WorldWideScience

Sample records for antitumoral das tiossemicarbazonas

  1. Characterization of the anti tumoral activity of the thiosemicarbazones derived from N(4)-methyl-tolyl-2acetylpyridine And 2-pyridinoformamide and its metal complex: evaluation of the radiopharmaceutical potential; Caracterizacao da atividade antitumoral das tiossemicarbazonas derivadas de N(4)-metil-toluil-2-acetilpiridina e 2-piridinoformamida e seus complexos metalicos: avaliacao do potencial radiofarmaceutico

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Paulo Roberto Ornelas da

    2008-07-01

    Thiosemicarbazones have attracted great pharmacological interest because of their biological properties, such as cytotoxic activity against multiple strains of human tumors. The most studied compounds are pyridine-based because of their resemblance to pyridoxal metabolites that attach to co-enzyme B{sub 6}-dependant enzymes. This work aimed the characterization of the anti tumoral effect of N(4)-methyl-tolyl-2-acetylpyridine and 2-pyridinoformamide-derived thiosemicarbazones and the development of a radiopharmaceutical based on a thiosemicarbazone metal complex for positron emission tomography. In the first phase of this study were synthesized twenty-one thiosemicarbazones, derived from N(4)methyl-2 acetylpyridine and 2-pyridine formamide, as well as their metal complexes (Sn, Ga and Cu). Their cytotoxic potential were evaluated against brain and breast tumor cells in vitro. Our results showed all of them presented powerful cytotoxic and antiproliferative activities against glioblastoma multiform and breast adenocarcinoma at very low concentrations (nanomolar range). Morphological alterations characteristic of apoptosis, such as cell shrinkage, chromatin condensation were observed. Copper chloride was used as control and has presented IC50 at millimolar range suggesting that copper complexation with thiosemicarbazone significantly increases (more than 1 million) the anti tumoral effect of this metal. Due to the potent anti tumoral activity of N(4)-methyl-tolyl-2-acetylpyridine derived thiosemicarbazones and the excellent properties of {sup 64}Cu (T{sub 1/2} = 12.7 hours, {beta}{sup +}, {beta}{sup -}, and EC decay), at the second part for this work it was developed a new imaging agent (radiopharmaceutical) for tumor detection by positron emission tomography (PET). The radiopharmaceuticals were produced in the nuclear reactor TRIGA-IPR-R1 from CDTN, via neutron capture reaction {sup 63}Cu (n,{gamma}) {sup 64}Cu, of the copper complex N(4)-ortho-toluyl-2-acetylpyridine thiosemicarbazone (Culac). The induced specific activity was found to be 5.55 MBq /mg. After irradiation Culac samples were analyzed by the absorption of infrared spectroscopy (IR) to assess the structural integrity. The irradiated compound kept its structural integrity. The maintenance of {sup 64}Culac biological activity was also evaluated by MTT assay on RT2 (wild p53), T98 (mutant p53), MCF-7 (wild p53) and CAE cells (wild p53). The results showed that {sup 64}Culac kept its potent anti tumoral activity against all treated cells presenting IC50 values at nanomolar range. {sup 64}Culac biodistribution studies after intravenous injection in mice bearing Erlich tumor implanted in the paw, showed significant uptake in the tumor paw (tumor/skeletal muscle ratio 6.55), 240 minutes after administration. Histopathological studies have shown mild hepatotoxicity 144 hours (6 days) after intravenous administration of 308 mg/kg of Culac. However, no lethality, behavioural, or feeding changes were observed at this dose. Our results demonstrate that the complex of copper-64 N(4)-ortho-toluyl-2-acetylpyridine thiosemicarbazone ({sup 64}Culac) is a promising radiopharmaceutical for detection of solid tumors by positron emission tomography (PET). (author)

  2. Thiosemicarbazones: preparation methods, synthetic applications and biological importance; Tiossemicarbazonas: metodos de obtencao, aplicacoes sinteticas e importancia biologica

    Energy Technology Data Exchange (ETDEWEB)

    Tenorio, Romulo P.; Goes, Alexandre J.S. [Universidade Federal de Pernambuco, Recife, PE (Brazil). Dept. de Antibioticos]. E-mail: ajsg@ufpe.br; Lima, Jose G. de; Faria, Antonio R. de; Alves, Antonio J.; Aquino, Thiago M. de [Universidade Federal de Pernambuco, Recife, PE (Brazil). Dept. de Ciencias Farmaceuticas

    2005-11-15

    Thiosemicarbazones are a class of compounds known by their chemical and biological properties, such as antitumor, antibacterial, antiviral and antiprotozoal activity. Their ability to form chelates with metals has great importance in their biological activities. Their synthesis is very simple, versatile and clean, usually giving high yields. They are largely employed as intermediates, in the synthesis of others compounds. This article is a survey of some of these characteristics showing their great importance to organic and medicinal chemistry. (author)

  3. Kalyan Das

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education. Kalyan Das. Articles written in Resonance – Journal of Science Education. Volume 5 Issue 12 December 2000 pp 76-76 Book Review. Linear Algebra and Linear Models · Kalyan Das · More Details Fulltext PDF ...

  4. S Das

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. S Das. Articles written in Bulletin of Materials Science. Volume 25 Issue 6 November 2002 pp 557-560. 3-D mapping with ellipsometrically determined physical thickness/refractive index of spin coated sol–gel silica layer · S Das P Pal S Roy S Chakraboarty P K Biswas.

  5. Evaluation of the potential application of 2-acetylpyridine N4- phenyl thiosemicarbazones derivatives for cancer therapy and diagnosis; Avaliacao da potencial aplicacao de derivados de 2-acetilpiridina N-4 fenil tiossemicarbazonas em terapia e diagnostico oncologico

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Marcella Araugio

    2013-08-01

    Despite the wide range of antineoplastic agents available, resistance of some types of cancer and toxicity to normal cells have been identified as the main causes of treatment failure and death. The lack of early and precise diagnosis is also responsible for reducing survival of cancer patients. In this context, the development of substances with low toxicity and therapeutic potential and/or diagnosis purpose, is the major tool in an attempt to increase the survival of patients and assure the safety and efficacy of treatment. Thiosemicarbazones (TSC) are a class of synthetic compounds that have several biological activities, including antitumor. Although several studies have shown the great potential of TSC as therapeutic and / or diagnostic agents, different chemical modifications performed on this class of molecules indicate new possibilities for applications and still require further studies. The objective of this study was to evaluate the potential applicability of 2-acetylpyridine N-4-phenyl thiosemicarbazones derivatives for cancer therapy and diagnosis. The results showed that all 13 TSC tested were cytotoxic to breast and glioblastoma tumor cell lines, presenting higher in vitro antitumor activity than etoposide, an antineoplastic and inhibitor of topoisomerase II frequently used for cancer therapy. The TSC that have halogen or nitro on ortho position showed higher antitumor activity in vitro than their isomers with halogen or nitro on meta or para position of the phenyl group. H2Ac4oFPh and H2Ac4oClPh compounds showed the highest antitumor activity among all tested compounds, with IC{sub 50} in nanomolar order. These TSC induced cell death by apoptosis and oxidative stress was responsible, at least in part, for this type of cell death. The 5 mg.kg{sup -1} H2Ac4oFPh dose, administered s.c., for 4 consecutive days, did not induce important toxicity; however, the same treatment protocol was not effective for tumor growth reduction in an animal model of brain

  6. Rhenium–platinum antitumor systems

    Directory of Open Access Journals (Sweden)

    A. V. Shtemenko

    2017-04-01

    Full Text Available This review provides an overlook of design (in short, antitumor and other biological activity of quadruple-bonded cluster dirhenium(III compounds and their synergism with cisplatin. In particular, we describe the work of the rhenium-platinum antitumor system (introduction of rhenium and platinum compounds. Among known metal-based anticancer drugs and drug candidates dirhenium(III compounds differ profoundly due to their strong antiradical and antioxidant properties determined by quadruple bond unsaturation. Such advantages of metal complexes as more expressed redox chemical propertie should be exploited for creating more efficient anticancer drugs. Combination of drugs leads to synergistic effects and/or to lowe­ring toxicity of platinides and is very promising in cancer chemotherapy. The review covers the follo­wing items: design of quadruple bonded dirhenium(III clusters, their spectral and antiradical properties (in short; interaction of the dirhenium(III compounds with lipids and formation of liposomes; interaction of the dirhenium(III compounds with erythrocytes and their antihemolytic activity in the models of hemolytic anemia; anticancer activity of dirhenium clusters and work of the rhenium-platinum antitumor system; antianemic and antioxidant properties of the dirhenium(III compounds in the model of tumor growth; interaction of the dirhenium(III compounds with nucleobases and DNA. Some modern trends in the field of bioinorganic and medicinal chemi­stry are also considered regarding their connection to the rhenium-platinum system efficiency: use of combinational therapy and nanomaterials; involvement of some biologically active ligands and redox-activation strategy, etc.

  7. DAS performance analysis

    International Nuclear Information System (INIS)

    Bates, G.; Bodine, S.; Carroll, T.; Keller, M.

    1984-02-01

    This report begins with an overview of the Data Acquisition System (DAS), which supports several of PPPL's experimental devices. Performance measurements which were taken on DAS and the tools used to make them are then described

  8. Antitumoral activity of marine organism

    International Nuclear Information System (INIS)

    Valdes Iglesias, O; Perez Gil, R; Colom, Y

    2010-01-01

    The study of the natural products from marine organism constitute a relatively recent scientific researcher field with high potentialities tanking in consideration that the oceans cover the three of the four parts of the earth. Poryphera and Bryozoans have been the Phylum more studied owning to the vulnerability, their soft body, their habitat on rocks, their slow movement and bright colors, for these reason these organisms are able to produce chemical substances as defense methods against depredators. Same mechanism is exhibit by the seaweeds with the production of secondary metabolites . In the present communication are exposed the main results obtained on the world a Cuba until the present in the looking for of substances with antitumor action from marine organism

  9. B P Das

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. B P Das. Articles written in Bulletin of Materials Science. Volume 25 Issue 6 November 2002 pp 517-519. Structural, dielectric and electrical properties of Sm-modified Pb(SnTi)O3 ferroelectric system · B P Das R N P Choudhary P K Mahapatra · More Details Abstract Fulltext ...

  10. A K Das

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. A K Das. Articles written in Bulletin of Materials Science. Volume 28 Issue 2 April 2005 pp 131-136 Fly Ash. Some studies on the reaction between fly ash and lime · A Basumajumdar A K Das N Bandyopadhyay S Maitra · More Details Abstract Fulltext PDF. The reaction between ...

  11. S K Das

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. S K Das. Articles written in Bulletin of Materials Science. Volume 24 Issue 4 August 2001 pp 373-378 Metals and Alloys. Evaluation of solid–liquid interface profile during continuous casting by a spline based formalism · S K Das · More Details Abstract Fulltext PDF. A numerical ...

  12. P Chaitanya Das

    Indian Academy of Sciences (India)

    P Chaitanya Das G Srinivasa Murthy C P Gopalakrishnan P C Deshmukh · More Details Fulltext PDF. Volume 9 Issue 7 July 2004 pp 77-85 Classroom. Motion of Charged Particles in Electromagnetic Fields and Special Theory of Relativity · P Chaitanya Das G Srinivasa Murthy P C Deshmukh K Satish Kumar T A Venkatesh.

  13. I M L Das

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. I M L Das. Articles written in Bulletin of Materials Science. Volume 33 Issue 4 August 2010 pp 383-390 Electrical Properties. Temperature dependence of electromechanical properties of PLZT /57/43 ceramics · A K Shukla V K Agrawal I M L Das Janardan Singh S L Srivastava.

  14. P K Das

    Indian Academy of Sciences (India)

    Home; Journals; Bulletin of Materials Science. P K Das. Articles written in Bulletin of Materials Science. Volume 23 Issue 4 August 2000 pp 249-253 Nitride Ceramics. Optimization of time–temperature schedule for nitridation of silicon compact on the basis of silicon and nitrogen reaction kinetics · J Rakshit P K Das.

  15. MiDAS

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Saunders, Aaron Marc; Albertsen, Mads

    2015-01-01

    The Microbial Database for Activated Sludge (MiDAS) field guide is a freely available online resource linking the identity of abundant and process critical microorganisms in activated sludge wastewater treatment systems to available data related to their functional importance. Phenotypic properties...... of some of these genera are described, but most are known only from sequence data. The MiDAS taxonomy is a manual curation of the SILVA taxonomy that proposes a name for all genus-level taxa observed to be abundant by large-scale 16 S rRNA gene amplicon sequencing of full-scale activated sludge...... communities. The taxonomy can be used to classify unknown sequences, and the online MiDAS field guide links the identity to the available information about their morphology, diversity, physiology and distribution. The use of a common taxonomy across the field will provide a solid foundation for the study...

  16. Redox cycling of potential antitumor aziridinylquinones

    NARCIS (Netherlands)

    Lusthof, Klaas J.; de Mol, Nicolaas J.; Richter, Wilma; Janssen, Lambert H.M.; Butler, John; Hoey, Brigid M.; Verboom, Willem; Reinhoudt, David

    1992-01-01

    The formation of reactive oxygen intermediates (ROI) during redox cycling of newly synthetized potential antitumor 2,5-bis (1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives has been studied by assaying the production of ROI (superoxide, hydroxyl radical, and hydrogen peroxide) by xanthine oxidase

  17. Hypoxia-targeting antitumor prodrugs and photosensitizers

    International Nuclear Information System (INIS)

    Zhang Zhouen; Nishimoto, S.I.

    2006-01-01

    Tumor hypoxia has been identified as a key subject for tumor therapy, since hypoxic tumor cells show resistance to treatment of tumor tissues by radiotherapy, chemotherapy and phototherapy. For improvement of tumor radiotherapy, we have proposed a series of radiation-activated prodrugs that could selectively release antitumor agent 5-fluorouracil or 5-fluorodeoxyuridine under hypoxic conditions. Recently, we attempted to develop two families of novel hypoxia-targeting antitumor agents, considering that tumor-hypoxic environment is favorable to biological and photochemical reductions. The first family of prodrugs was derived from camptothecin as a potent topoisomerase I inhibitor and several bioreductive motifs. These prodrugs could be activated by NADPH-cytochrome P450 reductase or DT-diaphorase to release free camptothecin, and thereby showed hypoxia-selective cytotoxictiy towards tumor cells. These prodrugs were also applicable to the real-time monitoring of activation and antitumor effect by fluorometry. Furthermore, the camptothecin-bioreductive motif conjugates was confirmed to show an oxygen-independent DAN photocleaving activity, which could overcome a drawback of back electron transfer occurring in the photosensitized one-electron oxidation of DNA. Thus, these camptothecin derivatives could be useful to both chemotherapy and phototherapy for hypoxic tumor cells. The second family of prodrugs harnessed UV light for cancer therapy, incorporating the antitumor agent 5-fluorourcil and the photolabile 2-nitrobenzyl chromophores. The attachment of a tumor-homing cyclic peptide CNGRC was also employed to construct the prototype of tumor-targeting photoactiaved antitumor prodrug. These novel prodrugs released high yield of 5-fluorourcil upon UV irradiation at λ ex =365 nm, while being quite stable in the dark. The photoactivation mechanism was also clarified by means of nanosecond laser flash photolysis. (authors)

  18. Das, Prof. Gobardhan

    Indian Academy of Sciences (India)

    Das, Prof. Gobardhan Ph.D. (Imtech), FNASc. Date of birth: 10 December 1966. Specialization: Immunology, Infectious Diseases, Cell Biology Address: Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110 067, U.T.. Contact: Office: (011) 2670 4559, 2673 8824. Residence: (0124) 424 2351

  19. Sarma, Prof. Dipankar Das

    Indian Academy of Sciences (India)

    Home; Fellowship. Fellow Profile. Elected: 1993 Section: Chemistry. Sarma, Prof. Dipankar Das Ph.D. (IISc), FNA, FNASc, FTWAS Council Service: 2016-. Date of birth: 15 September 1955. Specialization: Strongly Interacting Electron Systems, Disordered Systems, Nanomaterials and Energy Materials Address: Professor ...

  20. Ikea das Rendas

    OpenAIRE

    Bergman, Aeron; Salinas, Alejandra

    2008-01-01

    FIALENA fabric design by Anna Svanfeldt for IKEA of Sweden. It took Maria da Guia 2 months to reproduce the Ikea pattern using traditional Portuguese improvised knots. 2008 Installasjon i Museu das Rendas, Vila do Conde, Portugal, 01.09.2008 - 01.10.2008. Sponsor: City of Villa do Conde.

  1. Das Kapital e Eu

    Directory of Open Access Journals (Sweden)

    David Schweickart

    2017-11-01

    Full Text Available A partir da sua própria biografia, o autor ensaia sobre sua interpretação de Das Kapital, de Karl Marx. Argumenta sobre a exploração capitalista, sobre o fetichismo e aponta para o problema central do capitalismo: a falta de controle dos concernidos sobre a produção de produtor úteis.

  2. Das, Prof. Saumitra

    Indian Academy of Sciences (India)

    Fellow Profile. Elected: 2009 Section: General Biology. Das, Prof. Saumitra Ph.D. (Calcutta), FNASc, FNA. Date of birth: 20 January 1962. Specialization: Molecular Virology, Molecular Biology and Cell Biology Address: Microbiology and Cell Biology Department, Indian Institute of Science, Bengaluru 560 012, Karnataka

  3. Antitumor and immunomodulatory activity of Inonotus obliquus

    Directory of Open Access Journals (Sweden)

    Staniszewska Justyna

    2017-06-01

    Full Text Available The article presents the antitumor and immunomodulatory activity of compounds and extracts from Inonotus obliquus. Polysaccharides isolated from sclerotium have a direct antitumor effect due to protein synthesis inhibition in tumor cells. Polysaccharides derived from the mycelium function by activating the immune system. Due to the limited toxicity of these substances, both extracts as well as isolated and purified chemicals may be a good alternative to current chemotherapy and play a role in cancer prevention. In vitro experiments have shown the inhibition of inflammation with the influence of action of I. obliquus extracts; however, in vivo experiments on animals implanted with tumor cells of different types have shown the activation of the host immune system. This led to decrease in tumor mass and prolonged survival. The immunomodulatory mechanism of action is complex and it seems that stimulation of macrophages and induction of apoptosis in cancer cells is of great importance.

  4. Antitumor Activities of Kushen: Literature Review

    Directory of Open Access Journals (Sweden)

    Mingyu Sun

    2012-01-01

    Full Text Available To discover and develop novel natural compounds with therapeutic selectivity or that can preferentially kill cancer cells without significant toxicity to normal cells is an important area in cancer chemotherapy. Kushen, the dried roots of Sophora flavescens Aiton, has a long history of use in traditional Chinese medicine to treat inflammatory diseases and cancer. Kushen alkaloids (KS-As and kushen flavonoids (KS-Fs are well-characterized components in kushen. KS-As containing oxymatrine, matrine, and total alkaloids have been developed in China as anticancer drugs. More potent antitumor activities were identified in KS-Fs than in KS-As in vitro and in vivo. KS-Fs may be developed as novel antitumor agents.

  5. PENGELOLAAN DAS CITARUM BERKELANJUTAN

    OpenAIRE

    kurniasih, nia

    2011-01-01

    Sungai citarum merupakan sungai utama di DAS Citarum yang dimanfaatkan untuk berbagai keperluan, tidak hanya digunakan oleh 7 kabupaten dan 2 Kota di Jawa Barat tetapi juga sebagai sumber air baku air minum Kota Jakarta. Penurunan kualitas maupun kuantitas Sungai Citarum sudah sangat memprihatinkan, kondisi tersebut diakibatkan oleh kesadaran masyarakat dan pemerintah yang belu optimal. Peraturan-peraturan Pemerintah sudah ada tetapi pelaksanaan dilapangan belum maksimal dibarengi penegakan h...

  6. Das DNA-Puzzle

    Science.gov (United States)

    Kirchner, Stefan

    Im Jahre 1953 wurde von James Watson und Francis Crick erstmalig der strukturelle Aufbau der sogenannten DNA (Desoxyribonukleinsäure) beschrieben, welche das Erbgut jedes Lebewesens enthält. Der wesentliche Teil des Erbguts wird dabei durch eine sehr lange Folge der vier Basen Adenin (A), Cytosin (C), Guanin (G) und Thymin (T) codiert. Seit einigen Jahren ist es möglich, die Folge der vier Basen zu einer gegebenen DNA zu bestimmen. Biologen bezeichnen diesen Vorgang als Sequenzierung.

  7. Impact of antitumor therapy on nutrition

    International Nuclear Information System (INIS)

    Kokal, W.A.

    1985-01-01

    The treatment of the cancer patient by surgery, chemotherapy or radiation therapy can impose significant nutritional disabilities on the host. The nutritional disabilities seen in the tumor-bearing host from antitumor therapy are produced by factors which either limit oral intake or cause malabsorption of nutrients. The host malnutrition caused as a consequence of surgery, chemotherapy or radiation therapy assumes even more importance when one realizes that many cancer patients are already debilitated from their disease

  8. Systematic screening of bryophytes for antitumor agents

    OpenAIRE

    Spjut, Richard W.; Kingston, David G. I.; Cassady, John M.

    1992-01-01

    References are made to cytotoxic and/or antitumor compounds that have been isolated - ansamitocin P-3 from Claopodium crispifolium (Hook.) Ren. & Card. and Anomodon attenuatus Hueb., or an associated actinomycete, and ohioensins and pallidisetums from Polytrichum spp. Several hundred collections, which have been obtained from temperate regions of North America during 1990 and 1991, are currently being screened in new bioassays; active sesquiterpene lactones have been recently isolated from sp...

  9. Antitumor Immunity Is Controlled by Tetraspanin Proteins

    Directory of Open Access Journals (Sweden)

    Fleur Schaper

    2018-05-01

    Full Text Available Antitumor immunity is shaped by the different types of immune cells that are present in the tumor microenvironment (TME. In particular, environmental signals (for instance, soluble factors or cell–cell contact transmitted through the plasma membrane determine whether immune cells are activated or inhibited. Tetraspanin proteins are emerging as central building blocks of the plasma membrane by their capacity to cluster immune receptors, enzymes, and signaling molecules into the tetraspanin web. Whereas some tetraspanins (CD81, CD151, CD9 are widely and broadly expressed, others (CD53, CD37, Tssc6 have an expression pattern restricted to hematopoietic cells. Studies using genetic mouse models have identified important immunological functions of these tetraspanins on different leukocyte subsets, and as such, may be involved in the immune response against tumors. While multiple studies have been performed with regards to deciphering the function of tetraspanins on cancer cells, the effect of tetraspanins on immune cells in the antitumor response remains understudied. In this review, we will focus on tetraspanins expressed by immune cells and discuss their potential role in antitumor immunity. New insights in tetraspanin function in the TME and possible prognostic and therapeutic roles of tetraspanins will be discussed.

  10. MiDAS

    DEFF Research Database (Denmark)

    McIlroy, Simon Jon; Kirkegaard, Rasmus Hansen; McIlroy, Bianca

    A deep understanding of the microbial communities and dynamics in wastewater treatment systems is a powerful tool for process optimization and design (Rittmann et al., 2006). With the advent of amplicon sequencing of the 16S rRNA gene, the diversity within the microbial communities can now...... web platform about the microbes in activated sludge and their associated ADs. The MiDAS taxonomy proposes putative names for each genus-level-taxon that can be used as a common vocabulary for all researchers in the field....

  11. Das ATHENA-Projekt: [

    Directory of Open Access Journals (Sweden)

    Passenheim, Renate

    2006-02-01

    Full Text Available [english] Since the winter semester of 2002/03, the Medical Faculty of the University of Heidelberg has been using the electronic learning environment ATHENA. It is the "virtual bulletin board" for the exchange and provision of information on the study of medicine within the faculty. Since 2004/05, the platform has been operated using the open source system LRN. The system is used with the focus on document management. The use of the interactive learning contents and programme takes place as a web-based support of the required attendance classes and independent study. The tools available on the platform are used within the departments for the integration of computer-assisted examination concepts, and the conducting of online course evaluations. [german] Seit dem Wintersemester 2002/03 setzt die Medizinische Fakultät Heidelberg die elektronische Lernumgebung ATHENA ein. Sie ist das "Virtuelle Schwarze Brett" für den Austausch und die Bereitstellung von Informationen zum Medizinstudium an der Fakultät. Seit 2004/05 wird die Plattform mit dem Open-Source-System .LRN betrieben. Das System wird eingesetzt mit dem Schwerpunkt der Kurs- und Dokumentenverwaltung. Die Nutzung der interaktiven Lerninhalte und -programme erfolgt als webbasierte Unterstützung der Präsenzveranstaltungen sowie im Selbststudium. Die in der Plattform verfügbaren Tools werden in den Fachbereichen zur Integration computerunterstützter Prüfungskonzepte sowie zur Durchführung von Online-Kursevaluationen eingesetzt.

  12. Antitumor activity of Annona squamosa seed oil.

    Science.gov (United States)

    Chen, Yong; Chen, Yayun; Shi, Yeye; Ma, Chengyao; Wang, Xunan; Li, Yue; Miao, Yunjie; Chen, Jianwei; Li, Xiang

    2016-12-04

    Custard apple (Annona squamosa Linn.) is an edible tropical fruit, and its seeds have been used to treat "malignant sore" (cancer) and other usage as insecticide. A comparison of extraction processes, chemical composition analysis and antitumor activity of A. squamosa seed oil (ASO) were investigated. The optimal extraction parameters of ASO were established by comparing percolation, soxhlet, ultrasonic and SFE-CO 2 extraction methods. The chemical composition of fatty acid and content of total annonaceous acetogenins (ACGs) of ASO was investigated by GC-MS and colorimetric assay, and anti-tumor activity of ASO was tested using H 22 xenografts bearing mice. The optimal extraction parameters of ASO were obtained as follows: using soxhlet extraction method with extraction solvent of petroleum ether, temperature of 80°C, and extraction time of 90min. Under these conditions, the yield of ASO was 22.65%. GC-MS analysis results showed that the main chemical compositions of fatty acid of ASO were palmitic acid (9.92%), linoleic acid (20.49%), oleic acid (56.50%) and stearic acid (9.14%). The total ACGs content in ASO was 41.00mg/g. ASO inhibited the growth of H 22 tumor cells in mice with a maximum inhibitory rate of 53.54% by oral administration. Furthermore, it was found that ASO exerted an antitumor effect via decreasing interleukin-6 (IL-6), janus kinase (Jak) and phosphorylated signal transducers and activators of transcription (p-Stat3) expression. The results demonstrated that ASO suppressed the H 22 solid tumor development may due to its main chemical constituents unsaturated fatty acid and ACGs via IL-6/Jak/Stat3 pathway. ASO may be a potential candidate for the treatment of cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Das Reflektierende Team

    DEFF Research Database (Denmark)

    Gaarden, Marianne; Lorensen, Marlene Ringgaard

    2015-01-01

    Jüngere empirische Forschung dazu, wie Predigthörende Predigten wahrnehmen und mit ihnen interagieren, deutet darauf hin, dass Predigende als Gesprächspartner und als theologischer Spiegel der Gemeinde wahrgenommen werden. Die Gemeinde gelangt im Dialog mit den Worten der Predigt zu eigenen...... Bedeutungszuschreibungen. Marianne Gaardens Forschung zeigt, dass zwischen Predigenden und Hörenden ein ›dritter Raum‹ entsteht, wie sie das nennt. Dabei handelt es sich um einen liminalen, rituell konturierten Raum, in dem Hörende Predigtelemente rezipieren und in ihre eigenen gelebten Erfahrungen einbauen. Komplementär...... die Wahrnehmung der Predigt als eines dialogischen Geschehens – und zwar von der Predigtvorbereitung über die Interaktion mit Hörenden und anschließende Rückmeldungen bis hin zu Umarbeitungen und Überlegungen für die nächsten Predigt. Die Methode geht davon aus, dass einzelne Subjekte Teil einer...

  14. Anti-tumor effect of polysaccharides from rhizome of Curculigo ...

    African Journals Online (AJOL)

    The anti-tumor effect of PDC on cervical cancer was investigated in vivo in mice injected with Hela cells. The parameters measured were tumor volume and weight. In vitro anti-tumor effects of PDC were assessed by measuring expressions of caspase-3, caspase-9 and P53 proteins in Hela cells via ELISA assay. Thymus ...

  15. Smart Mesoporous Nanomaterials for Antitumor Therapy

    Directory of Open Access Journals (Sweden)

    Marina Martínez-Carmona

    2015-11-01

    Full Text Available The use of nanomaterials for the treatment of solid tumours is receiving increasing attention by the scientific community. Among them, mesoporous silica nanoparticles (MSNs exhibit unique features that make them suitable nanocarriers to host, transport and protect drug molecules until the target is reached. It is possible to incorporate different targeting ligands to the outermost surface of MSNs to selectively drive the drugs to the tumour tissues. To prevent the premature release of the cargo entrapped in the mesopores, it is feasible to cap the pore entrances using stimuli-responsive nanogates. Therefore, upon exposure to internal (pH, enzymes, glutathione, etc. or external (temperature, light, magnetic field, etc. stimuli, the pore opening takes place and the release of the entrapped cargo occurs. These smart MSNs are capable of selectively reaching and accumulating at the target tissue and releasing the entrapped drug in a specific and controlled fashion, constituting a promising alternative to conventional chemotherapy, which is typically associated with undesired side effects. In this review, we overview the recent advances reported by the scientific community in developing MSNs for antitumor therapy. We highlight the possibility to design multifunctional nanosystems using different therapeutic approaches aimed at increasing the efficacy of the antitumor treatment.

  16. Induction of antitumor immunity through xenoplacental immunization

    Directory of Open Access Journals (Sweden)

    Agadjanyan Michael G

    2006-05-01

    Full Text Available Abstract Historically cancer vaccines have yielded suboptimal clinical results. We have developed a novel strategy for eliciting antitumor immunity based upon homology between neoplastic tissue and the developing placenta. Placenta formation shares several key processes with neoplasia, namely: angiogenesis, activation of matrix metalloproteases, and active suppression of immune function. Immune responses against xenoantigens are well known to break self-tolerance. Utilizing xenogeneic placental protein extracts as a vaccine, we have successfully induced anti-tumor immunity against B16 melanoma in C57/BL6 mice, whereas control xenogeneic extracts and B16 tumor extracts where ineffective, or actually promoted tumor growth, respectively. Furthermore, dendritic cells were able to prime tumor immunity when pulsed with the placental xenoantigens. While vaccination-induced tumor regression was abolished in mice depleted of CD4 T cells, both CD4 and CD8 cells were needed to adoptively transfer immunity to naïve mice. Supporting the role of CD8 cells in controlling tumor growth are findings that only freshly isolated CD8 cells from immunized mice were capable of inducing tumor cell caspases-3 activation ex vivo. These data suggest feasibility of using xenogeneic placental preparations as a multivalent vaccine potently targeting not just tumor antigens, but processes that are essential for tumor maintenance of malignant potential.

  17. easyDAS: Automatic creation of DAS servers

    Directory of Open Access Journals (Sweden)

    Jimenez Rafael C

    2011-01-01

    Full Text Available Abstract Background The Distributed Annotation System (DAS has proven to be a successful way to publish and share biological data. Although there are more than 750 active registered servers from around 50 organizations, setting up a DAS server comprises a fair amount of work, making it difficult for many research groups to share their biological annotations. Given the clear advantage that the generalized sharing of relevant biological data is for the research community it would be desirable to facilitate the sharing process. Results Here we present easyDAS, a web-based system enabling anyone to publish biological annotations with just some clicks. The system, available at http://www.ebi.ac.uk/panda-srv/easydas is capable of reading different standard data file formats, process the data and create a new publicly available DAS source in a completely automated way. The created sources are hosted on the EBI systems and can take advantage of its high storage capacity and network connection, freeing the data provider from any network management work. easyDAS is an open source project under the GNU LGPL license. Conclusions easyDAS is an automated DAS source creation system which can help many researchers in sharing their biological data, potentially increasing the amount of relevant biological data available to the scientific community.

  18. Origens das formas budistas

    Directory of Open Access Journals (Sweden)

    Fernando Carlos Chamas

    Full Text Available RESUMO As características de uma imagem de Buda são o resultado do processo milenar que uniu três fatores: as mitologias orientais mais antigas que o budismo, sua capacidade de se adequar às crenças locais e as suas próprias reinterpretações. Após o surgimento das primeiras estátuas que representavam o Buda histórico, o ideal de beleza para um ser que alcançou a Iluminação baseou-se nas antigas "ciências" orientais, predominantemente mentais e de energias sutis. Enquanto a estética ocidental discutia as idealizações da arte com racionalidade, ignorando um oriente "pagão e supersticioso", as imagens budistas personificavam estados mentais que o ocidente só cogitaria na sua modernidade. A arte budista transmite o legado ancestral e imutável de chaves místicas da consciência e do equilíbrio..

  19. Bingo das Ervilhas

    Directory of Open Access Journals (Sweden)

    Luciana Bonato Lovato

    2016-12-01

    Full Text Available Este artigo analisa a utilização de um jogo didático sobre conteúdos de Genética ministrados no Ensino Fundamental. O material utilizado foi elaborado a partir da literatura existente e trabalhado sob a forma de uma oficina ministrada a professores de Ensino Fundamental e Médio de escolas de abrangência da 4a. Coordenadoria Regional de Educação do Rio Grande do Sul. A oferta desta oficina partiu do pressuposto de que os jogos educacionais são uma importante estratégia no processo de ensino-aprendizagem por se tratarem de uma ferramenta facilitadora nas aulas de Ciências, uma vez que contribuem para a aprendizagem de conceitos e termos complexos de maneira lúdica e estimulam o desenvolvimento das competências dos educandos. Todos os participantes consideraram que a oficina realizada contribuirá para sua prática docente, e acreditam que os jogos didáticos oferecem experiências de aprendizado que contribuem para construção do conhecimento.

  20. Desvelando a Internet das Coisas

    Directory of Open Access Journals (Sweden)

    Lucia Santaella

    2013-12-01

    Full Text Available O presente artigo pretende relatar as origens da Internet das Coisas, seu estado de arte e evidenciar seus principais vetores. Para tal, o estudo percorrerá as eras midiáticas de Santaella (2007, p. 179-189, a par da discussão das máquinas de Turing, da arquitetura Von Neumann até chegar à Internet e seu estado atual, implementada nas coisas.

  1. Assessment of in vitro antitumoral and antimicrobial activities of ...

    African Journals Online (AJOL)

    Assessment of in vitro antitumoral and antimicrobial activities of marine algae harvested from the eastern Mediterranean sea. ... African Journal of Biotechnology ... algal extracts obtained from the marine algae Scytosiphon lomentaria, Padina pavonica, Cystoseira mediterranea (Phaeophyceae), Hypnea musciformis and ...

  2. Effects of Androgen Ablation on Anti-Tumor Immunity

    National Research Council Canada - National Science Library

    Kast, Martin

    2004-01-01

    .... This AA induced autoimmune-like response exerts limited anti-tumor activity in a murine prostate cancer model, but could be synergistic with CTLA-4 blockade that promotes the development of autoreactive T cell...

  3. Gut microbiome can control antitumor immune function in liver

    Science.gov (United States)

    An NCI study in mice that found a connection between gut bacteria and antitumor immune responses in the liver has implications for understanding mechanisms that lead to liver cancer and for potential treatments. The study was published in Science.

  4. Antitumor effects and mechanisms of Ganoderma extracts and spores oil

    OpenAIRE

    Chen, Chun; Li, Peng; Li, Ye; Yao, Guan; Xu, Jian-Hua

    2016-01-01

    Ganoderma lucidum is a popular herbal medicine used in China to promote health. Modern studies have disclosed that the active ingredients of Ganoderma can exhibit several effects, including antitumor effects and immunomodulation. The present study evaluated the antitumor effects of self-prepared Ganoderma extracts and spores oil, and investigated the possible underlying mechanisms by observing the effects of the extracts and oil on topoisomerases and the cell cycle. The results showed that Ga...

  5. Advanced nanocarriers for an antitumor peptide

    Energy Technology Data Exchange (ETDEWEB)

    Pippa, Natassa [National and Kapodistrian University of Athens, Department of Pharmaceutical Technology, Faculty of Pharmacy (Greece); Pispas, Stergios [National Hellenic Research Foundation, Theoretical and Physical Chemistry Institute (Greece); Demetzos, Costas, E-mail: demetzos@pharm.uoa.gr [National and Kapodistrian University of Athens, Department of Pharmaceutical Technology, Faculty of Pharmacy (Greece); Sivolapenko, Gregory [University of Patras, Laboratory of Pharmacokinetics, Department of Pharmacy (Greece)

    2013-11-15

    In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic, and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Egg phosphatidylcholine (EggPC) and dipalmytoylphosphatidylcholine (DPPC) (EggPC:PCK3145 and DPPC:PCK3145, 9:0.2 molar ratio), into cationic liposomes composed of EggPC:SA:PCK3145 and DPPC:SA:PCK3145 (9:1:0.2 molar ratio) into complexes with the block polyelectrolyte (quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO) and finally into dendrimeric structures (i.e., PAMAM G4). Light scattering techniques are used in order to examine the size, the size distribution and the Z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules.

  6. Antitumor Effect of Burchellin Derivatives Against Neuroblastoma.

    Science.gov (United States)

    Kurita, Masahiro; Takada, Tomomi; Wakabayashi, Noriko; Asami, Satoru; Ono, Shinichi; Uchiyama, Taketo; Suzuki, Takashi

    2018-02-01

    Neuroblastoma is one of the most commonly encountered malignant solid tumors in the pediatric age group. We examined the antitumor effects of five burchellin derivatives against human neuroblastoma cell lines. We evaluated cytotoxicity by the MTT assay for four human neuroblastoma and two normal cell lines. We also performed analysis of the apoptotic induction effect by flow cytometry, and examined the expression levels of apoptosis- and cell growth-related proteins by western blot analysis. We found that one of the burchellin derivatives (compound 4 ) exerted cytotoxicity against the neuroblastoma cell lines. Compound 4 induced caspase-dependent apoptosis via a mitochondrial pathway. The apoptosis mechanisms induced by compound 4 involved caspase-3, -7 and -9 activation and poly (ADP-ribose) polymerase cleavage. In addition, compound 4 induced cell death through inhibition of the cell growth pathway (via extracellular signal-regulated kinase 1 and 2, AKT8 virus oncogene cellular homolog, and signal transducer and activator of transcription 3). Compound 4 exerted cellular cytotoxicity against neuroblastoma cells via induction of caspase-dependent apoptosis, and may offer promise for further development as a useful drug for the treatment of advanced neuroblastoma. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Advanced nanocarriers for an antitumor peptide

    International Nuclear Information System (INIS)

    Pippa, Natassa; Pispas, Stergios; Demetzos, Costas; Sivolapenko, Gregory

    2013-01-01

    In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic, and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Egg phosphatidylcholine (EggPC) and dipalmytoylphosphatidylcholine (DPPC) (EggPC:PCK3145 and DPPC:PCK3145, 9:0.2 molar ratio), into cationic liposomes composed of EggPC:SA:PCK3145 and DPPC:SA:PCK3145 (9:1:0.2 molar ratio) into complexes with the block polyelectrolyte (quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO) and finally into dendrimeric structures (i.e., PAMAM G4). Light scattering techniques are used in order to examine the size, the size distribution and the Z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules

  8. Antitumoral activity of marine organism; Actividad antitumoral de los organismos marinos

    Energy Technology Data Exchange (ETDEWEB)

    Valdes Iglesias, O [Centro de Bioproductos Marinos, La Habana (Cuba); Perez Gil, R; Colom, Y [Instituno Nacional de Oncologia y Radiobiologia (INOR), La Habana (Cuba)

    2010-07-01

    The study of the natural products from marine organism constitute a relatively recent scientific researcher field with high potentialities tanking in consideration that the oceans cover the three of the four parts of the earth. Poryphera and Bryozoans have been the Phylum more studied owning to the vulnerability, their soft body, their habitat on rocks, their slow movement and bright colors, for these reason these organisms are able to produce chemical substances as defense methods against depredators. Same mechanism is exhibit by the seaweeds with the production of secondary metabolites . In the present communication are exposed the main results obtained on the world a Cuba until the present in the looking for of substances with antitumor action from marine organism.

  9. Fractionated photothermal antitumor therapy with multidye nanoparticles

    Directory of Open Access Journals (Sweden)

    Gutwein LG

    2012-01-01

    Full Text Available Luke G Gutwein1, Amit K Singh2, Megan A Hahn2, Michael C Rule3, Jacquelyn A Knapik4, Brij M Moudgil2, Scott C Brown2, Stephen R Grobmyer11Division of Surgical Oncology, Department of Surgery, College of Medicine, 2Particle Engineering Research Center, 3Cell and Tissue Analysis Core, McKnight Brain Institute, 4Department of Pathology, University of Florida, Gainesville, FL, USAPurpose: Photothermal therapy is an emerging cancer treatment paradigm which involves highly localized heating and killing of tumor cells, due to the presence of nanomaterials that can strongly absorb near-infrared (NIR light. In addition to having deep penetration depths in tissue, NIR light is innocuous to normal cells. Little is known currently about the fate of nanomaterials post photothermal ablation and the implications thereof. The purpose of this investigation was to define the intratumoral fate of nanoparticles (NPs after photothermal therapy in vivo and characterize the use of novel multidye theranostic NPs (MDT-NPs for fractionated photothermal antitumor therapy.Methods: The photothermal and fluorescent properties of MDT-NPs were first characterized. To investigate the fate of nanomaterials following photothermal ablation in vivo, novel MDT-NPs and a murine mammary tumor model were used. Intratumoral injection of MDT-NPs and real-time fluorescence imaging before and after fractionated photothermal therapy was performed to study the intratumoral fate of MDT-NPs. Gross tumor and histological changes were made comparing MDT-NP treated and control tumor-bearing mice.Results: The dual dye-loaded mesoporous NPs (ie, MDT-NPs; circa 100 nm retained both their NIR absorbing and NIR fluorescent capabilities after photoactivation. In vivo MDT-NPs remained localized in the intratumoral position after photothermal ablation. With fractionated photothermal therapy, there was significant treatment effect observed macroscopically (P = 0.026 in experimental tumor-bearing mice

  10. Homeostatic T Cell Expansion to Induce Anti-Tumor Autoimmunity in Breast Cancer

    National Research Council Canada - National Science Library

    Baccala, Roberto

    2007-01-01

    ... that (a) homeostatic T-cell proliferation consistently elicits anti-tumor responses; (b) irradiation is more effective than Tcell depletion by antibodies in inducing anti-tumor responses mediated by homeostatic T-cell proliferation...

  11. Hydroxyurea derivatives of irofulven with improved antitumor efficacy.

    Science.gov (United States)

    Staake, Michael D; Kashinatham, Alisala; McMorris, Trevor C; Estes, Leita A; Kelner, Michael J

    2016-04-01

    Irofulven is a semi-synthetic derivative of Illudin S, a toxic sesquiterpene isolated from the mushroom Omphalotus illudens. Irofulven has displayed significant antitumor activity in various clinical trials but displayed a limited therapeutic index. A new derivative of irofulven was prepared by reacting hydroxyurea with irofulven under acidic conditions. Acetylation of this new compound with acetic anhydride produced a second derivative. Both of these new derivatives displayed significant antitumor activity in vitro and in vivo comparable to or exceeding that of irofulven. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Modification of carcinogenic and antitumor radiation effects (biomedical aspects)

    International Nuclear Information System (INIS)

    Vilenchik, M.M.

    1985-01-01

    In the book the data on modification of carcinogenic radiation effects by physiologicaly active compounds (caffeine, hormones, promoters and others) as well as on potentiation of antitumor radiation effects by means of hyperthermia are systematized. It is shown that as a basis of synergetic (superadditive) carcinogenic or antitumor radiation effects combined with other factor can be the inhibiting effects of the latter on the reparation process of radiation-induced DNA injuries. The results of experimental investigations and the data on quantitative analysis can be used as a theoretical basis for improvement of the ways and means of the prophylaxis of tumor diseases as well as for increasing the efficiency of radiotherapy

  13. An Update on Antitumor Activity of Naturally Occurring Chalcones

    Directory of Open Access Journals (Sweden)

    En-Hui Zhang

    2013-01-01

    Full Text Available Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades.

  14. The anti-tumor effect and biological activities of the extract JMM6 ...

    African Journals Online (AJOL)

    Juglans mandshurica Maxim is a traditional herbal medicines in China, and its anti-tumor bioactivities are of research interest. Bioassay-guided fractionation method was employed to isolate anti-tumor compounds from the stem barks of the Juglans mandshurica Maxim. The anti-tumor effect and biological activities of the ...

  15. Antitumor Properties of Modified Detonation Nanodiamonds and Sorbed Doxorubicin on the Model of Ehrlich Ascites Carcinoma.

    Science.gov (United States)

    Medvedeva, N N; Zhukov, E L; Inzhevatkin, E V; Bezzabotnov, V E

    2016-01-01

    We studied antitumor properties of modified detonation nanodiamonds loaded with doxorubicin on in vivo model of Ehrlich ascites carcinoma. The type of tumor development and morphological characteristics of the liver, kidneys, and spleen were evaluated in experimental animals. Modified nanodiamonds injected intraperitoneally produced no antitumor effect on Ehrlich carcinoma. However, doxorubicin did not lose antitumor activity after sorption on modified nanodiamonds.

  16. Das DELA-NOBA Projekt

    DEFF Research Database (Denmark)

    Daryai-Hansen, Petra; Meister, Maive; Tonello, Elisa

    2015-01-01

    in the English language classroom in Argentina and Denmark var et delprojekt under et større internationalt samarbejde, koordineret af Michael Byram, og belyste, hvordan interkulturelt medborgerskab kan styrkes i grundskolens læringsrum (Byram et al. under udgivelse). Grundidéen i interkulturelle......Artiklen præsenterer et udviklings- og forskningsprojekt på Randersgades Skole. I projektet deltog elever fra 7.v og en 5./6. klasse fra Argentina i et arrangeret kultur- og sprogmøde inden for rammerne af deres engelskundervisning. Projektet Green Kidz. Intercultural environmental citizenship...... langues-Ansatz noch weitreichend unbekannt. Das Projekt Developing the Language Awareness/ Éveil aux langues Approach in the Nordic and Baltic Countries (DELA- NOBA), das von 2013 bis 2016 von NordPlus Horizontal finanziert wird, etabliert eine Zusammenarbeit zwischen Universitäten und Pilotschulen aus...

  17. Update of PPPL's DAS-1800

    International Nuclear Information System (INIS)

    Booth, K.H.

    1976-01-01

    Demand for real-time computer assistance of experiments at PPPL has increased in volume and complexity. The PPPL data acquisition system based on an IBM-1800 has been servicing three experimental devices, ST, FM, and ATC, often concurrently. The requirements of real-time computer support, the acquisition, archiving, analysis, and display of data for these devices, are described. A presentation of the current DAS-1800 system which supports two devices, FM and ATC, includes summaries of additional experiments serviced

  18. Psicoterapia das depressões

    Directory of Open Access Journals (Sweden)

    Sidnei Schestatsky

    1999-05-01

    Full Text Available Os autores examinam o status atual das psicoterapias no tratamento das depressões, principalmente das quatro formas melhor testadas empiricamente nos últimos 10 anos: psicoterapia interpessoal, psicoterapia cognitiva e comportamental, e psicoterapia psicodinâmica breve. São descritos os principais estudos de eficácia dessas psicoterapias assim como uma revisão metaanalítica sobre o assunto. Conclui-se que já há sólidas evidências de bons resultados nas depressões ambulatoriais e unipolares quando tratadas por intervenções psicossociais, combinadas ou não com farmacoterapia.It is examined the present status of psychotherapeutic treatment of depression, specially the impact of the four types of psychotherapy best empirically tested for the past 10 years: interpersonal therapy, cognitive and behavioral therapies, and brief psychodynamic therapy. Both the main efficacy studies of those therapies as well as a meta-analytic review of their results are described. The conclusion is that there are already strong evidences of good outcome when ambulatorial unipolar depression is treated by psychossocial interventions, alone or in combination with pharmacotherapy.

  19. Biochemical and histological evidences for the antitumor potential of ...

    African Journals Online (AJOL)

    Biochemical and histological evidences for the antitumor potential of Teucrium Oliverianum and Rhazya stricta in chemically-induced hepatocellular carcinoma. ... Photomicrograph of liver tissue sections of rats in HCC revealed hepatic parenchyma with foci of anaplastic hepatocellular carcinoma as well as other foci of ...

  20. Cisplatin carbonato complexes. Implications for uptake, antitumor properties, and toxicity.

    Science.gov (United States)

    Centerwall, Corey R; Goodisman, Jerry; Kerwood, Deborah J; Dabrowiak, James C

    2005-09-21

    The reaction of aquated cisplatin with carbonate which is present in culture media and blood is described. The first formed complex is a monochloro monocarbonato species, which upon continued exposure to carbonate slowly forms a biscarbonato complex. The formation of carbonato species under conditions that simulate therapy may have important implications for uptake, antitumor properties, and toxicity of cisplatin.

  1. Juglans regia Hexane Extract Exerts Antitumor Effect, Apoptosis ...

    African Journals Online (AJOL)

    Original Research Article. Juglans regia Hexane Extract Exerts Antitumor Effect,. Apoptosis Induction and Cell Circle Arrest in Prostate. Cancer Cells In vitro. Wei Li1, De-Yuan Li2*, ... composition of walnut is juglone (5-hydroxy-1, 4- naphthoquinone), the .... extract was confirmed by studying apoptotic body formation using ...

  2. Anti-tumor activity of polysaccharides extracted from Senecio ...

    African Journals Online (AJOL)

    *, Bao Zhang, Mingming Han, Xin Jin, Liyuan Sun and Tao Li. Department of ..... Yang J, Li X, Xue Y, Wang N, Liu W. Anti-hepatoma activity and mechanism of corn ... Peng W, Wu JG, Jiang YB, Liu YJ, Sun T, Wu N, Wu CJ. Antitumor activity of ...

  3. Indicine-N-oxide: the antitumor principle of Heliotropium indicum.

    Science.gov (United States)

    Kugelman, M; Liu, W C; Axelrod, M; McBride, T J; Rao, K V

    1976-01-01

    Extracts of Heliotropium indicum Linn. (Boraginaceae) showed significant activity in several experimental tumor systems. The active principle is isolated and shown to be the N-oxide of the alkaloid, indicine, previously isolated from this plant. Supporting structural data and anti-tumor data are provided.

  4. Mechanisms of reduction of antitumor drug toxicity by liposome encapsulation

    Energy Technology Data Exchange (ETDEWEB)

    Rahman, Y. E.; Hanson, W. R.; Bharucha, J.; Ainsworth, E. J.; Jaroslow, B.

    1977-01-01

    The antitumor drug Actinomycin D is effective against the growth of some human solid tumors but its use is limited by its extreme toxicity. The development of a method of administering Act. D to reduce its systemic toxicity by incorporating the drug within liposomes reduced its toxicity but its tumoricidal activity was retained.

  5. Antitumor activity of doxorubicine-loaded nanoemulsion against ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights ... Keywords: Doxorubicine, Anti-tumor activity, Mean survival time, Heart histology, Nanoemulsion, Lipid profile .... the standard kit methods using fully Automated ..... effects of this new formulation in human patients.

  6. Reprogramming Antitumor Immune Responses with microRNAs

    Science.gov (United States)

    2013-10-01

    disease, including cancer etiology (4) and the generation and inhibition of antitumor immune responses (5–9). Biologically active miRNAs bind to MREs...breast, colorectal, lung, pancreatic , and thyroid carcinomas and in liquid tumors including lymphomas and some acute myeloid leukemias (9, 35). The...immunity [9], underscoring the potential of targeting this major microenvironmental compartment. Accumulating evidence suggests that chronic

  7. Anti-tumor effect of polysaccharides isolated from Taraxacum ...

    African Journals Online (AJOL)

    The effects of extraction temperature, liquid-solid ratio and extraction time on the yield of PTM were investigated using a Box-Behnken design (BBD). The in vitro anti-tumor effect of PTM on MCF-7 cells was investigated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, while the mechanism of PTM-induced ...

  8. Anti-tumor activity of polysaccharides extracted from Senecio ...

    African Journals Online (AJOL)

    Purpose: To optimize the extraction conditions of polysaccharides from the root of Senecio scandens Buch,-Ham. (PRS) and evaluate its anti-tumor effect on hepatocellular carcinoma. Methods: Response surface methodology (RSM) applied with a Box-Behnken design (BBD, three levels and three factors) was employed to ...

  9. Antitumor effects and mechanisms of Ganoderma extracts and spores oil.

    Science.gov (United States)

    Chen, Chun; Li, Peng; Li, Ye; Yao, Guan; Xu, Jian-Hua

    2016-11-01

    Ganoderma lucidum is a popular herbal medicine used in China to promote health. Modern studies have disclosed that the active ingredients of Ganoderma can exhibit several effects, including antitumor effects and immunomodulation. The present study evaluated the antitumor effects of self-prepared Ganoderma extracts and spores oil, and investigated the possible underlying mechanisms by observing the effects of the extracts and oil on topoisomerases and the cell cycle. The results showed that Ganoderma extracts and spores oil presented dose-dependent inhibitory effects on tumor cells. The half maximal inhibitory concentration (IC 50 ) values of Ganoderma extracts on HL60, K562 and SGC-7901 cells for 24 h were 0.44, 0.39 and 0.90 mg/ml, respectively; for Ganoderma spores oil, the IC 50 values were 1.13, 2.27 and 6.29 mg/ml, respectively. In the in vivo study, the inhibitory rates of Ganoderma extracts (4 g/kg/d, intragastrically) on S180 and H22 cells were 39.1 and 44.6%, respectively, and for Ganoderma spores oil (1.2 g/kg/d, intragastrically) the inhibitory rates were 30.9 and 44.9%, respectively. Ganoderma extracts and spores oil inhibited the activities of topoisomerase I and II. Ganoderma spores oil was shown block the cell cycle at the transition between the G1 and S phases and induce a marked decrease in cyclin D1 levels in K562 cells, with no significant change in cyclin E level. These results suggest that the Ganoderma extracts and spores oil possessed antitumor effects in the in vitro and in vivo studies. The antitumor mechanisms of the extracts and spores oil were associated with inhibitory effects on topoisomerase I and II activities, and for Ganoderma spores oil, the antitumor effects may also be associated with decreased cyclin D1 levels, thus inducing G1 arrest in the cell cycle.

  10. Antitumor effects and mechanisms of Ganoderma extracts and spores oil

    Science.gov (United States)

    Chen, Chun; Li, Peng; Li, Ye; Yao, Guan; Xu, Jian-Hua

    2016-01-01

    Ganoderma lucidum is a popular herbal medicine used in China to promote health. Modern studies have disclosed that the active ingredients of Ganoderma can exhibit several effects, including antitumor effects and immunomodulation. The present study evaluated the antitumor effects of self-prepared Ganoderma extracts and spores oil, and investigated the possible underlying mechanisms by observing the effects of the extracts and oil on topoisomerases and the cell cycle. The results showed that Ganoderma extracts and spores oil presented dose-dependent inhibitory effects on tumor cells. The half maximal inhibitory concentration (IC50) values of Ganoderma extracts on HL60, K562 and SGC-7901 cells for 24 h were 0.44, 0.39 and 0.90 mg/ml, respectively; for Ganoderma spores oil, the IC50 values were 1.13, 2.27 and 6.29 mg/ml, respectively. In the in vivo study, the inhibitory rates of Ganoderma extracts (4 g/kg/d, intragastrically) on S180 and H22 cells were 39.1 and 44.6%, respectively, and for Ganoderma spores oil (1.2 g/kg/d, intragastrically) the inhibitory rates were 30.9 and 44.9%, respectively. Ganoderma extracts and spores oil inhibited the activities of topoisomerase I and II. Ganoderma spores oil was shown block the cell cycle at the transition between the G1 and S phases and induce a marked decrease in cyclin D1 levels in K562 cells, with no significant change in cyclin E level. These results suggest that the Ganoderma extracts and spores oil possessed antitumor effects in the in vitro and in vivo studies. The antitumor mechanisms of the extracts and spores oil were associated with inhibitory effects on topoisomerase I and II activities, and for Ganoderma spores oil, the antitumor effects may also be associated with decreased cyclin D1 levels, thus inducing G1 arrest in the cell cycle. PMID:27900038

  11. Adenosine can thwart antitumor immune responses elicited by radiotherapy. Therapeutic strategies alleviating protumor ADO activities

    Energy Technology Data Exchange (ETDEWEB)

    Vaupel, Peter [Klinikum rechts der Isar, Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Munich (Germany); Multhoff, Gabriele [Klinikum rechts der Isar, Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Munich (Germany); Helmholtz Zentrum Muenchen, Institute for innovative Radiotherapy (iRT), Experimental Immune Biology, Neuherberg (Germany)

    2016-05-15

    By studying the bioenergetic status we could show that the development of tumor hypoxia is accompanied, apart from myriad other biologically relevant effects, by a substantial accumulation of adenosine (ADO). ADO has been shown to act as a strong immunosuppressive agent in tumors by modulating the innate and adaptive immune system. In contrast to ADO, standard radiotherapy (RT) can either stimulate or abrogate antitumor immune responses. Herein, we present ADO-mediated mechanisms that may thwart antitumor immune responses elicited by RT. An overview of the generation, accumulation, and ADO-related multifaceted inhibition of immune functions, contrasted with the antitumor immune effects of RT, is provided. Upon hypoxic stress, cancer cells release ATP into the extracellular space where nucleotides are converted into ADO by hypoxia-sensitive, membrane-bound ectoenzymes (CD39/CD73). ADO actions are mediated upon binding to surface receptors, mainly A2A receptors on tumor and immune cells. Receptor activation leads to a broad spectrum of strong immunosuppressive properties facilitating tumor escape from immune control. Mechanisms include (1) impaired activity of CD4 + T and CD8 + T, NK cells and dendritic cells (DC), decreased production of immuno-stimulatory lymphokines, and (2) activation of Treg cells, expansion of MDSCs, promotion of M2 macrophages, and increased activity of major immunosuppressive cytokines. In addition, ADO can directly stimulate tumor proliferation and angiogenesis. ADO mechanisms described can thwart antitumor immune responses elicited by RT. Therapeutic strategies alleviating tumor-promoting activities of ADO include respiratory hyperoxia or mild hyperthermia, inhibition of CD39/CD73 ectoenzymes or blockade of A2A receptors, and inhibition of ATP-release channels or ADO transporters. (orig.) [German] Untersuchungen des bioenergetischen Status ergaben, dass Tumorhypoxie neben vielen anderen bedeutsamen biologischen Effekten zu einem starken

  12. Studies on anti-tumor effect of electromagnetic waves

    International Nuclear Information System (INIS)

    Kadota, Ikuhito; Wakabayashi, Toshio; Ogoshi, Kyoji; Kamijo, Akemi

    1995-01-01

    Hyperthermia have treated cancer with thermal effect of electromagnetic waves for biological systems, but the expected effect is not shown. Also non-thermal effect of electromagnetic waves is out of consideration. If irradiation conditions of electromagnetic waves with non-thermal anti-tumor effect are obtained, we can expect newly spread in cancer therapy. We had in vivo experiments that electromagnetic waves were irradiated to mice. In some irradiation conditions, the non-thermal anti-tumor effect of electromagnetic waves showed. In order to specify the irradiation conditions, we had in vitro experiments. We found that activity ratio of tumor cells which was measured by MTT method depended on irradiation time and power of electromagnetic waves. These results are useful for the cancer therapy. (author)

  13. Antitumor Activity of Monoterpenes Found in Essential Oils

    Directory of Open Access Journals (Sweden)

    Marianna Vieira Sobral

    2014-01-01

    Full Text Available Cancer is a complex genetic disease that is a major public health problem worldwide, accounting for about 7 million deaths each year. Many anticancer drugs currently used clinically have been isolated from plant species or are based on such substances. Accumulating data has revealed anticancer activity in plant-derived monoterpenes. In this review the antitumor activity of 37 monoterpenes found in essential oils is discussed. Chemical structures, experimental models, and mechanisms of action for bioactive substances are presented.

  14. Antitumor evaluation of epigallocatechin gallate by colorimetric methods

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Soon Ok [Korean Ginseng and Tobacco Research institute, Daejon (Korea, Republic of); Kim, Il Kwang; Baek, Seung Hwa; Han, Du Seok [Wonkwang Unvi., Iksan (Korea, Republic of)

    1998-08-01

    In the present study, we were evaluated cytotoxic effects of epigallocatechin gallate in human skin melanoma cells such as HTB-69. The light microscopic study showed morphological changes of the treated cells. Disruptions in cell organelles were determined by colorimetric methods; 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, neutral red (NR) assay and sulforhodamine B protein (SRB) as-say. These results suggest that epigallocatechin gallate retains a potential antitumor activity.

  15. Antitumor mechanisms of metformin: Signaling, metabolism, immunity and beyond

    OpenAIRE

    Duque, Jorge Eduardo; Grupo de Terapia Celular y Molecular, Pontificia Universidad Javeriana, Bogotá D.C.; López, Catalina; Grupo de Investigación en Terapia Regenerativa, Universidad de Caldas, Manizales; Cruz, Nataly; Grupo de Terapia Celular y Molecular, Pontificia Universidad Javeriana, Bogotá D.C.; Samudio, Ismael; Grupo de Terapia Celular y Molecular, Pontificia Universidad Javeriana, Bogotá D.C.

    2010-01-01

    Metformin is a synthetic biguanide first described in the 1920´s as a side product of the synthesis of N,N-dimethylguanidine. Like other related biguanides, metformin displays antihyperglycemic properties, and has become the most widely prescribed oral antidiabetic medicine around the world. Intriguing recent evidence suggests that metformin has chemopreventive and direct antitumor properties, and several ongoing clinical studies around the world are using this agent alone or in combi...

  16. Jungle Honey Enhances Immune Function and Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Miki Fukuda

    2011-01-01

    Full Text Available Jungle honey (JH is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal. After seven injections, peritoneal cells (PC were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2 cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261.

  17. Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential.

    Science.gov (United States)

    Alam, Badrul; Majumder, Rajib; Akter, Shahina; Lee, Sang-Han

    2015-02-01

    The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (PPiper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential.

  18. In Vitro Antitumor Activity of Sesquiterpene Lactones from Lychnophora trichocarpha

    Directory of Open Access Journals (Sweden)

    D.A. Saúde-Guimarães

    2014-06-01

    Full Text Available The sesquiterpene lactones lychnopholide and eremantholide C were isolated from Lychnophora trichocarpha Spreng. (Asteraceae, which is a plant species native to the Brazilian Savannah or Cerrado and popularly known as arnica. Sesquiterpene lactones are known to present a variety of biological activities including antitumor activity. The present paper reports on the evaluation of the in vitro antitumor activity of lychnopholide and eremantholide C, in the National Cancer Institute, USA (NCI, USA, against a panel of 52 human tumor cell lines of major human tumors derived from nine cancer types. Lychnopholide disclosed significant activity against 30 cell lines of seven cancer types with IC100 (total growth concentration inhibition values between 0.41 µM and 2.82 µM. Eremantholide C showed significant activity against 30 cell lines of eight cancer types with IC100 values between 21.40 µM and 53.70 µM. Lychnopholide showed values of lethal concentration 50% (LC50 for 30 human tumor cell lines between 0.72 and 10.00 µM, whereas eremantholide C presented values of LC50 for 21 human tumor cell lines between 52.50 and 91.20 µM. Lychnopholide showed an interesting profile of antitumor activity. The α-methylene-γ-lactone present in the structure of lychnopholide, besides two α,β- unsaturated carbonyl groups, might be responsible for the better activity and higher cytotoxicity of this compound in relation to eremantholide C.

  19. Zoledronic acid enhances antitumor efficacy of liposomal doxorubicin.

    Science.gov (United States)

    Hattori, Yoshiyuki; Shibuya, Kazuhiko; Kojima, Kaori; Miatmoko, Andang; Kawano, Kumi; Ozaki, Kei-Ichi; Yonemochi, Etsuo

    2015-07-01

    Previously, we found that the injection of zoledronic acid (ZOL) into mice bearing tumor induced changes of the vascular structure in the tumor. In this study, we examined whether ZOL treatment could decrease interstitial fluid pressure (IFP) via change of tumor vasculature, and enhance the antitumor efficacy of liposomal doxorubicin (Doxil®). When ZOL solution was injected at 40 µg/mouse per day for three consecutive days into mice bearing murine Lewis lung carcinoma LLC tumor, depletion of macrophages in tumor tissue and decreased density of tumor vasculature were observed. Furthermore, ZOL treatments induced inflammatory cytokines such as interleukin (IL)-10 and -12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-α in serum of LLC tumor-bearing mice, but not in normal mice, indicating that ZOL treatments might induce an inflammatory response in tumor tissue. Furthermore, ZOL treatments increased antitumor activity by Doxil in mice bearing a subcutaneous LLC tumor, although they did not significantly increase the tumor accumulation of doxorubicin (DXR). These results suggest that ZOL treatments might increase the therapeutic efficacy of Doxil via improvement of DXR distribution in a tumor by changing the tumor vasculature. ZOL treatment can be an alternative approach to increase the antitumor effect of liposomal drugs.

