassica-derived phytochemicals regarding chemopreventive, anti-inflammatory, and epigenetic pathways.

  15. Chemopreventive effects of NSAIDs as inhibitors of cyclooxygenase-2 and inducers of apoptosis in experimental lung carcinogenesis.

    Science.gov (United States)

    Setia, Shruti; Vaish, Vivek; Sanyal, Sankar Nath

    2012-07-01

    Roles of cyclooxygenase (COX) enzyme and intrinsic pathway of apoptosis have been explored for the chemopreventive effects of non-steroidal anti-inflammatory drugs (NSAIDs) on 9,10-dimethyl benz(a)anthracene (DMBA)-induced lung cancer in rat model. 16 weeks after the administration of DMBA, morphological analysis revealed the occurrences of tumours and lesions, which were regressed considerably with the co-administration of indomethacin and etoricoxib, the two NSAIDs under investigation. DMBA group was marked by hyperplasia and dysplasia as observed by histological examination, and these features were corrected to a large extent by the two NSAIDs. Elevated levels of COX-2 were seen in the DMBA group, the enzyme responsible for prostaglandin synthesis during inflammation and cancer, whilst the expression of the constitutive isoform, COX-1, was equally expressed in all the groups. Apoptosis was quantified by studying the activities of apaf-1, caspase-9, and 3 by immunofluorescence and western blots. Their activities were found to diminish in the DMBA-treated animals as compared to the other groups. Fluorescent co-staining of the isolated broncho-alveolar lavage cells showed reduced number of apoptotic cells in the DMBA group, indicating decrease in apoptosis after carcinogen administration. The present results thus suggest that the mechanism of cancer chemoprevention of NSAIDs may include the suppression of COX-2 and the induction of apoptosis.

  16. Chemoprevention of colorectal cancer by black raspberry anthocyanins involved the modulation of gut microbiota and SFRP2 demethylation.

    Science.gov (United States)

    Chen, Lili; Jiang, Bowen; Zhong, Chunge; Guo, Jun; Zhang, Lihao; Mu, Teng; Zhang, Qiuhua; Bi, Xiuli

    2018-03-08

    Freeze-dried black raspberry (BRB) powder is considered as a potential cancer chemopreventive agent. In this study, we fed azoxymethane (AOM)/dextran sodium sulfate (DSS)-treated C57BL/6J mice with a diet containing BRB anthocyanins for 12 weeks, and this led to a reduction in colon carcinogenesis. These animals had consistently lower tumor multiplicity compared with AOM/DSS-treated mice not receiving BRB anthocyanins. In AOM/DSS-treated mice, the number of pathogenic bacteria, including Desulfovibrio sp. and Enterococcus spp., was increased significantly, whereas probiotics such as Eubacterium rectale, Faecalibacterium prausnitzii and Lactobacillus were dramatically decreased, but BRB anthocyanins supplement could reverse this imbalance in gut microbiota. BRB anthocyanins also caused the demethylation of the SFRP2 gene promoter, resulting in increased expression of SFRP2, both at the mRNA and protein levels. Furthermore, the expression levels of DNMT31 and DNMT3B, as well as of p-STAT3 were downregulated by BRB anthocyanins in these animals. Taken together, these results suggested that BRB anthocyanins could modulate the composition of gut commensal microbiota, and changes in inflammation and the methylation status of the SFRP2 gene may play a central role in the chemoprevention of CRC.

  17. In Vivo Immunomodulation and Lipid Peroxidation Activities Contributed to Chemoprevention Effects of Fermented Mung Bean against Breast Cancer

    Directory of Open Access Journals (Sweden)

    Swee Keong Yeap

    2013-01-01

    Full Text Available Mung bean has been reported to have antioxidant, cytotoxic, and immunomodulatory effects in vitro. Fermented products are reported to have enhanced immunomodulation and cancer chemopreventive effects. In this study, fermented mung bean treatments in vivo were studied by monitoring tumor development, spleen immunity, serum cytokine (interleukin 2 and interferon gamma levels, and spleen/tumor antioxidant levels after injection with low and high risk 4T1 breast cancer cells. Pretreatment with fermented mung bean was associated with delayed tumor formation in low risk mice. Furthermore, this treatment was connected with higher serum anticancer cytokine levels, spleen T cell populations, splenocyte cytotoxicity, and spleen/tumor antioxidant levels. Histopathological evaluation of fermented mung bean treated tumor revealed lower event of mitotic division. On the other hand, antioxidant and nitric oxide levels that were significantly increased in the untreated mice were inhibited in the fermented mung bean treated groups. These results suggested that fermented mung bean has potential cancer chemoprevention effects through the stimulation of immunity, lipid peroxidation, and anti-inflammation.

  18. Breast Cancer Chemoprevention: A Network Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Mocellin, Simone; Pilati, Pierluigi; Briarava, Marta; Nitti, Donato

    2016-02-01

    Several agents have been advocated for breast cancer primary prevention. However, few of them appear effective, the associated severe adverse effects limiting their uptake. We performed a comprehensive search for randomized controlled trials (RCTs) reporting on the ability of chemoprevention agents (CPAs) to reduce the incidence of primary breast carcinoma. Using network meta-analysis, we ranked CPAs based simultaneously on efficacy and acceptability (an inverse measure of toxicity). All statistical tests were two-sided. We found 48 eligible RCTs, enrolling 271 161 women randomly assigned to receive either placebo or one of 21 CPAs. Aromatase inhibitors (anastrozole and exemestane, considered a single CPA class because of the lack of between-study heterogeneity; relative risk [RR] = 0.468, 95% confidence interval [CI] = 0.346 to 0.634), arzoxifene (RR = 0.415, 95% CI = 0.253 to 0.682), lasofoxifene (RR = 0.208, 95% CI = 0.079 to 0.544), raloxifene (RR = 0.572, 95% CI = 0.372 to 0.881), tamoxifen (RR = 0.708, 95% CI = 0.595 to 0.842), and tibolone (RR = 0.317, 95% CI = 0.127 to 0.792) were statistically significantly associated with a therapeutic effect, which was restricted to estrogen receptor-positive tumors of postmenopausal women (except for tamoxifen, which is active also during premenopause). Network meta-analysis ranking showed that the new selective estrogen receptor modulators (SERMs) arzoxifene, lasofoxifene, and raloxifene have the best benefit-risk ratio. Aromatase inhibitors and tamoxifen ranked second and third, respectively. These results provide physicians and health care regulatory agencies with RCT-based evidence on efficacy and acceptability of currently available breast cancer CPAs; at the same time, we pinpoint how much work still remains to be done before pharmacological primary prevention becomes a routine option to reduce the burden of this disease. © The Author 2015. Published by Oxford University Press. All rights reserved. For

  19. Network protocols and sockets

    OpenAIRE

    BALEJ, Marek

    2010-01-01

    My work will deal with network protocols and sockets and their use in programming language C#. It will therefore deal programming network applications on the platform .NET from Microsoft and instruments, which C# provides to us. There will describe the tools and methods for programming network applications, and shows a description and sample applications that work with sockets and application protocols.

  20. Chemopreventive glucosinolate accumulation in various broccoli and collard tissues: Microfluidic-based targeted transcriptomics for by-product valorization.

    Science.gov (United States)

    Lee, Young-Sang; Ku, Kang-Mo; Becker, Talon M; Juvik, John A

    2017-01-01

    Floret, leaf, and root tissues were harvested from broccoli and collard cultivars and extracted to determine their glucosinolate and hydrolysis product profiles using high performance liquid chromatography and gas chromotography. Quinone reductase inducing bioactivity, an estimate of anti-cancer chemopreventive potential, of the extracts was measured using a hepa1c1c7 murine cell line. Extracts from root tissues were significantly different from other tissues and contained high levels of gluconasturtiin and glucoerucin. Targeted gene expression analysis on glucosinolate biosynthesis revealed that broccoli root tissue has elevated gene expression of AOP2 and low expression of FMOGS-OX homologs, essentially the opposite of what was observed in broccoli florets, which accumulated high levels of glucoraphanin. Broccoli floret tissue has significantly higher nitrile formation (%) and epithionitrile specifier protein gene expression than other tissues. This study provides basic information of the glucosinolate metabolome and transcriptome for various tissues of Brassica oleracea that maybe utilized as potential byproducts for the nutraceutical market.

  1. Chemoprevention of colon carcinogenesis by polyethylene glycol: suppression of epithelial proliferation via modulation of SNAIL/beta-catenin signaling.

    Science.gov (United States)

    Roy, Hemant K; Kunte, Dhananjay P; Koetsier, Jennifer L; Hart, John; Kim, Young L; Liu, Yang; Bissonnette, Marc; Goldberg, Michael; Backman, Vadim; Wali, Ramesh K

    2006-08-01

    Polyethylene glycol (PEG) is one of the most potent chemopreventive agents against colorectal cancer; however, the mechanisms remain largely unexplored. In this study, we assessed the ability of PEG to target cyclin D1-beta-catenin-mediated hyperproliferation in the azoxymethane-treated rat model and the human colorectal cancer cell line, HT-29. Azoxymethane-treated rats were randomized to AIN-76A diet alone or supplemented with 5% PEG-8000. After 30 weeks, animals were euthanized and biopsies of aberrant crypt foci and uninvolved crypts were subjected to immunohistochemical and immunoblot analyses. PEG markedly suppressed both early and late markers of azoxymethane-induced colon carcinogenesis (fractal dimension by 80%, aberrant crypt foci by 64%, and tumors by 74%). In both azoxymethane-treated rats and HT-29 cells treated with 5% PEG-3350 for 24 hours, PEG decreased proliferation (45% and 52%, respectively) and cyclin D1 (78% and 56%, respectively). Because beta-catenin is the major regulator of cyclin D1 in colorectal cancer, we used the T-cell factor (Tcf)-TOPFLASH reporter assay to show that PEG markedly inhibited beta-catenin transcriptional activity. PEG did not alter total beta-catenin expression but rather its nuclear localization, leading us to assess E-cadherin expression (a major determinant of beta-catenin subcellular localization), which was increased by 73% and 71% in the azoxymethane-rat and HT-29 cells, respectively. We therefore investigated the effect of PEG treatment on levels of the negative regulator of E-cadherin, SNAIL, and observed a 50% and 75% decrease, respectively. In conclusion, we show, for the first time, a molecular mechanism through which PEG imparts its antiproliferative and hence profound chemopreventive effect.

  2. Chemopreventive effect and angiogenic activity of punicalagin isolated from leaves of Lafoensia pacari A. St.-Hil

    Energy Technology Data Exchange (ETDEWEB)

    Costa Carneiro, Cristiene, E-mail: profacristiene@gmail.com [Instituto de Ciências Biológicas, Universidade Federal de Goiás, 74001970 Goiânia, GO (Brazil); Costa Santos, Suzana da [Instituto de Química, Universidade Federal de Goiás, 74001970 Goiânia, GO (Brazil); Souza Lino, Ruy de [Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, 74605050 Goiânia, GO (Brazil); Bara, Maria Teresa Freitas; Chaibub, Beatriz Abdallah [Faculdade de Farmácia, Universidade Federal de Goiás, 74605170 Goiânia, GO (Brazil); Melo Reis, Paulo Roberto de; Chaves, Dwight Assis [Laboratório de Estudos Experimentais e Biotecnológicos, Pontifícia Universidade Católica de Goiás, 74605010 Goiânia, GO (Brazil); Ribeiro da Silva, Antônio Jorge [Núcleo de Pesquisas de Produtos Naturais, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, 21941590 Rio de Janeiro, RJ (Brazil); Santos Silva, Luana; Melo e Silva, Daniela de; Chen-Chen, Lee [Instituto de Ciências Biológicas, Universidade Federal de Goiás, 74001970 Goiânia, GO (Brazil)

    2016-11-01

    Punicalagin is the major ellagitannin constituent from leaves of Lafoensia pacari, a Brazilian medicinal plant widely used for the treatment of peptic ulcer and wound healing. Genotoxic, cytotoxic, antigenotoxic, and anticytotoxic effects of punicalagin were assessed using micronucleus (MN) test and comet assay in mice. Due to the extensive use of L. pacari in the wound healing process, we also assessed the angiogenic activity of punicalagin using the chick chorioallantoic membrane (CAM) angiogenic assay. The highest dose of punicalagin (50 mg/kg) showed significant cytotoxic effect by MN test and in the co-treatment with cyclophosphamide (CPA), this cytotoxicity was enhanced. Co-treatment, pre-treatment and post-treatment of punicalagin with CPA led to a significant reduction in the number of DNA breaks and in the frequency of CPA-induced MN, indicating antigenotoxic effect. Using the CAM model, punicalagin exhibited angiogenic activity in all doses mainly at the lowest concentration (12.5 μg/μL). Therefore, these findings indicate an effective chemopreventive role of punicalagin and a high capacity to induce DNA repair. Also, the angiogenic activity presented by punicalagin in this study could contribute for the processes of tissue repairing and wound healing. - Highlights: • The ellagitannin punicalagin was isolated for the first time from L. pacari leaves. • The genotoxic and chemopreventive effects of punicalagin were evaluated in mice. • The highest dose of punicalagin showed significant cytotoxic effect. • Punicalagin exhibited antigenotoxic effects by the co-, pre- and post-treatment. • Punicalagin showed angiogenic activity and could be applied for tissue repairing.

  3. 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.

    2014-01-01

    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

  4. Nitrates and NO-NSAIDs in cancer chemoprevention and therapy: in vitro evidence querying the NO donor functionality.

    Science.gov (United States)

    Dunlap, Tareisha; Abdul-Hay, Samer O; Chandrasena, R Esala P; Hagos, Ghenet K; Sinha, Vaishali; Wang, Zhiqiang; Wang, Huali; Thatcher, Gregory R J

    2008-09-01

    Properties of the NO-ASA family of NO-donating NSAIDs (NO-NSAIDs), notably NCX 4016 (mNO-ASA) and NCX 4040 (pNO-ASA), reported in more than one hundred publications, have included positive preclinical data in cancer chemoprevention and therapy. Evidence is presented that the antiproliferative, the chemopreventive (antioxidant/electrophile response element (ARE) activation), and the anti-inflammatory activity of NO-ASA in cell cultures is replicated by X-ASA derivatives that are incapable of acting as NO donors. pBr-ASA and mBr-ASA are conisogenic with NO-ASA, but are not NO donors. The biological activity of pNO-ASA is replicated by pBr-ASA; and both pNO-ASA and pBr-ASA are bioactivated to the same quinone methide electrophile. The biological activity of mNO-ASA is replicated by mBr-ASA; mNO-ASA and mBr-ASA are bioactivated to different benzyl electrophiles. The observed activity is likely initiated by trapping of thiol biomolecules by the quinone and benzyl electrophiles, leading to depletion of GSH and modification of Cys-containing sensor proteins. Whereas all NO-NSAIDs containing the same structural "linker" as NCX 4040 and NCX 4016 are anticipated to possess activity resulting from bioactivation to electrophilic metabolites, this expectation does not extend to other linker structures. Nitrates require metabolic bioactivation to liberate NO bioactivity, which is often poorly replicated in vitro, and NO bioactivity provided by NO-NSAIDs in vivo provides proven therapeutic benefits in mitigation of NSAID gastrotoxicity. The in vivo properties of X-ASA drugs await discovery.

  5. Nitrates and NO-NSAIDs in Cancer Chemoprevention & Therapy: In Vitro Evidence Querying the NO Donor Functionality

    Science.gov (United States)

    Dunlap, Tareisha; Abdul-Hay, Samer; Chandrasena, R. Esala P.; Hagos, Ghenet K; Sinha, Vaishali; Wang, Zhiqiang; Wang, Huali; Thatcher, Gregory R. J.

    2008-01-01

    Properties of the NO-ASA family of NO-donating NSAIDs (NO-NSAIDs), notably NCX 4016 (mNO-ASA) and NCX 4040 (pNO-ASA), reported in more than a hundred publications, have included positive preclinical data in cancer chemoprevention and therapy. Evidence is presented that the antiproliferative, the chemopreventive (antioxidant/electrophile response element (ARE) activation), and the anti-inflammatory activity of NO-ASA in cell cultures is replicated by X-ASA derivatives that are incapable of acting as NO donors. pBr-ASA and mBr-ASA are conisogenic with NO-ASA, but are not NO donors. The biological activity of pNO-ASA is replicated by pBr-ASA; and both pNO-ASA and pBr-ASA are bioactivated to the same quinone methide electrophile. The biological activity of mNO-ASA is replicated by mBr-ASA; mNO-ASA and mBr-ASA are bioactivated to different benzyl electrophiles. The observed activity is likely initiated by trapping of thiol biomolecules by the quinone and benzyl electrophiles, leading to depletion of GSH and modification of Cys-containing sensor proteins. Whereas all NO-NSAIDs containing the same structural “linker” as NCX 4040 and NCX 4016 are anticipated to possess activity resulting from bioactivation to electrophilic metabolites, this expectation does not extend to other linker structures. Nitrates require metabolic bioactivation to liberate NO bioactivity, which is often poorly replicated in vitro, and NO bioactivity provided by NO-NSAIDs in vivo provides proven therapeutic benefits in mitigation of NSAID gastrotoxicity. The in vivo properties of X-ASA drugs await discovery. PMID:18485921

  6. Chemopreventive potential of β-Sitosterol in experimental colon cancer model - an In vitro and In vivo study

    Directory of Open Access Journals (Sweden)

    Paulraj Gabriel M

    2010-06-01

    Full Text Available Abstract Background Asclepias curassavica Linn. is a traditional medicinal plant used by tribal people in the western ghats, India, to treat piles, gonorrhoea, roundworm infestation and abdominal tumours. We have determined the protective effect of β-sitosterol isolated from A. curassavica in colon cancer, using in vitro and in vivo models. Methods The active molecule was isolated, based upon bioassay guided fractionation, and identified as β-sitosterol on spectral evidence. The ability to induce apoptosis was determined by its in vitro antiradical activity, cytotoxic studies using human colon adenocarcinoma and normal monkey kidney cell lines, and the expression of β-catenin and proliferating cell nuclear antigen (PCNA in human colon cancer cell lines (COLO 320 DM. The chemopreventive potential of β-sitosterol in colon carcinogenesis was assessed by injecting 1,2-dimethylhydrazine (DMH, 20 mg/kg b.w. into male Wistar rats and supplementing this with β-sitosterol throughout the experimental period of 16 weeks at 5, 10, and 20 mg/kg b.w. Results β-sitosterol induced significant dose-dependent growth inhibition of COLO 320 DM cells (IC50 266.2 μM, induced apoptosis by scavenging reactive oxygen species, and suppressed the expression of β-catenin and PCNA antigens in human colon cancer cells. β-sitosterol supplementation reduced the number of aberrant crypt and crypt multiplicity in DMH-initiated rats in a dose-dependent manner with no toxic effects. Conclusion We found doses of 10-20 mg/kg b.w. β-sitosterol to be effective for future in vivo studies. β-sitosterol had chemopreventive potential by virtue of its radical quenching ability in vitro, with minimal toxicity to normal cells. It also attenuated β-catenin and PCNA expression, making it a potential anticancer drug for colon carcinogenesis.

  7. Chemopreventive potential of β-Sitosterol in experimental colon cancer model - an In vitro and In vivo study

    Science.gov (United States)

    2010-01-01

    Background Asclepias curassavica Linn. is a traditional medicinal plant used by tribal people in the western ghats, India, to treat piles, gonorrhoea, roundworm infestation and abdominal tumours. We have determined the protective effect of β-sitosterol isolated from A. curassavica in colon cancer, using in vitro and in vivo models. Methods The active molecule was isolated, based upon bioassay guided fractionation, and identified as β-sitosterol on spectral evidence. The ability to induce apoptosis was determined by its in vitro antiradical activity, cytotoxic studies using human colon adenocarcinoma and normal monkey kidney cell lines, and the expression of β-catenin and proliferating cell nuclear antigen (PCNA) in human colon cancer cell lines (COLO 320 DM). The chemopreventive potential of β-sitosterol in colon carcinogenesis was assessed by injecting 1,2-dimethylhydrazine (DMH, 20 mg/kg b.w.) into male Wistar rats and supplementing this with β-sitosterol throughout the experimental period of 16 weeks at 5, 10, and 20 mg/kg b.w. Results β-sitosterol induced significant dose-dependent growth inhibition of COLO 320 DM cells (IC50 266.2 μM), induced apoptosis by scavenging reactive oxygen species, and suppressed the expression of β-catenin and PCNA antigens in human colon cancer cells. β-sitosterol supplementation reduced the number of aberrant crypt and crypt multiplicity in DMH-initiated rats in a dose-dependent manner with no toxic effects. Conclusion We found doses of 10-20 mg/kg b.w. β-sitosterol to be effective for future in vivo studies. β-sitosterol had chemopreventive potential by virtue of its radical quenching ability in vitro, with minimal toxicity to normal cells. It also attenuated β-catenin and PCNA expression, making it a potential anticancer drug for colon carcinogenesis. PMID:20525330

  8. Quantitation of chemopreventive synergism between (-)-epigallocatechin-3-gallate and curcumin in normal, premalignant and malignant human oral epithelial cells.

    Science.gov (United States)

    Khafif, A; Schantz, S P; Chou, T C; Edelstein, D; Sacks, P G

    1998-03-01

    An in vitro model for oral cancer was used to examine the growth inhibitory effects of chemopreventive agents when used singly and in combination. The model consists of primary cultures of normal oral epithelial cells, newly established cell lines derived from dysplastic leukoplakia and squamous cell carcinoma. Two naturally occurring substances, (-)-epigallocatechin-3-gallate (EGCG) from green tea and curcumin from the spice turmeric were tested. Cells were treated singly and in combination and effects on growth determined in 5-day growth assays and by cell cycle analysis. Effective dose 50s and the combination index were calculated with the computerized Chou-Talalay method which is based on the median-effect principle. Agents were shown to differ in their inhibitory potency. EGCG was less effective with cell progression; the cancer cells were more resistant than normal or dysplastic cells. In contrast, curcumin was equally effective regardless of the cell type tested. Cell cycle analysis indicated that EGCG blocked cells in G1, whereas curcumin blocked cells in S/G2M. The combination of both agents showed synergistic interactions in growth inhibition and increased sigmoidicity (steepness) of the dose-effect curves, a response that was dose and cell type dependent. Combinations allowed for a dose reduction of 4.4-8.5-fold for EGCG and 2.2-2.8-fold for curcumin at ED50s as indicated by the dose reduction index (DRI). Even greater DRI values were observed above ED50 levels. Our results demonstrate that this model which includes normal, premalignant and malignant oral cells can be used to analyse the relative potential of various chemopreventive agents. Two such naturally-occurring agents, EGCG and curcumin, were noted to inhibit growth by different mechanisms, a factor which may account for their demonstrable interactive synergistic effect.

  9. Identification of an unintended consequence of Nrf2-directed cytoprotection against a key tobacco carcinogen plus a counteracting chemopreventive intervention

    Science.gov (United States)

    Paonessa, Joseph D.; Ding, Yi; Randall, Kristen L.; Munday, Rex; Argoti, Dayana; Vouros, Paul; Zhang, Yuesheng

    2011-01-01

    Nrf2 is a major cytoprotective gene and is a key chemopreventive target against cancer and other diseases. Here we show that Nrf2 faces a dilemma in defense against 4-aminobiphenyl (ABP), a major human bladder carcinogen from tobacco smoke and other environmental sources. While Nrf2 protected mouse liver against ABP (which is metabolically activated in liver), the bladder level of N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-C8-ABP), the predominant ABP-DNA adduct formed in bladder cells and tissues, was markedly higher in Nrf2+/+ mice than in Nrf2−/− mice after ABP exposure. Notably, Nrf2 protected bladder cells against ABP in vitro. Mechanistic investigations showed that the dichotomous effects of Nrf2 could be explained at least partly by upregulation of UDP-glucuronosyltransferase (UGT). Nrf2 promoted conjugation of ABP with glucuronic acid in the liver, increasing urinary excretion of the conjugate. While glucuronidation of ABP and its metabolites is a detoxification process, these conjugates, which are excreted in urine, are known to be unstable in acidic urine, leading to delivery of the parent compounds to bladder. Hence, while higher liver UGT activity may protect the liver against ABP it increases bladder exposure to ABP. These findings raise concerns of potential bladder toxicity when Nrf2-activating chemopreventive agents are used in humans exposed to ABP, especially in smokers. We further demonstrate that 5,6-dihydrocyclopenta[c][1,2]-dithiole-3(4H)-thione (CPDT) significantly inhibits dG-C8-ABP formation in bladder cells and tissues, but does not appear to significantly modulate ABP-catalyzing UGT in liver. Thus, CPDT exemplifies a counteracting solution to the dilemma posed by Nrf2. PMID:21487034

  10. Inhibition of Pro-inflammatory and Anti-apoptotic Biomarkers during Experimental Oral Cancer Chemoprevention by Dietary Black Raspberries

    Directory of Open Access Journals (Sweden)

    Steve Oghumu

    2017-10-01

    Full Text Available Oral cancer continues to be a significant public health problem worldwide. Recently conducted clinical trials demonstrate the ability of black raspberries (BRBs to modulate biomarkers of molecular efficacy that supports a chemopreventive strategy against oral cancer. However, it is essential that a preclinical animal model of black raspberry (BRB chemoprevention which recapitulates human oral carcinogenesis be developed, so that we can validate biomarkers and evaluate potential mechanisms of action. We therefore established the ability of BRBs to inhibit oral lesion formation in a carcinogen-induced rat oral cancer model and examined potential mechanisms. F344 rats were administered 4-nitroquinoline 1-oxide (4NQO (20 µg/ml in drinking water for 14 weeks followed by regular drinking water for 6 weeks. At week 14, rats were fed a diet containing either 5 or 10% BRB, or 0.4% ellagic acid (EA, a BRB phytochemical. Dietary administration of 5 and 10% BRB reduced oral lesion incidence and multiplicity by 39.3 and 28.6%, respectively. Histopathological analyses demonstrate the ability of BRBs and, to a lesser extent EA, to inhibit the progression of oral cancer. Oral lesion inhibition by BRBs was associated with a reduction in the mRNA expression of pro-inflammatory biomarkers Cxcl1, Mif, and Nfe2l2 as well as the anti-apoptotic and cell cycle associated markers Birc5, Aurka, Ccna1, and Ccna2. Cellular proliferation (Ki-67 staining in tongue lesions was inhibited by BRBs and EA. Our study demonstrates that, in the rat 4NQO oral cancer model, dietary administration of BRBs inhibits oral carcinogenesis via inhibition of pro-inflammatory and anti-apoptotic pathways.

  11. Protocol Fuel Mix reporting

    International Nuclear Information System (INIS)

    2002-07-01

    The protocol in this document describes a method for an Electricity Distribution Company (EDC) to account for the fuel mix of electricity that it delivers to its customers, based on the best available information. Own production, purchase and sale of electricity, and certificates trading are taken into account. In chapter 2 the actual protocol is outlined. In the appendixes additional (supporting) information is given: (A) Dutch Standard Fuel Mix, 2000; (B) Calculation of the Dutch Standard fuel mix; (C) Procedures to estimate and benchmark the fuel mix; (D) Quality management; (E) External verification; (F) Recommendation for further development of the protocol; (G) Reporting examples

  12. Coded Splitting Tree Protocols

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Stefanovic, Cedomir; Popovski, Petar

    2013-01-01

    This paper presents a novel approach to multiple access control called coded splitting tree protocol. The approach builds on the known tree splitting protocols, code structure and successive interference cancellation (SIC). Several instances of the tree splitting protocol are initiated, each...... instance is terminated prematurely and subsequently iterated. The combined set of leaves from all the tree instances can then be viewed as a graph code, which is decodable using belief propagation. The main design problem is determining the order of splitting, which enables successful decoding as early...

  13. Playing With Population Protocols

    Directory of Open Access Journals (Sweden)

    Xavier Koegler

    2009-06-01

    Full Text Available Population protocols have been introduced as a model of sensor networks consisting of very limited mobile agents with no control over their own movement: A collection of anonymous agents, modeled by finite automata, interact in pairs according to some rules. Predicates on the initial configurations that can be computed by such protocols have been characterized under several hypotheses. We discuss here whether and when the rules of interactions between agents can be seen as a game from game theory. We do so by discussing several basic protocols.

  14. ATM and Internet protocol

    CERN Document Server

    Bentall, M; Turton, B

    1998-01-01

    Asynchronous Transfer Mode (ATM) is a protocol that allows data, sound and video being transferred between independent networks via ISDN links to be supplied to, and interpreted by, the various system protocols.ATM and Internet Protocol explains the working of the ATM and B-ISDN network for readers with a basic understanding of telecommunications. It provides a handy reference to everyone working with ATM who may not require the full standards in detail, but need a comprehensive guide to ATM. A substantial section is devoted to the problems of running IP over ATM and there is some discussion o

  15. Mobile Internet Protocol Analysis

    National Research Council Canada - National Science Library

    Brachfeld, Lawrence

    1999-01-01

    ...) and User Datagram Protocol (UDP). Mobile IP allows mobile computers to send and receive packets addressed with their home network IP address, regardless of the IP address of their current point of attachment on the Internet...

  16. USA-USSR protocol

    CERN Multimedia

    1970-01-01

    On 30 November the USA Atomic Energy Commission and the USSR State Committee for the Utilization of Atomic Energy signed, in Washington, a protocol 'on carrying out of joint projects in the field of high energy physics at the accelerators of the National Accelerator Laboratory (Batavia) and the Institute for High Energy Physics (Serpukhov)'. The protocol will be in force for five years and can be extended by mutual agreement.

  17. Drugs with potential chemopreventive properties in relation to epithelial ovarian cancer--a nationwide case-control study.

    Science.gov (United States)

    Baandrup, Louise

    2015-07-01

    Ovarian cancer has a poor prognosis because the disease in the majority of patients is diagnosed at an advanced stage as a result of nonspecific symptoms and lack of efficient screening methods. Because of the poor prognosis of ovarian cancer and the challenge of early detection of the disease, identification of protective factors is important. It has been suggested that some commonly used drugs may have a protective effect against cancer, including ovarian cancer; however, the literature on chemopreventive measures for ovarian cancer is sparse and the results are inconclusive. Most previous studies have substantial methodological constraints, including limited study size and self-reporting of drug use, which introduces potential recall bias and misclassification. This PhD thesis includes a nationwide case-control study to evaluate associations between use of drugs with potential chemopreventive properties and risk of epithelial ovarian cancer. The study is nested in the entire Danish female population using data from the following nationwide registries: the Danish Cancer Registry, the Danish Civil Registration System, the Danish Prescription Registry, the Danish National Patient Register, and registries in Statistics Denmark on fertility, education, and income. Information from the included registries is linked by use of the unique personal identification number assigned to all Danish citizens. The cases were all women in Denmark with epithelial ovarian cancer diagnosed during 2000-2009 (Paper 1) and 2000-2011 (Papers 2 and 3), identified in the Cancer Registry. Age-matched female population controls were randomly selected from the Civil Registration System by risk-set sampling. We required that cases and controls have no history of cancer (except non-melanoma skin cancer) and that controls not previously have undergone bilateral oophorectomy or salpingo-oophorectomy. The total study population comprised 3741 epithelial ovarian cancer cases and 50,576 controls in

  18. Feasibility, safety and effectiveness of combining home based malaria management and seasonal malaria chemoprevention in children less than 10 years in Senegal

    DEFF Research Database (Denmark)

    Tine, Roger C K; Ndour, Cheikh T; Faye, Babacar

    2014-01-01

    Home-based management of malaria (HMM) may improve access to diagnostic testing and treatment with artemisinin combination therapy (ACT). In the Sahel region, seasonal malaria chemoprevention (SMC) is now recommended for the prevention of malaria in children. It is likely that combinations...... of antimalarial interventions can reduce the malaria burden. This study assessed the feasibility, effectiveness and safety of combining SMC and HMM delivered by community health workers (CHWs)....

  19. The chemopreventive action of bromelain, from pineapple stem (Ananas comosus L.), on colon carcinogenesis is related to antiproliferative and proapoptotic effects.

    Science.gov (United States)

    Romano, Barbara; Fasolino, Ines; Pagano, Ester; Capasso, Raffaele; Pace, Simona; De Rosa, Giuseppe; Milic, Natasa; Orlando, Pierangelo; Izzo, Angelo A; Borrelli, Francesca

    2014-03-01

    Colorectal cancer is an important health problem across the world. Here, we investigated the possible antiproliferative/proapoptotic effects of bromelain (from the pineapple stem Ananas comosus L., family Bromeliaceae) in a human colorectal carcinoma cell line and its potential chemopreventive effect in a murine model of colon cancer. Proliferation and apoptosis were evaluated in human colon adenocarcinoma (Caco-2) cells by the (3) H-thymidine incorporation assay and caspase 3/7 activity measurement, respectively. Extracellular signal-related kinase (ERK) and Akt expression were evaluated by Western blot analysis, reactive oxygen species production by a fluorimetric method. In vivo, bromelain was evaluated using the azoxymethane murine model of colon carcinogenesis. Bromelain reduced cell proliferation and promoted apoptosis in Caco-2 cells. The effect of bromelain was associated to downregulation of pERK1/2/total, ERK, and pAkt/Akt expression as well as to reduction of reactive oxygen species production. In vivo, bromelain reduced the development of aberrant crypt foci, polyps, and tumors induced by azoxymethane. Bromelain exerts antiproliferative and proapoptotic effects in colorectal carcinoma cells and chemopreventive actions in colon carcinogenesis in vivo. Bromelain-containing foods and/or bromelain itself may represent good candidates for colorectal cancer chemoprevention. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Lipid-based oral delivery systems for skin deposition of a potential chemopreventive DIM derivative: characterization and evaluation.