  20. Snake venoms components with antitumor activity in murine melanoma cells

    International Nuclear Information System (INIS)

    Queiroz, Rodrigo Guimaraes

    2012-01-01

    Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)

  1. O livro das pequenas coisas

    Directory of Open Access Journals (Sweden)

    Alckmar Santos

    2016-12-01

    Full Text Available http://dx.doi.org/10.5007/1807-9288.2016v12n2p209 O livro das pequenas coisas foi produzido a partir da oficina “Criação poética digital” ministrada pelo coletivo formado por Nupill, 1maginári0: poéticas computacionais e Ateliê Ciclope de arte e publicação digital durante o VI Simpósio Internacional e VIII Simpósio Nacional de Literatura e Informática, realizado na Universidade de Passo Fundo entre os dias 9 e 11 de novembro de 2016. Atualmente está disponível na internete em http://ciclope.com.br/livrocoisas/.

  2. Das Konzept des 'Medialen Habitus'

    Directory of Open Access Journals (Sweden)

    Sven Kommer

    2013-12-01

    Full Text Available Sven Kommer fragt in seinem Beitrag, inwieweit das Habitus-Konzept als Erklärungsmuster für die beobachtbare Zementierung sozialer Ungleichheit im Schulsystem greift. Dabei konstatiert der Beitrag, dass alle an der Weiterschreibung des Habitus-Konzepts beteiligten AutorInnen sich darin einig sind, dass es wichtige Beiträge für die Selbst-Aufklärung einer weitestgehend mediatisierten Gesellschaft leistet. Der Artikel geht dabei – auch angesichts der PISA-Studien – von dem empirischen Befund aus, dass die individuelle Ausprägung der Medienkompetenz aufs engste mit den Ressourcen des Elternhauses verbunden ist und sich dabei die elterlichen Formen der Medienerziehung unübersehbar mit den aktuellen medialen Handlungspraxen verbinden. Dieser Befund deckt sich auf weite Strecken auch mit den Ergebnissen der Bildungssoziologie Pierre Bourdieus, weshalb die Diskussionen zum medialen Habitus im Rahmen dieser Ausführungen auch mit empirischen Argumenten unterfüttert werden. Ganz in diesem Sinne arbeitet der Artikel auch heraus, dass die aus dem Kontext der Cultural Studies stammenden Thesen zur Nivellierung kultureller Milieu-Unterschiede wenig empirisch fundiert sind. Der Artikel betont dahingehend, dass hier eine unreflektierte Infiltration durch genuin neoliberales Gedankengut vorliegt, da mit ihr auch die Annahme einer "freien Wahl" von Lebensweg, Milieuzugehörigkeit oder Gender verbunden werden kann. Dabei wir auch eingehend der "Clash of Habitus" diskutiert, der zwischen Lehrenden und Lernenden stattfindet und das Augenmerk ein Mal mehr auf die Tatsache lenkt, das unser Bildungssystem auf dieser pädagogisch relevanten Ebene durch soziale Ungleichheiten gekennzeichnet ist. In his essay, Sven Kommer questions whether the notion of habitus is suitable to support the understanding of the obvious consolidation of inequality in the school system. He shows that all authors active in the continued use of the notion of habitus agree that it

  3. Folksonomia: a linguagem das tags

    Directory of Open Access Journals (Sweden)

    Juliana de Assis

    2013-01-01

    Full Text Available A radicalização do potencial colaborativo da web atual aponta uma tendência de personalização da recuperação da informação através de ferramentas que exploram a linguagem natural na representação e no compartilhamento de conteúdos ao longo das redes sociais. Tal configuração sócio-técnica traz desafios aos profissionais da informação tanto para a descrição e compreensão dos fenômenos informacionais que ocorrem neste âmbito, quanto para a elaboração de produtos e serviços voltados para um usuário que se apresenta cada vez mais como sujeito informacional ao assumir um papel ativo diante da complexidade que caracteriza a organização da informação em contextos digitais. Este artigo apresenta conclusões de pesquisa, relacionadas às analises da linguagem utilizada em três ambientes colaborativos que utilizam a folksonomia (Social Tagging Systems. A partir de uma perspectiva fundamentada na Semiótica e na Análise de Redes Sociais, são identificadas e descritas as principais manifestações da linguagem gerada e compartilhada pelas redes sociais através destes ambientes.

  4. Partial characterization, antioxidant and antitumor activities of polysaccharides from Philomycusbilineatus.

    Science.gov (United States)

    He, Rongjun; Ye, Jiaming; Zhao, Yuejun; Su, Weike

    2014-04-01

    Four polysaccharides (PBP60-A, PBP60-B, PBP60-C and PBP60-D) were purified from slug (Philomycusbilineatus) by ion-exchange chromatography. The antioxidant activities were studied by ABTS, DPPH, hydroxyl radical, superoxide radical and reducing power assay. In vitro antitumor activities were evaluated by MTT assay. Results demonstrated that PBP60-A was mainly composed of Man, Rha, Glc, Gal, Xyl and Fuc in a mole ratio of 6.13:3.08:8.97:5.22:2.46:1.13. PBP60-B was composed of Man, GlcN, Rha, GalN, GlcU, Glc, Gal, Xyl and Fuc in a mole ratio of 0.90:0.31:1.15:0.37:0.24:1.02:3.84:0.93:1.99. PBP60-C and PBP60-D were composed of Man, GlcN, Rha, GalN, GlcU, Glc, Gal, Xyl, Fuc and an unknown monosaccharide. Antioxidant tests indicated that four polysaccharides exhibited significant antioxidant activities in a dose-dependent manner. PBP60-D presented relative stronger antioxidant activity. PBP60-C showed higher antitumor activity against A549 and MCF-7 cells in vitro. At concentration of500 μg/mL, the antitumor activities of PBP60-C on theA549 and MCF-7 cells were 65.30% and 42.45%, respectively. These results indicated that polysaccharides from Philomycusbilineatus could be explored as potential natural antioxidants and cancer prevention agents. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Silencing of Foxp3 enhances the antitumor efficacy of GM-CSF genetically modified tumor cell vaccine against B16 melanoma

    Directory of Open Access Journals (Sweden)

    Miguel A

    2017-01-01

    Full Text Available Antonio Miguel,1 Luis Sendra,1 Verónica Noé,2 Carles J Ciudad,2 Francisco Dasí,3,4 David Hervas,5 María José Herrero,1,6 Salvador F Aliño17 1Department of Pharmacology, Faculty of Medicine, University of Valencia, 2Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Barcelona, 3Research University Hospital of Valencia, INCLIVA Health Research Institute, 4Department of Physiology, Faculty of Medicine, University of Valencia Foundation, 5Biostatistics Unit, 6Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe (IIS La Fe, 7Clinical Pharmacology Unit, ACM Hospital Universitario y Politécnico La Fe, Valencia, Spain Abstract: The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg, which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment. This study aims to evaluate whether combining therapeutic vaccination with CTLA4 or Foxp3 gene silencing enhances the antitumor response. First, the “in vitro” cell entrance and gene silencing efficacy of two tools, 2'-O-methyl phosphorotioate-modified oligonucleotides (2'-OMe-PS-ASOs and polypurine reverse Hoogsteen hairpins (PPRHs, were evaluated in EL4 cells and cultured primary lymphocytes. Following B16 tumor transplant, C57BL6 mice were vaccinated with irradiated B16 tumor cells engineered to produce granulocyte-macrophage colony-stimulating factor (GM-CSF and were intraperitoneally treated with CTLA4 and Foxp3 2'-OMe-PS-ASO before and after vaccination. Tumor growth, mice survival, and CTLA4 and Foxp3 expression in blood cells were measured. The following

  6. Synthesis and Antitumor Activity of Triazole-Containing Sorafenib Analogs

    Directory of Open Access Journals (Sweden)

    Wenjing Ye

    2017-10-01

    Full Text Available Using a highly effective binuclear Cu complex as the catalyst, the 1,3-dipolar cycloaddition reactions between 16 alkynes and two azides were successfully performed and resulted in the production of 25 new triazole-containing sorafenib analogs. Several compounds were evaluated as potent antitumor agents. Among them, 4-(4-(4-(3-fluorophenyl-1H-1,2,3-triazol-1-ylphenoxy-N-methylpicolinamide (8f potently suppressed the proliferation of HT-29 cancer cells by inducing apoptosis and almost completely inhibited colony formation at a low micromolar concentration.

  7. Anti-tumor Study of Chondroitin Sulfate-Methotrexate Nanogels

    Science.gov (United States)

    Wang, Jinyu; Zhao, Weibo; Chen, Haixiao; Qin, An; Zhu, Peizhi

    2017-10-01

    Self-assembly nanogels (NGs) were formed by bioconjugating methotrexate (MTX) with chondroitin sulfate (CS). MTX-CS NGs can greatly enhance the solubility and improve the delivery efficacy of MTX due to the CD44 binding property of CS. Vivo experiments revealed that MTX-CS NGs showed less toxicity than MTX. MTX-CS NGs can improve the anti-tumor effect while reducing the side effects of MTX. Due to their CD44 binding property, chondroitin sulfate-drug conjugates could be a promising and efficient platform for improving the solubility of sparingly soluble drug molecules as well as targeted delivery to cancer cells and tumor tissues.

  8. Das biochemische Rezidiv beim Prostatakarzinom

    Directory of Open Access Journals (Sweden)

    Rauchenwald M

    2010-01-01

    Full Text Available Als biochemisches Rezidiv (BCR wird der Wiederanstieg des nach kurativer Therapie des Prostatakarzinoms (PCa abgefallenen PSA-Werts bezeichnet. Der PSA-Verlauf nach kurativer Therapie ist von der primären Behandlungsmethode abhängig, weshalb auch unterschiedliche Definitionen dafür vorliegen. Der Verlauf selbst scheint prognostische Bedeutung zu haben. Ein Wiederanstieg des PSA-Werts geht der klinischen Progression voraus, wodurch frühzeitig eine Therapie eingeleitet werden kann. Der ideale Zeitpunkt für eine Sekundärbehandlung ist allerdings noch ungenügend definiert. Fast die Hälfte der BCR treten innerhalb der ersten 2 Jahre, ¾ innerhalb der ersten 5 Jahre nach Primärtherapie auf. Als Risikofaktoren für einen BCR werden ein primäres Tumorstadium ≥ T2c, PSA 15, Samenblaseninvasion, Lymphknotenbefall sowie Gleason-Score ≥ 8 angesehen. Von klinischer Bedeutung ist vor allem die Unterscheidung zwischen lokoregionärem und systemischem Rezidiv. Hierzu werden als Parameter neben dem primären Tumorstadium und Gleason-Score das posttherapeutische Intervall und die PSA-Dynamik empfohlen. Als diagnostische Maßnahmen erscheinen nur die Skelettszintigraphie und die Positronenemissionstomographie mit Acetat- oder Cholintracern und diese ebenfalls nur bei entsprechend hohen PSA-Werten sinnvoll. Therapeutisch kommt nach primärer Radikaloperation und Verdacht auf einen lokalen Progress in erster Linie die Salvagebestrahlung zur Anwendung, nach primärer Radiatio wird allerdings vorwiegend die hormonelle Manipulation einer Salvageoperation oder alter“nativen lokaltherapeutischen Maßnahmen vorgezogen.

  9. Folksonomia: a linguagem das tags

    Directory of Open Access Journals (Sweden)

    Juliana de Assis

    2013-04-01

    Full Text Available http://dx.doi.org/10.5007/1518-2924.2013v18n36p85   A radicalização do potencial colaborativo da web atual aponta uma tendência de personalização da recuperação da informação através de ferramentas que exploram a linguagem natural na representação e no compartilhamento de conteúdos ao longo das redes sociais. Tal configuração sócio-técnica traz desafios aos profissionais da informação tanto para a descrição e compreensão dos fenômenos informacionais que ocorrem neste âmbito, quanto para a elaboração de produtos e serviços voltados para um usuário que se apresenta cada vez mais como sujeito informacional ao assumir um papel ativo diante da complexidade que caracteriza a organização da informação em contextos digitais. Este artigo apresenta conclusões de pesquisa, relacionadas às analises da linguagem utilizada em três ambientes colaborativos que utilizam a folksonomia (Social Tagging Systems. A partir de uma perspectiva fundamentada na Semiótica e na Análise de Redes Sociais, são identificadas e descritas as principais manifestações da linguagem gerada e compartilhada pelas redes sociais através destes ambientes.

  10. DNA strand scission by the novel antitumor antibiotic leinamycin

    International Nuclear Information System (INIS)

    Hara, Mitsunobu; Saitoh, Yutaka; Nakano, Hirofumi

    1990-01-01

    Leinamycin is a recently discovered antitumor antibiotic with an unusual 1,3-dioxo-1,2-dithiolane structure. It preferentially inhibits the incorporation of [ 3 H]thymidine into the acid-insoluble fraction of Bacillus subtilis. In vitro, leinamycin causes single-strand cleavage of supercoiled double-helical pBR322 DNA in the presence of thiol cofactors. Scavengers of oxygen radical did not suppress the DNA-cleaving activity. Thiol-activated leinamycin binds calf thymus DNA at 4 degree C and thermal treatment of the leinamycin-DNA adduct released a chemically modified leinamycin from the complex. The lack of cytotoxicity and DNA-cleaving activity for S-deoxyleinamycin indicates that the 1,3-dioxo-1,2-dithiolane moiety is essential for the activity of leinamycin. Thus, the primary cellular target of leinamycin appears to be DNA. It binds DNA and causes single-strand break at low concentrations, which may account for the potent antitumor activity

  11. Improved Antitumor Efficacy and Pharmacokinetics of Bufalin via PEGylated Liposomes

    Science.gov (United States)

    Yuan, Jiani; Zhou, Xuanxuan; Cao, Wei; Bi, Linlin; Zhang, Yifang; Yang, Qian; Wang, Siwang

    2017-11-01

    Bufalin was reported to show strong pharmacological effects including cardiotonic, antiviral, immune-regulation, and especially antitumor effects. The objective of this study was to determine the characterization, antitumor efficacy, and pharmacokinetics of bufalin-loaded PEGylated liposomes compared with bufalin entity, which were prepared by FDA-approved pharmaceutical excipients. Bufalin-loaded PEGylated liposomes and bufalin-loaded liposomes were prepared reproducibly with homogeneous particle size by the combination of thin film evaporation method and high-pressure homogenization method. Their mean particle sizes were 127.6 and 155.0 nm, mean zeta potentials were 2.24 and - 18.5 mV, and entrapment efficiencies were 76.31 and 78.40%, respectively. In vitro release profile revealed that the release of bufalin in bufalin-loaded PEGylated liposomes was slower than that in bufalin-loaded liposomes. The cytotoxicity of blank liposomes has been found within acceptable range, whereas bufalin-loaded PEGylated liposomes showed enhanced cytotoxicity to U251 cells compared with bufalin entity. In vivo pharmacokinetics indicated that bufalin-loaded PEGylated liposomes could extend or eliminate the half-life time of bufalin in plasma in rats. The results suggested that bufalin-loaded PEGylated liposomes improved the solubility and increased the drug concentration in plasma.

  12. Antitumor effects of Marginisporum crassissimum (Rhodophyceae), a marine red alga.

    Science.gov (United States)

    Hiroishi, S; Sugie, K; Yoshida, T; Morimoto, J; Taniguchi, Y; Imai, S; Kurebayashi, J

    2001-06-26

    Marginisporum crassissimum (Yendo) Ganesan, a marine red alga found in the ordinal coastal sea around Japan, revealed antitumor (antimetastatic) effects in vitro and in vivo. In in vitro experiments, extracts of this alga inhibited not only the growth of several tumor cell lines, such as B16-BL6 (a mouse melanoma cell line), JYG-B (a mouse mammary carcinoma cell line) and KPL-1 (a human mammary carcinoma cell line), but also invasion of B16-BL6 cells in a culture system. In in vivo experiments, the lung metastasis of B16-BL6 cells inoculated to the tail vein of B57BL/6J mice was inhibited by intraperitoneal administration of an extract from the alga. In addition, life prolongation of B57BL/6J mice inoculated with B16-BL6 cells was also observed by the intraperitoneal administration of the extract. An effective substance showing B16-BL6 growth inhibition in vitro was partially purified by filtration and hydrophobic column chromatography, and was revealed to be sensitive to trypsin-digestion and heat-treatment. The molecular weight of the substance was greater than 100 kDa. This is the first study demonstrating antitumor (antimetastatic) effects of M. crassissimum.

  13. Das IHS und die Rolle der Forschungsinstitute

    OpenAIRE

    Keuschnigg, Christian

    2014-01-01

    Das Institut für Höhere Studien und wissenschaftliche Forschung (IHS) ist ein unabhängiges Forschungsinstitut und leistet Forschung und Ausbildung auf Spitzenniveau für Politik, Wirtschaft und Gesellschaft. Im Wettbewerb zwischen Universitäten und angewandten Forschungsinstituten ist das IHS einzigartig, weil es unter einem Dach Grundlagenforschung und forschungsnahe Lehre mit angewandter Forschung für die wissenschaftliche Politikberatung verbindet. Mit den drei Disziplinen Ökonomie, Soziolo...

  14. Das Muťafi-Lazische

    OpenAIRE

    Kutscher, Silvia; Mattissen, Johanna; Wodarg, Anke

    1995-01-01

    Die in der vorliegenden Publikation untersuchte Sprache ist ein Dialekt des Lazischen, der in Muťafi und Umgebung gesprochen wird. Dieser Dialekt ist bis zu diesem Zeitpunkt noch nicht wissenschaftlich untersucht worden. Da er einige Charakteristika aufweist, die in anderen lazischen Dialekten nicht zu finden sind, hielten wir es für notwendig, unsere Untersuchungsergebnisse zu veröffentlichen. Eine auffällige Besonderheit findet sich z.B. im Kasussystem: Sowohl das Georgische als auch das Za...

  15. QUAL O FUTURO DAS ESCOLAS NO CAMPO?

    Directory of Open Access Journals (Sweden)

    Célia Regina Vendramini

    2015-09-01

    Full Text Available RESUMO:Tendo como ponto de partida a questão sobre o futuro das escolas rurais ou do campo, o artigo aborda o contexto social, político e econômico que suporta ou não a existência das escolas, bem como uma análise sobre a situação das escolas em diferentes contextos, particularmente no Brasil, em Portugal e nos Estados Unidos. Problematizamos as respostas dadas pelo poder público, acadêmicos e organizações e movimentos sociais sobre o fechamento, a redução do número de alunos e de comunidades rurais com escola, as condições de funcionamento, a distância percorrida pelos alunos, além das implicações das escolas para a vitalidade do campo. Concluímos que o futuro das escolas está diretamente relacionado com o futuro do campo.

  16. Enhanced antitumor efficacy of doxorubicin-encapsulated halloysite nanotubes

    Directory of Open Access Journals (Sweden)

    Li K

    2017-12-01

    Full Text Available Kai Li,1,* Yongxing Zhang,2,* Mengting Chen,1 Yangyang Hu,1 Weiliang Jiang,1 Li Zhou,1 Sisi Li,1 Min Xu,1 Qinghua Zhao,2 Rong Wan1 1Department of Gastroenterology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Orthopaedics, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: To improve the antitumor efficacy of doxorubicin (DOX and provide novel clinical treatment of gastric cancer, halloysite nanotubes (HNTs loaded with DOX were encapsulated by soybean phospholipid (LIP and the formed HNTs/DOX/LIP was systematically characterized via different techniques. The in vitro anticancer activity of HNTs/DOX/LIP was examined using an MTT assay. The antitumor efficacy and biocompatibility were monitored by measuring the tumor volume and assessing the blood routine and serum biochemistry using an ectopic implantation cancer model. The results show that when the concentration of HNTs was 3 mg/mL and the concentration of DOX was 1 mg/mL the optimal DOX loading efficiency was as high as 22.01%±0.43%. In vitro drug release behavior study demonstrated that HNTs/DOX/LIP shows a pH-responsive release property with fast drug release under acidic conditions (pH =5.4. MTT assays and in vivo experimental results revealed that HNTs/DOX/LIP exhibits a significantly higher inhibitory efficacy on the growth of mouse gastric cancer cells than free DOX at the same drug concentration. In addition, the life span of tumor-bearing mice in the HNTs/DOX/LIP-treated group was obviously prolonged compared with the control groups. Moreover, HNTs/DOX/LIP possessed excellent hemocompatibility as shown in the blood and histology studies. These findings indicated that the formed HNTs/DOX/LIP possesses higher antitumor efficacy and may be used as a targeted

  17. Antitumor function and mechanism of phycoerythrin from Porphyra haitanensis

    Directory of Open Access Journals (Sweden)

    Qunwen Pan

    2013-01-01

    Full Text Available The anti-tumor effect of R-Phycoerythrin (R-PE from Porphyra haitanensis was studied using cell line HeLa as an in vitro model and Sarcoma-180 (S180 tumor-bearing mice as an in vivo model. The results showed that the combination treatment of R-PE and photodynamic therapy PDT significantly inhibited the growth of HeLa cells up to 81.5%, with a fair dose-effect relationship, but did not inhibit endothelial cells. The annexin v-fitc/PI fluorescence staining experiments demonstrated that at doses between 0~60µg/mL, apoptosis cells and later stage apoptosis cells or necrosis cells increased significantly as the R-PE dosage increased. DNA electrophoresis showed that after R-PE+PDT treatment of HeLa cells for 24 hours, a light "smear" band between 100~400bp appeared to indicate the degradation of genomic DNA. The QRT-PCR results showed that R-PE+PDT treatment increased caspase-3 and caspase-10 gene expression and decreased the Bcl-2 gene expression level significantly as the R-PE dose increased, implying that R-PE promoted HeLa cell apoptosis. Compared with untreated S180 tumor-bearing mice, R-PE injection significantly inhibited the growth of S180 in tumor-bearing mice up to 41.3% at a dose of 300mg-kg-1. Simultaneously, the significant increase of superoxide dismutase (SOD activity in serum (p < 0.01 and the decrease of the malondialdehyde (MDA level in liver suggests that R-PE improved the anti-oxidant ability of the S180 tumor-bearing mice, which may related to its antitumor effect. In addition, the R-PE caused a significant increase (p < 0.05 in the spleen index and thymus index, and a significant increase (p < 0.01 in lymphocyte proliferation, NK cell kill activity and the TNF-α level in the serum of S180 tumor-bearing mice. These results strongly suggest that the antitumor effect of R-PE from Porphyra haitanensis functioned by increasing the immunity and antioxidant ability of S180 tumor-bearing mice, promoting apoptosis by increasing protease

  18. Pharmocokinetics of the antitumor drug oxoplatinum labelled with 191Pt

    International Nuclear Information System (INIS)

    Lobanova, E.A.

    1985-01-01

    A pharmacokinetic study of the antitumor drug oxoplatinum labeled with 191 Pt when agministered to control mice and mice with B-16 melanoma have shown that distribution of the drug in organs and tissues in both groups of animals is nonuniform. The drug is more tropic to the kidneys, liver, spleen, adrenals, thymus, skin and tumor. Correlation was established between the values of the coefficient ratios of differential accumulation (CDA) of the organ/blood in the f;.nal and initial periods of observation and the period of the drug half-life in the organs. The higher the CDA of the organ/blood the longer the period of the drug half-life. The excretion of the drug from the blood and most other organs is described by a bioexponential curve

  19. Potential Antitumor Effects of Pomegranates and Its Ingredients.

    Science.gov (United States)

    Rahmani, Arshad H; Alsahli, Mohammed A; Almatroodi, Saleh A

    2017-01-01

    The treatment based on plant or plant derivatives is a promising strategy in the killing of cancers cells. Moreover, wide-ranging finding has established that medicinal plant and its ingredient modulate several cells signaling pathways or inhibiting the carcinogenesis process. In this vista, pomegranates fruits, seeds and peels illustrate cancer preventive role seems to be due to rich source of antioxidant and other valuable ingredients. Furthermore, anti-tumour activities of pomegranates have been evidences through the modulation of cell signaling pathways including transcription factor, apoptosis and angiogenesis. In this review article, anti-tumor activity of pomegranates and its components or its different type of extracts are described to understand the mechanism of action of pomegranates in cancer therapy.

  20. Antitumor effects of radioiodinated antisense oligonucleotide mediated by VIP receptor

    International Nuclear Information System (INIS)

    Ou Xiaohong; Tan Tianzhi; Li Yunchun; Kuang Anren

    2004-01-01

    Purpose: we had constructed a targeting delivery system based on intestinal peptide (VIP) for antisense oligonucleotide (ASON) transfer into VIP receptor-positive cells in previous study. The aims of present studies are to observe the antitumor effect of VIP-131I-ASON in HT29 human colon adenocarcinoma xenografts. Methods: A 15-met phosphorothioate ASON, which was complementary to the translation start region of the C-myc oncogene mRNA, was labeled with 131I and the labelled compound was linked to the VIP bound covalently 'to a polylysine chain so as to deliver oligonucleotide into tumor cells. Distribution experiments for evaluating the radiolabeled antisense complexe uptake in tumor tissue were performed in BALB/c nude mice bearing with HT29 tumor xenografts. Nude mice beating HT29 tumor xenografts were adminstered VIP-131I-ASON (3.7,7.4 MBq) or 131I-ASON (3.7 MBq), 131I labeled control sense and nosense DNA (3.7 MBq), or saline. Antitumor effects were assessed using endpoints of tumor growth delay. C-myc-encoded protein expression of tumor was measured by immunocytohistochemical staining. Results: Distribution experiment performed with athymic mice bearing human colon tumor xenografts revealed maximal accumulation of conjugated ASON in the tumor tissue 2 h after administration and significantly higher than that in nude mice injected unconjngated ASON [(5.89±1.03)%ID/g and(1.56±0.31)%ID/g, respectively; t=7.7954 P<0.001]. The radioratio of tumor to muscle was peaked 4h after administration. VIP-131I-ASON exhibited strong antitumor effects against HT29 xenografts, decreasing their growth rate 7-fold compare with that in saline-treated mice(tumor growth delay, 25.4±0.89 day). The antitumor effects of unconjugated 131I-ASON were much less profound than VIP-131I-ASON (tumor growth delay, 3.2±1.3 and 25.4±0.89 day, respectively; q=51.4126 P<0.01). Sense, nosense control ON with VIP carder caused no therapeutic effect. There was no progressive weight loss or

  1. OFFICIAL MEDICATIONS FOR ANTI-TUMOR GENE THERAPY

    Directory of Open Access Journals (Sweden)

    E. R. Nemtsova

    2016-01-01

    Full Text Available This is a review of modern literature data of official medications for anti-tumor gene therapy as well as of medications that finished clinical trials.The article discusses the concept of gene therapy, the statistical analysis results of initiated clinical trials of gene products, the most actively developing directions of anticancer gene therapy, and the characteristics of anti-tumor gene medications.Various delivery systems for gene material are being examined, including viruses that are defective in  replication (Gendicine™ and Advexin and oncolytic (tumor specific conditionally replicating viruses (Oncorine™, ONYX-015, Imlygic®.By now three preparations for intra-tumor injection have been introduced into oncology clinical practice: two of them – Gendicine™ and Oncorine™ have been registered in China, and one of them – Imlygic® has been registered in the USA. Gendicine™ and Oncorine™ are based on the wild type p53 gene and are designed for treatment of patients with head and neck malignancies. Replicating adenovirus is the delivery system in Gendicine™, whereas oncolytic adenovirus is the vector for gene material in Oncorine™. Imlygic® is based on the  recombinant replicating HSV1 virus with an introduced GM–CSF gene and is designed for treatment of  melanoma patients. These medications are well tolerated and do not cause any serious adverse events. Gendicine™ and Oncorine™ are not effective in monotherapy but demonstrate pronounced synergism with chemoand radiation therapy. Imlygic® has just started the post marketing trials.

  2. Radiation protection and antitumor effects in Hatakeshimeji (Lyophyllum decastes sing)

    International Nuclear Information System (INIS)

    Ukawa, Yuuichi; Gu, Yeunhwa; Suzuki, Ikukatsu; Park, Sangrae; Hasegawa, Takeo; Tsukada, Sekihito; Terai, Kaoru; Tawaraya, Hitoshi

    2002-01-01

    The effect on an anti-tumor is admitted in the lyophyllum decastes sing extraction thing, and it has the action mechanism cleared to depend on the immunity action. The existence of the synergistic effect in effect on an anti-tumor radiation irradiation, an individual with the medication of lyophyllum decastes sing and effect on combination and the effect on protection of the leukocyte decrease by the radiation was examined by this research. After about 2x10 6 inoculated sarcoma 180 on the ICR mice, a lyophyllum decastes sing extraction thing gave 100mg/kg for 2 weeks in endoceliac at the every other day. After that, the radiation irradiation of 2 Gy was done three times, and it went to the sutra time target the number of the leukocytes, the lymph node ball some prizes of measurement. And, weight and tumor size were measured after the cancer cell inoculation two weeks. The decrease of the clear tumor size was recognized by the group that only a cancer cell was inoculated by the radiation independent irradiation group, lyophyllum decastes sing and the radiation combination group though tumor size increased as it passed. It faced by the group that only a cancer cell was inoculated after the irradiation 15 days though it died the precedent, and a half existed by lyophyllum decastes sing and the radiation combination group. And, the numbers of the leukocytes, the number of the lymphocyte were on the increase regardless of the existence of the radiation irradiation by the medication of lyophyllum decastes sing. It thinks with the thing that the effect is shown for the effect on immunity recovery in the radiotherapy and the prevention of a side effect of the radiation from this result. Showing the effect for not only effect on prevention of the cancer and effect on healing but also the effect on immunity recovery in the radiotherapy, the prevention of a side effect by taking lyophyllum decastes sing is considered

  3. Design of novel antitumor DNA alkylating agents: the benzacronycine series.

    Science.gov (United States)

    David-Cordonnier, Marie-Hélène; Laine, William; Gaslonde, Thomas; Michel, Sylvie; Tillequin, Francois; Koch, Michel; Léonce, Stéphane; Pierré, Alain; Bailly, Christian

    2004-03-01

    Acronycine, a natural alkaloid originally extracted from the bark of the Australian ash scrub Acronychia baueri, has shown a significant antitumor activity in animal models. Acronycine has been tested against human cancers in the early 1980s, but the clinical trials showed modest therapeutic effects and its development was rapidly discontinued. In order to optimize the antineoplastic effect, different benzoacronycine derivatives were synthesized. Among those, the di-acetate compound S23906-1 was recently identified as a promising anticancer drug candidate and a novel alkylating agent specifically reacting with the exocylic 2-NH2 group of guanines in DNA. The study of DNA bonding capacity of acronycine derivatives leads to the identification of the structural requirements for DNA alkylation. In nearly all cases, the potent alkylating agents, such as S23906-1, were found to be much more cytotoxic than the unreactive analogs such as acronycine itself or diol derivatives. Alkylation of DNA by the monoacetate derivative S28687-1, which is a highly reactive hydrolysis metabolite of S23906-1, occurs with a marked preference for the N2 position of guanine. Other bionucleophiles can react with S23906-1. The benzacronycine derivatives, which efficiently alkylate DNA, also covalently bind to the tripeptide glutathione (GSH) but not to the oxidized product glutathione disulfide. Here we review the reactivity of S23906-1 and some derivatives toward DNA and GSH. The structure-activity relationships in the benzacronycine series validate the reaction mechanism implicating DNA as the main molecular target. S23906-1 stands as the most promising lead of a medicinal chemistry program aimed at discovering novel antitumor drugs based on the acronycine skeleton.

  4. Antitumor and angiostatic peptides from frog skin secretions.

    Science.gov (United States)

    van Zoggel, Hanneke; Hamma-Kourbali, Yamina; Galanth, Cécile; Ladram, Ali; Nicolas, Pierre; Courty, José; Amiche, Mohamed; Delbé, Jean

    2012-01-01

    The discovery of new molecules with potential antitumor activity continues to be of great importance in cancer research. In this respect, natural antimicrobial peptides isolated from various animal species including humans and amphibians have been found to be of particular interest. Here, we report the presence of two anti-proliferative peptides active against cancer cells in the skin secretions of the South American tree frog, Phyllomedusa bicolor. The crude skin exudate was fractioned by size exclusion gel followed by reverse-phase HPLC chromatography. After these two purification steps, we identified two fractions that exhibited anti-proliferative activity. Sequence analysis indicated that this activity was due to two antimicrobial α-helical cationic peptides of the dermaseptin family (dermaseptins B2 and B3). This result was confirmed using synthetic dermaseptins. When tested in vitro, synthetic B2 and B3 dermaseptins inhibited the proliferation of the human prostatic adenocarcinoma PC-3 cell line by more than 90%, with an EC(50) of around 2-3 μM. No effect was observed on the growth of the NIH-3T3 non-tumor mouse cell line with Drs B2, whereas a slight inhibiting effect was observed with Drs B3 at high dose. In addition, the two fractions obtained after size exclusion chromatography also inhibited PC-3 cell colony formation in soft agar. Interestingly, inhibition of the proliferation and differentiation of activated adult bovine aortic endothelial cells was observed in cells treated with these two fractions. Dermaseptins B2 and B3 could, therefore, represent interesting new pharmacological molecules with antitumor and angiostatic properties for the development of a new class of anticancer drugs.

  5. Números reais e curiosidades das somas infinitas

    OpenAIRE

    Moreno, Priscila Klitzke

    2016-01-01

    Podemos encontrar muitas surpresas interessantes no estudo das somas infinitas de números reais (series). Nessa perspectiva, este trabalho traz um estudo sobre as somas infinitas e mostra algumas curiosidades sobre elas, em especial sobre a serie harmônica. Começamos nosso estudo sobre somas infinitas, considerando exemplos com interpretações geométricas que tornam o estudo de series mais atraente. Discutimos também propriedades aritméticas, comutativa e associativa, das somas ...

  6. Das Bild behinderter Menschen in den Medien

    OpenAIRE

    Radtke, Peter

    2006-01-01

    Das Bild von Behinderung und behinderten Menschen in den Medien“ - dieses Thema führt sehr leicht zur Schwarz-Weiß-Malerei. Bekanntlich fällt es schwer, es allen recht zu machen. So nimmt es nicht Wunder, dass sich Betroffene und ihre Angehörigen in den Medien sowohl quantitativ als auch qualitativ oftmals nicht angemessen repräsentiert fühlen. [...] In dieser Situation bilden die Medien die wichtigste und oft einzige Informationsquelle über das Leben und die Möglichkeiten von Menschen mit e...

  7. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    Science.gov (United States)

    Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and PARP, which resulted from suppression of MCL-1 and BCL-2 expression in the cells. APA also inactivated the Akt/mTOR pathway in breast cancer cells. Thus, APA exerts a strong anti-tumor effect on breast cancer cells, most likely through induction of apoptosis. Our study is the first to identify this novel anti-tumor compound and provides a new strategy for isolation and separation of single compounds from herbs. PMID:26943775

  8. PEGylation of α-momorcharin retained its anti-tumor activity with ...

    African Journals Online (AJOL)

    user

    the anti-tumor activity of α-MMC-PEG decreased by about 30% in vitro. This sensitivity increase of 50 ... experiments and were acclimatized in the animal room. They were housed on aspen ..... PEGylation, successful approach to drug delivery.

  9. Study of Antitumor Activity of Sodium Phenylbutyrate, Histon Deacetylase Inhibitor, on Ehrlich Carcinoma Model.

    Science.gov (United States)

    Fadeev, N P; Kharisov, R I; Kovan'ko, E G; Pustovalov, Yu I

    2015-09-01

    Antitumor activity of sodium phenylbutyrate was studied on 120 outbred female mice with transplanted Ehrlich ascites carcinoma. The animals received the drug in doses of 400, 800, and 1200 mg/kg with drinking water daily for 21 days. The antitumor effect was evaluated by tumor growth inhibition and lifespan prolongation. Phenylbutyrate in the dose of 800 mg/kg was most effective. The drug inhibited the tumor growth by 71%, prolonged the lifespan of animals by 28, and was low-toxic.

  10. RhoB mediates antitumor synergy of combined ixabepilone and sunitinib in human ovarian serous cancer.

    Science.gov (United States)

    Vishnu, Prakash; Colon-Otero, Gerardo; Kennedy, Gregory T; Marlow, Laura A; Kennedy, William P; Wu, Kevin J; Santoso, Joseph T; Copland, John A

    2012-03-01

    The aim was to evaluate antitumor activity of the combination of ixabepilone and sunitinib in pre-clinical models of chemotherapy naïve and refractory epithelial ovarian tumors, and to investigate the mechanism of synergy of such drug combination. HOVTAX2 cell line was derived from a metastatic serous papillary epithelial ovarian tumor (EOC) and a paclitaxel-resistant derivative was established. Dose response curves for ixabepilone and sunitinib were generated and synergy was determined using combination indexes. The molecular mechanism of antitumor synergy was examined using shRNA silencing. The combination of ixabepilone and sunitinib demonstrated robust antitumor synergy in naïve and paclitaxel-resistant HOVTAX2 cell lines due to increased apoptosis. The GTPase, RhoB, was synergistically upregulated in cells treated with ixabepilone and sunitinib. Using shRNA, RhoB was demonstrated to mediate antitumor synergy. These results were validated in two other EOC cell lines. Ixabepilone plus sunitinib demonstrated antitumor synergy via RhoB in naïve and paclitaxel-resistant cells resulting in apoptosis. This study demonstrates a novel mechanism of action leading to antitumor synergy and provides 'proof-of-principle' for combining molecular targeted agents with cytotoxic chemotherapy to improve antitumor efficacy. RhoB could be envisioned as an early biomarker of response to therapy in a planned Phase II clinical trial to assess the efficacy of ixabepilone combined with a receptor tyrosine kinase inhibitor such as sunitinib. To the best of our knowledge, this is the first demonstration of antitumor synergy between these two classes of drugs in EOC and the pivotal role of RhoB in this synergy. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Amplexicaule A exerts anti-tumor effects by inducing apoptosis in human breast cancer

    OpenAIRE

    Xiang, Meixian; Su, Hanwen; Shu, Guangwen; Wan, Dingrong; He, Feng; Loaec, Morgann; Ding, Yali; Li, Jun; Dovat, Sinisa; Yang, Gaungzhong; Song, Chunhua

    2016-01-01

    Chemotherapy is the main treatment for patients with breast cancer metastases, but natural alternatives have been receiving attention for their potential as novel anti-tumor reagents. Amplexicaule A (APA) is a flavonoid glucoside isolated from rhizomes of Polygonum amplexicaule D. Don var. sinense Forb (PADF). We found that APA has anti-tumor effects in a breast cancer xenograft mouse model and induces apoptosis in breast cancer cell lines. APA increased levels of cleaved caspase-3,-8,-9 and ...

  12. New cysteamine (2-chloroethyl)nitrosoureas. Synthesis and preliminary antitumor results.

    Science.gov (United States)

    Madelmont, J C; Godeneche, D; Parry, D; Duprat, J; Chabard, J L; Plagne, R; Mathe, G; Meyniel, G

    1985-09-01

    Three chemical pathways were used for the synthesis of four new N'-(2-chloroethyl)-N-[2-(methylsulfinyl)ethyl]- and N'-(2-chloroethyl)-N-[2-(methylsulfonyl)ethyl]-N- or N'-nitrosoureas. These compounds are plasma metabolites of CNCC, a promising antineoplastic (2-chloroethyl)nitrosourea. Preliminary antitumor evaluation was performed against L1210 leukemia implanted intraperitoneally in mice. Among these compounds, two of them exhibited a greater antitumor activity compared to that of the parent mixture.

  13. Design and Syntheses of Novel Fluoroporphyrin-Anthraquinone Complexes as Antitumor Agents.

    Science.gov (United States)

    Yang, Gu-Liang; Zhao, Sheng-Fang; Chen, Nian-You; Li, Shiming

    2016-01-01

    A novel fluoroporphyrin-anthraquinone hybrid with dipeptide link and its metal complexes were synthesized and evaluated for anti-proliferation activity in human cancer cell line HeLa. The preliminary results demonstrated that all the compounds showed moderate to excellent antitumor activities. Among the active compounds, compound 3 which contains fluorinated porphyrin-anthraquinone and zinc ion exhibited the highest potency with IC50 value of 8.83 µM, indicating that it was a promising antitumor candidate.

  14. The Das-Popowicz Moyal momentum algebra

    International Nuclear Information System (INIS)

    Boulahoual, A.; Sedra, M.B.

    2002-08-01

    We introduce in this short note some aspects of the Moyal momentum algebra that we call the Das-Popowicz Mm algebra. Our interest on this algebra is motivated by the central role that it can play in the formulation of integrable models and in higher conformal spin theories. (author)

  15. Die Gestalten und das Gestalten der Welt

    NARCIS (Netherlands)

    Ierna, Carlo; Höfer, Ulf; Valent, Juta

    2017-01-01

    In seiner Kosmogonie bespricht Ehrenfels den Ursprung, die Entwicklung, und das endgültige Schicksal des Universums: die Gestalt der Welt. Einerseits ist sie ein Kosmos, ein Geschöpf des Ordnungsprinzips, andererseits ein Chaos, als Resultat des Prinzips des Zufalls und der Entropie. Diese beiden

  16. Antitumor effect of degalactosylated gc-globulin on orthotopic grafted lung cancer in mice.

    Science.gov (United States)

    Hirota, Keiji; Nakagawa, Yoshinori; Takeuchi, Ryota; Uto, Yoshihiro; Hori, Hitoshi; Onizuka, Shinya; Terada, Hiroshi

    2013-07-01

    Group-specific component (Gc)-globulin-derived macrophage-activating factor (GcMAF) generated by a cascade of catalytic reactions with deglycosidase enzymes exerts antitumor activity. We hypothesized that degalactosyl Gc-globulin (DG3), a precursor of GcMAF, also plays a role in recovery from cancer as well as GcMAF due to progression of deglycosylation by generally resident sialidases and mannosidases. We prepared the subtypes of DG3, such as 1f1f and 1s1s and its 22 homodimers, by using vitamin D3-binding Sepharose CL-6B and examined their antitumor activity in mice bearing Lewis lung carcinoma cells, by counting the number of nodules formed in their lungs. Antitumor activity of DG3 was observed regardless of its subtype, being equivalent to that of GcMAF. The injection route of DG3 affected its antitumor activity, with subcutaneous and intramuscular administration being more favorable than the intraperitoneal or intravenous route. In order to obtain significant antitumor activity, more than 160 ng/kg of DG3 were required. DG3 proved to be promising as an antitumor agent, similarly to GcMAF.

  17. Fermented Mistletoe Extract as a Multimodal Antitumoral Agent in Gliomas

    Directory of Open Access Journals (Sweden)

    Oliver Podlech

    2012-01-01

    Full Text Available In Europe, commercially available extracts from the white-berry mistletoe (Viscum album L. are widely used as a complementary cancer therapy. Mistletoe lectins have been identified as main active components and exhibit cytotoxic effects as well as immunomodulatory activity. Since it is still not elucidated in detail how mistle toe extracts such as ISCADOR communicate their effects, we analyzed the mechanisms that might be responsible for their antitumoral function on a molecular and functional level. ISCADOR-treated glioblastoma (GBM cells down-regulate central genes involved in glioblastoma progression and malignancy such as the cytokine TGF-β and matrix-metalloproteinases. Using in vitro glioblastoma/immune cell co-cultivation assays as well as measurement of cell migration and invasion, we could demonstrate that in glioblastoma cells, lectin-rich ISCADOR M and ISCADOR Q significantly enforce NK-cell-mediated GBM cell lysis. Beside its immune stimulatory effect, ISCADOR reduces the migratory and invasive potential of glioblastoma cells. In a syngeneic as well as in a xenograft glioblastoma mouse model, both pretreatment of tumor cells and intratumoral therapy of subcutaneously growing glioblastoma cells with ISCADOR Q showed delayed tumor growth. In conclusion, ISCADOR Q, showing multiple positive effects in the treatment of glioblastoma, may be a candidate for concomitant treatment of this cancer.

  18. Antitumor Responses of Invariant Natural Killer T Cells

    Directory of Open Access Journals (Sweden)

    Jennie B. Altman

    2015-01-01

    Full Text Available Natural killer T (NKT cells are innate-like lymphocytes that were first described in the late 1980s. Since their initial description, numerous studies have collectively shed light on their development and effector function. These studies have highlighted the unique requirements for the activation of these lymphocytes and the functional responses that distinguish these cells from other effector lymphocyte populations such as conventional T cells and NK cells. This body of literature suggests that NKT cells play diverse nonredundant roles in a number of disease processes, including the initiation and propagation of airway hyperreactivity, protection against a variety of pathogens, development of autoimmunity, and mediation of allograft responses. In this review, however, we focus on the role of a specific lineage of NKT cells in antitumor immunity. Specifically, we describe the development of invariant NKT (iNKT cells and the factors that are critical for their acquisition of effector function. Next, we delineate the mechanisms by which iNKT cells influence and modulate the activity of other immune cells to directly or indirectly affect tumor growth. Finally, we review the successes and failures of clinical trials employing iNKT cell-based immunotherapies and explore the future prospects for the use of such strategies.

  19. Biomedical potentials of crown ethers: prospective antitumor agents.

    Science.gov (United States)

    Kralj, Marijeta; Tusek-Bozić, Ljerka; Frkanec, Leo

    2008-10-01

    Crown ethers are of enormous interest and importance in chemistry, biochemistry, materials science, catalysis, separation, transport and encapsulated processes, as well as in the design and synthesis of various synthetic systems with specific properties, diverse capabilities, and programmable functions. Classical crown ethers are macrocyclic polyethers that contain 3-20 oxygen atoms separated from each other by two or more carbon atoms. They are exceptionally versatile in selectively binding a range of metal ions and a variety of organic neutral and ionic species. Crown ethers are currently being studied and used in a variety of applications beyond their traditional place in chemistry. This review presents additional applications and the ever-increasing biomedical potentials of these intriguing compounds, with particular emphasis on the prospects of their relevance as anticancer agents. We believe that further research in this direction should be encouraged, as crown compounds could either induce toxicities that are different from those of conventional antitumor drugs, or complement drugs in current use, thereby providing a valuable adjunct to therapy.

  20. Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy

    International Nuclear Information System (INIS)

    Paraskar, Abhimanyu; Soni, Shivani; Basu, Sudipta; Srivats, Shyam; Roy, Rituparna Sinha; Sengupta, Shiladitya; Amarasiriwardena, Chitra J; Lupoli, Nicola

    2011-01-01

    The use of cisplatin, a first line chemotherapy for most cancers, is dose-limited due to nephrotoxicity. While this toxicity can be addressed through nanotechnology, previous attempts at engineering cisplatin nanoparticles have been limited by the impact on the potency of cisplatin. Here we report the rational engineering of a novel cisplatin nanoparticle by harnessing a novel polyethylene glycol-functionalized poly-isobutylene-maleic acid (PEG-PIMA) copolymer, which can complex with cis-platinum (II) through a monocarboxylato and a coordinate bond. We show that this complex self-assembles into a nanoparticle, and exhibits an IC 50 = 0.77 ± 0.11 μM comparable to that of free cisplatin (IC 50 = 0.44 ± 0.09 μM). The nanoparticles are internalized into the endolysosomal compartment of cancer cells, and release cisplatin in a pH-dependent manner. Furthermore, the nanoparticles exhibit significantly improved antitumor efficacy in a 4T1 breast cancer model in vivo, with limited nephrotoxicity, which can be explained by preferential biodistribution in the tumor with reduced kidney concentrations. Our results suggest that the PEG-PIMA-cisplatin nanoparticle can emerge as an attractive solution to the challenges in cisplatin chemotherapy.

  1. Design, Synthesis and Antitumor Evaluation of Novel Pyrazolopyrimidines and Pyrazoloquinazolines

    Directory of Open Access Journals (Sweden)

    Mohamed El-Naggar

    2018-05-01

    Full Text Available A series of N-aryl-7-aryl-pyrazolo[1,5-a]pyrimidines 18a–u and N-aryl-pyrazolo[1,5-a]quinazolines 25a–c were designed and synthesized via the reaction of 5-aminopyrazoles 11a–c with enaminones 12a–g or 19, respectively. The new compounds were screened for their in vitro antitumor activity toward liver (HepG-2 and breast (MCF-7 human cancer cells using 3-[4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide MTT assay. From the results, it was found that all compounds showed dose-dependent cytotoxic activities against both HepG-2 and MCF-7 cells. Two compounds 18o and 18a were selected for further investigations. Cell cycle analysis of liver (HepG-2 cells treated with 18o and breast (MCF-7 cells treated with 18a showed cell cycle arrest at G2/M phase and pro-apoptotic activity as indicated by annexin V-FITC staining.

  2. Anti-Tumor Activity of a Polysaccharide from Blueberry

    Directory of Open Access Journals (Sweden)

    Xiyun Sun

    2015-02-01

    Full Text Available Blueberries (Vaccinium spp. are rich in bioactive compounds. However, the biological activity of polysaccharides from blueberry has not been reported so far. This study evaluated the anti-tumor and immunological activities of a polysaccharide (BBP3-1 from blueberry in S180-bearing mice. The experimental results indicated that BBP3-1 (100 mg·kg−1·d−1 inhibited the tumor growth rate by 73.4%. Moreover, this group, compared with the model control, had shown an effect of increasing both the spleen and thymus indices (p < 0.05, increasing phagocytosis by macrophages (p < 0.05, boosting the proliferation and transformation of lymphocytes (p < 0.01, promoting the secretion of TNF-α, IFN-γ, and IL-2 (p < 0.05 and improving NK cell activity (p < 0.01. From this study, we could easily conclude that BBP3-1 has the ability to inhibit tumor progression and could act as a good immunomodulator.

  3. Antimicrobial peptides with selective antitumor mechanisms: prospect for anticancer applications.

    Science.gov (United States)

    Deslouches, Berthony; Di, Y Peter

    2017-07-11

    In the last several decades, there have been significant advances in anticancer therapy. However, the development of resistance to cancer drugs and the lack of specificity related to actively dividing cells leading to toxic side effects have undermined these achievements. As a result, there is considerable interest in alternative drugs with novel antitumor mechanisms. In addition to the recent approach using immunotherapy, an effective but much cheaper therapeutic option of pharmaceutical drugs would still provide the best choice for cancer patients as the first line treatment. Ribosomally synthesized cationic antimicrobial peptides (AMPs) or host defense peptides (HDP) display broad-spectrum activity against bacteria based on electrostatic interactions with negatively charged lipids on the bacterial surface. Because of increased proportions of phosphatidylserine (negatively charged) on the surface of cancer cells compared to normal cells, cationic amphipathic peptides could be an effective source of anticancer agents that are both selective and refractory to current resistance mechanisms. We reviewed herein the prospect for AMP application to cancer treatment, with a focus on modes of action of cationic AMPs.

  4. Meroterpenoids with Antitumor Activities from Guava (Psidium guajava).

    Science.gov (United States)

    Qin, Xu-Jie; Yu, Qian; Yan, Huan; Khan, Afsar; Feng, Mi-Yan; Li, Pan-Pan; Hao, Xiao-Jiang; An, Lin-Kun; Liu, Hai-Yang

    2017-06-21

    Psidium guajava L., a species native to South America, has been widely cultivated in the tropical and subtropical areas of China for its popular fruits. The preliminary analysis by liquid chromatography-ultraviolet (LC-UV) indicated the presence of meroterpenoids in the fruits of P. guajava (guava). Subsequent fractionation of the petroleum ether extract resulted in the identification of two new meroterpenoids, psiguajavadials A (1) and B (2), together with 14 previously described meroterpenoids (3-16). Their structures were fully elucidated by comprehensive spectroscopic techniques and theoretical calculations. All of the meroterpenoids showed cytotoxicities against five human cancer cell lines, with guajadial B (12) being the most effective having an IC 50 value of 150 nM toward A549 cells. Furthermore, biochemical topoisomerase I (Top1) assay revealed that psiguajavadial A (1), psiguajavadial B (2), guajadial B (12), guajadial C (14), and guajadial F (16) acted as Top1 catalytic inhibitors and delayed Top1 poison-mediated DNA damage. The flow cytometric analysis indicated that the new meroterpenoids psiguajavadials A (1) and B (2) could induce apoptosis of HCT116 cells. These data suggest that meroterpenoids from guava fruit could be used for the development of antitumor agents.

  5. Experimental study of anti-tumor activity of direct current

    International Nuclear Information System (INIS)

    Ito, Hisao; Hashimoto, Shozo

    1989-01-01

    The anti-tumor activity of direct current combined with radiation was studied. The experiments were performed with fibrosarcomas (FSA, NFSA) syngenetic to C3H mice. Direct current (0.6mA, 120min) alone was effective to reduce the tumor sizes, but could not cure the tumors. When the direct current therapy (DC therapy) was combined with radiation the DC therapy following radiation was more effective than that before radiation. Using TCD 50 assay, the DC therapy enhanced the effect of a single dose of radiation with the dose-modifying factor of 1.2. However, tumor control rates by the combination therapy were more improved at the smaller doses of radiation than at the larger ones. When the single DC therapy (0.6mA, 120min) was applied immediately after the first radiation of fractionated one the combination therapy still showed the enhanced effect. However, both DC therapy and the radiation therapy were divided in three fractions, and the DC therapy (0.6mA, 40min) was applied after each radiation. Tumor growth retardation by the combination therapy was no different from that by radiation alone. This result suggests that there might be a minimum required dose of coulombs to show the effect of the combination therapy. (author)

  6. Stimulation of granulocytic cell iodination by pine cone antitumor substances

    International Nuclear Information System (INIS)

    Unten, S.; Sakagami, H.; Konno, K.

    1989-01-01

    Antitumor substances (Fractions VI and VII) prepared from the NaOH extract of pine cone significantly stimulated the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood adherent mononuclear cells, polymorphonuclear cells (PMN), and human promyelocytic leukemic HL-60 cells. In contrast, these fractions did not significantly increase the iodination of nonadherent mononuclear cells, red blood cells, other human leukemic cell lines (U-937, THP-1, K-562), human diploid fibroblast (UT20Lu), or mouse cell lines (L-929, J774.1). Iodination of HL-60 cells, which were induced to differentiate by treatment with either retinoic acid or tumor necrosis factor, were stimulated less than untreated cells. The stimulation of iodination of both PMN and HL-60 cells required the continuous presence of these fractions and was almost completely abolished by the presence of myeloperoxidase inhibitors. The stimulation activity of these fractions was generally higher than that of various other immunopotentiators. Possible mechanisms of extract stimulation of myeloperoxidase-containing cell iodination are discussed

  7. Antitumor Lipids--Structure, Functions, and Medical Applications.

    Science.gov (United States)

    Kostadinova, Aneliya; Topouzova-Hristova, Tanya; Momchilova, Albena; Tzoneva, Rumiana; Berger, Martin R

    2015-01-01

    Cell proliferation and metastasis are considered hallmarks of tumor progression. Therefore, efforts have been made to develop novel anticancer drugs that inhibit both the proliferation and the motility of tumor cells. Synthetic antitumor lipids (ATLs), which are chemically divided into two main classes, comprise (i) alkylphospholipids (APLs) and (ii) alkylphosphocholines (APCs). They represent a new entity of drugs with distinct antiproliferative properties in tumor cells. These compounds do not interfere with the DNA or mitotic spindle apparatus of the cell, instead, they incorporate into cell membranes, where they accumulate and interfere with lipid metabolism and lipid-dependent signaling pathways. Recently, it has been shown that the most commonly studied APLs inhibit proliferation by inducing apoptosis in malignant cells while leaving normal cells unaffected and are potent sensitizers of conventional chemo- and radiotherapy, as well as of electrical field therapy. APLs resist catabolic degradation to a large extent, therefore accumulate in the cell and interfere with lipid-dependent survival signaling pathways, notably PI3K-Akt and Raf-Erk1/2, and de novo phospholipid biosynthesis. They are internalized in the cell membrane via raft domains and cause downstream reactions as inhibition of cell growth and migration, cell cycle arrest, actin stress fibers collapse, and apoptosis. This review summarizes the in vitro, in vivo, and clinical trials of most common ATLs and their mode of action at molecular and biochemical levels. © 2015 Elsevier Inc. All rights reserved.

  8. Estimativa do vigor das sementes e das plântulas de Bixa orellana L.

    Directory of Open Access Journals (Sweden)

    Roberta Leopoldo Ferreira

    Full Text Available RESUMO A multiplicação de espécies como as da planta de urucum tem limitações em função do conhecimento limitado das características morfológicas e fisiológicas das sementes e das plântulas e da restrição de métodos para determinar a qualidade dessas sementes. Nessa pesquisa, o objetivo foi estudar a adequação do teste de envelhecimento acelerado para estimar o vigor das sementes de urucum (Bixa orellana L., relacionando os resultados desse teste com a formação das plântulas e as diferenças de genótipo dos acessos genéticos. As sementes de urucum, representadas por quatro acessos genéticos, e por três lotes, foram avaliadas pelos testes de germinação, primeira contagem da germinação, classificação do vigor das plântulas e emergência das plântulas (total e índice de velocidade. No teste de envelhecimento acelerado foram avaliados a temperatura, de 41 ºC, e os períodos, de 48; 72 e 96 horas, de exposição das sementes às umidades relativas de 100% (água e de 76% (solução saturada de NaCl. A solução saturada reduz a quantidade de água absorvida pelas sementes de urucum, expostas às condições do teste de envelhecimento acelerado, reduzindo a deterioração das sementes, favorecendo a uniformidade dos resultados e a redução da proliferação de fungos, comuns na germinação das sementes de urucum. O teste de envelhecimento acelerado, com água ou solução salina, por 72 horas ou 96 horas, é eficiente para classificar as sementes de urucum quanto à qualidade. Assim, as variações dos teores de água das sementes de urucum devem ser entre 23;6 e 28;9% (72 horas e 29;7 e 32;9% (96 horas para a utilização da água e entre 7,3 e 9,5% para a utilização da solução salina de NaCl.

  9. Das Bauhaus in Bewegung - wie das Bauhausgebäude in Dessau funktioniert

    OpenAIRE

    Seyler Thomas

    2016-01-01

    Analyse und Deutung des Bauhausentwurfs - wie das Bauhaus funktioniert Ein Architekt analysiert und deutet den Bauhausentwurf Das Bauhaus in Dessau gilt als Inbegriff einer räumlich freien Anordnung. Diese lässt sich jedoch auf den Prozess einer Entfaltung zurückführen. Der Autor erklärt Schritt für Schritt die Systematik des Entwurfs aus seiner beruflichen Erfahrung.

  10. MENYOAL KESENJANGAN ANTARA DAS SOLLEN ISLAM DENGAN DAS SEIN PRAKSIS KEHIDUPAN KAUM MUSLIMIN

    Directory of Open Access Journals (Sweden)

    Yusuf Suyono

    2016-03-01

    Full Text Available Abstract:This paper embarks from the question why the valuable Islamic ethics cannot be ethos grounded in the nation-state Muslim majority country-including in Indonesia? Phenomena such as the majlis taklim, majlis dhikr, interest pilgrimage exceeds the quota, the Islamic banking activity is equally excited, is real. However, it is not enough. Muslims should master the science, economics, and the strategic role of national politics. Islamic ethics is Dassollen, the Muslims condition is DasSein. ProphetMuḥammad has abled to unite Das sein andDassollenin his life, because Islam hasbecomehis bloodso that he is a mirror and store front of Islampar excellence. Muslims, as his follower, not been able todo like him. Al-Amir ArsalanSyākib, Muḥammad ‘Abduh, MohammadIqbal, Muḥammadal-Ghazālī, Ḥassan Ḥanafihavetried to formulatehow tobridge the gapbetween Das sollenandDasSein forMuslims. Theyhave adeep concern about thewide gapbetweenDasSeinpraxis in life of Muslims with DassollenIslamicteachings in slogan ya’lu walā yu’la ‘alaih. Whileatthe same timetheyseehowthe berufethos of Calvinismcouldencouragethe ethos ofmoderncapitalismto its adherentsin Western Europe, a Zen Buddhistethoscouldpushthe Japaneseintothe Asiantigers, andspirit Confucius encouragethe Korean peopleintothe Asiandragon. Abstrak:Tulisan ini berangkat dari pertanyaan mengapa etika Islam yang adiluhung itu tidak bisa membumi menjadi etos bangsa di negara-negara yang mayoritas penduduknya Muslim–termasuk di Indonesia. Fenomena seperti majlis taklim, majlis zikir, minat menunaikan ibadah haji melebihi kuota, aktivitas perbankan syariah tak kalah bersemangat, adalah nyata. Namun, itu tidak cukup. Umat Islam seharusnya lebih dari itu dalam penguasaan ilmu pengetahuan, ekonomi, dan peran strategis politik kebangsaan. Etika Islam itulah Das Sollen, keadaan kaum Muslimin itulah Das Sein. Muhammad Rasulullah telah mampu menyatukan Das Sein dan Das Sollen dalam hidupnya. Hal

  11. Potentiation of antitumor immunity in tumor-bearing mice by a degraded D-manno-D-glucan (DMG), a new antitumor polysaccharide.

    Science.gov (United States)

    Nakajima, H; Kita, Y; Hashimoto, S; Tsukada, W; Abe, S; Mizuno, D

    1983-12-01

    DMG, a degraded D-manno-D-glucan from the culture fluid of Microellobosporia grisea, inhibited the growth of murine syngeneic MM46 mammary carcinoma. Mice in which the tumor had completely regressed by DMG treatment showed tumor-specific antitumor resistance. The antitumor action of DMG was studied by examining the influences of DMG on tumor-specific and non-specific immune responses in tumor-bearing hosts. The tumor-specific delayed hypersensitivity reaction appeared transiently on day 7 after tumor inoculation but had decreased by day 15 in untreated tumor-bearing mice. In contrast, the reaction was retained and augmented in DMG-treated tumor-bearing mice. The tumor-neutralizing activity of spleen cells from DMG-treated tumor-bearing mice, tested by a Winn assay, was tumor-specific and significantly higher than that of untreated tumor-bearing mice. The tumor-neutralizing activity of peritoneal cells and the in vitro cytostatic activity of peritoneal macrophages in response to lymphokine supernatants containing macrophage activation factor were also augmented by DMG treatment. In contrast, the level of antitumor antibody in the serum increased with time, irrespective of DMG administration. Thus, DMG potentiated cellular antitumor effector mechanisms.

  12. Moisture Forecast Bias Correction in GEOS DAS

    Science.gov (United States)

    Dee, D.

    1999-01-01

    Data assimilation methods rely on numerous assumptions about the errors involved in measuring and forecasting atmospheric fields. One of the more disturbing of these is that short-term model forecasts are assumed to be unbiased. In case of atmospheric moisture, for example, observational evidence shows that the systematic component of errors in forecasts and analyses is often of the same order of magnitude as the random component. we have implemented a sequential algorithm for estimating forecast moisture bias from rawinsonde data in the Goddard Earth Observing System Data Assimilation System (GEOS DAS). The algorithm is designed to remove the systematic component of analysis errors and can be easily incorporated in an existing statistical data assimilation system. We will present results of initial experiments that show a significant reduction of bias in the GEOS DAS moisture analyses.

  13. Das Selenoproteom des Malariaerregers Plasmodium falciparum

    OpenAIRE

    Röseler, Anne

    2010-01-01

    Die Protozoen des Genus Plasmodium verursachen weltweit rund 247 Millionen Malariafälle jedes Jahr. Da der Malariaparasit schnell und effektiv Resistenzen gegen neue Antimalaria-Medikamente entwickelt, ist es notwendig, stets innovative Wirkstoffe zu finden. Dabei spielen das Verständnis der grundlegenden Stoffwechselfunktionen und die Entdeckung neuer potenzieller drug targets wichtige Rollen in der präklinischen Forschung. Während ihrer Lebensphasen in menschlichen Erythrozyten und dem ...

  14. Droht den "kleinen Sprachen" das Aussterben?

    Directory of Open Access Journals (Sweden)

    Anita Lemić

    2014-12-01

    Full Text Available Die Prozesse der Globalisierung sind die Ursache für viele Änderungen in der Weltgemeinschaft, vor allem die Entfernung von Unterscheidungsmerkmalen (in Bezug darauf, dass „zwischen vielen ethnischen Zeichen, das was dauernd ist, ist die Dichotomisierung/Differenzierung eines „Wir-und-die-Anderen“ (Grbić, 2003, 93-64. Diese Zeichen wirken als Zeichen der Resozialisierung, die die bestehenden Identitäten löschen und sich an der Schaffung neuer Strukturen beteiligen. Die Zeit der Romantik in Europa ermöglichte die Schaffung von Nationalstaaten und ihr Hauptmerkmal war die Nationalsprache. Diese Art der sozialen Differenzierung hatte das Ziel, die Illusion einer vollständig homogenisierten Gesellschaft zu schaffen und damit den Prozess der Zerstörung der „kleinen“ Sprachen zu beginnen. Sprache und Kultur erwiesen sich als Grundlage der Gemeinschaftserhaltung. Die Homogenisierung ermöglicht Aktivitäten mit dem Ziel, einem Individuum zu helfen, sich als Individuum und als Mitglied der Gemeinschaft zu behaupten. Keine dieser beiden Identitäten kann ohne die Wechselwirkung mit der Umgebung erreicht werden. Die sprachliche Interaktion mit anderen Mitgliedern ist das Schlüsselsegment, das Menschen von anderen Lebensformen unterscheidet. Durch den Austausch von Erfahrungen mit anderen kommt der Mensch auf allen Ebenen voran und mit der Erfindung der Schrift öffnete er die Tür zur Entwicklung der Zivilisation. In dieser Arbeit beschäftigen wir uns mit der Frage der „Prestige“-Sprachen, die auf der Grundlage der Macht der Gemeinschaft der Muttersprachler ihren Bereich weit über die Grenzen des eigenen Landes hinaus erweitern und so eine politische und wirtschaftliche Vormachtstellung schaffen, aber auch mit den Auswirkungen jener Sprachen auf die Dekonstruktion oder möglicherweise vollständige Ausrottung der Sprachen, die auf diese Weise an Einfluss verlieren, unmodern werden und sich die Frage der Notwendigkeit ihrer

  15. DISPOSITIVO DAS DROGAS E GOVERNO DA VIDA

    Directory of Open Access Journals (Sweden)

    Wanderson Vilton Silva

    Full Text Available Resumo Na perspectiva da Psicologia Social em diálogo com as teorizações de Michel Foucault e Giorgio Agamben, o objetivo deste artigo é problematizar de que maneira as drogas são constituídas como explicação para assassinatos de moradores de rua, construindo práticas e discursos relacionados ao governo da vida e da morte nas cidades. O material que apresentamos consiste em textos midiáticos e documentos públicos elaborados entre julho de 2010 e novembro de 2012 abordando tais assassinatos. Analisamos como o dispositivo das drogas formula uma ambiguidade e uma complexidade importantes para o governo dos moradores de rua a partir da construção de oposições: criminoso ou em situação de vulnerabilidade social. Procuramos contribuir criticamente com políticas públicas que visem os diversos modos de existir na cidade, pensar os espaços urbanos, os modos de governo e os processos de subjetivação, considerando a análise da ambiguidade e da complexidade produzidas em torno do dispositivo das drogas.

  16. Curcumin exerts its antitumor effects in a context dependent fashion.

    Science.gov (United States)

    Kreutz, Dominique; Sinthuvanich, Chomdao; Bileck, Andrea; Janker, Lukas; Muqaku, Besnik; Slany, Astrid; Gerner, Christopher

    2018-06-30

    Proteome profiling profoundly contributes to the understanding of cell response mechanisms to drug actions. Such knowledge may become a key to improve personalized medicine. In the present study, the effects of the natural remedy curcumin on breast cancer model systems were investigated. MCF-7, ZR-75-1 and TGF-β1 pretreated fibroblasts, mimicking cancer-associated fibroblasts (CAFs), were treated independently as well as in tumor cell/CAF co-cultures. Remarkably, co-culturing with CAF-like cells (CLCs) induced different proteome alterations in MCF-7 and ZR-75-1 cells, respectively. Curcumin significantly induced HMOX1 in single cell type models and co-cultures. However, other curcumin effects differed. In the MCF-7/CLC co-culture, curcumin significantly down-regulated RC3H1, a repressor of inflammatory signaling. In the ZR-75-1/CLC co-culture, curcumin significantly down-regulated PEG10, an anti-apoptotic protein, and induced RRAGA, a pro-apoptotic protein involved in TNF-alpha signaling. Furthermore, curcumin induced AKR1C2, an important enzyme for progesterone metabolism. None of these specific curcumin effects were observed in single cell type cultures. All high-resolution mass spectrometry data are available via ProteomeXchange with the identifier PXD008719. The present data demonstrate that curcumin induces proteome alterations, potentially accounting for its known antitumor effects, in a strongly context-dependent fashion. Better means to understand and potentially predict individual variations of drug effects are urgently required. The present proteome profiling study of curcumin effects demonstrates the massive impact of the cell microenvironment on cell responses to drug action. Co-culture models apparently provide more biologically relevant information regarding curcumin effects than single cell type cultures. Copyright © 2018. Published by Elsevier B.V.

  17. Anti-tumor therapy with macroencapsulated endostatin producer cells.

    Science.gov (United States)

    Rodrigues, Danielle B; Chammas, Roger; Malavasi, Natália V; da Costa, Patrícia L N; Chura-Chambi, Rosa M; Balduino, Keli N; Morganti, Ligia

    2010-03-02

    Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors. Mice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments. This study indicates that immunoisolation devices containing endostatin

  18. The antitumor natural product tanshinone IIA inhibits protein kinase C and acts synergistically with 17-AAG.

    Science.gov (United States)

    Lv, Chao; Zeng, Hua-Wu; Wang, Jin-Xin; Yuan, Xing; Zhang, Chuang; Fang, Ting; Yang, Pei-Ming; Wu, Tong; Zhou, Yu-Dong; Nagle, Dale G; Zhang, Wei-Dong

    2018-02-07

    Tanshinone IIA (Tan IIA), the primary bioactive compound derived from the traditional Chinese medicine (TCM) Salvia miltiorrhiza Bunge, has been reported to possess antitumor activity. However, its antitumor mechanisms are not fully understood. To resolve the potential antitumor mechanism(s) of Tan IIA, its gene expression profiles from our database was analyzed by connectivity map (CMAP) and the CMAP-based mechanistic predictions were confirmed/validated in further studies. Specifically, Tan IIA inhibited total protein kinase C (PKC) activity and selectively suppressed the expression of cytosolic and plasma membrane PKC isoforms ζ and ε. The Ras/MAPK pathway that is closely regulated by the PKC signaling is also inhibited by Tan IIA. While Tan IIA did not inhibit heat shock protein 90 (Hsp90), it synergistically enhanced the antitumor efficacy of the Hsp90 inhibitors 17-AAG and ganetespib in human breast cancer MCF-7 cells. In addition, Tan IIA significantly inhibited PI3K/Akt/mTOR signaling, and induced both cell cycle arrest and autophagy. Collectively, these studies provide new insights into the molecular mechanisms responsible for antitumor activity of Tan IIA.

  19. Oncolytic Immunotherapy: Dying the Right Way is a Key to Eliciting Potent Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Zong Sheng eGuo

    2014-04-01

    Full Text Available Oncolytic viruses (OVs are novel immunotherapeutic agents whose anticancer effects come from both oncolysis and elicited antitumor immunity. OVs induce mostly immunogenic cancer cell death (ICD, including immunogenic apoptosis, necrosis/necroptosis, pyroptosis and autophagic cell death, leading to exposure of calreticulin and heat-shock proteins to the cell surface, and/or released ATP, high mobility group box-1 [HMGB1], uric acid, and other DAMPs as well as PAMPs as danger signals, along with tumor-associated antigens, to activate dendritic cells (DCs and elicit adaptive antitumor immunity. Dying the right way may greatly potentiate adaptive antitumor immunity. The mode of cancer cell death may be modulated by individual OVs and cancer cells as they often encode and express genes that inhibit/promote apoptosis, necroptosis or autophagic cell death. We can genetically engineer OVs with death-pathway-modulating genes and thus skew the infected cancer cells towards certain death pathways for the enhanced immunogenicity. Strategies combining with some standard therapeutic regimens may also change the immunological consequence of cancer cell death. In this review, we discuss recent advances in our understanding of danger signals, modes of cancer cell death induced by OVs, the induced danger signals and functions in eliciting subsequent antitumor immunity. We also discuss potential combination strategies to target cells into specific modes of ICD and enhance cancer immunogenicity, including blockade of immune checkpoints, in order to break immune tolerance, improve antitumor immunity and thus the overall therapeutic efficacy.

  20. Antitumor Effects of Palladium-α-Lipoic Acid Complex Formulation as an Adjunct in Radiotherapy.

    Science.gov (United States)

    Veena, Ravindran Kalathil; Ajith, Thekkuttuparambil Ananthanarayanan; Janardhanan, Kainoor Krishnankutty; Antonawich, Francis

    2016-01-01

    Several investigations have been initiated to enhance the antitumor effect of radiation and ameliorate its adverse effects such as reducing blood cell counts and causing DNA damage in normal cells. Compounds that enhance the antitumor activity of radiation without reducing blood cell counts or damaging DNA in normal cells can be of immense use as an adjunct in radiotherapy. We evaluated the antitumor effect of a specific set of minerals, vitamins, and amino acids (Poly-MVA) (2 mL/kg, per os), with and without radiation, against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines that were transplanted in a solid-tumor model. Whole-body γ-radiation exposure (2 Gy) was performed using 60Co. Poly-MVA enhanced the antitumor effect of radiation when administered beforehand. Furthermore, Poly-MVA administered once daily for 2 wk, immediately after 4 Gy irradiation, protected DNA damage in peripheral blood. It also rendered protection against the radiation-induced reduction of platelet count. The unique electronic and redox properties of palladium-α-lipoic acid complex in Poly-MVA appear to be responsible for the exhibited effect. The results conclude that the antitumor-enhancing and normal cell-protective effect of Poly-MVA warrants additional studies for its potential clinical application.

  1. Antibacterial, antioxidant and antitumor properties of Moroccan medicinal plants: A review

    Directory of Open Access Journals (Sweden)

    Abdelhakim Bouyahya

    2017-01-01

    Full Text Available Aromatic and medicinal plants have been traditionally used since antiquity to fight against illnesses. Recently, several researches have focused on the pharmacological properties and various bioactivities of natural products are extracted from medicinal plants, including the properties of antibacterial, antitumor and antioxidant activities. The products of medicinal plants are the secondary metabolites belonging to different compound classes such as essential oils, polyphenols, flavonoids and other phytochemical classes. In Morocco, medicinal plants are the major source of bioactive compounds and the majority of them are used in phytotherapy. The biological potential of various Moroccan medicinal plants attracts a lot of interest in the literature. They include antibacterial, antioxidant and antitumor investigations. In this context, this work aims at discussing antibacterial, antitumor and antioxidant properties of Moroccan medicinal plants.

  2. Synthesis and antitumor testing of certain new fused triazolopyrimidine and triazoloquinazoline derivatives

    Directory of Open Access Journals (Sweden)

    Ghada S. Hassan

    2017-02-01

    Full Text Available New series of 1,2,4-triazolopyrimidine and 1,2,4-triazoloquinazoline derivatives were designed, synthesized, and evaluated for their antitumor activity. Compounds 6, 11, 26, 29, 41, 44, 48, 49 and 58 were tested as antitumor agents by the use of DNA-binding assay on TLC-plates, colorimetric assay for the degree of DNA-binding (Methyl green-DNA displacement assay, evaluation of antineoplastic activity against Ehrlich Ascites Carcinoma in mice, and finally modulation of apoptosis. 5-Flurouracil, vitamin C and ethidium bromide were used as positive controls in these techniques. Compound 26 proved to be the most active member of these series as antitumor agent with IC50 value of 47 ± 1. Several characteristic features were observed to be essential for activity such as the morpholine group and the phenylazo group, in addition the electron-withdrawing groups favor the activity than the electron-donating ones.

  3. NKT cells as an ideal anti-tumor immunotherapeutic.

    Science.gov (United States)

    Fujii, Shin-Ichiro; Shimizu, Kanako; Okamoto, Yoshitaka; Kunii, Naoki; Nakayama, Toshinori; Motohashi, Shinichiro; Taniguchi, Masaru

    2013-12-02

    Human natural killer T (NKT) cells are characterized by their expression of an invariant T cell antigen receptor α chain variable region encoded by a Vα24Jα18 rearrangement. These NKT cells recognize α-galactosylceramide (α-GalCer) in conjunction with the MHC class I-like CD1d molecule and bridge the innate and acquired immune systems to mediate efficient and augmented immune responses. A prime example of one such function is adjuvant activity: NKT cells augment anti-tumor responses because they can rapidly produce large amounts of IFN-γ, which acts on NK cells to eliminate MHC negative tumors and also on CD8 cytotoxic T cells to kill MHC positive tumors. Thus, upon administration of α-GalCer-pulsed DCs, both MHC negative and positive tumor cells can be effectively eliminated, resulting in complete tumor eradication without tumor recurrence. Clinical trials have been completed in a cohort of 17 patients with advanced non-small cell lung cancers and 10 cases of head and neck tumors. Sixty percent of advanced lung cancer patients with high IFN-γ production had significantly prolonged median survival times of 29.3 months with only the primary treatment. In the case of head and neck tumors, 10 patients who completed the trial all had stable disease or partial responses 5 weeks after the combination therapy of α-GalCer-DCs and activated NKT cells. We now focus on two potential powerful treatment options for the future. One is to establish artificial adjuvant vector cells containing tumor mRNA and α-GalCer/CD1d. This stimulates host NKT cells followed by DC maturation and NK cell activation but also induces tumor-specific long-term memory CD8 killer T cell responses, suppressing tumor metastasis even 1 year after the initial single injection. The other approach is to establish induced pluripotent stem (iPS) cells that can generate unlimited numbers of NKT cells with adjuvant activity. Such iPS-derived NKT cells produce IFN-γ in vitro and in vivo upon

  4. Anti-tumor therapy with macroencapsulated endostatin producer cells

    Directory of Open Access Journals (Sweden)

    Balduino Keli N

    2010-03-01

    Full Text Available Abstract Background Theracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors. Results Mice were inoculated subcutaneously with melanoma (B16F10 cells or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments. Conclusions This study indicates that

  5. Das Widerspenstige bändigen

    OpenAIRE

    Ittner, Helmut

    2016-01-01

    Dem Handeln von Lehrkräften wird in der schulischen Praxis wie in der wissenschaftlichen Literatur ein wesentlicher Einfluss auf die Qualität von schulischem Unterricht zugesprochen. Auch wenn umfangreiche normative Vorstellungen über ein gutes Lehr-Handeln bestehen, so gibt es wenig Erkenntnis darüber, welche Gründe Lehrkräfte für ihr pädagogisches Handeln haben. Das Handeln von Lehrkräften kann nur dann adäquat erfasst werden, wenn Bildung einerseits als Weitergabe von Kultur an die nachfol...

  6. Das COSO Enterprise Risk Management-Framework

    OpenAIRE

    Ruud, Flemming; Reichert, Felix

    2007-01-01

    Der Verwaltungsrat und die Geschäftsleitung tragen die Verantwortung, ein Internes Kontrollsystem (IKS) im Unternehmen auszugestalten. Ab dem Geschäftsjahr 2008 wird die Existenz eines IKS durch den externen Revisor geprüft (Art. 728a, 728b revOR). Auch sind im Anhang Angaben über die Durchführung einer Risikobeurteilung zu publizieren (Art. 663b revOR). Das Enterprise-Risk-Management-Framework von COSO (COSO ERM) kann als Führungsinstrument helfen, wichtige Chancen und Risiken zu erkennen...

  7. Macht auf das Tor! - Opens the gate!

    Directory of Open Access Journals (Sweden)

    Claudemir de Quadros

    2011-09-01

    Full Text Available Macht auf das Tor! (Abra o portão foi publicado, possivelmente, na primeira metade do século 20. Editado por Max Dirkschneider, Raimund Heuler e Felix Oberborbeck, apresenta músicas, rimas, piadas, jogos e canções.A edição apresentada nesse espaço é de um livro que pertence à família de Carolina Drebes, estudante do curso de Pedagogia do Centro Universitário Franciscano, Santa Maria/RS.

  8. Para politizar o mundo das coisas

    Directory of Open Access Journals (Sweden)

    Thiago Machado Balbi

    2014-12-01

    Full Text Available To politicize the world of things – This review presents A comunicação das coisas: teoria ator-rede e cibercultura [The communication of things: Actor-network theory and cyberculture], by André Lemos, raising its key aspects. In a constant dialogue with Bruno Latour's theory, and other like-minded authors, Lemos offers to Brazilian readers more than a book about cyberculture, but a deep reflection about communication and hybridization between people and things, namely, humans and non-humans, dealing with the political, ethical and pedagogical consequences of the hybrids in society.

  9. Evaluasi perubahan penutupan lahan di DAS Babalan

    OpenAIRE

    Restiana, Inda

    2015-01-01

    Evaluation of land use changes was conducted at DAS Babalan. The research was conducted since July 2012 until December 2012. The purpose of this research are to assess changes in forest land into oil palm land, mapping land suitability classes for palm oil and to know the quality of forest land and land oil palm. Method to assess changes in the land area is done by utilizing remote sensing and geographic information systems (GIS). assessing the changes was conducted by overlayed land use maps...

  10. Perfil das pacientes submetidas a gluteoplastia

    OpenAIRE

    José Horácio Costa Aboudib Júnior

    2014-01-01

    Durante nossas frequentes apresentações em cursos, congressos e jornadas e mesmo em nossas publicações, existiam constantes perguntas sobre o perfil dessas pacientes. O crescente interesse da mídia e das pacientes a este respeito e também a crescente procura pela cirurgia nos estimulou a realizar este trabalho. Segundo dados da Sociedade Brasileira de Cirurgia Plástica (SBPC) e da American Society of Plastic Surgery (ASPS), referem que 20.000 pacientes foram submetidas a esta cirurgia. Em 201...

  11. O Comportamento das Aves Poultry Behavior

    Directory of Open Access Journals (Sweden)

    EJ Campos

    2000-08-01

    Full Text Available Os estudos sobre o comportamento das aves, principalmente as galinhas, datam de 1912, quando o gênero Gallus passou a ser estudado com mais intensidade na área da Genética. Tais estudos eram simplesmente filosóficos até o início da década de 80, quando uma nova era da produção industrial avícola surgiu, objetivando um maior volume de produção econômica em todas as áreas de exploração. Esse objetivo reativou de maneira científica os estudos de comportamento das aves face à tecnologia de produção empregada nos sistemas de exploração, tornando-os mais acentuados já na década de 90, culminando com um simpósio internacional realizado nos Estados Unidos onde foram traçados os objetivos ou linhas de pesquisas na exploração avícola. O intuito era evitar problemas com os movimentos ambientalistas, traçando novos rumos para uma produção eficiente sem interferir no comportamento das aves já no início do novo milênio. Esta revisão, tem como objetivo principal uma análise científica e filosófica sobre o comportamento das aves em diversos métodos de exploração.Studies on poultry behavior initiated in 1972, at that time, fowls from Gallus domesticus species were the most important animal for the initial studies of Genetic. Since then, just the philosophical concepts where involved in those studies. However, at the beginning of 80 decade, these studies were intensified taking into account technological approaches for an economical industrial poultry production. Meanwhile, the reactions from activists involved in the behavior of the animal subjected to production became more strong at the beginning of 90's as well as those studies on chicken behavior. Finally, in 1998, an international symposium, promoted by chicken behavior scientists were held in the United States, in order to establish new methods of exploitation of poultry without interfering in its normal behavior, at the beginning of new millenium. The main

  12. Das CARNOTsche Paradigma und seine erkenntnistheoretischen Implikationen

    Science.gov (United States)

    Schöpf, Hans-Georg

    Der vorliegende historisch-kritische Essay führt die Eigentümlichkeiten der klassischen phänomenologischen Thermodynamik auf das von CARNOT geschaffene Paradigma zurück und greift einige damit zusammenhängende Fragen auf.Translated AbstractCARNOT's Paradigm and its Epistemological ImplicationsThe present historic-critical essay traces the pecularities of classical phenomenological thermodynamics back to the paradigm, created by CARNOT, and takes up some questions to which this paradigm gives rise.

  13. Intermittent Metronomic Drug Schedule Is Essential for Activating Antitumor Innate Immunity and Tumor Xenograft Regression

    Directory of Open Access Journals (Sweden)

    Chong-Sheng Chen

    2014-01-01

    Full Text Available Metronomic chemotherapy using cyclophosphamide (CPA is widely associated with antiangiogenesis; however, recent studies implicate other immune-based mechanisms, including antitumor innate immunity, which can induce major tumor regression in implanted brain tumor models. This study demonstrates the critical importance of drug schedule: CPA induced a potent antitumor innate immune response and tumor regression when administered intermittently on a 6-day repeating metronomic schedule but not with the same total exposure to activated CPA administered on an every 3-day schedule or using a daily oral regimen that serves as the basis for many clinical trials of metronomic chemotherapy. Notably, the more frequent metronomic CPA schedules abrogated the antitumor innate immune and therapeutic responses. Further, the innate immune response and antitumor activity both displayed an unusually steep dose-response curve and were not accompanied by antiangiogenesis. The strong recruitment of innate immune cells by the 6-day repeating CPA schedule was not sustained, and tumor regression was abolished, by a moderate (25% reduction in CPA dose. Moreover, an ~20% increase in CPA dose eliminated the partial tumor regression and weak innate immune cell recruitment seen in a subset of the every 6-day treated tumors. Thus, metronomic drug treatment must be at a sufficiently high dose but also sufficiently well spaced in time to induce strong sustained antitumor immune cell recruitment. Many current clinical metronomic chemotherapeutic protocols employ oral daily low-dose schedules that do not meet these requirements, suggesting that they may benefit from optimization designed to maximize antitumor immune responses.

  14. The effect of anti-tumor necrosis factor alpha agents on postoperative anastomotic complications in Crohn's disease

    DEFF Research Database (Denmark)

    El-Hussuna, Alaa Abdul-Hussein H; Krag, Aleksander; Olaison, Gunnar

    2013-01-01

    Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications.......Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications....

  15. Hydrogels based on polysaccharide-calcium phosphate with antibacterial / antitumor activity for 3D printing

    Science.gov (United States)

    Teterina, A. Yu; Fedotov, A. Yu; Zobkov, Yu V.; Sergeeva, N. S.; Sviridova, I. K.; Kirsanova, V. A.; Karalkin, P. A.; Komlev, V. S.

    2018-04-01

    The purpose of this study was to develop hydrogels for 3D printing of sodium alginate/gelatin/octacalcium phosphate-based constructs with antibacterial and antitumor activity intended for bone defects replacement in patients with malignant diseases. In this work, we evaluated the drug release kinetic and physico-chemical characteristics of constructs, as well as their specific activity, biocompatibility and osteoplastic properties by means of in vitro and in vivo tests. The principal possibility of creating the biocompatible bone substitutes with antibacterial/antitumor activity and osteoconductive-retaining properties of 3D printing method was demonstrated.

  16. Synthesis of sulfadimethoxine based surfactants and their evaluation as antitumor agents

    Directory of Open Access Journals (Sweden)

    Manal Mohmed Khowdiary

    2016-01-01

    Summary: The main goal of cancer therapy is to attain the maximum therapeutic damage of tumor cells in combination with a minimum concentration of the drug. This can be achieved in principle via selective antitumor preparations, the cytostatic effects of which would be restricted within tumor tissue. While 100% selectivity may be impractical, the achievement of reasonably high selectivity seems to be a feasible aim. Platinum and cobalt complex surfactants in our research affect tumor tissue at a very low concentration at values lower than their CMC values; this indicate that the sulfadimethoxine complexes merit further investigation as potential antitumor drugs.

  17. [Effective productions of plant secondary metabolites having antitumor activity by plant cell and tissue cultures].

    Science.gov (United States)

    Taniguchi, Shoko

    2005-06-01

    Methods for the effective production of plant secondary metabolites with antitumor activity using plant cell and tissue cultures were developed. The factors in tannin productivity were investigated using culture strains producing different types of hydrolyzable tannins, i.e., gallotannins (mixture of galloylglucoses), ellagi-, and dehydroellagitannins. Production of ellagi- and dehydroellagitannins was affected by the concentrations and ratio of nitrogen sources in the medium. The formation of oligomeric ellagitannins in shoots of Oenothera tetraptera was correlated with the differentiation of tissues. Cultured cells of Eriobotrya japonica producing ursane- and oleanane-type triterpenes with antitumor activities were also established.

  18. Das fantasias vazias ao referencial discursivo

    Directory of Open Access Journals (Sweden)

    Ricardo Salztrager

    2008-06-01

    Full Text Available Pretende-se analisar o estatuto de uma modalidade peculiar de fantasmatização para a qual propomos o nome de 'fantasias vazias'. No campo das fantasias vazias, a ambigüidade e a polissemia das palavras são postas de lado e seus enunciados se tornam absolutos e unívocos, de modo a anularem quaisquer possibilidades metafóricas ou simbólicas. Investigamos os limites que as fantasias em questão impõem à teoria do significante, propondo, em seguida, concebê-las como uma escritura balizada por uma série de elementos que denominamos 'referenciais discursivos'.From empty fantasies to dissertational reference. The purpose of the article is to analyze the state of a peculiar modality of fantasizing which we have named empty fantasies. Thus, in the field of empty fantasies, the ambiguity and the multiple meaning of the words are put aside and, for that reason, their statement becomes obsolete and univocal, in a way that they eliminate any metaphoric or symbolic possibilities. We investigate the limits that those fantasies impose to the theory of the signifier, proposing, then, to conceive them as a writing delimitated by a series of elements that we have called discourse references.

  19. Waste free drilling; Das abfallfreie Bohrkonzept

    Energy Technology Data Exchange (ETDEWEB)

    Hofstaetter, H. [Rohoel-Aufsuchungs AG, Wien (Austria)

    2001-07-01

    After several years of preparatory research and in cooperation with several universities and organisations, Rohloel-Aufsuchungs AG were successful in recycling not only the flushings but also the cuttings of the drilling process, i.e. there is no need for dumping the residues. This is important as the regional authorities in that region are highly reluctant to grant permits for constructing new landfills, owing to the fact that it is a region of freshwater reserves for a large part of Europe and also a region much frequented by tourists. The 'waste-free drilling concept' has been applied for almost one year now. Further optimisation measures are projected. [German] Der Rohoel-Aufsuchungs AG ist es nach mehrjaehrigen Vorarbeiten gemeinsam mit verschiedenen Universitaeten und Institutionen gelungen, nicht nur die gesamte Bohrspuelung sondern auch die im Zuge des Bohrprozesses anfallenden Cuttings einer vollstaendigen Wiederverwertung zuzufuehren: Durch eine triviale Veraenderung des Spuelungschemismus, die den vollstaendigen Ersatz von Kaliumchlorid durch Kaliumkarbonate vorsieht, konnte das Bohrklein vom ''Abfall'' zum ''Wirtschaftsgut'' augewertet werden. Mit diesem entscheidenden Schritt wird der Bau neuer Borschlammdeponien ueberfluessig, deren behoerdliche Genehmigung ohnehin als unwahrscheinlich angesehen werden muss, zumal in dieser Region Grundwasserreserven fuer einen Teil Europas liegen und der Tourismus zur Haupteinnahmequelle dieses Gebietes zaehlt. Das ''abfallfreie Bohrkonzept'' wird bei der Rohoel-Aufsuchungs AG seit nahezu einem Jahr erfolgreich umgesetzt. Weitere Optimierungsschritte sind noch geplant. (orig.)

  20. Determinação das curvas de secagem das sementes de andiroba em secador solar

    Directory of Open Access Journals (Sweden)

    Andreza P. Mendonça

    2015-04-01

    Full Text Available Comumente, o óleo de andiroba é extraído na Amazônia pelo método tradicional ou ainda por prensa. A eficiência na extração está relacionada ao aquecimento e ao teor de água das sementes. Desta forma, a determinação de um modelo de secagem que represente satisfatoriamente os dados experimentais é de suma importância para minimizar as alterações promovidas pelo processo obtendo-se, consequentemente, produto de qualidade. O objetivo do trabalho foi descrever a cinética de secagem das sementes de andiroba, tal como ajustar os modelos matemáticos aos dados experimentais usando-se secador solar. Foi utilizado, como critério do ajuste dos modelos matemáticos, o coeficiente de determinação, a magnitude do erro médio relativo e o desvio-padrão da estimativa. A secagem em menor tempo (14 dias da Carapa surinamensis para atingir o teor de água de equilíbrio (12,28% se deve, possivelmente, ao menor tamanho das sementes e à maior quantidade de óleo em relação à Carapa guianensis. O modelo Logarítmico e o de Midilli et al. foram os que melhor se ajustaram aos dados experimentais para as sementes das duas espécies de andiroba.

  1. HUMANIZAÇÃO DO DISCURSO DAS MARCAS DIANTE DAS NOVAS EXPERIÊNCIAS DE CONSUMO

    Directory of Open Access Journals (Sweden)

    Rogério Luiz Covaleski

    2014-01-01

    Full Text Available Tendo em vista que o processo de consumo não se resume à compra de mercadorias, e que vivenciamos um momento de negociação de discursos entre consumidores e anunciantes, potencializado pelas ferramentas dos meios de comunicação pós-massivos, este artigo pretende refletir sobre o fenômeno da humanização do discurso das marcas. Para isso, tomaremos como referência as considerações sobre a mudança do fluxo comunicacional da linguagem publicitária (BEKESAS, 2012, as características da cibercultura (LEMOS; LÉVY, 2010, a cultura da participação (SHIRKY, 2011 e a necessidade de uma conduta ética para a manutenção da credibilidade das empresas (BLACKSHAW, 2010. Neste trabalho, também citaremos casos ilustrativos da humanização dos discursos das marcas colhidas nas redes sociais na Internet, como forma de exemplificar os esforços das empresas em manter a integridade da imagem da marca no atual cenário do refluxo comunicacional. Palavras-chave: Discurso. Marcas. Consumo. Refluxo comunicacional. Mídias sociais.

  2. Snake venoms components with antitumor activity in murine melanoma cells; Componentes derivados de venenos de serpentes com acao antitumoral em celulas de melanoma murino

    Energy Technology Data Exchange (ETDEWEB)

    Queiroz, Rodrigo Guimaraes

    2012-07-01

    Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)

  3. Anticancer Effect of AntiMalarial Artemisinin Compounds | Das ...

    African Journals Online (AJOL)

    A PubMed search of about 127 papers on anti‑cancer effects of antimalarials has revealed that this class of drug, including other antimalarials, have several biological characteristics that include anticancer properties. ... Keywords: Anticancer agents, Antimalarials, Antitumor activity, Artemisinins, Novel chemotherapy ...

  4. As Muitas Arqueologias das Minas Gerais

    Directory of Open Access Journals (Sweden)

    André Prous

    2013-12-01

    Full Text Available Apresentamos uma história crítica das pesquisas em arqueologia - particularmente pré-histórica - realizadas em território mineiro desde o século XIX. Após a fase do pioneirismo (P. Lund, amadores diversos, missões internacionais estudam a região de Lagoa Santa no terceiro quarto do século XX, enquanto o Programa Nacional de Pesquisas Arqueológicas (PRONAPA inicia levantamentos no alto vale do rio São Francisco. Com a abertura de pesquisas mais sistemáticas pelo Instituto de Arqueologia Brasileira (IAB no Norte mineiro e a criação do Setor de Pesquisa da UFMG, na segunda metade dos anos de 1970, abre-se uma fase de pesquisas mais intensivas e regionais, tematicamente diversificadas. O início deste século XXI é marcado pela multiplicação das pesquisas preventivas e de resgate, a emergência de novos centros de pesquisa e a criação de cursos de formação de arqueólogos na UFMG. O Patrimônio pré-histórico de Minas Gerais é notável pela importância de preservação de materiais perecíveis, de restos esqueletais humanos de grande antiguidade, pela riqueza dos registros rupestres e a variedade regional das indústrias realizadas sobre matérias-primas muito diversas. A arqueologia histórica, cuja importância cresceu exponencialmente nos dois últimos decênios, é marcada pela importância dos vestígios da mineração de pedras e metais preciosos, dos assentamentos de escravos fugitivos e os remanescentes de fazendas antigas, cujo estudo se desenvolveu comparativamente mais que a arqueologia da urbanização e dos monumentos barrocos.

  5. Antitumor and antimicrobial activities and inhibition of in-vitro lipid ...

    African Journals Online (AJOL)

    The antitumor activity was measured in DLA cell line induced mice. Inhibition of in vitro lipid peroxidation activity of the D. nobile in both liver homogenate and RBC ghosts was also carried out. The aqueous extracts of stem and flower of D. nobile showed better zone of bacterial inhibition than that of ethanol and chloroform

  6. Effects of antitumor derivatives of ineffective transplatin on bacterial cells: Is DNA a pharmacological target?

    Czech Academy of Sciences Publication Activity Database

    Kašpárková, Jana; Brabec, Viktor

    2015-01-01

    Roč. 153, DEC2015 (2015), s. 206-210 ISSN 0162-0134 R&D Projects: GA ČR(CZ) GA14-21053S; GA MŠk(CZ) LD14019 Institutional support: RVO:68081707 Keywords : Transplatinum * Antitumor * Cellular target Subject RIV: BO - Biophysics Impact factor: 3.205, year: 2015

  7. TCR-Engineered, Customized, Antitumor T Cells for Cancer Immunotherapy: Advantages and Limitations

    Directory of Open Access Journals (Sweden)

    Arvind Chhabra

    2011-01-01

    Full Text Available The clinical outcome of the traditional adoptive cancer immunotherapy approaches involving the administration of donor-derived immune effectors, expanded ex vivo, has not met expectations. This could be attributed, in part, to the lack of sufficient high-avidity antitumor T-cell precursors in most cancer patients, poor immunogenicity of cancer cells, and the technological limitations to generate a sufficiently large number of tumor antigen-specific T cells. In addition, the host immune regulatory mechanisms and immune homeostasis mechanisms, such as activation-induced cell death (AICD, could further limit the clinical efficacy of the adoptively administered antitumor T cells. Since generation of a sufficiently large number of potent antitumor immune effectors for adoptive administration is critical for the clinical success of this approach, recent advances towards generating customized donor-specific antitumor-effector T cells by engrafting human peripheral blood-derived T cells with a tumor-associated antigen-specific transgenic T-cell receptor (TCR are quite interesting. This manuscript provides a brief overview of the TCR engineering-based cancer immunotherapy approach, its advantages, and the current limitations.

  8. TCR-engineered, customized, antitumor T cells for cancer immunotherapy: advantages and limitations.

    Science.gov (United States)

    Chhabra, Arvind

    2011-01-05

    The clinical outcome of the traditional adoptive cancer immunotherapy approaches involving the administration of donor-derived immune effectors, expanded ex vivo, has not met expectations. This could be attributed, in part, to the lack of sufficient high-avidity antitumor T-cell precursors in most cancer patients, poor immunogenicity of cancer cells, and the technological limitations to generate a sufficiently large number of tumor antigen-specific T cells. In addition, the host immune regulatory mechanisms and immune homeostasis mechanisms, such as activation-induced cell death (AICD), could further limit the clinical efficacy of the adoptively administered antitumor T cells. Since generation of a sufficiently large number of potent antitumor immune effectors for adoptive administration is critical for the clinical success of this approach, recent advances towards generating customized donor-specific antitumor-effector T cells by engrafting human peripheral blood-derived T cells with a tumor-associated antigen-specific transgenic T-cell receptor (TCR) are quite interesting. This manuscript provides a brief overview of the TCR engineering-based cancer immunotherapy approach, its advantages, and the current limitations.

  9. Medicinal Plants and Other Living Organisms with Antitumor Potential against Lung Cancer

    Directory of Open Access Journals (Sweden)

    Luara de Sousa Monteiro

    2014-01-01

    Full Text Available Lung cancer is a disease with high morbidity and mortality rates. As a result, it is often associated with a significant amount of suffering and a general decrease in the quality of life. Herbal medicines are recognized as an attractive approach to lung cancer therapy with little side effects and are a major source of new drugs. The aim of this work was to review the medicinal plants and other living organisms with antitumor potential against lung cancer. The assays were conducted with animals and humans, and Lewis lung carcinoma was the most used experimental model. China, Japan, South Korea, and Ethiopia were the countries that most published studies of species with antitumor activity. Of the 38 plants evaluated, 27 demonstrated antitumor activity. In addition, six other living organisms were cited for antitumor activity against lung cancer. Mechanisms of action, combination with chemotherapeutic drugs, and new technologies to increase activity and reduce the toxicity of the treatment are discussed. This review was based on the NAPRALERT databank, Web of Science, and Chemical Abstracts. This work shows that natural products from plants continue to be a rich source of herbal medicines or biologically active compounds against cancer.

  10. In vitro antioxidant, antibacterial and anti-tumor activities of total ...

    African Journals Online (AJOL)

    Purpose: To investigate the in vitro antioxidant, antibacterial and anti-tumor activities of total flavonoids from Elsholtzia densa Benth of Sichuan Province, China. Methods: The total flavonoids of Elsholtzia densa Bent were extracted utilizing the ultrasonic extraction method, and purified by D101 macroporous adsorption resin ...

  11. A novel, polymer-coated oncolytic measles virus overcomes immune suppression and induces robust antitumor activity

    Directory of Open Access Journals (Sweden)

    Kaname Nosaki

    2016-01-01

    Full Text Available Although various therapies are available to treat cancers, including surgery, chemotherapy, and radiotherapy, cancer has been the leading cause of death in Japan for the last 30 years, and new therapeutic modalities are urgently needed. As a new modality, there has recently been great interest in oncolytic virotherapy, with measles virus being a candidate virus expected to show strong antitumor effects. The efficacy of virotherapy, however, was strongly limited by the host immune response in previous clinical trials. To enhance and prolong the antitumor activity of virotherapy, we combined the use of two newly developed tools: the genetically engineered measles virus (MV-NPL and the multilayer virus-coating method of layer-by-layer deposition of ionic polymers. We compared the oncolytic effects of this polymer-coated MV-NPL with the naked MV-NPL, both in vitro and in vivo. In the presence of anti-MV neutralizing antibodies, the polymer-coated virus showed more enhanced oncolytic activity than did the naked MV-NPL in vitro. We also examined antitumor activities in virus-treated mice. Complement-dependent cytotoxicity and antitumor activities were higher in mice treated with polymer-coated MV-NPL than in mice treated with the naked virus. This novel, polymer-coated MV-NPL is promising for clinical cancer therapy in the future.

  12. Reprogramming antitumor immunity against chemoresistant ovarian cancer by a CXCR4 antagonist-armed viral oncotherapy

    Directory of Open Access Journals (Sweden)

    Marcin P Komorowski

    2016-01-01

    Full Text Available Ovarian cancer remains the most lethal gynecologic malignancy owing to late detection, intrinsic and acquired chemoresistance, and remarkable heterogeneity. Here, we explored approaches to inhibit metastatic growth of murine and human ovarian tumor variants resistant to paclitaxel and carboplatin by oncolytic vaccinia virus expressing a CXCR4 antagonist to target the CXCL12 chemokine/CXCR4 receptor signaling axis alone or in combination with doxorubicin. The resistant variants exhibited augmented expression of the hyaluronan receptor CD44 and CXCR4 along with elevated Akt and ERK1/2 activation and displayed an increased susceptibility to viral infection compared with the parental counterparts. The infected cultures were more sensitive to doxorubicin-mediated killing both in vitro and in tumor-challenged mice. Mechanistically, the combination treatment increased apoptosis and phagocytosis of tumor material by dendritic cells associated with induction of antitumor immunity. Targeting syngeneic tumors with this regimen increased intratumoral infiltration of antitumor CD8+ T cells. This was further enhanced by reducing the immunosuppressive network by the virally-delivered CXCR4 antagonist, which augmented antitumor immune responses and led to tumor-free survival. Our results define novel strategies for treatment of drug-resistant ovarian cancer that increase immunogenic cell death and reverse the immunosuppressive tumor microenvironment, culminating in antitumor immune responses that control metastatic tumor growth.

  13. Anti-tumor activity of tetrodotoxin extracted from the Masked Puffer ...

    African Journals Online (AJOL)

    Anti-tumor activity of tetrodotoxins extracted from the skin of the Masked Puffer fish (Arothron diadematus) from the Red Sea was evaluated using the Ehrlich ascite carcinoma tumor model in mice. Activity was assessed using a variety of cellular and liver biochemical parameters. Experimental mice were divided into 4 equal ...

  14. Curcuma increasing antitumor effect of Rhizoma paridis saponins through absorptive enhancement of paridis saponins.

    Science.gov (United States)

    Man, Shuli; Li, Yuanyuan; Fan, Wei; Gao, Wenyuan; Liu, Zhen; Li, Nan; Zhang, Yao; Liu, Changxiao

    2013-09-15

    Rhizoma paridis saponins (RPS) played a good antitumor role in many clinical applications. However, low oral bioavailability limited its application. In this research, water extract of Curcuma (CW) significantly increased antitumor effect of Rhizoma paridis saponins (RPS). GC-MS was used to identify its polar composition. HPLC was applied for determination of the content of curcuminoids in CW. As a result, 47 analytes with 0.65% of curcuminoids were identified in CW. According to the in vivo anti-tumor data, the best proportion of curcuminoids in CW with RPS was 16:500 (w/w). Using this ratio, curcuminoids significantly increased absorption of RPS in the everted rat duodenum sac system. In addition, curcuminoids decreased the promotion of RPS on rhodamine 123 efflux. The effect of curcuminoids was similar to that of the P-gp inhibitor, cyclosporin A in combination with RPS. In conclusion, drug combination of water extract of Curcuma with RPS was a good method to increase the antitumor effect of RPS. This combination would be a potent anticancer agent used in the prospective application. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  15. Unique DNA binding mode of antitumor trinuclear tridentate platinum(II) compound

    Czech Academy of Sciences Publication Activity Database

    Olivová, R.; Kašpárková, Jana; Vrána, Oldřich; Vojtíšková, Marie; Suchánková, T.; Nováková, Olga; He, W.; Guo, Z.; Brabec, Viktor

    2011-01-01

    Roč. 8, č. 6 (2011), s. 2368-2378 ISSN 1543-8384 R&D Projects: GA MŠk(CZ) ME10066 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : platinum * antitumor * DNA Subject RIV: BO - Biophysics Impact factor: 4.782, year: 2011

  16. Comparison of the fibronectin-binding ability and antitumor efficacy of various mycobacteria.

    Science.gov (United States)

    Hudson, M A; Ritchey, J K; Catalona, W J; Brown, E J; Ratliff, T L

    1990-07-01

    Although the mechanism by which Bacillus Calmette-Guerin (BCG) exerts an antitumor effect on superficial bladder tumors is not fully understood, recent evidence has implicated binding of BCG organisms to fibronectin (FN) as requisite for this antitumor efficacy. Various substrains of BCG and other mycobacteria were tested in vitro for their relative capacities to bind both matrix and soluble FN. A substrain of Mycobacterium kansasii, designated the "high-binding strain," was found to bind FN more readily (P less than 0.05) in in vitro studies, when compared to commercially available substrains of BCG (Tice, Connaught, and Armand Frappier). The binding by the three commercial strains of BCG to FN in vitro appeared to be equivalent. The high-binding strain was further demonstrated to attach more readily in vivo to the acutely injured murine bladder (P less than 0.005) than the Armand Frappier substrain. Finally, using the MB49 murine bladder tumor model, an enhanced antitumor effect (P less than 0.05) was noted in mice treated with intravesical high-binding strain, in comparison to the Armand Frappier substrain, during five weekly treatments. It appears not only that the commercial substrains of BCG bind FN in an equivalent manner but also that the relative binding capacities of the substrains correlate directly with antitumor activity. A substrain of M. kansasii appears to have been identified which may prove more clinically effective than the currently available strains of BCG.

  17. Antitumor effects of traditional Chinese medicine targeting the cellular apoptotic pathway

    Directory of Open Access Journals (Sweden)

    Xu HL

    2015-05-01

    Full Text Available Huanli Xu,1 Xin Zhao,2 Xiaohui Liu,1 Pingxiang Xu,1 Keming Zhang,2 Xiukun Lin11Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, 2Department of Hepatobiliary Surgery, 302 Hospital of Chinese People’s Liberation Army, Beijing, People’s Republic of ChinaAbstract: Defects in apoptosis are common phenomena in many types of cancer and are also a critical step in tumorigenesis. Targeting the apoptotic pathway has been considered an intriguing strategy for cancer therapy. Traditional Chinese medicine (TCM has been used in the People’s Republic of China for thousands of years, and many of the medicines have been confirmed to be effective in the treatment of a number of tumors. With increasing cancer rates worldwide, the antitumor effects of TCMs have attracted more and more attention globally. Many of the TCMs have been shown to have antitumor activity through multiple targets, and apoptosis pathway-related targets have been extensively studied and defined to be promising. This review focuses on several antitumor TCMs, especially those with clinical efficacy, based on their effects on the apoptotic signaling pathway. The problems with and prospects of development of TCMs as anticancer agents are also presented.Keywords: traditional Chinese medicine, antitumor effects, apoptotic pathway

  18. Antitumor and Antimicrobial Activity of Some Cyclic Tetrapeptides and Tripeptides Derived from Marine Bacteria

    Directory of Open Access Journals (Sweden)

    Subrata Chakraborty

    2015-05-01

    Full Text Available Marine derived cyclo(Gly-l-Ser-l-Pro-l-Glu was selected as a lead to evaluate antitumor-antibiotic activity. Histidine was chosen to replace the serine residue to form cyclo(Gly-l-His-l-Pro-l-Glu. Cyclic tetrapeptides (CtetPs were then synthesized using a solution phase method, and subjected to antitumor and antibiotic assays. The benzyl group protected CtetPs derivatives, showed better activity against antibiotic-resistant Staphylococcus aureus in the range of 60–120 μM. Benzyl group protected CtetPs 3 and 4, exhibited antitumor activity against several cell lines at a concentration of 80–108 μM. However, shortening the size of the ring to the cyclic tripeptide (CtriP scaffold, cyclo(Gly-l-Ser-l-Pro, cyclo(Ser-l-Pro-l-Glu and their analogues showed no antibiotic or antitumor activity. This phenomenon can be explained from their backbone structures.

  19. Ginsenoside Rh2 enhances the antitumor immunological response of a melanoma mice model.

    Science.gov (United States)

    Wang, Meng; Yan, Shi-Ju; Zhang, Hong-Tao; Li, Nan; Liu, Tao; Zhang, Ying-Long; Li, Xiao-Xiang; Ma, Qiong; Qiu, Xiu-Chun; Fan, Qing-Yu; Ma, Bao-An

    2017-02-01

    The treatment of malignant tumors following surgery is important in preventing relapse. Among all the post-surgery treatments, immunomodulators have demonstrated satisfactory effects on preventing recurrence according to recent studies. Ginsenoside is a compound isolated from panax ginseng, which is a famous traditional Chinese medicine. Ginsenoside aids in killing tumor cells through numerous processes, including the antitumor processes of ginsenoside Rh2 and Rg1, and also affects the inflammatory processes of the immune system. However, the role that ginsenoside serves in antitumor immunological activity remains to be elucidated. Therefore, the present study aimed to analyze the effect of ginsenoside Rh2 on the antitumor immunological response. With a melanoma mice model, ginsenoside Rh2 was demonstrated to inhibit tumor growth and improved the survival time of the mice. Ginsenoside Rh2 enhanced T-lymphocyte infiltration in the tumor and triggered cytotoxicity in spleen lymphocytes. In addition, the immunological response triggered by ginsenoside Rh2 could be transferred to other mice. In conclusion, the present study provides evidence that ginsenoside Rh2 treatment enhanced the antitumor immunological response, which may be a potential therapy for melanoma.

  20. Study on in vitro anti-tumor activity of Bidens bipinnata L. extract ...

    African Journals Online (AJOL)

    We studied the in vitro anti-tumor activity of Bidens Bipinnata L. extract. MTT assay was used to investigate the inhibitory effect of different concentrations of the extracts on human hepatocellular carcinoma (HepG2) cell lines and human cervical carcinoma (Hela) cell lines, and the IC50 values were calculated. The Bidens ...

  1. Unique antitumor property of the Mg-Ca-Sr alloys with addition of Zn

    Science.gov (United States)

    Wu, Yuanhao; He, Guanping; Zhang, Yu; Liu, Yang; Li, Mei; Wang, Xiaolan; Li, Nan; Li, Kang; Zheng, Guan; Zheng, Yufeng; Yin, Qingshui

    2016-02-01

    In clinical practice, tumor recurrence and metastasis after orthopedic prosthesis implantation is an intensely troublesome matter. Therefore, to develop implant materials with antitumor property is extremely necessary and meaningful. Magnesium (Mg) alloys possess superb biocompatibility, mechanical property and biodegradability in orthopedic applications. However, whether they possess antitumor property had seldom been reported. In recent years, it showed that zinc (Zn) not only promote the osteogenic activity but also exhibit good antitumor property. In our present study, Zn was selected as an alloying element for the Mg-1Ca-0.5Sr alloy to develop a multifunctional material with antitumor property. We investigated the influence of the Mg-1Ca-0.5Sr-xZn (x = 0, 2, 4, 6 wt%) alloys extracts on the proliferation rate, cell apoptosis, migration and invasion of the U2OS cell line. Our results show that Zn containing Mg alloys extracts inhibit the cell proliferation by alteration the cell cycle and inducing cell apoptosis via the activation of the mitochondria pathway. The cell migration and invasion property were also suppressed by the activation of MAPK (mitogen-activated protein kinase) pathway. Our work suggests that the Mg-1Ca-0.5Sr-6Zn alloy is expected to be a promising orthopedic implant in osteosarcoma limb-salvage surgery for avoiding tumor recurrence and metastasis.

  2. Phase I trial with BMS-275183, a novel oral taxane with promising antitumor activity

    NARCIS (Netherlands)

    Broker, LE; de Vos, FYFL; van Groeningen, CJ; Kuenen, BC; Gall, HE; Woo, MH; Voi, M; Gietema, JA; deVries, EGE; Giaccone, G

    2006-01-01

    Purpose: BMS-275183 is an orally administered C-4 methyl carbonate analogue of paclitaxel. We did a dose-escalating phase I study to investigate its safety, tolerability, pharmacokinetics, and possible antitumor activity. Experimental Design: A cycle consisted of four weekly doses of BMS-275183. The

  3. Electrostatic Interaction of Negatively Charged Core–Shell Nanoparticles with Antitumoral Cationic Platinum-Based Complexes

    Czech Academy of Sciences Publication Activity Database

    Gál, Miroslav; Híveš, J.; Laus, M.; Sparnacci, K.; Ravera, M.; Gabano, E.; Osella, D.

    -, č. 22 (2011), s. 3289-3294 ISSN 1434-1948 R&D Projects: GA ČR GP203/09/P502 Institutional research plan: CEZ:AV0Z40400503 Keywords : platinum * Antitumor agents * nanoparticles Subject RIV: CG - Electrochemistry Impact factor: 3.049, year: 2011

  4. Colloidally stable surface-modified iron oxide nanoparticles: Preparation, characterization and anti-tumor activity

    Energy Technology Data Exchange (ETDEWEB)

    Macková, Hana [Institute of Macromolecular Chemistry, AS CR, Heyrovsky Sq. 2, 162 06 Prague 6 (Czech Republic); Horák, Daniel, E-mail: horak@imc.cas.cz [Institute of Macromolecular Chemistry, AS CR, Heyrovsky Sq. 2, 162 06 Prague 6 (Czech Republic); Donchenko, Georgiy Viktorovich; Andriyaka, Vadim Ivanovich; Palyvoda, Olga Mikhailovna; Chernishov, Vladimir Ivanovich [Palladin Institute of Biochemistry, NASU, 9 Leontovich St., 01601 Kiev (Ukraine); Chekhun, Vasyl Fedorovich; Todor, Igor Nikolaevich [R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, 45 Vasylkivska St., 03022 Kiev (Ukraine); Kuzmenko, Oleksandr Ivanovich [Palladin Institute of Biochemistry, NASU, 9 Leontovich St., 01601 Kiev (Ukraine)

    2015-04-15

    Maghemite (γ-Fe{sub 2}O{sub 3}) nanoparticles were obtained by co-precipitation of Fe(II) and Fe(III) chlorides and subsequent oxidation with sodium hypochlorite and coated with poly(N,N-dimethylacrylamide-co-acrylic acid) [P(DMAAm-AA)]. They were characterized by a range of methods including transmission electron microscopy (TEM), elemental analysis, dynamic light scattering (DLS) and zeta potential measurements. The effect of superparamagnetic P(DMAAm-AA)-γ-Fe{sub 2}O{sub 3} nanoparticles on oxidation of blood lipids, glutathione and proteins in blood serum was detected using 2-thiobarbituric acid and the ThioGlo fluorophore. Finally, mice received magnetic nanoparticles administered per os and the antitumor activity of the particles was tested on Lewis lung carcinoma (LLC) in male mice line C57BL/6 as an experimental in vivo metastatic tumor model; the tumor size was measured and the number of metastases in lungs was determined. Surface-modified γ-Fe{sub 2}O{sub 3} nanoparticles showed higher antitumor and antimetastatic activities than commercial CuFe{sub 2}O{sub 4} particles and the conventional antitumor agent cisplatin. - Highlights: • Maghemite nanoparticles were prepared and characterized. • Poly(N,N-dimethylacrylamide-co-acrylic acid) coating was synthetized. • Blood lipid, glutathione and protein peroxidation/oxidation was determined. • Antitumor effect of coated particles on Lewis lung carcinoma in mice was observed.

  5. Antitumor and biological effects of black pine (Pinus nigra) pollen nuclease

    Czech Academy of Sciences Publication Activity Database

    Lipovová, P.; Podzimek, T.; Orctová, Lidmila; Matoušek, Jaroslav; Poučková, P.; Souček, J.; Matoušek, Josef

    2008-01-01

    Roč. 55, - (2008), s. 158-164 ISSN 0028-2685 Institutional research plan: CEZ:AV0Z50510513; CEZ:AV0Z50450515 Keywords : pollen nuclease * Antitumor effect Subject RIV: FD - Oncology ; Hematology Impact factor: 1.179, year: 2008

  6. Antitumor and apoptotic effects of cucurbitacin a in A-549 lung ...

    African Journals Online (AJOL)

    Background: The main aim of this study was to demonstrate the antitumor potential of cucurbitacin A on A-549 NSCLC (non-small cell lung cancer cells). The effects of Cucurbitacin A on apoptotic induction, cell physic, cell cycle failure and m-TOR/PI3K/Akt signalling pathway were also investigated in the present study.

  7. Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant

    NARCIS (Netherlands)

    Overwijk, Willem W.; de Visser, Karin E.; Tirion, Felicia H.; de Jong, Laurina A.; Pols, Thijs W. H.; van der Velden, Yme U.; van den Boorn, Jasper G.; Keller, Anna M.; Buurman, Wim A.; Theoret, Marc R.; Blom, Bianca; Restifo, Nicholas P.; Kruisbeek, Ada M.; Kastelein, Robert A.; Haanen, John B. A. G.

    2006-01-01

    The promising, but modest, clinical results of many human cancer vaccines indicate a need for vaccine adjuvants that can increase both the quantity and the quality of vaccine-induced, tumor-specific T cells. In this study we tested the immunological and antitumor effects of the proinflammatory

  8. Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results

    Science.gov (United States)

    Mut-Salud, Nuria; Álvarez, Pablo Juan; Garrido, Jose Manuel; Carrasco, Esther; Aránega, Antonia; Rodríguez-Serrano, Fernando

    2016-01-01

    The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous) or incorporated through the diet and nutritional supplements (exogenous). In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency. PMID:26682013

  9. Cholesterol negatively regulates IL-9-producing CD8+ T cell differentiation and antitumor activity.

    Science.gov (United States)

    Ma, Xingzhe; Bi, Enguang; Huang, Chunjian; Lu, Yong; Xue, Gang; Guo, Xing; Wang, Aibo; Yang, Maojie; Qian, Jianfei; Dong, Chen; Yi, Qing

    2018-05-09

    CD8 + T cells can be polarized into IL-9-secreting (Tc9) cells. We previously showed that adoptive therapy using tumor-specific Tc9 cells generated stronger antitumor responses in mouse melanoma than classical Tc1 cells. To understand why Tc9 cells exert stronger antitumor responses, we used gene profiling to compare Tc9 and Tc1 cells. Tc9 cells expressed different levels of cholesterol synthesis and efflux genes and possessed significantly lower cholesterol content than Tc1 cells. Unique to Tc9, but not other CD8 + or CD4 + T cell subsets, manipulating cholesterol content in polarizing Tc9 cells significantly affected IL-9 expression and Tc9 differentiation and antitumor response in vivo. Mechanistic studies showed that IL-9 was indispensable for Tc9 cell persistence and antitumor effects, and cholesterol or its derivatives inhibited IL-9 expression by activating liver X receptors (LXRs), leading to LXR Sumoylation and reduced p65 binding to Il9 promoter. Our study identifies cholesterol as a critical regulator of Tc9 cell differentiation and function. © 2018 Ma et al.

  10. Evaluation of Anti-tumor and Chemoresistance-lowering Effects of ...

    African Journals Online (AJOL)

    Evaluation of Anti-tumor and Chemoresistance-lowering Effects of Pectolinarigenin from Cirsium japonicum Fisch ex DC in Breast Cancer. Mingqian Lu, Xinhua Xu, Hongda Lu, Zhongxin Lu, Bingqing Xu, Chao Tan, Kezhi Shi, Rong Guo, Qingzhi Kong ...

  11. Antioxidant Intake and Antitumor Therapy: Toward Nutritional Recommendations for Optimal Results

    Directory of Open Access Journals (Sweden)

    Nuria Mut-Salud

    2016-01-01

    Full Text Available The role of the induction of oxidative stress as the mechanism of action of many antitumor drugs is acquiring an increasing interest. In such cases, the antitumor therapy success may be conditioned by the antioxidants present in our own body, which can be synthesized de novo (endogenous or incorporated through the diet and nutritional supplements (exogenous. In this paper, we have reviewed different aspects of antioxidants, including their classification, natural sources, importance in diet, consumption of nutritional supplements, and the impact of antioxidants on health. Moreover, we have focused especially on the study of the interaction between antioxidants and antitumor therapy, considering both radiotherapy and chemotherapy. In this regard, we found that the convenience of administration of antioxidants during cancer treatment still remains a very controversial issue. In general terms, antioxidants could promote or suppress the effectiveness of antitumor treatment and even protect healthy tissues against damage induced by oxidative stress. The effects may depend on many factors discussed in the paper. These factors should be taken into consideration in order to achieve precise nutritional recommendations for patients. The evidence at the moment suggests that the supplementation or restriction of exogenous antioxidants during cancer treatment, as appropriate, could contribute to improving its efficiency.

  12. Anti-tumor potential of total alkaloid extract of Prosopis juliflora DC ...

    African Journals Online (AJOL)

    The total alkaloid extract from Prosopis juliflora DC. leaves was obtained using acid/base modified extraction method. The in vitro anti-tumor potential of the extract was evaluated using MTT (3-(4,5- dimethythiazol-2yl)2,5-diphenyl tetrazolium bromide) based cytotoxicity monitoring after 24, 48 and 72 h exposure of the ...

  13. A Novel Synthesis of Fused Uracils: Indenopyrimidopyridazines, Pyrimidopyridazines, and Pyrazolopyrimidines for Antimicrobial and Antitumor Evalution

    Directory of Open Access Journals (Sweden)

    Samar El-Kalyoubi

    2016-12-01

    Full Text Available A variety of different compounds of fused uracils were prepared simply by the heating of 6-hydrazinyl-1-methyl-, 6-hydrazinyl-1-propyl-, or 6-hydrazinyl-1,3-dipropyluracil under reflux with ninhydrin, isatin, benzylidene malononitrile, benzylylidene ethyl cyanoacetate, benzil, and phenacyl bromide derivatives. The newly synthesized compounds were completely screened for antimicrobial and antitumor activity.

  14. Fraction From Lycium barbarum Polysaccharides Reduces Immunotoxicity and Enhances Antitumor Activity of Doxorubicin in Mice.

    Science.gov (United States)

    Deng, Xiangliang; Luo, Shuang; Luo, Xia; Hu, Minghua; Ma, Fangli; Wang, Yuanyuan; Zhou, Lian; Huang, Rongrong

    2018-01-01

    The aim of the present study was to investigate whether fraction from Lycium barbarum polysaccharide (LBP) could reduce immunotoxicity and enhance antitumor activity of doxorubicin (Dox) in mice. A water-soluble LBP fraction, designated LBP3, was isolated from edible Chinese herbal Lycium barbarum and used in this study. To investigate the effect of LBP3 on Dox-induced immunotoxicity, tumor-free mice were used and treated with either normal saline, Dox, or Dox plus LBP3. To investigate the effect of LBP3 on antitumor activity of Dox, H22 tumor-bearing mice were used and treated with either normal saline, Dox, LBP3, or Dox plus LBP3. The results showed that LBP3 did not protect against the body weight loss caused by Dox, but it promoted the recovery of body weight starting at day 5 after Dox treatment in tumor-free mice. LBP3 also improved peripheral blood lymphocyte counts, promoted cell cycle recovery in bone marrow cells, and restored the cytotoxicity of natural killer cells. Furthermore, in H22 tumor-bearing mice, LBP3 enhanced antitumor activity of Dox and improved peripheral blood lymphocyte counts and the cytotoxicity of splenocytes. In brief, our results demonstrated that LBP3 could reduce the immunotoxicity and enhance antitumor activity of Dox.

  15. Effect of Paris saponin on antitumor and immune function in U14 ...

    African Journals Online (AJOL)

    bearing mice, and reduced the serum IL-4 level. The Paris saponin can inhibit U14 cell growth and prolong survival time of mice; it is speculated that the Paris saponin may express its anti-tumor activity by improving the body's immune system.

  16. Kajian Degradasi Lahan Sebagai Dasar Pengendalian Banjir di DAS Juwana

    Directory of Open Access Journals (Sweden)

    Arina Miardini

    2016-10-01

    Full Text Available Adanya pemanfaatan lahan yang intensif dan ekspolitatif dapat menurunkan daya dukung dan fungsi lingkungan DAS yang menyebabkan lahan menjadi terdegradasi. Tingginya luasan lahan kritis menjadi ancaman terhadap daya dukung DAS yang akan berdampak pada ketidakseimbangan hidrologi dalam DAS. Salah satu akibat ketidakseimbangan hidrologi dalam DAS adalah terjadinya banjir. DAS Juwana merupakan DAS Prioritas I berdasarkan penetapan 108 DAS prioritas. Salah satu indikator untuk menentukan degradasi dalam DAS dapat diketahui berdasarkan nilai koefisien aliran. Penelitian ini bertujuan untuk mengidentifikasi karakteristik fisik DAS yang berpengaruh dalam penentuan koefisien aliran, menghitung koefisien aliran dengan mempertimbangkan parameter karakteristik fisik DAS dan memberikan rekomendasi pengelolaan banjir di DAS Juwana yang potensial banjir dalam mendukung upaya pengelolaan DAS dari hulu sampai hilir. Koefisien aliran dihitung denggan menggunakan metode cook yang memperhitungkan parameter kemiringan lereng, infiltrasi tanah, tutupan vegetasi dan simpanan permukaan. Perumusan pengendalian banjir dilakukan dengan melakukan penatagunaan lahan yang disesuaikan dengan arahan fungsi penggunaan lahan sehingga diharapkan menurunkan nilai koefisien aliran dan debit banjir. Karakteristik fisik DAS Juwana yang mempengaruhi penentuan koefisien aliran berdasarkan metode Cook yaitu Kemiringan lereng dengan rata-rata skor C sebesar 0,178, kerapatan aliran dengan rata-rata skor 0,084, infiltrasi dengan rata-rata skor 0,115 dan tutupan vegetasi dengan rata-rata skor 0,127. Kontribusi masing masing parameter dalam penilaian koefisien aliran yang memiliki pengaruh paling terbesar sampai paling terkecil dalam besarnya koefisien aliran yaitu kemiringan lereng yang memiliki pengaruh sebesar 35,39%, kemudian tutupan vegetasi sebesar 25,25%, infiltrasi sebesar 22,86% dan terakhir adalah kerapatan aliran yang berkontribusi sebesar 16,70%. Nilai koefisien aliran di DAS

  17. O impacto das redes sociais no marketing: perspectiva portuguesa

    OpenAIRE

    Rosa, Nuno Gonçalo Henriques da

    2010-01-01

    Mestrado em Marketing As mudanças ocorridas nos últimos anos, no panorama dos media, associados aos desenvolvimentos tecnológicos, originaram novos comportamentos no consumidor. O poder das comunicações das marcas deixou de estar centrada apenas nas iniciativas das empresas, o que permitiu um novo relacionamento das marcas com o consumidor, transformando-o num Prosumer. As Redes Sociais e a importância que as suas plataformas assumem na nossa vida, o que para alguns autores é uma extensão ...