    Science.gov (United States)

    Boakye, Cedar H A; Patel, Ketan; Patel, Apurva R; Faria, Henrique A M; Zucolotto, Valtencir; Safe, Stephen; Singh, Mandip

    2016-10-01

    The objective of this study was to explore the oral route as a viable potential for the skin deposition of a novel diindolylmethane derivative (DIM-D) for chemoprevention activity. Various lipid-based oral delivery systems were optimized and compared for enhancing DIM-D's oral bioavailability and skin deposition. Preformulation studies were performed to evaluate the log P and solubility of DIM-D. Microsomal metabolism, P-glycoprotein efflux, and caco-2 monolayer permeability of DIM-D were determined. Comparative evaluation of the oral absorption and skin deposition of DIM-D-loaded various lipid-based formulations was performed in rats. DIM-D showed pH-dependent solubility and a high log P value. It was not a strong substrate of microsomal degradation and P-glycoprotein. SMEDDs comprised of medium chain triglycerides, monoglycerides, and kolliphor-HS15 (36.70 ± 0.42 nm). SNEDDs comprised of long chain triglycerides, cremophor RH40, labrasol, and TPGS (84.00 ± 14.14 nm). Nanostructured lipid carriers (NLC) consisted of compritol, miglyol, and surfactants (116.50 ± 2.12 nm). The blank formulations all showed >70 % cell viability in caco-2 cells. Differential Scanning Calorimetry confirmed the amorphization of DIM-D within the lipid matrices while Atomic Force Microscopy showed particle size distribution similar to the dynamic light scattering data. DIM-D also showed reduced permeation across caco-2 monolayer that was enhanced (p < 0.05) by SNEDDs in comparison to SMEDDs and NLC. Fabsolute for DIM-D SNEDDs, SMEDDs, and NLC was 0.14, 0.04, and 0.007, respectively. SNEDDs caused 53.90, 11.32, and 15.08-fold more skin deposition of DIM-D than the free drug, SMEDDs, and NLC, respectively, at 2 h following oral administration and shows a viable potential for use in skin cancer chemoprevention. Graphical Abstract ᅟ.

  1. Chemoprevention of Basal and Squamous Cell Carcinoma With a Single Course of Fluorouracil, 5%, Cream: A Randomized Clinical Trial.

    Science.gov (United States)

    Weinstock, Martin A; Thwin, Soe Soe; Siegel, Julia A; Marcolivio, Kimberly; Means, Alexander D; Leader, Nicholas F; Shaw, Fiona M; Hogan, Daniel; Eilers, David; Swetter, Susan M; Chen, Suephy C; Jacob, Sharon E; Warshaw, Erin M; Stricklin, George P; Dellavalle, Robert P; Sidhu-Malik, Navjeet; Konnikov, Nellie; Werth, Victoria P; Keri, Jonette E; Robinson-Bostom, Leslie; Ringer, Robert J; Lew, Robert A; Ferguson, Ryan; DiGiovanna, John J; Huang, Grant D

    2018-02-01

    Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31

  2. In silico toxicology protocols.

    Science.gov (United States)

    Myatt, Glenn J; Ahlberg, Ernst; Akahori, Yumi; Allen, David; Amberg, Alexander; Anger, Lennart T; Aptula, Aynur; Auerbach, Scott; Beilke, Lisa; Bellion, Phillip; Benigni, Romualdo; Bercu, Joel; Booth, Ewan D; Bower, Dave; Brigo, Alessandro; Burden, Natalie; Cammerer, Zoryana; Cronin, Mark T D; Cross, Kevin P; Custer, Laura; Dettwiler, Magdalena; Dobo, Krista; Ford, Kevin A; Fortin, Marie C; Gad-McDonald, Samantha E; Gellatly, Nichola; Gervais, Véronique; Glover, Kyle P; Glowienke, Susanne; Van Gompel, Jacky; Gutsell, Steve; Hardy, Barry; Harvey, James S; Hillegass, Jedd; Honma, Masamitsu; Hsieh, Jui-Hua; Hsu, Chia-Wen; Hughes, Kathy; Johnson, Candice; Jolly, Robert; Jones, David; Kemper, Ray; Kenyon, Michelle O; Kim, Marlene T; Kruhlak, Naomi L; Kulkarni, Sunil A; Kümmerer, Klaus; Leavitt, Penny; Majer, Bernhard; Masten, Scott; Miller, Scott; Moser, Janet; Mumtaz, Moiz; Muster, Wolfgang; Neilson, Louise; Oprea, Tudor I; Patlewicz, Grace; Paulino, Alexandre; Lo Piparo, Elena; Powley, Mark; Quigley, Donald P; Reddy, M Vijayaraj; Richarz, Andrea-Nicole; Ruiz, Patricia; Schilter, Benoit; Serafimova, Rositsa; Simpson, Wendy; Stavitskaya, Lidiya; Stidl, Reinhard; Suarez-Rodriguez, Diana; Szabo, David T; Teasdale, Andrew; Trejo-Martin, Alejandra; Valentin, Jean-Pierre; Vuorinen, Anna; Wall, Brian A; Watts, Pete; White, Angela T; Wichard, Joerg; Witt, Kristine L; Woolley, Adam; Woolley, David; Zwickl, Craig; Hasselgren, Catrin

    2018-04-17

    The present publication surveys several applications of in silico (i.e., computational) toxicology approaches across different industries and institutions. It highlights the need to develop standardized protocols when conducting toxicity-related predictions. This contribution articulates the information needed for protocols to support in silico predictions for major toxicological endpoints of concern (e.g., genetic toxicity, carcinogenicity, acute toxicity, reproductive toxicity, developmental toxicity) across several industries and regulatory bodies. Such novel in silico toxicology (IST) protocols, when fully developed and implemented, will ensure in silico toxicological assessments are performed and evaluated in a consistent, reproducible, and well-documented manner across industries and regulatory bodies to support wider uptake and acceptance of the approaches. The development of IST protocols is an initiative developed through a collaboration among an international consortium to reflect the state-of-the-art in in silico toxicology for hazard identification and characterization. A general outline for describing the development of such protocols is included and it is based on in silico predictions and/or available experimental data for a defined series of relevant toxicological effects or mechanisms. The publication presents a novel approach for determining the reliability of in silico predictions alongside experimental data. In addition, we discuss how to determine the level of confidence in the assessment based on the relevance and reliability of the information. Copyright © 2018. Published by Elsevier Inc.

  3. Business protocol in integrated Europe

    OpenAIRE

    Pavelová, Nina

    2009-01-01

    The first chapter devotes to definitions of basic terms such as protocol or business protocol, to differences between protocol and etiquette, and between social etiquette and business etiquette. The second chapter focuses on the factors influencing the European business protocol. The third chapter is devoted to the etiquette of business protocol in the European countries. It touches the topics such as punctuality and planning of business appointment, greeting, business cards, dress and appear...

  4. Security Protocols in a Nutshell

    OpenAIRE

    Toorani, Mohsen

    2016-01-01

    Security protocols are building blocks in secure communications. They deploy some security mechanisms to provide certain security services. Security protocols are considered abstract when analyzed, but they can have extra vulnerabilities when implemented. This manuscript provides a holistic study on security protocols. It reviews foundations of security protocols, taxonomy of attacks on security protocols and their implementations, and different methods and models for security analysis of pro...

  5. Cancer chemoprevention and cancer preventive vaccines--a call to action: leaders of diverse stakeholder groups present strategies for overcoming multiple barriers to meet an urgent need.

    Science.gov (United States)

    Herberman, Ronald B; Pearce, Homer L; Lippman, Scott M; Pyenson, Bruce S; Alberts, David S

    2006-12-15

    The emerging field of cancer prevention through chemoprevention agents and cancer vaccines offers significant promise for reducing suffering and death from cancer. However, that promise may not be kept unless major barriers to progress are lowered or eliminated. Among the most significant barriers are the relatively small investment from government and industry in research and development of cancer preventive agents; a predominant emphasis of translational cancer research on therapeutic interventions for metastatic or advanced cancer; complexities of prevention trial design; a relatively uncharted Food and Drug Administration (FDA) approval process for preventive agents; insufficient public and patient understanding of the importance and potential for cancer preventive measures, with consequent unpredictable public and patient willingness to take preventive agents; an uncertain reimbursement from payors; and limitations in patent law, liability protection, and data package exclusivity that undermine the opportunity for recouping investment. Viewed individually or collectively, each of these barriers serves as a substantial deterrent to intellectual and financial investment by all sectors of the cancer community. In an effort to ultimately overcome these barriers, a Cancer Prevention Research Summit was assembled June 12-13, 2006 in Bethesda, Maryland, organized by C-Change with support from the AACR. The Summit brought together some 120 leaders from private, public, and not-for-profit entities, including cancer researchers and clinicians; federal health officials; regulatory agency representatives; pharmaceutical, biotech, and food industry leaders; patent attorneys; economists; public and private provider group executives; and advocates. Participants engaged in a detailed process to more carefully define the major barriers, identify potential solutions, and formulate initial priorities and recommendations for action. At the conclusion of this dialogue among

  6. DNA repair protocols

    DEFF Research Database (Denmark)

    Bjergbæk, Lotte

    In its 3rd edition, this Methods in Molecular Biology(TM) book covers the eukaryotic response to genomic insult including advanced protocols and standard techniques in the field of DNA repair. Offers expert guidance for DNA repair, recombination, and replication. Current knowledge of the mechanisms...... that regulate DNA repair has grown significantly over the past years with technology advances such as RNA interference, advanced proteomics and microscopy as well as high throughput screens. The third edition of DNA Repair Protocols covers various aspects of the eukaryotic response to genomic insult including...... recent advanced protocols as well as standard techniques used in the field of DNA repair. Both mammalian and non-mammalian model organisms are covered in the book, and many of the techniques can be applied with only minor modifications to other systems than the one described. Written in the highly...

  7. Does a role for selenium in DNA damage repair explain apparent controversies in its use in chemoprevention?

    Science.gov (United States)

    Diamond, Alan M.

    2013-01-01

    The trace element selenium is an essential micronutrient that has received considerable attention for its potential use in the prevention of cancer. In spite of this interest, the mechanism(s) by which selenium might function as a chemopreventive remain to be determined. Considerable experimental evidence indicates that one possible mechanism by which selenium supplementation may exert its benefits is by enhancing the DNA damage repair response, and this includes data obtained using cultured cells, animal models as well as in human clinical studies. In these studies, selenium supplementation has been shown to be beneficial in reducing the frequency of DNA adducts and chromosome breaks, consequentially reducing the likelihood of detrimental mutations that ultimately contribute to carcinogenesis. The benefits of selenium can be envisioned as being due, at least in part, to it being a critical constituent of selenoproteins such as glutathione peroxidases and thioredoxin reductases, proteins that play important roles in antioxidant defence and maintaining the cellular reducing environment. Selenium, therefore, may be protective by preventing DNA damage from occurring as well as by increasing the activity of repair enzymes such as DNA glycosylases and DNA damage repair pathways that involve p53, BRCA1 and Gadd45. An improved understanding of the mechanism of selenium’s impact on DNA repair processes may help to resolve the apparently contradicting data obtained from decades of animal work, human epidemiology and more recently, clinical supplementation studies. PMID:23204505

  8. Chemopreventive and Antioxidant Effect of Polyphenol Free Spirulina maxima and Its Hydrolyzed Protein Content: Investigation on Azoxymethane Treated Mice.

    Science.gov (United States)

    Martínez-Palma, Nikte Y; Dávila-Ortiz, Gloria; Jiménez-Martínez, Cristian; Madrigal-Bujaidar, Eduardo; Álvarez-González, Isela

    2017-07-01

    Spirulina maxima (Sm) is known to have nutritive value as well as a number of potentially useful biomedical properties. The initial purpose of this report was to evaluate the inhibitory effect of the alga (without its polyphenol content), on the induction of azoxymethane (AOM)-induced colon aberrant crypts (AC) in mouse. Besides, we hydrolyzed the protein content of such mixture. Our second aim was to determine the inhibitory potential of this last plant mixture on the AOM-induced colon AC in mouse. Moreover, we also determined the effect of the two indicated Sm samples on the oxidative damage caused by AOM in the colon and liver of treated mice. The experiment lasted 5 weeks. At the end, we registered the level of AC, nitric oxide, and the lipid and protein oxidation. Our results showed the following: (1) the carcinogen increased more than 18 times the amount of the AC found in the control group. (2) On the contrary, the two tested mixtures of Sm produced a significant reduction over this damage (about 45%). (3) The two tested Sm mixtures were generally able to reduce the oxidative stress markers although with variable effects which go from 59% to 100% with respect to the control mice. Therefore, the present report established that the tested Sm fractions have mouse colon anticarcinogenic potential, partially related with their antioxidant capacity. Our report also suggested the need to further evaluate specific Sm chemicals as chemopreventive agents.

  9. DuCLOX-2/5 Inhibition Attenuates Inflammatory Response and Induces Mitochondrial Apoptosis for Mammary Gland Chemoprevention

    Directory of Open Access Journals (Sweden)

    Swetlana Gautam

    2018-04-01

    Full Text Available The present study is a pursuit to define implications of dual cyclooxygenase-2 (COX-2 and 5-lipoxygenase (5-LOX (DuCLOX-2/5 inhibition on various aspects of cancer augmentation and chemoprevention. The monotherapy and combination therapy of zaltoprofen (COX-2 inhibitor and zileuton (5-LOX inhibitor were validated for their effect against methyl nitrosourea (MNU induced mammary gland carcinoma in albino wistar rats. The combination therapy demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count and restoration of the histopathological architecture when compared to toxic control. DuCLOX-2/5 inhibition also upregulated levels of caspase-3 and caspase-8, and restored oxidative stress markers (GSH, TBARs, protein carbonyl, SOD and catalase. The immunoblotting and qRT-PCR studies revealed the participation of the mitochondrial mediated death apoptosis pathway along with favorable regulation of COX-2, 5-LOX. Aforementioned combination restored the metabolic changes to normal when scrutinized through 1H NMR studies. Henceforth, the DuCLOX-2/5 inhibition was recorded to import significant anticancer effects in comparison to either of the individual treatments.

  10. Zileuton, 5-lipoxygenase inhibitor, acts as a chemopreventive agent in intestinal polyposis, by modulating polyp and systemic inflammation.

    Directory of Open Access Journals (Sweden)

    Elias Gounaris

    Full Text Available Leukotrienes and prostaglandins, products of arachidonic acid metabolism, sustain both systemic and lesion-localized inflammation. Tumor-associated Inflammation can also contribute to the pathogenesis of colon cancer. Patients with inflammatory bowel disease (IBD have increased risk of developing colon cancer. The levels of 5-lipoxygenase (5-LO, the key enzyme for leukotrienes production, are increased in colon cancer specimens and colonic dysplastic lesions. Here we report that Zileuton, a specific 5-LO inhibitor, can prevent polyp formation by efficiently reducing the tumor-associated and systemic inflammation in APCΔ468 mice.In the current study, we inhibited 5-LO by dietary administration of Zileuton in the APCΔ468 mouse model of polyposis and analyzed the effect of in vivo 5-LO inhibition on tumor-associated and systemic inflammation.Zileuton-fed mice developed fewer polyps and displayed marked reduction in systemic and polyp-associated inflammation. Pro-inflammatory cytokines and pro-inflammatory innate and adaptive immunity cells were reduced both in the lesions and systemically. As part of tumor-associated inflammation Leukotriene B4 (LTB4, product of 5-LO activity, is increased focally in human dysplastic lesions. The 5-LO enzymatic activity was reduced in the serum of Zileuton treated polyposis mice.This study demonstrates that dietary administration of 5-LO specific inhibitor in the polyposis mouse model decreases polyp burden, and suggests that Zileuton may be a potential chemo-preventive agent in patients that are high-risk of developing colon cancer.

  11. Protocol Monitoring Energy Conservation; Protocol Monitoring Energiebesparing

    Energy Technology Data Exchange (ETDEWEB)

    Boonekamp, P.G.M. [ECN Beleidsstudies, Petten (Netherlands); Mannaerts, H. [Centraal Planburea CPB, Den Haag (Netherlands); Tinbergen, W. [Centraal Bureau voor de Statistiek CBS, Den Haag (Netherlands); Vreuls, H.H.J. [Nederlandse onderneming voor energie en milieu Novem, Utrecht (Netherlands); Wesselink, B. [Rijksinstituut voor Volksgezondheid en Milieuhygiene RIVM, Bilthoven (Netherlands)

    2001-12-01

    On request of the Dutch ministry of Economic Affairs five institutes have collaborated to create a 'Protocol Monitoring Energy Conservation', a common method and database to calculate the amount of energy savings realised in past years. The institutes concerned are the Central Bureau of Statistics (CBS), the Netherlands Bureau for Economic Policy Analysis (CPB), the Energy research Centre of the Netherlands (ECN), the National Agency for Energy and Environment (Novem) and the Netherlands Institute of Public Health and the Environment (RIVM). The institutes have agreed upon a clear definition of energy use and energy savings. The demarcation with renewable energy, the saving effects of substitution between energy carriers and the role of import and export of energy have been elaborated. A decomposition method is used to split up the observed change in energy use in a number of effects, on a national and sectoral level. This method includes an analysis of growth effects, effects of structural changes in production and consumption activities and savings on end use or with more efficient conversion processes. To calculate these effects the total energy use is desegregated as much as possible. For each segment a reference energy use is calculated according to the trend in a variable which is supposed to be representative for the use without savings. The difference with the actual energy use is taken as the savings realised. Results are given for the sectors households, industry, agriculture, services and government, transportation and the energy sector; as well as a national figure. A special feature of the protocol method is the application of primary energy use figures in the determination of savings for end users. This means that the use of each energy carrier is increased with a certain amount, according to the conversion losses caused elsewhere in the energy system. The losses concern the base year energy sector and losses abroad for imports of secondary

  12. Immunocytochemical methods and protocols

    National Research Council Canada - National Science Library

    Javois, Lorette C

    1999-01-01

    ... monoclonal antibodies to study cell differentiation during embryonic development. For a select few disciplines volumes have been published focusing on the specific application of immunocytochemical techniques to that discipline. What distinguished Immunocytochemical Methods and Protocols from earlier books when it was first published four years ago was i...

  13. Critical Response Protocol

    Science.gov (United States)

    Ellingson, Charlene; Roehrig, Gillian; Bakkum, Kris; Dubinsky, Janet M.

    2016-01-01

    This article introduces the Critical Response Protocol (CRP), an arts-based technique that engages students in equitable critical discourse and aligns with the "Next Generation Science Standards" vision for providing students opportunities for language learning while advancing science learning (NGSS Lead States 2013). CRP helps teachers…

  14. Linear Logical Voting Protocols

    DEFF Research Database (Denmark)

    DeYoung, Henry; Schürmann, Carsten

    2012-01-01

    Current approaches to electronic implementations of voting protocols involve translating legal text to source code of an imperative programming language. Because the gap between legal text and source code is very large, it is difficult to trust that the program meets its legal specification. In r...

  15. Principles of Protocol Design

    DEFF Research Database (Denmark)

    Sharp, Robin

    This is a new and updated edition of a book first published in 1994. The book introduces the reader to the principles used in the construction of a large range of modern data communication protocols, as used in distributed computer systems of all kinds. The approach taken is rather a formal one...

  16. Model Additional Protocol

    International Nuclear Information System (INIS)

    Rockwood, Laura

    2001-01-01

    Since the end of the cold war a series of events has changed the circumstances and requirements of the safeguards system. The discovery of a clandestine nuclear weapons program in Iraq, the continuing difficulty in verifying the initial report of Democratic People's Republic of Korea upon entry into force of their safeguards agreement, and the decision of the South African Government to give up its nuclear weapons program and join the Treaty on the Non-Proliferation of Nuclear Weapons have all played a role in an ambitious effort by IAEA Member States and the Secretariat to strengthen the safeguards system. A major milestone in this effort was reached in May 1997 when the IAEA Board of Governors approved a Model Protocol Additional to Safeguards Agreements. The Model Additional Protocol was negotiated over a period of less than a year by an open-ended committee of the Board involving some 70 Member States and two regional inspectorates. The IAEA is now in the process of negotiating additional protocols, State by State, and implementing them. These additional protocols will provide the IAEA with rights of access to information about all activities related to the use of nuclear material in States with comprehensive safeguards agreements and greatly expanded physical access for IAEA inspectors to confirm or verify this information. In conjunction with this, the IAEA is working on the integration of these measures with those provided for in comprehensive safeguards agreements, with a view to maximizing the effectiveness and efficiency, within available resources, the implementation of safeguards. Details concerning the Model Additional Protocol are given. (author)

  17. Satellite Communications Using Commercial Protocols

    Science.gov (United States)

    Ivancic, William D.; Griner, James H.; Dimond, Robert; Frantz, Brian D.; Kachmar, Brian; Shell, Dan

    2000-01-01

    NASA Glenn Research Center has been working with industry, academia, and other government agencies in assessing commercial communications protocols for satellite and space-based applications. In addition, NASA Glenn has been developing and advocating new satellite-friendly modifications to existing communications protocol standards. This paper summarizes recent research into the applicability of various commercial standard protocols for use over satellite and space- based communications networks as well as expectations for future protocol development. It serves as a reference point from which the detailed work can be readily accessed. Areas that will be addressed include asynchronous-transfer-mode quality of service; completed and ongoing work of the Internet Engineering Task Force; data-link-layer protocol development for unidirectional link routing; and protocols for aeronautical applications, including mobile Internet protocol routing for wireless/mobile hosts and the aeronautical telecommunications network protocol.

  18. Epistemic Protocols for Distributed Gossiping

    Directory of Open Access Journals (Sweden)

    Krzysztof R. Apt

    2016-06-01

    Full Text Available Gossip protocols aim at arriving, by means of point-to-point or group communications, at a situation in which all the agents know each other's secrets. We consider distributed gossip protocols which are expressed by means of epistemic logic. We provide an operational semantics of such protocols and set up an appropriate framework to argue about their correctness. Then we analyze specific protocols for complete graphs and for directed rings.

  19. Symmetric cryptographic protocols

    CERN Document Server

    Ramkumar, Mahalingam

    2014-01-01

    This book focuses on protocols and constructions that make good use of symmetric pseudo random functions (PRF) like block ciphers and hash functions - the building blocks for symmetric cryptography. Readers will benefit from detailed discussion of several strategies for utilizing symmetric PRFs. Coverage includes various key distribution strategies for unicast, broadcast and multicast security, and strategies for constructing efficient digests of dynamic databases using binary hash trees.   •        Provides detailed coverage of symmetric key protocols •        Describes various applications of symmetric building blocks •        Includes strategies for constructing compact and efficient digests of dynamic databases

  20. Large-scale delivery of seasonal malaria chemoprevention to children under 10 in Senegal: an economic analysis

    Science.gov (United States)

    Pitt, Catherine; Ndiaye, Mouhamed; Conteh, Lesong; Sy, Ousmane; Hadj Ba, El; Cissé, Badara; Gomis, Jules F; Gaye, Oumar; Ndiaye, Jean-Louis

    2017-01-01

    Abstract Seasonal Malaria Chemoprevention (SMC) is recommended for children under 5 in the Sahel and sub-Sahel. The burden in older children may justify extending the age range, as has been done effectively in Senegal. We examine costs of door-to-door SMC delivery to children up to 10 years by community health workers (CHWs). We analysed incremental financial and economic costs at district level and below from a health service perspective. We examined project accounts and prospectively collected data from 405 CHWs, 46 health posts, and 4 district headquarters by introducing questionnaires in advance and completing them after each monthly implementation round. Affordability was explored by comparing financial costs of SMC to relevant existing health expenditure levels. Costs were disaggregated by administration month and by health service level. We used linear regression models to identify factors associated with cost variation between health posts. The financial cost to administer SMC to 180 000 children over one malaria season, reaching ∼93% of children with all three intended courses of SMC was $234 549 (constant 2010 USD) or $0.50 per monthly course administered. Excluding research–participation incentives, the financial cost was $0.32 per resident (all ages) in the catchment area, which is 1.2% of Senegal’s general government expenditure on health per capita. Economic costs were 18.7% higher than financial costs at $278 922 or $0.59 per course administered and varied widely between health posts, from $0.38 to $2.74 per course administered. Substantial economies of scale across health posts were found, with the smallest health posts incurring highest average costs per monthly course administered. SMC for children up to 10 is likely to be affordable, particularly where it averts substantial curative care costs. Estimates of likely costs and cost-effectiveness of SMC in other contexts must account for variation in average costs across delivery months

  1. Evaluation of chemopreventive and cytotoxic effect of lemon seed extracts on human breast cancer (MCF-7) cells.

    Science.gov (United States)

    Kim, Jinhee; Jayaprakasha, Guddadarangavvanahally K; Uckoo, Ram M; Patil, Bhimanagouda S

    2012-02-01

    Extracts from lemon seed were investigated for the radical scavenging activity and apoptotic effects in human breast adenocarcinoma (MCF-7) cells and non-malignant breast (MCF-12F) cells for the first time. Defatted seed powder was successively extracted with ethyl acetate (EtOAc), acetone, methanol (MeOH), and MeOH:water (80:20). The chemical constituents were identified and quantified by LC-MS and HPLC analysis, respectively. The highest radical scavenging activity of 62.2% and 91.3% was exhibited by MeOH:water (80:20) at 833μg/mL in 1,1-diphenyl-2-picryl hydrazyl (DPPH) and 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS(+)), respectively. In addition, the MeOH:water (80:20) extract showed the highest (29.1%, Pwater (80:20) extract induced DNA fragmentation and poly(ADP-ribose) polymerase (PARP) cleavage. Increased levels of Bax and cytosolic cytochrome C and decreased levels of Bcl2 were also observed in MeOH:water (80:20) treated MCF-7 cells. In conclusion, the MeOH:water (80:20) extract from lemon seed has potent antioxidant activity and induces apoptosis in MCF-7 cells, leading to the inhibition of proliferation. These results suggest that aglycones and glucosides of the limonoids and flavonoid present in MeOH:water (80:20) extract may potentially serve as a chemopreventive agent for breast cancer. Copyright © 2011 Elsevier Ltd. All rights reserved.

  2. The chemopreventive potential of Curcuma purpurascens rhizome in reducing azoxymethane-induced aberrant crypt foci in rats

    Science.gov (United States)

    Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Al-Henhena, Nawal; Kunasegaran, Thubasni; Hasanpourghadi, Mohadeseh; Looi, Chung Yeng; Abd Malek, Sri Nurestri; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

    2015-01-01

    Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation

  3. Quantification of 4'-geranyloxyferulic acid, a new natural colon cancer chemopreventive agent, by HPLC-DAD in grapefruit skin extract.

    Science.gov (United States)

    Genovese, S; Epifano, F; Carlucci, G; Marcotullio, M C; Curini, M; Locatelli, M

    2010-10-10

    Oxyprenylated natural products (isopentenyloxy-, geranyloxy- and the less spread farnesyloxy-compounds and their biosynthetic derivatives) represent a family of secondary metabolites that have been consider for years merely as biosynthetic intermediates of the most abundant C-prenylated derivatives. Many of the isolated oxyprenylated natural products were shown to exert in vitro and in vivo remarkable anti-cancer and anti-inflammatory effects. 4'-Geranyloxyferulic acid [3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic] has been discovered as a valuable chemopreventive agent of several types of cancer. After development of a high yield and "eco-friendly" synthetic scheme of this secondary metabolite, starting from cheap and non-toxic reagents and substrates, we developed a new HPLC-DAD method for its quantification in grapefruit skin extract. A preliminary study on C18 column showed the separation between GOFA and boropinic acid (having the same core but with an isopentenyloxy side chain), used as internal standard. The tested column were thermostated at 28+/-1 degrees C and the separation was achieved in gradient condition at a flow rate of 1 mL/min with a starting mobile phase of H(2)O:methanol (40:60, v/v, 1% formic acid). The limit of detection (LOD, S/N=3) was 0.5 microg/mL and the limit of quantification (LOQ, S/N=10) was 1 microg/mL. Matrix-matched standard curves showed linearity up to 75 microg/mL. In the analytical range the precision (RSD%) values were extract of grapefruit. In conclusion, this method showed LOQ values able to selective quantification of this analyte in grapefruit skin extract.

  4. The inactivation of human CYP2E1 by phenethyl isothiocyanate, a naturally occurring chemopreventive agent, and its oxidative bioactivation.

    Science.gov (United States)

    Yoshigae, Yasushi; Sridar, Chitra; Kent, Ute M; Hollenberg, Paul F

    2013-04-01

    Phenethylisothiocyanate (PEITC), a naturally occurring isothiocyanate and potent cancer chemopreventive agent, works by multiple mechanisms, including the inhibition of cytochrome P450 (P450) enzymes, such as CYP2E1, that are involved in the bioactivation of carcinogens. PEITC has been reported to be a mechanism-based inactivator of some P450s. We describe here the possible mechanism for the inactivation of human CYP2E1 by PEITC, as well as the putative intermediate that might be involved in the bioactivation of PEITC. PEITC inactivated recombinant CYP2E1 with a partition ratio of 12, and the inactivation was not inhibited in the presence of glutathione (GSH) and not fully recovered by dialysis. The inactivation of CYP2E1 by PEITC is due to both heme destruction and protein modification, with the latter being the major pathway for inactivation. GSH-adducts of phenethyl isocyanate (PIC) and phenethylamine were detected during the metabolism by CYP2E1, indicating formation of PIC as a reactive intermediate following P450-catalyzed desulfurization of PEITC. Surprisingly, PIC bound covalently to CYP2E1 to form protein adducts but did not inactivate the enzyme. Liquid chromatography mass spectroscopy analysis of the inactivated CYP2E1 apo-protein suggests that a reactive sulfur atom generated during desulfurization of PEITC is involved in the inactivation of CYP2E1. Our data suggest that the metabolism of PEITC by CYP2E1 that results in the inactivation of CYP2E1 may occur by a mechanism similar to that observed with other sulfur-containing compounds, such as parathion. Digestion of the inactivated enzyme and analysis by SEQUEST showed that Cys 268 may be the residue modified by PIC.

  5. Diplomacy and Diplomatic Protocol

    Directory of Open Access Journals (Sweden)

    Lect. Ph.D Oana Iucu

    2008-12-01

    Full Text Available The present study aims to observe relationships and determining factors between diplomacyand diplomatic protocol as outlined by historical and contextual analyses. The approach is very dynamic,provided that concepts are able to show their richness, antiquity and polyvalence at the level of connotations,semantics, grammatical and social syntax. The fact that this information is up to date determines anattitude of appreciation and a state of positive contamination.

  6. Automatic Validation of Protocol Narration

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Degano, Pierpablo

    2003-01-01

    We perform a systematic expansion of protocol narrations into terms of a process algebra in order to make precise some of the detailed checks that need to be made in a protocol. We then apply static analysis technology to develop an automatic validation procedure for protocols. Finally, we...

  7. Dysphonia risk screening protocol

    Directory of Open Access Journals (Sweden)

    Katia Nemr

    2016-03-01

    Full Text Available OBJECTIVE: To propose and test the applicability of a dysphonia risk screening protocol with score calculation in individuals with and without dysphonia. METHOD: This descriptive cross-sectional study included 365 individuals (41 children, 142 adult women, 91 adult men and 91 seniors divided into a dysphonic group and a non-dysphonic group. The protocol consisted of 18 questions and a score was calculated using a 10-cm visual analog scale. The measured value on the visual analog scale was added to the overall score, along with other partial scores. Speech samples allowed for analysis/assessment of the overall degree of vocal deviation and initial definition of the respective groups and after six months, the separation of the groups was confirmed using an acoustic analysis. RESULTS: The mean total scores were different between the groups in all samples. Values ranged between 37.0 and 57.85 in the dysphonic group and between 12.95 and 19.28 in the non-dysphonic group, with overall means of 46.09 and 15.55, respectively. High sensitivity and specificity were demonstrated when discriminating between the groups with the following cut-off points: 22.50 (children, 29.25 (adult women, 22.75 (adult men, and 27.10 (seniors. CONCLUSION: The protocol demonstrated high sensitivity and specificity in differentiating groups of individuals with and without dysphonia in different sample groups and is thus an effective instrument for use in voice clinics.

  8. Dysphonia risk screening protocol

    Science.gov (United States)

    Nemr, Katia; Simões-Zenari, Marcia; da Trindade Duarte, João Marcos; Lobrigate, Karen Elena; Bagatini, Flavia Alves

    2016-01-01

    OBJECTIVE: To propose and test the applicability of a dysphonia risk screening protocol with score calculation in individuals with and without dysphonia. METHOD: This descriptive cross-sectional study included 365 individuals (41 children, 142 adult women, 91 adult men and 91 seniors) divided into a dysphonic group and a non-dysphonic group. The protocol consisted of 18 questions and a score was calculated using a 10-cm visual analog scale. The measured value on the visual analog scale was added to the overall score, along with other partial scores. Speech samples allowed for analysis/assessment of the overall degree of vocal deviation and initial definition of the respective groups and after six months, the separation of the groups was confirmed using an acoustic analysis. RESULTS: The mean total scores were different between the groups in all samples. Values ranged between 37.0 and 57.85 in the dysphonic group and between 12.95 and 19.28 in the non-dysphonic group, with overall means of 46.09 and 15.55, respectively. High sensitivity and specificity were demonstrated when discriminating between the groups with the following cut-off points: 22.50 (children), 29.25 (adult women), 22.75 (adult men), and 27.10 (seniors). CONCLUSION: The protocol demonstrated high sensitivity and specificity in differentiating groups of individuals with and without dysphonia in different sample groups and is thus an effective instrument for use in voice clinics. PMID:27074171

  9. Colon cancer chemoprevention by a novel NO chimera that shows anti-inflammatory and antiproliferative activity in vitro and in vivo.

    Science.gov (United States)

    Hagos, Ghenet K; Carroll, Robert E; Kouznetsova, Tatiana; Li, Qian; Toader, Violeta; Fernandez, Patricia A; Swanson, Steven M; Thatcher, Gregory R J

    2007-08-01

    Chemopreventive agents in colorectal cancer possess either antiproliferative or anti-inflammatory actions. Nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase-2 inhibitors have shown promise, but are compromised by side effects. Nitric oxide donor NSAIDs are organic nitrates conjugated via a labile linker to an NSAID, originally designed for use in pain relief, that have shown efficacy in colorectal cancer chemoprevention. The NO chimera, GT-094, is a novel nitrate containing an NSAID and disulfide pharmacophores, a lead compound for the design of agents specifically for colorectal cancer. GT-094 is the first nitrate reported to reduce aberrant crypt foci (by 45%) when administered after carcinogen in the standard azoxymethane rat model of colorectal cancer. Analysis of proximal and distal colon tissue from 8- and 28-week rat/azoxymethane studies showed that GT-094 treatment reduced colon crypt proliferation by 30% to 69%, reduced inducible NO synthase (iNOS) levels by 33% to 67%, reduced poly(ADP-ribose)polymerase-1 expression and cleavage 2- to 4-fold, and elevated levels of p27 in the distal colon 3-fold. Studies in cancer cell cultures recapitulated actions of GT-094: antiproliferative activity and transient G(2)-M phase cell cycle block were measured in Caco-2 cells; apoptotic activity was examined but not observed; anti-inflammatory activity was seen in the inhibition of up-regulation of iNOS and endogenous NO production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. In summary, antiproliferative, anti-inflammatory, and cytoprotective activity observed in vivo and in vitro support GT-094 as a lead compound for the design of NO chimeras for colorectal cancer chemoprevention.

  10. 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.

  11. Pharmacokinetics of Dietary Cancer Chemopreventive Compound Dibenzoylmethane in the Rats and Impacts of Nanoemulsion and Genetic knockout of Nrf2 on its Disposition

    OpenAIRE

    Lin, Wen; Hong, Jin-Liern; Shen, Guoxiang; Wu, Rachel T.; Wu, Yuwen; Huang, Mou-Tuan; Newmark, Harold L.; Huang, Qingrong; Khor, Tin Oo; Heimbach, Tycho; Kong, Ah-Ng

    2010-01-01

    The pharmacokinetic disposition of a dietary cancer chemopreventive compound dibenzoylmethane (DBM) was studied in male Sprague-Dawley rats after intravenous (i.v.) and oral (p.o.) administrations. Following a single i.v. bolus dose, the mean plasma clearance (CL) of DBM was low as compared to the hepatic blood flow. DBM displayed a high volume of distribution (Vss). The elimination terminal t1/2 was long. The mean CL, Vss and AUC0-∞/dose were similar between the i.v. 10 and 10 mg/kg doses. A...

  12. 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)

    Heidor, Renato; Furtado, Kelly Silva; Ortega, Juliana Festa; Oliveira, Tiago Franco de; Tavares, Paulo Eduardo Latorre Martins; Vieira, Alessandra; Miranda, Mayara Lilian Paulino; Purgatto, Eduardo; Moreno, Fernando Salvador

    2014-01-01

    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

  13. FRENCH PROTOCOL CARDS

    CERN Multimedia

    Division du Personnel

    1999-01-01

    Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.1999, are requested to return these cards and those of family members, for extension to:Bureau des cartes, bâtiment 33.1-025Should the 3 spaces for authentication on the back of the card be full, please enclose 2 passport photographs for a new card.In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.Personnel DivisionTel. 79494/74683

  14. FRENCH PROTOCOL CARDS

    CERN Multimedia

    Human Resources Division

    2000-01-01

    Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.2000, are requested to return these cards and those of family members, for extension to: Bureau des cartes, Bât 33.1-009/1-015 Should the three spaces for authentication on the back of the card be full, please enclose two passport photographs for a new card. In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.

  15. Sincalide - the final protocol

    International Nuclear Information System (INIS)

    Clarke, E.A.; Notghi, A.; Hesslewood, S.R.; Harding, L.K.

    2002-01-01

    Full text: HIDA biliary studies examine the gallbladder (GB) to give a percentage ejection fraction (EF). Porcine CCK was an accepted agent for stimulating the GB prior to being withdrawn in the UK from 1998. Sincalide (a synthetic CCK) was the suggested replacement. We have tried many administration regimes in an attempt to get results comparable with our established CCK protocols. Dose concentration and length of infusion times have been studied. Initially a dose of 10 ngm/kg/min given over 2 minutes (manufacturer's recommended dose) was used. This gave falsely low ejection fractions. The dose was reduced to 3 ngm/kg/min over 3 minutes as it was felt the higher dose may be causing constriction of the sphincter of Oddi. This gave a slight improvement with 22 % of patients having normal EF (>35 %). The length of infusion was extended to 15 minutes and the dose concentration reduced again to 0.6 ngm/kg/min. 62 % of patients had a normal EF. However, on many of the curves the gallbladder was still contracting on completion of the 15 minute infusion and began to refill immediately after stopping Sincalide. A further change of protocol was indicated. The infusion time was extended to 30 minutes and the dose concentration per minute kept the same. Imaging began at 30 minutes post HIDA injection and continued for a total of 50 minutes. Sincalide infusion began at 35 minutes if a GB was visualized. This protocol has been performed on 17 patients. 53 % of these had a normal result (comparable with a normal rate of 40 % previously established with CCK) with a mean EF of 60 %. The mean EF of patients with abnormal studies was 15 %. Curves showed a plateau by 30 minutes in 94 % of patients indicating that gallbladder contraction was complete. No normal range is available so results were compared with ultrasound (US). All patients who had an abnormal US scan also had abnormal HIDA results. Three patients had a normal US scan and abnormal HIDA study. These are currently

  16. Distributed Network Protocols

    Science.gov (United States)

    1980-07-01

    MONITORING AGENCY NAME & ADDRESS(II different from Controlting Office) IS. SECURITY CLASS. (of this report) S Office of Naval Research Unclassified...All protocols are extended to networks with changing. topology. S80 8 4 246 DD0I iA 1473 EDITION OF INOV 65 IS OBSOLETE 8 0 24 SECURITY CLASSIFICATION...to the netowrk . f) Each node knows its adjacent links, but not necessarily the identity of its neighbors, i.e. the nodes at the other end of the links

  17. The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers.

    Science.gov (United States)

    Omenn, G S; Goodman, G; Thornquist, M; Grizzle, J; Rosenstock, L; Barnhart, S; Balmes, J; Cherniack, M G; Cullen, M R; Glass, A

    1994-04-01

    CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk populations, namely, heavy smokers and asbestos-exposed workers. The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers (44% female). Accrual is complete everywhere except Irvine, which was the last center added (1991), and the safety profile of the regimen to date has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and 114,100 person-years through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finland and the Harvard Physicians Health Study (beta-carotene alone) in the National Cancer Institute portfolio of major cancer chemoprevention trials.

  18. A Review of the Potential of Phytochemicals from Prunus africana (Hook f. Kalkman Stem Bark for Chemoprevention and Chemotherapy of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Richard Komakech

    2017-01-01

    Full Text Available Prostate cancer remains one of the major causes of death worldwide. In view of the limited treatment options for patients with prostate cancer, preventive and treatment approaches based on natural compounds can play an integral role in tackling this disease. Recent evidence supports the beneficial effects of plant-derived phytochemicals as chemopreventive and chemotherapeutic agents for various cancers, including prostate cancer. Prunus africana has been used for generations in African traditional medicine to treat prostate cancer. This review examined the potential roles of the phytochemicals from P. africana, an endangered, sub-Saharan Africa plant in the chemoprevention and chemotherapy of prostate cancer. In vitro and in vivo studies have provided strong pharmacological evidence for antiprostate cancer activities of P. africana-derived phytochemicals. Through synergistic interactions between different effective phytochemicals, P. africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells. However, further preclinical and clinical studies ought to be done to advance and eventually use these promising phytochemicals for the prevention and chemotherapy of human prostate cancer.

  19. The REDUCE metagram: a comprehensive prediction tool for determining the utility of dutasteride chemoprevention in men at risk for prostate cancer

    Directory of Open Access Journals (Sweden)

    Carvell eNguyen

    2012-10-01

    Full Text Available Introduction: 5-alpha reductase inhibitors can reduce the risk of prostate cancer but can be associated with significant side effects. A library of nomograms which predict the risk of clinical endpoints relevant to dutasteride treatment may help determine if chemoprevention is suited to the individual patient. Methods: Data from the REDUCE trial was used to identify predictive factors for nine endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biopsy cohort, Cox proportional hazards and competing risks regression models were used to build 18 nomograms, whose predictive ability was measured by concordance index and calibration plots. Results: A total of 18 nomograms assessing the risks of cancer, high-grade cancer, high grade prostatic intraepithelial neoplasia (HGPIN, atypical small acinar proliferation (ASAP, erectile dysfunction (ED, acute urinary retention (AUR, gynecomastia, urinary tract infection (UTI and BPH-related surgery either on or off dutasteride were created. The nomograms for cancer, high grade cancer, ED, AUR, and BPH-related surgery demonstrated good discrimination and calibration while those for gynecomastia, UTI, HGPIN, and ASAP predicted no better than random chance. Conclusions: To aid patients in determining whether the benefits of dutasteride use outweigh the risks, we have developed a comprehensive metagram that can generate individualized risks of 9 outcomes relevant to men considering chemoprevention. Better models based on more predictive markers are needed for some of the endpoints but the current metagram demonstrates potential as a tool for patient counseling and decision making that is accessible, intuitive, and clinically relevant.

  20. Potential Impact of Seasonal Malaria Chemoprevention on the Acquisition of Antibodies Against Glutamate-Rich Protein and Apical Membrane Antigen 1 in Children Living in Southern Senegal

    DEFF Research Database (Denmark)

    Ndiaye, Magatte; Sylla, Khadime; Sow, Doudou

    2015-01-01

    Seasonal malaria chemoprevention (SMC) is defined as the intermittent administration of full treatment courses of an antimalarial drug to children during the peak of malaria transmission season with the aim of preventing malaria-associated mortality and morbidity. SMC using sulfadoxine-pyrimetham......Seasonal malaria chemoprevention (SMC) is defined as the intermittent administration of full treatment courses of an antimalarial drug to children during the peak of malaria transmission season with the aim of preventing malaria-associated mortality and morbidity. SMC using sulfadoxine......-pyrimethamine (SP) combined with amodiaquine (AQ) is a promising strategy to control malaria morbidity in areas of highly seasonal malaria transmission. However, a concern is whether SMC can delay the natural acquisition of immunity toward malaria parasites in areas with intense SMC delivery. To investigate this......, total IgG antibody (Ab) responses to Plasmodium falciparum antigens glutamate-rich protein R0 (GLURP-R0) and apical membrane antigen 1 (AMA-1) were measured by enzyme-linked immunosorbent assay in Senegalese children under the age of 10 years in 2010 living in Saraya and Velingara districts (with SMC...

  1. Security and SCADA protocols

    International Nuclear Information System (INIS)

    Igure, V. M.; Williams, R. D.

    2006-01-01

    Supervisory control and data acquisition (SCADA) networks have replaced discrete wiring for many industrial processes, and the efficiency of the network alternative suggests a trend toward more SCADA networks in the future. This paper broadly considers SCADA to include distributed control systems (DCS) and digital control systems. These networks offer many advantages, but they also introduce potential vulnerabilities that can be exploited by adversaries. Inter-connectivity exposes SCADA networks to many of the same threats that face the public internet and many of the established defenses therefore show promise if adapted to the SCADA differences. This paper provides an overview of security issues in SCADA networks and ongoing efforts to improve the security of these networks. Initially, a few samples from the range of threats to SCADA network security are offered. Next, attention is focused on security assessment of SCADA communication protocols. Three challenges must be addressed to strengthen SCADA networks. Access control mechanisms need to be introduced or strengthened, improvements are needed inside of the network to enhance security and network monitoring, and SCADA security management improvements and policies are needed. This paper discusses each of these challenges. This paper uses the Profibus protocol as an example to illustrate some of the vulnerabilities that arise within SCADA networks. The example Profibus security assessment establishes a network model and an attacker model before proceeding to a list of example attacks. (authors)

  2. 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

  3. Impact and Lessons Learned from Mass Drug Administrations of Malaria Chemoprevention during the Ebola Outbreak in Monrovia, Liberia, 2014.

    Science.gov (United States)

    Kuehne, Anna; Tiffany, Amanda; Lasry, Estrella; Janssens, Michel; Besse, Clement; Okonta, Chibuzo; Larbi, Kwabena; Pah, Alfred C; Danis, Kostas; Porten, Klaudia

    2016-01-01

    In October 2014, during the Ebola outbreak in Liberia healthcare services were limited while malaria transmission continued. Médecins Sans Frontières (MSF) implemented a mass drug administration (MDA) of malaria chemoprevention (CP) in Monrovia to reduce malaria-associated morbidity. In order to inform future interventions, we described the scale of the MDA, evaluated its acceptance and estimated the effectiveness. MSF carried out two rounds of MDA with artesunate/amodiaquine (ASAQ) targeting four neighbourhoods of Monrovia (October to December 2014). We systematically selected households in the distribution area and administered standardized questionnaires. We calculated incidence ratios (IR) of side effects using poisson regression and compared self-reported fever risk differences (RD) pre- and post-MDA using a z-test. In total, 1,259,699 courses of ASAQ-CP were distributed. All households surveyed (n = 222; 1233 household members) attended the MDA in round 1 (r1) and 96% in round 2 (r2) (212/222 households; 1,154 household members). 52% (643/1233) initiated ASAQ-CP in r1 and 22% (256/1154) in r2. Of those not initiating ASAQ-CP, 29% (172/590) saved it for later in r1, 47% (423/898) in r2. Experiencing side effects in r1 was not associated with ASAQ-CP initiation in r2 (IR 1.0, 95%CI 0.49-2.1). The incidence of self-reported fever decreased from 4.2% (52/1229) in the month prior to r1 to 1.5% (18/1229) after r1 (p<0.001) and decrease was larger among household members completing ASAQ-CP (RD = 4.9%) compared to those not initiating ASAQ-CP (RD = 0.6%) in r1 (p<0.001). The reduction in self-reported fever cases following the intervention suggests that MDAs may be effective in reducing cases of fever during Ebola outbreaks. Despite high coverage, initiation of ASAQ-CP was low. Combining MDAs with longer term interventions to prevent malaria and to improve access to healthcare may reduce both the incidence of malaria and the proportion of respondents saving their

  4. Impact and Lessons Learned from Mass Drug Administrations of Malaria Chemoprevention during the Ebola Outbreak in Monrovia, Liberia, 2014.

    Directory of Open Access Journals (Sweden)

    Anna Kuehne

    Full Text Available In October 2014, during the Ebola outbreak in Liberia healthcare services were limited while malaria transmission continued. Médecins Sans Frontières (MSF implemented a mass drug administration (MDA of malaria chemoprevention (CP in Monrovia to reduce malaria-associated morbidity. In order to inform future interventions, we described the scale of the MDA, evaluated its acceptance and estimated the effectiveness.MSF carried out two rounds of MDA with artesunate/amodiaquine (ASAQ targeting four neighbourhoods of Monrovia (October to December 2014. We systematically selected households in the distribution area and administered standardized questionnaires. We calculated incidence ratios (IR of side effects using poisson regression and compared self-reported fever risk differences (RD pre- and post-MDA using a z-test.In total, 1,259,699 courses of ASAQ-CP were distributed. All households surveyed (n = 222; 1233 household members attended the MDA in round 1 (r1 and 96% in round 2 (r2 (212/222 households; 1,154 household members. 52% (643/1233 initiated ASAQ-CP in r1 and 22% (256/1154 in r2. Of those not initiating ASAQ-CP, 29% (172/590 saved it for later in r1, 47% (423/898 in r2. Experiencing side effects in r1 was not associated with ASAQ-CP initiation in r2 (IR 1.0, 95%CI 0.49-2.1. The incidence of self-reported fever decreased from 4.2% (52/1229 in the month prior to r1 to 1.5% (18/1229 after r1 (p<0.001 and decrease was larger among household members completing ASAQ-CP (RD = 4.9% compared to those not initiating ASAQ-CP (RD = 0.6% in r1 (p<0.001.The reduction in self-reported fever cases following the intervention suggests that MDAs may be effective in reducing cases of fever during Ebola outbreaks. Despite high coverage, initiation of ASAQ-CP was low. Combining MDAs with longer term interventions to prevent malaria and to improve access to healthcare may reduce both the incidence of malaria and the proportion of respondents saving their

  5. Chemoprevention of LA7-Induced Mammary Tumor Growth by SM6Met, a Well-Characterized Cyclopia Extract

    Directory of Open Access Journals (Sweden)

    Omolola R. Oyenihi

    2018-06-01

    Full Text Available Breast cancer (BC is the leading cause of cancer-related deaths in women. Chemoprevention of BC by using plant extracts is gaining attention. SM6Met, a well-characterized extract of Cyclopia subternata with reported selective estrogen receptor subtype activity, has shown tumor suppressive effects in a chemically induced BC model in rats, which is known to be estrogen responsive. However, there is no information on the estrogen sensitivity of the relatively new orthotopic model of LA7 cell-induced mammary tumors. In the present study, the potential chemopreventative and side-effect profile of SM6Met on LA7 cell-induced tumor growth was evaluated, as was the effects of 17β-estradiol and standard-of-care (SOC endocrine therapies, such as tamoxifen (TAM, letrozole (LET, and fulvestrant (FUL. Tumor growth was observed in the tumor-vehicle control group until day 10 post tumor induction, which declined afterward on days 12–14. SM6Met suppressed tumor growth to the same extent as TAM, while LET, but not FUL, also showed substantial anti-tumor effects. Short-term 17β-estradiol treatment reduced tumor volume on days prior to day 10, whereas tumor promoting effects were observed during long-term treatment, which was especially evident at later time points. Marked elevation in serum markers of liver injury, which was further supported by histological evaluation, was observed in the vehicle-treated tumor control, TAM, LET, and long-term 17β-estradiol treatment groups. Alterations in the lipid profiles were also observed in the 17β-estradiol treatment groups. In contrast, SM6Met did not augment the increase in serum levels of liver injury biomarkers caused by tumor induction and no effect was observed on lipid profiles. In summary, the results from the current study demonstrate the chemopreventative effect of SM6Met on mammary tumor growth, which was comparable to that of TAM, without eliciting the negative side-effects observed with this SOC endocrine

  6. Effect of seasonal malaria chemoprevention on the acquisition of antibodies to Plasmodium falciparum antigens in Ouelessebougou, Mali.

    Science.gov (United States)

    Mahamar, Almahamoudou; Issiaka, Djibrilla; Barry, Amadou; Attaher, Oumar; Dembele, Adama B; Traore, Tiangoua; Sissoko, Adama; Keita, Sekouba; Diarra, Bacary Soumana; Narum, David L; Duffy, Patrick E; Dicko, Alassane; Fried, Michal

    2017-07-18

    Seasonal malaria chemoprevention (SMC) is a new strategy to reduce malaria burden in young children in Sahelian countries. It consists of the administration of full treatment courses of sulfadoxine-pyrimethamine plus amodiaquine to children at monthly intervals during the malaria season. However, it is not clear if there is a cumulative effect of SMC over time on acquisition of antibodies to malaria antigens. A cross-sectional serosurvey was carried out 1 month after the last dose of SMC in 2016. Children aged 3-4 years were randomly selected from areas where SMC was given for 1, 2 or 3 years during the malaria season. Children in the areas where SMC had been implemented for 1 year but who failed to receive SMC were used as comparison group. Antibody extracted from dry blood spots was used to measure IgG levels to CSP, MSP-1 42 and AMA1. The prevalence of antibodies to AMA-1 were high and similar in children who received SMC for 1, 2 or 3 years and also when compared to those who never received SMC (96.3 vs 97.5%, adjusted OR = 0.99, 95% CI 0.33-2.97, p = 0.99). The prevalence of antibodies to MSP-1 42 and to CSP were similar in children that received SMC for 1, 2 or 3 years, but were lower in these children compared to those who did not receive SMC (87.1 vs 91.2%, adjusted OR = 0.55, 95% CI 0.29-1.01, p = 0.05 for MSP-1 42 ; 79.8 vs 89.2%, adjusted OR = 0.52, 95% CI 0.30-0.90, p = 0.019 for CSP). SMC reduced seropositivity to MSP-1 42 and CSP, but the duration of SMC did not further reduce seropositivity. Exposure to SMC did not reduce the seropositivity to AMA1.

  7. [Computerized clinical protocol for occlusion].

    Science.gov (United States)

    Salsench, J; Ferrer, J; Nogueras, J

    1988-11-01

    In making a protocol it is necessary that all members of the team who are going to collect information have the same unity of criterion about the different variables that compose it. The drawing up of this document is as much or more necessary than the protocol itself. In this work we all data collected in the protocol and we give the explanations of each concept.

  8. Static Validation of Security Protocols

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Degano, P.

    2005-01-01

    We methodically expand protocol narrations into terms of a process algebra in order to specify some of the checks that need to be made in a protocol. We then apply static analysis technology to develop an automatic validation procedure for protocols. Finally, we demonstrate that these techniques ...... suffice to identify several authentication flaws in symmetric and asymmetric key protocols such as Needham-Schroeder symmetric key, Otway-Rees, Yahalom, Andrew secure RPC, Needham-Schroeder asymmetric key, and Beller-Chang-Yacobi MSR...

  9. Unconditionally Secure Protocols

    DEFF Research Database (Denmark)

    Meldgaard, Sigurd Torkel

    This thesis contains research on the theory of secure multi-party computation (MPC). Especially information theoretically (as opposed to computationally) secure protocols. It contains results from two main lines of work. One line on Information Theoretically Secure Oblivious RAMS, and how....... We construct an oblivious RAM that hides the client's access pattern with information theoretic security with an amortized $\\log^3 N$ query overhead. And how to employ a second server that is guaranteed not to conspire with the first to improve the overhead to $\\log^2 N$, while also avoiding...... they are used to speed up secure computation. An Oblivious RAM is a construction for a client with a small $O(1)$ internal memory to store $N$ pieces of data on a server while revealing nothing more than the size of the memory $N$, and the number of accesses. This specifically includes hiding the access pattern...

  10. Protocols for Scholarly Communication

    CERN Document Server

    Pepe, Alberto; Pepe, Alberto; Yeomans, Joanne

    2007-01-01

    CERN, the European Organization for Nuclear Research, has operated an institutional preprint repository for more than 10 years. The repository contains over 850,000 records of which more than 450,000 are full-text OA preprints, mostly in the field of particle physics, and it is integrated with the library's holdings of books, conference proceedings, journals and other grey literature. In order to encourage effective propagation and open access to scholarly material, CERN is implementing a range of innovative library services into its document repository: automatic keywording, reference extraction, collaborative management tools and bibliometric tools. Some of these services, such as user reviewing and automatic metadata extraction, could make up an interesting testbed for future publishing solutions and certainly provide an exciting environment for e-science possibilities. The future protocol for scientific communication should naturally guide authors towards OA publication and CERN wants to help reach a full...

  11. Chemoprevention of Ovarian Cancer

    National Research Council Canada - National Science Library

    Gershenson, David

    2006-01-01

    ... A) and oral contraceptives (OCP) induce apoptosis, possibly through induction of TGF production by stromal cells, as well as by direct interaction with the surface epithelial cells, and these two cell types may act synergistically...

  12. Chemoprevention of Ovarian Cancer

    National Research Council Canada - National Science Library

    Gershenson, David

    2003-01-01

    ... A) and oral contraceptives (OCP) induce apoptosis, possibly through induction of TGFb production by stromal cells, as well as by direct interaction with the surface epithelial cells and these two cell types may act synergistically...

  13. Chemoprevention of Ovarian Cancer

    Science.gov (United States)

    2006-10-01

    288: 390-402. 51. Shin DM, Xu XC, Lippman SM, Lee JJ, Lee JS, Batsakis JG, Ro JY, Martin JW, Hittelman WN, Lotan R, Hong WK. Accumulation of p53...epithelial carcinoma of the ovary. Am. J. Epidemiol., 114: 398–405, 1981. 8. Joly , J. D., Lilienfeld, A. M., Diamond, E. L., and Borss, I. D. J. An

  14. Natural antioxidants in chemoprevention

    Energy Technology Data Exchange (ETDEWEB)

    Dragsted, L.O. [Danish Veterinary and Food Administration, Soeberg (Denmark). Inst. of Toxicology

    1998-12-31

    It is well documented that diets rich in fruits and vegetables can reduce the risk of most common cancers, and that some food items from this class may be protective against heart disease. Several explanations have been offered, one of which relates to the natural presence of potent antioxidants in plant products. Destructive oxidation of lipids, proteins, DNA, and other important biomolecules, often involving radical chain reactions, affect vital cellular structures and their normal functions. Such processes are involved in the development of cancer as well as heart disease, and it seems logical to assume that antioxidants might be preventive. Large human trials with natural antioxidants have not provided a uniform support, however, for the hypothesis that antioxidation per se may prevent cancer or coronary heart disease (CHD). One reason is that other effects, unrelated to antioxidation, may compromise their preventive effects. Another reason may be that many potent antioxidants can also act as pro-oxidants under certain conditions. The interpretation of animal trials is likewise often compromised by the fact that most antioxidants have other physiological effects which might very well explain their protective action or lead to toxic side-effects. (orig.)

  15. Gene probes: principles and protocols

    National Research Council Canada - National Science Library

    Aquino de Muro, Marilena; Rapley, Ralph

    2002-01-01

    ... of labeled DNA has allowed genes to be mapped to single chromosomes and in many cases to a single chromosome band, promoting significant advance in human genome mapping. Gene Probes: Principles and Protocols presents the principles for gene probe design, labeling, detection, target format, and hybridization conditions together with detailed protocols, accom...

  16. Developing frameworks for protocol implementation

    NARCIS (Netherlands)

    de Barros Barbosa, C.; de barros Barbosa, C.; Ferreira Pires, Luis

    1999-01-01

    This paper presents a method to develop frameworks for protocol implementation. Frameworks are software structures developed for a specific application domain, which can be reused in the implementation of various different concrete systems in this domain. The use of frameworks support a protocol

  17. Protocols for Scholarly Communication

    Science.gov (United States)

    Pepe, A.; Yeomans, J.

    2007-10-01

    CERN, the European Organization for Nuclear Research, has operated an institutional preprint repository for more than 10 years. The repository contains over 850,000 records of which more than 450,000 are full-text OA preprints, mostly in the field of particle physics, and it is integrated with the library's holdings of books, conference proceedings, journals and other grey literature. In order to encourage effective propagation and open access to scholarly material, CERN is implementing a range of innovative library services into its document repository: automatic keywording, reference extraction, collaborative management tools and bibliometric tools. Some of these services, such as user reviewing and automatic metadata extraction, could make up an interesting testbed for future publishing solutions and certainly provide an exciting environment for e-science possibilities. The future protocol for scientific communication should guide authors naturally towards OA publication, and CERN wants to help reach a full open access publishing environment for the particle physics community and related sciences in the next few years.

  18. Genotoxic and chemopreventive assessment of Cynara scolymus L. aqueous extract in a human-derived liver cell line.

    Science.gov (United States)

    da Silva, Regiane Pereira; Jacociunas, Laura Vicedo; de Carli, Raíne Fogliati; de Abreu, Bianca Regina Ribas; Lehmann, Mauricio; da Silva, Juliana; Ferraz, Alexandre de Barros Falcão; Dihl, Rafael Rodrigues

    2017-10-01

    Cynara scolymus L., popularly known as artichoke, is consumed as food and used as tea infusions for pharmacological purposes to treat liver dysfunctions and other conditions. Scientific data on the safety and protective effect of artichoke in human-derived liver cells is missing. This study investigated the genotoxic and modulatory effect of a liophilized extract suspended in water of C. scolymus L. leaves. Four extract concentrations (0.62, 1.25, 2.5 and 5.0 mg/mL) were evaluated using the comet assay on human hepatocyte cultures, HepG2 cells. Genotoxicity was assessed after two treatment periods, 1 and 24 h. Antigenotoxicity was evaluated against oxidative lesions induced by hydrogen peroxide in pre-, simultaneous and post-treatment protocols. Artichoke leaves aqueous extract induced genotoxic effects in HepG2 cells after 1- and 24-h treatments. In turn, extract concentrations of 0.62, 1.25 and 2.5 mg/mL, exhibited a protective effect in pretreatment, compared to hydrogen peroxide alone. However, in simultaneous and post-treatment protocols, only the lowest concentration reduced the frequency of DNA damage induced by hydrogen peroxide. In addition, in the simultaneous treatment protocol, the highest artichoke extract concentration increased hydrogen peroxide genotoxicity. It can be concluded that artichoke is genotoxic, in vitro, to HepG2 cells, but can also modulate hydrogen peroxide DNA damage.

  19. Scientific Evidence of Rice By-Products for Cancer Prevention: Chemopreventive Properties of Waste Products from Rice Milling on Carcinogenesis In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Bee Ling Tan

    2017-01-01

    Full Text Available Cancer is a significant global health concern affecting men and women worldwide. Although current chemopreventive drugs could inhibit the growth of cancer cells, they exert many adverse side effects. Dietary factor plays a crucial role in the management of cancers and has drawn the attention of researchers to be used as an option to combat this disease. Both in vitro and in vivo studies showed that rice and its by-products display encouraging results in the prevention of this disease. The mechanism of anticancer effect is suggested partly through potentiation of bioactive compounds like vitamin E, phytic acid, γ-aminobutyric acid (GABA, γ-oryzanol, and phenolics. Nevertheless, the bioactivity of rice and its by-products is still incompletely understood. In this review, we present the findings from a preclinical study both in in vitro and in animal experiments on the promising role of rice by-products with focus on cancer prevention.

  20. Chemopreventive Effects of Germinated Rough Rice Crude Extract in Inhibiting Azoxymethane-Induced Aberrant Crypt Foci Formation in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Elnaz Saki

    2017-01-01

    Full Text Available Chemoprevention has become an important area in cancer research due to low success rate of current therapeutic modalities. Diet plays a vital role in the etiology of cancer. This research was carried out to study the chemopreventive properties of germinated rough rice (GRR crude extract in Sprague-Dawley rats induced with azoxymethane. Germination of rough rice causes significant changes in several chemical compositions of presently bioactive compounds. These compounds may prevent or postpone the inception of cancer. Fifty male Sprague-Dawley rats (6 weeks of age were randomly divided into 5 groups which were (G1 induced with azoxymethane (AOM and not given GRR (positive control, (G2 induced with AOM and given 2000 mg/kg GRR, (G3 induced with AOM and given 1000 mg/kg GRR, (G4 induced with AOM and given 500 mg/kg GRR, and (G5 not induced with AOM and not given GRR crude extract (negative control. To induce colon cancer, rats received two IP injections of AOM in saline (15 mg/kg for two subsequent weeks. Organs were removed and weighed. Aberrant crypt foci (ACF were evaluated histopathologically. β-Catenin expressions were determined by Western blot. Treatment with 2000 mg/kg GRR crude extract not only resulted in the greatest reduction in the size and number of ACF but also displayed the highest percentage of nondysplastic ACF. Treatment with 2000 mg/kg GRR also gave the lowest level of expression in β-catenin. Thus, GRR could be a promising dietary supplement for prevention of CRC.

  1. The REDUCE metagram: a comprehensive prediction tool for determining the utility of dutasteride chemoprevention in men at risk for prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Carvell T.; Isariyawongse, Brandon [Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic Foundation, Cleveland, OH (United States); Yu, Changhong; Kattan, Michael W., E-mail: kattanm@ccf.org [Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH (United States)

    2012-10-11

    Introduction: 5-alpha reductase inhibitors can reduce the risk of prostate cancer (PCa) but can be associated with significant side effects. A library of nomograms which predict the risk of clinical endpoints relevant to dutasteride treatment may help determine if chemoprevention is suited to the individual patient. Methods: Data from the REDUCE trial was used to identify predictive factors for 9 endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biopsy cohort, Cox proportional hazards (PH) and competing risks regression (CRR) models were used to build 18 nomograms, whose predictive ability was measured by concordance index (CI) and calibration plots. Results: A total of 18 nomograms assessing the risks of cancer, high grade cancer, high grade prostatic intraepithelial neoplasia (HGPIN), atypical small acinar proliferation (ASAP), erectile dysfunction (ED), acute urinary retention (AUR), gynecomastia, urinary tract infection (UTI) and BPH-related surgery either on or off dutasteride were created. The nomograms for cancer, high grade cancer, ED, AUR, and BPH-related surgery demonstrated good discrimination and calibration while those for gynecomastia, UTI, HGPIN, and ASAP predicted no better than random chance. Conclusions: To aid patients in determining whether the benefits of dutasteride use outweigh the risks, we have developed a comprehensive metagram that can generate individualized risks of 9 outcomes relevant to men considering chemoprevention. Better models based on more predictive markers are needed for some of the endpoints but the current metagram demonstrates potential as a tool for patient counseling and decision-making that is accessible, intuitive, and clinically relevant.

  2. The intriguing role of fibroblasts and c-Jun in the chemopreventive and therapeutic effect of finasteride on xenograft models of prostate cancer

    Directory of Open Access Journals (Sweden)

    Yi-Nong Niu

    2016-01-01

    Full Text Available In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer (PCa while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP (PC3 cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERK1/2 were evaluated. In LNCaP (PC3 mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, fibroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERK1/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERK1/2 were noted in the presence of c-Jun−/− fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride′s therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.