  18. Das ovarielle Überstimulationssyndrom (OHSS

    Directory of Open Access Journals (Sweden)

    Sander T

    2011-01-01

    Full Text Available Das ovarielle Überstimulationssyndrom (OHSS ist eine relativ häufige Komplikation bei der künstlichen Befruchtung bzw. bei einer ovariellen Stimulationsbehandlung. Es wird über die Pathophysiologie berichtet, die durch eine erhöhte Gefäßpermeabilität mit einer Flüssigkeitsverschiebung in den extravasalen Raum bedingt ist, vermutlich getriggert durch den vaskulären endothelialen Wachstumsfaktor (VEGF. Junge Frauen mit hyperandrogenämischen Zyklusstörungen und polyzystischem Ovarsyndrom (PCOS haben ein erhöhtes Risiko und eine Ovulationsinduktion mit HCG (humanem Choriongonadotropin sollte vermieden werden. Erscheinungsbild, Präventionsmaßnahmen und Therapie werden mit dem Ziel erläutert, die Komplikationsrate niedrig und die Schwangerschaftsrate so hoch wie möglich zu halten.

  19. Adolescentes e crack: pelo caminho das pedras

    Directory of Open Access Journals (Sweden)

    Eduardo Tomm

    2013-12-01

    Full Text Available Nos últimos anos, a sociedade tem observado uma rápida expansão no uso de crack, especialmente por adolescentes e jovens. É evidente a necessidade de ouvir esses sujeitos de para melhor compreender sua situação. Para atender a essa necessidade, desenvolvemos uma pesquisa qualitativa descritivo-exploratória cujo foco foi um grupo terapêutico para adolescentes usuários de crack que ocorreu no Centro de Atenção Psicossocial Infanto-Juvenil (CAPSi em uma cidade do interior do Rio Grande do Sul, Brasil. Amparados na modalidade expost-facto, analisamos documentos produzidos nessa instituição. O resultado foi uma cartografia que acompanhou discursivamente os adolescentes pelo "caminho das pedras": os lugares, tratamentos, pessoas, ideias e momentos dos quais falam.

  20. As lições das coisas

    OpenAIRE

    Pimentel, Álamo

    2015-01-01

    Os museus constituem espaços para o ensino de antropologia. A partir de um projeto didático de antropologia da educação em um museu de antropologia de uma universidade pública brasileira, emergem importantes significados para a experiência do estranhamento etnográfico com os objetos da exposição permanente. Mediante uma análise de relatórios de visita produzidos pelos estudantes, o autor apresenta os diferentes arranjos discursivos que compõem os acervos da exposição e revela, a partir das co...

  1. Lista atualizada das Orchidaceae do Distrito Federal

    Directory of Open Access Journals (Sweden)

    Batista João Aguiar Nogueira

    2003-01-01

    Full Text Available É apresentada a relação atualizada de Orchidaceae para o Distrito Federal (DF, a unidade da federação onde se situa a capital brasileira, localizada no centro do país. São reconhecidos 72 gêneros e 254 táxons (246 espécies e oito táxons subespecíficos, dos quais 17 (6,7% são conhecidos apenas localmente. Os gêneros mais significativos no DF são Habenaria (74 espécies e três táxons subespecíficos, Cyrtopodium (17 espécies, Cleistes (13 espécies e a subtribo Spiranthinae (11 gêneros com 34 espécies e dois táxons subespecíficos. Gêneros como Epidendrum (oito espécies, Pleurothallis (sete espécies, Oncidium (seis espécies e Maxillaria (três espécies são abundantes na Mata Atlântica no sudeste brasileiro, mas pouco representados na região. Cerca de 73% das Orchidaceae do DF apresentam hábito terrestre, o que contrasta marcadamente com a Mata Atlântica e a região Amazônica, onde predominam espécies epifíticas. Dentro do Cerrado, o DF representa o local mais bem amostrado e com o maior número de espécies conhecidas, compreendendo cerca de 51% das orquídeas listadas para todo o bioma. Esta relação tem como objetivo subsidiar a monografia desta família para a flora do Distrito Federal.

  2. Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Song Zhang

    Full Text Available Hepatocellular carcinoma (HCC is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL, an antioxidant derived from the milk thistle plant (Silybum marianum, has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH levels and total antioxidant capability (T-AOC but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS. Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD, RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro or DAPT (a known Notch1 inhibitor, in vivo further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.

  3. Study on fluorouracil–chitosan nanoparticle preparation and its antitumor effect

    Directory of Open Access Journals (Sweden)

    Gaimin Chen

    2016-05-01

    Full Text Available To successfully prepare fluorouracil–chitosan nanoparticles, and further analyze its anti-tumor activity mechanism, this paper makes a comprehensive study of existing preparation prescription and makes a detailed analysis of fluorouracil–chitosan in vitro release and pharmacodynamic behavior of animals. Two-step synthesis method is adopted to prepare 5-FU–CS–mPEG prodrugs, and infrared, 1H NMR and differential thermal analysis are adopted to analyze characterization synthetic products of prepared drugs. To ensure clinical efficacy of prepared drugs, UV spectrophotometry is adopted for determination of drug loading capacity of prepared drugs, transmission electron microscopy is adopted to observe the appearance, dynamic dialysis method is used to observe in vitro drug release of prepared drugs and fitting of various release models is done. Anti-tumor effect is studied via level of animal pharmacodynamics. After the end of the experiment, tumor inhibition rate, spleen index and thymus index of drugs are calculated. Experimental results show that the prepared drugs are qualified in terms of regular shape, dispersion, drug content, etc. Animal pharmacodynamics experiments have shown that concentration level of drug loading capacity of prepared drugs has a direct impact on anti-tumor rate. The higher the concentration, the higher the anti-tumor rate. Results of pathological tissue sections of mice show that the prepared drugs cause varying degrees of damage to receptor cells, resulting in cell necrosis or apoptosis problem. It can thus be concluded that ion gel method is an effective method to prepare drug-loading nanoparticles, with prepared nanoparticles evenly distributed in regular shape which demonstrate good slow-release characteristics in receptor vitro and vivo. At the same time, after completion of drug preparation, relatively strong anti-tumor activity can be generated for the receptor, so this mode of preparation enjoys broad

  4. Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis

    Directory of Open Access Journals (Sweden)

    Lindhofer Horst

    2009-02-01

    Full Text Available Abstract Peritoneal carcinomatosis (PC from epithelial tumors is a fatal diagnosis without efficient treatment. Trifunctional antibodies (trAb are novel therapeutic approaches leading to a concerted anti-tumor activity resulting in tumor cell destruction. In addition, preclinical data in mouse tumor models demonstrated the induction of long lasting tumor immunity after treatment with trAb. We describe the induction of anti-tumor specific T-lymphocytes after intraperitoneal administration of trAb in patients with PC. 9 patients with progressive PC from gastric (n = 6 and ovarian cancer (n = 2, and cancer of unknown primary (n = 1 received 3 escalating doses of trAb after surgery and/or ineffective chemotherapy. The trAb EpCAM × CD3 (10, 20, 40 μg or HER2/neu × CD3 (10, 40, 80 μg were applicated by intraperitoneal infusion. Four weeks after the last trAb application, all patients were restimulated by subdermal injection of trAb + autologous PBMC + irradiated autologous tumor cells. Immunological reactivity was tested by analyzing PBMC for specific tumor reactive CD4+/CD8+ T lymphocytes using an IFN-γ secretion assay. In 5 of 9 patients, tumor reactive CD4+/CD8+ T-lymphocytes increased significantly, indicating specific anti-tumor immunity. A clinical response (stable disease, partial regression has been observed in 5 of 9 patients, with a mean time to progression of 3.6 months. Follow-up showed a mean survival of 11.8 months (median 8.0 months after trAb therapy. TrAb are able to induce anti-tumor immunity after intraperitoneal application and restimulation. The induction of long-lasting anti-tumor immunity may provide an additional benefit of the intraperitoneal therapy with trAb and should be further elevated in larger clinical trials.

  5. The in vitro sustained release profile and antitumor effect of etoposide-layered double hydroxide nanohybrids

    Directory of Open Access Journals (Sweden)

    Qin LL

    2013-05-01

    Full Text Available Lili Qin,1 Mei Wang,2 Rongrong Zhu,3 Songhui You,1 Ping Zhou,1 Shilong Wang31Department of Physical Education, Tongji University, Shanghai, People's Republic of China; 2Department of Chemistry, Tongji University, Shanghai, People's Republic of China; 3School of Life Science and Technology, Tongji University, Shanghai, People's Republic of ChinaAbstract: Magnesium-aluminum layered double hydroxides intercalated with antitumor drug etoposide (VP16 were prepared for the first time using a two-step procedure. The X-ray powder diffraction data suggested the intercalation of VP16 into layers with the increased basal spacing from 0.84–1.18 nm was successful. Then, it was characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, thermogravimetry and differential thermal analysis, and transmission electron microscopy. The prepared nanoparticles, VP16-LDH, showed an average diameter of 62.5 nm with a zeta potential of 20.5 mV. Evaluation of the buffering effect of VP16-LDH indicated that the nanohybrids were ideal for administration of the drugs that treat human stomach irritation. The loading amount of intercalated VP16 was 21.94% and possessed a profile of sustained release. The mechanism of VP16-LDH release in the phosphate buffered saline solution at pH 7.4 is likely controlled by the diffusion of VP16 anions from inside to the surface of LDH particles. The in vitro cytotoxicity and antitumor assays indicated that VP16-LDH hybrids were less toxic to GES-1 cells while exhibiting better antitumor efficacy on MKN45 and SGC-7901 cells. These results imply that VP16-LDH is a potential antitumor drug for a broad range of gastric cancer therapeutic applications.Keywords: layered double hydroxides, etoposide, drug delivery, antitumor effect, sustained release

  6. Tumor-altered dendritic cell function: implications for anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Kristian Michael Hargadon

    2013-07-01

    Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti-tumor

  7. The anti-tumor effect of ACNU and x-irradiation on mouse glioma

    International Nuclear Information System (INIS)

    Nakagawa, Hidemitsu; Hori, Masaharu; Hasegawa, Hiroshi; Mogami, Heitaro; Hayakawa, Toru.

    1979-01-01

    Anti-tumor activities of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and x-irradiation on methylcholanthrene induced glioma in C 57 BL mice were studied in vitro and in vivo. In vitro experiments using cultured glioma cells (MGB cells), the synchronization of cell cycle was done by excess addition of thymidine, and the anti-tumor cell effect were investigated by mean of determinations of DNA synthesis, mitotic index and the number of the living cells following the treatments. As the results, it appeared obvious that ACNU was most effective on MGB cells in S phase and x-irradiation in M phase. As to the combined therapy of ACNU and x-irradiation, the anti-tumor effect was most remarkable when the cells were treated by x-irradiation in the G 2 , M phase, which were hervested by addition of ACNU 44 hours before irradiation. However simultaneous treatment of ACNU and x-irradiation on the cells in G 1 phase was not so remarkable. In vivo experiments the anti-tumor effect of ACNU and x-irradiation on subcutaneously or intracranially transplanted glioma in mice was investigated. Either ACNU 10 mg/kg or local x-irradiation 1240 rads showed inhibitory effect on the tumor growth and prolonged the survival time of the tumor bearing mice. The combination therapy was more effective than ACNU or x-irradiation alone, particularly combination therapy of ACNU and repeated small doses irradiation of x-ray was remarkably effective. Evidence obtained indicated that the combination therapy of ACNU and x-irradiation have synergistic anti-tumor effect on experimental mouse glioma. (author)

  8. Antioxidative and antitumor properties of in vitro-cultivated broccoli (Brassica oleracea var. italica).

    Science.gov (United States)

    Cakar, Jasmina; Parić, Adisa; Maksimović, Milka; Bajrović, Kasim

    2012-02-01

    Broccoli [Brassica oleracea L. var. italica Plenck. (Brassicaceae)] contains substantial quantities of bioactive compounds, which are good free radical scavengers and thus might have strong antitumor properties. Enhancing production of plant secondary metabolites could be obtained with phytohormones that have significant effects on the metabolism of secondary metabolites. In that manner, in vitro culture presents good model for manipulation with plant tissues in order to affect secondary metabolite production and thus enhance bioactive properties of plants. Estimation of the antioxidative and antitumor properties of broccoli cultivated in different in vitro conditions. In vitro germinated and cultivated broccoli seedlings, as well as spontaneously developed calli, were subjected to Soxhlet extraction. Antioxidative activity of the herbal extracts was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH(•)) radical method. Antitumor properties of the extracts were determined using crown-gall tumor inhibition (potato disc) assay. Three, 10, 20, and 30 days old broccoli seedlings, cultivated in vitro on three different Murashige-Skoog media, two types of callus, and seedlings from sterile filter paper were used for extraction. In total, 15 aqueous extracts were tested for antioxidative and antitumor potential. Three day-old seedlings showed the highest antioxidative activity. Eleven out of 15 aqueous extracts demonstrated above 50% of crown-gall tumor inhibition in comparison with the control. Tumor inhibition was in association with types and concentrations of phytohormones presented in growing media. It is demonstrated that phytohormones in plant-growing media could affect the bioactive properties of broccoli either through increasing or decreasing their antioxidative and antitumor potential.

  9. Antitumor activity of Bulgarian herb Tribulus terrestris L. on human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Svetla Angelova

    2013-01-01

    Full Text Available Medicinal plants have been intensively studied as a source of antitumor compounds. Due to the beneficial climate conditions Bulgarian herbs have high pharmacological potential. Currently, the antitumor effect of the Bulgarian medicinal plant Tribulus terrestris L. on human cancer cell lines is not studied. The main active compounds of the plant are the steroid saponins.The present study aims to analyze the effect on cell viability and apoptotic activity of total extract and saponin fraction of Bulgarian Tribulus terrestris L. on human breast cancer (MCF7 and normal (MCF10A cell lines. Antitumor effect was established by МТТ cell viability assay and assessment of apoptotic potential was done through analysis of genomic integrity (DNA fragmentation assay and analysis of morphological cell changes (Fluorescence microscopy. The results showed that total extract of the herb has a marked dose-dependent inhibitory effect on viability of MCF7 cells (half maximal inhibitory concentration is 15 μg/ml. Cell viability of MCF10A was moderately decreased without visible dose-dependent effect. The saponin fraction has increased inhibitory effect on breast cancer cells compared to total extract. Morphological changes and DNA fragmentation were observed as markers for early and late apoptosis predominantly in tumor cells after treatment. Apoptotic processes were intensified with the increase of treatment duration.The obtained results are the first showing selective antitumor activity of Bulgarian Tribulus terrestris L. on human cancer cells in vitro. Apoptotic processes are involved in the antitumor mechanisms induced by the herb. This results give directions for future investigations concerning detailed assessment of its pharmacological potential.

  10. Targeting Gene-Viro-Therapy with AFP driving Apoptin gene shows potent antitumor effect in hepatocarcinoma

    Directory of Open Access Journals (Sweden)

    Zhang Kang-Jian

    2012-02-01

    Full Text Available Abstract Background Gene therapy and viral therapy are used for cancer therapy for many years, but the results are less than satisfactory. Our aim was to construct a new recombinant adenovirus which is more efficient to kill hepatocarcinoma cells but more safe to normal cells. Methods By using the Cancer Targeting Gene-Viro-Therapy strategy, Apoptin, a promising cancer therapeutic gene was inserted into the double-regulated oncolytic adenovirus AD55 in which E1A gene was driven by alpha fetoprotein promoter along with a 55 kDa deletion in E1B gene to form AD55-Apoptin. The anti-tumor effects and safety were examined by western blotting, virus yield assay, real time polymerase chain reaction, 3-(4,5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium bromide assay, Hoechst33342 staining, Fluorescence-activated cell sorting, xenograft tumor model, Immunohistochemical assay, liver function analysis and Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling assay. Results The recombinant virus AD55-Apoptin has more significant antitumor effect for hepatocelluar carcinoma cell lines (in vitro than that of AD55 and even ONYX-015 but no or little impair on normal cell lines. Furthermore, it also shows an obvious in vivo antitumor effect on the Huh-7 liver carcinoma xenograft in nude mice with bigger beginning tumor volume till about 425 mm3 but has no any damage on the function of liver. The induction of apoptosis is involved in AD55-Apoptin induced antitumor effects. Conclusion The AD55-Apoptin can be a potential anti-hepatoma agent with remarkable antitumor efficacy as well as higher safety in cancer targeting gene-viro-therapy system.

  11. Host-mediated antitumor effect of DMG, a degraded D-manno-D-glucan from Microellobosporia grisea culture fluid.

    Science.gov (United States)

    Nakajima, H; Hashimoto, S; Nagao, S; Kita, Y; Khono, M; Ogawa, H; Abe, S; Mizuno, D

    1984-03-01

    DMG, a new polysaccharide with a well-characterized structure, isolated from the culture filtrate of an actinomycetes and then degraded by acid treatment, was tested for antitumor activity on allogeneic and syngeneic tumors in mice. In the allogeneic Ehrlich solid tumor system, DMG showed antitumor activity over a wide dose range, its optimal dose being 10-100 mg/kg. The optimal time of DMG administration was 1-2 weeks after tumor inoculation, but DMG was also effective when given before tumor inoculation. DMG was effective when given ip, sc, it (intratumorally) or iv. DMG also had antitumor effects on syngeneic tumors. It rapidly inhibited the growth of MM46 mammary carcinoma, MH134 hepatoma, and Meth A fibrosarcoma, and also inhibited spontaneous pulmonary metastases of B16-BL6 melanoma. However, it had no direct cytocidal action on tumor cells in vitro. Its antitumor activity was much less in athymic nude mice and in mice immunosuppressed by whole-body X-irradiation than in normal hosts.Thus, DMG was shown to exert antitumor activity via host-mediated mechanisms. Its antitumor activity is discussed in comparison with those of other antitumor polysaccharides.

  12. Enhancement of intrinsic antitumor activity in spore-endotoxin mixtures of Bacillus thuringiensis by exposure to ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Zamola, B; Karminski-Zamola, G; Fuks, Z; Kubovic, M [Zagreb Univ. (Yugoslavia); Wrishcer, M [Institut Rudjer Boskovic, Zagreb (Yugoslavia)

    1985-03-01

    Irradiation of spore-endotoxin mixtures from Bacillus thuringiensis cultures at 254 nm (60 ..mu..W cm/sup -2/) enhances their intrinsic antitumor potency as well as that of either component. The extent of enhancement depends on the length of exposure (optimum: 35 min) and may thus be due to photochemical changes of the endotoxin protein or/and to photoproduction of additional compounds with antitumor activity. Antitumor effects, expressed as survival rates of C57BL/6 mice inoculated with Lewis' mouse lung carcinoma and subjected to treatments 24 h later, depended on the number of doses of preparations administered (mixture, separated components).

  13. Transporte de ovos férteis: Influência das idades das matrizes, tempos de estocagem e das estradas

    Directory of Open Access Journals (Sweden)

    Aérica C. Nazareno

    2014-03-01

    Full Text Available Propôs-se, com esta pesquisa, avaliar a influência de diferentes idades das matrizes e tempos de estocagem no número de ovos trincados durante a operação de transporte em diferentes estradas. A pesquisa foi conduzida na empresa integradora avícola em Mogi-Mirim - SP, por meio do acompanhamento de três carregamentos em diferentes estações do ano (primavera, verão e outono. Foi utilizado um caminhão climatizado do tipo baú com capacidade para 592 caixas de ovos. Foram registrados, por meio de quatro acelerômetros, os níveis de vibração (m s-2 e choques em percursos realizados nas estradas de terra e asfalto. O número de ovos trincados foi obtido por meio da contabilização de 18 caixas de ovos transportadas que apresentavam três idades de matrizes e três tempos de estocagem, pelo método visual. Foi utilizado o delineamento experimental inteiramente aleatorizado com esquema fatorial 3 x 3. Conclui-se que as matrizes velhas e intermediárias apresentaram o maior número de ovos trincados; os maiores níveis de vibração e choques da carga ocorreram no sentido horizontal enquanto a estrada de asfalto ofereceu as piores condições para o transporte de ovos.

  14. "Das Konkrete ist das Abstrakte, an das man sich schließlich gewöhnt hat." (Laurent Schwartz) Über den Ablauf des mathematischen Verstehens

    Science.gov (United States)

    Lowsky, Martin

    Die im Titel genannte Aussage findet sich in den Lebenserinnerungen von Laurent Schwartz (1915-2002), einem der fruchtbarsten Mathematiker, Mitglied der Gruppe Bourbaki. Im Original lautet die Aussage: "un objet concret est un objet abstrait auquel on a fini par s'habituer." Schwartz erläutert sie am Beispiel des Integrals über {e^{-1/2{x^2}}} , das den Wert Wurzel aus 2π hat und in dem sich also die Zahlen e und π verknüpfen. Was Schwartz aber vor allem ausdrücken will, ist dies: Das mathematische Verständnisd geht langsam vor sich und es bedarf der Anstrengung. "Es ist eine Frage der Zeit und der Energie", sagt Schwartz, und gerade dies mache es so schwer, die höhere Mathematik unter das Volk zu bringen. Das Lernen und Lehren von Mathematik laufe eben mühevoll und langsam ab.

  15. Processing Approaches for DAS-Enabled Continuous Seismic Monitoring

    Science.gov (United States)

    Dou, S.; Wood, T.; Freifeld, B. M.; Robertson, M.; McDonald, S.; Pevzner, R.; Lindsey, N.; Gelvin, A.; Saari, S.; Morales, A.; Ekblaw, I.; Wagner, A. M.; Ulrich, C.; Daley, T. M.; Ajo Franklin, J. B.

    2017-12-01

    Distributed Acoustic Sensing (DAS) is creating a "field as laboratory" capability for seismic monitoring of subsurface changes. By providing unprecedented spatial and temporal sampling at a relatively low cost, DAS enables field-scale seismic monitoring to have durations and temporal resolutions that are comparable to those of laboratory experiments. Here we report on seismic processing approaches developed during data analyses of three case studies all using DAS-enabled seismic monitoring with applications ranging from shallow permafrost to deep reservoirs: (1) 10-hour downhole monitoring of cement curing at Otway, Australia; (2) 2-month surface monitoring of controlled permafrost thaw at Fairbanks, Alaska; (3) multi-month downhole and surface monitoring of carbon sequestration at Decatur, Illinois. We emphasize the data management and processing components relevant to DAS-based seismic monitoring, which include scalable approaches to data management, pre-processing, denoising, filtering, and wavefield decomposition. DAS has dramatically increased the data volume to the extent that terabyte-per-day data loads are now typical, straining conventional approaches to data storage and processing. To achieve more efficient use of disk space and network bandwidth, we explore improved file structures and data compression schemes. Because noise floor of DAS measurements is higher than that of conventional sensors, optimal processing workflow involving advanced denoising, deconvolution (of the source signatures), and stacking approaches are being established to maximize signal content of DAS data. The resulting workflow of data management and processing could accelerate the broader adaption of DAS for continuous monitoring of critical processes.

  16. Analisis Laju Sedimen DAS Serayu Hulu dengan Menggunakan Model SWAT

    Directory of Open Access Journals (Sweden)

    Nugroho Christanto

    2018-03-01

    Full Text Available Wilayah DAS Serayu Hulu merupakan DAS prioritas yang memerlukan langkah pengelolaan yang komprehensif. Aplikasi model Soil and Water Assessment Tool (SWAT dapat digunakan sebagai media untuk  perencanaan konservasi ataupun evaluasi respon DAS (debit aliran permukaan, sedimen dan pencemaran sungai. Tujuan utama dari penelitian ini adalah menjalankan model SWAT di DAS Serayu Hulu untuk mengetahui laju sedimen di wilayah ini. Pemodelan SWAT membutuhkan sejumlah input parameter berupa relief, tanah, tutupan lahan dan pengelolaan lahan. Pedogeomorfologi digunakan sebagai batas satuan tanah karena tidak tersedianya peta tanah di wilayah penelitian. Hasil Penerapan model SWAT di DAS Serayu Hulu menghasilkan nilai yang cukup memuaskan, hal ini ditunjukkan nilai R2 mencapai 0,94. Hasil pemodelan SWAT dengan menggunakan data selama 10 tahun (2004-2013 menunjukkan bahwa DAS Serayu Hulu memiliki rerata hasil sedimen sebesar 1.926.900 ton/tahun. Sub DAS 8,9 11, 17, 18, dan 19 merupakan penghasil sedimen tertinggi di DAS Serayu Hulu dengan hasil sedimen 43.931– 121.434 ton/ha/tahun.

  17. Poly (I:C) enhances the anti-tumor activity of canine parvovirus NS1 protein by inducing a potent anti-tumor immune response.

    Science.gov (United States)

    Gupta, Shishir Kumar; Yadav, Pavan Kumar; Tiwari, A K; Gandham, Ravi Kumar; Sahoo, A P

    2016-09-01

    The canine parvovirus NS1 (CPV2.NS1) protein selectively induces apoptosis in the malignant cells. However, for an effective in vivo tumor treatment strategy, an oncolytic agent also needs to induce a potent anti-tumor immune response. In the present study, we used poly (I:C), a TLR3 ligand, as an adjuvant along with CPV2.NS1 to find out if the combination can enhance the oncolytic activity by inducing a potent anti-tumor immune response. The 4T1 mammary carcinoma cells were used to induce mammary tumor in Balb/c mice. The results suggested that poly (I:C), when given along with CPV2.NS1, not only significantly reduced the tumor growth but also augmented the immune response against tumor antigen(s) as indicated by the increase in blood CD4+ and CD8+ counts and infiltration of immune cells in the tumor tissue. Further, blood serum analysis of the cytokines revealed that Th1 cytokines (IFN-γ and IL-2) were significantly upregulated in the treatment group indicating activation of cell-mediated immune response. The present study reports the efficacy of CPV2.NS1 along with poly (I:C) not only in inhibiting the mammary tumor growth but also in generating an active anti-tumor immune response without any visible toxicity. The results of our study may help in developing CPV2.NS1 and poly (I: C) combination as a cancer therapeutic regime to treat various malignancies.

  18. Identification, characterization and potent antitumor activity of ECO-4601, a novel peripheral benzodiazepine receptor ligand.

    Science.gov (United States)

    Gourdeau, Henriette; McAlpine, James B; Ranger, Maxime; Simard, Bryan; Berger, Francois; Beaudry, Francis; Farnet, Chris M; Falardeau, Pierre

    2008-05-01

    ECO-4601 is a structurally novel farnesylated dibenzodiazepinone discovered through DECIPHER technology, Thallion's proprietary drug discovery platform. The compound was shown to have a broad cytotoxic activity in the low micromolar range when tested in the NCI 60 cell line panel. In the work presented here, ECO-4601 was further evaluated against brain tumor cell lines. Preliminary mechanistic studies as well as in vivo antitumor evaluation were performed. Since ECO-4601 has a benzodiazepinone moiety, we first investigated if it binds the central and/or peripheral benzodiazepine receptors. ECO-4601 was tested in radioligand binding assays on benzodiazepine receptors obtained from rat hearts. The ability of ECO-4601 to inhibit the growth of CNS cancers was evaluated on a panel of mouse, rat and human glioma cell lines using a standard MTT assay. Antitumor efficacy studies were performed on gliomas (rat and human), human breast and human prostate mouse tumor xenografts. Antitumor activity and pharmacokinetic analysis of ECO-4601 was evaluated following intravenous (i.v.), subcutaneous (s.c.), and intraperitoneal (i.p.) bolus administrations. ECO-4601 was shown to bind the peripheral but not the central benzodiazepine receptor and inhibited the growth of CNS tumor cell lines. Bolus s.c. and i.p. administration gave rise to low but sustained drug exposure, and resulted in moderate to significant antitumor activity at doses that were well tolerated. In a rat glioma (C6) xenograft model, ECO-4601 produced up to 70% tumor growth inhibition (TGI) while in a human glioma (U-87MG) xenograft, TGI was 34%. Antitumor activity was highly significant in both human hormone-independent breast (MDA-MB-231) and prostate (PC-3) xenografts, resulting in TGI of 72 and 100%, respectively. On the other hand, i.v. dosing was followed by rapid elimination of the drug and was ineffective. Antitumor efficacy of ECO-4601 appears to be associated with the exposure parameter AUC and/or sustained

  19. Sistema das Artes Visuais no Brasil

    Directory of Open Access Journals (Sweden)

    Nei Vargas da Rosa

    2017-10-01

    Full Text Available O Dossiê Sistema das Artes Visuais no Brasil se oferece como um profícuo dispositivo de análise do sistema da arte e de seu crescimento e avanço como objeto de reflexão e investigação. Reúne um grupo de pesquisadoras e pesquisadores que respondem por estudos de temas diversos, como a compreensão dos processos de valoração, considerando seus aspectos simbólicos e mercadológicos; a discussão sobre a gestão dos aparelhos culturais em meio ao receituário da política econômica centrada no mercado; a inserção recente de instrumentos de visibilidade e circulação da arte, como as ferias de arte e a Internet; o papel de colecionadores e colecionadoras no sistema de arte; entre outros assuntos; e os estudos sobre educação em museu de arte. Assim, o Dossiê segue uma ordenação que busca oferecer uma lógica conceitual e factual para compreensão do tema proposto, não excluindo a possibilidade de leitura direta a textos que ofereçam conteúdo de interesses específicos dos leitores e leitoras.

  20. O TETO DE VIDRO DAS EXECUTIVAS BRASILEIRAS

    Directory of Open Access Journals (Sweden)

    Gustavo Simão Lima

    2014-04-01

    Full Text Available Apesar da ampliação da equidade entre os gêneros, a desigualdade ainda é real, inclusive nas organizações. Este trabalho objetiva analisar as barreiras que compõem o teto de vidro na carreira das mulheres executivas no Brasil, segundo as categorias de análise: esforço investido no trabalho; disposição para assumir riscos; empatia e agressividade para negociar; racionalidade em relação aos gêneros; expressão de sentimentos; vida pessoal versus vida profissional. A sustentação teórica apoia-se na discussão sobre a atuação da mulher no mercado de trabalho, sob a perspectiva dos principais desafios para a progressão da mulher em cargos executivos. Na pesquisa qualitativa foram entrevistados 40 executivos de nível estratégico de grandes empresas, homens e mulheres. Os resultados indicam que a mulher ainda sofre com uma inserção subalterna, preconceito e discriminação. Elas enfrentam um conjunto de barreiras que formam o chamado “teto de vidro”, que ainda limita a ascensão delas aos cargos mais altos.

  1. "POVO DE DEUS RENASCENDO DAS CULTURAS OPRIMIDAS"

    Directory of Open Access Journals (Sweden)

    Afonso Murad

    1992-01-01

    Full Text Available Os encontros íntereclesiais das CEBs se revestem de uma importância ímpar para a Igreja do Brasil. Reconhecidamente as Comunidades Eclesiais de Base são não somente símbolo, mas também o campo privilegiado onde se mostram as feições da Igreja dos pobres. Por isso cada encontro ao mesmo tempo que sinaliza os passos da caminhada realizada nos últimos anos, desentranhando aspectos não tão visíveis, explicita desafios e impulsiona novas práticas, É um grande concilio dos leigos pobres da Igreia do Brasil. Importam pouco as conclusões intelectuais, já que não há documento final c om decisões, mas simplesmente uma carta enviada às comunidades. Decisivo mesmo é o clima que se cria na preparação, realização e aprofundamento deste encontro, tendo grande valor a narração e análise do acontecimento.

  2. Os Simpsons no dia das bruxas

    Directory of Open Access Journals (Sweden)

    Chantal Herskovic

    2014-07-01

      Este artigo tem como objetivo resgatar paródias da série de TV Os Simpsons a partir de histórias inspiradas em obras da literatura gótica, visando verificar de que forma dialogam com os textos de partda e com o tema de Halloween ou o Dia das Bruxas. Serão utilizadas para análise reflexões teóricas propostas por Umberto Eco (2001 em que o autor discute o papel da cultura de massa na atualidade; por David Punter, (1996 em que analisa as características da literatura gótica; por Alberto Manguel (2005 em que distingue os conceitos de terror e horror; por Julio Plaza (2001 em que propõe estudos sobre transcriação sígnica e o conceito de intertextualidade; e, finalmente, por Linda Hutcheon (1986 em que analisa a questão da adaptação e o conceito de paródia.

  3. Time-dependent Influence of Procaine Hydrochloride on Cisplatin Antitumor Activity in P388 Tumor Bearing Mice

    Czech Academy of Sciences Publication Activity Database

    Viale, M.; Vánnozzi, M. O.; Mandys, Václav; Esposito, M.

    2001-01-01

    Roč. 21, - (2001), s. 485-488 ISSN 0250-7005 Institutional research plan: CEZ:AV0Z5039906 Keywords : cisplatin * procaine * antitumor activity Subject RIV: EA - Cell Biology Impact factor: 1.416, year: 2001

  4. Proton pump inhibitors while belonging to the same family of generic drugs show different anti-tumor effect.

    Science.gov (United States)

    Lugini, Luana; Federici, Cristina; Borghi, Martina; Azzarito, Tommaso; Marino, Maria Lucia; Cesolini, Albino; Spugnini, Enrico Pierluigi; Fais, Stefano

    2016-08-01

    Tumor acidity represents a major cause of chemoresistance. Proton pump inhibitors (PPIs) can neutralize tumor acidity, sensitizing cancer cells to chemotherapy. To compare the anti-tumor efficacy of different PPIs in vitro and in vivo. In vitro experiments PPIs anti-tumor efficacy in terms of cell proliferation and cell death/apoptosis/necrosis evaluation were performed. In vivo PPIs efficacy experiments were carried out using melanoma xenograft model in SCID mice. Lansoprazole showed higher anti-tumor effect when compared to the other PPIs. The lansoprazole effect lasted even upon drug removal from the cell culture medium and it was independent from the lipophilicity of the PPIs formulation. These PPIs have shown different anti-tumoral efficacy, and the most effective at low dose was lansoprazole. The possibility to contrast tumor acidity by off-label using PPIs opens a new field of oncology investigation.

  5. Antioxidants Impair Anti-Tumoral Effects of Vorinostat, but Not Anti-Neoplastic Effects of Vorinostat and Caspase-8 Downregulation

    OpenAIRE

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat...

  6. Anti-tumor Activity of Toll-Like Receptor 7 Agonists

    Directory of Open Access Journals (Sweden)

    Huju Chi

    2017-05-01

    Full Text Available Toll-like receptors (TLRs are a class of pattern recognition receptors that play a bridging role in innate immunity and adaptive immunity. The activated TLRs not only induce inflammatory responses, but also elicit the development of antigen specific immunity. TLR7, a member of TLR family, is an intracellular receptor expressed on the membrane of endosomes. TLR7 can be triggered not only by ssRNA during viral infections, but also by immune modifiers that share a similar structure to nucleosides. Its powerful immune stimulatory action can be potentially used in the anti-tumor therapy. This article reviewed the anti-tumor activity and mechanism of TLR7 agonists that are frequently applied in preclinical and clinical investigations, and mainly focused on small synthetic molecules, including imiquimod, resiquimod, gardiquimod, and 852A, etc.

  7. The role of radiotherapy for the induction of antitumor immune responses

    International Nuclear Information System (INIS)

    Multhoff, G.; Helmholtz-Zentrum Muenchen; Gaipl, U.S.; Niedermann, G.

    2012-01-01

    Effective radiotherapy is aimed to control the growth of the primary carcinoma and to induce a long-term specific antitumor immune response against the primary tumor, recurrence and metastases. The contribution covers the following issues: T cells and tumor specific immune responses, dendritic cells (DCs) start adaptive immune responses, NK (natural killer) cells for HLA independent tumor control, abscopal effects of radiotherapy, combination of radiotherapy and immune therapy, radiotherapy contribution to the induction of immunogenic cell death, combinability of radiotherapy and DC activation, combinability of radiotherapy and NK cell therapy. It turns out that the combination of radio-chemotherapy and immune therapy can change the microenvironment initiating antitumor immune reactions that inhibit the recurrence risk and the development of metastases.

  8. Role of CD1A and HSP60 in the antitumoral response of oesophageal cancer

    Directory of Open Access Journals (Sweden)

    Simona Corrao

    2011-12-01

    Full Text Available Oesophageal cancer (OC is one of the most common and severe forms of tumor. A wider knowledge of molecular mechanisms which lead to a normal epithelium becoming a neoplasm may reveal new strategies to improve treatment and outcome of this disease. In this review, we report recent findings concerning molecular events which take place during carcinogenesis of the oesophagus. In particular, we focus on the role of two molecules, CD1a and Hsp60, which are overexpressed in oesophageal and many other types of tumor. Both molecules may present tumor antigens and promote in situ the stimulation of an antitumoral immune activity. We suggest there is a synergistic action between these molecules. Further knowledge about their intracellular pathways and extracellular roles may help develop new antitumoral tools for OC.

  9. Clinical pharmacology of CAR-T cells: Linking cellular pharmacodynamics to pharmacokinetics and antitumor effects.

    Science.gov (United States)

    Norelli, M; Casucci, M; Bonini, C; Bondanza, A

    2016-01-01

    Adoptive cell transfer of T cells genetically modified with tumor-reactive chimeric antigen receptors (CARs) is a rapidly emerging field in oncology, which in preliminary clinical trials has already shown striking antitumor efficacy. Despite these premises, there are still a number of open issues related to CAR-T cells, spanning from their exact mechanism of action (pharmacodynamics), to the factors associated with their in vivo persistence (pharmacokinetics), and, finally, to the relative contribution of each of the two in determining the antitumor effects and accompanying toxicities. In light of the unprecedented curative potential of CAR-T cells and of their predicted wide availability in the next few years, in this review we will summarize the current knowledge on the clinical pharmacology aspects of what is anticipated to be a brand new class of biopharmaceuticals to join the therapeutic armamentarium of cancer doctors. Copyright © 2015. Published by Elsevier B.V.

  10. Spin-labeled 1-alkyl-1-nitrosourea synergists of antitumor antibiotics.

    Science.gov (United States)

    Gadjeva, V; Koldamova, R

    2001-01-01

    A new method for synthesis of four spin-labeled structural analogues of the antitumor drug 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), using ethyl nitrite for nitrosation of the intermediate spin-labeled ureas has been described. In vitro synergistic effects of 1-ethyl-3-[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)]-1-nitrosourea (3b) on the cytotoxicity of bleomycin and farmorubicin were found in human lymphoid leukemia tumor cells. We measured the tissue distribution of 3b in organ homogenates of C57BL mice by an electron paramagnetic resonance method. The spin-labeled nitrosourea was mainly localized in the lungs. Our results strongly support the development and validation of a new approach for synthesis of less toxic nitrosourea derivatives as potential synergists of antitumor drugs.

  11. Recent advance on the antitumor and antioxidant activity of grape seed extracts

    Directory of Open Access Journals (Sweden)

    Zhu FM

    2015-05-01

    Full Text Available Fengmei Zhu, Bin Du, Jun Li College of Food Science and Technology, Hebei Normal University of Science and Technology, Qinhuangdao, Hebei Province, People's Republic of China Abstract: The grape pomace (including seeds and stems poses potential disposal and pollution problems along with loss of valuable biomass and nutrients. The utilization of grape seeds processing as a source of functional ingredients is a promising field. Grape seed extract provides a concentrated source of polyphenols. Grape seed extract is known as an effective antioxidant that protects the body from premature aging and disease. A number of phytochemicals including resveratrol, proanthocyanidins, etc, have demonstrated significant benefits in cancer chemoprevention. In this review, we summarize the existing knowledge on the antitumor and antioxidant activity of grape seeds polyphenols. Keywords: grape seed, antitumor activity, antioxidant activity, polyphenol, proanthocyanidin

  12. Structure, chain conformation and antitumor activity of a novel polysaccharide from Lentinus edodes.

    Science.gov (United States)

    Yu, Zhang; Ming, Gu; Kaiping, Wang; Zhixiang, Chen; Liquan, Dai; Jingyu, Liu; Fang, Zeng

    2010-12-01

    A water-soluble polysaccharide LT1 was isolated from the basidiocarps of Lentinus edodes by hot water extraction and ethanol precipitations, further purified by gel chromatography. The Mw of LT1 was estimated to be 642 kDa by using HPGPC. Chemical and spectroscopic studies illustrated that LT1 has a backbone chain composed of 1 → 4-linked and 1 → 3-linked glucopyranosyl residues and has branches of single glucosyl stubs at C-6 of β-(1 → 4)-linked glucopyranosyl. AFM and Congo-red test revealed that LT1 existed as triple helix chain in 0.10 M NaOH solution or distilled water. Our studies showed that LT1 presented significant antitumor bioactivities on Sarcoma180 solid tumor cell implanted in BALB/c mice, which implies that LT1 could be potentially applied as a natural antitumor drug. Copyright © 2010 Elsevier B.V. All rights reserved.

  13. Orogenias: das margens continentais ao interior remoto das placas, uma revisão no tema

    Directory of Open Access Journals (Sweden)

    Benjamim Bley de Brito Neves

    2016-05-01

    Full Text Available Esta síntese do conceito de orogenias abrange desde a Tectônica de Placas dos anos 1970, adendos e modelos "alternativos", que buscam explicar orogenias distantes das zonas de interação de placas. A análise crítica dos modelos originais resultou em adendos que incluem domínios proterozoicos e paleozoicos e observações sobre reologia e história termo-tectônica da litosfera. Os modelos alternativos explicam a orogênese por subdução local de litosfera continental, sem envolver litosfera oceânica. Nos anos 1990, houve notável avanço no estudo das causas da subsidência (tectônica formadora de bacias e estudos que contestam a rigidez das placas e propõem modelos de enfraquecimento devido à ação termal. Orogenias intracontinentais, entendidas como caso extremo da inversão de bacias, ocorrem em praticamente todos os continentes. Esforços gerados em zonas de interação de placas podem ser transmitidas continente adentro por milhares de quilômetros e gerar tectônica deformadora longe de suturas. Embora esteja ainda em estágio de fluxo, o conceito de orogenias intracontinentais ("telessuturais" vem se consolidando, embora não tenha sido incorporado a livros-texto. O histórico e o reexame do tema possibilitam classificar os orógenos segundo três variáveis principais: posição em relação às zonas de sutura, organização geométrico-geológica (em planta e nível de exumação.

  14. T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor

    Directory of Open Access Journals (Sweden)

    Kim Tae-Sik

    2011-06-01

    Full Text Available Abstract Background Although the graft-versus-tumor (GVT effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB transplantation have not been well studied. Methods We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells. Results We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays. Conclusions Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.

  15. Antitumor effects of regorafenib and sorafenib in preclinical models of hepatocellular carcinoma

    OpenAIRE

    Kissel, Maria; Berndt, Sandra; Fiebig, Lukas; Kling, Simon; Ji, Qunsheng; Gu, Qingyang; Lang, Tina; Hafner, Frank-Thorsten; Teufel, Michael; Zopf, Dieter

    2017-01-01

    The purpose of this study was to investigate the antitumor activity of regorafenib and sorafenib in preclinical models of HCC and to assess their mechanism of action by associated changes in protein expression in a HCC-PDX mouse model. Both drugs were administered orally once daily at 10 mg/kg (regorafenib) or 30 mg/kg (sorafenib), which recapitulate the human exposure at the maximally tolerated dose in mice. In a H129 hepatoma model, survival times differed significantly between regorafenib ...

  16. Effects of a piperidine ligand on DNA modification by antitumor cisplatin analogues

    Czech Academy of Sciences Publication Activity Database

    Kašpárková, Jana; Nováková, Olga; Najajreh, Y.; Gibson, D.; Perez, J.M.; Brabec, Viktor

    2003-01-01

    Roč. 16, č. 11 (2003), s. 1424-1432 ISSN 0893-228X R&D Projects: GA ČR GA305/02/1552; GA AV ČR KJB5004301; GA AV ČR IBS5004009 Institutional research plan: CEZ:AV0Z5004920 Keywords : DNA * piperidine ligand * antitumor cisplatin analogues Subject RIV: BO - Biophysics Impact factor: 3.332, year: 2003

  17. Total synthesis and stereochemical assignment of the salicylate antitumor macrolide lobatamide C(1).

    Science.gov (United States)

    Shen, Ruichao; Lin, Cheng Ting; Porco, John A

    2002-05-22

    The total synthesis and stereochemical assignment of the potent antitumor macrolide lobatamide C is reported. The synthesis involves Cu(I)-mediated enamide formation and Na(2)CO(3)-mediated esterification of a beta-hydroxy acid and a salicylate cyanomethyl ester. Macrolactonization was accomplished using a Mitsunobu protocol. The stereochemical assignment of lobatamide C was achieved by Mosher ester analysis and comparison with prepared stereoisomers.

  18. Two new phenolic compounds and antitumor activities of asparinin A from Asparagus officinalis.

    Science.gov (United States)

    Li, Xue-Mei; Cai, Jin-Long; Wang, Le; Wang, Wen-Xiang; Ai, Hong-Lian; Mao, Zi-Chao

    2017-02-01

    Two new phenolic acid compounds, asparoffin C (1) and asparoffin D (2), together with four known compounds, asparenyol (3), gobicusin B (4), 1-methoxy-2-hydroxy-4-[5-(4-hydroxyphenoxy)-3-penten-1-ynyl] phenol (5), and asparinin A (6), have been isolated from the stems of Asparagus officinalis. The structures were established by extensive spectroscopic methods (MS and 1D and 2D NMR). Compound 6 has obvious antitumor activities both in vitro and in vivo.

  19. Development of CAR T cells designed to improve antitumor efficacy and safety

    OpenAIRE

    Jaspers, Janneke E.; Brentjens, Renier J.

    2017-01-01

    Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are ‘on-target, off-tumor’ toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how ...

  20. Antitumor activity and carrier properties of novel hemocyanins coupled to a mimotope of GD2 ganglioside.

    Science.gov (United States)

    Palacios, Miriam; Tampe, Ricardo; Del Campo, Miguel; Zhong, Ta-Ying; López, Mercedes N; Salazar-Onfray, Flavio; Becker, María Inés

    2018-04-25

    Conjugation to carrier proteins is a way to improve the immunogenicity of peptides. Such is the case for peptides mimicking carbohydrate tumor-associated antigens in cancer vaccine development. The most used protein for this purpose is the keyhole limpet hemocyanin (KLH) from Megathura crenulata. Its limited bioavailability has prompted interest in finding new candidates; nevertheless, it is not known whether other hemocyanins might be equally efficient as carrier of carbohydrate peptide mimotopes to promotes anti-tumor responses. Here, we evaluated the carrier and antitumor activity of novel hemocyanins with documented immunogenicity obtained from Concholepas concholepas (CCH) and Fissurella latimarginata (FLH), coupled through sulfo-SMCC to P10, a mimetic peptide of GD2, the major ganglioside constituent of neuroectodermal tumors, and incorporating AddaVax as an adjuvant. The humoral immune responses of mice showed that CCH-P10 and FLH-P10 conjugates elicited specific IgM and IgG antibodies against P10 mimotope, similar to those obtained with KLH-P10, which was used as a positive control. The CCH-P10 and FLH-P10 antisera, exhibited cross-reactivity with murine and human melanoma cells, like anti-CCH and anti-FLH sera suggesting a cross-reaction of CCH and FLH glycosylations with carbohydrate epitopes on the tumor cell surfaces, similar to the KLH antisera. When mice were primed with each hemocyanin-P10 and challenged with melanoma cells, better antitumor effects were observed for FLH-P10 than for CCH-P10 and, as for KLH-P10, irrespective of conjugation. These data demonstrate that CCH and FLH are useful carriers of carbohydrate mimotopes; however, the best antitumor activity of FLH preparations, indicate that is a suitable candidate for further cancer vaccines research. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  1. Pulse radiolysis study of the reduction mechanism of an antitumor antibiotic, mitomycin C

    International Nuclear Information System (INIS)

    Machtalere, G.; Houee-Levin, C.; Gardes-Albert, M.; Ferradini, C.; Hickel, B.

    1988-01-01

    Mitomycin C is a quinonic antitumor metabolized in vivo by one-electron reduction. We have studied the mechanism of the one-electron reduction of this drug by pulse radiolysis using C00 .- free radicals as reductants. Semiquinonic and hydroquinonic intermediates are formed. The hydroquinonic form undergoes a methanol elimination leading to a transient which can disappear in one of two ways: by either internal redox reaction or hydrolysis of the aziridine. 17 refs [fr

  2. Activation of Anti-tumor Immune Response by Ablation of HCC with Nanosecond Pulsed Electric Field.

    Science.gov (United States)

    Xu, Xiaobo; Chen, Yiling; Zhang, Ruiqing; Miao, Xudong; Chen, Xinhua

    2018-03-28

    Locoregional therapy is playing an increasingly important role in the non-surgical management of hepatocellular carcinoma (HCC). The novel technique of non-thermal electric ablation by nanosecond pulsed electric field has been recognized as a potential locoregional methodology for indicated HCC. This manuscript explores the most recent studies to indicate its unique anti-tumor immune response. The possible immune mechanism, termed as nano-pulse stimulation, was also analyzed.

  3. Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer.

    Science.gov (United States)

    Telli, M L; Stover, D G; Loi, S; Aparicio, S; Carey, L A; Domchek, S M; Newman, L; Sledge, G W; Winer, E P

    2018-05-07

    Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit. We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection. Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise. HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of 'immune cold' TNBCs.

  4. Doxil Synergizes with Cancer Immunotherapies to Enhance Antitumor Responses in Syngeneic Mouse Models

    Directory of Open Access Journals (Sweden)

    Jonathan Rios-Doria

    2015-08-01

    Full Text Available Based on the previously described roles of doxorubicin in immunogenic cell death, both doxorubicin and liposomal doxorubicin (Doxil were evaluated for their ability to boost the antitumor response of different cancer immunotherapies including checkpoint blockers (anti–PD-L1, PD-1, and CTLA-4 mAbs and TNF receptor agonists (OX40 and GITR ligand fusion proteins in syngeneic mouse models. In a preventative CT26 mouse tumor model, both doxorubicin and Doxil synergized with anti–PD-1 and CTLA-4 mAbs. Doxil was active when CT26 tumors were grown in immunocompetent mice but not immunocompromised mice, demonstrating that Doxil activity is increased in the presence of a functional immune system. Using established tumors and maximally efficacious doses of Doxil and cancer immunotherapies in either CT26 or MCA205 tumor models, combination groups produced strong synergistic antitumor effects, a larger percentage of complete responders, and increased survival. In vivo pharmacodynamic studies showed that Doxil treatment decreased the percentage of tumor-infiltrating regulatory T cells and, in combination with anti–PD-L1, increased the percentage of tumor-infiltrating CD8+ T cells. In the tumor, Doxil administration increased CD80 expression on mature dendritic cells. CD80 expression was also increased on both monocytic and granulocytic myeloid cells, suggesting that Doxil may induce these tumor-infiltrating cells to elicit a costimulatory phenotype capable of activating an antitumor T-cell response. These results uncover a novel role for Doxil in immunomodulation and support the use of Doxil in combination with checkpoint blockade or TNFR agonists to increase response rates and antitumor activity.

  5. DNA crosslinking and cytotoxicity in normal and transformed human cells treated with antitumor nitrosoureas.

    OpenAIRE

    Erickson, L C; Bradley, M O; Ducore, J M; Ewig, R A; Kohn, K W

    1980-01-01

    Normal (IMR-90) and simian virus 40-transformed (VA-13) human embryo cells were treated with antitumor nitrosoureas, and the effects on cell viability and cell DNA were compared. All six nitrosoureas tested were more toxic to VA-13 cells than to IMR-90 cells as measured by decrease in cell proliferation or in colony formation. The nitrosoureas capable of generating alkylisocyanates produced a smaller difference between the cell types than did derivatives lacking this capacity. DNA damage was ...

  6. Thermodynamics of translesion synthesis across a major DNA adduct of antitumor oxaliplatin: Differential scanning calorimetric study

    Czech Academy of Sciences Publication Activity Database

    Florian, Jakub; Brabec, Viktor

    2012-01-01

    Roč. 18, č. 6 (2012), s. 1634-1639 ISSN 0947-6539 R&D Projects: GA ČR(CZ) GD301/09/H004; GA ČR(CZ) GAP301/10/0598 Institutional research plan: CEZ:AV0Z50040702 Keywords : antitumor platinum * DNA * calorimetry Subject RIV: BO - Biophysics Impact factor: 5.831, year: 2012

  7. Novel T cells with improved in vivo anti-tumor activity generated by RNA electroporation

    Directory of Open Access Journals (Sweden)

    Xiaojun Liu

    2017-05-01

    Full Text Available ABSTRACT The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cell-based adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB (OKT3-28BB. The expanded T cells were phenotypically and functionally similar to T cells expanded by OKT3/IL-2. Moreover, co-electroporation of CD86 and 4-1BBL could further change the phenotype and enhance the in vivo anti-tumor activity. Although T cells expanded by the co-electroporation of OKT3-28BB with CD86 and 4-1BBL showed an increased central memory phenotype, the T cells still maintained tumor lytic activities as potent as those of OKT3/IL-2 or OKT3-28BB-stimulated T cells. In different tumor mouse models, T cells expanded by OKT3-28BB RNA electroporation showed anti-tumor activities superior to those of OKT3/IL-2 T cells. Hence, T cells with both a less differentiated phenotype and potent tumor killing ability can be generated by RNA electroporation, and this T cell manufacturing procedure can be further optimized by simply co-delivering other splices of RNA, thus providing a simple and cost-effective method for generating high-quality T cells for adoptive immunotherapy.

  8. The Therapeutic Effect of the Antitumor Drug 11 Beta and Related Molecules on Polycystic Kidney Disease

    Science.gov (United States)

    2017-10-01

    models (Somlo, Yale). Preparation work to assemble a collection of probes specific for oxidative stress genes and other PKD specific genes (as part... Worked : 6 Contribution to Project: Performance of experiments including those related to mitochondrial biology in vivo and unfolded protein...1 AWARD NUMBER: W81XWH-15-1-0364 TITLE: THE THERAPEUTIC EFFECT OF THE ANTITUMOR DRUG 11 BETA AND RELATED MOLECULES ON POLYYSTIC KIDNEY DISEASE

  9. Das Anreizargument in Wirtschaftsethik und Gerechtigkeitstheorie

    Directory of Open Access Journals (Sweden)

    Neuhäuser Christian

    2016-12-01

    Full Text Available Die Idee, dass vor allem monetäre Anreize das Verhalten von Wirtschaftsakteuren in gewünschte Richtungen lenken und sogar dabei helfen können, durch Leistungssteigerung zusätzliche Wohlfahrtseffekte zu generieren, spielt in der politischen Ökonomie seit ihren Anfängen eine zentrale Rolle. Es spricht sogar einiges dafür, dass dieser Gedanke das verbindende Glied der Ökonomik als Gesellschaftstheorie im Gegensatz zu anderen gesellschaftstheoretischen Entwürfen ausmacht. Dennoch halte ich dieses Anreizargument aus normativer Perspektive für unterentwickelt, wie ich in Auseinandersetzung mit der Ökonomischen Ethik bzw. Ordnungsethik nach Karl Homann und der Integrativen Wirtschaftsethik zeigen möchte. Weder gelingt es der Ordnungsethik nach Karl Homann, die Bedeutung von Anreizstrukturen hinreichend zu begründen, obwohl sie in Ansätzen wichtige Argumente formuliert. Noch gelingt es der Integrativen Wirtschaftsethik, die zentrale Rolle von Anreizstrukturen für die normative Theoriebildung überzeugend zurückzuweisen. Mir geht es nicht darum, den einen oder anderen wirtschaftsethischen Ansatz grundsätzlich zurückzuweisen, sondern vielmehr, auf Lücken in der Argumentation und sich daraus ergebende Forschungsfragen hinzuweisen. Vor diesem Hintergrund könnte es helfen, einen verwandten Diskurs aus der gegenwärtigen Gerechtigkeitstheorie in die Überlegungen mit einzubeziehen. Denn die grundlegende Idee der ökonomischen Gesellschaftstheorie einer Wohlfahrtssteigerung durch die gezielte Manipulation von Anreizstrukturen hat auch in der gegenwärtigen Gerechtigkeitstheorie ihre Wirkung entfaltet. In seiner Theorie der Gerechtigkeit hat John Rawls argumentiert, dass selbst Egalitaristen bestimmte Einkommensunterschiede zulassen müssen, wenn dadurch für Leistungsträgerinnen solche Anreize gesetzt werden, die gleichzeitig auch den Schlechtestgestellten zum Vorteil gereichen. Diese Argumentation ist von Gerald Cohen einer harschen

  10. Editorial das organizadoras do VI ENANCIB

    Directory of Open Access Journals (Sweden)

    Ligia Maria Arruda Café

    2006-07-01

    Full Text Available EDITORIAL A história das idéias, em um determinado campo do conhecimento, se faz por meio de seus cientistas e de suas instituições. Ela torna visível a produção intelectual deste campo, construída por seus atores individuais e coletivos. Neste sentido, o ENANCIB é um elemento-chave neste processo de construção, o momento por excelência da disseminação do conhecimento nesta área. Ele permite a continuidade da história, o desenvolvimento da Ciência da Informação que se faz no Brasil e a coesão de sua comunidade. Por meio de debates, da troca de idéias e de experiências, promovem a construção da identidade deste campo científico, sua visibilidade, a delimitação de suas fronteiras e sua interrelação com outras áreas do conhecimento. O ENANCIB permite, além disso, a construção de novas parcerias científicas e a consolidação dos grupos de trabalho existentes. Este evento vem se estabelecendo, desde 1994, como fundamental para a consolidação e estruturação da área da Ciência da Informação brasileira, influenciando o desenvolvimento dos cursos de pós-graduação do país. Um campo se constrói somente se compreender as especificidades dos processos que atravessam o seu caminho. Em sua evolução, a Ciência da Informação, nos últimos 50 anos, tem se caracterizado pela diversidade de suas abordagens buscando definir a sua essência, por diferentes estudos e teorias. Nestes estudos, inúmeros aportes conceituais vêm sendo apresentados por diferentes pensadores por meio da visão particular de cada um deles. Na realidade, cada um adota uma forma distinta de observar, representar e explicitar a realidade com base na sua visão de mundo. Alguns autores enfatizam os aspectos comunicacionais da Ciência da Informação; outros destacam sua função social; outros, ainda, ressaltam sua forte ligação com as tecnologias. Este número da revista Encontros Bibli traz quatorze artigos apresentados no VI ENANCIB

  11. Evaluation of the antitumor effects of vitamin K2 (menaquinone-7) nanoemulsions modified with sialic acid-cholesterol conjugate.

    Science.gov (United States)

    Shi, Jia; Zhou, Songlei; Kang, Le; Ling, Hu; Chen, Jiepeng; Duan, Lili; Song, Yanzhi; Deng, Yihui

    2018-02-01

    Numerous studies have recently shown that vitamin K 2 (VK 2 ) has antitumor effects in a variety of tumor cells, but there are few reports demonstrating antitumor effects of VK 2 in vivo. The antitumor effects of VK 2 in nanoemulsions are currently not known. Therefore, we sought to characterize the antitumor potential of VK 2 nanoemulsions in S180 tumor cells in the present study. Furthermore, a ligand conjugate sialic acid-cholesterol, with enhanced affinity towards the membrane receptors overexpressed in tumors, was anchored on the surface of the nanoemulsions to increase VK 2 distribution to the tumor tissue. VK 2 was encapsulated in oil-in-water nanoemulsions, and the physical and chemical stability of the nanoemulsions were characterized during storage at 25 °C. At 25 °C, all nanoemulsions remained physically and chemically stable with little change in particle size. An in vivo study using syngeneic mice with subcutaneously established S180 tumors demonstrated that intravenous or intragastric administration of VK 2 nanoemulsions significantly suppressed the tumor growth. The VK 2 nanoemulsions modified with sialic acid-cholesterol conjugate showed higher tumor growth suppression than the VK 2 nanoemulsions, while neither of them exhibited signs of drug toxicity. In summary, VK 2 exerted effective antitumor effects in vivo, and VK 2 nanoemulsions modified with sialic acid-cholesterol conjugate enhanced the antitumor activity, suggesting that these VK 2 may be promising agents for the prevention or treatment of tumor in patients.

  12. Immunomodulatory and antitumor effects in vivo by the cytoplasmic fraction of Lactobacillus casei and Bifidobacterium longum.

    Science.gov (United States)

    Lee, Jung-Woo; Shin, Jung-Gul; Kim, Eun Hee; Kang, Hae Eun; Yim, In Been; Kim, Ji Yeon; Joo, Hong-Gu; Woo, Hee Jong

    2004-03-01

    The immunomodulatory and antitumor effects of lactic acid bacteria (LABs) were investigated. Cytoplasmic fraction of Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium longum were tested for the antiproliferative activity in vitro to SNUC2A, SNU1, NIH/3T3 and Jurkat cell lines by crystal violet assay. All cytoplasmic fraction suppressed proliferation of tumor cells, though L. casei and B. longum were more effective. From these results, cytoplasmic fraction of L. casei and B. longum with Y400 as a control were administered as dietary supplements to Balb/c mice for 2, and 4 consecutive wks. Administration for 4 wks enhanced the number of total T cells, NK cells and MHC class II+ cells, and CD4-CD8+ T cells in flow cytometry analysis. To determine of antitumor activity of LABs preparation in vivo, F9 teratocarcinoma cells were inoculated on mice at 14th day. Body weight was decreased with increased survival rate in all groups with the cytoplasm of LABs. Our results showed that cytoplasmic fraction of LABs had direct antiproliferative effects on tumor cell lines in vitro, effects on immune cells in vivo, and antitumor effects on tumor-bearing mice with prolonged survival periods.

  13. Ficus umbellata Vahl. (Moraceae Stem Bark Extracts Exert Antitumor Activities In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Kevine Kamga Silihe

    2017-05-01

    Full Text Available A Ficus umbellata is used to treat cancer. The present work was therefore designed to assess antitumor potentials of F. umbellata extracts in nine different cell lines. Cell cycle, apoptosis, cell migration/invasion, levels of reactive oxygen species (ROS, mitochondrial membrane potential (MMP, caspases activities as well as Bcl-2 and Bcl-xL protein content were assessed in MDA-MB-231 cells. The 7,12-dimethylbenz(aanthracene (DMBA-induced carcinogenesis in rats were also used to investigate antitumor potential of F. umbellata extracts. The F. umbellata methanol extract exhibited a CC50 of 180 μg/mL in MDA-MB-231 cells after 24 h. It induced apoptosis in MCF-7 and MDA-MB-231 cells, while it did not alter their cell cycle phases. Further, it induced a decrease in MMP, an increase in ROS levels and caspases activities as well as a downregulation in Bcl-2 and Bcl-xL protein contents in MDA-MB-231 cells. In vivo, F. umbellata aqueous (200 mg/kg and methanol (50 mg/kg extracts significantly (p < 0.001 reduced ovarian tumor incidence (10%, total tumor burden (58% and 46%, respectively, average tumor weight (57.8% and 45.6%, respectively as compared to DMBA control group. These results suggest antitumor potential of F. umbellata constituents possibly due to apoptosis induction mediated through ROS-dependent mitochondrial pathway.

  14. Anti-tumor bioactivities of curcumin on mice loaded with gastric carcinoma.

    Science.gov (United States)

    Wang, Xiao-Ping; Wang, Qiao-Xia; Lin, Huan-Ping; Chang, Na

    2017-09-20

    Curcumin, a derivative from the dried rhizome of curcuma longa, has been proven to possess anti-tumor effects. However, the detailed molecular mechanisms have not been fully elucidated. In this study, we aimed to explore the anti-tumor mechanisms of curcumin in treating gastric cancer. BALB/C mice grafted with a mouse gastric adenocarcinoma cell line (MFC) were used as the experimental model. Mice received different doses of curcumin after grafting. Tumor size was measured and tumor weight was determined after tumor inoculation. TUNEL assay and flow cytometric analysis were applied to evaluate the apoptosis of the cancer cells. Serum cytokines IFN-γ, TNF-α, granzyme B and perforin were detected by ELISA assay. The anti-tumor effect was determined using cytotoxic T-lymphocyte (CTL) assays and in vivo tumor prevention tests. The expression of DEC1, HIF-1α, STAT3 and VEGF in tumor tissues was examined by immunostaining and analyzed using an Image J analysis system. Compared with controls, tumor growth (size and weight) was significantly inhibited by curcumin treatment (P curcumin treatment group. Splenocyte cells from mice treated with curcumin exhibited higher cytolytic effects on MFC cancer cells than those from mice treated with saline (P curcumin treatment. Our results indicate that curcumin inhibits the proliferation of gastric carcinoma by inducing the apoptosis of tumor cells, activating immune cells to secrete a large amount of cytokines, and down-regulating the DEC1, HIF-1α, VEGF and STAT3 signal transduction pathways.