  3. Linking genomic responses of gonads with reproductive impairment in marine medaka (Oryzias melastigma) exposed chronically to the chemopreventive and antifouling agent, 3,3′-diindolylmethane (DIM)

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Lianguo [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Au, Doris W.T. [State Key Laboratory in Marine Pollution, Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong SAR (China); Hu, Chenyan [School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430072 (China); Zhang, Weipeng [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Zhou, Bingsheng [State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072 (China); Cai, Lin [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China); Giesy, John P. [Department of Veterinary Biomedical Sciences and Toxicology Centre, University of Saskatchewan, 44 Campus Drive, Saskatoon, SK S7N 5B3 (Canada); Department of Zoology, and Center for Integrative Toxicology, Michigan State University, East Lansing, MI (United States); Qian, Pei-Yuan, E-mail: boqianpy@ust.hk [Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong SAR (China)

    2017-02-15

    Highlights: • Marine medaka were exposed chronically to low-doses of DIM. • Toxicogenomic responses of gonads were profiled at transcript and protein levels. • Molecular initiating events were linked to adverse apical outcomes. • VTG mobilization was blocked by lower abundance of cathepsin enzyme in ovary. • Eggshell proteins were more indicative of reproductive failure than VTG. - Abstract: 3,3′-Diindolylmethane (DIM) has been promoted as an effective chemopreventive and antifouling additive. However, the concurrent risks or side effects of DIM are not fully understood, especially on tissues responsive to estrogen. Therefore, this study employed marine medaka (Oryzias melastigma) as a test model to evaluate relative safety and explore mechanisms of toxic action of DIM on development and function of gonad after chronic (28 days) aqueous exposure to relatively low doses (0 μg/L or 8.5 μg/L). Integration of comprehensive toxicogenomic analysis at the transcriptome and proteome levels with apical endpoints, such as production of eggs and swimming performance of larvae, elucidated the molecular linkage in gonad from bottom up along the reproductive adverse outcome pathway. A series of sequential changes at the transcript and protein levels were linked to lesser fecundity and viability of larvae exposed to DIM. Anomalous production of vitellogenin (VTG) and eggshell proteins in testis confirmed the estrogenic potency of DIM. In the ovary, although storage of VTG was greater, lesser expressions of cathepsin enzymes blocked cleavage and incorporation of VTG into oocytes as yolk, which acted together with lower eggshell proteins to inhibit maturation of primary oocyte and thus contributed to impairment of fecundity. Overall, this study demonstrated that exposure to DIM impaired reproductive fitness. Diverse molecular initiating changes in gonads were linked to apical endpoints that could be used in assessment of risks posed by DIM on gametogenesis. In

  4. Teriflunomide (Leflunomide Promotes Cytostatic, Antioxidant, and Apoptotic Effects in Transformed Prostate Epithelial Cells: Evidence Supporting a Role for Teriflunomide in Prostate Cancer Chemoprevention

    Directory of Open Access Journals (Sweden)

    Numsen Hail, Jr

    2010-06-01

    Full Text Available Teriflunomide (TFN is an inhibitor of de novo pyrimidine synthesis and the active metabolite of leflunomide. Leflunomide is prescribed to patients worldwide as an immunomodulatory and anti-inflammatory disease-modifying prodrug. Leflunomide inhibited the growth of human prostate cancer xenographs in mice, and leflunomide or TFN promoted cytostasis and/or apoptosis in cultured cells. These findings suggest that TFN could be useful in prostate cancer chemoprevention. We investigated the possible mechanistic aspects of this tenet by characterizing the effects of TFN using premalignant PWR-1E and malignant DU-145 human prostate epithelial cells. TFN promoted a dose- and time-dependent cytostasis or apoptosis induction in these cells. The cytostatic effects of TFN, which were reversible but not by the presence of excess uridine in the culture medium, included diminished cellular uridine levels, an inhibition in oxygen consumption, a suppression of reactive oxygen species (ROS generation, S-phase cell cycle arrest, and a conspicuous reduction in the size and number of the nucleoli in the nuclei of these cells. Conversely, TFN's apoptogenic effects were characteristic of catastrophic mitochondrial disruption (i.e., a dissipation of mitochondrial inner transmembrane potential, enhanced ROS production, mitochondrial cytochrome c release, and cytoplasmic vacuolization and followed by DNA fragmentation. The respiration-deficient derivatives of the DU-145 cells, which are also uridine auxotrophs, were markedly resistant to the cytostatic and apoptotic effects of TFN, implicating de novo pyrimidine synthesis and mitochondrial bioenergetics as the primary targets for TFN in the respiration competent cells. These mechanistic findings advocate a role for TFN and mitochondrial bioenergetics in prostate cancer chemoprevention.

  5. Compounds from the Fruits of the Popular European Medicinal Plant Vitex agnus-castus in Chemoprevention via NADP(H):Quinone Oxidoreductase Type 1 Induction.

    Science.gov (United States)

    Li, Shenghong; Qiu, Shengxiang; Yao, Ping; Sun, Handong; Fong, Harry H S; Zhang, Hongjie

    2013-01-01

    As part of our continuing efforts in the search for potential biologically active compounds from medicinal plants, we have isolated 18 compounds including two novel nitrogen containing diterpenes from extracts of the fruits of Vitex agnus-castus. These isolates, along with our previously obtained novel compound vitexlactam A (1), were evaluated for potential biological effects, including cancer chemoprevention. Chemically, the nitrogenous isolates were found to be two labdane diterpene alkaloids, each containing an α , β -unsaturated γ -lactam moiety. Structurally, they were elucidated to be 9 α -hydroxy-13(14)-labden-16,15-amide (2) and 6 β -acetoxy-9 α -hydroxy-13(14)-labden-15,16-amide (3), which were named vitexlactams B and C, respectively. The 15 known isolates were identified as vitexilactone (4), rotundifuran (5), 8-epi-manoyl oxide (6), vitetrifolin D (7), spathulenol (8), cis-dihydro-dehydro-diconiferylalcohol-9-O- β -D-glucoside (9), luteolin-7-O-glucoside (10), 5-hydroxy-3,6,7,4'-tetramethoxyflavone (11), casticin (12), artemetin (13), aucubin (14), agnuside (15), β -sitosterol (16), p-hydroxybenzoic acid (17), and p-hydroxybenzoic acid glucose ester (18). All compound structures were determined/identified on the basis of 1D and/or 2D NMR and mass spectrometry techniques. Compounds 6, 8, 9, and 18 were reported from a Vitex spieces for the first time. The cancer chemopreventive potentials of these isolates were evaluated for NADP(H):quinone oxidoreductase type 1 (QR1) induction activity. Compound 7 demonstrated promising QR1 induction effect, while the new compound vitexlactam (3) was only slightly active.

  6. 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.

  7. Compounds from the Fruits of the Popular European Medicinal Plant Vitex agnus-castus in Chemoprevention via NADP(H:Quinone Oxidoreductase Type 1 Induction

    Directory of Open Access Journals (Sweden)

    Shenghong Li

    2013-01-01

    Full Text Available As part of our continuing efforts in the search for potential biologically active compounds from medicinal plants, we have isolated 18 compounds including two novel nitrogen containing diterpenes from extracts of the fruits of Vitex agnus-castus. These isolates, along with our previously obtained novel compound vitexlactam A (1, were evaluated for potential biological effects, including cancer chemoprevention. Chemically, the nitrogenous isolates were found to be two labdane diterpene alkaloids, each containing an α, β-unsaturated γ-lactam moiety. Structurally, they were elucidated to be 9α-hydroxy-13(14-labden-16,15-amide (2 and 6β-acetoxy-9α-hydroxy-13(14-labden-15,16-amide (3, which were named vitexlactams B and C, respectively. The 15 known isolates were identified as vitexilactone (4, rotundifuran (5, 8-epi-manoyl oxide (6, vitetrifolin D (7, spathulenol (8, cis-dihydro-dehydro-diconiferylalcohol-9-O-β-D-glucoside (9, luteolin-7-O-glucoside (10, 5-hydroxy-3,6,7,4′-tetramethoxyflavone (11, casticin (12, artemetin (13, aucubin (14, agnuside (15, β-sitosterol (16, p-hydroxybenzoic acid (17, and p-hydroxybenzoic acid glucose ester (18. All compound structures were determined/identified on the basis of 1D and/or 2D NMR and mass spectrometry techniques. Compounds 6, 8, 9, and 18 were reported from a Vitex spieces for the first time. The cancer chemopreventive potentials of these isolates were evaluated for NADP(H:quinone oxidoreductase type 1 (QR1 induction activity. Compound 7 demonstrated promising QR1 induction effect, while the new compound vitexlactam (3 was only slightly active.

  8. Chemoprevention by Quercetin of Oral Squamous Cell Carcinoma by Suppression of the NF-κB Signaling Pathway in DMBA-treated Hamsters.

    Science.gov (United States)

    Zhang, Wen; Yin, Gang; Dai, Jianguo; Sun, Y U; Hoffman, Robert M; Yang, Zhijian; Fan, Yuan

    2017-08-01

    The aim of this study was to investigate the effects of the flavonoid quercetin on chemoprevention of oral squamous cell carcinoma (OSCC). The study involved molecular signaling pathways in 7,12-dimethylbenz(a) anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. DMBA (0.5%) was painted at the right buccal pouches of hamsters for 14 weeks to induce carcinoma. DMBA-treated hamsters received simultaneous doses of quercetin. Animals without DMBA induction were used as normal controls. The incidence of OSCC and the severity of pre-malignant lesions were determined histologically. Apoptosis in the pouch tissue was determined by TUNEL staining. The mRNA and protein expression of NF-κB p50 and p65, as well as Bcl-2 and Bax genes were analyzed using RT-PCR and Western blotting, respectively. Quercetin, at various doses, significantly reduced OSCC incidence and severity of hyperplasia and dysplasia compared to the DMBA-induction-only group (p<0.01). Apoptosis was induced by quercetin treatment compared to the DMBA-induction-only group (p<0.01). mRNA and protein expression of NF-κB p50, p65 as well as Bcl-2 genes were significantly suppressed by quercetin at high doses compared to DMBA induction only (p<0.05). However, mRNA and protein expression of the Bax gene was increased by quercetin treatment at medium and high doses, compared to the DMBA-induction-only group (p<0.05). Quercetin significantly reduced body-weight loss compared to the DMBA-induction-only group (p<0.05). Quercetin reduced tumor incidence and induced apoptosis through modulation of NF-κB signaling and its target genes Bcl-2 and Bax in the DMBA-induced carcigenesis hamster model, suggesting the potential of quercetin as a candidate for OSCC chemoprevention. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Linking genomic responses of gonads with reproductive impairment in marine medaka (Oryzias melastigma) exposed chronically to the chemopreventive and antifouling agent, 3,3′-diindolylmethane (DIM)

    International Nuclear Information System (INIS)

    Chen, Lianguo; Au, Doris W.T.; Hu, Chenyan; Zhang, Weipeng; Zhou, Bingsheng; Cai, Lin; Giesy, John P.; Qian, Pei-Yuan

    2017-01-01

    Highlights: • Marine medaka were exposed chronically to low-doses of DIM. • Toxicogenomic responses of gonads were profiled at transcript and protein levels. • Molecular initiating events were linked to adverse apical outcomes. • VTG mobilization was blocked by lower abundance of cathepsin enzyme in ovary. • Eggshell proteins were more indicative of reproductive failure than VTG. - Abstract: 3,3′-Diindolylmethane (DIM) has been promoted as an effective chemopreventive and antifouling additive. However, the concurrent risks or side effects of DIM are not fully understood, especially on tissues responsive to estrogen. Therefore, this study employed marine medaka (Oryzias melastigma) as a test model to evaluate relative safety and explore mechanisms of toxic action of DIM on development and function of gonad after chronic (28 days) aqueous exposure to relatively low doses (0 μg/L or 8.5 μg/L). Integration of comprehensive toxicogenomic analysis at the transcriptome and proteome levels with apical endpoints, such as production of eggs and swimming performance of larvae, elucidated the molecular linkage in gonad from bottom up along the reproductive adverse outcome pathway. A series of sequential changes at the transcript and protein levels were linked to lesser fecundity and viability of larvae exposed to DIM. Anomalous production of vitellogenin (VTG) and eggshell proteins in testis confirmed the estrogenic potency of DIM. In the ovary, although storage of VTG was greater, lesser expressions of cathepsin enzymes blocked cleavage and incorporation of VTG into oocytes as yolk, which acted together with lower eggshell proteins to inhibit maturation of primary oocyte and thus contributed to impairment of fecundity. Overall, this study demonstrated that exposure to DIM impaired reproductive fitness. Diverse molecular initiating changes in gonads were linked to apical endpoints that could be used in assessment of risks posed by DIM on gametogenesis. In

  10. Asbestos Induces Oxidative Stress and Activation of Nrf2 Signaling in Murine Macrophages: Chemopreventive Role of the Synthetic Lignan Secoisolariciresinol Diglucoside (LGM2605

    Directory of Open Access Journals (Sweden)

    Ralph A. Pietrofesa

    2016-03-01

    Full Text Available The interaction of asbestos fibers with macrophages generates harmful reactive oxygen species (ROS and subsequent oxidative cell damage that are key processes linked to malignancy. Secoisolariciresinol diglucoside (SDG is a non-toxic, flaxseed-derived pluripotent compound that has antioxidant properties and may thus function as a chemopreventive agent for asbestos-induced mesothelioma. We thus evaluated synthetic SDG (LGM2605 in asbestos-exposed, elicited murine peritoneal macrophages as an in vitro model of tissue phagocytic response to the presence of asbestos in the pleural space. Murine peritoneal macrophages (MFs were exposed to crocidolite asbestos fibers (20 µg/cm2 and evaluated at various times post exposure for cytotoxicity, ROS generation, malondialdehyde (MDA, and levels of 8-iso Prostaglandin F2α (8-isoP. We then evaluated the ability of LGM2605 to mitigate asbestos-induced oxidative stress by administering LGM2605 (50 µM 4-h prior to asbestos exposure. We observed a significant (p < 0.0001, time-dependent increase in asbestos-induced cytotoxicity, ROS generation, and the release of MDA and 8-iso Prostaglandin F2α, markers of lipid peroxidation, which increased linearly over time. LGM2605 treatment significantly (p < 0.0001 reduced asbestos-induced cytotoxicity and ROS generation, while decreasing levels of MDA and 8-isoP by 71%–88% and 41%–73%, respectively. Importantly, exposure to asbestos fibers induced cell protective defenses, such as cellular Nrf2 activation and the expression of phase II antioxidant enzymes, HO-1 and Nqo1 that were further enhanced by LGM2605 treatment. LGM2605 boosted antioxidant defenses, as well as reduced asbestos-induced ROS generation and markers of oxidative stress in murine peritoneal macrophages, supporting its possible use as a chemoprevention agent in the development of asbestos-induced malignant mesothelioma.

  11. Evaluation of sestamibi scanning as a predictor of risk of development of breast cancer and as a non-invasive biomarker for breast cancer chemoprevention trials

    International Nuclear Information System (INIS)

    Kimler, B.F.; Preston, D.; McMillin, C.H.; Dusing, R.; Zalles, C.M.; Fabian, C.J.

    2003-01-01

    Sestamibi scintimammography is becoming increasingly accepted as an adjunct to conventional breast imaging by mammography and ultrasound. We sought to determine whether it might serve to detect/quantify pre-cancerous breast lesions, specifically hyperplasia with atypia which, when detected by random periareolar fine needle aspiration (FNA), is known to be associated with increased risk for subsequent development of breast cancer. If a parameter derived from sestamibi scanning could be shown to correlate with and predict for atypia, then this could serve 1) to refine estimates of risk of development of breast cancer; and 2) as a surrogate endpoint biomarker in clinical breast cancer chemoprevention trials. To this end, we performed sestamibi scanning on both breasts of 65 women at high risk for development of breast cancer who also underwent FNA. Seventeen women (26%) exhibited non-proliferative cytology; 30 (46%) had hyperplasia; and 18 (28%) had hyperplasia with atypia in the FNA specimen. Since the fine needle aspiration specimens from both breasts are pooled to provide a single result, we likewise pooled the sestamibi results from both breasts so as to consider the most abnormal finding. Twenty-five women (39%) were characterized as having an abnormal sestamibi scan with heterogenous, focal, intense uptake. There was no correlation between an abnormal scan and cytologic evidence of hyperplasia with atypia. Neither was there a correlation between any of a variety of quantitative measures of the sestamibi scans and the cytological classification. At this time, there is no indication for the use of sestamibi scanning for the prediction of risk of subsequent development of breast cancer, or as a surrogate endpoint biomarker in clinical breast cancer chemoprevention trials

  12. The REDUCE metagram: a comprehensive prediction tool for determining the utility of dutasteride chemoprevention in men at risk for prostate cancer

    International Nuclear Information System (INIS)

    Nguyen, Carvell T.; Isariyawongse, Brandon; Yu, Changhong; Kattan, Michael W.

    2012-01-01

    Introduction: 5-alpha reductase inhibitors can reduce the risk of prostate cancer (PCa) but can be associated with significant side effects. A library of nomograms which predict the risk of clinical endpoints relevant to dutasteride treatment may help determine if chemoprevention is suited to the individual patient. Methods: Data from the REDUCE trial was used to identify predictive factors for 9 endpoints relevant to dutasteride treatment. Using the treatment and placebo groups from the biopsy cohort, Cox proportional hazards (PH) and competing risks regression (CRR) models were used to build 18 nomograms, whose predictive ability was measured by concordance index (CI) and calibration plots. Results: A total of 18 nomograms assessing the risks of cancer, high grade cancer, high grade prostatic intraepithelial neoplasia (HGPIN), atypical small acinar proliferation (ASAP), erectile dysfunction (ED), acute urinary retention (AUR), gynecomastia, urinary tract infection (UTI) and BPH-related surgery either on or off dutasteride were created. The nomograms for cancer, high grade cancer, ED, AUR, and BPH-related surgery demonstrated good discrimination and calibration while those for gynecomastia, UTI, HGPIN, and ASAP predicted no better than random chance. Conclusions: To aid patients in determining whether the benefits of dutasteride use outweigh the risks, we have developed a comprehensive metagram that can generate individualized risks of 9 outcomes relevant to men considering chemoprevention. Better models based on more predictive markers are needed for some of the endpoints but the current metagram demonstrates potential as a tool for patient counseling and decision-making that is accessible, intuitive, and clinically relevant.

  13. Effectiveness of oxaliplatin desensitization protocols.

    Science.gov (United States)

    Cortijo-Cascajares, Susana; Nacle-López, Inmaculada; García-Escobar, Ignacio; Aguilella-Vizcaíno, María José; Herreros-de-Tejada, Alberto; Cortés-Funes Castro, Hernán; Calleja-Hernández, Miguel-Ángel

    2013-03-01

    Hypersensitivity reaction (HSR) to antineoplastic drugs can force doctors to stop treatment and seek other alternatives. These alternatives may be less effective, not as well tolerated and/or more expensive. Another option is to use desensitization protocols that induce a temporary state of tolerance by gradually administering small quantities of the antineoplastic drug until the therapeutic dosage is reached. The aim of this study is to assess the effectiveness of oxaliplatin desensitization protocols. A retrospective observational study was carried out between January 2006 and May 2011. The inclusion criteria were patients undergoing chemotherapy treatment with oxaliplatin who had developed an HSR to the drug and who were candidates for continuing the treatment using a desensitization protocol. The patients' clinical records were reviewed and variables were gathered relating to the patient, the treatment, the HSR, and the desensitization protocol administered. The data were analysed using version 18.0 of the statistics program SPSS. A total of 53 desensitization protocols were administered to 21 patients. In 89 % of these cases, no new reactions occurred while the drug was being administered. New reactions of mild severity only occurred in 11 % of cases, and none of these reactions were severe enough for treatment to be stopped. All patients were able to complete the desensitization protocol. This study confirms that oxaliplatin desensitization protocols are safe and effective and allow patients to continue with the treatment that initially caused an HSR.

  14. Deterministic secure communication protocol without using entanglement

    OpenAIRE

    Cai, Qing-yu

    2003-01-01

    We show a deterministic secure direct communication protocol using single qubit in mixed state. The security of this protocol is based on the security proof of BB84 protocol. It can be realized with current technologies.

  15. SIP protocol model for OMNET++

    Directory of Open Access Journals (Sweden)

    Jan Kucerak

    2016-01-01

    Full Text Available The article describes our new SIP protocol implementation for the OMNeT++ simulation framework. OMNeT++ simulation framework provides an extensive support of IP related protocols, nevertheless a working SIP protocol implementation is missing. Real measurements were also done using a SIPp traffic generator and the results are compared to those obtained by our new SIP model. Since this work is a part of bigger project concerned strictly on measuring "first response times" over networks with a faulty transmission links, the actually collected statistics are focused only this way.

  16. The HPA photon protocol and proposed electron protocol

    International Nuclear Information System (INIS)

    Pitchford, W.G.

    1985-01-01

    The Hospital Physicists Association (HPA) photon dosimetry protocol has been produced and was published in 1983. Revised values of some components of Csub(lambda) and refinements introduced into the theory in the last few years have enabled new Csub(lambda) values to be produced. The proposed HPA electron protocol is at present in draft form and will be published shortly. Both protocels are discussed. (Auth.)

  17. Antibody engineering: methods and protocols

    National Research Council Canada - National Science Library

    Chames, Patrick

    2012-01-01

    "Antibody Engineering: Methods and Protocols, Second Edition was compiled to give complete and easy access to a variety of antibody engineering techniques, starting from the creation of antibody repertoires and efficient...

  18. Implementation of postoperative handoff protocol

    African Journals Online (AJOL)

    Background: Standardised handoff protocols have become necessary patient ... improve the perioperative handoff communications from the cardiac operating theatres to the ICU. ..... as you can imagine, there was push-back to the change.

  19. Data Exchange Protocol in Repsail

    Directory of Open Access Journals (Sweden)

    Gucma Maciej

    2017-12-01

    Full Text Available Article presents implantation and theoretical considerations of data exchange protocol developed for the RepSail project, where main objective was design and building innovative hybrid yacht. One of problems during the design process was improper functioning of data exchange protocols that were available in the commercially available devices to mention navigation purpose NMEA183 or 2000 as well as automation dedicated ones (CAN and similar. Author shows the basis of the dedicated format of exchange for in board devices.

  20. The Groningen protocol: another perspective

    OpenAIRE

    Jotkowitz, A B; Glick, S

    2006-01-01

    The Groningen protocol allows for the euthanasia of severely ill newborns with a hopeless prognosis and unbearable suffering. We understand the impetus for such a protocol but have moral and ethical concerns with it. Advocates for euthanasia in adults have relied on the concept of human autonomy, which is lacking in the case of infants. In addition, biases can potentially influence the decision making of both parents and physicians. It is also very difficult to weigh the element of quality of...

  1. Monoclonal antibodies technology. Protocols

    International Nuclear Information System (INIS)

    Acevado Castro, B.E.

    1997-01-01

    Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 μg/ml. It is recommended that the antigen under consideration be incorporated into the emulsion adjuvants in 1:1 volumetric relation. We commonly use Frend's adjuvant (FA) to prepared immunized solution. The first immunization should be prepared with complete FA, and the another could be prepared with incomplete FA. It is recommended to inject mice with 0.2 ml intraperitoneal (ip) or subcutaneous (sc). Our experience suggests the sc route is the preferred route. A minimum protocol for immunizing mice to generate cells for preparing hybridomas is s follows: immunize sc on day 0, boost sc on day 21, take a trial bleeding on day 26; if antibody titters are satisfactory, boost ip on day 35 with antigen only, and remove the spleen to obtain cells for fusion on day 38. Fusion protocol. The myeloma cell line we are using is X63 Ag8.653. At the moment of fusion myeloma cells need a good viability (at least a 95%). 1. Remove the spleen cells from immunized mice using sterile conditions. An immune spleen should yield between 7 a 10x10 7 nucleated cells. 2. Place the spleen in 20 ml of serum-free RPMI 1640 in a Petri dish. Using a needle and syringe, inject the spleen with medium to distend and disrupt the spleen stroma and free the nucleated cells. 3. Flush the cell suspension with a Pasteur pipet to disperse clumps of cells. 4. Centrifuge the spleen cell suspension at 250g for 10 min. Resuspend the pellet in serum-free RPMI 1640. Determine cell concentration using Neuhabuer chamber. 5. Mix the myeloma cells and spleen cells in a conical 50-ml tube in serum-free RPMI 1640, 1 x10 7 spleen cells to 1x10 6 myeloma cells (ratio 10:1). Centrifuge

  2. Families of quantum fingerprinting protocols

    Science.gov (United States)

    Lovitz, Benjamin; Lütkenhaus, Norbert

    2018-03-01

    We introduce several families of quantum fingerprinting protocols to evaluate the equality function on two n -bit strings in the simultaneous message passing model. The original quantum fingerprinting protocol uses a tensor product of a small number of O (logn ) -qubit high-dimensional signals [H. Buhrman et al., Phys. Rev. Lett. 87, 167902 (2001), 10.1103/PhysRevLett.87.167902], whereas a recently proposed optical protocol uses a tensor product of O (n ) single-qubit signals, while maintaining the O (logn ) information leakage of the original protocol [J. M. Arazola and N. Lütkenhaus, Phys. Rev. A 89, 062305 (2014), 10.1103/PhysRevA.89.062305]. We find a family of protocols which interpolate between the original and optical protocols while maintaining the O (logn ) information leakage, thus demonstrating a tradeoff between the number of signals sent and the dimension of each signal. There has been interest in experimental realization of the recently proposed optical protocol using coherent states [F. Xu et al., Nat. Commun. 6, 8735 (2015), 10.1038/ncomms9735; J.-Y. Guan et al., Phys. Rev. Lett. 116, 240502 (2016), 10.1103/PhysRevLett.116.240502], but as the required number of laser pulses grows linearly with the input size n , eventual challenges for the long-time stability of experimental setups arise. We find a coherent state protocol which reduces the number of signals by a factor 1/2 while also reducing the information leakage. Our reduction makes use of a simple modulation scheme in optical phase space, and we find that more complex modulation schemes are not advantageous. Using a similar technique, we improve a recently proposed coherent state protocol for evaluating the Euclidean distance between two real unit vectors [N. Kumar et al., Phys. Rev. A 95, 032337 (2017), 10.1103/PhysRevA.95.032337] by reducing the number of signals by a factor 1/2 and also reducing the information leakage.

  3. NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

    Science.gov (United States)

    Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A.; Kashfi, Khosrow

    2015-01-01

    Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: Nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. PMID:26394025

  4. Adlay (薏苡 yì yĭ; “soft-shelled job's tears”; the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf is a Potential Cancer Chemopreventive Agent toward Multistage Carcinogenesis Processes

    Directory of Open Access Journals (Sweden)

    Ching-Chuan Kuo, Ph.D.

    2012-10-01

    Full Text Available Adlay (薏苡 yì yĭ; “soft-shelled job’s tears”, the seeds of Coix lachryma-jobi L. var. ma-yuen Stapf is a grass crop that has long been used in traditional Chinese medicine (TCM and as a nourishing food in China for the treatment of warts, chapped skin, rheumatism, neuralgia, inflammatory, and neoplastic diseases. In addition, adlay also has been said to have stomachic, diuretic, antipholgistic, anodynic, and antispasmodic effects. Carcinogenesis is a multistage process that begins with exposure of viruses or chemicals that are found in the environment. Chemoprevention refers to the use of natural or synthetic, non-toxic chemical substances to reverse, repress, or prevent carcinogenesis. In this review, we summarize recent research attempting to study the chemopreventive blocking and suppressing potential of adlay and its active components in scavenging electrophiles and reactive oxygen species, antimutagenicity, enhancing Nrf2-mediated detoxification and antioxidant effect, altering carcinogen metabolism, suppressing proliferation, decreasing inflammation, and enhancing antitumor immunity. In addition, several active components with diverse chemopreventive properties have been also mentioned in this review article.

  5. The Network Protocol Analysis Technique in Snort

    Science.gov (United States)

    Wu, Qing-Xiu

    Network protocol analysis is a network sniffer to capture data for further analysis and understanding of the technical means necessary packets. Network sniffing is intercepted by packet assembly binary format of the original message content. In order to obtain the information contained. Required based on TCP / IP protocol stack protocol specification. Again to restore the data packets at protocol format and content in each protocol layer. Actual data transferred, as well as the application tier.

  6. Understanding protocol performance: impact of test performance.

    Science.gov (United States)

    Turner, Robert G

    2013-01-01

    This is the second of two articles that examine the factors that determine protocol performance. The objective of these articles is to provide a general understanding of protocol performance that can be used to estimate performance, establish limits on performance, decide if a protocol is justified, and ultimately select a protocol. The first article was concerned with protocol criterion and test correlation. It demonstrated the advantages and disadvantages of different criterion when all tests had the same performance. It also examined the impact of increasing test correlation on protocol performance and the characteristics of the different criteria. To examine the impact on protocol performance when individual tests in a protocol have different performance. This is evaluated for different criteria and test correlations. The results of the two articles are combined and summarized. A mathematical model is used to calculate protocol performance for different protocol criteria and test correlations when there are small to large variations in the performance of individual tests in the protocol. The performance of the individual tests that make up a protocol has a significant impact on the performance of the protocol. As expected, the better the performance of the individual tests, the better the performance of the protocol. Many of the characteristics of the different criteria are relatively independent of the variation in the performance of the individual tests. However, increasing test variation degrades some criteria advantages and causes a new disadvantage to appear. This negative impact increases as test variation increases and as more tests are added to the protocol. Best protocol performance is obtained when individual tests are uncorrelated and have the same performance. In general, the greater the variation in the performance of tests in the protocol, the more detrimental this variation is to protocol performance. Since this negative impact is increased as

  7. The Geneva Protocol of 1925

    International Nuclear Information System (INIS)

    Mc Elroy, R.J.

    1991-01-01

    This paper reports that when President Gerald Ford signed the instruments of ratification for the Geneva Protocol of 1925 on January 22, 1975, a tortured, half-century-long chapter in U.S. arms control policy was brought to a close. Fifty years earlier, at the Geneva Conference for the Control of the International Trade in Arms, Munitions and Implements of War, the United States had played a key role in drafting and reaching agreement on the Protocol for the Prohibition of the Use in War of Asphyxiating, Poisonous or Other Gases and of Bacteriological Methods of Warfare. The protocol, signed by thirty nations, including the United States, on June 17, 1925, prohibits the use in war of asphyxiating, poisonous or other gases, and of all analogous liquids, materials or devices as well as the use of bacteriological methods of warfare

  8. 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

  9. A randomized phase II chemoprevention trial of 13-CIS retinoic acid with or without alpha tocopherol or observation in subjects at high risk for lung cancer.

    Science.gov (United States)

    Kelly, Karen; Kittelson, John; Franklin, Wilbur A; Kennedy, Timothy C; Klein, Catherine E; Keith, Robert L; Dempsey, Edward C; Lewis, Marina; Jackson, Mary K; Hirsch, Fred R; Bunn, Paul A; Miller, York E

    2009-05-01

    No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without alpha tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus alpha tocopherol (13-cis RA/alpha toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment "failure" defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to observations/13-cis RA/13-cis RA/alpha toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/alpha toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36-2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, -0.18; 95% confidence interval, -1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The

  10. A Randomized Phase II Chemoprevention Trial of 13-CIS Retinoic Acid with Or without α Tocopherol or Observation in Subjects at High Risk for Lung Cancer

    Science.gov (United States)

    Kelly, Karen; Kittelson, John; Franklin, Wilbur A.; Kennedy, Timothy C.; Klein, Catherine E.; Keith, Robert L.; Dempsey, Edward C.; Lewis, Marina; Jackson, Mary K.; Hirsch, Fred R.; Bunn, Paul A.; Miller, York E.

    2011-01-01

    No chemoprevention strategies have been proven effective for lung cancer. We evaluated the effect of 13-cis retinoic acid (13-cis RA), with or without α tocopherol, as a lung cancer chemoprevention agent in a phase II randomized controlled clinical trial of adult subjects at high risk for lung cancer as defined by the presence of sputum atypia, history of smoking, and airflow obstruction, or a prior surgically cured nonsmall cell lung cancer (disease free, >3 years). Subjects were randomly assigned to receive either 13-cis RA, 13-cis RA plus α tocopherol (13-cis RA/α toco) or observation for 12 months. Outcome measures are derived from histologic evaluation of bronchial biopsy specimens obtained by bronchoscopy at baseline and follow-up. The primary outcome measure is treatment “failure” defined as histologic progression (any increase in the maximum histologic score) or failure to return for follow-up bronchoscopy. Seventy-five subjects were randomized (27/22/26 to obervations/13-cis RA/13-cis RA/α toco); 59 completed the trial; 55 had both baseline and follow-up bronchoscopy. The risk of treatment failure was 55.6% (15 of 27) and 50% (24 of 48) in the observation and combined (13 cis RA plus 13 cis RA/α toco) treatment arms, respectively (odds ratio adjusted for baseline histology, 0.97; 95% confidence interval, 0.36–2.66; P = 0.95). Among subjects with complete histology data, maximum histology score in the observation arm increased by 0.37 units and by 0.03 units in the treated arms (difference adjusted for baseline, −0.18; 95% confidence interval, −1.16 to 0.81; P = 0.72). Similar (nonsignificant) results were observed for treatment effects on endobronchial proliferation as assessed by Ki-67 immunolabeling. Twelve-month treatment with 13-cis RA produced nonsignificant changes in bronchial histology, consistent with results in other trials. Agents advancing to phase III randomized trials should produce greater histologic changes. The addition of

  11. Chemoprevention of skin cancer with 1,1-Bis (3'-indolyl-1-(aromatic methane analog through induction of the orphan nuclear receptor, NR4A2 (Nurr1.

    Directory of Open Access Journals (Sweden)

    Cedar H A Boakye

    Full Text Available The objective of this study was to demonstrate the anti-skin cancer and chemopreventive potential of 1,1-bis(3'-indolyl-1-(p-chlorophenyl methane (DIM-D using an in vitro model.In vitro cell cytotoxicity and viability assays were carried out in A431 human epidermoid carcinoma cell line and normal human epidermal keratinocytes (NHEK respectively by crystal violet staining. Apoptosis induction in A431 cells (DIM-D treated and NHEK cells pretreated with DIM-D (2 hr prior to UVB irradiation, were assessed. The accumulation of reactive oxygen species (ROS in DIM-D pretreated NHEK cells (2 hr prior to UVB exposure was also determined. Immunocytochemistry and western blot analysis was performed to determine cleaved caspase 3 and DNA damage markers in DIM-D treated A431 cells and in DIM-D pretreated NHEK cells prior to UVB irradiation.The IC50 values of DIM-D were 68.7 ± 7.3, 48.3 ± 10.1 and 11.5 ± 3.1 μM whilst for Epigallocatechin gallate (EGCG were 419.1 ± 8.3, 186.1 ± 5.2 and 56.7 ± 3.1 μM for 24, 48 and 72 hr treatments respectively. DIM-D exhibited a significantly (p<0.05 greater induction of DNA fragmentation in A431 cells compared to EGCG with percent cell death of 38.9. In addition, DIM-D induced higher expression in A431 cells compared to EGCG of cleaved caspase 3 (3.0-fold vs. 2.4-fold changes, Nurr1 (2.7-fold vs. 1.7-fold changes and NFκB (1.3-fold vs. 1.1-fold changes. DIM-D also exhibited chemopreventive activity in UVB-irradiated NHEK cells by significantly (p<0.05 reducing UVB-induced ROS formation and apoptosis compared to EGCG. Additionally, DIM-D induced expression of Nurr1 but reduced expression of 8-OHdG significantly in UVB-irradiated NHEK cells compared to EGCG and UV only.Our results suggest that DIM-D exhibits Nurr1-dependent transactivation in the induction of apoptosis in A431 cells and it protects NHEK cells against UVB-induced ROS formation and DNA damage.

  12. The Kyoto protocol development; La viabilite du protocole de Kyoto

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, R. [Harvard Univ., Barrow, AK (United States); Guesneris, R. [College de France, 75 - Paris (France)

    2002-04-01

    From the author R. Cooper point of view the Kyoto Protocol is a flawed concept. The reasons for dropping Kyoto are presented in this paper insisting that rejecting Kyoto not means to imply that global climate change is not a serious problem. After a presentation of the US policy facing the Climatic Change, some concluding propositions are proposed. (A.L.B.)