  15. In vitro and in vivo antitumor activity of crude extracts obtained from Brazilian Chromobacterium sp isolates

    Energy Technology Data Exchange (ETDEWEB)

    Menezes, C.B.A.; Silva, B.P. [Universidade Estadual de Campinas, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Campinas, SP (Brazil); Universidade de São Paulo, Interunidades em Biotecnologia, São Paulo, SP (Brazil); Sousa, I.M.O.; Ruiz, A.L.T.G.; Spindola, H.M. [Universidade Estadual de Campinas, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Campinas, SP (Brazil); Cabral, E.; Eberlin, M.N. [Instituto de Química, Universidade Estadual de Campinas, Laboratório Thomson Mass Spectrometry, Campinas, SP (Brazil); Tinti, S.V.; Carvalho, J.E. [Universidade Estadual de Campinas, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Campinas, SP (Brazil); Foglio, M.A.; Fantinatti-Garboggini, F. [Universidade Estadual de Campinas, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Campinas, SP (Brazil); Universidade de São Paulo, Interunidades em Biotecnologia, São Paulo, SP (Brazil)

    2012-10-23

    Natural products produced by microorganisms have been an important source of new substances and lead compounds for the pharmaceutical industry. Chromobacterium violaceum is a Gram-negative β-proteobacterium, abundant in water and soil in tropical and subtropical regions and it produces violacein, a pigment that has shown great pharmaceutical potential. Crude extracts of five Brazilian isolates of Chromobacterium sp (0.25, 2.5, 25, and 250 µg/mL) were evaluated in an in vitro antitumor activity assay with nine human tumor cells. Secondary metabolic profiles were analyzed by liquid chromatography and electrospray ionization mass spectrometry resulting in the identification of violacein in all extracts, whereas FK228 was detected only in EtCE 308 and EtCE 592 extracts. AcCE and EtCE 310 extracts showed selectivity for NCI/ADR-RES cells in the in vitro assay and were evaluated in vivo in the solid Ehrlich tumor model, resulting in 50.3 and 54.6% growth inhibition, respectively. The crude extracts of Chromobacterium sp isolates showed potential and selective antitumor activities for certain human tumor cells, making them a potential source of lead compounds. Furthermore, the results suggest that other compounds, in addition to violacein, deoxyviolacein and FK228, may be involved in the antitumor effect observed.

  16. Regulatory T cells as suppressors of anti-tumor immunity: Role of metabolism.

    Science.gov (United States)

    De Rosa, Veronica; Di Rella, Francesca; Di Giacomo, Antonio; Matarese, Giuseppe

    2017-06-01

    Novel concepts in immunometabolism support the hypothesis that glucose consumption is also used to modulate anti-tumor immune responses, favoring growth and expansion of specific cellular subsets defined in the past as suppressor T cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto Warburg and colleagues observed that tumors consumed high amounts of glucose compared to normal tissues, even in the presence of oxygen and completely functioning mitochondria. However, the role of the Warburg Effect is still not completely understood, particularly in the context of an ongoing anti-tumor immune response. Current experimental evidence suggests that tumor-derived metabolic restrictions can drive T cell hyporesponsiveness and immune tolerance. For example, several glycolytic enzymes, deregulated in cancer, contribute to tumor progression independently from their canonical metabolic activity. Indeed, they can control apoptosis, gene expression and activation of specific intracellular pathways, thus suggesting a direct link between metabolic switches and pro-tumorigenic transcriptional programs. Focus of this review is to define the specific metabolic pathways controlling Treg cell immunobiology in the context of anti-tumor immunity and tumor progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. The roots of modern oncology: from discovery of new antitumor anthracyclines to their clinical use.

    Science.gov (United States)

    Cassinelli, Giuseppe

    2016-06-02

    In May 1960, the Farmitalia CEO Dr. Bertini and the director of the Istituto Nazionale dei Tumori of Milan Prof. Bucalossi (talent scout and city's Mayor) signed a research agreement for the discovery and development up to clinical trials of new natural antitumor agents. This agreement can be considered as a pioneering and fruitful example of a translational discovery program with relevant transatlantic connections. Owing to an eclectic Streptomyces, found near Castel del Monte (Apulia), and to the skilled and motivated participants of both institutions, a new natural antitumor drug, daunomycin, was ready for clinical trials within 3 years. Patent interference by the Farmitalia French partner was overcome by the good quality of the Italian drug and by the cooperation between Prof. Di Marco, director of the Istituto Ricerche Farmitalia Research Laboratories for Microbiology and Chemotherapy, and Prof. Karnofsky, head of the Sloan-Kettering Cancer Institute of New York, leading to the first transatlantic clinical trials. The search for daunomycin's sister anthracyclines led to the discovery and development of adriamycin, one of the best drugs born in Milan. This was the second act prologue of the history of Italian antitumor discovery and clinical oncology, which started in July 1969 when Prof. Di Marco sent Prof. Bonadonna the first vials of adriamycin (doxorubicin) to be tested in clinical trials. This article reviews the Milan scene in the 1960s, a city admired and noted for the outstanding scientific achievements of its private and public institutions in drugs and industrial product discovery.

  18. Increasing antitumor effects of chemoradiotherapy by drug efflux inhibition with encapsulated anti-RLIP-76

    International Nuclear Information System (INIS)

    Harada, Satoshi; Ehara, Shigeru; Ishii, Keizo

    2011-01-01

    Microencapsulated anti-RLIP76 was tested in vivo using C3He/J mice to determine the increasing of antitumor effects by chemotherapeutic agent efflux inhibition during chemoradiotherapy. Microcapsules were produced by spraying a mixture of 3.0% hyaluronic acid, 2.0% alginate, 3.0% H 2 O 2 , and 0.3 mmol carboplatin onto a mixture of 0.3 mol FeCl 2 and 0.15 mol CaCl 2 . Microcapsules were subcutaneously injected into MM46 tumors previously inoculated into the left hind legs of C3He/J mice. Subsequent radiotherapy consisted of tumor irradiation with 10 Gy or 20 Gy 60 Co. The antitumor effects of microcapsules were tested by measuring tumor size and monitoring tumor growth. Three types of adverse effects were considered: fuzzy hair, loss of body weight, and mortality. Carboplatin levels were monitored using particle-induced X-ray emission (PIXE) and a micro-PIXE camera. Anti-RLIP76 inhibited the efflux of carboplatin from tumor tissue, which led to an increase in the concentration of carboplatin. Higher carboplatin concentration significantly increased the combined antitumor effect of radiation and chemotherapy. A significant decrease in adverse effects was also observed with microencapsulated anti-RLIP76. (author)

  19. Nanovectorized radiotherapy: a new strategy to induce anti-tumor immunity

    International Nuclear Information System (INIS)

    Vanpouille-Box, Claire; Hindré, François

    2012-01-01

    Recent experimental findings show that activation of the host immune system is required for the success of chemo- and radiotherapy. However, clinically apparent tumors have already developed multiple mechanisms to escape anti-tumor immunity. The fact that tumors are able to induce a state of tolerance and immunosuppression is a major obstacle in immunotherapy. Hence, there is an overwhelming need to develop new strategies that overcome this state of immune tolerance and induce an anti-tumor immune response both at primary and metastatic sites. Nanovectorized radiotherapy that combines ionizing radiation and nanodevices, is one strategy that could boost the quality and magnitude of an immune response in a predictable and designable fashion. The potential benefits of this emerging treatment may be based on the unique combination of immunostimulatory properties of nanoparticles with the ability of ionizing radiation to induce immunogenic tumor cell death. In this review, we will discuss available data and propose that the nanovectorized radiotherapy could be a powerful new strategy to induce anti-tumor immunity required for positive patient outcome.

  20. In vitro testing of curcumin based composites coatings as antitumoral systems against osteosarcoma cells

    Science.gov (United States)

    Tirca, I.; Mitran, V.; Marascu, V.; Brajnicov, S.; Ion, V.; Stokker-Cheregi, F.; Popovici, I. A.; Cimpean, A.; Dinca, V.; Dinescu, M.

    2017-12-01

    In this work, we propose a new design for biodegradable composite coatings obtained by laser methods, which are aimed at evaluating the effects of active antitumoral elements on osteosarcoma cells. Our approach relies on embedding curcumin, which is a natural polyphenol having antitumoral properties, within biodegradable copolymer coatings (i.e. polyvinyl alcohol-polyethylene glycol - PVA-PEG) by using matrix assisted pulsed laser evaporation (MAPLE). The structural and morphological characteristics of the coatings were tailored by using different solvents (water, ethanol, benzene, dimethylsufoxide) as deposition matrix. The morphological characteristics of the resulting films were investigated by atomic force microscopy (AFM), whereas their chemical composition was characterized by Fourier transform infrared spectroscopy (FTIR). These characteristics were correlated with the degradation behavior by using ellipsometry (SE) and AFM measurements data. The in vitro study of the MG-63 osteosarcoma cell behavior indicates that the developed hybrid coatings significantly decreased osteosarcoma cell viability and proliferation potential. The physico-chemical characteristics of the thin films, along with the preliminary in vitro analyses, suggest that our developed polymeric hybrid coatings represent an efficient way to tackle the design of antitumoral surfaces, with applications in biomedicine.

  1. Purification and characterization of an antitumor polysaccharide from Portulaca oleracea L.

    Science.gov (United States)

    Shen, Huan; Tang, Guo; Zeng, Guang; Yang, Yongjin; Cai, Xingwei; Li, Dongli; Liu, Hongchen; Zhou, Ningxin

    2013-04-02

    In the present study, we purified a unique polysaccharide component (POP) from Portulaca oleracea and found that it had pronounced anti-tumor effects in vivo model. Tumor weight, immune organ index and T lymphocyte subsets were employed to detect the immunoregulatory and antitumor effects of POP after administration. Hematological and biochemical analyses were also investigated in order to evaluate the toxicological aspects related to POP treatment. POP could significantly inhibit the growth of transplantable sarcoma 180 and potentiate the animal's immune responses including an increase in the number of white blood cell (WBC) and CD4(+) T-lymphocytes, as well as the ratio of CD4(+)/CD8(+). Furthermore the serum aspartate transanimase (AST), alanine transaminase (ALT), urea nitrogen (BUN), and creatinine levels in S180-bearing mice were significantly reversed by POP. Considering all these results, it is suggested that the anti-tumor effect elicited by POP could be associated with its immunostimulating properties. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Anti-tumor effect of a recombinant plasmid expressing human interleukin-12: an initial research

    International Nuclear Information System (INIS)

    Zheng Chuansheng; Xia Xiangwen; Feng Gansheng; Li Xin; Liang Huimin; Liang Bin

    2010-01-01

    Objective: To study the anti-tumor effect of a recombinant plasmid expressing human interleukin-12 (pEGFP-CI I L- 12) in vivo and in vitro. Methods: We transduct the recombinant gene (pEGFP-CI I L-12) to liver cancer cell HepG 2 in vitro, and detect reproductive activity of the cell using MTT and the activity of expressing vascular endothelial growth factor(VEGF) using semiquantitative PCR. And then, we deliver the gene to rabbit liver tumor tissue intraarterial and combine with chemoembolization to observe the anti- tumor effect to VX 2 tumor in vivo. Results: There are no statistical difference compared With control group in activity of reproductive and expressing VEGF in vitro. In vivo, tumor growth rate significantly reduce in gene therapy combined with chemoembolization group. Conclusion: Recombinant gene (pEGFP-Cl I L-12) exhibit significant anti-tumor effect in vivo but not in vitro, perhaps the anti-tumor effect is associated with an indirect pathway instead of a direct pathway. (authors)

  3. Transcutaneous carbon dioxide enhances the antitumor effect of radiotherapy on oral squamous cell carcinoma.

    Science.gov (United States)

    Iwata, Eiji; Hasegawa, Takumi; Ueha, Takeshi; Takeda, Daisuke; Saito, Izumi; Kawamoto, Teruya; Akisue, Toshihiro; Sakai, Yoshitada; Sasaki, Ryohei; Kuroda, Ryosuke; Komori, Takahide

    2018-05-16

    Radiotherapy (RT) is one of the main treatment modalities for oral squamous cell carcinoma (OSCC), however, radioresistance is a major impediment to its clinical success and poses as a concern that needs to be addressed. Tumor hypoxia is known to be significantly associated with radioresistance in various malignancies, hence, resolving the hypoxic state of a tumor may improve the antitumor effect of RT on OSCC. We have previously revealed that transcutaneous CO2 induced mitochondrial apoptosis and suppressed tumor growth in OSCC by resolving hypoxia. Considering the previous study, we hypothesized that transcutaneous CO2 may enhance the antitumor effect of RT on OSCC by improving intratumoral hypoxia, thereby overcoming radioresistance. In the present study, the combination of transcutaneous CO2 and RT significantly inhibited tumor growth compared with other treatments. This combination therapy also led to decreased expression of HIF-1α in parallel with increased expression of the cleaved forms of caspase-3-8-9 and PARP, which play essential roles in mitochondrial apoptosis. Additionally, the combination therapy increased the expression of ROS modulator 1 and subsequent mitochondrial ROS production, compared to RT alone. These results indicated that transcutaneous CO2 could potentially improve the antitumor effect of RT by decreasing the intratumoral hypoxia and increasing the mitochondrial apoptosis. Our findings indicated that CO2 therapy may be a novel adjuvant therapy in combination with RT for OSCC.

  4. Antitumor effects evaluation of a novel porphyrin derivative in photodynamic therapy.

    Science.gov (United States)

    Li, Jian-Wei; Wu, Zhong-Ming; Magetic, Davor; Zhang, Li-Jun; Chen, Zhi-Long

    2015-12-01

    In this paper, the antitumor activity of a novel porphyrin-based photosensitizer 5,10,15,20-tetrakis[(5-diethylamino)pentyl] porphyrin (TDPP) was reported in vitro and in vivo. The photophysical and cellular properties of TDPP were investigated. The singlet oxygen generation quantum yield of TDPP was detected; it showed a high singlet oxygen quantum yield of 0.52. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The efficiency of TDPP-photodynamic therapy (PDT) in vitro was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and in situ trypan blue exclusion test. Treated with a 630-nm laser, TDPP can kill cultured human esophageal cancer cell line (Eca-109) cells and reduce the growth of Eca-109 xenograft tumors significantly in BABL/c nude mice. And histopathological study was also used to confirm the antitumor effect. It has the perspective to be developed as a new antitumor drug in photodynamic therapy and deserves further investigation.

  5. Antitumor Active Protein-containing Glycans from the Body of Ganoderma tsugae

    Institute of Scientific and Technical Information of China (English)

    LIU Ying; LI Yue-fei; ZHENG Ke-yan; FEI Xiao-fang

    2012-01-01

    To explore the effects of traditional herbal medicine Ganoderma tsugae(G.tsugae) on immunomodulatory and antitumor activities,the crude polysaccharides ofG.tsugae were purified by filtration,diethylaminoethyl(DEAE)sepharose-fast flow chromatography and sephadex G-100 size-exclusion chromatography.Two main fractions,protein-containing glycans CSSLP-I and CSSLP-2,were obtained via the gradient elution.The protein content,molecular weight,and monosaccharide composition of the two fractions were analyzed.Furthermore,the influence of the protein-containing glycans from G.tsugae on the activation of human acute monocytic leukemia cell line(THP-1 ) and their antitumor activities to the human hepatocellular liver carcinoma cell(HepG-2) in vitro were evaluated.The results indicate that CSSLP-I and CSSLP-2 could increase the pinocytic activity of THP-1 cells and induce THP-1 cells to produce the cytokines of TNFa and IL-2,significantly.CSSLP-1 and CSSLP-2 also played an inhibiting effect on the cancer cell(NepG-2).Moreover,the anti-proliferation activity of CSSLP-1 and CSSLP-2 increased with the participation of TNFa and 1L-2 or other antitumor factors induced from THP-1 cclls by G.tsugae protein-containing glycan fractions.

  6. Effect of immunomodifier on radiation-induced antitumor immunity following local irradiation to tumor, 2

    International Nuclear Information System (INIS)

    Mukae, Shiro; Norimura, Toshiyuki; Tsuchiya, Takehiko

    1988-01-01

    This study was carried out to clarify whether or not the antitumor cell-mediated immunity of host is more effectively induced by the combined use of mouse interferon-α/β (MuIFN-α/β) with local irradiation than by simple local irradiation to tumor. C3H/He female mice, MM46 tumor cells and mouse interferon-α/β (MuIFN-α/β) were used in the experiment. Antitumor activity in mice was evaluated by the inhibition of tumor growth and mean survival days after treatment. Spleen cell killing activity to MM46 tumor cells was measured to evaluate the antitumor activity in vitro. In the case of single use of MuIFN-α/β, tumor growth was more rapid than in the non-treated group (control) in vivo. The mean survival days were also reduced. There was no siginificant difference in tumor growth inhibition between combined therapy using X-irradiation and MuIFN-α/β, and single therapy by local irradiation. However, in the case of administration of MuIFN-α/β after irradiation, the mean survival days was significantly increased compared with the group receiving X-ray irradiation only. (author)

  7. Effects of Different Temperatures on the Chemical Structure and Antitumor Activities of Polysaccharides from Cordyceps militaris

    Directory of Open Access Journals (Sweden)

    Eliyas Nurmamat

    2018-04-01

    Full Text Available The effects of different extraction temperatures (4 and 80 °C on the physicochemical properties and antitumor activity of water soluble polysaccharides (CMPs-4 and CMPs-80 from Cordyceps militaris (C. militaris were evaluated in this study. The results of gas chromatography (GC and high-performance gel permeation chromatography (HPGPC showed that a higher extraction temperature could degrade the polysaccharides with 188 kDa, mainly composed of glucose, and increase the dissolution rate of polysaccharides about 308 kDa, mainly consisting of rhamnose and galactose. In addition, the CMPs displayed the same sugar ring and category of glycosidic linkage based on Fourier-transform infrared spectroscopy (FTIR analysis, however, their invisible structural difference occurred in the specific rotation and conformational characteristics according to the results of specific optical rotation measurement and Congo red test. In vitro antitumor experiments indicated that CMPs-4 possessed stronger inhibitory effects on human esophagus cancer Eca-109 cells by inducing cell apoptosis more than CMPs-80 did. These findings demonstrated that the polysaccharides extracted with cold water (4 °C could be applied as a novel alternative chemotherapeutic agent or dietary supplement with its underlying antitumor property.

  8. GE11 Peptide as an Active Targeting Agent in Antitumor Therapy: A Minireview

    Directory of Open Access Journals (Sweden)

    Ida Genta

    2017-12-01

    Full Text Available A lot of solid tumors are characterized by uncontrolled signal transduction triggered by receptors related to cellular growth. The targeting of these cell receptors with antitumor drugs is essential to improve chemotherapy efficacy. This can be achieved by conjugation of an active targeting agent to the polymer portion of a colloidal drug delivery system loaded with an antitumor drug. The goal of this minireview is to report and discuss some recent results in epidermal growth factor receptor targeting by the GE11 peptide combined with colloidal drug delivery systems as smart carriers for antitumor drugs. The minireview chapters will focus on explaining and discussing: (i Epidermal growth factor receptor (EGFR structures and functions; (ii GE11 structure and biologic activity; (iii examples of GE11 conjugation and GE11-conjugated drug delivery systems. The rationale is to contribute in gathering information on the topic of active targeting to tumors. A case study is introduced, involving research on tumor cell targeting by the GE11 peptide combined with polymer nanoparticles.

  9. Vaccination with OK-432 followed by TC-1 tumor lysate leads to significant antitumor effects.

    Science.gov (United States)

    Chen, I-Ju; Yen, Chih-Feng; Lin, Kun-Ju; Lee, Chyi-Long; Soong, Yung-Kuei; Lai, Chyong-Huey; Lin, Cheng-Tao

    2011-07-01

    Human papillomavirus (HPV) infects large numbers of women worldwide and is present in more than 99% of all cervical cancer. TC-1 cell is a cell line with high expression of E7 antigen of HPV type 16 and its cell lysate has been demonstrated as an ideal inducer of E7-specific, antitumor immunity. OK-432 (Picibanil), a penicillin-killed Streptococcus pyogenes, has been reported with potent immunomodulation properties in cancer treatment by stimulating the maturation of dendritic cells (DCs) and secretion of Th-1 type cytokines. The current study demonstrated that a protocol to immunize the C57BL/6 mice with OK-432 followed by treatment with TC-1 lysate can generate markedly increased immune responses of E7-specific CD4(+) T cells and a moderate increase of natural killer (NK) cell, as well as a satisfactorily protective and therapeutic antitumor effect by triggering the DCs to prime T cells. Depletion of lymphocyte subset in vivo suggested that the antitumor effects could be dominantly executed by CD8+ T cells and followed by NK cells, and both of these reactions were induced by the generation of robust E7-specific CD4(+) T helper cell response. These findings warrant OK-432 combination with tumor-lysate as an effective and safe vaccine in future clinical application of cervical cancer.

  10. Antitumor Action of a Novel Histone Deacetylase Inhibitor, YF479, in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2014-08-01

    Full Text Available Accumulating evidence demonstrates important roles for histone deacetylase in tumorigenesis (HDACs, highlighting them as attractive targets for antitumor drug development. Histone deactylase inhibitors (HDACIs, which have shown favorable anti-tumor activity with low toxicity in clinical investigations, are a promising class of anticancer therapeutics. Here, we screened our compound library to explore small molecules that possess anti-HDAC activity and identified a novel HDACI, YF479. Suberoylanilide hydroxamic acid (SAHA, which was the first approved HDAC inhibitor for clinical treatment by the FDA, was as positive control in our experiments. We further demonstrated YF479 abated cell viability, suppressed colony formation and tumor cell motility in vitro. To investigate YF479 with superior pharmacodynamic properties, we developed spontaneous and experimental breast cancer animal models. Our results showed YF479 significantly inhibited breast tumor growth and metastasis in vivo. Further study indicated YF479 suppressed both early and end stages of metastatic progression. Subsequent adjuvant chemotherapy animal experiment revealed the elimination of local-regional recurrence (LRR and distant metastasis by YF479. More important, YF479 remarkably prolonged the survival of tumor-bearing mice. Intriguingly, YF479 displayed more potent anti-tumor activity in vitro and in vivo compared with SAHA. Together, our results suggest that YF479, a novel HDACI, inhibits breast tumor growth, metastasis and recurrence. In light of these results, YF479 may be an effective therapeutic option in clinical trials for patients burdened by breast cancer.

  11. Experimental study on anti-tumor effect of pcEgr-IFNγ gene-radiotherapy

    International Nuclear Information System (INIS)

    Wu Congmei; Li Xiuyi; Liu Shuzheng

    2001-01-01

    Objective: To study the anti-tumor effect of IFN γ gene-radiotherapy to murine melanoma and its immunologic mechanism. Methods: pcEgr-IFNγ plasmids were injected locally into tumor, and 36 hours later, the tumors were given 20 Gy X-ray irradiation. Tumor growth at different time, IFN γ expression 3 days later and immunologic indexes 15 days later were detected. Results: At 3-15 days after pcEgr-IFNγ gene-radiotherapy, the tumor growth rate was lower than that of irradiation alone group. It was also lower than that of gene therapy alone group and control plasmid combined with X-ray irradiation group significantly. Day 3 tumor IFN γ expression was higher than that of plasmid treatment alone group. NK activity, IL-2 and IFN γ secretion activities were higher than those of gene therapy alone and irradiation alone groups significantly. Conclusion: The antitumor effect of IFN γ gene-radiotherapy is better than that of either of them applied solely. Its mechanism might be concerned with the higher expression of IFN γ induced by irradiation in tumors and activation of anti-tumor immunologic functions

  12. Novel Therapeutic Strategies for Solid Tumor Based on Body's Intrinsic Antitumor Immune System.

    Science.gov (United States)

    Duan, Haifeng

    2018-05-22

    The accumulation of mutated somatic cells due to the incompetency of body's immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor-targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumor-targeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloid-derived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body's internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly. © 2018 The Author(s). Published by S. Karger AG, Basel.

  13. Antitumor Properties of the Essential Oil From the Leaves of Duguetia gardneriana.

    Science.gov (United States)

    Rodrigues, Ana Carolina B C; Bomfim, Larissa M; Neves, Sara P; Menezes, Leociley R A; Dias, Rosane B; Soares, Milena B P; Prata, Ana Paula N; Rocha, Clarissa A Gurgel; Costa, Emmanoel V; Bezerra, Daniel P

    2015-07-01

    Duguetia gardneriana, popularly known in the Brazilian northeast as "jaquinha", is a species belonging to the family Annonaceae. The aim of this work was to assess the chemical composition and antitumor properties of the essential oil from the leaves of D. gardneriana in experimental models. The chemical composition of the essential oil was analyzed via gas chromatography-flame ionization detector and gas chromatography-mass spectrometry. In vitro cytotoxic activity was determined in cultured tumor cells, and in vivo antitumor activity was assessed in B16-F10-bearing mice. The identified compounds were β-bisabolene (80.99%), elemicin (8.04%), germacrene D (4.15%), and cyperene (2.82%). The essential oil exhibited a cytotoxic effect, with IC50 values of 16.89, 19.16, 13.08, and 19.33 µg/mL being obtained for B16-F10, HepG2, HL-60, and K562 cell lines, respectively. On the other hand, β-bisabolene was inactive in all of the tested tumor cell lines (showing IC50 values greater than 25 µg/mL). The in vivo analysis revealed tumor growth inhibition rates of 5.37-37.52% at doses of 40 and 80 mg/kg/day, respectively. Herein, the essential oil from the leaves of D. gardneriana presented β-bisabolene as the major constituent and showed cytotoxic and antitumor potential. Georg Thieme Verlag KG Stuttgart · New York.

  14. Augmentation of Antitumor Immunity by Human and Mouse CAR T Cells Secreting IL-18

    Directory of Open Access Journals (Sweden)

    Biliang Hu

    2017-09-01

    Full Text Available The effects of transgenically encoded human and mouse IL-18 on T cell proliferation and its application in boosting chimeric antigen receptor (CAR T cells are presented. Robust enhancement of proliferation of IL-18-secreting human T cells occurred in a xenograft model, and this was dependent on TCR and IL-18R signaling. IL-18 augmented IFN-γ secretion and proliferation of T cells activated by the endogenous TCR. TCR-deficient, human IL-18-expressing CD19 CAR T cells exhibited enhanced proliferation and antitumor activity in the xenograft model. Antigen-propelled activation of cytokine helper ensemble (APACHE CAR T cells displayed inducible expression of IL-18 and enhanced antitumor immunity. In an intact mouse tumor model, CD19-IL-18 CAR T cells induced deeper B cell aplasia, significantly enhanced CAR T cell proliferation, and effectively augmented antitumor effects in mice with B16F10 melanoma. These findings point to a strategy to develop universal CAR T cells for patients with solid tumors.

  15. Predicting Antitumor Activity of Peptides by Consensus of Regression Models Trained on a Small Data Sample

    Directory of Open Access Journals (Sweden)

    Ivanka Jerić

    2011-11-01

    Full Text Available Predicting antitumor activity of compounds using regression models trained on a small number of compounds with measured biological activity is an ill-posed inverse problem. Yet, it occurs very often within the academic community. To counteract, up to some extent, overfitting problems caused by a small training data, we propose to use consensus of six regression models for prediction of biological activity of virtual library of compounds. The QSAR descriptors of 22 compounds related to the opioid growth factor (OGF, Tyr-Gly-Gly-Phe-Met with known antitumor activity were used to train regression models: the feed-forward artificial neural network, the k-nearest neighbor, sparseness constrained linear regression, the linear and nonlinear (with polynomial and Gaussian kernel support vector machine. Regression models were applied on a virtual library of 429 compounds that resulted in six lists with candidate compounds ranked by predicted antitumor activity. The highly ranked candidate compounds were synthesized, characterized and tested for an antiproliferative activity. Some of prepared peptides showed more pronounced activity compared with the native OGF; however, they were less active than highly ranked compounds selected previously by the radial basis function support vector machine (RBF SVM regression model. The ill-posedness of the related inverse problem causes unstable behavior of trained regression models on test data. These results point to high complexity of prediction based on the regression models trained on a small data sample.

  16. Activation of antitumor immune responses by Ganoderma formosanum polysaccharides in tumor-bearing mice.

    Science.gov (United States)

    Wang, Cheng-Li; Lu, Chiu-Ying; Hsueh, Ying-Chao; Liu, Wen-Hsiung; Chen, Chun-Jen

    2014-11-01

    Fungi of the genus Ganoderma are basidiomycetes that have been used as traditional medicine in Asia and have been shown to exhibit various pharmacological activities. We recently found that PS-F2, a polysaccharide fraction purified from the submerged culture broth of Ganoderma formosanum, stimulates the maturation of dendritic cells and primes a T helper 1 (Th1)-polarized adaptive immune response in vivo. In this study, we investigated whether the immune adjuvant function of PS-F2 can stimulate antitumor immune responses in tumor-bearing mice. Continuous intraperitoneal or oral administration of PS-F2 effectively suppressed the growth of colon 26 (C26) adenocarcinoma, B16 melanoma, and sarcoma 180 (S180) tumor cells in mice without adverse effects on the animals' health. PS-F2 did not cause direct cytotoxicity on tumor cells, and it lost the antitumor effect in mice with severe combined immunodeficiency (SCID). CD4(+) T cells, CD8(+) T cells, and serum from PS-F2-treated tumor-bearing mice all exhibited antitumor activities when adoptively transferred to naïve animals, indicating that PS-F2 treatment stimulates tumor-specific cellular and humoral immune responses. These data demonstrate that continuous administration of G. formosanum polysaccharide PS-F2 can activate host immune responses against ongoing tumor growth, suggesting that PS-F2 can potentially be developed into a preventive/therapeutic agent for cancer immunotherapy.

  17. Antitumor Effects of Saffron-Derived Carotenoids in Prostate Cancer Cell Models

    Directory of Open Access Journals (Sweden)

    Claudio Festuccia

    2014-01-01

    Full Text Available Crocus sativus L. extracts (saffron are rich in carotenoids. Preclinical studies have shown that dietary intake of carotenoids has antitumor effects suggesting their potential preventive and/or therapeutic roles. We have recently reported that saffron (SE and crocin (CR exhibit anticancer activity by promoting cell cycle arrest in prostate cancer (PCa cells. It has also been demonstrated that crocetin esters are produced after SE gastrointestinal digestion by CR hydrolysis. The aim of the present report was to investigate if SE, crocetin (CCT, and CR affected in vivo tumor growth of two aggressive PCa cell lines (PC3 and 22rv1 which were xenografted in male nude mice treated by oral gavage with SE, CR, and CCT. We demonstrated that the antitumor effects of CCT were higher when compared to CR and SE and treatments reverted the epithelial-mesenchymal transdifferentiation (EMT as attested by the significant reduction of N-cadherin and beta-catenin expression and the increased expression of E-cadherin. Additionally, SE, CR, and CCT inhibited PCa cell invasion and migration through the downmodulation of metalloproteinase and urokinase expression/activity suggesting that these agents may affect metastatic processes. Our findings suggest that CR and CCT may be dietary phytochemicals with potential antitumor effects in biologically aggressive PCa cells.

  18. Nanovectorized radiotherapy, a new strategy to induce anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Claire eVanpouille-Box

    2012-10-01

    Full Text Available Recent experimental findings show that activation of the host immune system is required for the success of chemo- and radio-therapy. However, clinically-apparent tumors have already developed multiple mechanisms to escape anti-tumor immunity. The fact that tumors are able to induce a state of tolerance and immunosuppression is a major obstacle in immunotherapy. Hence, there is an overwhelming need to develop new strategies that overcome this state of immune tolerance and induce an anti-tumor immune response both at primary and metastatic sites. Nanovectorized radiotherapy that combines ionizing radiation and nano-devices, is one strategy that could boost the quality and magnitude of an immune response in a predictable and designable fashion. The potential benefits of this emerging treatment may be based on the unique combination of immuno-stimulatory properties of nanoparticles with the ability of ionizing radiation to induce immunogenic tumor cell death. In this review, we will discuss available data and propose that the nanovectorized radiotherapy could be a powerful new strategy to induce anti-tumor immunity required for positive patient outcome.

  19. Characterization and anti-tumor effects of chondroitin sulfate-chitosan nanoparticles delivery system

    Science.gov (United States)

    Hu, Chieh-Shen; Tang, Sung-Ling; Chiang, Chiao-Hsi; Hosseinkhani, Hossein; Hong, Po-Da; Yeh, Ming-Kung

    2014-11-01

    We prepared chondroitin sulfate (ChS)-chitosan (CS) nanoparticles (NPs) as a delivery carrier, and doxorubicin (Dox) was used as a model drug. The physicochemical properties and biological activities of the Dox-ChS-CS NPs including the release profile, cell cytotoxicity, cellular internalization, and in vivo anti-tumor effects were evaluated. The ChS-CS NPs and Dox-ChS-CS NPs had a mean size of 262.0 ± 15.0 and 369.4 ± 77.4 nm, and a zeta potential of 30.2 ± 0.9 and 20.6 ± 3.1 mV, respectively. In vitro release tests showed that the 50 % release time for the Dox-ChS-CS NPs was 20 h. Two hepatoma cell models, HepG2 and HuH6, were used for evaluating the cytotoxicity and cell uptake efficiency of the Dox-ChS-CS NPs. A significant difference was observed between doxorubicin solution and the Dox-ChS-CS NPs in the cellular uptake within 60 min ( p < 0.01). For the in vivo human xenograft-nude mouse model, the Dox-ChS-CS NPs were more effective with less body weight loss and anti-tumor growth suppression in comparison with the Dox solution. The prepared Dox-ChS-CS NPs offer a new effective targeting nanoparticle delivery system platform for anti-tumor therapy.

  20. In vitro and in vivo antitumor activity of crude extracts obtained from Brazilian Chromobacterium sp isolates

    Directory of Open Access Journals (Sweden)

    C.B.A. Menezes

    2013-01-01

    Full Text Available Natural products produced by microorganisms have been an important source of new substances and lead compounds for the pharmaceutical industry. Chromobacterium violaceum is a Gram-negative β-proteobacterium, abundant in water and soil in tropical and subtropical regions and it produces violacein, a pigment that has shown great pharmaceutical potential. Crude extracts of five Brazilian isolates of Chromobacterium sp (0.25, 2.5, 25, and 250 µg/mL were evaluated in an in vitro antitumor activity assay with nine human tumor cells. Secondary metabolic profiles were analyzed by liquid chromatography and electrospray ionization mass spectrometry resulting in the identification of violacein in all extracts, whereas FK228 was detected only in EtCE 308 and EtCE 592 extracts. AcCE and EtCE 310 extracts showed selectivity for NCI/ADR-RES cells in the in vitro assay and were evaluated in vivo in the solid Ehrlich tumor model, resulting in 50.3 and 54.6% growth inhibition, respectively. The crude extracts of Chromobacterium sp isolates showed potential and selective antitumor activities for certain human tumor cells, making them a potential source of lead compounds. Furthermore, the results suggest that other compounds, in addition to violacein, deoxyviolacein and FK228, may be involved in the antitumor effect observed.

  1. In vitro and in vivo antitumor activity of crude extracts obtained from Brazilian Chromobacterium sp isolates

    International Nuclear Information System (INIS)

    Menezes, C.B.A.; Silva, B.P.; Sousa, I.M.O.; Ruiz, A.L.T.G.; Spindola, H.M.; Cabral, E.; Eberlin, M.N.; Tinti, S.V.; Carvalho, J.E.; Foglio, M.A.; Fantinatti-Garboggini, F.

    2012-01-01

    Natural products produced by microorganisms have been an important source of new substances and lead compounds for the pharmaceutical industry. Chromobacterium violaceum is a Gram-negative β-proteobacterium, abundant in water and soil in tropical and subtropical regions and it produces violacein, a pigment that has shown great pharmaceutical potential. Crude extracts of five Brazilian isolates of Chromobacterium sp (0.25, 2.5, 25, and 250 µg/mL) were evaluated in an in vitro antitumor activity assay with nine human tumor cells. Secondary metabolic profiles were analyzed by liquid chromatography and electrospray ionization mass spectrometry resulting in the identification of violacein in all extracts, whereas FK228 was detected only in EtCE 308 and EtCE 592 extracts. AcCE and EtCE 310 extracts showed selectivity for NCI/ADR-RES cells in the in vitro assay and were evaluated in vivo in the solid Ehrlich tumor model, resulting in 50.3 and 54.6% growth inhibition, respectively. The crude extracts of Chromobacterium sp isolates showed potential and selective antitumor activities for certain human tumor cells, making them a potential source of lead compounds. Furthermore, the results suggest that other compounds, in addition to violacein, deoxyviolacein and FK228, may be involved in the antitumor effect observed

  2. Planejamento das Atividades de Auditoria Interna na UFSC

    OpenAIRE

    Platt Neto, Orion Augusto; Vieira, Audí Luiz

    2006-01-01

    Este artigo aborda o planejamento das unidades de auditoria interna que integram o sistema de controle interno do Poder Executivo Federal junto às instituições Federais de Ensino Superior (IFES). O objetivo deste artigo é apresentar noções e instrumentos do planejamento das atividades nas unidades de auditoria interna vinculadas às IFES. Neste sentido, apresenta-se o embasamento normativo, as competências e as atividades das unidades de auditoria interna. Para auxiliar a consec...

  3. Aspectos das fortalezas e fragilidades no uso das metodologias ativas de aprendizagem

    Directory of Open Access Journals (Sweden)

    Maria José Sanches Marin

    Full Text Available A implementação de novos modelos de ensino-aprendizagem vem ocorrendo na Faculdade de Medicina de Marília (Famema há mais de uma década. O presente estudo analisa as fortalezas e fragilidades dos métodos ativos de aprendizagem na ótica dos estudantes. Para a coleta de dados, realizaram-se entrevistas com estudantes dos cursos de Enfermagem e Medicina. Os dados foram interpretados por meio dos parâmetros da hermenêutica dialética. Os sentidos extraídos das falas dos estudantes indicam que as metodologias ativas estimulam o estudo constante, a independência e a responsabilidade, possibilitam a integração das dimensões biopsicossociais, preparam para o trabalho em equipe e aproximam os alunos dos usuários e da equipe. No entanto, nem todos estão preparados para isso; algumas vezes, sentem-se perdidos em busca de conhecimentos, além de apresentarem dificuldades quanto a sua inserção na equipe de saúde. A construção de novos modelos de aprendizagem requer constante empenho, visando ao seu aperfeiçoamento.

  4. Ambientes Colaborativos Virtuais: potencial das redes sociais. O caso das empresas do Algarve

    Directory of Open Access Journals (Sweden)

    Ana Belo

    2013-12-01

    Full Text Available O objetivo do presente artigo é analisar o potencial das redes sociais no desempenho das pequenas e médias empresas da região do Algarve, tendo sido efectuado um questionário para o efeito. O estudo empírico realizado revela que os dados recolhidos (de 70 empresas possuem boas qualidades psico-métricas. Procedeu-se a uma análise categórica de componentes principais, a qual identificou duas principais tipologias de objectivos nas redes sociais: redes sociais para interacção produto-cliente e pesquisa ou conhecimento; e redes sociais com potencial para o marketing. Uma análise suplementar - análise hierárquica de clusters (com recurso ao método de agrupamento de Ward - identificou três padrões de empresas consoante o seu grau de envolvimento em redes sociais: cluster Social Tec Grau 1; cluster Social Tec Grau 2 e cluster Social Tec Grau 3. Estas análises permitem validar uma metodologia sustentável para este tipo de avaliação.

  5. Successful pipeline installation for Parque das Conchas development; Subsea installation

    Energy Technology Data Exchange (ETDEWEB)

    Bartz, Cesar

    2010-07-01

    Subsea 7 has successfully delivered again in Brazilian deep-waters. The subsea engineering and construction company has recently completed pipeline installation activities for the Parque das Conchas (BC-10) development, offshore Brazil. (AG)

  6. 2015 - das Jahr der RDA - ein erster Statusbericht

    Directory of Open Access Journals (Sweden)

    Inge Neuböck

    2015-06-01

    geben. Manchmal bin ich selbst erstaunt, wieviel eine so kleine Gruppe bewegen kann – Motor dazu ist das wirklich intensive Interesse und die Freude an der Mitarbeit von etwas Neuem bei jedem einzelnen Mitglied der AGs...

  7. Lageroptimierung 2.0: Das Online-WMS

    OpenAIRE

    Wolf, Oliver; Geißen, Tim; Rahn, Jonas; Haselberger, Julia

    2012-01-01

    Das Fraunhofer-Institut für Materialfluss und Logistik IML unterstützt zahlreiche Unternehmen sowohl bei der Auswahl des richtigen Warehouse Management Systems als auch durch die Entwicklung einer Plattform, die das Anbieten, Mieten und Anwenden logistischer IT-Unterstützung in der Cloud möglich macht. Von »warehouse logistics« zur »Logistics Mall« - vom konventionell betriebenen Warehouse Management System zum WMS aus der Steckdose.

  8. Secretion of Rhoptry and Dense Granule Effector Proteins by Nonreplicating Toxoplasma gondii Uracil Auxotrophs Controls the Development of Antitumor Immunity.

    Directory of Open Access Journals (Sweden)

    Barbara A Fox

    2016-07-01

    Full Text Available Nonreplicating type I uracil auxotrophic mutants of Toxoplasma gondii possess a potent ability to activate therapeutic immunity to established solid tumors by reversing immune suppression in the tumor microenvironment. Here we engineered targeted deletions of parasite secreted effector proteins using a genetically tractable Δku80 vaccine strain to show that the secretion of specific rhoptry (ROP and dense granule (GRA proteins by uracil auxotrophic mutants of T. gondii in conjunction with host cell invasion activates antitumor immunity through host responses involving CD8α+ dendritic cells, the IL-12/interferon-gamma (IFN-γ TH1 axis, as well as CD4+ and CD8+ T cells. Deletion of parasitophorous vacuole membrane (PVM associated proteins ROP5, ROP17, ROP18, ROP35 or ROP38, intravacuolar network associated dense granule proteins GRA2 or GRA12, and GRA24 which traffics past the PVM to the host cell nucleus severely abrogated the antitumor response. In contrast, deletion of other secreted effector molecules such as GRA15, GRA16, or ROP16 that manipulate host cell signaling and transcriptional pathways, or deletion of PVM associated ROP21 or GRA3 molecules did not affect the antitumor activity. Association of ROP18 with the PVM was found to be essential for the development of the antitumor responses. Surprisingly, the ROP18 kinase activity required for resistance to IFN-γ activated host innate immunity related GTPases and virulence was not essential for the antitumor response. These data show that PVM functions of parasite secreted effector molecules, including ROP18, manipulate host cell responses through ROP18 kinase virulence independent mechanisms to activate potent antitumor responses. Our results demonstrate that PVM associated rhoptry effector proteins secreted prior to host cell invasion and dense granule effector proteins localized to the intravacuolar network and host nucleus that are secreted after host cell invasion coordinately

  9. A CONFIABILIDADE DO TAMANHO DAS CISTERNAS RURAIS

    Directory of Open Access Journals (Sweden)

    Eduardo Henrique Borges Cohim Silva

    2015-11-01

    Full Text Available O Programa de Formação e Mobilização Social para a Convivência com o Semiárido – P1MC construiu mais de 400 mil cisternas, com o volume definido em 16 mil litros com base na demanda de uma família média de cinco pessoas em um período de 280 dias. Porém dada a diversidade vários fatores como área de captação, precipitação e número de usuários, as demanda devem portanto serem diferentes. O objetivo deste trabalho é avaliar a confiabilidade do suprimento de água por meio de sistemas de captação de água de chuva, no âmbito do Programa P1MC. Foi utilizado o modelo comportamental que simula a operação do reservatório num período de tempo, simulando fluxos de massas com algoritmos que descrevem a operação de um reservatório, adotando-se um intervalo de um dia para o balanço. O universo amostral foi constituído por 947 cisternas cujas informações, tais como área de captação e número de moradores, foram obtidas na ASA – Articulação para o Semiárido. Para cada cenário analisado, definido pela precipitação, área de captação e demanda (número de moradores e demanda per capita foi calculada a confiabilidade. Verificou-se que para os 947 sistemas de aproveitamento implantados, o valor médio do número de moradores encontrado foi de 5, com 99% dos casos abaixo de 10. Constatou-se que 99,9% das áreas de captação têm superfície inferior a 120 m2, e uma média de 51,9 m2. O volume máximo armazenado na cisterna decresce, evidenciando uma ociosidade da capacidade de reservação de 16 mil litros, o que faz com que o uso de cisternas com essa capacidade deveria ser associado a uma área de telhado compatível com seu volume de armazenamento, sendo mais recomendável que uma ampliação na área de coleta que resultaria em um maior benefício para a família. Cerca de 25% dos casos o volume adequado da cisterna seria inferior a 6 mil litros. O uso de cisternas com volumes diferentes, mais ajustados às situa

  10. DAS: A Data Management System for Instrument Tests and Operations

    Science.gov (United States)

    Frailis, M.; Sartor, S.; Zacchei, A.; Lodi, M.; Cirami, R.; Pasian, F.; Trifoglio, M.; Bulgarelli, A.; Gianotti, F.; Franceschi, E.; Nicastro, L.; Conforti, V.; Zoli, A.; Smart, R.; Morbidelli, R.; Dadina, M.

    2014-05-01

    The Data Access System (DAS) is a and data management software system, providing a reusable solution for the storage of data acquired both from telescopes and auxiliary data sources during the instrument development phases and operations. It is part of the Customizable Instrument WorkStation system (CIWS-FW), a framework for the storage, processing and quick-look at the data acquired from scientific instruments. The DAS provides a data access layer mainly targeted to software applications: quick-look displays, pre-processing pipelines and scientific workflows. It is logically organized in three main components: an intuitive and compact Data Definition Language (DAS DDL) in XML format, aimed for user-defined data types; an Application Programming Interface (DAS API), automatically adding classes and methods supporting the DDL data types, and providing an object-oriented query language; a data management component, which maps the metadata of the DDL data types in a relational Data Base Management System (DBMS), and stores the data in a shared (network) file system. With the DAS DDL, developers define the data model for a particular project, specifying for each data type the metadata attributes, the data format and layout (if applicable), and named references to related or aggregated data types. Together with the DDL user-defined data types, the DAS API acts as the only interface to store, query and retrieve the metadata and data in the DAS system, providing both an abstract interface and a data model specific one in C, C++ and Python. The mapping of metadata in the back-end database is automatic and supports several relational DBMSs, including MySQL, Oracle and PostgreSQL.

  11. Identification of anti-CD98 antibody mimotopes for inducing antibodies with antitumor activity by mimotope immunization.

    Science.gov (United States)

    Saito, Misa; Kondo, Masahiro; Ohshima, Motohiro; Deguchi, Kazuki; Hayashi, Hideki; Inoue, Kazuyuki; Tsuji, Daiki; Masuko, Takashi; Itoh, Kunihiko

    2014-04-01

    A mimotope is an antibody-epitope-mimicking peptide retrieved from a phage display random peptide library. Immunization with antitumor antibody-derived mimotopes is promising for inducing antitumor immunity in hosts. In this study, we isolated linear and constrained mimotopes from HBJ127, a tumor-suppressing anti-CD98 heavy chain mAb, and determined their abilities for induction of antitumor activity equal to that of the parent antibody. We detected elevated levels of antipeptide responses, but failed to detect reactivity against native CD98-expressing HeLa cells in sera of immunized mice. Phage display panning and selection of mimotope-immunized mouse spleen-derived antibody Fab library showed that HeLa cell-reactive Fabs were successfully retrieved from the library. This finding indicates that native antigen-reactive Fab clones represented an undetectable minor population in mimotope-induced antibody repertoire. Functional and structural analysis of retrieved Fab clones revealed that they were almost identical to the parent antibody. From these results, we confirmed that mimotope immunization was promising for retrieving antitumor antibodies equivalent to the parent antibody, although the co-administration of adjuvant compounds such as T-cell epitope peptides and Toll-like receptor 4 agonist peptides is likely to be necessary for inducing stronger antitumor immunity than mimotope injection alone. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  12. How Does Ionizing Irradiation Contribute to the Induction of Anti-Tumor Immunity?

    International Nuclear Information System (INIS)

    Rubner, Yvonne; Wunderlich, Roland; Rühle, Paul-Friedrich; Kulzer, Lorenz; Werthmöller, Nina; Frey, Benjamin; Weiss, Eva-Maria; Keilholz, Ludwig; Fietkau, Rainer; Gaipl, Udo S.

    2012-01-01

    Radiotherapy (RT) with ionizing irradiation is commonly used to locally attack tumors. It induces a stop of cancer cell proliferation and finally leads to tumor cell death. During the last years it has become more and more evident that besides a timely and locally restricted radiation-induced immune suppression, a specific immune activation against the tumor and its metastases is achievable by rendering the tumor cells visible for immune attack. The immune system is involved in tumor control and we here outline how RT induces anti-inflammation when applied in low doses and contributes in higher doses to the induction of anti-tumor immunity. We especially focus on how local irradiation induces abscopal effects. The latter are partly mediated by a systemic activation of the immune system against the individual tumor cells. Dendritic cells are the key players in the initiation and regulation of adaptive anti-tumor immune responses. They have to take up tumor antigens and consecutively present tumor peptides in the presence of appropriate co-stimulation. We review how combinations of RT with further immune stimulators such as AnnexinA5 and hyperthermia foster the dendritic cell-mediated induction of anti-tumor immune responses and present reasonable combination schemes of standard tumor therapies with immune therapies. It can be concluded that RT leads to targeted killing of the tumor cells and additionally induces non-targeted systemic immune effects. Multimodal tumor treatments should therefore tend to induce immunogenic tumor cell death forms within a tumor microenvironment that stimulates immune cells.

  13. How does ionizing irradiation contribute to the induction of anti-tumor immunity?

    Directory of Open Access Journals (Sweden)

    Yvonne eRubner

    2012-07-01

    Full Text Available Radiotherapy (RT with ionizing irradiation is commonly used to locally attack tumors. It induces a stop of cancer cell proliferation and finally leads to tumor cell death. During the last years it has become more and more evident that besides a timely and locally restricted radiation-induced immune suppression, a specific immune activation against the tumor and its metastases is achievable by rendering the tumor cells visible for immune attack. The immune system is involved in tumor control and we here outline how RT induces anti-inflammation when applied in low doses and contributes in higher doses to the induction of anti-tumor immunity. We especially focus on how local irradiation induces abscopal effects. The latter are partly mediated by a systemic activation of the immune system against the individual tumor cells. Dendritic cells are the key players in the initiation and regulation of adaptive anti-tumor immune responses. They have to take up tumor antigens and consecutively present tumor peptides in the presence of appropriate co-stimulation. We review how combinations of RT with further immune stimulators such as AnnexinA5 and hyperthermia foster the dendritic cell-mediated induction of anti-tumor immune responses and present reasonable combination schemes of standard tumor therapies with immune therapies. It can be concluded that RT leads to targeted killing of the tumor cells and additionally induces non-targeted systemic immune effects. Multimodal tumor treatments should therefore tend to induce immunogenic tumor cell death forms within a tumor microenvironment that stimulates immune cells.

  14. Antitumor activity of extract and isolated compounds from Drechslera rostrata and Eurotium tonophilum

    Directory of Open Access Journals (Sweden)

    Fatmah A.S. Alasmary

    2018-02-01

    Full Text Available Total extracts of Drechslera rostrata and Eurotium tonophilum in addition of two isolated compounds from their cultures [di-2-ethylhexyl phthalate (H1 and 1,8-Dihydroxy-3-methoxy-6-methyl-anthraquinone (H2] were tested for their antitumor activity using four human carcinoma cell lines. Antitumor activity was assessed by performing MTT assay to check the % cell viability. The % viability of HCT-116 (colon carcinoma, HeLa (cervical carcinoma, HEp-2 (larynx carcinoma and HepG-2 (hepatocellular carcinoma cells decreased after treatment with Drechslera rostrata and Eurotium tonophilum extracts, these effects were ranged from 059.0 ±  0.1 to 217.0  ±  0.3 µg/ml on all types of cancer cells. The best activity was recorded for Eurotium tonpholium extract (054.5 ± 0.3, 059.0 ± 0.5 and 059.0 ± 0.1 for HEp-2, Hela, and HepG-2 respectively. The isolated compounds (H1&H2 were found to be responsible about the activities because they recorded the lowest IC50 on tested cell lines with range of 9.5–20.3 μg/ml. Vinblastine sulphate was used as a reference standard and showed in vitro anticancer activity. This study demonstrated that all extracts and isolated compounds have antitumor activity against HCT-116, HeLa, HEp-2 and HepG-2 cells.

  15. Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo.

    Science.gov (United States)

    Inami, Koichi; Abe, Masaaki; Takeda, Kazuyoshi; Hagiwara, Yoshiaki; Maeda, Masahiro; Segawa, Tatsuya; Suyama, Masafumi; Watanabe, Sumio; Hino, Okio

    2010-04-01

    Mesothelioma is an aggressive cancer often caused by chronic asbestos exposure, and its prognosis is very poor despite the therapies currently used. Due to the long latency period between asbestos exposure and tumor development, the worldwide incidence will increase substantially in the next decades. Thus, novel effective therapies are warranted to improve the prognosis. The ERC/mesothelin gene (MSLN) is expressed in wide variety of human cancers, including mesotheliomas, and encodes a precursor protein cleaved by proteases to generate C-ERC/mesothelin and N-ERC/mesothelin. In this study, we investigated the antitumor activity of C-ERC/mesothelin-specific mouse monoclonal antibody, 22A31, against tumors derived from a human mesothelioma cell line, ACC-MESO-4, in a xenograft experimental model using female BALB/c athymic nude mice. Treatment with 22A31 did not inhibit cell proliferation of ACC-MESO-4 in vitro; however, therapeutic treatment with 22A31 drastically inhibited tumor growth in vivo. 22A31 induced antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells, but not macrophages, in vitro. Consistently, the F(ab')(2) fragment of 22A31 did not inhibit tumor growth in vivo, nor did it induce antibody-dependent cell mediated cytotoxicity (ADCC) in vitro. Moreover, NK cell depletion diminished the antitumor effect of 22A31. Thus, 22A31 induced NK cell-mediated ADCC and exerted antitumor activity in vivo. 22A31 could have potential as a therapeutic tool to treat C-ERC/mesothelin-expressing cancers including mesothelioma.

  16. Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis.

    Science.gov (United States)

    Kim, Seongyeong; Min, Ahrum; Lee, Kyung-Hun; Yang, Yaewon; Kim, Tae-Yong; Lim, Jee Min; Park, So Jung; Nam, Hyun-Jin; Kim, Jung Eun; Song, Sang-Hyun; Han, Sae-Won; Oh, Do-Youn; Kim, Jee Hyun; Kim, Tae-You; Hangauer, David; Lau, Johnson Yiu-Nam; Im, Kyongok; Lee, Dong Soon; Bang, Yung-Jue; Im, Seock-Ah

    2017-07-01

    KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo . The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects. KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho-Src and proliferative-signaling molecules were down-regulated in KX-01-sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01-induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01-sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model. KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.

  17. Selected anti-tumor vaccines merit a place in multimodal tumor therapies

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, Eva-Maria; Wunderlich, Roland [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Ebel, Nina [Department of Process Technology and Machinery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Rubner, Yvonne [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Schlücker, Eberhard [Department of Process Technology and Machinery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany); Meyer-Pittroff, Roland [Competence Pool Weihenstephan, Technische Universität München, Freising (Germany); Ott, Oliver J.; Fietkau, Rainer; Gaipl, Udo S.; Frey, Benjamin, E-mail: benjamin.frey@uk-erlangen.de [Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen (Germany)

    2012-10-09

    Multimodal approaches are nowadays successfully applied in cancer therapy. Primary locally acting therapies such as radiotherapy (RT) and surgery are combined with systemic administration of chemotherapeutics. Nevertheless, the therapy of cancer is still a big challenge in medicine. The treatments often fail to induce long-lasting anti-tumor responses. Tumor recurrences and metastases result. Immunotherapies are therefore ideal adjuncts to standard tumor therapies since they aim to activate the patient's immune system against malignant cells even outside the primary treatment areas (abscopal effects). Especially cancer vaccines may have the potential both to train the immune system against cancer cells and to generate an immunological memory, resulting in long-lasting anti-tumor effects. However, despite promising results in phase I and II studies, most of the concepts finally failed. There are some critical aspects in development and application of cancer vaccines that may decide on their efficiency. The time point and frequency of medication, usage of an adequate immune adjuvant, the vaccine's immunogenic potential, and the tumor burden of the patient are crucial. Whole tumor cell vaccines have advantages compared to peptide-based ones since a variety of tumor antigens (TAs) are present. The master requirements of cell-based, therapeutic tumor vaccines are the complete inactivation of the tumor cells and the increase of their immunogenicity. Since the latter is highly connected with the cell death modality, the inactivation procedure of the tumor cell material may significantly influence the vaccine's efficiency. We therefore also introduce high hydrostatic pressure (HHP) as an innovative inactivation technology for tumor cell-based vaccines and outline that HHP efficiently inactivates tumor cells by enhancing their immunogenicity. Finally studies are presented proving that anti-tumor immune responses can be triggered by combining RT with selected

  18. In vitro antibacterial and antitumor activities of some medicinal plant extracts, growing in Turkey.

    Science.gov (United States)

    Yildirim, Arzu Birinci; Karakas, Fatma Pehlivan; Turker, Arzu Ucar

    2013-08-01

    To investigate antibacterial and antitumor activities of 51 different extracts prepared with 3 types of solvents (water, ethanol and methanol) of 16 different plant species (Ajuga reptans (A. reptans) L., Phlomis pungens (P. pungens) Willd., Marrubium astracanicum (M. astracanicum) Jacq., Nepeta nuda (N. nuda) L., Stachys annua (S. annua) L., Genista lydia (G. lydia) Boiss., Nuphar lutea (N. lutea) L., Nymphaea alba (N. alba) L., Vinca minor (V. minor) L., Stellaria media (S. media) L., Capsella bursa-pastoris (C. bursa-pastoris) L., Galium spurium (G. spurium) L., Onosma heterophyllum (O. heterophyllum) Griseb., Reseda luteola (R. luteola) L., Viburnum lantana (V. lantana) L. and Mercurialis annua (M. annua) L.) grown in Turkey was conducted. Antibacterial activity was evaluated with 10 bacteria including Streptococcus pyogenes (S. pyogenes), Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), Escheria coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Salmonella typhimurium (S. typhimurium), Serratia marcescens (S. marcescens), Proteus vulgaris (P. vulgaris), Enterobacter cloacae (E. cloacea), and Klebsiella pneumoniae (K. pneumoniae) by using disc diffusion method. Antitumor activity was evaluated with Agrobacterium tumefaciens (A. tumefaciens)-induced potato disc tumor assay. Best antibacterial activity was obtained with ethanolic extract of P. pungens against S. pyogenes. Ethanolic and methanolic extract of N. alba and ethanolic extract of G. lydia also showed strong antibacterial activities. Results indicated that alcoholic extracts especially ethanolic extracts exhibited strong antibacterial activity against both gram-positive and gram-negative bacteria. Best antitumor activity was obtained with methanolic extracts of N. alba and V. lantana (100% tumor inhibition). Ethanolic extract of N. alba, alcoholic extracts of N. lutea, A. reptans and V. minor flowers, methanolic extracts of G. lydia and O. heterophyllum and ethanolic

  19. Anti-tumor effects of an engineered 'killer' transfer RNA

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Dong-hui [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States); Lee, Jiyoung; Frankenberger, Casey [Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637 (United States); Geslain, Renaud, E-mail: rgeslain@depaul.edu [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States); Department of Biology, DePaul University, Chicago, IL 60614 (United States); Rosner, Marsha, E-mail: m-rosner@uchicago.edu [Ben May Department for Cancer Research, University of Chicago, Chicago, IL 60637 (United States); Pan, Tao, E-mail: taopan@uchicago.edu [Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637 (United States)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer tRNA with anti-cancer effects. Black-Right-Pointing-Pointer tRNA induced protein misfolding. Black-Right-Pointing-Pointer tRNA as anti-tumor agent. -- Abstract: A hallmark of cancer cells is their ability to continuously divide; and rapid proliferation requires increased protein translation. Elevating levels of misfolded proteins can elicit growth arrest due to ER stress and decreased global translation. Failure to correct prolonged ER stress eventually results in cell death via apoptosis. tRNA{sup Ser}(AAU) is an engineered human tRNA{sup Ser} with an anticodon coding for isoleucine. Here we test the possibility that tRNA{sup Ser}(AAU) can be an effective killing agent of breast cancer cells and can effectively inhibit tumor-formation in mice. We found that tRNA{sup Ser}(AAU) exert strong effects on breast cancer translation activity, cell viability, and tumor formation. Translation is strongly inhibited by tRNA{sup Ser}(AAU) in both tumorigenic and non-tumorigenic cells. tRNA{sup Ser}(AAU) significantly decreased the number of viable cells over time. A short time treatment with tRNA{sup Ser}(AAU) was sufficient to eliminate breast tumor formation in a xenograft mouse model. Our results indicate that tRNA{sup Ser}(AAU) can inhibit breast cancer metabolism, growth and tumor formation. This RNA has strong anti-cancer effects and presents an opportunity for its development into an anti-tumor agent. Because tRNA{sup Ser}(AAU) corrupts the protein synthesis mechanism that is an integral component of the cell, it would be extremely difficult for tumor cells to evolve and develop resistance against this anti-tumor agent.

  20. Anti-tumor effects of an engineered “killer” transfer RNA

    International Nuclear Information System (INIS)

    Zhou, Dong-hui; Lee, Jiyoung; Frankenberger, Casey; Geslain, Renaud; Rosner, Marsha; Pan, Tao

    2012-01-01

    Highlights: ► tRNA with anti-cancer effects. ► tRNA induced protein misfolding. ► tRNA as anti-tumor agent. -- Abstract: A hallmark of cancer cells is their ability to continuously divide; and rapid proliferation requires increased protein translation. Elevating levels of misfolded proteins can elicit growth arrest due to ER stress and decreased global translation. Failure to correct prolonged ER stress eventually results in cell death via apoptosis. tRNA Ser (AAU) is an engineered human tRNA Ser with an anticodon coding for isoleucine. Here we test the possibility that tRNA Ser (AAU) can be an effective killing agent of breast cancer cells and can effectively inhibit tumor-formation in mice. We found that tRNA Ser (AAU) exert strong effects on breast cancer translation activity, cell viability, and tumor formation. Translation is strongly inhibited by tRNA Ser (AAU) in both tumorigenic and non-tumorigenic cells. tRNA Ser (AAU) significantly decreased the number of viable cells over time. A short time treatment with tRNA Ser (AAU) was sufficient to eliminate breast tumor formation in a xenograft mouse model. Our results indicate that tRNA Ser (AAU) can inhibit breast cancer metabolism, growth and tumor formation. This RNA has strong anti-cancer effects and presents an opportunity for its development into an anti-tumor agent. Because tRNA Ser (AAU) corrupts the protein synthesis mechanism that is an integral component of the cell, it would be extremely difficult for tumor cells to evolve and develop resistance against this anti-tumor agent.