  13. Symbolic Analysis of Cryptographic Protocols

    DEFF Research Database (Denmark)

    Dahl, Morten

    We present our work on using abstract models for formally analysing cryptographic protocols: First, we present an ecient method for verifying trace-based authenticity properties of protocols using nonces, symmetric encryption, and asymmetric encryption. The method is based on a type system...... of Gordon et al., which we modify to support fully-automated type inference. Tests conducted via an implementation of our algorithm found it to be very ecient. Second, we show how privacy may be captured in a symbolic model using an equivalencebased property and give a formal denition. We formalise...

  14. Petri Nets in Cryptographic Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico; Winskel, Glynn

    2001-01-01

    A process language for security protocols is presented together with a semantics in terms of sets of events. The denotation of process is a set of events, and as each event specifies a set of pre and postconditions, this denotation can be viewed as a Petri net. By means of an example we illustrate...

  15. Improving the DGK comparison protocol

    NARCIS (Netherlands)

    Veugen, P.J.M.

    2012-01-01

    When processing signals in the encrypted domain, homomorphic encryption can be used to enable linear operations on encrypted data. Comparison of encrypted data however requires an additional protocol between the parties and will be relatively expensive. A well-known and frequently used comparison

  16. Performance Evaluation of Security Protocols

    DEFF Research Database (Denmark)

    Bodei, Chiara; Buchholtz, Mikael; Curti, Michele

    2005-01-01

    We use a special operational semantics which drives us in inferring quantitative measures on systems describing cryptographis cryptographic protocols. We assign rates to transitions by only looking at these labels. The rates reflect the distributed architecture running applications and the use...... of possibly different cryptosystems. We then map transition systems to Markov chains and evaluate performance of systems, using standard tools....

  17. Art. 1 Eerste Protocol EVRM

    NARCIS (Netherlands)

    Poelmann, E.

    2014-01-01

    Het recht op bezit is niet in het Europees Verdrag ter bescherming van de rechten van de mens en de fundamentele vrijheden (hierna: EVRM) neergelegd, maar in het Eerste Protocol daarbij (hierna: EP), dat in 1954 in werking is getreden. Het is van belang voor ogen te houden dat de Tweede Wereldoorlog

  18. Bundle Security Protocol for ION

    Science.gov (United States)

    Burleigh, Scott C.; Birrane, Edward J.; Krupiarz, Christopher

    2011-01-01

    This software implements bundle authentication, conforming to the Delay-Tolerant Networking (DTN) Internet Draft on Bundle Security Protocol (BSP), for the Interplanetary Overlay Network (ION) implementation of DTN. This is the only implementation of BSP that is integrated with ION.

  19. Affinity biosensors: techniques and protocols

    National Research Council Canada - National Science Library

    Rogers, Kim R; Mulchandani, Ashok

    1998-01-01

    ..., and government to begin or expand their biosensors research. This volume, Methods in Biotechnology vol. 7: Affinity Biosensors: Techniques and Protocols, describes a variety of classical and emerging transduction technologies that have been interfaced to bioaffinity elements (e.g., antibodies and receptors). Some of the reas...

  20. High Entropy Random Selection Protocols

    NARCIS (Netherlands)

    H. Buhrman (Harry); M. Christandl (Matthias); M. Koucky (Michal); Z. Lotker (Zvi); B. Patt-Shamir; M. Charikar; K. Jansen; O. Reingold; J. Rolim

    2007-01-01

    textabstractIn this paper, we construct protocols for two parties that do not trust each other, to generate random variables with high Shannon entropy. We improve known bounds for the trade off between the number of rounds, length of communication and the entropy of the outcome.

  1. A Student Teamwork Induction Protocol

    Science.gov (United States)

    Kamau, Caroline; Spong, Abigail

    2015-01-01

    Faulty group processes have harmful effects on performance but there is little research about intervention protocols to pre-empt them in higher education. This naturalistic experiment compared a control cohort with an inducted cohort. The inducted cohort attended a workshop, consultations, elected a leader and used tools (a group log and group…

  2. Cognitive Communications Protocols for SATCOM

    Science.gov (United States)

    2017-10-20

    communications protocols for satellite and space communications with possible broad applications in defense, homeland-security as well as consumer ...communications with possible broad applications in defense, homeland-security, and civilian as well as consumer telecommunications. Such cognitive...vulnerable against smart jammers that may attempt to learn the cognitive radios own behavior . In response, our second class of proposed algorithms

  3. Non-classical mechanisms of transcriptional regulation by the vitamin D receptor: insights into calcium homeostasis, immune system regulation and cancer chemoprevention.

    Science.gov (United States)

    Dimitrov, Vassil; Salehi-Tabar, Reyhaneh; An, Beum-Soo; White, John H

    2014-10-01

    Hormonal 1,25-dihydroxyvitamin D [1,25(OH)2D] signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. Gene expression profiling studies have revealed that 1,25(OH)2D signaling through the VDR can lead to activation or repression of target gene transcription in roughly equal proportions. Classically, transcriptional regulation by the VDR, similar to other nuclear receptors, has been characterized by its capacity to recognize high affinity cognate vitamin D response elements (VDREs), located in the regulatory regions of target genes. Several biochemical studies revealed that the VDRE-bound receptor recruits a series of coregulatory proteins, leading to transactivation of adjacent target genes. However, genome-wide and other analyses of VDR binding have revealed that a subset of VDR binding sites does not contain VDREs, and that VDREs are not associated with transcriptionally repressed VDR target genes. Work over the last ∼20 years and in particular recent findings have revealed a diverse array of mechanisms by which VDR can form complexes with several other classes of transcriptional activators, leading to repression of gene transcription. Moreover, these efforts have led to several insights into the molecular basis for the physiological regulation of calcium homeostasis, immune system function and cancer chemoprevention by 1,25(OH)2D/VDR signaling. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. 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.

  5. Designing the selenium and bladder cancer trial (SELEBLAT, a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

    Directory of Open Access Journals (Sweden)

    Goossens Maria E

    2012-03-01

    Full Text Available Abstract Background In Belgium, bladder cancer is the fifth most common cancer in males (5.2% and the sixth most frequent cause of death from cancer in males (3.8%. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence. Method The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org. Patients are randomly assigned to selenium yeast (200 μg/day supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study. Design The SELEnium and BLAdder cancer Trial (SELEBLAT is a phase III randomized, placebo-controlled, academic, double-blind superior trial. Discussion This is the first report on a selenium randomized trial in bladder cancer patients. Trial registration ClinicalTrials.gov identifier: NCT00729287

  6. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Cancer Chemoprevention by Traditional Chinese Herbal Medicine and Dietary Phytochemicals: Targeting Nrf2-Mediated Oxidative Stress/Anti-Inflammatory Responses, Epigenetics, and Cancer Stem Cells

    Directory of Open Access Journals (Sweden)

    Jong Hun Lee

    2013-01-01

    Full Text Available Excessive oxidative stress induced by reactive oxygen species (ROS, reactive nitrogen species (RNS, and reactive metabolites of carcinogens alters cellular homeostasis, leading to genetic/epigenetic changes, genomic instability, neoplastic transformation, and cancer initiation/progression. As a protective mechanism against oxidative stress, antioxidant/detoxifying enzymes reduce these reactive species and protect normal cells from endo-/exogenous oxidative damage. The transcription factor nuclear factor-erythroid 2 p45 (NF-E2-related factor 2 (Nrf2, a master regulator of the antioxidative stress response, plays a critical role in the expression of many cytoprotective enzymes, including NAD(PH:quinine oxidoreductase (NQO1, heme oxygenase-1 (HO-1, UDP-glucuronosyltransferase (UGT, and glutathione S-transferase (GST. Recent studies demonstrated that many dietary phytochemicals derived from various vegetables, fruits, spices, and herbal medicines induce Nrf2-mediated antioxidant/detoxifying enzymes, restore aberrant epigenetic alterations, and eliminate cancer stem cells (CSCs. The Nrf2-mediated antioxidant response prevents many age-related diseases, including cancer. Owing to their fundamental contribution to carcinogenesis, epigenetic modifications and CSCs are novel targets of dietary phytochemicals and traditional Chinese herbal medicine (TCHM. In this review, we summarize cancer chemoprevention by dietary phytochemicals, including TCHM, which have great potential as a safer and more effective strategy for preventing cancer.

  8. 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)

    Perocco, Paolo; Bronzetti, Giorgio; Canistro, Donatella; Valgimigli, Luca; Sapone, Andrea; Affatato, Alessandra; Pedulli, Gian Franco; Pozzetti, Laura; Broccoli, Massimiliano; Iori, Renato; Barillari, Jessica; Sblendorio, Valeriana; Legator, Marvin S.; Paolini, Moreno; Abdel-Rahman, Sherif Z.

    2006-01-01

    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

  9. Group covariant protocols for quantum string commitment

    International Nuclear Information System (INIS)

    Tsurumaru, Toyohiro

    2006-01-01

    We study the security of quantum string commitment (QSC) protocols with group covariant encoding scheme. First we consider a class of QSC protocol, which is general enough to incorporate all the QSC protocols given in the preceding literatures. Then among those protocols, we consider group covariant protocols and show that the exact upperbound on the binding condition can be calculated. Next using this result, we prove that for every irreducible representation of a finite group, there always exists a corresponding nontrivial QSC protocol which reaches a level of security impossible to achieve classically

  10. Improvement In MAODV Protocol Using Location Based Routing Protocol

    Directory of Open Access Journals (Sweden)

    Kaur Sharnjeet

    2016-01-01

    Full Text Available Energy saving is difficult in wireless sensor network (WSN due to limited resources. Each node in WSN is constrained by their limited battery power for their energy. The energy is reduced as the time goes off due to the packet transmission and reception. Energy management techniques are necessary to minimize the total power consumption of all the nodes in the network in order to maximize its life span. Our proposed protocol Location based routing (LBR aimed to find a path which utilizes the minimum energy to transmit the packets between the source and the destination. The required energy for the transmission and reception of data is evaluated in MATLAB. LBR is implemented on Multicast Ad hoc On Demand Distance Vector Routing Protocol (MAODV to manage the energy consumption in the transmission and reception of data. Simulation results of LBR show the energy consumption has been reduced.

  11. Using Ovsynch protocol versus Cosynch protocol in dairy cows

    Directory of Open Access Journals (Sweden)

    Ion Valeriu Caraba

    2013-10-01

    Full Text Available As a research on the reproductive physiology and endocrinology surrounding the estrous cycle in dairy cattle has been compiled, several estrous synchronization programs have been developed for use with dairy cows. These include several programs that facilitate the mass breeding of all animals at a predetermined time (timed-AI rather than the detection of estrus. We studied on 15 dary cows which were synchronized by Ovsynch and Cosynch programs. The estrus response for cows in Ovsynch protocol was of 63%. Pregnancy per insemination at 60 days was of 25%. Estrus response for cow in Cosynch protocol was of 57%. Pregnancy per insemination at 60 days was of 57%. Synchronization of ovulation using Ovsynch protocols can provide an effective way to manage reproduction in lactating dairy cows by eliminating the need for estrus detection. These are really efficient management programs for TAI of dairy cows that are able to reduce both the labour costs and the extra handling to daily estrus detection and AI.

  12. Phase Transition in Protocols Minimizing Work Fluctuations

    Science.gov (United States)

    Solon, Alexandre P.; Horowitz, Jordan M.

    2018-05-01

    For two canonical examples of driven mesoscopic systems—a harmonically trapped Brownian particle and a quantum dot—we numerically determine the finite-time protocols that optimize the compromise between the standard deviation and the mean of the dissipated work. In the case of the oscillator, we observe a collection of protocols that smoothly trade off between average work and its fluctuations. However, for the quantum dot, we find that as we shift the weight of our optimization objective from average work to work standard deviation, there is an analog of a first-order phase transition in protocol space: two distinct protocols exchange global optimality with mixed protocols akin to phase coexistence. As a result, the two types of protocols possess qualitatively different properties and remain distinct even in the infinite duration limit: optimal-work-fluctuation protocols never coalesce with the minimal-work protocols, which therefore never become quasistatic.

  13. Database communication protocol analyses and security detection

    International Nuclear Information System (INIS)

    Luo Qun; Liu Qiushi

    2003-01-01

    In this paper we introduced the analysis of TDS protocol in the communication application between Client and Server about SYBASE and MICROSOFT SQL SERVER and do some test for some bugs existed in the protocol. (authors)

  14. Developing security protocols in χ-Spaces

    DEFF Research Database (Denmark)

    Crazzolara, Federico; Milicia, Giuseppe

    2002-01-01

    It is of paramount importance that a security protocol effectively enforces the desired security requirements. The apparent simplicity of informal protocol descriptions hides the inherent complexity of their interactions which, often, invalidate informal correctness arguments and justify the effort...

  15. From protocol to published report

    DEFF Research Database (Denmark)

    Berendt, Louise; Callréus, Torbjörn; Petersen, Lene Grejs

    2016-01-01

    and published reports of academic clinical drug trials. METHODS: A comparison was made between study protocols and their corresponding published reports. We assessed the overall consistency, which was defined as the absence of discrepancy regarding study type (categorized as either exploratory or confirmatory...... in 1999, 2001, and 2003, 95 of which fulfilled the eligibility criteria and had at least one corresponding published report reporting data on trial subjects. Overall consistency was observed in 39% of the trials (95% CI: 29 to 49%). Randomized controlled trials (RCTs) constituted 72% (95% CI: 63 to 81......%) of the sample, and 87% (95% CI: 80 to 94%) of the trials were hospital based. CONCLUSIONS: Overall consistency between protocols and their corresponding published reports was low. Motivators for the inconsistencies are unknown but do not seem restricted to economic incentives....

  16. Superposition Attacks on Cryptographic Protocols

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Funder, Jakob Løvstad; Nielsen, Jesper Buus

    2011-01-01

    of information. In this paper, we introduce a fundamentally new model of quantum attacks on classical cryptographic protocols, where the adversary is allowed to ask several classical queries in quantum superposition. This is a strictly stronger attack than the standard one, and we consider the security......Attacks on classical cryptographic protocols are usually modeled by allowing an adversary to ask queries from an oracle. Security is then defined by requiring that as long as the queries satisfy some constraint, there is some problem the adversary cannot solve, such as compute a certain piece...... of several primitives in this model. We show that a secret-sharing scheme that is secure with threshold $t$ in the standard model is secure against superposition attacks if and only if the threshold is lowered to $t/2$. We use this result to give zero-knowledge proofs for all of NP in the common reference...

  17. Feasible quantum communication complexity protocol

    International Nuclear Information System (INIS)

    Galvao, Ernesto F.

    2002-01-01

    I show that a simple multiparty communication task can be performed more efficiently with quantum communication than with classical communication, even with low detection efficiency η. The task is a communication complexity problem in which distant parties need to compute a function of the distributed inputs, while minimizing the amount of communication between them. A realistic quantum optical setup is suggested that can demonstrate a five-party quantum protocol with higher-than-classical performance, provided η>0.33

  18. Cost estimation of Kyoto Protocol

    International Nuclear Information System (INIS)

    Di Giulio, Enzo

    2005-01-01

    This article proposes a reflection on important aspects in the costs determination performance of Kyoto Protocol. The evaluation of the main models evidence possible impacts on the economies. A key role in the determination of the cost is represented by the relative hypothesis to emission trading and the projects CDM-JI and from the political capacity at the cost negative or equal to zero [it

  19. Building America House Simulation Protocols

    Energy Technology Data Exchange (ETDEWEB)

    Hendron, Robert [National Renewable Energy Lab. (NREL), Golden, CO (United States); Engebrecht, Cheryn [National Renewable Energy Lab. (NREL), Golden, CO (United States)

    2010-09-01

    The House Simulation Protocol document was developed to track and manage progress toward Building America's multi-year, average whole-building energy reduction research goals for new construction and existing homes, using a consistent analytical reference point. This report summarizes the guidelines for developing and reporting these analytical results in a consistent and meaningful manner for all home energy uses using standard operating conditions.

  20. Behavior Protocols for Software Components

    Czech Academy of Sciences Publication Activity Database

    Plášil, František; Višňovský, Stanislav

    2002-01-01

    Roč. 28, č. 11 (2002), s. 1056-1076 ISSN 0098-5589 R&D Projects: GA AV ČR IAA2030902; GA ČR GA201/99/0244 Grant - others:Eureka(XE) Pepita project no.2033 Institutional research plan: AV0Z1030915 Keywords : behavior protocols * component-based programming * software architecture Subject RIV: JC - Computer Hardware ; Software Impact factor: 1.170, year: 2002

  1. Desensitization protocols and their outcome.

    Science.gov (United States)

    Marfo, Kwaku; Lu, Amy; Ling, Min; Akalin, Enver

    2011-04-01

    In the last decade, transplantation across previously incompatible barriers has increasingly become popular because of organ donor shortage, availability of better methods of detecting and characterizing anti-HLA antibodies, ease of diagnosis, better understanding of antibody-mediated rejection, and the availability of effective regimens. This review summarizes all manuscripts published since the first publication in 2000 on desensitized patients and discusses clinical outcomes including acute and chronic antibody-mediated rejection rate, the new agents available, kidney paired exchange programs, and the future directions in sensitized patients. There were 21 studies published between 2000 and 2010, involving 725 patients with donor-specific anti-HLA antibodies (DSAs) who underwent kidney transplantation with different desensitization protocols. All studies were single center and retrospective. The patient and graft survival were 95% and 86%, respectively, at a 2-year median follow-up. Despite acceptable short-term patient and graft survivals, acute rejection rate was 36% and acute antibody-mediated rejection rate was 28%, which is significantly higher than in nonsensitized patients. Recent studies with longer follow-up of those patients raised concerns about long-term success of desensitization protocols. The studies utilizing protocol biopsies in desensitized patients also reported higher subclinical and chronic antibody-mediated rejection. An association between the strength of DSAs determined by median fluorescence intensity values of Luminex single-antigen beads and risk of rejection was observed. Two new agents, bortezomib, a proteasome inhibitor, and eculizumab, an anti-complement C5 antibody, were recently introduced to desensitization protocols. An alternative intervention is kidney paired exchange, which should be considered first for sensitized patients. © 2011 by the American Society of Nephrology

  2. Bioinspired Security Analysis of Wireless Protocols

    DEFF Research Database (Denmark)

    Petrocchi, Marinella; Spognardi, Angelo; Santi, Paolo

    2016-01-01

    work, this paper investigates feasibility of adopting fraglets as model for specifying security protocols and analysing their properties. In particular, we give concrete sample analyses over a secure RFID protocol, showing evolution of the protocol run as chemical dynamics and simulating an adversary...

  3. Formal analysis of a fair payment protocol

    NARCIS (Netherlands)

    J.G. Cederquist; M.T. Dashti (Mohammad)

    2004-01-01

    textabstractWe formally specify a payment protocol. This protocol is intended for fair exchange of time-sensitive data. Here the ?-CRL language is used to formalize the protocol. Fair exchange properties are expressed in the regular alternation-free ?-calculus. These properties are then verified

  4. Formal Analysis of a Fair Payment Protocol

    NARCIS (Netherlands)

    Cederquist, J.G.; Dashti, M.T.

    2004-01-01

    We formally specify a payment protocol. This protocol is intended for fair exchange of timesensitive data. Here the μCRL language is used to formalize the protocol. Fair exchange properties are expressed in the regular alternation-free μ-calculus. These properties are then verified using the finite

  5. Formal Analysis of a Fair Payment Protocol

    NARCIS (Netherlands)

    Cederquist, J.G.; Dashti, Muhammad Torabi; Dimitrakos, Theo; Martinelli, Fabio

    We formally specify a payment protocol described by Vogt et al. This protocol is intended for fair exchange of time-sensitive data. Here the mCRL language is used to formalize the protocol. Fair exchange properties are expressed in the regular alternation-free mu-calculus. These properties are then

  6. Advanced dementia pain management protocols.

    Science.gov (United States)

    Montoro-Lorite, Mercedes; Canalias-Reverter, Montserrat

    Pain management in advanced dementia is complex because of neurological deficits present in these patients, and nurses are directly responsible for providing interventions for the evaluation, management and relief of pain for people suffering from this health problem. In order to facilitate and help decision-makers, pain experts recommend the use of standardized protocols to guide pain management, but in Spain, comprehensive pain management protocols have not yet been developed for advanced dementia. This article reflects the need for an integrated management of pain in advanced dementia. From the review and analysis of the most current and relevant studies in the literature, we performed an approximation of the scales for the determination of pain in these patients, with the observational scale PAINAD being the most recommended for the hospital setting. In addition, we provide an overview for comprehensive management of pain in advanced dementia through the conceptual framework «a hierarchy of pain assessment techniques by McCaffery and Pasero» for the development and implementation of standardized protocols, including a four-phase cyclical process (evaluation, planning/performance, revaluation and recording), which can facilitate the correct management of pain in these patients. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  7. Use and interpretation of the dynamic cone penetrometer (DCP) test

    CSIR Research Space (South Africa)

    Paige-Green, P

    2009-09-01

    Full Text Available seldom becomes soaked. The test results are thus really incomparable with the actual conditions, which are likely to prevail in the field. The CBR test has been adapted for the field using a portable CBR but it is difficult and time consuming...

  8. Introducing you to satellite operated data collection platforms (DCP).

    CSIR Research Space (South Africa)

    Stavropoulos, CC

    1977-09-01

    Full Text Available and operate in the VHF, UHF or microwave bands. By using a satellite as a repeater, large distances over land and sea can be covered with a single repeater in the sky. Trans-continental links for communication purposes have been operational for many years...

  9. 78 FR 43190 - DCP Midstream, LP; Notice of Application

    Science.gov (United States)

    2013-07-19

    ... and accounting regulatory requirements regarding the proposed Lucerne Residue Pipeline. The filing may... internet in lieu of paper; see, 18 CFR 385.2001(a)(1)(iii) and the instructions on the Commission's Web...

  10. Effects of chemopreventive agents on the incidence of recurrent colorectal adenomas: a systematic review with network meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Veettil SK

    2017-05-01

    Full Text Available Sajesh K Veettil,1 Nattawat Teerawattanapong,2 Siew Mooi Ching,3,4 Kean Ghee Lim,5 Surasak Saokaew,6–9 Pochamana Phisalprapa,10 Nathorn Chaiyakunapruk7,8,11,12 1School of Pharmacy/School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia; 2Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand; 3Department of Family Medicine, Faculty of Medicine and Health Sciences, 4Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, 5Clinical School, Department of Surgery, International Medical University, Seremban, Negeri Sembilan, 6Center of Health Outcomes Research and Therapeutic Safety (Cohorts, School of Pharmaceutical Sciences, University of Phayao, Phayao, 7School of Pharmacy, Monash University Malaysia, Selangor, Malaysia; 8Centre of Pharmaceutical Outcomes Research, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand; 9Unit of Excellence on Herbal Medicine, School of Pharmaceutical Sciences, University of Phayao, Thailand; 10Division of Ambulatory Medicine, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 11School of Pharmacy, University of Wisconsin, Madison, USA; 12Health and Well-being Cluster, Global Asia Platform in the 21st Century (GA21 Platform, Monash University Malaysia, Selangor, Malaysia Background: Protective effects of several chemopreventive agents (CPAs against colorectal adenomas have been well documented in randomized controlled trials (RCTs; however, there is uncertainty regarding which agents are the most effective.Methods: We searched for RCTs published up until September 2016. Retrieved trials were evaluated using risk of bias. We performed both pairwise analysis and network meta-analysis (NMA of RCTs to compare the effects of CPAs on the recurrence of colorectal adenomas (primary outcome. Using NMA, we

  11. Nonblocking and orphan free message logging protocols

    Science.gov (United States)

    Alvisi, Lorenzo; Hoppe, Bruce; Marzullo, Keith

    1992-12-01

    Currently existing message logging protocols demonstrate a classic pessimistic vs. optimistic tradeoff. We show that the optimistic-pessimistic tradeoff is not inherent to the problem of message logging. We construct a message-logging protocol that has the positive features of both optimistic and pessimistic protocol: our protocol prevents orphans and allows simple failure recovery; however, it requires no blocking in failure-free runs. Furthermore, this protocol does not introduce any additional message overhead as compared to one implemented for a system in which messages may be lost but processes do not crash.

  12. 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.

  13. A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study

    Science.gov (United States)

    2012-01-01

    Background Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown. Methods Attrition (dropouts) and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥ 85% of the prescribed treatment packets) are the main outcome measures reported. Results There was a high rate of dropout (51%) from the study, and the rates were significantly higher among smokers (64%) than non-smokers (36%). Among participants who completed the study the rate of compliance was 72%. The highest rates of dropouts occurred between the first and second treatment visits in both smokers (38% dropout) and non-smokers (18% dropout). Throughout the study smokers were more likely to dropout than non-smokers. Black tea treatment was associated with the highest rates of dropout among smokers (37%), but was associated with the lowest rate of dropout among non-smokers (4%). Conclusions In a study conducted to test the feasibility of a four-treatment crossover tea trial, a high rate of dropout among smokers and non-smokers was observed. Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials. Trial registration number ISRCTN70410203 PMID:22800470

  14. The chemopreventive properties of chlorogenic acid reveal a potential new role for the microsomal glucose-6-phosphate translocase in brain tumor progression

    Directory of Open Access Journals (Sweden)

    Desgagnés Julie

    2006-03-01

    Full Text Available Abstract Background Chlorogenic acid (CHL, the most potent functional inhibitor of the microsomal glucose-6-phosphate translocase (G6PT, is thought to possess cancer chemopreventive properties. It is not known, however, whether any G6PT functions are involved in tumorigenesis. We investigated the effects of CHL and the potential role of G6PT in regulating the invasive phenotype of brain tumor-derived glioma cells. Results RT-PCR was used to show that, among the adult and pediatric brain tumor-derived cells tested, U-87 glioma cells expressed the highest levels of G6PT mRNA. U-87 cells lacked the microsomal catalytic subunit glucose-6-phosphatase (G6Pase-α but expressed G6Pase-β which, when coupled to G6PT, allows G6P hydrolysis into glucose to occur in non-glyconeogenic tissues such as brain. CHL inhibited U-87 cell migration and matrix metalloproteinase (MMP-2 secretion, two prerequisites for tumor cell invasion. Moreover, CHL also inhibited cell migration induced by sphingosine-1-phosphate (S1P, a potent mitogen for glioblastoma multiform cells, as well as the rapid, S1P-induced extracellular signal-regulated protein kinase phosphorylation potentially mediated through intracellular calcium mobilization, suggesting that G6PT may also perform crucial functions in regulating intracellular signalling. Overexpression of the recombinant G6PT protein induced U-87 glioma cell migration that was, in turn, antagonized by CHL. MMP-2 secretion was also inhibited by the adenosine triphosphate (ATP-depleting agents 2-deoxyglucose and 5-thioglucose, a mechanism that may inhibit ATP-mediated calcium sequestration by G6PT. Conclusion We illustrate a new G6PT function in glioma cells that could regulate the intracellular signalling and invasive phenotype of brain tumor cells, and that can be targeted by the anticancer properties of CHL.

  15. Pharmacokinetics of dietary cancer chemopreventive compound dibenzoylmethane in rats and the impact of nanoemulsion and genetic knockout of Nrf2 on its disposition.

    Science.gov (United States)

    Lin, Wen; Hong, Jin-Liern; Shen, Guoxiang; Wu, Rachel T; Wang, Yuwen; Huang, Mou-Tuan; Newmark, Harold L; Huang, Qingrong; Khor, Tin Oo; Heimbach, Tycho; Kong, Ah-Ng

    2011-03-01

    The pharmacokinetic disposition of a dietary cancer chemopreventive compound dibenzoylmethane (DBM) was studied in male Sprague-Dawley rats after intravenous (i.v.) and oral (p.o.) administrations. Following a single i.v. bolus dose, the mean plasma clearance (CL) of DBM was low compared with the hepatic blood flow. DBM displayed a high volume of distribution (Vss). The elimination terminal t1/2 was long. The mean CL, Vss and AUC0-∞/dose were similar between the i.v. 10 and 10 mg/kg doses. After single oral doses (10, 50 and 250 mg/kg), the absolute oral bioavailability (F*) of DBM was 7.4%-13.6%. The increase in AUC was not proportional to the oral doses, suggesting non-linearity. In silico prediction of oral absorption also demonstrated low DBM absorption in vivo. An oil-in-water nanoemulsion containing DBM was formulated to potentially overcome the low F* due to poor water solubility of DBM, with enhanced oral absorption. Finally, to examine the role of Nrf2 on the pharmacokinetics of DBM, since DBM activates the Nrf2-dependent detoxification pathways, Nrf2 wild-type (+/+) mice and Nrf2 knockout (-/-) mice were utilized. There was an increased systemic plasma exposure of DBM in Nrf2 (-/-) mice, suggesting that the Nrf2 genotype could also play a role in the pharmacokinetic disposition of DBM. Taken together, the results show that DBM has low oral bioavailability which could be due in part to poor water solubility and this could be overcome by a nanotechnology-based drug delivery system and furthermore the Nrf2 genotype could also play a role in the pharmacokinetics of DBM. Copyright © 2010 John Wiley & Sons, Ltd.

  16. Chemopreventive effects of PBI-Se, a selenium-containing analog of PBIT, on AOM-induced aberrant crypt foci in F344 rats.

    Science.gov (United States)

    Janakiram, Naveena B; Mohammed, Altaf; Ravillah, Durgadevi; Choi, Chang In; Zhang, Yuting; Desai, Dhimant; Amin, Shantu; Rao, Chinthalapally V

    2013-08-01

    Inducible nitric oxide synthase (iNOS) is a potential target for the treatment of inflammation and cancer. Previously, we showed that the selective iNOS inhibitor S,S'-1,4-phenylenebis(1,2-ethanediyl)bis-isothiourea (PBIT) caused significant inhibition of colon carcinogenesis induced by azoxymethane (AOM), although it did not completely abrogate NO production due to the exogenous bioavailability of NO and NO generation by eNOS in tumor tissues. To create an iNOS-targeting molecule that may have additional benefits, a novel isosteric analog of PBIT, PBI-Se, was developed, in which sulfur was replaced with selenium. Chemopreventive efficacy of PBI-Se was evaluated in an AOM-induced rat colon carcinogenesis model using aberrant crypt foci (ACF) as the endpoint. At 7 weeks of age, rats (12/group) were fed the control diet (AIN 76A) and then colonic ACF were induced with two AOM treatments. Three days later, rats were fed diets containing PBI-Se (0-20 ppm) for 8 weeks, and then ACF were evaluated histopathologically. Dietary administration of 10 or 20 ppm of PBI-Se significantly suppressed AOM-induced total colonic ACF formation (32 or 41%, pPBI-Se was dose-dependent and was half the dose of PBIT for inhibiting total ACF in rats. Both PBIT and PBI-Se induced dose-dependent apoptosis in CaCo2 cells and caused a significant decrease in the cell cycle proteins cyclin D1 (70%, pPBI-Se (2 and 4  µM) significantly decreased the LPS-induced cytokine interleukin-6 level. Incorporation of selenium into the structure of PBIT provided the agent with additional novel cytotoxic and immunologic properties. Results from the in vitro and in vivo bioassays suggest that PBI-Se could be developed further for the prevention and treatment of colon cancer.

  17. Chemopreventive effects of a curcumin-like diarylpentanoid [2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone] in cellular targets of rheumatoid arthritis in vitro.

    Science.gov (United States)

    Lee, Ka-Heng; Abas, Faridah; Mohamed Alitheen, Noorjahan Banu; Shaari, Khozirah; Lajis, Nordin Haji; Israf, Daud Ahmad; Syahida, Ahmad

    2015-07-01

    Synovial fibroblast has emerged as a potential cellular target in progressive joint destruction in rheumatoid arthritis development. In this study, BDMC33 (2,6-bis[2,5-dimethoxybenzylidene]cyclohexanone), a curcumin analogue with enhanced anti-inflammatory activity has been synthesized and the potency of BDMC33 on molecular and cellular basis of synovial fibroblasts (SF) were evaluated in vitro. Synovial fibroblast cells (HIG-82) were cultured in vitro and induced by phorbol-12-myristate acetate (PMA) to stimulate the expression of matrix metalloproteinase (MMPs) and pro-inflammatory cytokines. The protective effects of BDMC33 were evaluated toward MMP activities, pro-inflammatory cytokine expression and nuclear factor kappa-B (NF-κB) activation by using various bioassay methods, including zymography, Western blotting, reverse transcription polymerase chain reaction, immunofluorescense microscopy and electrophoretic mobility shift assay. The results showed that BDMC33 significantly inhibited the pro-gelatinase B (pro-MMP-9) and collagenase activities via suppression of MMP-1 in activated SF. In addition, BDMC33 strongly suppressed MMP-3 gene expression as well as inhibited COX-2 and IL-6 pro-inflammatory gene expression. We also demonstrated that BDMC33 abolished the p65 NF-κB nuclear translocation and NF-κB DNA binding activity in PMA-stimulated SF. BDMC33 represents an effective chemopreventive agent and could be used as a promising lead compound for further development of rheumatoid arthritis therapeutic intervention. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  18. Direct reduction of N-acetoxy-PhIP by tea polyphenols: a possible mechanism for chemoprevention against PhIP-DNA adduct formation

    International Nuclear Information System (INIS)

    Lin Dongxin; Thompson, Patricia A.; Teitel, Candee; Chen Junshi; Kadlubar, Fred F.