  1. Antitumor effect of the essential oil from leaves of Guatteria pogonopus (Annonaceae).

    Science.gov (United States)

    do N Fontes, José Eraldo; Ferraz, Rosana P C; Britto, Anny C S; Carvalho, Adriana A; Moraes, Manoel O; Pessoa, Claudia; Costa, Emmanoel V; Bezerra, Daniel P

    2013-04-01

    Guatteria pogonopus Martius, a plant belonging to the Annonaceae family, is found in the remaining Brazilian Atlantic Forest. In this study, the chemical composition and antitumor effects of the essential oil isolated from leaves of G. pogonopus was investigated. The chemical composition of the oil was determined by GC-FID and GC/MS analyses. The in vitro cytotoxicity was evaluated against three different tumor cell lines (OVCAR-8, NCI-H358M, and PC-3M), and the in vivo antitumor activity was tested in mice bearing sarcoma 180 tumor. A total of 29 compounds was identified and quantified in the oil. The major compounds were γ-patchoulene (13.55%), (E)-caryophyllene (11.36%), β-pinene (10.37%), germacrene D (6.72%), bicyclogermacrene (5.97%), α-pinene (5.33%), and germacrene B (4.69%). The essential oil, but neither (E)-caryophyllene nor β-pinene, displayed in vitro cytotoxicity against all three tumor cell lines tested. The obtained average IC50 values ranged from 3.8 to 20.8 μg/ml. The lowest and highest values were obtained against the NCI-H358M and the OVCAR-8 cell lines, respectively. The in vivo tumor-growth-inhibition rates in the tumor-bearing mice treated with essential oil (50 and 100 mg/kg/d) were 25.3 and 42.6%, respectively. Hence, the essential oil showed significant in vitro and in vivo antitumor activity. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

  2. Bovine lactoferrin binds oleic acid to form an anti-tumor complex similar to HAMLET.

    Science.gov (United States)

    Fang, Bing; Zhang, Ming; Tian, Mai; Jiang, Lu; Guo, Hui Yuan; Ren, Fa Zheng

    2014-04-04

    α-Lactalbumin (α-LA) can bind oleic acid (OA) to form HAMLET-like complexes, which exhibited highly selective anti-tumor activity in vitro and in vivo. Considering the structural similarity to α-LA, we conjectured that lactoferrin (LF) could also bind OA to obtain a complex with anti-tumor activity. In this study, LF-OA was prepared and its activity and structural changes were compared with α-LA-OA. The anti-tumor activity was evaluated by methylene blue assay, while the apoptosis mechanism was analyzed using flow cytometry and Western blot. Structural changes of LF-OA were measured by fluorescence spectroscopy and circular dichroism. The interactions of OA with LF and α-LA were evaluated by isothermal titration calorimetry (ITC). LF-OA was obtained by heat-treatment at pH8.0 with LD50 of 4.88, 4.95 and 4.62μM for HepG2, HT29, and MCF-7 cells, respectively, all of which were 10 times higher than those of α-LA-OA. Similar to HAMLET, LF-OA induced apoptosis in tumor cells through both death receptor- and mitochondrial-mediated pathways. Exposure of tryptophan residues and the hydrophobic regions as well as the loss of tertiary structure were observed in LF-OA. Besides these similarities, LF showed different secondary structure changes when compared with α-LA, with a decrease of α-helix and β-turn and an increase of β-sheet and random coil. ITC results showed that there was a higher binding number of OA to LF than to α-LA, while both of the proteins interacted with OA through van der Waals forces and hydrogen bonds. This study provides a theoretical basis for further exploration of protein-OA complexes. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Antitumor and Immunomodulatory Effects of Polysaccharides from Broken-Spore of Ganoderma lucidum

    Directory of Open Access Journals (Sweden)

    Peng-Yun eWang

    2012-07-01

    Full Text Available The antitumor activity of Gl-BSP, a polysaccharide isolated from boiling water extract of the broken-spores of Ganoderma lucidum (Leyss ex Fr Karst. and its possible mechanism were investigated in vivo and in vitro. It was showed that Gl-BSP (50, 100, 200 mg/kg exhibited antitumor effect against Sarcoma 180 (S180 in BALB/c mice. The Gl-BSP was not cytotoxicity in S180 cells and PG cells (human lung carcinoma cell in vitro. However, Gl-BSP-treated serum potently inhibited S180 cells and PG cells proliferation in vitro. Moreover, Gl-BSP could promote the splenic lymphocyte proliferation induced by Con A or LPS, enhance nature killer cell (NK cell cytotoxic activity, augment the percentage of neutral red (NR phagocytosis by macrophages, and increase the percentage of the CD4+ or CD8+ subset in S180-bearing BALB/c mice. The level of IFN-γ, TNF-α and NO of serum apparently was increased by Gl-BSP. Gl-BSP also showed immunomodulatory activities in tumor-bearing mice. Furthermore,It was proved that neutralization with anti-TNF-α and/or anti-IFN-γ significantly diminished growth inhibition induced by Gl-BSP –treated serum in S180 or PG cells. Blocking effect was noted in the combination of anti-TNF-α and anti-IFN-γ. These observations suggest that the antitumor activity of Gl-BSP may mainly relate to the activation of the immune response of the host organism by the stimulation of NK cells, T cells, and macrophages.

  4. Induction of mitophagy-mediated antitumor activity with folate-appended methyl-β-cyclodextrin.

    Science.gov (United States)

    Kameyama, Kazuhisa; Motoyama, Keiichi; Tanaka, Nao; Yamashita, Yuki; Higashi, Taishi; Arima, Hidetoshi

    2017-01-01

    Mitophagy is the specific autophagic elimination system of mitochondria, which regulates cellular survival via the removal of damaged mitochondria. Recently, we revealed that folate-appended methyl-β-cyclodextrin (FA-M-β-CyD) provides selective antitumor activity in folate receptor-α (FR-α)-expressing cells by the induction of autophagy. In this study, to gain insight into the detailed mechanism of this antitumor activity, we focused on the induction of mitophagy by the treatment of FR-α-expressing tumor cells with FA-M-β-CyD. In contrast to methyl-β-cyclodextrin, FA-M-β-CyD entered KB cells, human epithelial cells from a fatal cervical carcinoma (FR-α (+)) through FR-α-mediated endocytosis. The transmembrane potential of isolated mitochondria after treatment with FA-M-β-CyD was significantly elevated. In addition, FA-M-β-CyD lowered adenosine triphosphate (ATP) production and promoted reactive oxygen species production in KB cells (FR-α (+)). Importantly, FA-M-β-CyD enhanced light chain 3 (LC3) conversion (LC3-I to LC3-II) in KB cells (FR-α (+)) and induced PTEN-induced putative kinase 1 (PINK1) protein expression, which is involved in the induction of mitophagy. Furthermore, FA-M-β-CyD had potent antitumor activity in BALB/c nu/nu mice xenografted with KB cells (FR-α (+)) without any significant side effects. Taken together, these findings demonstrate that the autophagic cell death elicited by FA-M-β-CyD could be associated with mitophagy induced by an impaired mitochondrial function.

  5. Enhancement of hypoxia-activated prodrug TH-302 anti-tumor activity by Chk1 inhibition.

    Science.gov (United States)

    Meng, Fanying; Bhupathi, Deepthi; Sun, Jessica D; Liu, Qian; Ahluwalia, Dharmendra; Wang, Yan; Matteucci, Mark D; Hart, Charles P

    2015-05-21

    The hypoxia-activated prodrug TH-302 is reduced at its nitroimidazole group and selectively under hypoxic conditions releases the DNA cross-linker bromo-isophosphoramide mustard (Br-IPM). Here, we have explored the effect of Chk1 inhibition on TH-302-mediated pharmacological activities. We employed in vitro cell viability, DNA damage, cellular signaling assays and the in vivo HT29 human tumor xenograft model to study the effect of Chk1inhibition on TH-302 antitumor activities. TH-302 cytotoxicity is greatly enhanced by Chk1 inhibition in p53-deficient but not in p53-proficient human cancer cell lines. Chk1 inhibitors reduced TH-302-induced cell cycle arrest via blocking TH-302-induced decrease of phosphorylation of histone H3 and increasing Cdc2-Y15 phosphorylation. Employing the single-cell gel electrophoresis (comet) assay, we observed a potentiation of the TH-302 dependent tail moment. TH-302 induced γH2AX and apoptosis were also increased upon the addition of Chk1 inhibitor. Potentiation of TH-302 cytotoxicity by Chk1 inhibitor was only observed in cell lines proficient in, but not deficient in homology-directed DNA repair. We also show that combination treatment led to lowering of Rad51 expression levels as compared to either agent alone. In vivo data demonstrate that Chk1 inhibitor enhances TH-302 anti-tumor activity in p53 mutant HT-29 human tumor xenografts, supporting the hypothesis that these in vitro results can translate to enhanced in vivo efficacy of the combination. TH-302-mediated in vitro and in vivo anti-tumor activities were greatly enhanced by the addition of Chk1 inhibitors. The preclinical data presented in this study support a new approach for the treatment of p53-deficient hypoxic cancers by combining Chk1 inhibitors with the hypoxia-activated prodrug TH-302.

  6. Effect of electron beam-irradiation to b-glucan on its immunomodulating and antitumor activity

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Yeon Hwan; Lee, Jung Lim; Yoo, Yung Choon [Konyand Univ., Daejeon (Korea, Republic of); Kim, Jae Hoon; Lee, Ju Woon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2010-07-01

    In this study, in order investigated the effect of electron beam irradiation to b-glucan on its biological activities, we compared immunomodulating and antitumor activity between non-irradiated and electron beam-irradiated b-glucan. EB-glucan was irradiated by electron beam with 10, 30 and 50 kGy. Treatment with EB-glucan resulted in a slight increase of the proliferation of ConA-stimulated splenocytes, and the strongest activity was seen in 50 kGy-treated EB-glucan. EB-glucan teated with 50 kGy also showed increased secretion of cytokines such as IL-2 IFN-{gamma} and IL-6 from ConA-stimulated splenocytes. The activity of EB-glucan to enhance the proliferation of splenocytes and cytokine secretion from ConA-stimulated splenocytes was higher than that of NI-glucan. Furthermore, EB-glucan treated with 50 kGy showed higher activity to activate RAW 264.7 macrophages, comparing with that of NI-glucan. In experiments of antitumor activity, EB-glucan treated with 50 kGy prior to tumor inoculation inhibited an experimental lung metastasis produced by B16-BL6 melanoma cells in mice. But NI-glucan did show no effect. In addition, EB-glucan treated with 50 kGy induced a decrease a decrease of tumor growth in tumor-bearing mice. Collectivelt, these results indicates that electron beam irradiation {beta}-glucan leads its biological functions to enhance immunomodulating and antitumor activity.

  7. The antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo

    Science.gov (United States)

    Shi, Dayong; Li, Jing; Guo, Shuju; Su, Hua; Fan, Xiao

    2009-05-01

    To investigate the antitumor effect of bromophenol derivatives in vitro and Leathesia nana extract in vivo, six bromophenol derivatives 6-(2,3-dibromo-4,5-dihydroxybenzyl)-2,3-dibromo-4,5-dihydroxy benzyl methyl ether (1), (+)-3-(2,3-dibromo-4,5-dihydroxyphenyl)-4-bromo-5,6-dihydroxy-1,3-dihydroisobenzofuran (2), 3-bromo-4-(2,3-dibromo-4,5-dihydroxybenzyl)-5-methoxymethyl-pyrocatechol (3), 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxy-diphenylmethane (4), bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (5), 2,2',3-tribromo-3',4,4',5-tetrahydroxy-6'-ethyloxymethyldiphenylmethane (6) were isolated from brown alga Leathesia nana, and their cytotoxicity were tested by MTT assays in human cancer cell lines A549, BGC-823, MCF-7, B16-BL6, HT-1080, A2780, Bel7402 and HCT-8. Their inhibitory activity against protein tyrosine kinase (PTK) with over-expression of c-kit was analyzed also by ELISA. The antitumor activity of ethanolic extraction of Leathesia nana (EELN) was evaluated on S180-bearing mice. All compounds showed very potent cytotoxicity against all of the eight cancer cell lines with IC50 below 10 μg/mL. In PTK inhibition study, all bromophenol derivatives showed moderate inhibitory activity and compounds 2, 5 and 6 showed significant bioactivity with the inhibition ratio of 77.5%, 80.1% and 71.4%, respectively. Pharmacological studies reveal that EELN could inhibit the growth of Sarcoma 180 tumor and increase the indices of thymus and spleen to improve the immune system remarkably in vivo. Results indicated that the bromophenol derivatives and EELN can be used as potent antitumor agents for PTK over-expression of c-kit and considered in a new therapeutic strategy for treatment of cancer.

  8. Effect of electron beam-irradiation to b-glucan on its immunomodulating and antitumor activity

    International Nuclear Information System (INIS)

    Jung, Yeon Hwan; Lee, Jung Lim; Yoo, Yung Choon; Kim, Jae Hoon; Lee, Ju Woon

    2010-01-01

    In this study, in order investigated the effect of electron beam irradiation to b-glucan on its biological activities, we compared immunomodulating and antitumor activity between non-irradiated and electron beam-irradiated b-glucan. EB-glucan was irradiated by electron beam with 10, 30 and 50 kGy. Treatment with EB-glucan resulted in a slight increase of the proliferation of ConA-stimulated splenocytes, and the strongest activity was seen in 50 kGy-treated EB-glucan. EB-glucan teated with 50 kGy also showed increased secretion of cytokines such as IL-2 IFN-γ and IL-6 from ConA-stimulated splenocytes. The activity of EB-glucan to enhance the proliferation of splenocytes and cytokine secretion from ConA-stimulated splenocytes was higher than that of NI-glucan. Furthermore, EB-glucan treated with 50 kGy showed higher activity to activate RAW 264.7 macrophages, comparing with that of NI-glucan. In experiments of antitumor activity, EB-glucan treated with 50 kGy prior to tumor inoculation inhibited an experimental lung metastasis produced by B16-BL6 melanoma cells in mice. But NI-glucan did show no effect. In addition, EB-glucan treated with 50 kGy induced a decrease a decrease of tumor growth in tumor-bearing mice. Collectivelt, these results indicates that electron beam irradiation β-glucan leads its biological functions to enhance immunomodulating and antitumor activity

  9. A New in Vitro Anti-Tumor Polypeptide Isolated from Arca inflata

    Directory of Open Access Journals (Sweden)

    Jian Xu

    2013-12-01

    Full Text Available A new in vitro anti-tumor polypeptide, coded as J2-C3, was isolated from Arca inflata Reeve and purified by diethyl-aminoethanol (DEAE-sepharose Fast Flow anion exchange and phenyl sepharose CL-4B hydrophobic chromatography. J2-C3 was identified to be a homogeneous compound by native polyacrylamide gel electrophoresis (Native-PAGE. The purity of J2-C3 was over 99% in reversed phase-high performance liquid chromatography (RP-HPLC. The molecular weight was determined as 20,538.0 Da by electrospray-ionization mass spectrometry (ESI-MS/MS. J2-C3 was rich in Glx (Gln + Glu, Lys, and Asx (Asp + Asn according to amino acid analysis. Four partial amino acid sequences of this peptide were determined as L/ISMEDVEESR, KNGMHSI/LDVNHDGR, AMKI/LI/LNPKKGI/LVPR and AMGAHKPPKGNEL/IGHR via MALDI-TOF/TOF-MS and de novo sequencing. Secondary structural analysis by CD spectroscopy revealed that J2-C3 had the α-helix (45.2%, β-sheet (2.9%, β-turn (26.0% and random coil (25.9%. The anti-tumor effect of J2-C3 against human tumor cells was measured by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay, and the IC50 values of J2-C3 were 65.57, 93.33 and 122.95 µg/mL against A549, HT-29 and HepG2 cell lines, respectively. Therefore, J2-C3 might be developed as a potential anti-tumor agent.

  10. Oil-in-water biocompatible microemulsion as a carrier for the antitumor drug compound methyl dihydrojasmonate

    Directory of Open Access Journals (Sweden)

    Silva GB

    2015-01-01

    Full Text Available Gisela Bevilacqua Rolfsen Ferreira da Silva,1 Maria Virginia Scarpa,1 Iracilda Zepone Carlos,2 Marcela Bassi Quilles,2 Raphael Carlos Comeli Lia,3 Eryvaldo Socrates Tabosa do Egito,4 Anselmo Gomes de Oliveira1 1Departamento de Fármacos e Medicamentos, 2Departamento de Análises Clínicas, UNESP–Universidade Estadual Paulista, Faculdade de Ciências Farmacêuticas, PPG em Nanotecnologia Farmacêutica, Rodovia Araraquara-Jaú Km 01, Araraquara, SP, Brazil; 3Instituto de Patologia Cirúrgica e Citopatologia (IPC, Araraquara, SP, Brazil; 4UFRN–Universidade Federal do Rio Grande do Norte, Programa de Pós-graduação em Ciências da Saúde, Natal, RN, Brazil Abstract: Methyl dihydrojasmonate (MJ has been studied because of its application as an antitumor drug compound. However, as MJ is a poorly water-soluble compound, a suitable oil-in-water microemulsion (ME has been studied in order to provide its solubilization in an aqueous media and to allow its administration by the parenteral route. The ME used in this work was characterized on the pseudo-ternary phase diagram by dynamic light scattering and rheological measurements. Regardless of the drug presence, the droplet size was directly dependent on the oil/surfactant (O/S ratio. Furthermore, the drug incorporation into the ME significantly increased the ME diameter, mainly at low O/S ratios. The rheological evaluation of the systems showed that in the absence of drug a Newtonian behavior was observed. On the other hand, in the presence of MJ the ME systems revealed pseudoplastic behavior, independently of the O/S ratio. The in vivo studies demonstrated that not only was the effect on the tumor inhibition inversely dependent on the MJ-loaded ME administered dose, but also it was slightly higher than the doxorubicin alone, which was used as the positive control. Additionally, a small antiangiogenic effect for MJ-loaded ME was found at doses in which it possesses antitumor activity. MJ revealed to

  11. The HSP90 inhibitor 17-AAG exhibits potent antitumor activity for pheochromocytoma in a xenograft model.

    Science.gov (United States)

    Xu, Yunze; Zhu, Qi; Chen, Dongning; Shen, Zhoujun; Wang, Weiqing; Ning, Guang; Zhu, Yu

    2015-07-01

    This study aims to investigate the effect of heat shock protein 90 (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) in the malignant pheochromocytoma using a xenograft mouse model. Treatment with 17-AAG induced a marked reduction in the volume and weight of PC12 pheochromocytoma cell tumor xenografts in mice. Furthermore, 17-AAG also significantly inhibited the expression of HSP90 and its client proteins. Our results validated HSP90 as an important target in pheochromocytoma and provided rationale for the testing of HSP90 inhibitors as a promising therapeutic agent in the antitumor therapy of pheochromocytoma.

  12. Intensification of the antitumoral effect of ionizing radiations in combined use of metronidazole and hyperglycemia

    International Nuclear Information System (INIS)

    Vinskaya, N.P.; Voloshina, E.A.; Vygodskaya, A.L.; Yarmonenko, S.P.

    1984-01-01

    The authors have shown that a more pronounced antitumor effect of radiation in the combined use of metronidazole and induced short-term hyperglycemia (STH) may result not only from the summation of the two effects: the sensitizing effect of metronidazole and decreased viability of irradiated cells caused by STH but also from the intensified cytotoxic effect of metronidazole on hypoxic tumor cells. It was also noted that when hypoxic cells subjected to the sensitizing effect of electron acceptor sensitizers are found in the normal (skin) and tumorous tissues, STH use following irradiation in the presence of metronidazole enchances selectively the tumor radiation effect

  13. Selective potentiation of the antitumor radiation effect by means of short-term hyperglycemia

    International Nuclear Information System (INIS)

    Yarmonenko, S.P.; Shapot, V.S.; Voloshina, E.A.; Gorozhanskaya, Eh.G.; Dyuskaliev, Zh.D.; Krimker, V.M.

    1981-01-01

    Experiments on mice have shown that short-term induced hyperglycemia caused by 5-fold intraperitoneal administration of glucose at a dose of 2.6 and 1.3 g/kg increases notably the radiation injury to a solid type of Ehrlich carcinoma. Short-term induced hyperglycemia is mostly effective after irradiation. During irradiation together with its antitumor effect enhanced in the presence of short-term induced hyperglycemia there is observed selective protection of the normal tissues resulting from a decrease of oxygen pressure in them

  14. A new polyacetylene from Vernonia scorpioides (Lam.) Pers. (Asteraceae) and its in vitro antitumoral activity

    Energy Technology Data Exchange (ETDEWEB)

    Buskuhl, Humberto; Freitas, Rilton A.; Biavatti, Maique W. [Universidade do Vale do Itajai, Itajai, SC (Brazil). Centro de Ciencias da Saude], e-mail: maique@ccs.ufsc.br; Monache, Franco Delle [Universita ' La Sapienza' , Rome (Italy). Dipt. di Chimica e Tecnologia delle Sostanze Biologicamente Attive; Barison, Andersson; Campos, Francinete R. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Centro Politecnico. Dept. de Quimica; Corilo, Yuri E.; Eberlin, Marcos N. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Inst. de Quimica

    2009-07-01

    The dichloromethane fraction obtained from hydroalcoholic crude extract of leaves and flowers of Vernonia scorpioides (Asteraceae) was investigated, resulting in the isolation and structure elucidation of a new polyacetylene namely 5-octa-2,4,6-triynyl-furan-2(5H)-one. The structure of the isolated compound was determined based on IR, NMR (1D and 2D) and MS spectrometric data. The antitumor potential, including cytotoxicity to tumor cells and genotoxicity, was investigated. The results suggest that apoptotic cell death may have occurred, at least in part, via a caspase-dependent mechanism. (author)

  15. Antitumor-promoting activity of scopadulcic acid B, isolated from the medicinal plant Scoparia dulcis L.

    Science.gov (United States)

    Nishino, H; Hayashi, T; Arisawa, M; Satomi, Y; Iwashima, A

    1993-01-01

    Scopadulcic acid B (SDB), a tetracyclic diterpenoid isolated from a medicinal plant, Scoparia dulcis L., inhibited the effects of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in vitro and in vivo; SDB inhibited TPA-enhanced phospholipid synthesis in cultured cells, and also suppressed the promoting effect of TPA on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene. The potency of SDB proved to be stronger than that of other natural antitumor-promoting terpenoids, such as glycyrrhetinic acid.

  16. Influence of low dose ionizing radiation on amplification and antitumor activity of LAK/TIL cells

    International Nuclear Information System (INIS)

    Liu Wei; Hou Dianjun; Qiao Jianwei; Shang Ximei; Li Jieqing

    2000-01-01

    Objective: To study the influence of low dose ionization on amplification and antitumor activity of LAK/TIL cells. Methods: TIL cells isolated from Lewis lung cancer tissues and LAK cells from spleen of tumor-bearing mouse were irradiated with different low doses of X-rays and were cultured after irradiation. Results: Low dose ionizing radiation improved the amplification volume of LAK/TIL cells, decreased the cell death ratio in amplification process, and increased the toxicity of LAK/TIL cells, Conclusions: Low dose ionizing radiation can result in amplification of biologically activated lymphocytes, and decreases the death ratio of the cells in amplification process

  17. Flavonoids Isolated From the Flowers of Limonium bicolor and their In vitro Antitumor Evaluation.

    Science.gov (United States)

    Chen, Jian; Teng, Jiehui; Ma, Li; Tong, Haiying; Ren, Bingru; Wang, Linshan; Li, Weilin

    2017-01-01

    Limonium bicolor , a halophytic species, can grow in saline or saline-alkali soil, is well known as a traditional Chinese medicine. Recently it attracted much attention for its treatment for cancer. The present study was performed to evaluate this species from the phytochemical standpoint and the possible relationship between the antitumor activity and its natural products. The chemical constituents from the flowers of L. bicolor were investigated through bioassay-guided fractionation and isolation. All the individual compounds were characterized by spectroscopic analysis and their potential antitumor activity was tested against three different human tumor cell lines by MTT assays. The EtOAc extract was proven as the most potent fraction and further fractionation led to the isolation of 15 natural flavonoids, which were characterized as luteolin (1), acacetin (2), quercetin (3), isorhamnetin (4), kaempferol (5), eriodictyol (6), kaempferol-3-O-α-L-rhamnoside (7), kaempferol-3-O-β-D-glucoside (8), quercetin-3-O-α-L-rhamnoside (9), quercetin-3-O-β-D-glucoside (10), quercetin-3-O-β-D-galactoside (11), myricetin-3-O-α-L-rhamnoside (12), kaempferol-3-O-(6″-O-galloyl)-β-D-glucoside (13), hesperidin (14) and rutin (15). The biotesting results demonstrated that both compounds 1 and 3 showed good cytotoxicity against human colon cancer cells (LOVO). Compound 5 exhibited relative greater growth inhibition against both human breast cancer cells (MCF-7) and osteosarcoma cell lines (U2-OS) at the concentration of 100 μg/mL. On the basis of these findings, the flavonoids were deduced to be potentially responsible for the antitumor activity of L. bicolor . The preliminary structure-activity relationship analysis suggests that the 3-O-glycosylation moiety in natural flavonoids was not essential for the antiproliferative activity on LOVO and U2-OS cells. The phytochemical investigation of Limonium bicolor led to the isolation of 15 flavonoids.The biotesting of the

  18. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    International Nuclear Information System (INIS)

    Peters, Diane E.; Hoover, Benjamin; Cloud, Loretta Grey; Liu, Shihui; Molinolo, Alfredo A.; Leppla, Stephen H.; Bugge, Thomas H.

    2014-01-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti-tumor

  19. Antitumor Activity and Mechanism of a Reverse Transcriptase Inhibitor, Dapivirine, in Glioblastoma

    OpenAIRE

    Liu, Weiwen; Song, Xian-lu; Zhao, Shan-chao; He, Minyi; Wang, Hai; Chen, Ziyang; Xiang, Wei; Yi, Guozhong; Qi, Songtao; Liu, Yawei

    2018-01-01

    Ethnopharmacological relevance: Dapivirine is one of reverse transcriptase inhibitors (RTIs). It is the prototype of diarylpyrimidines (DAPY), formerly known as TMC120 or DAPY R147681 (IUPAC name: 4- [[4-(2, 4, 6-trimethylphenyl) amino]-2-pyrimidinyl] amino]-benzonitrile; CAS no.244767-67-7). Aim: The purpose of this study is to investigate the antitumor activity of dapivirine, one of the RTIs, on U87 glioblastoma (GBM) cells in vitro and in vivo. Materials and Methods: U87 GBM cells were cul...

  20. Electron-topological investigation of the structure-antitumor activity relationship of thiosemicarbazone derivatives.

    Science.gov (United States)

    Dimoglo, A S; Chumakov, Y M; Dobrova, B N; Saracoglu, M

    1997-04-01

    In the frameworks of the electron-topological method (ETM) the structure-antitumor activity relationship was investigated for a series of thiosemicarbazone derivatives. The series included 70 compounds. Conformational analysis and quantum-chemical calculations were carried out for each compound. The revealed activity feature showed a satisfactory description of the class of active compounds according to two different parameters P and alpha estimating the probabilities of the feature realization in the class of active compounds (they are equal to 0.94 and 0.86, correspondingly). The results of testing demonstrated the high ability of ETM in predicting the activity investigated.

  1. Comparative toxicity and efficacy of engineered anthrax lethal toxin variants with broad anti-tumor activities

    Energy Technology Data Exchange (ETDEWEB)

    Peters, Diane E. [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Program of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA (United States); Hoover, Benjamin [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Cloud, Loretta Grey [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Liu, Shihui [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Molinolo, Alfredo A. [Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States); Leppla, Stephen H. [Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD (United States); Bugge, Thomas H., E-mail: thomas.bugge@nih.go [Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD (United States)

    2014-09-01

    We have previously designed and characterized versions of anthrax lethal toxin that are selectively cytotoxic in the tumor microenvironment and which display broad and potent anti-tumor activities in vivo. Here, we have performed the first direct comparison of the safety and efficacy of three engineered anthrax lethal toxin variants requiring activation by either matrix-metalloproteinases (MMPs), urokinase plasminogen activator (uPA) or co-localized MMP/uPA activities. C57BL/6J mice were challenged with six doses of engineered toxins via intraperitoneal (I.P.) or intravenous (I.V.) dose routes to determine the maximum tolerated dose for six administrations (MTD6) and dose-limiting toxicities. Efficacy was evaluated using the B16-BL6 syngraft model of melanoma; mice bearing established tumors were treated with six I.P. doses of toxin and tumor measurements and immunohistochemistry, paired with terminal blood work, were used to elaborate upon the anti-tumor mechanism and relative efficacy of each variant. We found that MMP-, uPA- and dual MMP/uPA-activated anthrax lethal toxins exhibited the same dose-limiting toxicity; dose-dependent GI toxicity. In terms of efficacy, all three toxins significantly reduced primary B16-BL6 tumor burden, ranging from 32% to 87% reduction, and they also delayed disease progression as evidenced by dose-dependent normalization of blood work values. While target organ toxicity and effective doses were similar amongst the variants, the dual MMP/uPA-activated anthrax lethal toxin exhibited the highest I.P. MTD6 and was 1.5–3-fold better tolerated than the single MMP- and uPA-activated toxins. Overall, we demonstrate that this dual MMP/uPA-activated anthrax lethal toxin can be administered safely and is highly effective in a preclinical model of melanoma. This modified bacterial cytotoxin is thus a promising candidate for further clinical development and evaluation for use in treating human cancers. - Highlights: • Toxicity and anti-tumor

  2. O DESAFIO DA PRIVACIDADE NA INTERNET DAS COISAS

    Directory of Open Access Journals (Sweden)

    Carlos Cesar Santos

    2015-12-01

    Full Text Available Na ultima década a internet tornou-se uma ferramenta presente no cotidiano das pessoas e das organizações e por vez indispensável ao bom funcionamento dos negócios. Com o crescente incremento das infraestruturas de redes e popularização em massa da rede de alta velocidade, emerge um avanço relacionado à utilização da internet tornando-a uma plataforma global para deixar máquinas e objetos inteligentes capazes de comunicarem-se de forma autônoma. Esta possibilidade permite que conteúdos e serviços estejam em torno das pessoas, sempre disponíveis, facilitando a comunicação e abrindo o caminho para novas aplicações, possibilitando novas formas de trabalho, de interação e de entretenimento, fazendo com que um novo padrão de vida e de trabalho seja desenvolvido. Este novo padrão torna-se possível através dos avanços das Tecnologias da Informação e Comunicação - TICs até uma nova concepção definida como Internet of Things - IoT. Entretanto, com uma variada coleta de dados e informações, para variados fins, no cotidiano das pessoas e das organizações, a coleta autônoma dos dados e das informações torna a privacidade um dos principais desafios em relação à IoT. Neste contexto, este artigo objetiva discutir em âmbito teórico a privacidade dos usuários da tecnologias da Internet das Coisas, diante de sua legalidade, explorando possíveis soluções neste cenário ainda em construção.

  3. Uma leitura semiótica das multidões

    Directory of Open Access Journals (Sweden)

    Alexandre Rocha da Silva

    2016-12-01

    Full Text Available Uma leitura semiótica das multidões tem o objetivo de problematizar as funções do incomensurável na semiose. Tal problematização envolve os problemas da imanência, do primado da mediação que caracteriza o pensamento semiótico contemporâneo e da desconstrução das identidades operada pelas teorias queer. Para tanto, metodologicamente, (1 apresentamos os conceitos de multidão desenvolvidos por Charles Sanders Peirce, Antônio Negri e Michael Hardt; (2 discutimos o caráter descritivo das categorias faneroscópicas de Peirce para propor a Zeroidade como condição e imanência de toda a semiose; (3 identificamos a dupla face – virtual e mediada – da singularidade e (4 demonstramos de que maneira a singularidade, que é uma potência, dá lugar na semiose a identidades. É o caráter indissociável da singularidade, da identidade e das crenças/hábitos que permite a este artigo denunciar falsas dicotomias e afirmar o perspectivismo como horizonte fundamental para os estudos semióticos das multidões.

  4. Das Curriculum Health Technology Assessment (HTA, Version 2.0

    Directory of Open Access Journals (Sweden)

    Perleth, Matthias

    2017-10-01

    Full Text Available Health Technology Assessments (HTAs liefern für zahlreiche Entscheidungen im Gesundheitswesen relevante Informationen. Die Erstellung von HTA-Berichten erfordert gut ausgebildete, interdisziplinär arbeitende Spezialisten, die angemessene Interpretation und Umsetzung in Entscheidungen erfordert Verständnis seitens der Entscheidungsträger.Der Verein zur Förderung der Technologiebewertung im Gesundheitswesen (Health Technology Assessment e.V. und das Deutsche Netzwerk Evidenzbasierte Medizin e.V. haben bereits 2006 ein HTA-Curriculum entwickelt, das als Grundlage für HTA-Fortbildungskurse sowohl für Nutzer von HTA-Informationen wie auch für HTA-Autoren dient. Das Curriculum ist u.a. Grundlage für Fortbildungskurse an mehreren Universitäten. Aufgrund methodischer Weiterentwicklungen wurde nun eine Überarbeitung des Curriculums erforderlich. Das Curriculum greift auf Struktur und Inhalte international etablierter Studiengänge zurück, berücksichtigt aber auch die Besonderheiten der Regulation von Technologien und der Entscheidungsfindung in den Gesundheitssystemen der deutschsprachigen Länder. Es ist in insgesamt 10 Module untergliedert, die neben Grundlagen und Prinzipien von HTA u.a. auf die Statusbestimmung von Technologien, Prioritätensetzung, Wissens- und Informationsmanagement, Methodik der Erstellung von HTA-Berichten und Interessenkonflikte eingehen. Gegenüber der ursprünglichen Version wurden viele Inhalte präzisiert und Erfahrungen aus Lehrveranstaltungen, die das Curriculum umsetzen, wurden berücksichtigt.

  5. Manuscritos freudianos inéditos: das ich und das es

    Directory of Open Access Journals (Sweden)

    Juan Carlos Cosentino

    2013-04-01

    Full Text Available Apresentamos aqui uma leitura crítica e comparada entre o rascunho e a forma final de O ego e o id, no momento em que nasce uma dissimetria entre o inconsciente reprimido e o material inconsciente que permanece não reconhecido. Partimos do capítulo "Os dois tipos de pulsão". O próprio Freud nos lembra que as questões aí levantadas retomam pensamentos iniciados em 1920. A partir da redefinição do Inconsciente e, mais tarde, com a reformulação da ideia de pulsão de morte, tais considerações permanecem mais perto da psicanálise que do texto Além.... Não obstante, o que denomina "nossa especulação" retorna nas conclusões do capítulo IV sobre o pressuposto da pulsão de morte. Com a irrupção do não-ligado, quais são os propósitos da pulsão de morte, em 1923, quando esta tem as mãos livres? Em 1924, constata que não-toda a pulsão está inscrita na representação. Intervém o silêncio da pulsão: essa fronteira, onde o id fala, o id goza e nada sabe.Freudian unpublished manuscripts: das Ich und das Es. This is a critical and comparative reading of the manuscripts of The Ego and the Id. We can read in this work a dissymmetry between the repressed unconscious and the material that remains unknown. We depart from chapter IV, "The two kinds of Drives". As Freud announces, the matters he displays resume thoughts from his writings of 1920. So, starting with the redefinition of Ucs and afterwards, with the reformulation of the idea of Todestrieb, they remain much closer to psychoanalysis than Beyond the pleasure principle. But what he calls, "our speculation" returns in the conclusions of chapter IV about the assumption of the Todestrieb. With the breaking through of the not bound: what are the purposes the Todestrieb serves, when, as he says in 1923, it has its hands free? In 1924 he confirms that not-all the drive is inscribed in the representation. The silence of the drive intervenes: this border, where id speaks, id enjoys

  6. Audit Committee: Um Estudo das Características das Empresas Listadas na BM&FBOVESPA

    Directory of Open Access Journals (Sweden)

    Milena Araújo Rego Amorim

    2017-01-01

    Full Text Available Objetivo: O objetivo deste estudo foi comparar as características dos comitês de auditoria de 65 empresas listadas na BM&FBovespa nos anos de 2014 e 2015, com as obtidas anteriormente nos anos de 2012 e 2013. Fundamento: O comitê de auditoria pode ser considerado um instrumento da governança corporativa, sendo formado por membros do conselho de administração, e sua composição deverá ser representada por membros independentes e especialistas na área da contabilidade ou financeira. Método: Foram investigadas a expertise, a independência e o tamanho, sendo realizado um estudo descritivo, com abordagem quantitativa e pesquisa documental. Resultados: Foi possível identificar que, em 2014, as áreas mais significativas foram engenharia, economia, administração e contabilidade, havendo poucas variações no ano de 2015. Quanto à independência dos membros, a maioria das empresas cumpriu com as boas práticas de governança corporativa, sendo que em 2014 aproximadamente 14% das empresas não atenderam a este requisito. Com mediana de 3,0 membros e médias de 3,22 em 2014 e 3,20 membros em 2015, cumpriram-se, em sua maioria, as recomendações da Comissão de Valores Mobiliários contidas na instrução n° 509, na Lei Sarbanes-Oxley e na Resolução BACEN nº 3.198/04. No que se refere ao tamanho, os resultados mostram que 49 empresas, nos anos referenciados, continham três ou mais membros em seus comitês, correspondendo, respectivamente, a 75,3% e 74,3%. Contribuições: Verificou-se que os comitês de auditoria não se apresentam de forma homogênea nas empresas e, mesmo com as recomendações de órgãos internos e da Lei Sarbanes-Oxley, apresentam-se de formas diversas.

  7. Potent antitumor bifunctional DNA alkylating agents, synthesis and biological activities of 3a-aza-cyclopenta[a]indenes.

    Science.gov (United States)

    Kakadiya, Rajesh; Dong, Huajin; Lee, Pei-Chih; Kapuriya, Naval; Zhang, Xiuguo; Chou, Ting-Chao; Lee, Te-Chang; Kapuriya, Kalpana; Shah, Anamik; Su, Tsann-Long

    2009-08-01

    A series of bifunctional DNA interstrand cross-linking agents, bis(hydroxymethyl)- and bis(carbamates)-8H-3a-azacyclopenta[a]indene-1-yl derivatives were synthesized for antitumor evaluation. The preliminary antitumor studies revealed that these agents exhibited potent cytotoxicity in vitro and antitumor therapeutic efficacy against human tumor xenografts in vivo. Furthermore, these derivatives have little or no cross-resistance to either Taxol or Vinblastine. Remarkably, complete tumor remission in nude mice bearing human breast carcinoma MX-1 xenograft by 13a,b and 14g,h and significant suppression against prostate adenocarcinoma PC3 xenograft by 13b were achieved at the maximum tolerable dose with relatively low toxicity. In addition, these agents induce DNA interstrand cross-linking and substantial G2/M phase arrest in human non-small lung carcinoma H1299 cells. The current studies suggested that these agents are promising candidates for preclinical studies.

  8. Aspectos sociotécnicos das TI & Relacionamento Humano & Sinergia

    Directory of Open Access Journals (Sweden)

    Sergio Vieira Holtz Filho

    2008-06-01

    Full Text Available As Tecnologias de Informação (TI estão entre os principais agentes de mudança sociais. Para gerir tais mudanças, uma miríade de áreas do conhecimento humano têm muito a contribuir para a abordagem dos aspectos sociotécnicos das TI e promover sinergia. Como uma organização empresarial atua no sentido de provocar mudanças no comportamento das pessoas, visando a melhoria contínua, esse processo de mudança provocada chama-se aprendizagem. Isto posto, neste artigo apresentaremos resultados observados em empresas em processo de reengenharia e submetidas a utilização de metodologias integradas (PDCA, Método Paulo Freire e Roteiro Integração de Equipes, abordando os aspectos sociotécnicos das TI & relacionamentos humanos pela praxe da pedagogia como elemento de sinergia.

  9. The data acquisition system (DAS) for the improved CERN SC

    CERN Document Server

    Beger, H; Fiebig, A; Schroot, H

    1975-01-01

    A digital data acquisition system (DAS) based on a minicomputer is described which registers the failure sequences in various equipment areas of the CERN synchrocyclotron (henceforward referred to as the SC). The avalanches of failure signals which occur from time to time are tapped from the alarm/security systems, time-resolved to 10 msec and recorded on a printer in order to aid SC failure diagnosis. The mechanisms of the DAS and its relation to the SC equipment are explained in some detail. All programs were constructed at assembler language level for speed and for ease of on-line program maintenance. The alarm sequences recorded have been of considerable help during the running in of the new radiofrequency system. Now that the new SC is operational, the DAS furnishes useful data from several equipment areas to the operators and engineers.

  10. Neurofibromin 1 Impairs Natural Killer T-Cell-Dependent Antitumor Immunity against a T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Jianyun Liu

    2018-01-01

    Full Text Available Neurofibromin 1 (NF1 is a tumor suppressor gene encoding a Ras GTPase that negatively regulates Ras signaling pathways. Mutations in NF1 are linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. In terms of antitumor immunity, CD1d-dependent natural killer T (NKT cells play an important role in the innate antitumor immune response. Generally, Type-I NKT cells protect (and Type-II NKT cells impair host antitumor immunity. We have previously shown that CD1d-mediated antigen presentation to NKT cells is regulated by cell signaling pathways. To study whether a haploinsufficiency in NF1 would affect CD1d-dependent activation of NKT cells, we analyzed the NKT-cell population as well as the functional expression of CD1d in Nf1+/− mice. Nf1+/− mice were found to have similar levels of NKT cells as wildtype (WT littermates. Interestingly, however, reduced CD1d expression was observed in Nf1+/− mice compared with their WT littermates. When inoculated with a T-cell lymphoma in vivo, Nf1+/− mice survived longer than their WT littermates. Furthermore, blocking CD1d in vivo significantly enhanced antitumor activity in WT, but not in Nf1+/− mice. In contrast, a deficiency in Type-I NKT cells increased antitumor activity in Nf1+/− mice, but not in WT littermates. Therefore, these data suggest that normal NF1 expression impairs CD1d-mediated NKT-cell activation and antitumor activity against a T-cell lymphoma.

  11. Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity.

    Science.gov (United States)

    Chen, Lili; He, Zhengxiang; Qin, Li; Li, Qinyan; Shi, Xibao; Zhao, Siting; Chen, Ling; Zhong, Nanshan; Chen, Xiaoping

    2011-01-01

    Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL) staining and decreased Ki-67 expression in tumors. Through natural killer (NK) cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+) T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria parasite may provide a novel strategy or therapeutic vaccine vector for anti-lung cancer

  12. Antitumor effect of malaria parasite infection in a murine Lewis lung cancer model through induction of innate and adaptive immunity.

    Directory of Open Access Journals (Sweden)

    Lili Chen

    Full Text Available BACKGROUND: Lung cancer is the most common malignancy in humans and its high fatality means that no effective treatment is available. Developing new therapeutic strategies for lung cancer is urgently needed. Malaria has been reported to stimulate host immune responses, which are believed to be efficacious for combating some clinical cancers. This study is aimed to provide evidence that malaria parasite infection is therapeutic for lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Antitumor effect of malaria infection was examined in both subcutaneously and intravenously implanted murine Lewis lung cancer (LLC model. The results showed that malaria infection inhibited LLC growth and metastasis and prolonged the survival of tumor-bearing mice. Histological analysis of tumors from mice infected with malaria revealed that angiogenesis was inhibited, which correlated with increased terminal deoxynucleotidyl transferase-mediated (TUNEL staining and decreased Ki-67 expression in tumors. Through natural killer (NK cell cytotoxicity activity, cytokine assays, enzyme-linked immunospot assay, lymphocyte proliferation, and flow cytometry, we demonstrated that malaria infection provided anti-tumor effects by inducing both a potent anti-tumor innate immune response, including the secretion of IFN-γ and TNF-α and the activation of NK cells as well as adaptive anti-tumor immunity with increasing tumor-specific T-cell proliferation and cytolytic activity of CD8(+ T cells. Notably, tumor-bearing mice infected with the parasite developed long-lasting and effective tumor-specific immunity. Consequently, we found that malaria parasite infection could enhance the immune response of lung cancer DNA vaccine pcDNA3.1-hMUC1 and the combination produced a synergistic antitumor effect. CONCLUSIONS/SIGNIFICANCE: Malaria infection significantly suppresses LLC growth via induction of innate and adaptive antitumor responses in a mouse model. These data suggest that the malaria

  13. O desenvolvimento das competências coletivas no terceiro setor

    Directory of Open Access Journals (Sweden)

    Lorena Tello‐Gamarra

    2015-11-01

    Full Text Available Dentro da abordagem de competências que se focam na gestão de recursos humanos, a abordagem de competências coletivas é uma área de pesquisa emergente. O objetivo da presente pesquisa é compreender as competências coletivas em um projeto voluntário do terceiro setor. O método utilizado foi o estudo de caso, tendo como objeto de estudo o terceiro setor, mais especificamente um projeto social. Para isto, se fez a escolha da Organização Não Governamental Parceiros Voluntários (PV com o projeto «Desenvolvimento de Princípios de Transparência e Prestação de Contas em Organizações da Sociedade Civil». Entre os resultados teóricos se identificaram 7 dimensões das competências coletivas. No que tange aos resultados empíricos referidos ao entendimento das competências coletivas no projeto voluntário do terceiro setor, observaram‐se 4 resultados: (1 todas as dimensões das competências coletivas foram comprovadas no projeto; (2 essas dimensões conseguiram ser determinantes para o desempenho do projeto, (3 as 7 dimensões influenciaram também o desempenho de toda a ONG, (4 as dimensões das competências coletivas do projeto contribuíram para que as organizações sociais pratiquem os princípios da transparência e da prestação de contas em suas atividades. Finalmente, o fato da confirmação das dimensões das competências coletivas como elemento‐chave do desenvolvimento abre a possiblidade de avançar na operacionalização deste construto.

  14. Structural organization of C{sub 60} fullerene, doxorubicin, and their complex in physiological solution as promising antitumor agents

    Energy Technology Data Exchange (ETDEWEB)

    Prylutskyy, Yu. I. [Taras Shevchenko National University of Kyiv (Ukraine); Evstigneev, M. P., E-mail: max-evstigneev@mail.ru [Belgorod State University, Department of Biology and Chemistry (Russian Federation); Cherepanov, V. V. [Institute of Physics of NAS of Ukraine (Ukraine); Kyzyma, O. A.; Bulavin, L. A.; Davidenko, N. A. [Taras Shevchenko National University of Kyiv (Ukraine); Scharff, P. [Ilmenau University of Technology (Germany)

    2015-01-15

    Specific features of structural self-organization of C{sub 60} fullerene (1 nm size range), antitumor antibiotic doxorubicin (Dox) and their complex in physiological solution (0.9 % NaCl) have been investigated by means of atomic-force microscopy, dynamic light scattering, and small-angle X-ray scattering. Significant ordering of the mixed system, C{sub 60} + Dox, was observed, suggesting the complexation between these drugs, and giving insight into the mechanism of enhancement of Dox antitumor effect on simultaneous administration with C{sub 60} fullerene.

  15. Antioxidant Activity, Antitumor Effect, and Antiaging Property of Proanthocyanidins Extracted from Kunlun Chrysanthemum Flowers

    Directory of Open Access Journals (Sweden)

    Siqun Jing

    2015-01-01

    Full Text Available The objective of the present study was to evaluate the antioxidant activity, antitumor effect, and antiaging property of proanthocyanidins from Kunlun Chrysanthemum flowers (PKCF grown in Xinjiang. In vitro antioxidant experiments results showed that the total antioxidant activity and the scavenging capacity of hydroxyl radicals (•OH and 1,1-diphenyl-2-picrylhydrazyl (DPPH• radicals increased in a concentration-dependent manner and were stronger than those of vitamin C. To investigate the antioxidant activity of PKCF in vivo, we used serum, liver, and kidney from mouse for the measurement of superoxide dismutase (SOD, malondialdehyde (MDA, and total antioxidant capacity (T-AOC. Results indicated that PKCF had antioxidative effect in vivo which significantly improved the activity of SOD and T-AOC and decreased MDA content. To investigate the antitumor activity of PKCF, we used H22 cells, HeLa cells, and Eca-109 cells with Vero cells as control. Inhibition ratio and IC50 values were measured by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay; PKCF showed great inhibitory activity on H22 cells and HeLa cells. We also used fruit flies as a model for analyzing the anti-aging property of PKCF. Results showed that PKCF has antiaging effect on Drosophila. Results of the present study demonstrated that PKCF could be a promising agent that may find applications in health care, medicine, and cosmetics.

  16. Antitumor activity of a novel and orally available inhibitor of serine palmitoyltransferase

    International Nuclear Information System (INIS)

    Yaguchi, Masahiro; Shibata, Sachio; Satomi, Yoshinori; Hirayama, Megumi; Adachi, Ryutaro; Asano, Yasutomi; Kojima, Takuto; Hirata, Yasuhiro; Mizutani, Akio; Kiba, Atsushi; Sagiya, Yoji

    2017-01-01

    Metabolic reprogramming is an essential hallmark of neoplasia. Therefore, targeting cancer metabolism, including lipid synthesis, has attracted much interest in recent years. Serine palmitoyltransferase (SPT) plays a key role in the initial and rate-limiting step of de novo sphingolipid biosynthesis, and inhibiting SPT activity prevents the proliferation of certain cancer cells. Here, we identified a novel and orally available SPT inhibitor, compound-2. Compound-2 showed an anti-proliferative effect in several cancer cell models, reducing the levels of the sphingolipids ceramide and sphingomyelin. In the presence of compound-2, exogenously added S1P partially compensated the intracellular sphingolipid levels through the salvage pathway by partially rescuing compound-2-induced cytotoxicity. This suggested that the mechanism underlying the anti-proliferative effect of compound-2 involved the reduction of sphingolipid levels. Indeed, compound-2 promoted multinuclear formation with reduced endogenous sphingomyelin levels specifically in a compound-2-sensitive cell line, indicating that the effect was induced by sphingolipid reduction. Furthermore, compound-2 showed potent antitumor activity without causing significant body weight loss in the PL-21 acute myeloid leukemia mouse xenograft model. Therefore, SPT may be an attractive therapeutic anti-cancer drug target for which compound-2 may be a promising new drug. - Highlights: • We discovered compound-2, a novel and orally available SPT inhibitor. • Compound-2 was cytotoxic against PL-21 acute myeloid leukemia cells. • Compound-2 showed antitumor activity in the PL-21 mouse xenograft model.

  17. Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses.

    Science.gov (United States)

    Zeelenberg, Ingrid S; Ostrowski, Matias; Krumeich, Sophie; Bobrie, Angélique; Jancic, Carolina; Boissonnas, Alexandre; Delcayre, Alain; Le Pecq, Jean-Bernard; Combadière, Béhazine; Amigorena, Sebastian; Théry, Clotilde

    2008-02-15

    Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic cells). The modes of tumor antigen capture by dendritic cells in vivo remain unclear. Here we examine the immunogenicity of the same model antigen secreted by live tumors either in association with membrane vesicles (exosomes) or as a soluble protein. We have artificially addressed the antigen to secreted vesicles by coupling it to the factor VIII-like C1C2 domain of milk fat globule epidermal growth factor-factor VIII (MFG-E8)/lactadherin. We show that murine fibrosarcoma tumor cells that secrete vesicle-bound antigen grow slower than tumors that secrete soluble antigen in immunocompetent, but not in immunodeficient, host mice. This growth difference is due to the induction of a more potent antigen-specific antitumor immune response in vivo by the vesicle-bound than by the soluble antigen. Finally, in vivo secretion of the vesicle-bound antigen either by tumors or by vaccination with naked DNA protects against soluble antigen-secreting tumors. We conclude that the mode of secretion can determine the immunogenicity of tumor antigens and that manipulation of the mode of antigen secretion may be used to optimize antitumor vaccination protocols.

  18. Antimicrobial, antibiofilm and antitumor activities of essential oil of Agastache rugosa from Xinjiang, China

    Directory of Open Access Journals (Sweden)

    Gong Haiyan

    2016-07-01

    Full Text Available In the study, we evaluated chemical composition and antimicrobial, antibiofilm, and antitumor activities of essential oils from dried leaf essential oil of leaf and flower of Agastache rugosa for the first time. Essential oil of leaf and flower was evaluated with GC and GC–MS methods, and the essential oil of flower revealed the presence of 21 components, whose major compounds were pulegone (34.1%, estragole (29.5%, and p-Menthan-3-one (19.2%. 26 components from essential oil of leaf were identified, the major compounds were p-Menthan-3-one (48.8% and estragole (20.8%. At the same time, essential oil of leaf, there is a very effective antimicrobial activity with MIC ranging from 9.4 to 42 μg ml−1 and potential antibiofilm, antitumor activities for essential oils of flower and leaf essential oil of leaf. The study highlighted the diversity in two different parts of A. rugosa grown in Xinjiang region and other places, which have different active constituents. Our results showed that this native plant may be a good candidate for further biological and pharmacological investigations.

  19. Increased oxidative stress mediates the antitumor effect of PARP inhibition in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Dong Hou

    2018-07-01

    Full Text Available PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful. Because PARP primarily functions in sensing and repairing DNA strand breaks, the therapeutic effect of PARP inhibition is generally believed to be attributed to impaired DNA repair. We here report that oxidative stress is also increased by PARP inhibition and mediates the antitumor effect. We showed that PARP1 is highly expressed in specimens of high grade serous ovarian carcinoma and its activity is required for unperturbed proliferation of ovarian cancer cells. Inhibition or depletion of PARP leads to not only an increase in DNA damage, but also an elevation in the levels of reactive oxygen species (ROS. Importantly, antioxidant N-acetylcysteine (NAC significantly attenuated the induction of DNA damage and the perturbation of proliferation by PARP inhibition or depletion. We further showed that NADPH oxidases 1 and 4 were significantly upregulated by PARP inhibition and were partially responsible for the induction of oxidative stress. Depletion of NOX1 and NOX4 partially rescued the growth inhibition of PARP1-deficient tumor xenografts. Our findings suggest that in addition to compromising the repair of DNA damage, PARP inhibition or depletion may exert extra antitumor effect by elevating oxidative stress in ovarian cancer cells. Keywords: PARP1, Oxidative stress, NADPH oxidases, Ovarian cancer

  20. Phenolic compounds of Hibiscus sabdariffa and influence of organic residues on its antioxidant and antitumoral properties

    Directory of Open Access Journals (Sweden)

    ASN. Formagio

    Full Text Available The aim of this study was to evaluate the phenolic and flavonoids contents and the antioxidant and antitumoral activity of leaf and calyx methanolic extracts from Hibiscus sabdariffa (roselle cultivated with poultry litter and organosuper® under three modes of application. The total phenolic content in the each extract was determined using the Folin-Ciocalteu reagent and for aluminium chloride flavonoids. The antioxidant parameters were analyzed using a 2, 2-diphenyl-1-picrylhydrazyl (DPPH. free radical scavenging assay. An antitumor colorimetric assay using sulforhodamine B. The highest contents of phenolic and flavonoids were observed in leaf extracts (389.98 and 104.52 mg g–1, respectively and calyx extracts (474.09 and 148.35 mg g–1, respectively from plants cultivated with organosuper®, although these values did not differ significantly from those observed for the other treatments. The average IC50 of leaves (43.48 μg mL–1 and calyces (37.15 μg mL–1 demonstrated that both have substances that may contribute to free radical scavenging action. The methanol extract from calyces showed significant selective activity against a leukemia line (K-562, with IC50 values of 0.12 mg mL–1 (organosuper® and 1.16 mg mL–1 (poultry litter, with concentration-dependent, cytotoxic and cytocidal effects.

  1. Multifunctional antitumor magnetite/chitosan-l-glutamic acid (core/shell) nanocomposites

    International Nuclear Information System (INIS)

    Santos, Daniela P.; Ruiz, M. Adolfina; Gallardo, Visitación; Zanoni, Maria Valnice B.; Arias, José L.

    2011-01-01

    The development of anticancer drug delivery systems based on biodegradable nanoparticles has been intended to maximize the localization of chemotherapy agents within tumor interstitium, along with negligible drug distribution into healthy tissues. Interestingly, passive and active drug targeting strategies to cancer have led to improved nanomedicines with great tumor specificity and efficient chemotherapy effect. One of the most promising areas in the formulation of such nanoplatforms is the engineering of magnetically responsive nanoparticles. In this way, we have followed a chemical modification method for the synthesis of magnetite/chitosan-l-glutamic acid (core/shell) nanostructures. These magnetic nanocomposites (average size ≈340 nm) exhibited multifunctional properties based on its capability to load the antitumor drug doxorubicin (along with an adequate sustained release) and its potential for hyperthermia applications. Compared to drug surface adsorption, doxorubicin entrapment into the nanocomposites matrix yielded a higher drug loading and a slower drug release profile. Heating characteristics of the magnetic nanocomposites were investigated in a high-frequency alternating magnetic gradient: a stable maximum temperature of 46 °C was successfully achieved within 40 min. To our knowledge, this is the first time that such kind of stimuli-sensitive nanoformulation with very important properties (i.e., magnetic targeting capabilities, hyperthermia, high drug loading, and little burst drug release) has been formulated for combined antitumor therapy against cancer.

  2. Strategies to Genetically Modulate Dendritic Cells to Potentiate Anti-Tumor Responses in Hematologic Malignancies

    Directory of Open Access Journals (Sweden)

    Annelisa M. Cornel

    2018-05-01

    Full Text Available Dendritic cell (DC vaccination has been investigated as a potential strategy to target hematologic malignancies, while generating sustained immunological responses to control potential future relapse. Nonetheless, few clinical trials have shown robust long-term efficacy. It has been suggested that a combination of surmountable shortcomings, such as selection of utilized DC subsets, DC loading and maturation strategies, as well as tumor-induced immunosuppression may be targeted to maximize anti-tumor responses of DC vaccines. Generation of DC from CD34+ hematopoietic stem and progenitor cells (HSPCs may provide potential in patients undergoing allogeneic HSPC transplantations for hematologic malignancies. CD34+ HSPC from the graft can be genetically modified to optimize antigen presentation and to provide sufficient T cell stimulatory signals. We here describe beneficial (gene-modifications that can be implemented in various processes in T cell activation by DC, among which major histocompatibility complex (MHC class I and MHC class II presentation, DC maturation and migration, cross-presentation, co-stimulation, and immunosuppression to improve anti-tumor responses.

  3. The Antitumor Effects of Triterpenoid Saponins from the Anemone flaccida and the Underlying Mechanism

    Directory of Open Access Journals (Sweden)

    Lin-Tao Han

    2013-01-01

    Full Text Available Anemone flaccida Fr. Schmidt, a family of ancient hopanoids, have been used as traditional Asian herbs for the treatments of inflammation and convulsant diseases. Previous study on HeLa cells suggested that triterpenoid saponins from Anemone flaccida Fr. Schmidt may have potential antitumor effect due to their apoptotic activities. Here, we confirmed the apoptotic activities of the following five triterpenoid saponins: glycoside St-I4a (1, glycoside St-J (2, anhuienoside E (3, hedera saponin B (4, and flaccidoside II (5 on human BEL-7402 and HepG2 hepatoma cell lines, as well as the model of HeLa cells treated with lipopolysaccharide (LPS. We found that COX-2/PGE2 signaling pathway, which plays key roles in the development of cancer, is involved in the antitumor activities of these saponins. These data provide the evidence that triterpenoid saponins can induce apoptosis via COX-2/PGE2 pathway, implying a preventive role of saponins from Anemone flaccida in tumor.

  4. Synthesis and antitumor evaluation of arctigenin derivatives based on antiausterity strategy.

    Science.gov (United States)

    Kudou, Naoki; Taniguchi, Akira; Sugimoto, Kenji; Matsuya, Yuji; Kawasaki, Masashi; Toyooka, Naoki; Miyoshi, Chika; Awale, Suresh; Dibwe, Dya Fita; Esumi, Hiroyasu; Kadota, Shigetoshi; Tezuka, Yasuhiro

    2013-02-01

    A series of new (-)-arctigenin derivatives with variably modified O-alkyl groups were synthesized and their preferential cytotoxicity was evaluated against human pancreatic cancer cell line PANC-1 under nutrient-deprived conditions. The results showed that monoethoxy derivative 4i (PC(50), 0.49 μM), diethoxy derivative 4h (PC(50), 0.66 μM), and triethoxy derivative 4m (PC(50), 0.78 μM) showed the preferential cytotoxicities under nutrient-deprived conditions, which were identical to or more potent than (-)-arctigenin (1) (PC(50), 0.80 μM). Among them, we selected the triethoxy derivative 4m and examined its in vivo antitumor activity using a mouse xenograft model. Triethoxy derivative 4m exhibited also in vivo antitumor activity with the potency identical to or slightly more than (-)-arctigenin (1). These results would suggest that a modification of (-)-arctigenin structure could lead to a new drug based on the antiausterity strategy. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  5. Epigenetic regulation of cancer biology and anti-tumor immunity by EZH2.

    Science.gov (United States)

    Christofides, Anthos; Karantanos, Theodoros; Bardhan, Kankana; Boussiotis, Vassiliki A

    2016-12-20

    Polycomb group proteins regulate chromatin structure and have an important regulatory role on gene expression in various cell types. Two polycomb group complexes (Polycomb repressive complex 1 (PRC1) and 2 (PRC2)) have been identified in mammalian cells. Both PRC1 and PRC2 compact chromatin, and also catalyze histone modifications. PRC1 mediates monoubiquitination of histone H2A, whereas PRC2 catalyzes methylation of histone H3 on lysine 27. These alterations of histones can lead to altered gene expression patterns by regulating chromatin structure. Numerous studies have highlighted the role of the PRC2 catalytic component enhancer of zeste homolog 2 (EZH2) in neoplastic development and progression, and EZH2 mutations have been identified in various malignancies. Through modulating the expression of critical genes, EZH2 is actively involved in fundamental cellular processes such as cell cycle progression, cell proliferation, differentiation and apoptosis. In addition to cancer cells, EZH2 also has a decisive role in the differentiation and function of T effector and T regulatory cells. In this review we summarize the recent progress regarding the role of EZH2 in human malignancies, highlight the molecular mechanisms by which EZH2 aberrations promote the pathogenesis of cancer, and discuss the anti-tumor effects of EZH2 targeting via activating direct anti-cancer mechanisms and anti-tumor immunity.

  6. Phenolic compounds of Hibiscus sabdariffa and influence of organic residues on its antioxidant and antitumoral properties.

    Science.gov (United States)

    Formagio, A S N; Ramos, D D; Vieira, M C; Ramalho, S R; Silva, M M; Zárate, N A H; Foglio, M A; Carvalho, J E

    2015-01-01

    The aim of this study was to evaluate the phenolic and flavonoids contents and the antioxidant and antitumoral activity of leaf and calyx methanolic extracts from Hibiscus sabdariffa (roselle) cultivated with poultry litter and organosuper® under three modes of application. The total phenolic content in the each extract was determined using the Folin-Ciocalteu reagent and for aluminium chloride flavonoids. The antioxidant parameters were analyzed using a 2, 2-diphenyl-1-picrylhydrazyl (DPPH.) free radical scavenging assay. An antitumor colorimetric assay using sulforhodamine B. The highest contents of phenolic and flavonoids were observed in leaf extracts (389.98 and 104.52 mg g-1, respectively) and calyx extracts (474.09 and 148.35 mg g-1, respectively) from plants cultivated with organosuper®, although these values did not differ significantly from those observed for the other treatments. The average IC50 of leaves (43.48 μg mL-1) and calyces (37.15 μg mL-1) demonstrated that both have substances that may contribute to free radical scavenging action. The methanol extract from calyces showed significant selective activity against a leukemia line (K-562), with IC50 values of 0.12 mg mL-1 (organosuper®) and 1.16 mg mL-1 (poultry litter), with concentration-dependent, cytotoxic and cytocidal effects.

  7. Antitumor effect of combination of the inhibitors of two new oncotargets: proton pumps and reverse transcriptase.

    Science.gov (United States)

    Lugini, Luana; Sciamanna, Ilaria; Federici, Cristina; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Fais, Stefano

    2017-01-17

    Tumor therapy needs new approaches in order to improve efficacy and reduce toxicity of the current treatments. The acidic microenvironment and the expression of high levels of endogenous non-telomerase reverse transcriptase (RT) are common features of malignant tumor cells. The anti-acidic proton pump inhibitor Lansoprazole (LAN) and the non-nucleoside RT inhibitor Efavirenz (EFV) have shown independent antitumor efficacy. LAN has shown to counteract drug tumor resistance. We tested the hypothesis that combination of LAN and EFV may improve the overall antitumor effects. We thus pretreated human metastatic melanoma cells with LAN and then with EFV, both in 2D and 3D spheroid models. We evaluated the treatment effect by proliferation and cell death/apoptosis assays in classical and in pulse administration experiments. The action of EFV was negatively affected by the tumor microenvironmental acidity, and LAN pretreatment overcame the problem. LAN potentiated the cytotoxicity of EFV to melanoma cells and, when administered during the drug interruption period, prevented the replacement of tumor cell growth.This study supports the implementation of the current therapies with combination of Proton Pumps and Reverse Transcriptase inhibitors.

  8. Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma.

    Science.gov (United States)

    Canitano, Andrea; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Federici, Cristina; Fais, Stefano

    2016-07-01

    Multiple Myeloma (MM) is the second most common hematological malignancy and is responsive to a limited number of drugs. Unfortunately, to date, despite the introduction of novel drugs, no relevant increase in survival rates has been obtained. Proton pump inhibitors (PPIs) have been shown to have significant antitumor action as single agents as well as in combination with chemotherapy. This study investigates the potential anti-tumor effectiveness of two PPIs, Lansoprazole and Omeprazole, against human MM cells. We found that Lansoprazole exerts straightforward efficacy against myeloma cells, even at suboptimal concentrations (50 µM), while Omeprazole has limited cytotoxic action. The Lansoprazole anti-MM effect was mostly mediated by a caspase-independent apoptotic-like cytotoxicity, with only a secondary anti-proliferative action. This study provides clear evidence supporting the use of Lansoprazole in the strive against MM with an efficacy proven much higher than current therapeutical approaches and without reported side effects. It is however conceivable that, consistent with the results obtained in other human tumors, Lansoprazole may well be combined with existing anti-myeloma therapies with the aim to improve the low level of efficacy of the current strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. MicroRNA-22 impairs anti-tumor ability of dendritic cells by targeting p38.