    2003-01-01

    The chemopreventive effect of tea against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-DNA adduct formation and its mechanism were studied. Rats were exposed to freshly prepared aqueous extracts of green tea (3% (w/v)) as the sole source of drinking water for 10 days prior to administration with a single dose of PhIP (10 mg/kg body weight) by oral gavage. PhIP-DNA adducts in the liver, colon, heart, and lung were measured using the 32 P-postlabelling technique. Rats pre-treated with tea and given PhIP 20 h before sacrifice had significantly reduced levels of PhIP-DNA adducts as compared with controls given PhIP alone. The possible mechanism of protective effect of tea on PhIP-DNA adduct formation was then examined in vitro. It was found that an aqueous extract of green and black tea, mixtures of green and black tea polyphenols, as well as purified polyphenols could strongly inhibit the DNA binding of N-acetoxy-PhIP, a putative ultimate carcinogen of PhIP formed in vivo via metabolic activation. Among these, epigallocatechin gallate was exceptionally potent. HPLC analyses of these incubation mixtures containing N-acetoxy-PhIP and the tea polyphenols each revealed the production of the parent amine, PhIP, indicating the involvement of a redox mechanism. In view of the presence of relatively high levels of tea polyphenols in rat and human plasma after ingestion of tea, this study suggests that direct reduction of the ultimate carcinogen N-acetoxy-PhIP by tea polyphenols is likely to be involved in the mechanism of chemoprotection of tea against this carcinogen

  19. Ancestors protocol for scalable key management

    Directory of Open Access Journals (Sweden)

    Dieter Gollmann

    2010-06-01

    Full Text Available Group key management is an important functional building block for secure multicast architecture. Thereby, it has been extensively studied in the literature. The main proposed protocol is Adaptive Clustering for Scalable Group Key Management (ASGK. According to ASGK protocol, the multicast group is divided into clusters, where each cluster consists of areas of members. Each cluster uses its own Traffic Encryption Key (TEK. These clusters are updated periodically depending on the dynamism of the members during the secure session. The modified protocol has been proposed based on ASGK with some modifications to balance the number of affected members and the encryption/decryption overhead with any number of the areas when a member joins or leaves the group. This modified protocol is called Ancestors protocol. According to Ancestors protocol, every area receives the dynamism of the members from its parents. The main objective of the modified protocol is to reduce the number of affected members during the leaving and joining members, then 1 affects n overhead would be reduced. A comparative study has been done between ASGK protocol and the modified protocol. According to the comparative results, it found that the modified protocol is always outperforming the ASGK protocol.

  20. Generalized routing protocols for multihop relay networks

    KAUST Repository

    Khan, Fahd Ahmed

    2011-07-01

    Performance of multihop cooperative networks depends on the routing protocols employed. In this paper we propose the last-n-hop selection protocol, the dual path protocol, the forward-backward last-n-hop selection protocol and the forward-backward dual path protocol for the routing of data through multihop relay networks. The average symbol error probability performance of the schemes is analysed by simulations. It is shown that close to optimal performance can be achieved by using the last-n-hop selection protocol and its forward-backward variant. Furthermore we also compute the complexity of the protocols in terms of number of channel state information required and the number of comparisons required for routing the signal through the network. © 2011 IEEE.

  1. Asymptotic adaptive bipartite entanglement-distillation protocol

    International Nuclear Information System (INIS)

    Hostens, Erik; Dehaene, Jeroen; De Moor, Bart

    2006-01-01

    We present an asymptotic bipartite entanglement-distillation protocol that outperforms all existing asymptotic schemes. This protocol is based on the breeding protocol with the incorporation of two-way classical communication. Like breeding, the protocol starts with an infinite number of copies of a Bell-diagonal mixed state. Breeding can be carried out as successive stages of partial information extraction, yielding the same result: one bit of information is gained at the cost (measurement) of one pure Bell state pair (ebit). The basic principle of our protocol is at every stage to replace measurements on ebits by measurements on a finite number of copies, whenever there are two equiprobable outcomes. In that case, the entropy of the global state is reduced by more than one bit. Therefore, every such replacement results in an improvement of the protocol. We explain how our protocol is organized as to have as many replacements as possible. The yield is then calculated for Werner states

  2. Short Review on Quantum Key Distribution Protocols.

    Science.gov (United States)

    Giampouris, Dimitris

    2017-01-01

    Cryptographic protocols and mechanisms are widely investigated under the notion of quantum computing. Quantum cryptography offers particular advantages over classical ones, whereas in some cases established protocols have to be revisited in order to maintain their functionality. The purpose of this paper is to provide the basic definitions and review the most important theoretical advancements concerning the BB84 and E91 protocols. It also aims to offer a summary on some key developments on the field of quantum key distribution, closely related with the two aforementioned protocols. The main goal of this study is to provide the necessary background information along with a thorough review on the theoretical aspects of QKD, concentrating on specific protocols. The BB84 and E91 protocols have been chosen because most other protocols are similar to these, a fact that makes them important for the general understanding of how the QKD mechanism functions.

  3. Analyzing the effect of routing protocols on media access control protocols in radio networks

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, C. L. (Christopher L.); Drozda, M. (Martin); Marathe, A. (Achla); Marathe, M. V. (Madhav V.)

    2002-01-01

    We study the effect of routing protocols on the performance of media access control (MAC) protocols in wireless radio networks. Three well known MAC protocols: 802.11, CSMA, and MACA are considered. Similarly three recently proposed routing protocols: AODV, DSR and LAR scheme 1 are considered. The experimental analysis was carried out using GloMoSim: a tool for simulating wireless networks. The main focus of our experiments was to study how the routing protocols affect the performance of the MAC protocols when the underlying network and traffic parameters are varied. The performance of the protocols was measured w.r.t. five important parameters: (i) number of received packets, (ii) average latency of each packet, (iii) throughput (iv) long term fairness and (v) number of control packets at the MAC layer level. Our results show that combinations of routing and MAC protocols yield varying performance under varying network topology and traffic situations. The result has an important implication; no combination of routing protocol and MAC protocol is the best over all situations. Also, the performance analysis of protocols at a given level in the protocol stack needs to be studied not locally in isolation but as a part of the complete protocol stack. A novel aspect of our work is the use of statistical technique, ANOVA (Analysis of Variance) to characterize the effect of routing protocols on MAC protocols. This technique is of independent interest and can be utilized in several other simulation and empirical studies.

  4. Publication trends of study protocols in rehabilitation.

    Science.gov (United States)

    Jesus, Tiago S; Colquhoun, Heather L

    2017-09-04

    Growing evidence points for the need to publish study protocols in the health field. To observe whether the growing interest in publishing study protocols in the broader health field has been translated into increased publications of rehabilitation study protocols. Observational study using publication data and its indexation in PubMed. Not applicable. Not applicable. PubMed was searched with appropriate combinations of Medical Subject Headings up to December 2014. The effective presence of study protocols was manually screened. Regression models analyzed the yearly growth of publications. Two-sample Z-tests analyzed whether the proportion of Systematic Reviews (SRs) and Randomized Controlled Trials (RCTs) among study protocols differed from that of the same designs for the broader rehabilitation research. Up to December 2014, 746 publications of rehabilitation study protocols were identified, with an exponential growth since 2005 (r2=0.981; p<0.001). RCT protocols were the most common among rehabilitation study protocols (83%), while RCTs were significantly more prevalent among study protocols than among the broader rehabilitation research (83% vs. 35.8%; p<0.001). For SRs, the picture was reversed: significantly less common among study protocols (2.8% vs. 9.3%; p<0.001). Funding was more often reported by rehabilitation study protocols than the broader rehabilitation research (90% vs. 53.1%; p<0.001). Rehabilitation journals published a significantly lower share of rehabilitation study protocols than they did for the broader rehabilitation research (1.8% vs.16.7%; p<0.001). Identifying the reasons for these discrepancies and reverting unwarranted disparities (e.g. low rate of publication for rehabilitation SR protocols) are likely new avenues for rehabilitation research and its publication. SRs, particularly those aggregating RCT results, are considered the best standard of evidence to guide rehabilitation clinical practice; however, that standard can be improved

  5. Protein blotting protocol for beginners.

    Science.gov (United States)

    Petrasovits, Lars A

    2014-01-01

    The transfer and immobilization of biological macromolecules onto solid nitrocellulose or nylon (polyvinylidene difluoride (PVDF)) membranes subsequently followed by specific detection is referred to as blotting. DNA blots are called Southerns after the inventor of the technique, Edwin Southern. By analogy, RNA blots are referred to as northerns and protein blots as westerns (Burnette, Anal Biochem 112:195-203, 1981). With few exceptions, western blotting involves five steps, namely, sample collection, preparation, separation, immobilization, and detection. In this chapter, protocols for the entire process from sample collection to detection are described.

  6. Optical protocols for terabit networks

    Science.gov (United States)

    Chua, P. L.; Lambert, J. L.; Morookian, J. M.; Bergman, L. A.

    1991-01-01

    This paper describes a new fiber-optic local area network technology providing 100X improvement over current technology, has full crossbar funtionality, and inherent data security. Based on optical code-division multiple access (CDMA), using spectral phase encoding/decoding of optical pulses, networking protocols are implemented entirely in the optical domain and thus conventional networking bottlenecks are avoided. Component and system issues for a proof-of-concept demonstration are discussed, as well as issues for a more practical and commercially exploitable system. Possible terrestrial and aerospace applications of this technology, and its impact on other technologies are explored. Some initial results toward realization of this concept are also included.

  7. Using semantics for representing experimental protocols.

    Science.gov (United States)

    Giraldo, Olga; García, Alexander; López, Federico; Corcho, Oscar

    2017-11-13

    An experimental protocol is a sequence of tasks and operations executed to perform experimental research in biological and biomedical areas, e.g. biology, genetics, immunology, neurosciences, virology. Protocols often include references to equipment, reagents, descriptions of critical steps, troubleshooting and tips, as well as any other information that researchers deem important for facilitating the reusability of the protocol. Although experimental protocols are central to reproducibility, the descriptions are often cursory. There is the need for a unified framework with respect to the syntactic structure and the semantics for representing experimental protocols. In this paper we present "SMART Protocols ontology", an ontology for representing experimental protocols. Our ontology represents the protocol as a workflow with domain specific knowledge embedded within a document. We also present the S ample I nstrument R eagent O bjective (SIRO) model, which represents the minimal common information shared across experimental protocols. SIRO was conceived in the same realm as the Patient Intervention Comparison Outcome (PICO) model that supports search, retrieval and classification purposes in evidence based medicine. We evaluate our approach against a set of competency questions modeled as SPARQL queries and processed against a set of published and unpublished protocols modeled with the SP Ontology and the SIRO model. Our approach makes it possible to answer queries such as Which protocols use tumor tissue as a sample. Improving reporting structures for experimental protocols requires collective efforts from authors, peer reviewers, editors and funding bodies. The SP Ontology is a contribution towards this goal. We build upon previous experiences and bringing together the view of researchers managing protocols in their laboratory work. Website: https://smartprotocols.github.io/ .

  8. Physical Therapy Protocols for Arthroscopic Bankart Repair.

    Science.gov (United States)

    DeFroda, Steven F; Mehta, Nabil; Owens, Brett D

    Outcomes after arthroscopic Bankart repair can be highly dependent on compliance and participation in physical therapy. Additionally, there are many variations in physician-recommended physical therapy protocols. The rehabilitation protocols of academic orthopaedic surgery departments vary widely despite the presence of consensus protocols. Descriptive epidemiology study. Level 3. Web-based arthroscopic Bankart rehabilitation protocols available online from Accreditation Council for Graduate Medical Education (ACGME)-accredited orthopaedic surgery programs were included for review. Individual protocols were reviewed to evaluate for the presence or absence of recommended therapies, goals for completion of ranges of motion, functional milestones, exercise start times, and recommended time to return to sport. Thirty protocols from 27 (16.4%) total institutions were identified out of 164 eligible for review. Overall, 9 (30%) protocols recommended an initial period of strict immobilization. Variability existed between the recommended time periods for sling immobilization (mean, 4.8 ± 1.8 weeks). The types of exercises and their start dates were also inconsistent. Goals to full passive range of motion (mean, 9.2 ± 2.8 weeks) and full active range of motion (mean, 12.2 ± 2.8 weeks) were consistent with other published protocols; however, wide ranges existed within the reviewed protocols as a whole. Only 10 protocols (33.3%) included a timeline for return to sport, and only 3 (10%) gave an estimate for return to game competition. Variation also existed when compared with the American Society of Shoulder and Elbow Therapists' (ASSET) consensus protocol. Rehabilitation protocols after arthroscopic Bankart repair were found to be highly variable. They also varied with regard to published consensus protocols. This discrepancy may lead to confusion among therapists and patients. This study highlights the importance of attending surgeons being very clear and specific with

  9. Implementation of the Kyoto protocol

    International Nuclear Information System (INIS)

    2006-07-01

    The Rio Earth summit in 1992 has been the starting point of an international awareness about the global risk of climatic change. At this occasion, the richest countries committed themselves to stabilize their greenhouse gas emissions and to reach by the year 2000 an emissions level equivalent to the one of 1990. The Kyoto protocol in 1997 has permitted to convert this will into juridically constraining quantitative commitments. In 2005, Russia ratified the protocol while in 2001 the USA refused to do so. Because the commitments signed are ambitious, flexibility mechanisms have been implemented: 'emission permits' (emissions trading), 'joint implementation' allowing the investments abroad for greenhouse gases abatement in another developed country, and 'clean development mechanisms' when investments are made in a developing country. The Marrakech conference of December 2001 has permitted to fix up the eligibility criteria of projects belonging to the joint implementation and clean development mechanisms. The effective implementation of these mechanisms still raises technical difficulties to evaluate and measure the effective abatement of greenhouse gas emissions. (J.S.)

  10. Latest approaches of Kyoto protocol

    International Nuclear Information System (INIS)

    Matei, M.; Matei, L.

    2005-01-01

    Recently EURELECTRIC welcome the proposal of new EC Directive concerning the inclusion in the EU Emissions Trading Scheme (ETS) of credits from the project mechanisms - Joint Implementation (JI) and Clean Development Mechanism (CDM). The proposed Directive is an amendment to the EU Emissions Trading Directive adopted in June 2003. EURELECTRIC calls for unlimited use of credits in ETS. The draft Directive provides for the application of these mechanisms to begin as of 2008, on condition that the Kyoto Protocol does actually enter into force, an event which is still dependent on Russia's ratification. Such ratification has been subject to contradictory statements from the Russian Government, and the question of whether their signature to the Protocol is forthcoming is still fraught with uncertainty. Although it is not anticipated that significant quantities of JI or CDM certified credits will be available in the period 2005-2007, those that do become available would provide some additional liquidity in the emissions trading market. There is a direct relation between the coming ETS and electricity pricing: environmental policy is the driver, based on the need to switch to a low-carbon future and manage the necessary investments in a rational manner - and emissions trading is the best solution available. Romania has good opportunities to be involved in the greenhouse gases market, both in ETS and JI mechanisms. Some JI projects between Romanian and The Netherlands are already done or underway. (author)

  11. Summary Report on Unconditionally Secure Protocols

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre; Salvail, Louis; Cachin, Christian

    This document describes the state of the art snd some of the main open problems in the area of unconditionally secure cryptographic protocols. The most essential part of a cryptographic protocol is not its being secure. Imagine a cryptographic protocol which is secure, but where we do not know...... that it is secure. Such a protocol would do little in providing security. When all comes to all, cryptographic security is done for the sake of people, and the essential part of security is for people what it has always been, namely to feel secure. To feel secure employing a given cryptographic protocol we need...... to know that is is secure. I.e. we need a proof that it is secure. Today the proof of security of essentially all practically employed cryptographic protocols relies on computational assumptions. To prove that currently employed ways to communicate securely over the Internet are secure we e.g. need...

  12. In-memory interconnect protocol configuration registers

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Kevin Y.; Roberts, David A.

    2017-09-19

    Systems, apparatuses, and methods for moving the interconnect protocol configuration registers into the main memory space of a node. The region of memory used for storing the interconnect protocol configuration registers may also be made cacheable to reduce the latency of accesses to the interconnect protocol configuration registers. Interconnect protocol configuration registers which are used during a startup routine may be prefetched into the host's cache to make the startup routine more efficient. The interconnect protocol configuration registers for various interconnect protocols may include one or more of device capability tables, memory-side statistics (e.g., to support two-level memory data mapping decisions), advanced memory and interconnect features such as repair resources and routing tables, prefetching hints, error correcting code (ECC) bits, lists of device capabilities, set and store base address, capability, device ID, status, configuration, capabilities, and other settings.

  13. The Simplest Protocol for Oblivious Transfer

    DEFF Research Database (Denmark)

    Chou, Tung; Orlandi, Claudio

    2015-01-01

    Oblivious Transfer (OT) is the fundamental building block of cryptographic protocols. In this paper we describe the simplest and most efficient protocol for 1-out-of-n OT to date, which is obtained by tweaking the Diffie-Hellman key-exchange protocol. The protocol achieves UC-security against...... active and adaptive corruptions in the random oracle model. Due to its simplicity, the protocol is extremely efficient and it allows to perform m 1-out-of-n OTs using only: - Computation: (n+1)m+2 exponentiations (mn for the receiver, mn+2 for the sender) and - Communication: 32(m+1) bytes (for the group...... optimizations) is at least one order of magnitude faster than previous work. Category / Keywords: cryptographic protocols / Oblivious Transfer, UC Security, Elliptic Curves, Efficient Implementation...

  14. In-memory interconnect protocol configuration registers

    Science.gov (United States)

    Cheng, Kevin Y.; Roberts, David A.

    2017-09-19

    Systems, apparatuses, and methods for moving the interconnect protocol configuration registers into the main memory space of a node. The region of memory used for storing the interconnect protocol configuration registers may also be made cacheable to reduce the latency of accesses to the interconnect protocol configuration registers. Interconnect protocol configuration registers which are used during a startup routine may be prefetched into the host's cache to make the startup routine more efficient. The interconnect protocol configuration registers for various interconnect protocols may include one or more of device capability tables, memory-side statistics (e.g., to support two-level memory data mapping decisions), advanced memory and interconnect features such as repair resources and routing tables, prefetching hints, error correcting code (ECC) bits, lists of device capabilities, set and store base address, capability, device ID, status, configuration, capabilities, and other settings.

  15. Blockchain Consensus Protocols in the Wild

    OpenAIRE

    Cachin, Christian; Vukolić, Marko

    2017-01-01

    A blockchain is a distributed ledger for recording transactions, maintained by many nodes without central authority through a distributed cryptographic protocol. All nodes validate the information to be appended to the blockchain, and a consensus protocol ensures that the nodes agree on a unique order in which entries are appended. Consensus protocols for tolerating Byzantine faults have received renewed attention because they also address blockchain systems. This work discusses the process o...

  16. VANET Routing Protocols: Pros and Cons

    OpenAIRE

    Paul, Bijan; Ibrahim, Md.; Bikas, Md. Abu Naser

    2012-01-01

    VANET (Vehicular Ad-hoc Network) is a new technology which has taken enormous attention in the recent years. Due to rapid topology changing and frequent disconnection makes it difficult to design an efficient routing protocol for routing data among vehicles, called V2V or vehicle to vehicle communication and vehicle to road side infrastructure, called V2I. The existing routing protocols for VANET are not efficient to meet every traffic scenarios. Thus design of an efficient routing protocol h...

  17. Security analysis of session initiation protocol

    OpenAIRE

    Dobson, Lucas E.

    2010-01-01

    Approved for public release; distribution is unlimited The goal of this thesis is to investigate the security of the Session Initiation Protocol (SIP). This was accomplished by researching previously discovered protocol and implementation vulnerabilities, evaluating the current state of security tools and using those tools to discover new vulnerabilities in SIP software. The CVSS v2 system was used to score protocol and implementation vulnerabilities to give them a meaning that was us...

  18. Bitcoin-NG: A Scalable Blockchain Protocol

    OpenAIRE

    Eyal, Ittay; Gencer, Adem Efe; Sirer, Emin Gun; van Renesse, Robbert

    2015-01-01

    Cryptocurrencies, based on and led by Bitcoin, have shown promise as infrastructure for pseudonymous online payments, cheap remittance, trustless digital asset exchange, and smart contracts. However, Bitcoin-derived blockchain protocols have inherent scalability limits that trade-off between throughput and latency and withhold the realization of this potential. This paper presents Bitcoin-NG, a new blockchain protocol designed to scale. Based on Bitcoin's blockchain protocol, Bitcoin-NG is By...

  19. Telomerase Repeated Amplification Protocol (TRAP).

    Science.gov (United States)

    Mender, Ilgen; Shay, Jerry W

    2015-11-20

    Telomeres are found at the end of eukaryotic linear chromosomes, and proteins that bind to telomeres protect DNA from being recognized as double-strand breaks thus preventing end-to-end fusions (Griffith et al. , 1999). However, due to the end replication problem and other factors such as oxidative damage, the limited life span of cultured cells (Hayflick limit) results in progressive shortening of these protective structures (Hayflick and Moorhead, 1961; Olovnikov, 1973). The ribonucleoprotein enzyme complex telomerase-consisting of a protein catalytic component hTERT and a functional RNA component hTR or hTERC - counteracts telomere shortening by adding telomeric repeats to the end of chromosomes in ~90% of primary human tumors and in some transiently proliferating stem-like cells (Shay and Wright, 1996; Shay and Wright, 2001). This results in continuous proliferation of cells which is a hallmark of cancer. Therefore, telomere biology has a central role in aging, cancer progression/metastasis as well as targeted cancer therapies. There are commonly used methods in telomere biology such as Telomere Restriction Fragment (TRF) (Mender and Shay, 2015b), Telomere Repeat Amplification Protocol (TRAP) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this detailed protocol we describe Telomere Repeat Amplification Protocol (TRAP). The TRAP assay is a popular method to determine telomerase activity in mammalian cells and tissue samples (Kim et al. , 1994). The TRAP assay includes three steps: extension, amplification, and detection of telomerase products. In the extension step, telomeric repeats are added to the telomerase substrate (which is actually a non telomeric oligonucleotide, TS) by telomerase. In the amplification step, the extension products are amplified by the polymerase chain reaction (PCR) using specific primers (TS upstream primer and ACX downstream primer) and in the detection step, the presence or absence of telomerase is

  20. Search and nonsearch protocols for radiographic consultation

    International Nuclear Information System (INIS)

    Swensson, R.G.; Theodore, G.H.

    1989-01-01

    Six radiologists, acting as film reviewers, used two different consultation protocols to differentiate among 292 ambiguous findings on chest films: 120 simulated nodules and 172 normal findings (previous readers' false-positive reports of nodules). The non-search protocol identified each finding (by location), and reviewers rated its likelihood as a nodule. The search protocol, which asked reviewers to report and rate all locations regarded as possible nodules on each film, assigned a default negative rating to any unreported finding (nodule or normal). Receiver operator characteristic analyses demonstrated a significantly higher accuracy for each reviewer's search- protocol discriminations between these nodules and confusing normal findings

  1. Adaptive Protocols for Mobile Wireless Networks

    National Research Council Canada - National Science Library

    Pursley, Michael B

    2005-01-01

    .... Research results are presented on adaptive, energy-efficient, distributed protocols for mobile wireless networks that must operate effectively over unreliable communication links in highly dynamic...

  2. Mac protocols for cyber-physical systems

    CERN Document Server

    Xia, Feng

    2015-01-01

    This book provides a literature review of various wireless MAC protocols and techniques for achieving real-time and reliable communications in the context of cyber-physical systems (CPS). The evaluation analysis of IEEE 802.15.4 for CPS therein will give insights into configuration and optimization of critical design parameters of MAC protocols. In addition, this book also presents the design and evaluation of an adaptive MAC protocol for medical CPS, which exemplifies how to facilitate real-time and reliable communications in CPS by exploiting IEEE 802.15.4 based MAC protocols. This book wil

  3. Efficient secure two-party protocols

    CERN Document Server

    Hazay, Carmit

    2010-01-01

    The authors present a comprehensive study of efficient protocols and techniques for secure two-party computation -- both general constructions that can be used to securely compute any functionality, and protocols for specific problems of interest. The book focuses on techniques for constructing efficient protocols and proving them secure. In addition, the authors study different definitional paradigms and compare the efficiency of protocols achieved under these different definitions.The book opens with a general introduction to secure computation and then presents definitions of security for a

  4. Multimode Communication Protocols Enabling Reconfigurable Radios

    Directory of Open Access Journals (Sweden)

    Berlemann Lars

    2005-01-01

    Full Text Available This paper focuses on the realization and application of a generic protocol stack for reconfigurable wireless communication systems. This focus extends the field of software-defined radios which usually concentrates on the physical layer. The generic protocol stack comprises common protocol functionality and behavior which are extended through specific parts of the targeted radio access technology. This paper considers parameterizable modules of basic protocol functions residing in the data link layer of the ISO/OSI model. System-specific functionality of the protocol software is realized through adequate parameterization and composition of the generic modules. The generic protocol stack allows an efficient realization of reconfigurable protocol software and enables a completely reconfigurable wireless communication system. It is a first step from side-by-side realized, preinstalled modes in a terminal towards a dynamic reconfigurable anymode terminal. The presented modules of the generic protocol stack can also be regarded as a toolbox for the accelerated and cost-efficient development of future communication protocols.

  5. Tool Supported Analysis of Web Services Protocols

    DEFF Research Database (Denmark)

    Marques, Abinoam P.; Ravn, Anders Peter; Srba, Jiri

    2011-01-01

    We describe an abstract protocol model suitable for modelling of web services and other protocols communicating via unreliable, asynchronous communication channels. The model is supported by a tool chain where the first step translates tables with state/transition protocol descriptions, often used...... e.g. in the design of web services protocols, into an intermediate XML format. We further translate this format into a network of communicating state machines directly suitable for verification in the model checking tool UPPAAL. We introduce two types of communication media abstractions in order...

  6. Attack strategies on quantum cryptographic protocols

    International Nuclear Information System (INIS)

    Schauer, S.; Suda, M.

    2006-01-01

    Full text: Quantum key distribution (QKD) and quantum authentication (QA) have been a topic of extensive research in the last 20 years. In course of that many attacks on QKD and QA protocols have been studied. Among these, Zhang, Lee and Guo presented an attack on a QKD protocol using entanglement swapping. Based on that strategy we take a look at other protocols to inspect how much information an adversary may get if he shares entanglement with either one or both parties. We will present some protocols where an adversary can even get full information about the key using entanglement. (author)

  7. Molecular markers of resistance to amodiaquine plus sulfadoxine-pyrimethamine in an area with seasonal malaria chemoprevention in south central Niger.

    Science.gov (United States)

    Grais, Rebecca F; Laminou, Ibrahim M; Woi-Messe, Lynda; Makarimi, Rockyath; Bouriema, Seidou H; Langendorf, Celine; Amambua-Ngwa, Alfred; D'Alessandro, Umberto; Guérin, Philippe J; Fandeur, Thierry; Sibley, Carol H

    2018-02-27

    In Niger, malaria transmission is markedly seasonal with most of the disease burden occurring in children during the rainy season. Seasonal malaria chemoprevention (SMC) with amodiaquine plus sulfadoxine-pyrimethamine (AQ + SP) is recommended in the country to be administered monthly just before and during the rainy season. Moreover, clinical decisions on use of SP for intermittent preventive treatment in pregnancy (IPTp) now depend upon the validated molecular markers for SP resistance in Plasmodium falciparum observed in the local parasite population. However, little is known about molecular markers of resistance for either SP or AQ in the south of Niger. To address this question, clinical samples which met clinical and biological criteria, were collected in Gabi, Madarounfa district, Maradi region, Niger in 2011-2012 (before SMC implementation). Molecular markers of resistance to pyrimethamine (pfdhfr), sulfadoxine (pfdhps) and amodiaquine (pfmdr1) were assessed by DNA sequencing. Prior to SMC implementation, the samples showed a high proportion of clinical samples that carried the pfdhfr 51I/59R/108N haplotype associated with resistance to pyrimethamine and pfdhps 436A/F/H and 437G mutations associated with reduced susceptibility to sulfadoxine. In contrast mutations in codons 581G, and 613S in the pfdhps gene, and in pfmdr1, 86Y, 184Y, 1042D and 1246Y associated with resistance to amodiaquine, were less frequently observed. Importantly, pfdhfr I164L and pfdhps K540E mutations shown to be the most clinically relevant markers for high level clinical resistance to SP were not detected in Gabi. Although parasites with genotypes associated with the highest levels of resistance to AQ + SP are not yet common in this setting, their importance for deployment of SMC and IPTp dictates that monitoring of these markers of resistance should accompany these interventions. This study also highlights the parasite heterogeneity within a small spatial area and the need to

  8. Secure Multi-Player Protocols

    DEFF Research Database (Denmark)

    Fehr, Serge

    While classically cryptography is concerned with the problem of private communication among two entities, say players, in modern cryptography multi-player protocols play an important role. And among these, it is probably fair to say that secret sharing, and its stronger version verifiable secret...... sharing (VSS), as well as multi-party computation (MPC) belong to the most appealing and/or useful ones. The former two are basic tools to achieve better robustness of cryptographic schemes against malfunction or misuse by “decentralizing” the security from one single to a whole group of individuals...... (captured by the term threshold cryptography). The latter allows—at least in principle—to execute any collaboration among a group of players in a secure way that guarantees the correctness of the outcome but simultaneously respects the privacy of the participants. In this work, we study three aspects...

  9. Software for simulating IMRT protocol

    Energy Technology Data Exchange (ETDEWEB)

    Fonseca, Thelma C.F.; Campos, Tarcisio P.R. de, E-mail: tcff@ufmg.b, E-mail: campos@nuclear.ufmg.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear

    2009-07-01

    The Intensity Modulated Radiation Therapy - IMRT is an advanced technique to cancer treatment widely used on oncology around the world. The present paper describes the SOFT-RT software which is a tool for simulating IMRT protocol. Also, it will be present a cerebral tumor case of studied in which three irradiation windows with distinct orientation were applied. The SOFT-RT collect and export data to MCNP code. This code simulates the photon transport on the voxel model. Later, a out-module from SOFT-RT import the results and express the dose-response superimposing dose and voxel model in a tree-dimensional graphic representation. The present paper address the IMRT software and its function as well a cerebral tumor case of studied is showed. The graphic interface of the SOFT-RT illustrates the example case. (author)

  10. Software for simulating IMRT protocol

    International Nuclear Information System (INIS)

    Fonseca, Thelma C.F.; Campos, Tarcisio P.R. de

    2009-01-01

    The Intensity Modulated Radiation Therapy - IMRT is an advanced technique to cancer treatment widely used on oncology around the world. The present paper describes the SOFT-RT software which is a tool for simulating IMRT protocol. Also, it will be present a cerebral tumor case of studied in which three irradiation windows with distinct orientation were applied. The SOFT-RT collect and export data to MCNP code. This code simulates the photon transport on the voxel model. Later, a out-module from SOFT-RT import the results and express the dose-response superimposing dose and voxel model in a tree-dimensional graphic representation. The present paper address the IMRT software and its function as well a cerebral tumor case of studied is showed. The graphic interface of the SOFT-RT illustrates the example case. (author)

  11. Fetal MRI: techniques and protocols

    International Nuclear Information System (INIS)

    Prayer, Daniela; Brugger, Peter Christian; Prayer, Lucas

    2004-01-01

    The development of ultrafast sequences has led to a significant improvement in fetal MRI. Imaging protocols have to be adjusted to the rapidly developing fetal central nervous system (CNS) and to the clinical question. Sequence parameters must be changed to cope with the respective developmental stage, to produce images free from motion artefacts and to provide optimum visualization of the region and focus of interest. In contrast to postnatal studies, every suspect fetal CNS abnormality requires examination of the whole fetus and the extrafetal intrauterine structures including the uterus. This approach covers both aspects of fetal CNS disorders: isolated and complex malformations and cerebral lesions arising from the impaired integrity of the feto-placental unit. (orig.)

  12. Analysing Protocol Stacks for Services

    DEFF Research Database (Denmark)

    Gao, Han; Nielson, Flemming; Nielson, Hanne Riis

    2011-01-01

    We show an approach, CaPiTo, to model service-oriented applications using process algebras such that, on the one hand, we can achieve a certain level of abstraction without being overwhelmed by the underlying implementation details and, on the other hand, we respect the concrete industrial...... standards used for implementing the service-oriented applications. By doing so, we will be able to not only reason about applications at different levels of abstractions, but also to build a bridge between the views of researchers on formal methods and developers in industry. We apply our approach...... to the financial case study taken from Chapter 0-3. Finally, we develop a static analysis to analyse the security properties as they emerge at the level of concrete industrial protocols....

  13. Protocol Monitoring Passive Solar Energy

    International Nuclear Information System (INIS)

    Van den Ham, E.R.; Bosselaar, L.

    1998-01-01

    A method has been developed by means of which the contribution of passive solar energy to the Dutch energy balance can be quantified univocally. The contribution was 57 PJ in 1990 and also 57 PJ in 1995. The efficiency of passive solar energy systems increased from -31.5% to -28.1% in the period 1990-1995, mainly as a result of the use of extra insulating glazing. As a result of the reduction of energy consumption for heating in houses it is expected that the extra contribution of 2 PJ will not be realized in the year 2010. It is suggested that the method to determine the absolute contribution of passive solar energy to the energy demand of dwellings is to be included in the protocol monitoring renewable energy. For the method to be included in the energy statistics of Statistics Netherlands (CBS) it can be considered only to take into account the difference compared to 1990. 11 refs

  14. Fetal MRI: techniques and protocols

    Energy Technology Data Exchange (ETDEWEB)

    Prayer, Daniela [Department of Neuroradiology, University Clinics of Radiodiagnostics, Medical University Vienna, Waehringerguertel 18-10, 1090, Vienna (Austria); Brugger, Peter Christian [Department of Anatomy, Integrative Morphology Group, Medical University Vienna (Austria); Prayer, Lucas [Diagnosezentrum Urania, Vienna (Austria)

    2004-09-01

    The development of ultrafast sequences has led to a significant improvement in fetal MRI. Imaging protocols have to be adjusted to the rapidly developing fetal central nervous system (CNS) and to the clinical question. Sequence parameters must be changed to cope with the respective developmental stage, to produce images free from motion artefacts and to provide optimum visualization of the region and focus of interest. In contrast to postnatal studies, every suspect fetal CNS abnormality requires examination of the whole fetus and the extrafetal intrauterine structures including the uterus. This approach covers both aspects of fetal CNS disorders: isolated and complex malformations and cerebral lesions arising from the impaired integrity of the feto-placental unit. (orig.)

  15. Wind power agreement protocol; Protocole d'accord eolien

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-10-01

    The aim of this protocol of agreement is to propose to wind turbine fitters some models of contracts allowing the setting up of wind turbines on agricultural lots. These documents, which make an indissociable ensemble, apply to both phases of development of a wind power project: the feasibility study phase, for a duration comprised between 2 and 5 years (studies, administrative procedures, precise definition of the project), and the construction, exploitation and dismantling phase. These documents will serve as common guidelines for both the farmers and the wind turbine designers. Both parties agree to meet together in the future to propose some modifications of these texts if necessary. The four models of contracts are attached to the document: contract for the feasibility study phase, first contract between the landlord and the farmer for the cancellation of the rural lease, second contract between the landlord and the wind power exploitation company for the common right lease, and the third contract between the farmer and the wind power company for the indemnification convention. (J.S.)

  16. Analysis of a security protocol in ?CRL

    NARCIS (Netherlands)

    J. Pang

    2002-01-01

    textabstractNeedham-Schroeder public-key protocol; With the growth and commercialization of the Internet, the security of communication between computers becomes a crucial point. A variety of security protocols based on cryptographic primitives are used to establish secure communication over

  17. An Argument Approach to Observation Protocol Validity

    Science.gov (United States)

    Bell, Courtney A.; Gitomer, Drew H.; McCaffrey, Daniel F.; Hamre, Bridget K.; Pianta, Robert C.; Qi, Yi

    2012-01-01

    This article develops a validity argument approach for use on observation protocols currently used to assess teacher quality for high-stakes personnel and professional development decisions. After defining the teaching quality domain, we articulate an interpretive argument for observation protocols. To illustrate the types of evidence that might…

  18. Model checking the HAVi leader election protocol

    NARCIS (Netherlands)

    J.M.T. Romijn (Judi)

    1999-01-01

    textabstractThe HAVi specification proposes an architecture for audio/video interoperability in home networks. Part of the HAVi specification is a distributed leader election protocol. We have modelled this leader election protocol in Promela and Lotos and have checked several properties with the

  19. Climate Change And The Kyoto Protocol

    International Nuclear Information System (INIS)

    Comsan, M.N.H.

    2007-01-01

    The problem of global warming is addressed. Changes in earth surface temperature, emission of CO 2 and other four major green house gases are presented. Effect of global warming on weather, ocean, and ecosystem is discussed. A brief history of the Kyoto protocol starting from the 151 Earth Summit in 1972 is outlined. An overview of the protocol and a brief summary are given

  20. Kyoto Protocol: trade versus the environment

    International Nuclear Information System (INIS)

    Loose, H.

    2001-01-01

    Could the signatories to the Kyoto Protocol find themselves up against the WTO? This paper examines how the climate change agreement could conflict with trade rules, and shows that there are potentially serious conflicts in the interface between the WTO and the Kyoto Protocol. It argues for dialogue and debate before it is too late. (author)

  1. Network Coding Protocols for Smart Grid Communications

    DEFF Research Database (Denmark)

    Prior, Rui; Roetter, Daniel Enrique Lucani; Phulpin, Yannick

    2014-01-01

    We propose a robust network coding protocol for enhancing the reliability and speed of data gathering in smart grids. At the heart of our protocol lies the idea of tunable sparse network coding, which adopts the transmission of sparsely coded packets at the beginning of the transmission process b...

  2. Quantum Communication Attacks on Classical Cryptographic Protocols

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre

    , one can show that the protocol remains secure even under such an attack. However, there are also cases where the honest players are quantum as well, even if the protocol uses classical communication. For instance, this is the case when classical multiparty computation is used as a “subroutine......In the literature on cryptographic protocols, it has been studied several times what happens if a classical protocol is attacked by a quantum adversary. Usually, this is taken to mean that the adversary runs a quantum algorithm, but communicates classically with the honest players. In several cases......” in quantum multiparty computation. Furthermore, in the future, players in a protocol may employ quantum computing simply to improve efficiency of their local computation, even if the communication is supposed to be classical. In such cases, it no longer seems clear that a quantum adversary must be limited...

  3. Cryptanalysis of the arbitrated quantum signature protocols

    International Nuclear Information System (INIS)

    Gao Fei; Qin Sujuan; Guo Fenzhuo; Wen Qiaoyan

    2011-01-01

    As a new model for signing quantum messages, arbitrated quantum signature (AQS) has recently received a lot of attention. In this paper we study the cryptanalysis of previous AQS protocols from the aspects of forgery and disavowal. We show that in these protocols the receiver, Bob, can realize existential forgery of the sender's signature under known message attack. Bob can even achieve universal forgery when the protocols are used to sign a classical message. Furthermore, the sender, Alice, can successfully disavow any of her signatures by simple attack. The attack strategies are described in detail and some discussions about the potential improvements of the protocols are given. Finally we also present several interesting topics on AQS protocols that can be studied in future.

  4. Nucleic acid protocols: Extraction and optimization

    Directory of Open Access Journals (Sweden)

    Saeed El-Ashram

    2016-12-01

    Full Text Available Yield and quality are fundamental features for any researchers during nucleic acid extraction. Here, we describe a simplified, semi-unified, effective, and toxic material free protocol for extracting DNA and RNA from different prokaryotic and eukaryotic sources exploiting the physical and chemical properties of nucleic acids. Furthermore, this protocol showed that DNA and RNA are under triple protection (i.e. EDTA, SDS and NaCl during lysis step, and this environment is improper for RNase to have DNA liberated of RNA and even for DNase to degrade the DNA. Therefore, the complete removal of RNA under RNase influence is achieved when RNase is added after DNA extraction, which gives optimal quality with any protocols. Similarly, DNA contamination in an isolated RNA is degraded by DNase to obtain high-quality RNA. Our protocol is the protocol of choice in terms of simplicity, recovery time, environmental safety, amount, purity, PCR and RT-PCR applicability.

  5. Quantum Communication Attacks on Classical Cryptographic Protocols

    DEFF Research Database (Denmark)

    Damgård, Ivan Bjerre

    , one can show that the protocol remains secure even under such an attack. However, there are also cases where the honest players are quantum as well, even if the protocol uses classical communication. For instance, this is the case when classical multiparty computation is used as a “subroutine......” in quantum multiparty computation. Furthermore, in the future, players in a protocol may employ quantum computing simply to improve efficiency of their local computation, even if the communication is supposed to be classical. In such cases, it no longer seems clear that a quantum adversary must be limited......In the literature on cryptographic protocols, it has been studied several times what happens if a classical protocol is attacked by a quantum adversary. Usually, this is taken to mean that the adversary runs a quantum algorithm, but communicates classically with the honest players. In several cases...

  6. A Comparison Between Inter-Asterisk eXchange Protocol and Jingle Protocol: Session Time

    Directory of Open Access Journals (Sweden)

    H. S. Haj Aliwi

    2016-08-01

    Full Text Available Over the last few years, many multimedia conferencing and Voice over Internet Protocol (VoIP applications have been developed due to the use of signaling protocols in providing video, audio and text chatting services between at least two participants. This paper compares between two widely common signaling protocols: InterAsterisk eXchange Protocol (IAX and the extension of the eXtensible Messaging and Presence Protocol (Jingle in terms of delay time during call setup, call teardown, and media sessions.

  7. A family of multi-party authentication protocols

    NARCIS (Netherlands)

    Cremers, C.J.F.; Mauw, S.

    2006-01-01

    We introduce a family of multi-party authentication protocols and discuss six novel protocols, which are members of this family. The first three generalize the well-known Needham-Schroeder-Lowe public-key protocol, the Needham-Schroeder private-key protocol, and the Bilateral Key Exchange protocol.

  8. Universally composable protocols with relaxed set-up assumptions

    DEFF Research Database (Denmark)

    Barak, Boaz; Canetti, Ran; Nielsen, Jesper Buus

    2004-01-01

    A desirable goal for cryptographic protocols is to guarantee security when the protocol is composed with other protocol instances. Universally composable (UC) protocols provide this guarantee in a strong sense: A protocol remains secure even when composed concurrently with an unbounded number of ...

  9. Live chat alternative security protocol

    Science.gov (United States)

    Rahman, J. P. R.; Nugraha, E.; Febriany, A.

    2018-05-01

    Indonesia is one of the largest e-commerce markets in Southeast Asia, as many as 5 million people do transactions in e-commerce, therefore more and more people use live chat service to communicate with customer service. In live chat, the customer service often asks customers’ data such as, full name, address, e-mail, transaction id, which aims to verify the purchase of the product. One of the risks that will happen is sniffing which will lead to the theft of confidential information that will cause huge losses to the customer. The anticipation that will be done is build an alternative security protocol for user interaction in live chat by using a cryptographic algorithm that is useful for protecting confidential messages. Live chat requires confidentiality and data integration with encryption and hash functions. The used algorithm are Rijndael 256 bits, RSA, and SHA256. To increase the complexity, the Rijndael algorithm will be modified in the S-box and ShiftRow sections based on the shannon principle rule, the results show that all pass the Randomness test, but the modification in Shiftrow indicates a better avalanche effect. Therefore the message will be difficult to be stolen or changed.

  10. Selenium and Breast Cancer Chemoprevention

    National Research Council Canada - National Science Library

    Thompson, Henry J

    2005-01-01

    .... The intermediate biomarkers being studied are as follows: indicators of oxidative damage to cellular macromolecules such as DNA and lipids, indicators of IGF metabolic status, and cellular indicators of breast cancer risk...

  11. A Simple XML Producer-Consumer Protocol

    Science.gov (United States)

    Smith, Warren; Gunter, Dan; Quesnel, Darcy; Biegel, Bryan (Technical Monitor)

    2001-01-01

    There are many different projects from government, academia, and industry that provide services for delivering events in distributed environments. The problem with these event services is that they are not general enough to support all uses and they speak different protocols so that they cannot interoperate. We require such interoperability when we, for example, wish to analyze the performance of an application in a distributed environment. Such an analysis might require performance information from the application, computer systems, networks, and scientific instruments. In this work we propose and evaluate a standard XML-based protocol for the transmission of events in distributed systems. One recent trend in government and academic research is the development and deployment of computational grids. Computational grids are large-scale distributed systems that typically consist of high-performance compute, storage, and networking resources. Examples of such computational grids are the DOE Science Grid, the NASA Information Power Grid (IPG), and the NSF Partnerships for Advanced Computing Infrastructure (PACIs). The major effort to deploy these grids is in the area of developing the software services to allow users to execute applications on these large and diverse sets of resources. These services include security, execution of remote applications, managing remote data, access to information about resources and services, and so on. There are several toolkits for providing these services such as Globus, Legion, and Condor. As part of these efforts to develop computational grids, the Global Grid Forum is working to standardize the protocols and APIs used by various grid services. This standardization will allow interoperability between the client and server software of the toolkits that are providing the grid services. The goal of the Performance Working Group of the Grid Forum is to standardize protocols and representations related to the storage and distribution of

  12. The Development of Korea Additional Protocol System

    International Nuclear Information System (INIS)

    Shim, Hye Won; Yeo, Jin Kyun

    2008-01-01

    The Agreement between the Republic of Korea (ROK) and the IAEA for the Application of Safeguards in Connection with the Treaty on the Non-Proliferation of Nuclear Weapons (the Safeguards Agreement) entered into force on 14 November 1975. The Additional Protocol to the Safeguards Agreement (the Additional Protocol) was signed on 21 June 1999 and entered into force on 19 February 2004. ROK has been submitting annual updated reports of initial declaration on every May 15th since August 2004. Additional protocol reports were submitted through Protocol Reporter provided by IAEA. Annual declarations were simply uploaded and stored in the Accounting Information Treatment System of KINAC, which did not provide data analysis and management function. There have been demands for improvement to handle ever-increasing information. KAPS (Korea Additional Protocol System) has been developed to assist and administrate the additional protocol related works effectively. The new system enables integrated management including composition of additional protocol report and version control, periodical update of related information, results of IAEA complementary access to each facility

  13. New logistics protocols for distributed interactive simulation

    Science.gov (United States)

    Taylor, Darrin; Morrison, John; Katz, Warren; Felton, Erik; Herman, Deborah A.

    1995-06-01

    In today's environment, the transportation and maintenance of military forces is nearly as important as combat operations. Rapid deployment to regions of low-intensity conflict will become a very common training scenario for the U.S. military. Thus it is desirable to apply distributed simulation technology to train logistics personnel in their combat support roles. Currently, distributed interactive simulation (DIS) only contains rudimentary logistics protocols. This paper introduces new protocols designed to handle the logistics problem. The Newtonian protocol takes a physics-based approach to modeling interactions on the simulation network. This protocol consists of a family of protocol data units (PDUs) which are used to communicate forces in different circumstances. The protocol implements a small set of physical relations. This represents a flexible and general mechanism to describe battlefield interactions between network entities. The migratory object protocol (MOP) family addresses the transfer of control. General mechanisms provide the means to simulate resupply, repair, and maintenance of entities at any level of abstraction (individual soldier to division). It can also increase the fidelity of mine laying, enable handover of weapons for terminal guidance, allow for the distribution of aggregate-level simulation entities, provide capabilities for the simulation of personnel, etc.

  14. The Kyoto Protocol. An economic appraisal

    International Nuclear Information System (INIS)

    Grubb, M.

    2000-05-01

    This paper examines the overall economics of the Kyoto Protocol on climate change, in three main parts. The first part explores the structure of the Protocol and how this matches against classical economic criteria of an 'optimal' climate change agreement. This discussion also considers the nature of and reasons for shortcomings, and the prospects for its evolution. Given the various flexibilities in the agreement, the Kyoto Protocol is far more economically efficient in its structure than any previous global environmental agreement. The central conclusion is that, from an economic perspective, the Protocol's structure for industrialised country commitments is as good as could reasonably be expected. The second part of the paper explores more closely the economics of the commitments themselves and how they combine with the various flexibilities, briefly reviewing the available literature and using a simple spreadsheet model of how the commitments might combine with trading mechanisms under a range of assumptions. Flexibility is intrinsic and necessary, but it is argued that the allocations to Russia and Ukraine in particular mean that unlimited flexibility could render the Protocol's commitments weaker in their impacts than is economically desirable to address climate change. It is argued that, should this prove to be the case, access to the large surplus in the transition economies could be used as a control valve to limit the costs of the Protocol to within acceptable limits. Finally, the paper considers the issues of developing country involvement in the Kyoto Protocol, and the Protocol's longer-term impact and evolution, including its impact on technological evolution and dissemination and the evolution of future commitments. It is argued that taking account of such issues critically affects views of the Protocol

  15. An Authentication Protocol for Future Sensor Networks.

    Science.gov (United States)

    Bilal, Muhammad; Kang, Shin-Gak

    2017-04-28

    Authentication is one of the essential security services in Wireless Sensor Networks (WSNs) for ensuring secure data sessions. Sensor node authentication ensures the confidentiality and validity of data collected by the sensor node, whereas user authentication guarantees that only legitimate users can access the sensor data. In a mobile WSN, sensor and user nodes move across the network and exchange data with multiple nodes, thus experiencing the authentication process multiple times. The integration of WSNs with Internet of Things (IoT) brings forth a new kind of WSN architecture along with stricter security requirements; for instance, a sensor node or a user node may need to establish multiple concurrent secure data sessions. With concurrent data sessions, the frequency of the re-authentication process increases in proportion to the number of concurrent connections. Moreover, to establish multiple data sessions, it is essential that a protocol participant have the capability of running multiple instances of the protocol run, which makes the security issue even more challenging. The currently available authentication protocols were designed for the autonomous WSN and do not account for the above requirements. Hence, ensuring a lightweight and efficient authentication protocol has become more crucial. In this paper, we present a novel, lightweight and efficient key exchange and authentication protocol suite called the Secure Mobile Sensor Network (SMSN) Authentication Protocol. In the SMSN a mobile node goes through an initial authentication procedure and receives a re-authentication ticket from the base station. Later a mobile node can use this re-authentication ticket when establishing multiple data exchange sessions and/or when moving across the network. This scheme reduces the communication and computational complexity of the authentication process. We proved the strength of our protocol with rigorous security analysis (including formal analysis using the BAN

  16. Energy Efficient Network Protocols for Wireless and Mobile Networks

    National Research Council Canada - National Science Library

    Sivalingam, Krishna

    2001-01-01

    ... (also called power aware) network protocols for wireless and mobile networks. Battery power limitations are a very serious concern, and it is essential to study energy efficient protocol design at different layers of the network protocol stack...

  17. Event-by-event simulation of quantum cryptography protocols

    NARCIS (Netherlands)

    Zhao, S.; Raedt, H. De

    We present a new approach to simulate quantum cryptography protocols using event-based processes. The method is validated by simulating the BB84 protocol and the Ekert protocol, both without and with the presence of an eavesdropper.

  18. Protocolized hyperventilation enhances electroconvulsive therapy.

    Science.gov (United States)

    de Arriba-Arnau, Aida; Dalmau, Antonia; Soria, Virginia; Salvat-Pujol, Neus; Ribes, Carmina; Sánchez-Allueva, Ana; Menchón, José Manuel; Urretavizcaya, Mikel

    2017-08-01

    Hyperventilation is recommended in electroconvulsive therapy (ECT) to enhance seizures and to increase patients' safety. However, more evidence is needed regarding its effects and the optimum method of application. This prospective study involving 21 subjects compared two procedures, protocolized hyperventilation (PHV) and hyperventilation as usual (HVau), applied to the same patient in two consecutive sessions. Transcutaneous partial pressure of carbon dioxide (TcPCO 2 ) was measured throughout all sessions. Ventilation parameters, hemodynamic measures, seizure characteristics, and side effects were also explored. PHV resulted in lower TcPCO 2 after hyperventilation (p=.008) and over the whole session (p=.035). The lowest TcPCO 2 was achieved after voluntary hyperventilation. Changes in TcPCO 2 from baseline showed differences between HVau and PHV at each session time-point (all p<.05). Between- and within-subjects factors were statistically significant in a general linear model. Seizure duration was greater in PHV sessions (p=.028), without differences in other seizure quality parameters or adverse effects. Correlations were found between hypocapnia induction and seizure quality indexes. Secondary outcomes could be underpowered. PHV produces hypocapnia before the stimulus, modifies patients' TcPCO 2 values throughout the ECT session and lengthens seizure duration. Voluntary hyperventilation is the most important part of the PHV procedure with respect to achieving hypocapnia. A specific ventilation approach, CO 2 quantification and monitoring may be advisable in ECT. PHV is easy to apply in daily clinical practice and does not imply added costs. Ventilation management has promising effects in terms of optimizing ECT technique. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The protocol amending the 1963 Vienna Convention

    International Nuclear Information System (INIS)

    Lamm, V.

    2006-01-01

    Technically the Vienna Convention was revised by the adoption of the protocol to amend the instrument. and according to Article 19 of the protocol 'A State which is Party to this Protocol but not to the 1963 Vienna Convention shall be bound by the provisions of that Convention as amended by this Protocol in relation to other States Parties hereto, and failing an expression of a different intention by that State at the time of deposit of an instrument referred to in Article 20 shall be bound by the provisions of the 1963 Vienna Convention in relation to States which are only Parties thereto'. This solution has created a special situation, because after the entry into force of the protocol there will be living together or operating in practice 'two' Vienna Conventions, notably the convention's original text of 1963 and its new version as amended by the protocol. After the protocol has come into force, a state may only accede to the amended version, but in the inter se relations of the States Party to the 'old' Vienna Convention the provisions of that convention will remain in force until such time as they have acceded to the new protocol. This rather complicated situation is nevertheless understandable and is fully in accord with Article 40 of the 1969 Vienna Convention on the Law of Treaties, which provides for the amendment of multilateral treaties. In 1989 the negotiations on the revision of the Vienna Convention had begun with the aim of strengthening the existing nuclear liability regime and of improving the situation of potential victims of nuclear accidents. The Protocol to Amend the Vienna Convention serves those purposes; it also reflects a good compromise, since it is the outcome of a negotiation process in which experts from both nuclear and non-nuclear states, from Contacting Parties and non-Contracting Parties were very active. That affords some assurance that the compromise solution reached is acceptable to all States participating in the adoption of

  20. Advanced Internet Protocols, Services, and Applications

    CERN Document Server

    Oki, Eiji; Tatipamula, Mallikarjun; Vogt, Christian

    2012-01-01

    Today, the internet and computer networking are essential parts of business, learning, and personal communications and entertainment. Virtually all messages or transactions sent over the internet are carried using internet infrastructure- based on advanced internet protocols. Advanced internet protocols ensure that both public and private networks operate with maximum performance, security, and flexibility. This book is intended to provide a comprehensive technical overview and survey of advanced internet protocols, first providing a solid introduction and going on to discu

  1. Security Protocol Review Method Analyzer(SPRMAN)

    OpenAIRE

    Navaz, A. S. Syed; Narayanan, H. Iyyappa; Vinoth, R.

    2013-01-01

    This Paper is designed using J2EE (JSP, SERVLET), HTML as front end and a Oracle 9i is back end. SPRMAN is been developed for the client British Telecom (BT) UK., Telecom company. Actually the requirement of BT is, they are providing Network Security Related Products to their IT customers like Virtusa,Wipro,HCL etc., This product is framed out by set of protocols and these protocols are been associated with set of components. By grouping all these protocols and components together, product is...

  2. Analyzing security protocols in hierarchical networks

    DEFF Research Database (Denmark)

    Zhang, Ye; Nielson, Hanne Riis

    2006-01-01

    Validating security protocols is a well-known hard problem even in a simple setting of a single global network. But a real network often consists of, besides the public-accessed part, several sub-networks and thereby forms a hierarchical structure. In this paper we first present a process calculus...... capturing the characteristics of hierarchical networks and describe the behavior of protocols on such networks. We then develop a static analysis to automate the validation. Finally we demonstrate how the technique can benefit the protocol development and the design of network systems by presenting a series...

  3. Establishing treatment protocols for clinical mastitis.

    Science.gov (United States)

    Roberson, Jerry R

    2003-03-01

    Each farm has a unique mix of mastitis pathogens and management procedures that have evolved over time. The herd veterinarian should work with the manager/owner to systematically develop treatment protocols that meet the needs and management of the farm. To establish a mastitis treatment protocol, it is necessary to develop a system to routinely identify clinical mastitis cases, develop a herd-specific severity level assessment system, manage the clinical mastitis cases based on severity level and culture result (when available), avoid antibiotic residues, and monitor the success of the system and alter the protocol as necessary.

  4. Overview of the InterGroup protocols

    Energy Technology Data Exchange (ETDEWEB)

    Berket, Karlo [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Agarwal, Deborah A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Melliar-Smith, P. Michael [Univ. of California, Santa Barbara, CA (United States); Moser, Louise E. [Univ. of California, Santa Barbara, CA (United States)

    2001-03-01

    Existing reliable ordered group communication protocols have been developed for local-area networks and do not, in general, scale well to large numbers of nodes and wide-area networks. The InterGroup suite of protocols is a scalable group communication system that introduces a novel approach to handling group membership, and supports a receiver-oriented selection of service. The protocols are intended for a wide-area network, with a large number of nodes, that has highly variable delays and a high message loss rate, such as the Internet. The levels of the message delivery service range from unreliable unordered to reliable group timestamp ordered.

  5. The Singapore protocol [for quantum cryptography

    International Nuclear Information System (INIS)

    Englert, B.

    2005-01-01

    The qubit protocol for quantum key distribution presented in this talk is fully tomographic and more efficient than other tomographic protocols. Under ideal circumstances the efficiency is log 2 (4/3) = 0.415 key bits per qubit sent, which is 25% more than the efficiency of 1/3 = 0.333 for the standard 6-state protocol. One can extract 0.4 key bits per qubit by a simple two-way communication scheme, and can so get close to the information-theoretical limit. The noise thresholds for secure key bit generation in the presence of unbiased noise will be reported and discussed. (author)

  6. A Logical Analysis of Quantum Voting Protocols

    Science.gov (United States)

    Rad, Soroush Rafiee; Shirinkalam, Elahe; Smets, Sonja

    2017-12-01

    In this paper we provide a logical analysis of the Quantum Voting Protocol for Anonymous Surveying as developed by Horoshko and Kilin in (Phys. Lett. A 375, 1172-1175 2011). In particular we make use of the probabilistic logic of quantum programs as developed in (Int. J. Theor. Phys. 53, 3628-3647 2014) to provide a formal specification of the protocol and to derive its correctness. Our analysis is part of a wider program on the application of quantum logics to the formal verification of protocols in quantum communication and quantum computation.

  7. Taking an idea to a research protocol

    African Journals Online (AJOL)

    2013-11-13

    Nov 13, 2013 ... Review Article: Taking an idea to a research protocol ... step is to identify the knowledge gap within the intended field of research by examining the background ... be found by writing a critical narrative review of the literature.

  8. Security Protocols: Specification, Verification, Implementation, and Composition

    DEFF Research Database (Denmark)

    Almousa, Omar

    An important aspect of Internet security is the security of cryptographic protocols that it deploys. We need to make sure that such protocols achieve their goals, whether in isolation or in composition, i.e., security protocols must not suffer from any aw that enables hostile intruders to break...... results. The most important generalization is the support for all security properties of the geometric fragment proposed by [Gut14]....... their security. Among others, tools like OFMC [MV09b] and Proverif [Bla01] are quite efficient for the automatic formal verification of a large class of protocols. These tools use different approaches such as symbolic model checking or static analysis. Either approach has its own pros and cons, and therefore, we...

  9. Oxygen tolerance test : A standardised protocol

    Directory of Open Access Journals (Sweden)

    D K Ghosh

    2015-01-01

    Conclusion: By following a standardised protocol for Oxygen Tolerance Test, an objective assessment and recordkeeping is possible. This shall entail a more effective screening during the initial diving medical examination.

  10. Protocol to Exploit Waiting Resources for UASNs

    Directory of Open Access Journals (Sweden)

    Li-Ling Hung

    2016-03-01

    Full Text Available The transmission speed of acoustic waves in water is much slower than that of radio waves in terrestrial wireless sensor networks. Thus, the propagation delay in underwater acoustic sensor networks (UASN is much greater. Longer propagation delay leads to complicated communication and collision problems. To solve collision problems, some studies have proposed waiting mechanisms; however, long waiting mechanisms result in low bandwidth utilization. To improve throughput, this study proposes a slotted medium access control protocol to enhance bandwidth utilization in UASNs. The proposed mechanism increases communication by exploiting temporal and spatial resources that are typically idle in order to protect communication against interference. By reducing wait time, network performance and energy consumption can be improved. A performance evaluation demonstrates that when the data packets are large or sensor deployment is dense, the energy consumption of proposed protocol is less than that of existing protocols as well as the throughput is higher than that of existing protocols.

  11. Authentication Protocol using Quantum Superposition States

    Energy Technology Data Exchange (ETDEWEB)

    Kanamori, Yoshito [University of Alaska; Yoo, Seong-Moo [University of Alabama, Huntsville; Gregory, Don A. [University of Alabama, Huntsville; Sheldon, Frederick T [ORNL

    2009-01-01

    When it became known that quantum computers could break the RSA (named for its creators - Rivest, Shamir, and Adleman) encryption algorithm within a polynomial-time, quantum cryptography began to be actively studied. Other classical cryptographic algorithms are only secure when malicious users do not have sufficient computational power to break security within a practical amount of time. Recently, many quantum authentication protocols sharing quantum entangled particles between communicators have been proposed, providing unconditional security. An issue caused by sharing quantum entangled particles is that it may not be simple to apply these protocols to authenticate a specific user in a group of many users. An authentication protocol using quantum superposition states instead of quantum entangled particles is proposed. The random number shared between a sender and a receiver can be used for classical encryption after the authentication has succeeded. The proposed protocol can be implemented with the current technologies we introduce in this paper.

  12. Technical Analysis of SSP-21 Protocol

    Energy Technology Data Exchange (ETDEWEB)

    Bromberger, S. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2017-06-09

    As part of the California Energy Systems for the Twenty-First Century (CES-21) program, in December 2016 San Diego Gas and Electric (SDG&E) contracted with Lawrence Livermore National Laboratory (LLNL) to perform an independent verification and validation (IV&V) of a white paper describing their Secure SCADA Protocol for the Twenty-First Century (SSP-21) in order to analyze the effectiveness and propriety of cryptographic protocol use within the SSP-21 specification. SSP-21 is designed to use cryptographic protocols to provide (optional) encryption, authentication, and nonrepudiation, among other capabilities. The cryptographic protocols to be used reflect current industry standards; future versions of SSP-21 will use other advanced technologies to provide a subset of security services.

  13. Adaptive security protocol selection for mobile computing

    NARCIS (Netherlands)

    Pontes Soares Rocha, B.; Costa, D.N.O.; Moreira, R.A.; Rezende, C.G.; Loureiro, A.A.F.; Boukerche, A.

    2010-01-01

    The mobile computing paradigm has introduced new problems for application developers. Challenges include heterogeneity of hardware, software, and communication protocols, variability of resource limitations and varying wireless channel quality. In this scenario, security becomes a major concern for

  14. Entanglement distillation protocols and number theory

    International Nuclear Information System (INIS)

    Bombin, H.; Martin-Delgado, M.A.

    2005-01-01

    We show that the analysis of entanglement distillation protocols for qudits of arbitrary dimension D benefits from applying basic concepts from number theory, since the set Z D n associated with Bell diagonal states is a module rather than a vector space. We find that a partition of Z D n into divisor classes characterizes the invariant properties of mixed Bell diagonal states under local permutations. We construct a very general class of recursion protocols by means of unitary operations implementing these local permutations. We study these distillation protocols depending on whether we use twirling operations in the intermediate steps or not, and we study them both analytically and numerically with Monte Carlo methods. In the absence of twirling operations, we construct extensions of the quantum privacy algorithms valid for secure communications with qudits of any dimension D. When D is a prime number, we show that distillation protocols are optimal both qualitatively and quantitatively

  15. Saudi Arabia and CERN sign protocol

    CERN Multimedia

    2008-01-01

    On 9 May 2008, Mohammed I. Al Suwaiyel, President of the King Abdulaziz City of Science and Technology, representing the Government of Saudi Arabia, and CERN Director-General, Robert Aymar, signed a protocol to the 2006 cooperation agreement between CERN and Saudi Arabia. Members of the Saudi Arabian Government visit ATLAS.The purpose of the protocol is to define the operational framework needed to carry out various specific tasks provided for in the cooperation agreement in order to promote the development of a high energy particle physics community in Saudi Arabia and its ultimate visible participation as a member of the global CERN community. Signing the protocol, Mohammed I. Al-Suwaiyel said: "The Saudi Arabian Government has taken a number of initiatives to promote R&D in the interests of our country’s development and the advancement of science. Thanks to this protocol, Saudi scientists will be able to work towards this go...

  16. Verbal protocols as methodological resources: research evidence

    Directory of Open Access Journals (Sweden)

    Alessandra Baldo

    2012-01-01

    Full Text Available This article aims at reflecting on the use of verbal protocols as a methodological resource in qualitative research, more specifically on the aspect regarded as the main limitation of a study about lexical inferencing in L2 (BALDO; VELASQUES, 2010: its subjective trait. The article begins with a brief literature review on protocols, followed by a description of the study in which they were employed as methodological resources. Based on that, protocol subjectivity is illustrated through samples of unparalleled data classification, carried out independently by two researchers. In the final section, the path followed to minimize the problem is presented, intending to contribute to improve efficiency in the use of verbal protocols in future research.

  17. Real-Time Fault Tolerant Networking Protocols

    National Research Council Canada - National Science Library

    Henzinger, Thomas A

    2004-01-01

    We made significant progress in the areas of video streaming, wireless protocols, mobile ad-hoc and sensor networks, peer-to-peer systems, fault tolerant algorithms, dependability and timing analysis...

  18. Development of measurement protocols for quantum magnetometry

    DEFF Research Database (Denmark)

    Stark, Alexander

    and protocols to enhance the lifetime and the coherences of the NV center with the overall goal of enhancing the capabilities of this sensor in the field of magnetometry. In order to realize complex protocols, a sophisticated software control of the measurement setup is required. A general software framework......, is serving as rigorous framework to reduce the complexity of the setup configuration by a fundamental separation of tasks. As a consequence, the general idea of this framework is not limited to experiments with color centers in diamond, but can find application in any laboratory environment. The measurement...... of magnetic fields in the high-frequency GHz regimes is challenging. In this thesis, a continuous dynamical decoupling protocol is developed and implemented, which extends the capabilities of the NV sensor to probe GHz signals with a narrow bandwidth. Moreover, the protocol protects the system from noise...

  19. How to write a research protocol

    African Journals Online (AJOL)

    A research protocol is best viewed as a key to open the gates between the researcher and ... studies will be quantitative designs and these form the focus of this paper. ..... applied to the underlying clinical problem addressed by the study.

  20. Compiling symbolic attacks to protocol implementation tests

    Directory of Open Access Journals (Sweden)

    Michael Rusinowitch

    2013-07-01

    Full Text Available Recently efficient model-checking tools have been developed to find flaws in security protocols specifications. These flaws can be interpreted as potential attacks scenarios but the feasability of these scenarios need to be confirmed at the implementation level. However, bridging the gap between an abstract attack scenario derived from a specification and a penetration test on real implementations of a protocol is still an open issue. This work investigates an architecture for automatically generating abstract attacks and converting them to concrete tests on protocol implementations. In particular we aim to improve previously proposed blackbox testing methods in order to discover automatically new attacks and vulnerabilities. As a proof of concept we have experimented our proposed architecture to detect a renegotiation vulnerability on some implementations of SSL/TLS, a protocol widely used for securing electronic transactions.

  1. Language, Semantics, and Methods for Security Protocols

    DEFF Research Database (Denmark)

    Crazzolara, Federico

    events. Methods like strand spaces and the inductive method of Paulson have been designed to support an intensional, event-based, style of reasoning. These methods have successfully tackled a number of protocols though in an ad hoc fashion. They make an informal spring from a protocol to its......-nets. They have persistent conditions and as we show in this thesis, unfold under reasonable assumptions to a more basic kind of nets. We relate SPL-nets to strand spaces and inductive rules, as well as trace languages and event structures so unifying a range of approaches, as well as providing conditions under...... reveal. The last few years have seen the emergence of successful intensional, event-based, formal approaches to reasoning about security protocols. The methods are concerned with reasoning about the events that a security protocol can perform, and make use of a causal dependency that exists between...

  2. Implementation of the Additional Protocol in Japan

    International Nuclear Information System (INIS)

    Ogawa, T.