    Directory of Open Access Journals (Sweden)

    Xue Liang

    Full Text Available Dendritic cells (DCs play a critical role in triggering anti-tumor immune responses. Their intracellular p38 signaling is of great importance in controlling DC activity. In this study, we identified microRNA-22 (miR-22 as a microRNA inhibiting p38 protein expression by directly binding to the 3' untranslated region (3'UTR of its mRNA. The p38 down-regulation further interfered with the synthesis of DC-derived IL-6 and the differentiation of DC-driven Th17 cells. Moreover, overexpression of miR-22 in DCs impaired their tumor-suppressing ability while miR-22 inhibitor could reverse this phenomenon and improve the curative effect of DC-based immunotherapy. Thus, our results highlight a suppressive role for miR-22 in the process of DC-invoked anti-tumor immunity and that blocking this microRNA provides a new strategy for generating potent DC vaccines for patients with cancer.

  10. A Novel Time-Dependent CENP-E Inhibitor with Potent Antitumor Activity.

    Directory of Open Access Journals (Sweden)

    Akihiro Ohashi

    Full Text Available Centromere-associated protein E (CENP-E regulates both chromosome congression and the spindle assembly checkpoint (SAC during mitosis. The loss of CENP-E function causes chromosome misalignment, leading to SAC activation and apoptosis during prolonged mitotic arrest. Here, we describe the biological and antiproliferative activities of a novel small-molecule inhibitor of CENP-E, Compound-A (Cmpd-A. Cmpd-A inhibits the ATPase activity of the CENP-E motor domain, acting as a time-dependent inhibitor with an ATP-competitive-like behavior. Cmpd-A causes chromosome misalignment on the metaphase plate, leading to prolonged mitotic arrest. Treatment with Cmpd-A induces antiproliferation in multiple cancer cell lines. Furthermore, Cmpd-A exhibits antitumor activity in a nude mouse xenograft model, and this antitumor activity is accompanied by the elevation of phosphohistone H3 levels in tumors. These findings demonstrate the potency of the CENP-E inhibitor Cmpd-A and its potential as an anticancer therapeutic agent.

  11. The preparation of three selenium-containing Cordyceps militaris polysaccharides: Characterization and anti-tumor activities.

    Science.gov (United States)

    Liu, Fei; Zhu, Zhen-Yuan; Sun, Xiaoli; Gao, Hui; Zhang, Yong-Min

    2017-06-01

    In the present work, three fractions of selenized Cordyceps militaris polysaccharides (SeCPS) named SeCPS- I, SeCPS- II and SeCPS- III were isolated and purified by ultra-filtration. Their selenium content were measured as 541.3, 863.7 and 623.3μg/g respectively by a graphite furnace atomic absorption spectroscopy. The monosaccharide comformation analysis showed that they were mainly consisted of D-Mannose, D-Glucose, and D-Galactose in mole ratios of 1:7.63:0.83, 1:1.34:0.31 and 1:3.77:0.41 respectively. Their structure characteristics were compared by IFR and NMR spectroscopy. Scanning electron microscopy (SEM) and Congo red (CR) spectrophotometric method were used to investigate their morphological characteristics and conformational transition. SeCPS-II showed the strongest anti-tumor effects judging from the result of in vitro anti-tumor assays against two tumor cell lines (hepatocellular carcinoma HepG-2 cells and lung adenocarcinom A549 cells). Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Gold namoprtices enhance anti-tumor effect of radiotherapy to hypoxic tumor

    International Nuclear Information System (INIS)

    Kim, Mi Sun; Lee, Eun Jung; Kim, Jae Won; Keum, Ki Chang; Koom, Woong Sub; Chung, Ui Seok; Koh, Won Gun

    2016-01-01

    Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors

  13. Enhancement of antitumor activity of OK-432 (picibanil) by Triton X-114 phase partitioning.

    Science.gov (United States)

    Hashimoto, Masahito; Takashige, Katsuhiro; Furuyashiki, Maiko; Yoshidome, Keitaro; Sano, Ryoko; Kawamura, Yutaka; Ijichi, Shinji; Morioka, Hirofumi; Koide, Hiroyuki; Oku, Naoto; Moriya, Yoichiro; Kusumoto, Shoich; Suda, Yasuo

    2008-01-01

    OK-432 (Picibanil), a Streptococcal immunotherapeutic agent, has been used for immunotherapy of various cancers as a biological response modifier (BRM). However, OK-432 contains multiple components consisting of immunotherapeutic ones and contaminants which may weaken the effects or exert side-effects. In this study, we investigated extraction of contaminants from OK-432 using Triton X-114 (TX-114)-water phase partitioning and examined an antitumor effect of the resulting preparation. OK-432 was subjected to TX-114 partitioning to give residual precipitate designated as OK-TX-ppt. OK-TX-ppt exerted no TLR2-mediated activity, but induced interleukin (IL)-6 in human PBMC. OK-TX-ppt also induced tumor necrosis factor (TNF)-alpha, IL-10, IL-12, and interferon (IFN)-gamma in PBMC. Moreover, IFN-gamma-inducing activity of OK-TX-ppt was significantly higher and IL-10 production was lower than that of OK-432. In tumor-bearing mice model, administration of OK-TX-ppt i.p. extended the survival time of Meth-A-bearing mice compared to OK-432. OK-TX-ppt also increased the levels of IL-12 and IFN-gamma in mouse spleen cells in vitro. These results indicated that TX-114 partitioning removed some contaminants, which attenuates the antitumor effect, from OK-432 and increase the immunotherapeutic effects of OK-432.

  14. The Antitumor Activity of the Novel Compound Jesridonin on Human Esophageal Carcinoma Cells.

    Directory of Open Access Journals (Sweden)

    Cong Wang

    Full Text Available Jesridonin, a small molecule obtained through the structural modification of Oridonin, has extensive antitumor activity. In this study, we evaluated both its in vitro activity in the cancer cell line EC109 and its in vivo effect on tumor xenografts in nude mice. Apoptosis induced by Jesridonin was determined using an MTT assay, Annexin-V FITC assay and Hoechest 33258 staining. Apoptosis via mitochondrial and death receptor pathways were confirmed by detecting the regulation of MDM2, p53, and Bcl-2 family members and by activation of caspase-3/-8/-9. In addition, vena caudalis injection of Jesridonin showed significant inhibition of tumor growth in the xenograft model, and Jesridonin-induced cell apoptosis in tumor tissues was determined using TUNEL. Biochemical serum analysis of alkaline phosphatase (ALP, alanine transaminase (ALT, aspartate transaminase (AST, gamma-glutamyl transferase (GGT, total protein (TP and albumin (ALB indicated no obvious effects on liver function. Histopathological examination of the liver, kidney, lung, heart and spleen revealed no signs of JD-induced toxicity. Taken together, these results demonstrated that Jesridonin exhibits antitumor activity in human esophageal carcinomas EC109 cells both in vitro and in vivo and demonstrated no adverse effects on major organs in nude mice. These studies provide support for new drug development.

  15. Oridonin Loaded Solid Lipid Nanoparticles Enhanced Antitumor Activity in MCF-7 Cells

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2014-01-01

    Full Text Available Oridonin (ORI, a famous diterpenoid from Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis and autophagy-inducing activity in human cancer therapy, while clinical application of ORI is limited by its strong hydrophobicity and rapid plasma clearance. The purpose of this study was to evaluate whether the antitumor activity of ORI could be enhanced by loading into solid lipid nanoparticles (SLNs. ORI-loaded SLNs were prepared by hot high pressure homogenization with narrow size distribution and good entrapment efficacy. MTT assay indicated that ORI-loaded SLNs enhanced the inhibition of proliferation against several human cancer cell lines including breast cancer MCF-7 cells, hepatocellular carcinoma HepG 2 cells, and lung carcinoma A549 cells compared with free ORI, while no significant enhancement of toxicity to human mammary epithelial MCF-10A cells was shown. Meanwhile, flow cytometric analysis demonstrated that ORI-SLNs induced more significant cell cycle arrest at S and decreased cell cycle arrest at G1/G0 phase in MCF-7 cells than bulk ORI solution. Hoechst 33342 staining and Annexin V/PI assay indicated that apoptotic rates of cells treated with ORI-loaded SLNs were higher compared with free ORI. In summary, our data indicated that SLNs may be a potential carrier for enhancing the antitumor effect of hydrophobic drug ORI.

  16. Multifunctional antitumor magnetite/chitosan- l-glutamic acid (core/shell) nanocomposites

    Science.gov (United States)

    Santos, Daniela P.; Ruiz, M. Adolfina; Gallardo, Visitación; Zanoni, Maria Valnice B.; Arias, José L.

    2011-09-01

    The development of anticancer drug delivery systems based on biodegradable nanoparticles has been intended to maximize the localization of chemotherapy agents within tumor interstitium, along with negligible drug distribution into healthy tissues. Interestingly, passive and active drug targeting strategies to cancer have led to improved nanomedicines with great tumor specificity and efficient chemotherapy effect. One of the most promising areas in the formulation of such nanoplatforms is the engineering of magnetically responsive nanoparticles. In this way, we have followed a chemical modification method for the synthesis of magnetite/chitosan- l-glutamic acid (core/shell) nanostructures. These magnetic nanocomposites (average size ≈340 nm) exhibited multifunctional properties based on its capability to load the antitumor drug doxorubicin (along with an adequate sustained release) and its potential for hyperthermia applications. Compared to drug surface adsorption, doxorubicin entrapment into the nanocomposites matrix yielded a higher drug loading and a slower drug release profile. Heating characteristics of the magnetic nanocomposites were investigated in a high-frequency alternating magnetic gradient: a stable maximum temperature of 46 °C was successfully achieved within 40 min. To our knowledge, this is the first time that such kind of stimuli-sensitive nanoformulation with very important properties (i.e., magnetic targeting capabilities, hyperthermia, high drug loading, and little burst drug release) has been formulated for combined antitumor therapy against cancer.

  17. Antitumor and angiostatic activities of the antimicrobial peptide dermaseptin B2.

    Science.gov (United States)

    van Zoggel, Hanneke; Carpentier, Gilles; Dos Santos, Célia; Hamma-Kourbali, Yamina; Courty, José; Amiche, Mohamed; Delbé, Jean

    2012-01-01

    Recently, we have found that the skin secretions of the Amazonian tree frog Phyllomedusa bicolor contains molecules with antitumor and angiostatic activities and identified one of them as the antimicrobial peptide dermaseptin (Drs) B2. In the present study we further explored the in vitro and in vivo antitumor activity of this molecule and investigated its mechanism of action. We showed that Drs B2 inhibits the proliferation and colony formation of various human tumor cell types, and the proliferation and capillary formation of endothelial cells in vitro. Furthermore, Drs B2 inhibited tumor growth of the human prostate adenocarcinoma cell line PC3 in a xenograft model in vivo. Research on the mechanism of action of Drs B2 on tumor PC3 cells demonstrated a rapid increasing amount of cytosolic lactate dehydrogenase, no activation of caspase-3, and no changes in mitochondrial membrane potential. Confocal microscopy analysis revealed that Drs B2 can interact with the tumor cell surface, aggregate and penetrate the cells. These data together indicate that Drs B2 does not act by apoptosis but possibly by necrosis. In conclusion, Drs B2 could be considered as an interesting and promising pharmacological and therapeutic leader molecule for the treatment of cancer.

  18. Antitumor and angiostatic activities of the antimicrobial peptide dermaseptin B2.

    Directory of Open Access Journals (Sweden)

    Hanneke van Zoggel

    Full Text Available Recently, we have found that the skin secretions of the Amazonian tree frog Phyllomedusa bicolor contains molecules with antitumor and angiostatic activities and identified one of them as the antimicrobial peptide dermaseptin (Drs B2. In the present study we further explored the in vitro and in vivo antitumor activity of this molecule and investigated its mechanism of action. We showed that Drs B2 inhibits the proliferation and colony formation of various human tumor cell types, and the proliferation and capillary formation of endothelial cells in vitro. Furthermore, Drs B2 inhibited tumor growth of the human prostate adenocarcinoma cell line PC3 in a xenograft model in vivo. Research on the mechanism of action of Drs B2 on tumor PC3 cells demonstrated a rapid increasing amount of cytosolic lactate dehydrogenase, no activation of caspase-3, and no changes in mitochondrial membrane potential. Confocal microscopy analysis revealed that Drs B2 can interact with the tumor cell surface, aggregate and penetrate the cells. These data together indicate that Drs B2 does not act by apoptosis but possibly by necrosis. In conclusion, Drs B2 could be considered as an interesting and promising pharmacological and therapeutic leader molecule for the treatment of cancer.

  19. Melittin exerts an antitumor effect on non‑small cell lung cancer cells.

    Science.gov (United States)

    Zhang, Su-Fang; Chen, Zhe

    2017-09-01

    Lung cancer accounts for a significant percentage of all cancer‑associated mortalities in men and women, with non‑small cell lung cancer being the most frequently occurring type of lung cancer. Melittin is the principal active component of apitoxin (bee venom) that has been reported to exert anti‑chronic inflammatory and anti‑cancer effects. In the present study, the antitumor effect of melittin was evaluated using in vivo and in vitro analyses. The results demonstrated that melittin significantly inhibited the epidermal growth factor‑induced invasion and migration of non‑small cell lung cancer cells. Subcutaneous injection of melittin at doses of 1 and 10 mg/kg significantly suppressed non‑small cell lung cancer tumor growth by 27 and 61%, respectively. In addition, melittin significantly inhibited the secretion of vascular endothelial growth factor (VEGF) in non‑small cell lung cancer cells. Furthermore, melittin decreased the protein expression of VEGF and hypoxia‑inducible factor 1‑α. Therefore, the antitumor activity of melittin may be associated with the anti‑angiogenic actions of inhibiting the VEGF and hypoxia‑inducible factor signaling pathways.

  20. Antivascular and antitumor properties of the tubulin-binding chalcone TUB091.

    Science.gov (United States)

    Canela, María-Dolores; Noppen, Sam; Bueno, Oskía; Prota, Andrea E; Bargsten, Katja; Sáez-Calvo, Gonzalo; Jimeno, María-Luisa; Benkheil, Mohammed; Ribatti, Domenico; Velázquez, Sonsoles; Camarasa, María-José; Díaz, J Fernando; Steinmetz, Michel O; Priego, Eva-María; Pérez-Pérez, María-Jesús; Liekens, Sandra

    2017-02-28

    We investigated the microtubule-destabilizing, vascular-targeting, anti-tumor and anti-metastatic activities of a new series of chalcones, whose prototype compound is (E)-3-(3''-amino-4''-methoxyphenyl)-1-(5'-methoxy-3',4'-methylendioxyphenyl)-2-methylprop-2-en-1-one (TUB091). X-ray crystallography showed that these chalcones bind to the colchicine site of tubulin and therefore prevent the curved-to-straight structural transition of tubulin, which is required for microtubule formation. Accordingly, TUB091 inhibited cancer and endothelial cell growth, induced G2/M phase arrest and apoptosis at 1-10 nM. In addition, TUB091 displayed vascular disrupting effects in vitro and in the chicken chorioallantoic membrane (CAM) assay at low nanomolar concentrations. A water-soluble L-Lys-L-Pro derivative of TUB091 (i.e. TUB099) showed potent antitumor activity in melanoma and breast cancer xenograft models by causing rapid intratumoral vascular shutdown and massive tumor necrosis. TUB099 also displayed anti-metastatic activity similar to that of combretastatin A4-phosphate. Our data indicate that this novel class of chalcones represents interesting lead molecules for the design of vascular disrupting agents (VDAs). Moreover, we provide evidence that our prodrug approach may be valuable for the development of anti-cancer drugs.

  1. Assessment of antitumoral and antimicrobial effects of a maslinic acid derivative

    Directory of Open Access Journals (Sweden)

    Ioana Z. Pavel

    2016-12-01

    Full Text Available INTRODUCTION Maslinic acid, a naturally occurring triterpene, has been reported to possess several therapeutic effects including antioxidant, anti-inflammatory and antiparasitic properties. Structural changes of the compound led to the development of new derivatives in order to expand the spectrum of activities. OBJECTIVES AND BACKGROUND The present study was purposed to assess the in vitro antitumoral and antibacterial effects of a maslinic acid derivative, namely benzyl (2α, 3β 2,3-diacetoxy-olean-12- en-28-amide (EM2. MATERIALS AND METHODS Four compound concentrations (12.5, 25, 50 and 100 µM were evaluated for their cytotoxic effect on A375 human melanoma and B164A5 murine melanoma cell lines using the MTT assay. Furthermore, EM2 was tested on ten bacterial strains by means of agar disk diffusion method with the assessment of the inhibition zone diameters at 24h period of time. RESULTS EM2 elicited a dose-dependent cytotoxic effect on both melanoma cell lines. Regarding the antibacterial activity, EM2 determined a significant growth inhibition on Streptococcus pyogenes (20 ± 0.26 mm and Staphylococcus aureus (13 ± 0.19 mm. CONCLUSIONS The tested maslinic acid derivative is a promising antitumoral agent against skin cancer and antimicrobial agent against cocci bacteria. Graphical abstract: EM2 in vitro effects

  2. Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Mori Y

    2017-11-01

    Full Text Available Yuki Mori,1 Toshiharu Shirai,1 Ryu Terauchi,1 Shinji Tsuchida,1 Naoki Mizoshiri,1 Daichi Hayashi,1 Yuji Arai,2 Tunao Kishida,3 Osam Mazda,3 Toshikazu Kubo1 1Department of Orthopaedics, 2Department of Sports and Para-Sports Medicine, 3Department of Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan Abstract: There are very few treatments for musculoskeletal tumors, compared to other cancers; thus, novel therapeutic drugs are needed. Pristimerin (PM is a triterpene compound isolated from plant extracts that reportedly has antitumor effects on various cancers, such as of the breast and prostate. The purpose of this study was to evaluate the antitumor effects of PM on human osteosarcoma cells. Treatment of the human osteosarcoma cell lines, MNNG and 143B, with PM led to a dose-dependent decrease in cell viability. The effects of PM on apoptosis were evaluated with the Annexin V/propidium iodide assay and analysis of caspases 3, 8, and 9 activities. Western blot analysis showed that PM caused a decrease in the expression of Akt, mTOR, and NF-κB. The volumes and weights of human osteosarcoma xenografts decreased significantly with PM treatment. The results of this study revealed that PM can inhibit human osteosarcoma growth in vitro and in vivo, and may be a novel therapeutic agent for the disease. Keywords: pristimerin, osteosarcoma, apoptosis, caspase, Akt 

  3. Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo.

    Science.gov (United States)

    Mori, Yuki; Shirai, Toshiharu; Terauchi, Ryu; Tsuchida, Shinji; Mizoshiri, Naoki; Hayashi, Daichi; Arai, Yuji; Kishida, Tunao; Mazda, Osam; Kubo, Toshikazu

    2017-01-01

    There are very few treatments for musculoskeletal tumors, compared to other cancers; thus, novel therapeutic drugs are needed. Pristimerin (PM) is a triterpene compound isolated from plant extracts that reportedly has antitumor effects on various cancers, such as of the breast and prostate. The purpose of this study was to evaluate the antitumor effects of PM on human osteosarcoma cells. Treatment of the human osteosarcoma cell lines, MNNG and 143B, with PM led to a dose-dependent decrease in cell viability. The effects of PM on apoptosis were evaluated with the Annexin V/propidium iodide assay and analysis of caspases 3, 8, and 9 activities. Western blot analysis showed that PM caused a decrease in the expression of Akt, mTOR, and NF-κB. The volumes and weights of human osteosarcoma xenografts decreased significantly with PM treatment. The results of this study revealed that PM can inhibit human osteosarcoma growth in vitro and in vivo, and may be a novel therapeutic agent for the disease.

  4. Antitumor activity of biflorin, an o-naphthoquinone isolated from Capraria biflora.

    Science.gov (United States)

    Vasconcellos, Marne Carvalho de; Bezerra, Daniel Pereira; Fonseca, Aluísio Marques; Pereira, Márcio Roberto Pinho; Lemos, Telma Leda Gomes; Pessoa, Otília Deusdênia Loiola; Pessoa, Cláudia; Moraes, Manoel Odorico de; Alves, Ana Paula Negreiros Nunes; Costa-Lotufo, Letícia Veras

    2007-08-01

    Pharmacological studies with an aqueous extract obtained from leaves of Capraria biflora showed potent cytotoxic, analgesic, antimicrobial and anti-inflammatory activities. It has been demonstrated that biflorin possesses an in vitro cytotoxic activity against tumor cells. The in vivo antitumor activity of biflorin was evaluated on two mouse models, sarcoma 180 and Ehrlich carcinoma. Biflorin was active against both tumors with a very similar profile. In addition, biflorin was also able to increase the response elicited by 5-FU in mice inoculated with both tumors. The results showed a decrease in Ki67 staining in tumor cells from treated-animals when compared with non-treated groups, which suggests an inhibition of tumor proliferation rate. Histopathological analysis from kidneys and liver showed that biflorin possessed weak and reversible toxic effects. It was also demonstrated that biflorin acts as an immunoadjuvant agent, rising the production of ovalbumin-specific antibodies and inducing a discreet increase of the white pulp and nest of megakaryocytic in spleen of treated mice, which can be related to its antitumor properties.

  5. Macrophage PPARγ inhibits Gpr132 to mediate the anti-tumor effects of rosiglitazone

    Science.gov (United States)

    Cheng, Wing Yin; Huynh, HoangDinh; Chen, Peiwen; Peña-Llopis, Samuel; Wan, Yihong

    2016-01-01

    Tumor-associated macrophage (TAM) significantly contributes to cancer progression. Human cancer is enhanced by PPARγ loss-of-function mutations, but inhibited by PPARγ agonists such as TZD diabetes drugs including rosiglitazone. However, it remains enigmatic whether and how macrophage contributes to PPARγ tumor-suppressive functions. Here we report that macrophage PPARγ deletion in mice not only exacerbates mammary tumor development but also impairs the anti-tumor effects of rosiglitazone. Mechanistically, we identify Gpr132 as a novel direct PPARγ target in macrophage whose expression is enhanced by PPARγ loss but repressed by PPARγ activation. Functionally, macrophage Gpr132 is pro-inflammatory and pro-tumor. Genetic Gpr132 deletion not only retards inflammation and cancer growth but also abrogates the anti-tumor effects of PPARγ and rosiglitazone. Pharmacological Gpr132 inhibition significantly impedes mammary tumor malignancy. These findings uncover macrophage PPARγ and Gpr132 as critical TAM modulators, new cancer therapeutic targets, and essential mediators of TZD anti-cancer effects. DOI: http://dx.doi.org/10.7554/eLife.18501.001 PMID:27692066

  6. Gold namoprtices enhance anti-tumor effect of radiotherapy to hypoxic tumor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Sun; Lee, Eun Jung; Kim, Jae Won; Keum, Ki Chang; Koom, Woong Sub [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Chung, Ui Seok; Koh, Won Gun [Dept. of Chemical and Biomolecular Engineering, Yonsei University, Seoul (Korea, Republic of)

    2016-09-15

    Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

  7. Tertiary Lymphoid Structures in Cancer: Drivers of Antitumor Immunity, Immunosuppression, or Bystander Sentinels in Disease?

    Science.gov (United States)

    Colbeck, Emily Jayne; Ager, Ann; Gallimore, Awen; Jones, Gareth Wyn

    2017-01-01

    Secondary lymphoid organs are integral to initiation and execution of adaptive immune responses. These organs provide a setting for interactions between antigen-specific lymphocytes and antigen-presenting cells recruited from local infected or inflamed tissues. Secondary lymphoid organs develop as a part of a genetically preprogrammed process during embryogenesis. However, organogenesis of secondary lymphoid tissues can also be recapitulated in adulthood during de novo lymphoid neogenesis of tertiary lymphoid structures (TLSs). These ectopic lymphoid-like structures form in the inflamed tissues afflicted by various pathological conditions, including cancer, autoimmunity, infection, or allograft rejection. Studies are beginning to shed light on the function of such structures in different disease settings, raising important questions regarding their contribution to progression or resolution of disease. Data show an association between the tumor-associated TLSs and a favorable prognosis in various types of human cancer, attracting the speculation that TLSs support effective local antitumor immune responses. However, definitive evidence for the role for TLSs in fostering immune responses in vivo are lacking, with current data remaining largely correlative by nature. In fact, some more recent studies have even demonstrated an immunosuppressive, tumor-promoting role for cancer-associated TLSs. In this review, we will discuss what is known about the development of cancer-associated TLSs and the current understanding of their potential role in the antitumor immune response. PMID:29312327

  8. Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity.

    Science.gov (United States)

    Wang, Dongrui; Aguilar, Brenda; Starr, Renate; Alizadeh, Darya; Brito, Alfonso; Sarkissian, Aniee; Ostberg, Julie R; Forman, Stephen J; Brown, Christine E

    2018-05-17

    Chimeric antigen receptor-modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2). Upon stimulation with IL13Rα2+ GBM cells, the CD8+ CAR T cells exhibited robust short-term effector function but became rapidly exhausted. By comparison, the CD4+ CAR T cells persisted after tumor challenge and sustained their effector potency. Mixing with CD4+ CAR T cells failed to ameliorate the effector dysfunction of CD8+ CAR T cells, while surprisingly, CD4+ CAR T cell effector potency was impaired when coapplied with CD8+ T cells. In orthotopic GBM models, CD4+ outperformed CD8+ CAR T cells, especially for long-term antitumor response. Further, maintenance of the CD4+ subset was positively correlated with the recursive killing ability of CAR T cell products derived from GBM patients. These findings identify CD4+ CAR T cells as a highly potent and clinically important T cell subset for effective CAR therapy.

  9. Carcinogenic and antitumor effects of aminotriazole on acatalasemic and normal catalase mice

    International Nuclear Information System (INIS)

    Feinstein, R.N.; Fry, R.J.M.; Staffeidt, E.F.

    1978-01-01

    Dietary 3-amino-1H-1,2,4-triazole (AT), although carcinogenic when administered alone, was an antitumor agent when combined with certain other carcinogenic stimuli. The carcinogenic effect was prominent in the livers of C3H mice; thyroid tumors were less common because they required a longer period of development, and the life-span of the animal was shortened by the AT diet. The antitumor effects of AT included: delay in appearance of mammary tumors, striking reduction in γ-radiation-induced lymphomas, and sharp reduction in neutron radiation-induced harderian gland and ovarian tumors. On an AT diet, the inbred C3H acatalasemic mouse substrain developed more liver tumors, starting earlier, than did the C3H normal catalase substrain. We suggest that our findings pointed to a possible relevance of catalase and H 2 O 2 in carcinogenesis. The most probable mechanism for the increased incidence of liver tumors in AT-treated acatalasemic mice was the diminished rate of degradation of endogenous H 2 O 2

  10. Two photon microscopy intravital study of DC-mediated anti-tumor response of NK cells

    Science.gov (United States)

    Caccia, Michele; Gorletta, Tatiana; Sironi, Laura; Zanoni, Ivan; Salvetti, Cristina; Collini, Maddalena; Granucci, Francesca; Chirico, Giuseppe

    2010-02-01

    Recent studies have demonstrated that dendritic cells (DCs) play a crucial role in the activation of Natural Killer cells (NKs) that are responsible for anti-tumor innate immune responses. The focus of this report is on the role of pathogen associated molecular pattern (PAMP) activated-DCs in inducing NK cell-mediated anti-tumor responses. Mice transplanted sub-cute (s.c.) with AK7 cells, a mesothelioma cell line sensitive to NK cell responses, are injected with fluorescent NK cells and DC activation is then induced by s.c. injection of Lipopolysaccharide (LPS). Using 4 dimensional tracking we follow the kinetic behavior of NK cells at the Draining Lymph-Node (DLN). As control, noninflammatory conditions are also evaluated. Our data suggest that NK cells are recruited to the DLN where they can interact with activated-DCs with a peculiar kinetic behavior: short lived interactions interleaved by rarer longer ones. We also found that the changes in the NK dynamic behavior in inflammatory conditions clearly affect relevant motility parameters such as the instantaneous and average velocity and the effective diffusion coefficient. This observation suggests that NK cells and activated-DCs might efficiently interact in the DLN, where cells could be activated. Therefore the interaction between activated-DCs and NK cells in DLN is not only a reality but it may be also crucial for the start of the immune response of the NKs.

  11. Improved Production and Antitumor Properties of Triterpene Acids from Submerged Culture of Ganoderma lingzhi.

    Science.gov (United States)

    Wang, Xiao-Ling; Ding, Zhong-Yang; Liu, Gao-Qiang; Yang, Hailong; Zhou, Guo-Ying

    2016-10-20

    Triterpene acids (TAs) are the major bioactive constituents in the medicinal fungus Ganoderma lingzhi . However, fermentative production of TAs has not been optimized for commercial use, and whether the TAs isolated from G. lingzhi submerged culture mycelia possess antitumor activity needs to be further proven. In this study, enhanced TA yield and productivity were attained with G. lingzhi using response surface methodology. The interactions of three variables were studied using a Box-Benhnken design, namely initial pH, dissolved oxygen (DO) and fermentation temperature. The optimum conditions were an initial pH of 5.9, 20.0% DO and 28.6 °C. These conditions resulted in a TA yield of 308.1 mg/L in a 5-L stirred bioreactor. Furthermore, the optimized conditions were then successfully scaled up to a production scale of 200 L, and maximum TA production and productivity of 295.3 mg/L and 49.2 mg/L/day were achieved, which represented 80.9% and 111.5% increases, respectively, compared with the non-optimized conditions. Additionally, the triterpene acid extract (TAE) from G. lingzhi mycelia was found to be cytotoxic to the SMMC-7721 and SW620 cell lines in vitro, and the TAE exhibited dose-dependent antitumor activity against the solid tumor sarcoma 180 in vivo. Chemical analysis revealed that the key active triterpene compounds, ganoderic acid T and ganoderic acid Me, predominated in the extract.

  12. Anti-tumor and anti-angiogenic ergosterols from Ganoderma lucidum

    Science.gov (United States)

    Chen, Shaodan; Yong, Tianqiao; Zhang, Yifang; Su, Jiyan; Jiao, Chunwei; Xie, Yizhen

    2017-10-01

    This study was carried out to isolate chemical constituents from the lipid enriched fraction of Ganoderma lucidum extract and to evaluate their anti-proliferative effect on cancer cell lines and human umbilical vein endothelial cells. Ergosterol derivatives (1-14) were isolated from the lipid enriched fraction of G. lucidum. Their structures were established on the basis of spectroscopic analyses or by comparison of mass and NMR spectral data with those reported previously. Amongst, compound 1 was isolated and identified as a new compound. All the compounds were evaluated for their inhibitory effect on tumor cells and human umbilical vein endothelial cells in vitro. Compounds 9-13 displayed inhibitory activity against two tumor cell lines and human umbilical vein endothelial cells, which indicated that these four compounds had both anti-tumor and anti-angiogenesis activities. Compound 2 had significant selective inhibition against two tumor cell lines, while 3 exhibited selective inhibition against human umbilical vein endothelial cells. The structure–activity relationships for inhibiting human HepG2 cells were revealed by 3D-QASR. Ergosterol content in different parts of the raw material and products of G. lucidum was quantified. This study provides a basis for further development and utilization of ergosterol derivatives as natural nutraceuticals and functional food ingredients, or as source of new potential antitumor or anti-angiogenesis chemotherapy agent.

  13. Research progress of PARP-1 inhibitors in antitumor drugs and radionuclide markers

    International Nuclear Information System (INIS)

    Zhao Lingzhou; Zhang Huabei

    2011-01-01

    Poly(ADP-ribose)polymerase (PARP) is a new target in the cancer treatment nowadays. PARP not only can repair DNA damage, regulate and control transcription, maintain the stability of intracellular environment and genome, regulate the process of cell survival and death, but also is the main transcription factor in the development of inflammation and the process of cancer. To inhibit PARP activity can reduce the DNA repair function in tumor cells, and increase the sensibility to DNA damage agents, so as to improve the efficacy of radiation therapy and chemotherapy for tumor. A number of studies have suggested that, whether used alone or combination with other chemotherapy drugs, PARP inhibitors show the potential in the anti-tumor therapeutic areas. In this paper, PARP-1 inhibitors were reviewed in antitumor research progress. According to the stage of development , PARP-1 inhibitors are classified. Several representative PARP-1 inhibitors, in clinical trials, with potential clinical value were introduced. Positron emission tomography (PET), uses the main short half-life elementary in human body as tracer, and at the molecular level, achieve the no wound, quantitative and dynamic observation about the different changes of metabolites or drugs in the body. PET is the most advanced contemporary video diagnostic technology, and this paper simply introduce the research progress of PARP-1 inhibitors labeled with radioactive nuclides. (authors)

  14. Fluorescent nanodiamonds engage innate immune effector cells: A potential vehicle for targeted anti-tumor immunotherapy.

    Science.gov (United States)

    Suarez-Kelly, Lorena P; Campbell, Amanda R; Rampersaud, Isaac V; Bumb, Ambika; Wang, Min S; Butchar, Jonathan P; Tridandapani, Susheela; Yu, Lianbo; Rampersaud, Arfaan A; Carson, William E

    2017-04-01

    Fluorescent nanodiamonds (FNDs) are nontoxic, infinitely photostable, and emit fluorescence in the near infrared region. Natural killer (NK) cells and monocytes are part of the innate immune system and are crucial to the control of carcinogenesis. FND-mediated stimulation of these cells may serve as a strategy to enhance anti-tumor activity. FNDs were fabricated with a diameter of 70±28 nm. Innate immune cell FND uptake, viability, surface marker expression, and cytokine production were evaluated in vitro. Evaluation of fluorescence emission from the FNDs was conducted in an animal model. In vitro results demonstrated that treatment of immune cells with FNDs resulted in significant dose-dependent FND uptake, no compromise in cell viability, and immune cell activation. FNDs were visualized in an animal model. Hence, FNDs may serve as novel agents with "track and trace" capabilities to stimulate innate immune cell anti-tumor responses, especially as FNDs are amenable to surface-conjugation with immunomodulatory molecules. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Microencapsulation of anti-tumor, antibiotic and thrombolytic drugs in microgravity

    Science.gov (United States)

    Morrison, Dennis R.; Mosier, Benjamin; Cassanto, John

    1994-01-01

    Encapsulation of cytotoxic or labile drugs enables targeted delivery and sustained release kinetics that are not available with intravenous injection. A new liquid-liquid diffusion process has been developed for forming unique microcapsules that contain both aqueous and hydrocarbon soluble drugs. Microgravity experiments, on sounding rockets (1989-92) and Shuttle missions STS-52 (1992) and STS-56 (1993) using an automated Materials Dispersion Apparatus, produced multi-lamellar microcapsules containing both Cis-platinum (anti-tumor drug) and iodinated poppy seed oil (a radiocontrast medium), surrounded by a polyglyceride skin. Microcapsules formed with amoxicillin (antibiotic) or urokinase (a clot dissolving enzyme), co-encapsulated with IPO, are still intact after two years. Microcapsules were formed with the drug so concentrated that crystals formed inside. Multi-layered microspheres, with both hydrophobic drug compartments, can enable diffusion of complementary drugs from the same microcapsule, e.g. antibiotics and immuno-stimulants to treat resistant infections or multiple fibrinolytic drugs to dissolve emboli. Co-encapsulation of enough radio-contrast medium enables oncologists to monitor the delivery of anti-tumor microcapsules to target tumors using computerized tomography and radiography that would track the distribution of microcapsules after release from the intra-arterial catheter. These microcapsules could have important applications in chemotheraphy of certain liver, kidney, brain and other tumors.

  16. Qual a relevância das celebridades na publicidade?

    OpenAIRE

    Xara-Brasil, Maria Rita de Aguiar

    2013-01-01

    Esta dissertação tem por objectivo, estudar a relevância das celebridades em publicidade. A Publicidade tem um papel muito importante na sociedade em que vivemos. Desde sempre que foi um tema que me despertou muito interesse, assim como, as estratégias nela inseridas. A presença de celebridades em anúncios publicitários é uma prática muito comum para promover produtos e marcas. Com esta investigação tenho por objectivo perceber qual a relevância das celebridades em anúncios ...

  17. The project Petersbogen at Leipzig; Das Projekt Petersbogen in Leipzig

    Energy Technology Data Exchange (ETDEWEB)

    Wichmann, R. [Ingenieurbuero Wichmann GmbH, Berlin (Germany)

    2003-07-01

    The 'Petersbogen' project at Leipzig will house the main station, the law department of Leipzig University, shops, and a big cinema. The versatile applications of the building required careful planning of the technical facilities. [German] Im Zentrum der geschichtstraechtigen Universitaetsstadt Leipzig wurde von den Architekten, die auch den dortigen Hauptbahnhof zu einem mondaenen Einkaufszentrum ausbauten, das Bauvorhaben ''Petersbogen'' realisiert. Das Gebaeude beherbergt neben den Ladenflaechen der Juridicum Passage, die juristische Fakultaet der Uni Leipzig und ein Kinozentrum. Entsprechend der vielseitigen Aufgaben des Gebaeudes war eine planungsintensive Haustechnik notwendig. (orig.)

  18. Filosofia das ciências sociais: temas atuais

    OpenAIRE

    Kincaid, Harold

    2014-01-01

    A filosofia das ciências sociais, concebida da maneira adequada, tem algo a oferecer aos que praticam as ciências sociais. Os cientistas sociais adotam em suas pesquisas, ainda que de forma implícita, alguma filosofia de sua ciência. Para evitar impasses, é melhor explicitar essa filosofia e ser criticamente consciente dos seus méritos. A filosofia das ciências sociais, por sua vez, não pode ser praticada sem um envolvimento íntimo com a pesquisa social. O artigo esboça alguns desenvolvimento...

  19. Os conteúdos das visões da ayahuasca

    OpenAIRE

    Shanon,Benny

    2003-01-01

    Este artigo examina os conteúdos das alucinações visuais induzidas pela infusão psicotrópica ayahuasca. Ele faz parte de uma investigação fenomenológica mais ampla que busca estudar a ayahuasca de uma perspectiva psicológico-cognitiva. (Até agora, quase todos os estudos da ayahuasca partiram das ciências naturais ou da antropologia.) Análises comparativas quantitativas revelam que certos itens de conteúdo específico são especialmente prevalescentes em visões da ayahuasca e se reencontram em r...

  20. Auditoria de enfermagem: o impacto das anotaçóes de enfermagem no contexto das glosas hospitalares

    OpenAIRE

    Ferreira, Tânia S; de Souza-Braga, André Luiz; Cavalcanti-Valente, Geilsa Soraia; Ferreira de Souza, Deise; Moreira Carvalho-Alves, Enilda

    2009-01-01

    Este estudo tratou da nossa observação frente ao impacto das anotações de enfermagem no contexto das glosas hospitalares. Nesta perspectiva, a pesquisa se norteia pela seguinte questão: como o profissional de enfermagem pode contribuir através dos registros para não ocorrência da glosa? Temos como objetivo identificar o impacto causado pelo não registro de enfermagem contrapondo às eventuais glosas, evidenciando os principais tipos decorrentes destes registros. Metodologicamente a pesquisa ut...

  1. Cabaret Voltaire ja "Kabaret das Lust" / Marko Raat

    Index Scriptorium Estoniae

    Raat, Marko, 1973-

    2000-01-01

    Prantsuse režissööri Catherine Breillatþ "Romanss" ja pornograafia mõiste ning Andres Maimiku, Arbo Tammiksaare, Juhan Ulfsaki Kabaret das Lust kava "Elu mõte" ja selle raames näidatud Tammiksaare-Maimiku mängufilmi sugemetega dokumentaalfilm "Macbeth" : loominguline ühendus "Suits"

  2. Thrombus scintigraphy with Ga-67 DFO-DAS-Fibrinogen, 2

    International Nuclear Information System (INIS)

    Kawasaki, Yukiko

    1987-01-01

    In our previous in vivo study 67 Ga DFO-DAS-Fibrinogen was assessed for its usefulness as a radiopharmaceutical for the detection of thrombin in experimental animals (Report 1). The present study was undertaken to appraise the diagnostic value of 67 Ga DFO-DAS-Fibrinogen in human disease, especially in relation to blood coagulability as well as to thrombolytic drug regimen being given, in an effort to investigate its clinical applicability. Involved in this study were 48 patients with thrombosis proven by X-ray CT and other examinations. Of these 48, 42 had arterial thrombosis (20 with aortic aneurysm including the dissecting form, 11 in postoperative condition following vascular surgery with a prosthesis, 9 with intracardiac thrombosis accompanying heart disease, and 1 each with occlusive arteriosclerosis and cerebral infarction) and 6 had venous thrombosis. The 67 Ga DFO-DAS-Fibrinogen test proved to be positive in 55 % of arterial thrombin and in 50 % of venous thrombin. It is interesting to note that as high a positivity rate as 80 % was obtained for aortic aneurysm, although the positivity rate was disappointingly low for left atrial thrombin. No distinct correlation was noted to exist between the degree of accumulation of the tracer in thrombotic lesions and any of factors conceivably of clinical releavance, i.e. time elapsing from onset till testing, thrombolytic medication being given, and hematological factors. 67 Ga DFO-DAS-Fibrinogen appeared to be a radiodiagnostic agent that could possibly indicate the existing activity status of thrombosis. (author)

  3. Integrated analysis for genotypic adaptation in rice | Das | African ...

    African Journals Online (AJOL)

    Integrated analysis for genotypic adaptation in rice. S Das, RC Misra, MC Pattnaik, SK Sinha. Abstract. Development of varieties with high yield potential coupled with wide adaptability is an important plant breeding objective. The presence of genotype by environment (GxE) interaction plays a crucial role in determining the ...

  4. Gastroprotective Effects of DAS-77 (a Phytomedicine) in Ulcer ...

    African Journals Online (AJOL)

    Purpose: DAS-77 is a phytomedicine that contains the dried bark of Mangifera indica and root of Carica ... epithelial defense and repair (e.g. ... indica) and dried root of pawpaw tree (Carica .... was done without causing any damage to its ...

  5. Das Eismeer – Caspar David Friedrich and the North

    Directory of Open Access Journals (Sweden)

    Nina Hinrichs

    2008-02-01

    1840 created the work of art Das Eismeer in the years 1823/24. Besides his painting Mönch am Meer it is his most radical painting. It depicts a dramatic and grim subject: A shipwreck in the Arctic Sea. According to different cultural, historical and social contexts there have been many different interpretations of his painting since it was produced.

  6. Teaching Foreign Cultural Literacy with Margarethe von Trotta's "Das Versprechen"

    Science.gov (United States)

    Kuttenberg, Eva

    2003-01-01

    This article describes model units for an in-depth cultural analysis of "Das Versprechen" in undergraduate college courses including intermediate German, German culture and civilization, advanced conversation and composition, and film. Practical suggestions for pre-viewing, viewing, and post-viewing activities as well as assessment in…

  7. The sick-building syndrome; Das Sick-Building-Syndrom

    Energy Technology Data Exchange (ETDEWEB)

    Henne, A.; Neumann, H.F.; Winneke, G.

    1992-12-31

    The sick-building syndrome is characterized by the presence of general, non-specific symptoms (e.g., headache, tiredness, respiratory problems, eye trouble, vertigo, nausea, unspecific hypersensitivity) in association with a particular indoor ambience. It is clearly distinguishable from `building-related illness`, referring to a well-defined clinical syndrome due to staying in a building and for which a cause can, in general, be established. Disorders in the case of the sick-building syndrome are manifold and confirmed objectifiable results are hardly available so far. Yet there are some organ-related methods for the confirmation of findings concerning, for instance, the eyes, the skin and the area of the nose. The causes of the incidence of sick-building syndrome are more or less unclear. It is a multifactorial phenomenon involving physical, biological, chemical, individual-specific and psychological factors. Buildings where sick-building syndrome occurs typically exhibit certain properties. The European Community has already made proposals for the investigation of incriminated buildings. A systematic survey by questionnaire together with individual interviews plays an import part towards clarifying the syndrome. (orig./UWA) [Deutsch] Das Sick-Building-Syndrom beschreibt das Vorhandensein von allgemeinen, nicht spezifischen Symptomen (z.B. Kopfschmerzen, Muedigkeit, Atembeschwerden, Augenreizungen, Schwindelgefuehl, Uebelkeit, unspezifische Ueberempfindlichkeit), assoziiert mit einer besonderen Innenraumumgebung. Deutlich hiervon abzugrenzen ist die ``Building related illness``, bei der ein klinisch definiertes Krankheitsbild vorliegt, das durch den Aufenthalt im Gebaeude verursacht wird und fuer das im allgemeinen eine Ursache ermittelt werden kann. Das Beschwerdebild beim Sick-Building-Syndrom ist vielfaeltig, und gesicherte, objektivierbare Befunde liegen hierzu bisher kaum vor. Dennoch gibt es einige organbezogenen Methoden zur Befundabsicherung, z.B. fuer das

  8. Culture of Dendritic Cells in vitro and Its Anti-tumor Immonotherapy

    Directory of Open Access Journals (Sweden)

    Yanwen ZHOU

    2010-05-01

    Full Text Available Background and objective Immunocompromised patients with malignant tumor always lack of strong anti-tumor immune response, because the antigenicity of tumor cells is weak, and antigen-presenting cell function is low, so that can not be effectively presenting tumor antigens to the lymphocytes. Therefore, how to effectively induce anti-tumor immune response is the key issue. Through the study on establishing a method to culture dendritic cells (DC in vitro and to observe the anti-lung cancer immunological effect induced by DC, we provided definite experiment basis for the clinic application of vaccine based on DC. Methods Through the experiment we get the soluble antigen polypeptide from lung cancer cells GLC-82 by 3 mol/L potassium chloride. DCs are cultured and obtained from peripheral blood mononuclear cell by GM-CSF, IL-4 and TNF-a. DCs are identified by flow cytometer (FCM and immunostaining. DCs modified by lung cancer tumor soluble antigen (TSA and staphylococcal enterotox in A (SEA, DCs modified by TSA or DCs modified by SEA or DCs modified by nothing were cultivated together with T lymphocyte, and the obtained cells are named TSA-SEA-DCL or TSA-DCL or SEA-DCL or DCL as effector cells. The anti-tumor activity of every effector cells against target cells was assayed with MTT method. Shape of DCs and effector cells, and the process of killing target cells were observed in microscope. Results Induced DCs expressed more CD1a, CD80 and HLA-DR, which had typical cell traits such as tree branch. The killing ratio of the TSA-SEA-DCL in vitro to GLC-82 is larger than TSA-DCL, SEA-DCL and DCL, also larger than to K562. When the effector cells cultivate with target cells, we can observe the CTL approach and gather to the cancer cell, induce it necrosis and apoptosis. Conclusion Ripe DCs that have typical characteristic and phenotype could be induced successfully. High potency and relatively specific antilung caner effect can be prepared in virtue of

  9. Investigation of HIFU-induced anti-tumor immunity in a murine tumor model

    Directory of Open Access Journals (Sweden)

    Lyerly H Kim

    2007-07-01

    Full Text Available Abstract Background High intensity focused ultrasound (HIFU is an emerging non-invasive treatment modality for localized treatment of cancers. While current clinical strategies employ HIFU exclusively for thermal ablation of the target sites, biological responses associated with both thermal and mechanical damage from focused ultrasound have not been thoroughly investigated. In particular, endogenous danger signals from HIFU-damaged tumor cells may trigger the activation of dendritic cells. This response may play a critical role in a HIFU-elicited anti-tumor immune response which can be harnessed for more effective treatment. Methods Mice bearing MC-38 colon adenocarcinoma tumors were treated with thermal and mechanical HIFU exposure settings in order to independently observe HIFU-induced effects on the host's immunological response. In vivo dendritic cell activity was assessed along with the host's response to challenge tumor growth. Results Thermal and mechanical HIFU were found to increase CD11c+ cells 3.1-fold and 4-fold, respectively, as compared to 1.5-fold observed for DC injection alone. In addition, thermal and mechanical HIFU increased CFSE+ DC accumulation in draining lymph nodes 5-fold and 10-fold, respectively. Moreover, focused ultrasound treatments not only caused a reduction in the growth of primary tumors, with tumor volume decreasing by 85% for thermal HIFU and 43% for mechanical HIFU, but they also provided protection against subcutaneous tumor re-challenge. Further immunological assays confirmed an enhanced CTL activity and increased tumor-specific IFN-γ-secreting cells in the mice treated by focused ultrasound, with cytotoxicity induced by mechanical HIFU reaching as high as 27% at a 10:1 effector:target ratio. Conclusion These studies present initial encouraging results confirming that focused ultrasound treatment can elicit a systemic anti-tumor immune response, and they suggest that this immunity is closely related to

  10. Antibody complementarity-determining regions (CDRs can display differential antimicrobial, antiviral and antitumor activities.

    Directory of Open Access Journals (Sweden)

    Luciano Polonelli

    Full Text Available BACKGROUND: Complementarity-determining regions (CDRs are immunoglobulin (Ig hypervariable domains that determine specific antibody (Ab binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. The possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here. METHODOLOGY/PRINCIPAL FINDINGS: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a a protein epitope of Candida albicans cell wall stress mannoprotein; b a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. The inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains. CONCLUSIONS/SIGNIFICANCE: The high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. The easy production and low cost of small

  11. Ursolic acid liposomes with chitosan modification: Promising antitumor drug delivery and efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Meili; Zhao, Tingting; Liu, Yanping; Wang, Qianqian; Xing, Shanshan; Li, Lei; Wang, Longgang [Applying Chemistry Key Lab of Hebei Province, Yanshan University, No.438 Hebei Street, Qinhuangdao 066004 (China); Liu, Lanxiang [The First Hospital of Qinhuangdao, No. 258 Cultural Road, Qinhuangdao 066000 (China); Gao, Dawei, E-mail: dwgao@ysu.edu.cn [Applying Chemistry Key Lab of Hebei Province, Yanshan University, No.438 Hebei Street, Qinhuangdao 066004 (China)

    2017-02-01

    There are tremendous challenges on antitumor and its therapeutic drugs, and preparation of highly efficient nano-vehicles represents one of the novel topics in antitumor pharmaceutical field. Herein, the novel chitosan-coated ursolic acid (UA) liposome (CS-UA-L) was efficiently prepared with highly tumor targeting, drug controlled release and low side-effect. The CS-UA-L was uniformly spherical particles with diameter of ~ 130 nm, and the size was more easily trapped into the tumor tissues. Chitosan modification can make liposomes carrying positive charges, which were inclined to combine with the negative charges on the surface of tumor cells, and then the CS-UA-L could release UA rapidly at pH 5.0 comparing with pH 7.4. Meanwhile, the CS-UA-L exhibited obvious anti-proliferative effect (76.46%) on HeLa cells and significantly antitumor activity (61.26%) in mice bearing U14 cervical cancer. The tumor tissues of CS-UA-L treated mice had enhanced cell apoptosis, extensive necrosis and low cell proliferation activity. These results demonstrated that the multifunctional CS-UA-L allowed a precision treatment for localized tumor, and reducing the total drug dose and side-effect, which hold a great promise in new safe and effective tumor therapy. - Graphical abstract: Schematic diagram representing the principle of synthesis of CS-UA-L and pH-triggered sequential UA release after treatment on tumor bearing mouse. - Highlights: • The novel chitosan-coated ursolic acid liposomes (CS-UA-L) were successfully prepared. • CS-UA-L possessed sensitive pH-response, which could release UA rapidly at pH 5.0 comparing with pH 7.4. • CS-UA-L exhibited obvious anti-proliferative effect (76.46%) on HeLa cells than UA and UA-L. • CS-UA-L suppressed tumor growth more efficiently than those with UA and UA-L in mice bearing U14 cervical cancer. • The CS-UA-L allow for precision treatment of the tumor and potential to reduce the total drug dose and side-effect.

  12. Induction of mitophagy-mediated antitumor activity with folate-appended methyl-β-cyclodextrin

    Directory of Open Access Journals (Sweden)

    Kameyama K

    2017-04-01

    Full Text Available Kazuhisa Kameyama,1,* Keiichi Motoyama,1,* Nao Tanaka,1 Yuki Yamashita,1 Taishi Higashi,1 Hidetoshi Arima1,2,* 1Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, 2Program for Leading Graduate Schools “HIGO (Health Life Science: Interdisciplinary and Glocal Oriented Program,” Kumamoto University, Kumamoto, Japan *These authors contributed equally to this work Abstract: Mitophagy is the specific autophagic elimination system of mitochondria, which regulates cellular survival via the removal of damaged mitochondria. Recently, we revealed that folate-appended methyl-β-cyclodextrin (FA-M-β-CyD provides selective antitumor activity in folate receptor-α (FR-α-expressing cells by the induction of autophagy. In this study, to gain insight into the detailed mechanism of this antitumor activity, we focused on the induction of mitophagy by the treatment of FR-α-expressing tumor cells with FA-M-β-CyD. In contrast to methyl-β-cyclodextrin, FA-M-β-CyD entered KB cells, human epithelial cells from a fatal cervical carcinoma (FR-α (+ through FR-α-mediated endocytosis. The transmembrane potential of isolated mitochondria after treatment with FA-M-β-CyD was significantly elevated. In addition, FA-M-β-CyD lowered adenosine triphosphate (ATP production and promoted reactive oxygen species production in KB cells (FR-α (+. Importantly, FA-M-β-CyD enhanced light chain 3 (LC3 conversion (LC3-I to LC3-II in KB cells (FR-α (+ and induced PTEN-induced putative kinase 1 (PINK1 protein expression, which is involved in the induction of mitophagy. Furthermore, FA-M-β-CyD had potent antitumor activity in BALB/c nu/nu mice xenografted with KB cells (FR-α (+ without any significant side effects. Taken together, these findings demonstrate that the autophagic cell death elicited by FA-M-β-CyD could be associated with mitophagy induced by an impaired mitochondrial function. Keywords: mitophagy, autophagy, folate receptor, methyl

  13. Novel production method of innovative antiangiogenic and antitumor small peptides in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Setrerrahmane S

    2017-11-01

    Full Text Available Sarra Setrerrahmane,1 Jian Yu,1 Jingchao Hao,1,2 Heng Zheng,3 Hanmei Xu1,3 1The Engineering Research Center of Peptide Drug Discovery and Development, China Pharmaceutical University, Nanjing, Jiangsu, 2College of Pharmacy & the Provincial Key Laboratory of Natural Drug and Pharmacology, Kunming, Yunnan, 3State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China Background: Developing innovative drugs with potent efficacy, specificity, and high safety remains an ongoing task in antitumor therapy development. In the last few years, peptide drugs have become attractive agents in cancer therapy. HM-3, mainly with antiangiogenic effect, and AP25, with an additional antiproliferative effect, are two peptides designed in our laboratory targeting αvβ3 and α5β1 integrins, respectively. The low molecular weight of the two peptides renders their recombinant expression very difficult, and the complicated structure of AP25 makes its chemical synthesis restricted, which presents a big challenge for its development.Methods: Bifunctional peptides designed by the ligation of HM-3 and AP25, using linkers with different flexibility, were prepared using recombinant DNA technology in Escherichia coli. The fusion peptides were expressed in a modified auto-induction medium based on a mixture of glucose, glycerol, and lactose as carbon substrates and NH4+ as nitrogen source without any amino acid or other elements. Subsequently, the antiangiogenic, antiproliferative, and cell adhesion assays were conducted to evaluate the bioactivity of the two fusion peptides.Results: The peptides were successfully expressed in a soluble form without any induction, which allows the culture to reach higher cell density before protein expression occurs. Human umbilical vein endothelial cell migration assay and chick embryo chorioallantoic membrane assay showed, at low doses, a significantly

  14. In vitro and in vivo antitumor effects of 50 to 100-KDa components from B16 melanoma culture supernatant.

    Science.gov (United States)

    Qin, Ying-Song; Zhang, X U; Zhang, Xiang-Yu

    2015-07-01

    The development of immunological therapies for melanoma has been of considerable concern in recent years. Whole tumor cell lysates have been used to develop antitumor vaccines, but the effective components of the lysates have not been identified. In the present study, protein elements were purified from the B16 supernatant to analyze the in vitro chemotaxis towards mouse spleen lymphocytes using a Boyden chamber. Prior to establishing a B16 melanoma model, C57BL/6 mice were vaccinated with these proteins, and melanoma growth, tumor appearance time and behavioral changes were observed. Next, the cytotoxicity and subsets of the tumor infiltrating lymphocytes, and the histological characteristics of the melanoma were analyzed. The isolated purified fragments of B16 melanoma culture supernatant had strong antitumor effects. The possible antitumor mechanism was delineated, and was identified to possibly be through the activation of cluster of differentiation 8-positive T cells and the promotion of B16 cell differentiation. These methods will provide a novel insight into understanding antitumor immunological mechanisms and provide a potential avenue for immunotherapy.

  15. A Novel Paclitaxel Microemulsion Containing a Reduced Amount of Cremophor EL: Pharmacokinetics, Biodistribution, and In Vivo Antitumor Efficacy and Safety

    Science.gov (United States)

    Wang, Ying; Wu, Ke-Chun; Zhao, Bing-Xiang; Zhao, Xin; Wang, Xin; Chen, Su; Nie, Shu-Fang; Pan, Wei-San; Zhang, Xuan; Zhang, Qiang

    2011-01-01

    The purpose of this study was to prepare a novel paclitaxel (PTX) microemulsion containing a reduced amount of Cremophor EL (CrEL) which had similar pharmacokinetics and antitumor efficacy as the commercially available PTX injection, but a significantly reduced allergic effect due to the CrEL. The pharmacokinetics, biodistribution, in vivo antitumor activity and safety of PTX microemulsion was evaluated. The results of pharmacokinetic and distribution properties of PTX in the microemulsion were similar to those of the PTX injection. The antitumor efficacy of the PTX microemulsion in OVCRA-3 and A 549 tumor-bearing animals was similar to that of PTX injection. The PTX microemulsion did not cause haemolysis, erythrocyte agglutination or simulative reaction. The incidence and degree of allergic reactions exhibited by the PTX microemulsion group, with or without premedication, were significantly lower than those in the PTX injection group (P microemulsion had similar pharmacokinetics and anti-tumor efficacy to the PTX injection, but a significantly reduced allergic effect due to CrEL, indicating that the PTX microemulsion overcomes the disadvantages of the conventional PTX injection and is one way of avoiding the limitations of current injection product while providing suitable therapeutic efficacy. PMID:21331356

  16. Andrographolide enhanced 5-fluorouracil-induced antitumor effect in colorectal cancer via inhibition of c-MET pathway

    Directory of Open Access Journals (Sweden)

    Su M

    2017-11-01

    Full Text Available Meng Su,1 Baoli Qin,1 Fang Liu,2 Yuze Chen,2 Rui Zhang2 1Department of Internal Medicine, 2Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Liaoning, China Abstract: Colorectal cancer (CRC is the third most common malignant neoplasm worldwide. 5-Fluorouracil (5-Fu is the most important chemotherapeutic drug used for the treatment of CRC. However, resistance to 5-Fu therapies is a growing concern in CRC clinical practice recently. Andrographolide (Andro is a main bioactive constituent of the herb Andrographis paniculata, which has various biological effects including anti-inflammation and antitumor activities. In the present study, we investigated the effects of combined Andro with 5-Fu against CRC HCT-116 cells. In vitro studies showed that Andro synergistically enhanced the anti-proliferation effect of 5-Fu on HCT-116 cells due to increased apoptotic cells. Meanwhile, results of the enzyme linked immunosorbent assay indicated that the level of phosphorylated cellular-mesenchymal to epithelial transition factor (p-MET was decreased by the combination treatment. Further study suggested that Andro promoted the antitumor effect of 5-Fu by downregulating the level of p-MET. In conclusion, these results confirmed the synergistic antitumor activity of Andro on CRC and provide evidence for possible clinical application of Andro for enhancing the antitumor effect of 5-Fu in CRC treatment. Keywords: Andro, 5-Fu, HCT-116 cells, apoptosis, p-MET

  17. Spontaneous Translocation of Antitumor Oxaliplatin, its Enantiomeric Analogue, and Cisplatin from One Strand to Another in Double-Helical DNA

    Czech Academy of Sciences Publication Activity Database

    Malina, Jaroslav; Natile, G.; Brabec, Viktor

    2013-01-01

    Roč. 19, č. 36 (2013), s. 11984-11991 ISSN 0947-6539 R&D Projects: GA ČR(CZ) GAP205/11/0856; GA ČR(CZ) GAP301/10/0598 Institutional support: RVO:68081707 Keywords : antitumor agents * calorimetry * DNA Subject RIV: BO - Biophysics Impact factor: 5.696, year: 2013

  18. Targeting G-quadruplex DNA Structures by EMICORON has a strong antitumor efficacy against advanced models of human colon cancer

    DEFF Research Database (Denmark)

    Porru, Manuela; Artuso, Simona; Salvati, Erica

    2015-01-01

    We previously identified EMICORON as a novel G-quadruplex (G4) ligand showing high selectivity for G4 structures over the duplex DNA, causing telomere damage and inhibition of cell proliferation in transformed and tumor cells. Here, we evaluated the antitumoral effect of EMICORON on advanced mode...

  19. Saponin-based adjuvants create a highly effective anti-tumor vaccine when combined with in situ tumor destruction.

    NARCIS (Netherlands)

    Brok, M.H.M.G.M. den; Nierkens, S.; Wagenaars, J.A.L.; Ruers, T.J.M.; Schrier, C.C.; Rijke, E.O.; Adema, G.J.

    2012-01-01

    Today's most commonly used microbial vaccines are essentially composed of antigenic elements and a non-microbial adjuvant, and induce solid amounts of antibodies. Cancer vaccines mostly aim to induce anti-tumor CTL-responses, which require cross-presentation of tumor-derived antigens by dendritic

  20. GADD45ß, an anti-tumor gene, inhibits avian leukosis virus subgroup J replication in chickens

    Science.gov (United States)

    Avian leukosis virus subgroup J (ALV-J) is a retrovirus that induces neoplasia, hepatomegaly, immunosuppression and poor performance in chickens. The tumorigenic and pathogenic mechanisms of ALV-J remain a hot topic. To explore anti-tumor genes that confer genetic resistance to ALV-J infection in ch...

  1. Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

    NARCIS (Netherlands)

    Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

    2010-01-01

    OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total

  2. Optimizing the dosing schedule of l-asparaginase improves its anti-tumor activity in breast tumor-bearing mice

    Directory of Open Access Journals (Sweden)

    Shoya Shiromizu

    2018-04-01

    Full Text Available Proliferation of acute lymphoblastic leukemic cells is nutritionally dependent on the external supply of asparagine. l-asparaginase, an enzyme hydrolyzing l-asparagine in blood, is used for treatment of acute lymphoblastic leukemic and other related blood cancers. Although previous studies demonstrated that l-asparaginase suppresses the proliferation of cultured solid tumor cells, it remains unclear whether this enzyme prevents the growth of solid tumors in vivo. In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice. Cultures of several types of murine solid tumor cells were dependent on the external supply of asparagine. Among them, we selected murine 4T1 breast cancer cells and implanted them into BALB/c female mice kept under standardized light/dark cycle conditions. The growth of 4T1 tumor cells implanted in mice was significantly suppressed by intravenous administration of l-asparaginase during the light phase, whereas its administration during the dark phase failed to show significant anti-tumor activity. Decreases in plasma asparagine levels due to the administration of l-asparaginase were closely related to the dosing time-dependency of its anti-tumor effects. These results suggest that the anti-tumor efficacy of l-asparaginase in breast tumor-bearing mice is improved by optimizing the dosing schedule. Keywords: l-asparaginase, Asparagine, Solid tumor, Chrono-pharmacotherapy

  3. Poly(γ-glutamic acid)-coated lipoplexes loaded with Doxorubicin for enhancing the antitumor activity against liver tumors

    Science.gov (United States)

    Qi, Na; Tang, Bo; Liu, Guang; Liang, Xingsi

    2017-05-01

    The study was to develop poly-γ-glutamic acid (γ-PGA)-coated Doxorubicin (Dox) lipoplexes that enhance the antitumor activity against liver tumors. γ-PGA-coated lipoplexes were performed by electrostatistically attracting to the surface of cationic charge liposomes with anionic γ-PGA. With the increasing of γ-PGA concentration, the particle size of γ-PGA-coated Dox lipoplexes slightly increased, the zeta potential from positive shifted to negative, and the entrapment efficiency (EE) were no significant change. The release rate of γ-PGA-coated Dox lipoplexes slightly increased at acidic pH, the accelerated Dox release might be attributed to greater drug delivery to tumor cells, resulting in a higher antitumor activity. Especially, γ-PGA-coated Dox lipoplexes exhibited higher cellular uptake, significant in vitro cytotoxicity in HepG2 cells, and improved in vivo antitumor efficacy toward HepG2 hepatoma-xenografted nude models in comparison with Dox liposomes and free Dox solution. In addition, the analysis results via flow cytometry showed that γ-PGA-coated Dox lipoplexes induce S phase cell cycle arrest and significantly increased apoptosis rate of HepG2 cells. In conclusion, the presence of γ-PGA on the surface of Dox lipoplexes enhanced antitumor effects of liver tumors.