    2001-01-01

    The Additional Protocol between Japan and the IAEA entered into force in December 1999. To come into force a series of implementation trials of Additional Protocol was carried out at two Japanese representative nuclear research centers, i.e. Tokai Research Establishment of Japan Atomic Energy Research Institute (JAERI) and Oarai Engineering Center of Japan Nuclear Fuel Cycle Development Institute (JNC). These trials were proposed by Japan and were conducted in cooperation with the IAEA Secretariat. In addition, Japan amended 'the Law for the Regulation of Reactors etc.', to collect adequate information to submit to the IAEA, to arrange the surrounding for the complementary access, etc. In addition, Japan Submitted the Initial Declaration of the Additional Protocol within 180 days of the entry into force of the Protocol, in the middle of June, 2000

  3. Field Monitoring Protocol. Heat Pump Water Heaters

    Energy Technology Data Exchange (ETDEWEB)

    Sparn, B. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Earle, L. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Christensen, D. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Maguire, J. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Wilson, E. [National Renewable Energy Lab. (NREL), Golden, CO (United States); Hancock, C. E. [Mountain Energy Partnership, Longmont, CO (United States)

    2013-02-01

    This document provides a standard field monitoring protocol for evaluating the installed performance of Heat Pump Water Heaters in residential buildings. The report is organized to be consistent with the chronology of field test planning and execution. Research questions are identified first, followed by a discussion of analysis methods, and then the details of measuring the required information are laid out. A field validation of the protocol at a house near the NREL campus is included for reference.

  4. Field Monitoring Protocol: Heat Pump Water Heaters

    Energy Technology Data Exchange (ETDEWEB)

    Sparn, B.; Earle, L.; Christensen, D.; Maguire, J.; Wilson, E.; Hancock, E.

    2013-02-01

    This document provides a standard field monitoring protocol for evaluating the installed performance of Heat Pump Water Heaters in residential buildings. The report is organized to be consistent with the chronology of field test planning and execution. Research questions are identified first, followed by a discussion of analysis methods, and then the details of measuring the required information are laid out. A field validation of the protocol at a house near the NREL campus is included for reference.

  5. An Evaluation Methodology for Protocol Analysis Systems

    Science.gov (United States)

    2007-03-01

    Main Memory Requirement NS: Needham-Schroeder NSL: Needham-Schroeder-Lowe OCaml : Objective Caml POSIX: Portable Operating System...methodology is needed. A. PROTOCOL ANALYSIS FIELD As with any field, there is a specialized language used within the protocol analysis community. Figure...ProVerif requires that Objective Caml ( OCaml ) be installed on the system, OCaml version 3.09.3 was installed. C. WINDOWS CONFIGURATION OS

  6. Topology Discovery Using Cisco Discovery Protocol

    OpenAIRE

    Rodriguez, Sergio R.

    2009-01-01

    In this paper we address the problem of discovering network topology in proprietary networks. Namely, we investigate topology discovery in Cisco-based networks. Cisco devices run Cisco Discovery Protocol (CDP) which holds information about these devices. We first compare properties of topologies that can be obtained from networks deploying CDP versus Spanning Tree Protocol (STP) and Management Information Base (MIB) Forwarding Database (FDB). Then we describe a method of discovering topology ...

  7. Emulation of Industrial Control Field Device Protocols

    Science.gov (United States)

    2013-03-01

    today. The protocol operates at the application layer of the open systems interconnection ( OSI ) model, meaning it operates independently of the...the OSI model. Their job is to receive serial data from an MTU in the Modbus RTU or ASCII protocol, encapsulate and transmit the data to another modem...facing connection and out-of-band logging capabilities over the other LAN -facing connection. Despite the fact that the hardware configuration of the

  8. A Review of Fair Exchange Protocols

    OpenAIRE

    Abdullah AlOtaibi; Hamza Aldabbas

    2012-01-01

    Recently, the Internet has become an essential business platform, aiding trading, distribution and sales between organisations, consumers and even between consumers themselves. This technology revolution has brought e-commerce to an entirely new level, which therefore has raised some new security issues. Security protocols in e-commerce are required to manage the transactions between buyers and sellers. In order to engage customers in e-commerce, these protocols should be well formulated and ...

  9. Recursion vs. Replication in Simple Cryptographic Protocols

    DEFF Research Database (Denmark)

    Huttel, Hans; Srba, Jiri

    2005-01-01

    We use some recent techniques from process algebra to draw several conclusions about the well studied class of ping-pong protocols introduced by Dolev and Yao. In particular we show that all nontrivial properties, including reachability and equivalence checking wrt. the whole van Glabbeek's spect...... of messages in the sense of Amadio, Lugiez and Vanackere. We conclude by showing that reachability analysis for a replicative variant of the protocol becomes decidable....

  10. Broadening and Simplifying the First SETI Protocol

    Science.gov (United States)

    Michaud, M. A. G.

    The Declaration of Principles Concerning Activities Following the Detection of Extraterrestrial Intelligence, known informally as the First SETI Protocol, is the primary existing international guidance on this subject. During the fifteen years since the document was issued, several people have suggested revisions or additional protocols. This article proposes a broadened and simplified text that would apply to the detection of alien technology in our solar system as well as to electromagnetic signals from more remote sources.

  11. Hybrid Long-Distance Entanglement Distribution Protocol

    DEFF Research Database (Denmark)

    Brask, J.B.; Rigas, I.; Polzik, E.S.

    2010-01-01

    We propose a hybrid (continuous-discrete variable) quantum repeater protocol for long-distance entanglement distribution. Starting from states created by single-photon detection, we show how entangled coherent state superpositions can be generated by means of homodyne detection. We show that near......-deterministic entanglement swapping with such states is possible using only linear optics and homodyne detectors, and we evaluate the performance of our protocol combining these elements....

  12. Dynamic Aggregation Protocol for Wireless Sensor Networks

    OpenAIRE

    Mounir Said , Adel; William Ibrahim , Ashraf; Soua , Ahmed; Afifi , Hossam

    2013-01-01

    International audience; Sensor networks suffer from limited capabilities such as bandwidth, low processing power, and memory size. There is therefore a need for protocols that deliver sensor data in an energy-efficient way to the sink. One of those techniques, it gathers sensors' data in a small size packet suitable for transmission. In this paper, we propose a new Effective Data Aggregation Protocol (DAP) to reduce the energy consumption in Wireless Sensor Networks (WSNs), which prolongs the...

  13. Optimistic protocol for partitioned distributed database systems

    International Nuclear Information System (INIS)

    Davidson, S.B.

    1982-01-01

    A protocol for transaction processing during partition failures is presented which guarantees mutual consistency between copies of data-items after repair is completed. The protocol is optimistic in that transactions are processed without restrictions during the failure; conflicts are detected at repair time using a precedence graph and are resolved by backing out transactions according to some backout strategy. The protocol is then evaluated using simulation and probabilistic modeling. In the simulation, several parameters are varied such as the number of transactions processed in a group, the type of transactions processed, the number of data-items present in the database, and the distribution of references to data-items. The simulation also uses different backout strategies. From these results we note conditions under which the protocol performs well, i.e., conditions under which the protocol backs out a small percentage of the transaction run. A probabilistic model is developed to estimate the expected number of transactions backed out using most of the above database and transaction parameters, and is shown to agree with simulation results. Suggestions are then made on how to improve the performance of the protocol. Insights gained from the simulation and probabilistic modeling are used to develop a backout strategy which takes into account individual transaction costs and attempts to minimize total backout cost. Although the problem of choosing transactions to minimize total backout cost is, in general, NP-complete, the backout strategy is efficient and produces very good results

  14. Network-topology-adaptive quantum conference protocols

    International Nuclear Information System (INIS)

    Zhang Sheng; Wang Jian; Tang Chao-Jing; Zhang Quan

    2011-01-01

    As an important application of the quantum network communication, quantum multiparty conference has made multiparty secret communication possible. Previous quantum multiparty conference schemes based on quantum data encryption are insensitive to network topology. However, the topology of the quantum network significantly affects the communication efficiency, e.g., parallel transmission in a channel with limited bandwidth. We have proposed two distinctive protocols, which work in two basic network topologies with efficiency higher than the existing ones. We first present a protocol which works in the reticulate network using Greeberger—Horne—Zeilinger states and entanglement swapping. Another protocol, based on quantum multicasting with quantum data compression, which can improve the efficiency of the network, works in the star-like network. The security of our protocols is guaranteed by quantum key distribution and one-time-pad encryption. In general, the two protocols can be applied to any quantum network where the topology can be equivalently transformed to one of the two structures we propose in our protocols. (general)

  15. Simulation and Evaluation of CTP and Secure-CTP Protocols

    Directory of Open Access Journals (Sweden)

    P. Pecho

    2010-04-01

    Full Text Available The paper discusses characteristics and qualities of two routing protocols – Collection Tree Protocol and its secure modification. The original protocol, as well as other protocols for wireless sensors, solves only problems of ra- dio communication and limited resources. Our design of the secure protocol tries to solve also the essential security ob- jectives. For the evaluation of properties of our protocol in large networks, a TOSSIM simulator was used. Our effort was to show the influence of the modification of the routing protocol to its behavior and quality of routing trees. We have proved that adding security into protocol design does not necessarily mean higher demands for data transfer, power consumption or worse protocol efficiency. In the paper, we manifest that security in the protocol may be achieved with low cost and may offer similar performance as the original protocol.

  16. MDEP Protocol VICWG-01. MDEP Protocol: Witnessed, Joint, and Multinational Vendor Inspection Protocol

    International Nuclear Information System (INIS)

    2014-01-01

    The Multinational Design Evaluation Programme (MDEP) was launched in 2006 by the US Nuclear Regulatory Commission (NRC) and the French Nuclear Safety Authority (ASN) with the aim of developing innovative approaches to leverage the resources and knowledge of national regulatory authorities reviewing new reactor designs. MDEP full members are regulators from Canada, People's Republic of China, Finland, France, India, Japan, Republic of Korea, Russian Federation, South Africa, Sweden, the United Kingdom and the United States of America. The United Arab Emirates and Turkey are associate members. The OECD Nuclear Energy Agency (NEA) acts as the Technical Secretariat for the MDEP. The International Atomic Energy Agency (IAEA) participates in many of the MDEP activities, including harmonisation efforts. The Vendor Inspection Cooperation Working Group (VICWG) is one of the issue-specific working groups that the MDEP members are undertaking with one long term goal of the VICWG being to maximize the use of the results obtained from other regulator's efforts in inspecting vendors. To accomplish this goal, it is vital that the regulators learn about each other's procedures, processes, and regulations. To facilitate the learning process the VICWG is coordinating vendor inspections among the involved regulatory authorities with the purpose of enhancing the understanding of each other's vendor inspection procedures. This programme is administered by the NEA. Involvement in specific inspections provides a number of opportunities for member state regulators to witness other regulators' inspection methods, gain useful information on the quality systems and manufacturing arrangements of specific vendors and where appropriate, actively participate in the inspection. The purpose of this protocol is to provide guidance to regulators that wish to carry out vendor inspections or participate in or witness other regulators' vendor inspections. It also provides

  17. Protocol for Communication Networking for Formation Flying

    Science.gov (United States)

    Jennings, Esther; Okino, Clayton; Gao, Jay; Clare, Loren

    2009-01-01

    An application-layer protocol and a network architecture have been proposed for data communications among multiple autonomous spacecraft that are required to fly in a precise formation in order to perform scientific observations. The protocol could also be applied to other autonomous vehicles operating in formation, including robotic aircraft, robotic land vehicles, and robotic underwater vehicles. A group of spacecraft or other vehicles to which the protocol applies could be characterized as a precision-formation- flying (PFF) network, and each vehicle could be characterized as a node in the PFF network. In order to support precise formation flying, it would be necessary to establish a corresponding communication network, through which the vehicles could exchange position and orientation data and formation-control commands. The communication network must enable communication during early phases of a mission, when little positional knowledge is available. Particularly during early mission phases, the distances among vehicles may be so large that communication could be achieved only by relaying across multiple links. The large distances and need for omnidirectional coverage would limit communication links to operation at low bandwidth during these mission phases. Once the vehicles were in formation and distances were shorter, the communication network would be required to provide high-bandwidth, low-jitter service to support tight formation-control loops. The proposed protocol and architecture, intended to satisfy the aforementioned and other requirements, are based on a standard layered-reference-model concept. The proposed application protocol would be used in conjunction with conventional network, data-link, and physical-layer protocols. The proposed protocol includes the ubiquitous Institute of Electrical and Electronics Engineers (IEEE) 802.11 medium access control (MAC) protocol to be used in the datalink layer. In addition to its widespread and proven use in

  18. MODELLING AND VERIFICATION OF KITSAT PACKET COMMUNICATION PROTOCOLS

    Directory of Open Access Journals (Sweden)

    Young-Ro Lee

    1996-06-01

    Full Text Available In this paper, in order to verify KITSAT 1/2 packet communication protocols, we model the AX.25 protocol and PACSAT protocol by using an extended Petri net and then verify the correctness, boundedness, liveness and deadlock freeness of packet protocols by utilizing reachability trees.

  19. Differential phase-time shifting protocol for QKD (DPTS)

    DEFF Research Database (Denmark)

    Usuga Castaneda, Mario A.; Bacco, Davide; Christensen, Jesper Bjerge

    2016-01-01

    We explore the implementation of a novel protocol for fiber-based high-dimensional quantum key distribution (QKD) which improves over the traditional DPS-QKD and COW protocols.......We explore the implementation of a novel protocol for fiber-based high-dimensional quantum key distribution (QKD) which improves over the traditional DPS-QKD and COW protocols....

  20. Effectiveness of Seasonal Malaria Chemoprevention in Children under Ten Years of Age in Senegal: A Stepped-Wedge Cluster-Randomised Trial.

    Directory of Open Access Journals (Sweden)

    Badara Cissé

    2016-11-01

    Full Text Available Seasonal Malaria Chemoprevention (SMC with sulfadoxine-pyrimethamine (SP plus amodiaquine (AQ, given each month during the transmission season, is recommended for children living in areas of the Sahel where malaria transmission is highly seasonal. The recommendation for SMC is currently limited to children under five years of age, but, in many areas of seasonal transmission, the burden in older children may justify extending this age limit. This study was done to determine the effectiveness of SMC in Senegalese children up to ten years of age.SMC was introduced into three districts over three years in central Senegal using a stepped-wedge cluster-randomised design. A census of the population was undertaken and a surveillance system was established to record all deaths and to record all cases of malaria seen at health facilities. A pharmacovigilance system was put in place to detect adverse drug reactions. Fifty-four health posts were randomised. Nine started implementation of SMC in 2008, 18 in 2009, and a further 18 in 2010, with 9 remaining as controls. In the first year of implementation, SMC was delivered to children aged 3-59 months; the age range was then extended for the latter two years of the study to include children up to 10 years of age. Cluster sample surveys at the end of each transmission season were done to measure coverage of SMC and the prevalence of parasitaemia and anaemia, to monitor molecular markers of drug resistance, and to measure insecticide-treated net (ITN use. Entomological monitoring and assessment of costs of delivery in each health post and of community attitudes to SMC were also undertaken. About 780,000 treatments were administered over three years. Coverage exceeded 80% each month. Mortality, the primary endpoint, was similar in SMC and control areas (4.6 and 4.5 per 1000 respectively in children under 5 years and 1.3 and 1.2 per 1000 in children 5-9 years of age; the overall mortality rate ratio [SMC: no SMC

  1. A Cryptographic Moving-Knife Cake-Cutting Protocol

    Directory of Open Access Journals (Sweden)

    Yoshifumi Manabe

    2012-02-01

    Full Text Available This paper proposes a cake-cutting protocol using cryptography when the cake is a heterogeneous good that is represented by an interval on a real line. Although the Dubins-Spanier moving-knife protocol with one knife achieves simple fairness, all players must execute the protocol synchronously. Thus, the protocol cannot be executed on asynchronous networks such as the Internet. We show that the moving-knife protocol can be executed asynchronously by a discrete protocol using a secure auction protocol. The number of cuts is n-1 where n is the number of players, which is the minimum.

  2. Welfare Quality assessment protocol for laying hens = Welfare Quality assessment protocol voor leghennen

    NARCIS (Netherlands)

    Niekerk, van T.G.C.M.; Gunnink, H.; Reenen, van C.G.

    2012-01-01

    Results of a study on the Welfare Quality® assessment protocol for laying hens. It reports the development of the integration of welfare assessment as scores per criteria as well as simplification of the Welfare Quality® assessment protocol. Results are given from assessment of 122 farms.

  3. Nursing Music Protocol and Postoperative Pain.

    Science.gov (United States)

    Poulsen, Michael J; Coto, Jeffrey

    2018-04-01

    Pain has always been a major concern for patients and nurses during the postoperative period. Therapies, medicines, and protocols have been developed to improve pain and anxiety but have undesirable risks to the patient. Complementary and alternative medicine therapies have been studied but have not been applied as regular protocols in the hospital setting. Music is one type of complementary and alternative medicine therapy that has been reported to have favorable results on reducing postoperative pain, anxiety, and opioid usage. However, music lacks a protocol that nurses can implement during the perioperative process. This paper is an in-depth literature review assessing a best practice recommendation and protocol that establishes a consensus in the use of music therapy. The results suggest that music therapy may consist of calming, soft tones of 60-80 beats per minute for at least 15-30 minutes at least twice daily during the pre- and postoperative periods. It is suggested that music only be used in conjunction with standards of care and not as the primary intervention of pain or anxiety. This evidence suggests that proper use of music therapy can significantly reduce surgical pain. Implementing these protocols and allowing the freedom of nursing staff to use them may lead to greater reductions in surgical pain and anxiety and a reduction in opioid use. Copyright © 2017 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  4. WDM Network and Multicasting Protocol Strategies

    Directory of Open Access Journals (Sweden)

    Pinar Kirci

    2014-01-01

    Full Text Available Optical technology gains extensive attention and ever increasing improvement because of the huge amount of network traffic caused by the growing number of internet users and their rising demands. However, with wavelength division multiplexing (WDM, it is easier to take the advantage of optical networks and optical burst switching (OBS and to construct WDM networks with low delay rates and better data transparency these technologies are the best choices. Furthermore, multicasting in WDM is an urgent solution for bandwidth-intensive applications. In the paper, a new multicasting protocol with OBS is proposed. The protocol depends on a leaf initiated structure. The network is composed of source, ingress switches, intermediate switches, edge switches, and client nodes. The performance of the protocol is examined with Just Enough Time (JET and Just In Time (JIT reservation protocols. Also, the paper involves most of the recent advances about WDM multicasting in optical networks. WDM multicasting in optical networks is given as three common subtitles: Broadcast and-select networks, wavelength-routed networks, and OBS networks. Also, in the paper, multicast routing protocols are briefly summarized and optical burst switched WDM networks are investigated with the proposed multicast schemes.

  5. A Lightweight Protocol for Secure Video Streaming.

    Science.gov (United States)

    Venčkauskas, Algimantas; Morkevicius, Nerijus; Bagdonas, Kazimieras; Damaševičius, Robertas; Maskeliūnas, Rytis

    2018-05-14

    The Internet of Things (IoT) introduces many new challenges which cannot be solved using traditional cloud and host computing models. A new architecture known as fog computing is emerging to address these technological and security gaps. Traditional security paradigms focused on providing perimeter-based protections and client/server point to point protocols (e.g., Transport Layer Security (TLS)) are no longer the best choices for addressing new security challenges in fog computing end devices, where energy and computational resources are limited. In this paper, we present a lightweight secure streaming protocol for the fog computing "Fog Node-End Device" layer. This protocol is lightweight, connectionless, supports broadcast and multicast operations, and is able to provide data source authentication, data integrity, and confidentiality. The protocol is based on simple and energy efficient cryptographic methods, such as Hash Message Authentication Codes (HMAC) and symmetrical ciphers, and uses modified User Datagram Protocol (UDP) packets to embed authentication data into streaming data. Data redundancy could be added to improve reliability in lossy networks. The experimental results summarized in this paper confirm that the proposed method efficiently uses energy and computational resources and at the same time provides security properties on par with the Datagram TLS (DTLS) standard.

  6. Two Cheers for the Trafficking Protocol

    Directory of Open Access Journals (Sweden)

    Anne T Gallagher

    2015-04-01

    Full Text Available The Trafficking Protocol makes an easy target for attack. Its origins lie in an attempt to control a particularly exploitative form of migration that was challenging the ability of States to control their own borders. Its parent instrument is a framework agreement to address transnational organised crime. While paying fleeting attention to the rights of victims, the Protocol, with its emphasis on criminalisation and border protection is nowhere near being a human rights treaty. On top of all that it does not even have a credible enforcement mechanism, allowing states parties wide latitude in interpreting and applying their obligations. Strangely, these seemingly insurmountable flaws have not stopped the Protocol’s emergence as perhaps the single most important development in the fight against human trafficking. Without the Protocol, arguments around definitions would have continued to block the evolution of principles and rules. Without the Protocol it is likely that the human rights system would have continued its shameful tradition of sidelining issues such as forced labour, forced sex, forced marriage and the ritual exploitation of migrant workers through debt. Most critically, the Protocol provided the impetus and template for a series of legal and political developments that, over time, have served to ameliorate some of its greatest weaknesses, including the lack of human rights protections and of a credible oversight mechanism.

  7. Supporting Adaptation of Wireless Communication Protocols

    International Nuclear Information System (INIS)

    Dhomeja, L.D.; Soomro, I.A.; Malkani, Y.A.

    2016-01-01

    Pervasive devices such as mobile phones and PDAs (Personal Digital Assistants) come with different wireless communication capabilities, for example, WiFi (Wireless Fidelity), Bluetooth, IrDA (Infrared), etc. In order for pervasive devices to interact with each other, they need to have matching (alike) communication capabilities, otherwise such heterogeneous devices would not be able to interact with each other. In this paper we address this issue and propose a system that makes devices with heterogeneous wireless communication capabilities communicate with each other. The proposed system supports adaptation of wireless communication protocols through a proxy, which sits between a client and a server, and supports adaptation of wireless communication protocols. Its functionality involves intercepting a request made by a client with a different wireless communication capability (e.g. Bluetooth) from what the server has (e.g. WiFi), connecting to the server and then sending results back to the client. We have tested the system by implementing a messaging service application and running it on the system. The proxy supports all Bluetooth protocols, i.e. OBEX (Object Exchange), L2CAP (Logical Link Control and Adaptation Protocol), RFCOM (Radio Frequency Communication) and WiFi protocol and can run on (J2MW (Java 2 Micro Edition) enabled mobile phones which support both Bluetooth and WiFi capabilities. (author)

  8. Controlled Delegation Protocol in Mobile RFID Networks

    Directory of Open Access Journals (Sweden)

    Yang MingHour

    2010-01-01

    Full Text Available To achieve off-line delegation for mobile readers, we propose a delegation protocol for mobile RFID allowing its readers access to specific tags through back-end server. That is to say, reader-tag mutual authentication can be performed without readers being connected to back-end server. Readers are also allowed off-line access to tags' data. Compared with other delegation protocols, our scheme uniquely enables back-end server to limit each reader's reading times during delegation. Even in a multireader situation, our protocol can limit reading times and reading time periods for each of them and therefore makes back-end server's delegation more flexible. Besides, our protocol can prevent authorized readers from transferring their authority to the unauthorized, declining invalid access to tags. Our scheme is proved viable and secure with GNY logic; it is against certain security threats, such as replay attacks, denial of service (DoS attacks, Man-in-the-Middle attacks, counterfeit tags, and breaches of location and data privacy. Also, the performance analysis of our protocol proves that current tags can afford the computation load required in this scheme.

  9. Decellularization of placentas: establishing a protocol

    Directory of Open Access Journals (Sweden)

    L.C.P.C. Leonel

    2017-11-01

    Full Text Available Biological biomaterials for tissue engineering purposes can be produced through tissue and/or organ decellularization. The remaining extracellular matrix (ECM must be acellular and preserve its proteins and physical features. Placentas are organs of great interest because they are discarded after birth and present large amounts of ECM. Protocols for decellularization are tissue-specific and have not been established for canine placentas yet. This study aimed at analyzing a favorable method for decellularization of maternal and fetal portions of canine placentas. Canine placentas were subjected to ten preliminary tests to analyze the efficacy of parameters such as the type of detergents, freezing temperatures and perfusion. Two protocols were chosen for further analyses using histology, scanning electron microscopy, immunofluorescence and DNA quantification. Sodium dodecyl sulfate (SDS was the most effective detergent for cell removal. Freezing placentas before decellularization required longer periods of incubation in different detergents. Both perfusion and immersion methods were capable of removing cells. Placentas decellularized using Protocol I (1% SDS, 5 mM EDTA, 50 mM TRIS, and 0.5% antibiotic preserved the ECM structure better, but Protocol I was less efficient to remove cells and DNA content from the ECM than Protocol II (1% SDS, 5 mM EDTA, 0.05% trypsin, and 0.5% antibiotic.

  10. A More Efficient Contextuality Distillation Protocol

    Science.gov (United States)

    Meng, Hui-xian; Cao, Huai-xin; Wang, Wen-hua; Fan, Ya-jing; Chen, Liang

    2018-03-01

    Based on the fact that both nonlocality and contextuality are resource theories, it is natural to ask how to amplify them more efficiently. In this paper, we present a contextuality distillation protocol which produces an n-cycle box B ∗ B ' from two given n-cycle boxes B and B '. It works efficiently for a class of contextual n-cycle ( n ≥ 4) boxes which we termed as "the generalized correlated contextual n-cycle boxes". For any two generalized correlated contextual n-cycle boxes B and B ', B ∗ B ' is more contextual than both B and B '. Moreover, they can be distilled toward to the maximally contextual box C H n as the times of iteration goes to infinity. Among the known protocols, our protocol has the strongest approximate ability and is optimal in terms of its distillation rate. What is worth noting is that our protocol can witness a larger set of nonlocal boxes that make communication complexity trivial than the protocol in Brunner and Skrzypczyk (Phys. Rev. Lett. 102, 160403 2009), this might be helpful for exploring the problem that why quantum nonlocality is limited.

  11. Efficient Communication Protocols for Deciding Edit Distance

    DEFF Research Database (Denmark)

    Jowhari, Hossein

    2012-01-01

    In this paper we present two communication protocols on computing edit distance. In our first result, we give a one-way protocol for the following Document Exchange problem. Namely given x ∈ Σn to Alice and y ∈ Σn to Bob and integer k to both, Alice sends a message to Bob so that he learns x...... or truthfully reports that the edit distance between x and y is greater than k. For this problem, we give a randomized protocol in which Alice transmits at most O ˜ (klog 2 n) bits and each party’s time complexity is O ˜ (nlogn+k 2 log 2 n) . Our second result is a simultaneous protocol for edit distance over...... permutations. Here Alice and Bob both send a message to a third party (the referee) who does not have access to the input strings. Given the messages, the referee decides if the edit distance between x and y is at most k or not. For this problem we give a protocol in which Alice and Bob run a O...

  12. A Lightweight Buyer-Seller Watermarking Protocol

    Directory of Open Access Journals (Sweden)

    Yongdong Wu

    2008-01-01

    Full Text Available The buyer-seller watermarking protocol enables a seller to successfully identify a traitor from a pirated copy, while preventing the seller from framing an innocent buyer. Based on finite field theory and the homomorphic property of public key cryptosystems such as RSA, several buyer-seller watermarking protocols (N. Memon and P. W. Wong (2001 and C.-L. Lei et al. (2004 have been proposed previously. However, those protocols require not only large computational power but also substantial network bandwidth. In this paper, we introduce a new buyer-seller protocol that overcomes those weaknesses by managing the watermarks. Compared with the earlier protocols, ours is n times faster in terms of computation, where n is the number of watermark elements, while incurring only O(1/lN times communication overhead given the finite field parameter lN. In addition, the quality of the watermarked image generated with our method is better, using the same watermark strength.

  13. A class-chest for deriving transport protocols

    Energy Technology Data Exchange (ETDEWEB)

    Strayer, W.T.

    1996-10-01

    Development of new transport protocols or protocol algorithms suffers from the complexity of the environment in which they are intended to run. Modeling techniques attempt to avoid this by simulating the environment. Another approach to promoting rapid prototyping of protocols and protocol algorithms is to provide a pre-built infrastructure that is common to transport protocols, so that the focus is placed on the protocol-specific aspects. The Meta-Transport Library is a library of C++ base classes that implement or abstract out the mundane functions of a protocol, new protocol implementations are derived from base classes. The result is a fully viable user- level transport protocol implementation, with emphasis on modularity. The collection of base classes form a ``class-chest`` of tools .from which protocols can be developed and studied with as little change to a normal UNIX environment as possible.

  14. An one-time-pad key communication protocol with entanglement

    OpenAIRE

    Cai, Qing-yu

    2003-01-01

    We present an one-time-pad key communication protocol that allows secure direct communication with entanglement. Alice can send message to Bob in a deterministic manner by using local measurements and public communication. The theoretical efficiency of this protocol is double compared with BB84 protocol. We show this protocol is unconditional secure under arbitrary quantum attack. And we discuss that this protocol can be perfectly implemented with current technologies.

  15. Objective and automated protocols for the evaluation of biomedical search engines using No Title Evaluation protocols.

    Science.gov (United States)

    Campagne, Fabien

    2008-02-29

    The evaluation of information retrieval techniques has traditionally relied on human judges to determine which documents are relevant to a query and which are not. This protocol is used in the Text Retrieval Evaluation Conference (TREC), organized annually for the past 15 years, to support the unbiased evaluation of novel information retrieval approaches. The TREC Genomics Track has recently been introduced to measure the performance of information retrieval for biomedical applications. We describe two protocols for evaluating biomedical information retrieval techniques without human relevance judgments. We call these protocols No Title Evaluation (NT Evaluation). The first protocol measures performance for focused searches, where only one relevant document exists for each query. The second protocol measures performance for queries expected to have potentially many relevant documents per query (high-recall searches). Both protocols take advantage of the clear separation of titles and abstracts found in Medline. We compare the performance obtained with these evaluation protocols to results obtained by reusing the relevance judgments produced in the 2004 and 2005 TREC Genomics Track and observe significant correlations between performance rankings generated by our approach and TREC. Spearman's correlation coefficients in the range of 0.79-0.92 are observed comparing bpref measured with NT Evaluation or with TREC evaluations. For comparison, coefficients in the range 0.86-0.94 can be observed when evaluating the same set of methods with data from two independent TREC Genomics Track evaluations. We discuss the advantages of NT Evaluation over the TRels and the data fusion evaluation protocols introduced recently. Our results suggest that the NT Evaluation protocols described here could be used to optimize some search engine parameters before human evaluation. Further research is needed to determine if NT Evaluation or variants of these protocols can fully substitute

  16. Analysis of Security Protocols by Annotations

    DEFF Research Database (Denmark)

    Gao, Han

    . The development of formal techniques, e.g. control flow analyses, that can check various security properties, is an important tool to meet this challenge. This dissertation contributes to the development of such techniques. In this dissertation, security protocols are modelled in the process calculus LYSA......The trend in Information Technology is that distributed systems and networks are becoming increasingly important, as most of the services and opportunities that characterise the modern society are based on these technologies. Communication among agents over networks has therefore acquired a great...... deal of research interest. In order to provide effective and reliable means of communication, more and more communication protocols are invented, and for most of them, security is a significant goal. It has long been a challenge to determine conclusively whether a given protocol is secure or not...

  17. Breaking Megrelishvili protocol using matrix diagonalization

    Science.gov (United States)

    Arzaki, Muhammad; Triantoro Murdiansyah, Danang; Adi Prabowo, Satrio

    2018-03-01

    In this article we conduct a theoretical security analysis of Megrelishvili protocol—a linear algebra-based key agreement between two participants. We study the computational complexity of Megrelishvili vector-matrix problem (MVMP) as a mathematical problem that strongly relates to the security of Megrelishvili protocol. In particular, we investigate the asymptotic upper bounds for the running time and memory requirement of the MVMP that involves diagonalizable public matrix. Specifically, we devise a diagonalization method for solving the MVMP that is asymptotically faster than all of the previously existing algorithms. We also found an important counterintuitive result: the utilization of primitive matrix in Megrelishvili protocol makes the protocol more vulnerable to attacks.

  18. Automatic Generation of Network Protocol Gateways

    DEFF Research Database (Denmark)

    Bromberg, Yérom-David; Réveillère, Laurent; Lawall, Julia

    2009-01-01

    for describing protocol behaviors, message structures, and the gateway logic.  Z2z includes a compiler that checks essential correctness properties and produces efficient code. We have used z2z to develop a number of gateways, including SIP to RTSP, SLP to UPnP, and SMTP to SMTP via HTTP, involving a range......The emergence of networked devices in the home has made it possible to develop applications that control a variety of household functions. However, current devices communicate via a multitude of incompatible protocols, and thus gateways are needed to translate between them.  Gateway construction......, however, requires an intimate knowledge of the relevant protocols and a substantial understanding of low-level network programming, which can be a challenge for many application programmers. This paper presents a generative approach to gateway construction, z2z, based on a domain-specific language...

  19. Magnetic resonance imaging protocols for paediatric neuroradiology

    International Nuclear Information System (INIS)

    Saunders, Dawn E.; Thompson, Clare; Gunny, Roxanne; Jones, Rod; Cox, Tim; Chong, Wui Khean

    2007-01-01

    Increasingly, radiologists are encouraged to have protocols for all imaging studies and to include imaging guidelines in care pathways set up by the referring clinicians. This is particularly advantageous in MRI where magnet time is limited and a radiologist's review of each patient's images often results in additional sequences and longer scanning times without the advantage of improvement in diagnostic ability. The difficulties of imaging small children and the challenges presented to the radiologist as the brain develops are discussed. We present our protocols for imaging the brain and spine of children based on 20 years experience of paediatric neurological MRI. The protocols are adapted to suit children under the age of 2 years, small body parts and paediatric clinical scenarios. (orig.)

  20. Demarcation of Security in Authentication Protocols

    DEFF Research Database (Denmark)

    Ahmed, Naveed; Jensen, Christian D.

    2011-01-01

    Security analysis of communication protocols is a slippery business; many “secure” protocols later turn out to be insecure. Among many, two complains are more frequent: inadequate definition of security and unstated assumptions in the security model. In our experience, one principal cause...... for such state of affairs is an apparent overlap of security and correctness, which may lead to many sloppy security definitions and security models. Although there is no inherent need to separate security and correctness requirements, practically, such separation is significant. It makes security analysis...... easier, and enables us to define security goals with a fine granularity. We present one such separation, by introducing the notion of binding sequence as a security primitive. A binding sequence, roughly speaking, is the only required security property of an authentication protocol. All other...