  4. Effects of extraction methods on the yield, chemical structure and anti-tumor activity of polysaccharides from Cordyceps gunnii mycelia.

    Science.gov (United States)

    Zhu, Zhen-Yuan; Dong, Fengying; Liu, Xiaocui; Lv, Qian; YingYang; Liu, Fei; Chen, Ling; Wang, Tiantian; Wang, Zheng; Zhang, Yongmin

    2016-04-20

    This study was to investigate the effects of different extraction methods on the yield, chemical structure and antitumor activity of polysaccharides from Cordyceps gunnii (C. gunnii) mycelia. Five extraction methods were used to extract crude polysaccharides (CPS), which include room-temperature water extraction (RWE), hot-water extraction (HWE), microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE) and cellulase-assisted extraction (CAE). Then Sephadex G-100 was used for purification of CPS. As a result, the antitumor activities of CPS and PPS on S180 cells were evaluated. Five CPS and purified polysaccharides (PPS) were obtained. The yield of CPS by microwave-assisted extraction (CPSMAE) was the highest and its anti-tumor activity was the best and its macromolecular polysaccharide (3000-1000kDa) ratio was the largest. The PPS had the same monosaccharide composition, but their obvious difference was in the antitumor activity and the physicochemical characteristics, such as intrinsic viscosity, specific rotation, scanning electron microscopy and circular dichroism spectra. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Conformation and recognition of DNA damaged by antitumor cis-dichlorido platinum(II) complex of CDK inhibitor bohemine

    Czech Academy of Sciences Publication Activity Database

    Nováková, Olga; Lišková, Barbora; Vystrčilová, Jana; Suchánková, Tereza; Vrána, Oldřich; Starha, P.; Trávníček, Z.; Brabec, Viktor

    2014-01-01

    Roč. 78, MAY2014 (2014), s. 54-64 ISSN 0223-5234 R&D Projects: GA ČR(CZ) GA13-08273S Institutional support: RVO:68081707 Keywords : Antitumor * Platinum * DNA Subject RIV: BO - Biophysics Impact factor: 3.447, year: 2014

  6. Potent antitumor activities of recombinant human PDCD5 protein in combination with chemotherapy drugs in K562 cells

    International Nuclear Information System (INIS)

    Shi, Lin; Song, Quansheng; Zhang, Yingmei; Lou, Yaxin; Wang, Yanfang; Tian, Linjie; Zheng, Yi; Ma, Dalong; Ke, Xiaoyan; Wang, Ying

    2010-01-01

    Conventional chemotherapy is still frequently used. Programmed cell death 5 (PDCD5) enhances apoptosis of various tumor cells triggered by certain stimuli and is lowly expressed in leukemic cells from chronic myelogenous leukemia patients. Here, we describe for the first time that recombinant human PDCD5 protein (rhPDCD5) in combination with chemotherapy drugs has potent antitumor effects on chronic myelogenous leukemia K562 cells in vitro and in vivo. The antitumor efficacy of rhPDCD5 protein with chemotherapy drugs, idarubicin (IDR) or cytarabine (Ara-C), was examined in K562 cells in vitro and K562 xenograft tumor models in vivo. rhPDCD5 protein markedly increased the apoptosis rates and decreased the colony-forming capability of K562 cells after the combined treatment with IDR or Ara-C. rhPDCD5 protein by intraperitoneal administration dramatically improved the antitumor effects of IDR treatment in the K562 xenograft model. The tumor sizes and cell proliferation were significantly decreased; and TUNEL positive cells were significantly increased in the combined group with rhPDCD5 protein and IDR treatment compared with single IDR treatment groups. rhPDCD5 protein, in combination with IDR, has potent antitumor effects on chronic myelogenous leukemia K562 cells and may be a novel and promising agent for the treatment of chronic myelogenous leukemia.

  7. Composition and mechanism of anti-tumor effects of Hericium erinaceus mushroom extracts in tumor-bearing mice

    Science.gov (United States)

    We investigated anti-tumor effects of the following four extracts of freeze-dried Hericium erinaceus mushrooms in Balb/c mice intracutaneously transplanted on the backs with CT-26 colon cancer cells: HWE, hot-water extraction by boiling in water for 3 h; MWE, microwaving in 50% ethanol/water at 60 W...

  8. Optimizing the dosing schedule of l-asparaginase improves its anti-tumor activity in breast tumor-bearing mice.

    Science.gov (United States)

    Shiromizu, Shoya; Kusunose, Naoki; Matsunaga, Naoya; Koyanagi, Satoru; Ohdo, Shigehiro

    2018-04-01

    Proliferation of acute lymphoblastic leukemic cells is nutritionally dependent on the external supply of asparagine. l-asparaginase, an enzyme hydrolyzing l-asparagine in blood, is used for treatment of acute lymphoblastic leukemic and other related blood cancers. Although previous studies demonstrated that l-asparaginase suppresses the proliferation of cultured solid tumor cells, it remains unclear whether this enzyme prevents the growth of solid tumors in vivo. In this study, we demonstrated the importance of optimizing dosing schedules for the anti-tumor activity of l-asparaginase in 4T1 breast tumor-bearing mice. Cultures of several types of murine solid tumor cells were dependent on the external supply of asparagine. Among them, we selected murine 4T1 breast cancer cells and implanted them into BALB/c female mice kept under standardized light/dark cycle conditions. The growth of 4T1 tumor cells implanted in mice was significantly suppressed by intravenous administration of l-asparaginase during the light phase, whereas its administration during the dark phase failed to show significant anti-tumor activity. Decreases in plasma asparagine levels due to the administration of l-asparaginase were closely related to the dosing time-dependency of its anti-tumor effects. These results suggest that the anti-tumor efficacy of l-asparaginase in breast tumor-bearing mice is improved by optimizing the dosing schedule. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  9. Antioxidants impair anti-tumoral effects of Vorinostat, but not anti-neoplastic effects of Vorinostat and caspase-8 downregulation.

    Science.gov (United States)

    Bergadà, Laura; Yeramian, Andree; Sorolla, Annabel; Matias-Guiu, Xavier; Dolcet, Xavier

    2014-01-01

    We have recently demonstrated that histone deacetylase inhibitor, Vorinostat, applied as a single therapy or in combination with caspase-8 downregulation exhibits high anti-tumoral activity on endometrial carcinoma cell lines. In the present study, we have assessed the signalling processes underlying anti-tumoral effects of Vorinostat. Increasing evidence suggests that reactive oxygen species are responsible for histone deacetylase inhibitor-induced cell killing. We have found that Vorinostat induces formation of reactive oxygen species and DNA damage. To investigate the role of oxidative stress as anti-neoplastic mechanism, we have evaluated the effects of different antioxidants (Bha, Nac and Tiron) on endometrial carcinoma cell line Ishikawa treated with Vorinostat. We show that Bha, Nac and Tiron markedly inhibited the cytotoxic effects of Vorinostat, increasing cell viability in vitro. We found that all three antioxidants did not inhibited accumulation of acetyl Histone H4, so that antioxidants did not inhibit Vorinostat activity. Finally, we have evaluated the effects of antioxidants on anti-tumoral activity of Vorinostat as monotherapy or in combination with caspase-8 downregulation in vivo. Interestingly, antioxidants blocked the reduction of tumour growth caused by Vorinostat, but they were unable to inhibit anti-tumoral activity of Vorinostat plus caspase-8 inhibition.

  10. Comparison of two self-assembled macromolecular prodrug micelles with different conjugate positions of SN38 for enhancing antitumor activity

    Directory of Open Access Journals (Sweden)

    Liu Y

    2015-03-01

    Full Text Available Yi Liu,1 Hongyu Piao,1 Ying Gao,1 Caihong Xu,2 Ye Tian,1 Lihong Wang,1 Jinwen Liu,1 Bo Tang,1 Meijuan Zou,1 Gang Cheng1 1Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Food Science, Shenyang Normal University, Shenyang, Liaoning Province, People’s Republic of China Abstract: 7-Ethyl-10-hydroxycamptothecin (SN38, an active metabolite of irinotecan (CPT-11, is a remarkably potent antitumor agent. The clinical application of SN38 has been extremely restricted by its insolubility in water. In this study, we successfully synthesized two macromolecular prodrugs of SN38 with different conjugate positions (chitosan-(C10-OHSN38 and chitosan-(C20-OHSN38 to improve the water solubility and antitumor activity of SN38. These prodrugs can self-assemble into micelles in aqueous medium. The particle size, morphology, zeta potential, and in vitro drug release of SN38 and its derivatives, as well as their cytotoxicity, pharmacokinetics, and in vivo antitumor activity in a xenograft BALB/c mouse model were studied. In vitro, chitosan-(C10-OHSN38 (CS-(10sSN38 and chitosan-(C20-OHSN38 (CS-(20sSN38 were 13.3- and 25.9-fold more potent than CPT-11 in the murine colon adenocarcinoma cell line CT26, respectively. The area under the curve (AUC0–24 of SN38 after intravenously administering CS-(10sSN38 and CS-(20sSN38 to Sprague Dawley rats was greatly improved when compared with CPT-11 (both P<0.01. A larger AUC0–24 of CS-(20sSN38 was observed when compared to CS-(10sSN38 (P<0.05. Both of the novel self-assembled chitosan-SN38 prodrugs demonstrated superior anticancer activity to CPT-11 in the CT26 xenograft BALB/c mouse model. We have also investigated the differences between these macromolecular prodrug micelles with regards to enhancing the antitumor activity of SN38. CS-(20sSN38 exhibited better in vivo antitumor activity than CS-(10sSN38 at a dose of 2.5 mg/kg (P<0

  11. The antitumor effect of arsenic trioxide on hepatocellular carcinoma is enhanced by andrographolide.

    Science.gov (United States)

    Duan, Xuhua; Li, Tengfei; Han, Xinwei; Ren, Jianzhuang; Chen, Pengfei; Li, Hao; Gong, Shaojun

    2017-10-31

    High concentrations of arsenic trioxide (As 2 O 3 ) are used to treat acute promyelocytic leukemia and solid tumors, with negative side effects to normal cells. Andrographolide is a traditional Chinese medicine that exerts anti-cancer, anti-inflammatory, anti-virus, and anti-diabetic effects. Here, we tested the effects of combined andrographolide with As 2 O 3 against hepatocellular carcinoma (HCC). We found that by increasing apoptosis, andrographolide synergistically enhanced the anti-tumor effects of As2O3 in HepG2 cells in vitro and in vivo . Furthermore, results from our microarray assays and experiments with mouse xenografts showed that EphB4 was downregulated by the combination of As 2 O 3 plus andrographolide. These findings suggest that the combination of andrographolide and As 2 O 3 could yield therapeutic benefits in the treatment of HCC.

  12. Synthesis and antitumor evaluation of thiophene based azo dyes incorporating pyrazolone moiety

    Directory of Open Access Journals (Sweden)

    Moustafa A. Gouda

    2016-03-01

    Full Text Available A series of thiophene incorporating pyrazolone moieties 5a–f and 6a–c were synthesized via diazo coupling of diazonium salt of 3-substituted-2-amino-4,5,6,7-tetrahydrobenzo[b]thiophenes 1a–c with 3-methyl-1H-pyrazol-5(4H-one, 3-methyl-1-phenyl-1H-pyrazol-5(4H-one or 3-amino-1H-pyrazol-5(4H-one, respectively. Newly synthesized dyes were applied to polyester fabric as disperse dyes in which their color measurements and fastness properties were evaluated. These dyes showed generally red to blue shifted color with high extinction coefficient in comparison with aniline-based azo dyes. The antitumor activity of the synthesized dyes was evaluated. The results showed clearly that most of them exhibited good activity and compounds 5c and 5d exhibited moderate activity.

  13. The antitumor agent 3-bromopyruvate has a short half-life at physiological conditions.

    Science.gov (United States)

    Glick, Matthew; Biddle, Perry; Jantzi, Josh; Weaver, Samantha; Schirch, Doug

    2014-09-12

    Clinical research is currently exploring the validity of the anti-tumor candidate 3-bromopyruvate (3-BP) as a novel treatment for several types of cancer. However, recent publications have overlooked rarely-cited earlier work about the instability of 3-BP and its decay to 3-hydroxypyruvate (3-HP) which have obvious implications for its mechanism of action against tumors, how it is administered, and for precautions when preparing solutions of 3-BP. This study found the first-order decay rate of 3-BP at physiological temperature and pH has a half-life of only 77 min. Lower buffer pH decreases the decay rate, while choice of buffer and concentration do not affect it. A method for preparing more stable solutions is also reported. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. The in vitro antitumor activity of vitamins C and K3 against ovarian carcinoma.

    Science.gov (United States)

    von Gruenigen, Vivian E; Jamison, James M; Gilloteaux, Jacques; Lorimer, Heather E; Summers, Marcia; Pollard, Robert R; Gwin, Carley A; Summers, Jack L

    2003-01-01

    The objective was to evaluate the cytotoxic effect and mechanism of action of vitamins C (VC) and K3 (VK3) on ovarian carcinoma. Cytotoxicity assays were performed on ovarian cancer cell lines with VC, VK3 or a VC/VK3 combination. FIC index was employed to evaluate synergism. Flow cytometry was accomplished at 90% cytotoxic doses. Light, transmission electron microscopy and DNA isolation were performed. Antitumor activity was exhibited by both VC, VK3 and VC/VK3. VC/VK3 demonstrated synergistic activity. VC/VK3 may induce a G1 block in the cell cycle. Combined vitamin treatment resulted in cells that maintain apparently intact nuclei while extruding pieces of organelle-free cytoplasm. Degradation of chromosomal DNA was observed. Cell death (autoschizis) displayed characteristics of both apoptosis and necrosis. The cytotoxic effects observed may enable vitamins C and K3 to play an adjuvant role in the treatment of ovarian cancer.

  15. Production, Structural Elucidation, and In Vitro Antitumor Activity of Trehalose Lipid Biosurfactant from Nocardia farcinica Strain.

    Science.gov (United States)

    Christova, Nelly; Lang, Siegmund; Wray, Victor; Kaloyanov, Kaloyan; Konstantinov, Spiro; Stoineva, Ivanka

    2015-04-01

    The objective of this study was to isolate and identify the chemical structure of a biosurfactant produced by Nocardia farcinica strain BN26 isolated from soil, and evaluate its in vitro antitumor activity on a panel of human cancer cell lines. Strain BN26 was found to produce glycolipid biosurfactant on n-hexadecane as the sole carbon source. The biosurfactant was purified using medium-pressure liquid chromatography and characterized as trehalose lipid tetraester (THL) by nuclear magnetic resonance spectroscopy and mass spectrometry. Subsequently, the cytotoxic effects of THL on cancer cell lines BV-173, KE-37 (SKW-3), HL-60, HL-60/DOX, and JMSU-1 were evaluated by MTT assay. It was shown that THL exerted concentration-dependent antiproliferative activity against the human tumor cell lines and mediated cell death by the induction of partial oligonucleosomal DNA fragmentation. These findings suggest that THL could be of potential to apply in biomedicine as a therapeutic agent.

  16. Antitumoral action of interferons and interleukins in combination with radiotherapy. Pt. I. Immunologic basis

    International Nuclear Information System (INIS)

    Herskind, C.; Fleckenstein, K.; Wenz, F.; Lohr, F.; Lohr, J.; Li Chuan-Yuan

    2004-01-01

    Method: the cellular immune response toward tumor cells is reviewed. The role of cytokines in antigen presentation and activation of effector cells and their interactions with radiation are described. Preclinical strategies of the antitumor action of cytokines are presented and discussed based on the induction of IFN-γ by IL-12. Results: recent advances in immunology have demonstrated the importance of local interactions between antigen-presenting cells (APC) and effector cells such as natural killer (NK) cells and T-lymphocytes for an effective immune reaction against tumors. Interferons stimulate such interactions, while IL-2 plays a central role in the activation of NK cells and T-lymphocytes. The interactions between APC and effector cells are suppressed by many tumors but can be stimulated by irradiation. Since systemic application of interferons is quite toxic, present strategies aim at local expression, e.g., the induction of IFN-γ expression in Th1 cells by IL-12. (orig.) [de

  17. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    Energy Technology Data Exchange (ETDEWEB)

    Massi, Paola [Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Via Vanvitelli 32, 20129 Milan (Italy); Valenti, Marta; Solinas, Marta; Parolaro, Daniela [Department of Structural and Functional Biology, Section of Pharmacology, Center of Neuroscience, University of Insubria, Via A. da Giussano 10, 20152 Busto Arsizio, Varese (Italy)

    2010-05-26

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

  18. Snake venom L-amino acid oxidases: an overview on their antitumor effects

    Science.gov (United States)

    2014-01-01

    The L-amino acid oxidases (LAAOs) constitute a major component of snake venoms and have been widely studied due to their widespread presence and various effects, such as apoptosis induction, cytotoxicity, induction and/or inhibition of platelet aggregation, hemorrhage, hemolysis, edema, as well as antimicrobial, antiparasitic and anti-HIV activities. The isolated and characterized snake venom LAAOs have become important research targets due to their potential biotechnological applications in pursuit for new drugs of interest in the scientific and medical fields. The current study discusses the antitumor effects of snake venom LAAOs described in the literature to date, highlighting the mechanisms of apoptosis induction proposed for this class of proteins. PMID:24940304

  19. Fatal infections in older patients with inflammatory bowel disease on anti-tumor necrosis factor therapy

    Directory of Open Access Journals (Sweden)

    Way-Seah Lee

    2017-10-01

    Full Text Available Anti-tumor necrosis factor (anti-TNF is highly effective in inflammatory bowel disease (IBD; however, it is associated with an increased risk of infections, particularly in older adults. We reviewed 349 patients with IBD, who were observed over a 12-month period, 74 of whom had received anti-TNF therapy (71 patients were aged <60 years and 3 were aged ≥60 years. All the 3 older patients developed serious infectious complications after receiving anti-TNFs, although all of them were also on concomitant immunosuppressive therapy. One patient developed disseminated tuberculosis, another patient developed cholera diarrhea followed by nosocomial pneumonia, while the third patient developed multiple opportunistic infections (Pneumocystis pneumonia, cryptococcal septicemia and meningitis, Klebsiella septicemia. All 3 patients died within 1 year from the onset of the infection(s. We recommend that anti-TNF, especially when combined with other immunosuppressive therapy, should be used with extreme caution in older adult patients with IBD.

  20. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    International Nuclear Information System (INIS)

    Massi, Paola; Valenti, Marta; Solinas, Marta; Parolaro, Daniela

    2010-01-01

    Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells

  1. Visualization of liposomes by magnetic resonance imaging: an opportunity to improve antitumoral liposome therapies

    International Nuclear Information System (INIS)

    Martinez Bedoya, Darel

    2012-01-01

    Controlled release of drugs at the tumor site and the development of non-invasive monitoring techniques are two of the main challenges currently facing antitumoral therapies. The paper analyzes some of the potential uses of liposomes as vehicles for the transport of drugs to the tumors, particularly directionalized variants to tumor antigens through antibody coupling (immunoliposomes). These vesicles may also be used in combination with magnetic resonance, one of the most widely used imaging techniques, and one exhibiting great visualization potential at molecular level. Joint use of these two techniques makes it possible to control the amount of drug administered, as well as predict the efficacy of the treatment and monitor its progress

  2. Molecular Mechanisms Involved in the Antitumor Activity of Cannabinoids on Gliomas: Role for Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Paola Massi

    2010-05-01

    Full Text Available Cannabinoids, the active components of Cannabis sativa, have been shown to exert antiproliferative and proapoptotic effects on a wide spectrum of tumor cells and tissues. Of interest, cannabinoids have displayed great potency in reducing the growth of glioma tumors, one of the most aggressive CNS tumors, either in vitro or in animal experimental models curbing the growth of xenografts generated by subcutaneous or intrathecal injection of glioma cells in immune-deficient mice. Cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of non-transformed cells. This review will summarize the anti-cancer properties that cannabinoids exert on gliomas and discuss their potential action mechanisms that appear complex, involving modulation of multiple key cell signaling pathways and induction of oxidative stress in glioma cells.

  3. A Single Domain–Based Anti-Her2 Antibody Has Potent Antitumor Activities

    Directory of Open Access Journals (Sweden)

    Xiaoqiong Wu

    2018-04-01

    Full Text Available Human epidermal growth factor receptor 2 (HER2 is overexpressed in approximately 20% to 30% of breast cancers and various other types of cancers, which plays a vital role in the cancer progression. Monoclonal antibodies targeting Her2 are now used in the clinic to treat Her2 overexpression cancer patients. However, relapse or resistance is frequent with the current therapies. To generate a new treatment avenue against Her2, we immunized and selected a specific anti-Her2 single domain antibody C3 for further studies. The C3-Fc antibody drove antibody-dependent cell-mediated cytotoxicity against Her2-positive tumor cells in vitro and resulted in potent antitumor growth in vivo. These data suggest that the C3-Fc antibody may provide an alternative avenue for Her2-positive cancer therapy.

  4. Mechanisms Underlying the Anti-Aging and Anti-Tumor Effects of Lithocholic Bile Acid

    Directory of Open Access Journals (Sweden)

    Anthony Arlia-Ciommo

    2014-09-01

    Full Text Available Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research.

  5. Design, Synthesis and Biological Evaluation of C(6-Modified Celastrol Derivatives as Potential Antitumor Agents

    Directory of Open Access Journals (Sweden)

    Kaiyong Tang

    2014-07-01

    Full Text Available New six C6-celastrol derivatives were designed, synthesized, and evaluated for their in vitro cytotoxic activities against nine human cancer cell lines (BGC-823, H4, Bel7402, H522, Colo 205, HepG2 and MDA-MB-468. The results showed that most of the compounds displayed potent inhibition against BGC823, H4, and Bel7402, with IC50s of 1.84–0.39 μM. The best compound NST001A was tested in an in vivo antitumor assay on nude mice bearing Colo 205 xenografts, and showed significant inhibition of tumor growth at low concentrations. Therefore, celastrol C-6 derivatives are potential drug candidates for treating cancer.

  6. [Anti-tumor effects of DDP-PLLA-CNTs on human cholangiocarcinoma cell line in vitro].

    Science.gov (United States)

    Li, Maolan; Lu, Wei; Zhang, Fei; Ding, Qichen; Wu, Xiangsong; Tan, Zhujun; Wu, Wenguang; Weng, Hao; Wang, Xuefeng; Shi, Weibin; Dong, Ping; Gu, Jun; Liu, Yingbin

    2014-11-04

    To explore the antitumor effects of DDP-PLLA-CNTs on human cholangiocarcinoma cell line. DDP-PLLA-CNTs were prepared with the method of ultrasound emulsification. The morphology of DDP-PLLA-CNTs was determined by scanning electron microscope (SEM). And its drug loading and drug release curve in vitro was detected by UV-Vis-NIR spectrophotometer. CCK8 was used to test the cytotoxic effects of DDP-PLLA-CNTs at different concentrations on QBC939 cell proliferation.Flow cytometry was employed to measure the changes of apoptotic rate. With excellent controlled-release characteristic of in vitro drug release, DDP-PLLA-CNTs inhibited the proliferation and significantly increased the apoptotic rate of QBC939 cell line. DDP-PLLA-CNTs have drug sustained-release characteristics and can significantly inhibit the proliferation of QBC939 cell line.

  7. The Pig as a Large Animal Model for Studying Anti-Tumor Immune Responses

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr

    but also generates a selective pressure, which may lead to selection of tumor cell variants with reduced immunogenicity; thereby, increasing the risk of tumor escape. Cancer immunotherapy includes treatment strategies aimed at activating anti-tumor immune responses or inhibiting suppressive and tumor......-favorable immune mechanisms. One of the promising arms of cancer immunotherapy is peptide-based therapeutic vaccines; yet, no such vaccine has been approved for use in human oncology. For many years, mouse models have provided invaluable understanding of complex immunological pathways; however, the majority...... tolerance towards IDO and the establishment of an antigen-specific cell-mediated immune (CMI) response. When comparing the different CAF09-formulated antigen doses, we demonstrate the induction of a CMI-dominant response upon exposure to a low endogenous peptide dose. In contrast, a mixed CMI and humoral...

  8. Research on Characteristics, Antioxidant and Antitumor Activities of Dihydroquercetin and Its Complexes

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2017-12-01

    Full Text Available Dihydroquercetin is a kind of dihydroflavonol compounds with antioxidant, antitumor, antivirus and radioresistance activities. This study attempted to produce the dihydroquercetin complexes with lecithin and β-cyclodextrin, and research their characteristics and bioactivities via ultraviolet spectrum (UV, infrared spectroscopy (IR, scanning electron microscope (SEM, differential scanning calorimetry (DSC, X-ray diffraction spectrum (XRD, and MTT assay. Results showed that the complexes with lecithin and β-cyclodextrin could improve the solubility and dissolution rate, and remove the characteristic endothermic peak of dihydroquercetin. IR spectra proved their interaction, and results of SEM and XRD showed the amorphous characteristics of the dihydroquercetin compounds. These results indicated that dihydroquercetin was combined by lecithin or β-cyclodextrin with better physical and chemical properties, which would effectively improve the application value in the food and drug industries.

  9. Promotion of Tumor Invasion by Cooperation of Granulocytes and Macrophages Activated by Anti-tumor Antibodies

    Directory of Open Access Journals (Sweden)

    Emilio Barbera-Guillem

    1999-11-01

    Full Text Available We investigated the potential role of anti-tumor antibodies and tumor antigens in the formation of immune complexes which promote matrix degradation and angiogenesis. B-cell deficient or B-cell depleted mice showed a reduction in tumor invasion and metastasis. In vitro invasion assays and in vivo models of metastasis showed that anti-sTn antibodies and sTn tumor antigens form complexes which induce granulocytes and macrophages together to mediate tumor invasion and metastasis by processes including extracellular matrix degradation and angiogenesis. These results suggest the existence of a tumor promoting role of a B-cell immune response induced by shed tumor associated antigens of solid, nonlymphoid tumors.

  10. Antitumor and immunomodulatory effects of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

    Directory of Open Access Journals (Sweden)

    Rodrigo Rezende Kitagawa

    2011-12-01

    Full Text Available Large number of quinones has been associated with antitumor, antibacterial, antimalarial and antifungal activities. In this work we describe the effect of the naphthoquinone, 5-methoxy-3,4-dehydroxanthomegnin, on murine tumor cells (LP07 and LM2 and its immunomodulatory effect on nitric oxide (NO production on LPS-stimulated macrophages. The results have shown that 5-methoxy-3,4-dehydroxanthomegnin was a significant inhibitor of LPS-stimulated NO generation from macrophage (inhibition percentage ranged from 97.4 to 98.9% and a strong cytotoxic agent against both tumor cells LP07 and LM2 (CI50 6.2±0.36 µM and 74.6±1.9 µM, respectively. These results indicate that the 5-methoxy-3,4-dehydroxanthomegnin may show promising activity in the treatment of murine breast and lung cancer by immunomodulatory and antiproliferative activities.

  11. Antitumor and immunomodulatory effects of the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin

    Directory of Open Access Journals (Sweden)

    Rodrigo Rezende Kitagawa

    2011-08-01

    Full Text Available Large number of quinones has been associated with antitumor, antibacterial, antimalarial and antifungal activities. In this work we describe the effect of the naphthoquinone, 5-methoxy-3,4-dehydroxanthomegnin, on murine tumor cells (LP07 and LM2 and its immunomodulatory effect on nitric oxide (NO production on LPS-stimulated macrophages. The results have shown that 5-methoxy-3,4-dehydroxanthomegnin was a significant inhibitor of LPS-stimulated NO generation from macrophage (inhibition percentage ranged from 97.4 to 98.9% and a strong cytotoxic agent against both tumor cells LP07 and LM2 (CI50 6.2±0.36 µM and 74.6±1.9 µM, respectively. These results indicate that the 5-methoxy-3,4-dehydroxanthomegnin may show promising activity in the treatment of murine breast and lung cancer by immunomodulatory and antiproliferative activities.

  12. Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity

    Directory of Open Access Journals (Sweden)

    Tania Løve Aaes

    2016-04-01

    Full Text Available Successful immunogenic apoptosis in experimental cancer therapy depends on the induction of strong host anti-tumor responses. Given that tumors are often resistant to apoptosis, it is important to identify alternative molecular mechanisms that elicit immunogenic cell death. We have developed a genetic model in which direct dimerization of FADD combined with inducible expression of RIPK3 promotes necroptosis. We report that necroptotic cancer cells release damage-associated molecular patterns and promote maturation of dendritic cells, the cross-priming of cytotoxic T cells, and the production of IFN-γ in response to tumor antigen stimulation. Using both FADD-dependent and FADD-independent RIPK3 induction systems, we demonstrate the efficient vaccination potential of immunogenic necroptotic cells. Our study broadens the current concept of immunogenic cell death and opens doors for the development of new strategies in cancer therapy.

  13. Polaprezinc reduces paclitaxel-induced peripheral neuropathy in rats without affecting anti-tumor activity

    Directory of Open Access Journals (Sweden)

    Kuniaki Tsutsumi

    2016-06-01

    Full Text Available Paclitaxel, an anticancer drug, frequently causes painful peripheral neuropathy. In this study, we investigated the preventive effect of polaprezinc on paclitaxel-induced peripheral neuropathy in rats. Polaprezinc (3 mg/kg, p.o., once daily inhibited the development of mechanical allodynia induced by paclitaxel (4 mg/kg, i.p., on days 1, 3, 5 and 7 and suppressed the paclitaxel-induced increase in macrophage migration in dorsal root ganglion cells. In addition, polaprezinc did not affect the anti-tumor activity of paclitaxel in cultured cell lines or tumor-bearing mice. These results suggest a clinical indication for polaprezinc in the prevention of paclitaxel-induced neuropathy.

  14. Anti-tumor activity of metformin: from metabolic and epigenetic perspectives

    Science.gov (United States)

    Zhai, Yansheng; Tong, Chong; Liu, Min; Ma, Lixin; Yu, Xiaolan; Li, Shanshan

    2017-01-01

    Metformin has been used to treat type 2 diabetes for over 50 years. Epidemiological, preclinical and clinical studies suggest that metformin treatment reduces cancer incidence in diabetes patients. Due to its potential as an anti-cancer agent and its low cost, metformin has gained intense research interest. Its traditional anti-cancer mechanisms involve both indirect and direct insulin-dependent pathways. Here, we discussed the anti-tumor mechanism of metformin from the aspects of cell metabolism and epigenetic modifications. The effects of metformin on anti-cancer immunity and apoptosis were also described. Understanding these mechanisms will shed lights on application of metformin in clinical trials and development of anti-cancer therapy. PMID:27902459

  15. Cell-Centric View of Apoptosis and Apoptotic Cell Death-Inducing Antitumoral Strategies

    Directory of Open Access Journals (Sweden)

    Maria Dolores Boyano

    2011-03-01

    Full Text Available Programmed cell death and especially apoptotic cell death, occurs under physiological conditions and is also desirable under pathological circumstances. However, the more we learn about cellular signaling cascades, the less plausible it becomes to find restricted and well-limited signaling pathways. In this context, an extensive description of pathway-connections is necessary in order to point out the main regulatory molecules as well as to select the most appropriate therapeutic targets. On the other hand, irregularities in programmed cell death pathways often lead to tumor development and cancer-related mortality is projected to continue increasing despite the effort to develop more active and selective antitumoral compounds. In fact, tumor cell plasticity represents a major challenge in chemotherapy and improvement on anticancer therapies seems to rely on appropriate drug combinations. An overview of the current status regarding apoptotic pathways as well as available chemotherapeutic compounds provides a new perspective of possible future anticancer strategies.

  16. DNA crosslinking and cytotoxicity in normal and transformed human cells treated with antitumor nitrosoureas.

    Science.gov (United States)

    Erickson, L C; Bradley, M O; Ducore, J M; Ewig, R A; Kohn, K W

    1980-01-01

    Normal (IMR-90) and simian virus 40-transformed (VA-13) human embryo cells were treated with antitumor nitrosoureas, and the effects on cell viability and cell DNA were compared. All six nitrosoureas tested were more toxic to VA-13 cells than to IMR-90 cells as measured by decrease in cell proliferation or in colony formation. The nitrosoureas capable of generating alkylisocyanates produced a smaller difference between the cell types than did derivatives lacking this capacity. DNA damage was measured by alkaline elution in cells treated with four chloroethylnitrosoureas. Whereas VA-13 cells exhibited dose-dependent interstrand crosslinking, little or none was detected in IMR-90 cells. The IMR-90 cells, however, exhibited at least as much DNA-protein crosslinking as did VA-13 cells. The results can be interpreted in terms of a possible difference in DNA repair between the cell lines. PMID:6928639

  17. Regulatory T cell effects in antitumor laser immunotherapy: a mathematical model and analysis

    Science.gov (United States)

    Dawkins, Bryan A.; Laverty, Sean M.

    2016-03-01

    Regulatory T cells (Tregs) have tremendous influence on treatment outcomes in patients receiving immunotherapy for cancerous tumors. We present a mathematical model incorporating the primary cellular and molecular components of antitumor laser immunotherapy. We explicitly model developmental classes of dendritic cells (DCs), cytotoxic T cells (CTLs), primary and metastatic tumor cells, and tumor antigen. Regulatory T cells have been shown to kill antigen presenting cells, to influence dendritic cell maturation and migration, to kill activated killer CTLs in the tumor microenvironment, and to influence CTL proliferation. Since Tregs affect explicitly modeled cells, but we do not explicitly model dynamics of Treg themselves, we use model parameters to analyze effects of Treg immunosuppressive activity. We will outline a systematic method for assigning clinical outcomes to model simulations and use this condition to associate simulated patient treatment outcome with Treg activity.

  18. Chemical features of Ganoderma polysaccharides with antioxidant, antitumor and antimicrobial activities.

    Science.gov (United States)

    Ferreira, Isabel C F R; Heleno, Sandrina A; Reis, Filipa S; Stojkovic, Dejan; Queiroz, Maria João R P; Vasconcelos, M Helena; Sokovic, Marina

    2015-06-01

    Ganoderma genus comprises one of the most commonly studied species worldwide, Ganoderma lucidum. However, other Ganoderma species have been also reported as important sources of bioactive compounds. Polysaccharides are important contributors to the medicinal properties reported for Ganoderma species, as demonstrated by the numerous publications, including reviews, on this matter. Yet, what are the chemical features of Ganoderma polysaccharides that have bioactivity? In the present manuscript, the chemical features of Ganoderma polysaccharides with reported antioxidant, antitumor and antimicrobial activities (the most studied worldwide) are analyzed in detail. The composition of sugars (homo- versus hetero-glucans and other polysaccharides), type of glycosidic linkages, branching patterns, and linkage to proteins are discussed. Methods for extraction, isolation and identification are evaluated and, finally, the bioactivity of polysaccharidic extracts and purified compounds are discussed. The integration of data allows deduction of structure-activity relationships and gives clues to the chemical aspects involved in Ganoderma bioactivity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. A novel lipid-based nanomicelle of docetaxel: evaluation of antitumor activity and biodistribution

    Directory of Open Access Journals (Sweden)

    Ma M

    2012-07-01

    Full Text Available Mingshu Ma,1 Yanli Hao,1 Nan Liu,1 Zhe Yin,1 Lan Wang,1 Xingjie Liang,2 Xiaoning Zhang11Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing, China; 2National Center for Nanoscience and Technology, Beijing, ChinaPurpose: A lipid-based, nanomicelle-loaded docetaxel (M-DOC was designed and characterized. Optical imaging was employed to evaluate the pharmacokinetics and antitumor efficacy of docetaxel in vivo.Materials and methods: The M-DOC was prepared using the emulsion-diffusion method. Transmission electron microscopy and dynamic light scattering were used to assess the morphology and particle size of the M-DOC. Critical micelle concentrations, their stability under physiological conditions, and their encapsulation efficiency – as measured by high-performance liquid chromatography – were assessed. Pharmacological features were evaluated in two different animal models by comparing M-DOC treatments with docetaxel injections (I-DOC. Bioluminescence imaging was used to assess antitumor activity and docetaxel distribution in vivo, using nude mice injected with luciferase-expressing MDA-MB-231 human breast tumor cells. In addition, animals injected with B16 melanoma cells were used to measure survival time and docetaxel distribution.Results: The M-DOC was prepared as round, uniform spheres with an effective diameter of 20.8 nm. The critical micelle concentration of the original emulsion was 0.06%. Satisfactory encapsulation efficiency (87.6% ± 3.0% and 12-hour stability were achieved. Xenograft results demonstrated that the M-DOC was more effective in inhibiting tumor growth, without significantly changing body weight. Survival was prolonged by 12.6% in the M-DOC group. Tumor growth inhibitory rates in the M-DOC and I-DOC groups were 91.2% and 57.8% in volume and 71.8% and 44.9% in weight, respectively. Optical bioluminescence imaging of tumor growths yielded similar results. Area under the

  20. Generation of specific antitumor cytotoxic T-lymphocytes in the monoculture

    International Nuclear Information System (INIS)

    Lupatov, A.Yu.; Brondz, B.D.

    1992-01-01

    A new model for the generation of specific antitumor cytotoxic T-lymphocytes (CTL) was proposed. In contrast to other models, it allows to generate effector CTL without immunization in vitro. For estimation of cytotoxic activity, chromium-51 release assay was used. It has been shown that effector CTL were absent in the lymph nodes in 1-fold as well as 2-fold immunization. Specific CTL were detected only after secondary immunization and subsequent cultivation in vitro. Effector cells had Thy1.2 + , Lyt2 + , L3T4 - phenotypes. Presence in vitro of exogenous IL-2 was needed for the generation of CTL against MX-11 sarcoma but not against EL4 lymphoma. The release of IL-2 from lymphomas cells could stimulate generation of the effector cells through activation of the endogenous production of IL-2, or due to some other factors

  1. Evaluation of antitumor activity and in vivo antioxidant status of Anthocephalus cadamba on Ehrlich ascites carcinoma treated mice.

    Science.gov (United States)

    Dolai, Narayan; Karmakar, Indrajit; Suresh Kumar, R B; Kar, Biswakanth; Bala, Asis; Haldar, Pallab Kanti

    2012-08-01

    Anthocephalus cadamba (Roxb.) Miq. (Family: Rubiaceae) is commonly known as "Kadamba" in Sanskrit and Hindi in India. Various parts of this plant have been used as a folk medicine for the treatment of tumor, wound healing, inflammation and as a hypoglycemic agent. The purpose of this investigation was to evaluate the antitumor activity and antioxidant status of defatted methanol extract of A. cadamba (MEAC) on Ehrlich ascites carcinoma (EAC) treated mice. In vitro cytotoxicity assay has been evaluated by using the trypan blue method. The determination of in vivo antitumor activity was performed by using different EAC cells (2 × 10(6) cells, i.p.) inoculated mice groups (n=12). The groups were treated for 9 consecutive days with MEAC at the doses of 200 and 400 mg/kg b.w. respectively. After 24h of last dose and 18 h of fasting, half of the mice were sacrificed and the rest were kept alive for assessment of increase in life span. The antitumor potential of MEAC was assessed by evaluating tumor volume, viable and nonviable tumor cell count, tumor weight, hematological parameters and biochemical estimations. Furthermore, antioxidant parameters were assayed by estimating liver and kidney tissue enzymes. MEAC showed direct cytotoxicity on EAC cell line in a dose dependant manner. MEAC exhibited significant (P<0.01) decrease in the tumor volume, viable cell count, tumor weight and elevated the life span of EAC tumor bearing mice. The hematological profile, biochemical estimations and tissue antioxidant assay were reverted to normal level in MEAC treated mice. Experimental results revealed that MEAC possesses potent antitumor and antioxidant properties. Further research is going on to find out the active principle(s) of MEAC for better understanding of mechanism of its antitumor and antioxidant activity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Evaluation of cytotoxic and antitumoral properties of Tessaria absinthioides (Hook & Arn DC, "pájaro bobo", aqueous extract

    Directory of Open Access Journals (Sweden)

    Fabio A. Persia

    2017-08-01

    Full Text Available Higher plants have provided various natural derived drugs used currently in western medicine. Tessaria absinthioides (Hook. & Arn. DC, Asteraceae, is a native plant from South-America with reported ethnopharmacological and culinary uses. Despite recent scientific reports about plants properties, there is not a well conducted research about its anticancer and potential toxic effects. The current work demonstrates the plant aqueous extract composition; the in vitro induced cytotoxicity, and explores, in vivo, its oral toxicity and antitumoral effects. Composition of aqueous extract was determined by phytochemical reactions. Cytotoxicity was tested in tumoral (Hela, Gli-37, HCT-116 and MCF-7 and non-tumoral (HBL-100 cells, using MTT assay. Oral toxicity and the antitumor activity against colorectal carcinoma were studied in rodents. The chemical analysis revealed the presence of flavonoids, carbohydrates, sterols, terpenes and tannins. Cytotoxicity towards tumoral cells was observed (CV50: 3.0 to 14.8 ug/ml; while in non-tumoral cells, extracts evidenced a selective reduced toxicity (CV50: 29.5 ug/ml. Oral administration of the extract does not induce acute nor dose-repeated toxicity at doses up to 2000 mg/kg and 1000 mg/kg/day, respectively. The antitumoral effect was confirmed by a significant increase in a median survival from 24 weeks (non-treated to 30 weeks (T. absinthioides treated. The present data indicate that T. absinthioides extract exhibits cytotoxicity against cancer cell lines, with no-toxic effects and significant antitumoral effects in colorectal cancer when is orally administrated. In conclusion, T. absinthioides possesses selective cytotoxicity and antitumoral activities, making its plant derivatives products promising for cancer research and treatment.

  3. Delivery of vincristine sulfate-conjugated gold nanoparticles using liposomes: a light-responsive nanocarrier with enhanced antitumor efficiency

    Directory of Open Access Journals (Sweden)

    Liu Y

    2015-04-01

    Full Text Available Ying Liu,1,* Man He,1,* Mengmeng Niu,1 Yiqing Zhao,1 Yuanzhang Zhu,1 Zhenhua Li,2 Nianping Feng1 1Department of Pharmaceutical Sciences, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Cedars-Sinai Medical Center, Los Angeles, CA, USA *These authors contributed equally to this work Abstract: Rapid drug release at the specific site of action is still a challenge for antitumor therapy. Development of stimuli-responsive hybrid nanocarriers provides a promising strategy to enhance therapeutic effects by combining the unique features of each component. The present study explored the use of drug–gold nanoparticle conjugates incorporated into liposomes to enhance antitumor efficiency. A model drug, vincristine sulfate, was physically conjugated with gold nanoparticles and verified by UV-visible and fourier transform infrared spectroscopy, and differential scanning calorimetry. The conjugates were incorporated into liposomes by film dispersion to yield nanoparticles (113.4 nm with light-responsive release properties, as shown by in vitro release studies. Intracellular uptake and distribution was studied in HeLa cells using transmission electron microscopy and confocal laser scanning microscopy. This demonstrated liposome internalization and localization in endosomal–lysosomal vesicles. Fluorescence intensity increased in cells exposed to UV light, indicating that this stimulated intracellular drug release; this finding was confirmed by quantitative analyses using flow cytometry. Antitumor efficacy was evaluated in HeLa cells, both in culture and in implants in vivo in nude mice. HeLa cell viability assays showed that light exposure enhanced liposome cytotoxicity and induction of apoptosis. Furthermore, treatment with the prepared liposomes coupled with UV light exposure produced greater antitumor effects in nude mice and reduced side effects, as compared with free vincristine sulfate

  4. Immunotherapeutic effect of Concholepas hemocyanin in the murine bladder cancer model: evidence for conserved antitumor properties among hemocyanins.

    Science.gov (United States)

    Moltedo, Bruno; Faunes, Fernando; Haussmann, Denise; De Ioannes, Pablo; De Ioannes, Alfredo E; Puente, Javier; Becker, María Inés

    2006-12-01

    We determined the antitumor properties of a newly available hemocyanin obtained from the Chilean gastropod Concholepas concholepas (Biosonda Corp., Santiago, Chile) in a syngeneic heterotopic mouse bladder carcinoma model. Since keyhole limpet hemocyanin (Pierce, Rockford, Illinois) is used increasingly in biomedicine as a carrier for vaccines and an immunotherapeutic agent for bladder transitional cell carcinoma, there is a growing interest in finding new substances that share its potent immunomodulatory properties. Considering that keyhole limpet hemocyanin and Concholepas concholepas hemocyanin differ significantly, it was not possible to predict a priori the antitumor properties of Concholepas concholepas hemocyanin. C3H/He mice were primed with Concholepas concholepas hemocyanin before subcutaneous implantation of mouse bladder tumor-2 cells. Treatment consisted of a subcutaneous dose of Concholepas concholepas hemocyanin (1 mg or 100 mug) at different intervals after implantation. Keyhole limpet hemocyanin and phosphate buffered saline served as positive and negative controls, respectively. In addition, experiments were designed to determine which elements of the immune response were involved in its adjuvant immunostimulatory effect. Mice treated with Concholepas concholepas hemocyanin showed a significant antitumor effect, as demonstrated by decreased tumor growth and incidence, prolonged survival and lack of toxic effects. These effects were similar to those achieved with keyhole limpet hemocyanin. We found that each hemocyanin increased natural killer cell activity but the effect of Concholepas concholepas hemocyanin was stronger. Analysis of serum from treated mice showed an increased interferon-gamma and low interleukin-4, which correlated with antibody isotypes, confirming that hemocyanins induce a T helper type 1 cytokine profile. To our knowledge our results are the first demonstration of the antitumor effect of a hemocyanin other than keyhole limpet

  5. Cytotoxicity and anti-tumor effects of new ruthenium complexes on triple negative breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Cecília P Popolin

    Full Text Available Triple-negative breast cancer (TNBC is a highly aggressive breast cancer subtype. The high rate of metastasis associated to the fact that these cells frequently display multidrug resistance, make the treatment of metastatic disease difficult. Development of antitumor metal-based drugs was started with the discovery of cisplatin, however, the severe side effects represent a limitation for its clinical use. Ruthenium (Ru complexes with different ligands have been successfully studied as prospective antitumor drugs. In this work, we demonstrated the activity of a series of biphosphine bipyridine Ru complexes (1 [Ru(SO4(dppb(bipy], (2 [Ru(CO3(dppb(bipy], (3 [Ru(C2O4(dppb(bipy] and (4 [Ru(CH3CO2(dppb(bipy]PF6 [where dppb = 1,4-bis(diphenylphosphinobutane and bipy = 2,2'-bipyridine], on proliferation of TNBC (MDA-MB-231, estrogen-dependent breast tumor cells (MCF-7 and a non-tumor breast cell line (MCF-10A. Complex (4 was most effective among the complexes and was selected to be further investigated on effects on tumor cell adhesion, migration, invasion and in apoptosis. Moreover, DNA and HSA binding properties of this complex were also investigated. Results show that complex (4 was more efficient inhibiting proliferation of MDA-MB-231 cells over non-tumor cells. In addition, complex (4 was able to inhibit MDA-MB231 cells adhesion, migration and invasion and to induce apoptosis and inhibit MMP-9 secretion in TNBC cells. Complex (4 should be further investigated in vivo in order to stablish its potential to improve breast cancer treatment.

  6. Ibrutinib, a Bruton's tyrosine kinase inhibitor, exhibits antitumoral activity and induces autophagy in glioblastoma.

    Science.gov (United States)

    Wang, Jin; Liu, Xiaoyang; Hong, Yongzhi; Wang, Songtao; Chen, Pin; Gu, Aihua; Guo, Xiaoyuan; Zhao, Peng

    2017-07-17

    Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, is a novel anticancer drug used for treating several types of cancers. In this study, we aimed to determine the role of ibrutinib on GBM. Cell proliferation was determined by using cell viability, colony formation, and 5-ethynyl-2'-deoxyuridine (EdU) assays. Cell cycle and cell apoptosis were analyzed by flow cytometry. Cell migratory ability was evaluated by wound healing assays and trans-well migration assays. ATG7 expression was knocked-down by transfection with Atg7-specific small interfering RNA. Overexpression of active Akt protein was achieved by transfecting the cells with a plasmid expressing constitutively active Akt (CA-Akt). Transmission electron microscopy was performed to examine the formation of autophagosomes in cells. Immunofluorescence and western blot analyses were used to analyze protein expression. Tumor xenografts in nude mice and immunohistochemistry were performed to evaluate the effect of ibrutinib on tumor growth in vivo. Ibrutinib inhibited cellular proliferation and migration, and induced apoptosis and autophagy in LN229 and U87 cells. Overexpression of the active Akt protein decreased ibrutinib-induced autophagy, while inhibiting Akt by LY294002 treatment enhanced ibrutinib-induced autophagy. Specific inhibition of autophagy by 3-methyladenine (3MA) or Atg7 targeting with small interfering RNA (si-Atg7) enhanced the anti-GBM effect of ibrutinib in vitro and in vivo. Our results indicate that ibrutinib exerts a profound antitumor effect and induces autophagy through Akt/mTOR signaling pathway in GBM cells. Autophagy inhibition promotes the antitumor activity of ibrutinib in GBM. Our findings provide important insights into the action of an anticancer agent combining with autophagy inhibitor for malignant glioma.

  7. Antitumor effects of cecropin B-LHRH’ on drug-resistant ovarian and endometrial cancer cells

    International Nuclear Information System (INIS)

    Li, Xiaoyong; Shen, Bo; Chen, Qi; Zhang, Xiaohui; Ye, Yiqing; Wang, Fengmei; Zhang, Xinmei

    2016-01-01

    Luteinizing hormone-releasing hormone receptor (LHRHr) represents a promising therapeutic target for treating sex hormone-dependent tumors. We coupled cecropin B, an antimicrobial peptide, to LHRH’, a form of LHRH modified at carboxyl-terminal residues 4–10, which binds to LHRHr without interfering with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. This study aimed to assess the antitumor effects of cecropin B-LHRH’ (CB-LHRH’) in drug-resistant ovarian and endometrial cancers. To evaluate the antitumor effects of CB-LHRH’, three drug resistant ovarian cancer cell lines (SKOV-3, ES-2, NIH:OVCAR-3) and an endometrial cancer cell line (HEC-1A) were treated with CB-LHRH’. Cell morphology changes were assessed using inverted and electron microscopes. In addition, cell growth and cell cytotoxicity were measured by MTT assay and LDH release, respectively. In addition, hemolysis was measured. Furthermore, radioligand receptor binding, hypersensitization and minimal inhibitory concentrations (against Staphylococcus aureus, Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae, Pseudomonas aeruginosa, and Acinetobacter baumannii) were determined. Finally, the impact on tumor growth in BALB/c-nu mice was assessed in an ES-2 xenograft model. CB-LHRH’ bound LHRHr with high-affinity (dissociation constant, Kd = 0.252 ± 0.061nM). Interestingly, CB-LHRH’ significantly inhibited the cell viability of SKOV-3, ES-2, NIH:OVCAR-3 and HEC-1A, but not that of normal eukaryotic cells. CB-LHRH’ was active against bacteria at micromolar concentrations, and caused no hypersensitivity in guinea pigs. Furthermore, CB-LHRH’ inhibited tumor growth with a 23.8 and 20.4 % reduction in tumor weight at 50 and 25 mg/kg.d, respectively. CB-LHRH’ is a candidate for targeted chemotherapy against ovarian and endometrial cancers

  8. Extended Antitumor Responseof a BRAF V600E Papillary Thyroid Carcinoma to Vemurafenib

    Directory of Open Access Journals (Sweden)

    Siraj M. Ali

    2014-05-01

    Full Text Available Context: For patients with metastatic papillary thyroid carcinoma (PTC refractory to radioactive iodine (RAI treatment, systemic chemotherapy has limited efficacy. Such tumors frequently harbor BRAF V600E, and this alteration may predict responsiveness to vemura-fenib treatment. Objective: We report a metastatic PTC patient refractory to RAI treatment that underwent genomic profiling by next-generation sequencing. The sole genomic alteration identified was BRAF V600E on a near diploid genome with trisomy 1q. With vemurafenib treatment, the patient experienced a dramatic radiographic and clinical improvement, with the duration of an ongoing antitumor response exceeding 23 months. Design: Hybridization capture of 3,769 exons of 236 cancer-related genes and the introns of 19 genes frequently rearranged in cancer was applied to >50 ng of DNA extracted from a formalin-fixed, paraffin-embedded biopsy of a lymph node containing metastatic PTC and was sequenced to a high, uniform coverage of ×616. Results: A BRAF V600E alteration was identified with no other somatic genomic alterations present within a near diploid tumor genome. The patient initially received vemurafenib at 960 mg twice daily that was reduced to 480 mg twice daily due to rash and diarrhea and has experienced an ongoing antitumor response exceeding 23 months by both PET-CT and dedicated CT imaging. Conclusions: Genomic profiling in metastatic, RAI-refractory PTC can reveal a targetable BRAF V600E alteration without compounding somatic alterations, and such patients may derive a more prolonged benefit from vemurafenib treatment. Prospective clinical trials are ongoing to confirm our preliminary observation.

  9. Inhibition of angiogenesis: a novel antitumor mechanism of the herbal compound arctigenin.

    Science.gov (United States)

    Gu, Yuan; Scheuer, Claudia; Feng, Dilu; Menger, Michael D; Laschke, Matthias W

    2013-09-01

    Arctigenin, a functional ingredient of several traditional Chinese herbs, has been reported to have potential antitumor activity. However, its mechanisms of action are still not well elucidated. Because the establishment and metastatic spread of tumors is crucially dependent on angiogenesis, here we investigated whether arctigenin inhibits tumor growth by disturbing blood vessel formation. For this purpose, human dermal microvascular endothelial cells were exposed to different arctigenin doses to study their viability, proliferation, protein expression, migration, and tube formation compared with vehicle-treated controls. In addition, arctigenin action on vascular sprouting was analyzed in an aortic ring assay. Furthermore, we studied direct arctigenin effects on CT26.WT colon carcinoma cells. Spheroids of these tumor cells were transplanted into the dorsal skinfold chamber of arctigenin-treated and vehicle-treated BALB/c mice for the in-vivo analysis of tumor vascularization and growth by intravital fluorescence microscopy, histology, and immunohistochemistry. We found that noncytotoxic doses of arctigenin dose dependently reduced the proliferation of human dermal microvascular endothelial cells without affecting their migratory and tube-forming capacity. Arctigenin treatment also resulted in a decreased cellular expression of phosphorylated serine/threonine protein kinase AKT, vascular endothelial growth factor receptor 2, and proliferating cell nuclear antigen and inhibited vascular sprouting from aortic rings. In addition, proliferation, but not secretion of vascular endothelial growth factor, was decreased in arctigenin-treated tumor cells. Finally, arctigenin suppressed the vascularization and growth of engrafting CT26.WT tumors in the dorsal skinfold chamber model. Taken together, these results show for the first time an antiangiogenic action of arctigenin, which may contribute considerably toward its antitumor activity.

  10. Regorafenib: Antitumor Activity upon Mono and Combination Therapy in Preclinical Pediatric Malignancy Models.

    Directory of Open Access Journals (Sweden)

    Estelle Daudigeos-Dubus

    Full Text Available The multikinase inhibitor regorafenib (BAY 73-4506 exerts both anti-angiogenic and anti-tumorigenic activity in adult solid malignancies mainly advanced colorectal cancer and gastrointestinal stromal tumors. We intended to explore preclinically the potential of regorafenib against solid pediatric malignancies alone and in combination with anticancer agents to guide the pediatric development plan. In vitro effects on cell proliferation were screened against 33 solid tumor cell lines of the Innovative Therapies for Children with Cancer (ITCC panel covering five pediatric solid malignancies. Regorafenib inhibited cell proliferation with a mean half maximal growth inhibition of 12.5 μmol/L (range 0.7 μmol/L to 28 μmol/L. In vivo, regorafenib was evaluated alone at 10 or 30 mg/kg/d or in combination with radiation, irinotecan or the mitogen-activated protein kinase kinase (MEK inhibitor refametinib against various tumor types, including patient-derived brain tumor models with an amplified platelet-derived growth factor receptor A (PDGFRA gene. Regorafenib alone significantly inhibited tumor growth in all xenografts derived from nervous system and connective tissue tumors. Enhanced effects were observed when regorafenib was combined with irradiation and irinotecan against PDGFRA amplified IGRG93 glioma and IGRM57 medulloblastoma respectively, resulting in 100% tumor regressions. Antitumor activity was associated with decreased tumor vascularization, inhibition of PDGFR signaling, and induction of apoptotic cell death. Our work demonstrates that regorafenib exhibits significant antitumor activity in a wide spectrum of preclinical pediatric models through inhibition of angiogenesis and induction of apoptosis. Furthermore, radio- and chemosensitizing effects were observed with DNA damaging agents in PDGFR amplified tumors.

  11. Regorafenib: Antitumor Activity upon Mono and Combination Therapy in Preclinical Pediatric Malignancy Models.

    Science.gov (United States)

    Daudigeos-Dubus, Estelle; Le Dret, Ludivine; Lanvers-Kaminsky, Claudia; Bawa, Olivia; Opolon, Paule; Vievard, Albane; Villa, Irène; Pagès, Mélanie; Bosq, Jacques; Vassal, Gilles; Zopf, Dieter; Geoerger, Birgit

    2015-01-01

    The multikinase inhibitor regorafenib (BAY 73-4506) exerts both anti-angiogenic and anti-tumorigenic activity in adult solid malignancies mainly advanced colorectal cancer and gastrointestinal stromal tumors. We intended to explore preclinically the potential of regorafenib against solid pediatric malignancies alone and in combination with anticancer agents to guide the pediatric development plan. In vitro effects on cell proliferation were screened against 33 solid tumor cell lines of the Innovative Therapies for Children with Cancer (ITCC) panel covering five pediatric solid malignancies. Regorafenib inhibited cell proliferation with a mean half maximal growth inhibition of 12.5 μmol/L (range 0.7 μmol/L to 28 μmol/L). In vivo, regorafenib was evaluated alone at 10 or 30 mg/kg/d or in combination with radiation, irinotecan or the mitogen-activated protein kinase kinase (MEK) inhibitor refametinib against various tumor types, including patient-derived brain tumor models with an amplified platelet-derived growth factor receptor A (PDGFRA) gene. Regorafenib alone significantly inhibited tumor growth in all xenografts derived from nervous system and connective tissue tumors. Enhanced effects were observed when regorafenib was combined with irradiation and irinotecan against PDGFRA amplified IGRG93 glioma and IGRM57 medulloblastoma respectively, resulting in 100% tumor regressions. Antitumor activity was associated with decreased tumor vascularization, inhibition of PDGFR signaling, and induction of apoptotic cell death. Our work demonstrates that regorafenib exhibits significant antitumor activity in a wide spectrum of preclinical pediatric models through inhibition of angiogenesis and induction of apoptosis. Furthermore, radio- and chemosensitizing effects were observed with DNA damaging agents in PDGFR amplified tumors.

  12. Regorafenib (BAY 73-4506): antitumor and antimetastatic activities in preclinical models of colorectal cancer.

    Science.gov (United States)

    Schmieder, Roberta; Hoffmann, Jens; Becker, Michael; Bhargava, Ajay; Müller, Tina; Kahmann, Nicole; Ellinghaus, Peter; Adams, Robert; Rosenthal, André; Thierauch, Karl-Heinz; Scholz, Arne; Wilhelm, Scott M; Zopf, Dieter

    2014-09-15

    Regorafenib, a novel multikinase inhibitor, has recently demonstrated overall survival benefits in metastatic colorectal cancer (CRC) patients. Our study aimed to gain further insight into the molecular mechanisms of regorafenib and to assess its potential in combination therapy. Regorafenib was tested alone and in combination with irinotecan in patient-derived (PD) CRC models and a murine CRC liver metastasis model. Mechanism of action was investigated using in vitro functional assays, immunohistochemistry and correlation with CRC-related oncogenes. Regorafenib demonstrated significant inhibition of growth-factor-mediated vascular endothelial growth factor receptor (VEGFR) 2 and VEGFR3 autophosphorylation, and intracellular VEGFR3 signaling in human umbilical vascular endothelial cells (HuVECs) and lymphatic endothelial cells (LECs), and also blocked migration of LECs. Furthermore, regorafenib inhibited proliferation in 19 of 25 human CRC cell lines and markedly slowed tumor growth in five of seven PD xenograft models. Combination of regorafenib with irinotecan significantly delayed tumor growth after extended treatment in four xenograft models. Reduced CD31 staining indicates that the antiangiogenic effects of regorafenib contribute to its antitumor activity. Finally, regorafenib significantly delayed disease progression in a murine CRC liver metastasis model by inhibiting the growth of established liver metastases and preventing the formation of new metastases in other organs. In addition, our results suggest that regorafenib displays antimetastatic activity, which may contribute to its efficacy in patients with metastatic CRC. Combination of regorafenib and irinotecan demonstrated an increased antitumor effect and could provide a future treatment option for CRC patients. © 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  13. Improving aqueous solubility and antitumor effects by nanosized gambogic acid-mPEG2000 micelles

    Directory of Open Access Journals (Sweden)

    Cai LL

    2013-12-01

    Full Text Available Lulu Cai,1,* Neng Qiu,2,* Mingli Xiang,3,* Rongsheng Tong,1 Junfeng Yan,1 Lin He,1 Jianyou Shi,1 Tao Chen,4 Jiaolin Wen,3 Wenwen Wang,3 Lijuan Chen31Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, 2College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, 3State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, People's Republic of China; 4Faculty of Pharmacy, University of Montreal, Montreal, QC, Canada *These authors contributed equally to this paperAbstract: The clinical application of gambogic acid, a natural component with promising antitumor activity, is limited due to its extremely poor aqueous solubility, short half-life in blood, and severe systemic toxicity. To solve these problems, an amphiphilic polymer-drug conjugate was prepared by attachment of low molecular weight (ie, 2 kDa methoxy poly(ethylene glycol methyl ether (mPEG to gambogic acid (GA-mPEG2000 through an ester linkage and characterized by 1H nuclear magnetic resonance. The GA-mPEG2000 conjugates self-assembled to form nanosized micelles, with mean diameters of less than 50 nm, and a very narrow particle size distribution. The properties of the GA-mPEG2000 micelles, including morphology, stability, molecular modeling, and drug release profile, were evaluated. MTT (3-(4,5-dimethylthiazol-2-yl-2,5 diphenyl tetrazolium bromide tests demonstrated that the GA-mPEG2000 micelle formulation had obvious cytotoxicity to tumor cells and human umbilical vein endothelial cells. Further, GA-mPEG2000 micelles were effective in inhibiting tumor growth and prolonged survival in subcutaneous B16-F10 and C26 tumor models. Our findings suggest that GA-mPEG2000 micelles may have promising applications in tumor therapy.Keywords: gambogic acid, poly(ethylene glycol-drug conjugate, micelle, antitumor, toxicity

  14. Aspirin Has Antitumor Effects via Expression of Calpain Gene in Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Sang Koo Lee

    2008-01-01

    Full Text Available Aspirin and other nonsteroidal anti-inflammatory drugs show efficacy in the prevention of cancers. It is known that they can inhibit cyclooxygenases, and some studies have shown that they can induce apoptosis. Our objective in this study was to investigate the mechanism by which aspirin exerts its apoptosis effects in human cervical cancer HeLa cells. The effect of aspirin on the gene expression was studied by differential mRNA display RT-PCR. Among the isolated genes, mu-type calpain gene was upregulated by aspirin treatment. To examine whether calpain mediates the antitumor effects, HeLa cells were stably transfected with the mammalian expression vector pCR3.1 containing mu-type calpain cDNA (pCRCAL/HeLa, and tumor formations were measured in nude mice. When tumor burden was measured by day 49, HeLa cells and pCR/HeLa cells (vector control produced tumors of 2126 mm3 and 1638 mm3, respectively, while pCRCAL/HeLa cells produced markedly smaller tumor of 434 mm3 in volume. The caspase-3 activity was markedly elevated in pCRCAL/HeLa cells. The increased activity levels of caspase-3 in pCRCAL/HeLa cells, in parallel with the decreased tumor formation, suggest a correlation between caspase-3 activity and calpain protein. Therefore, we conclude that aspirin-induced calpain mediates an antitumor effect via caspase-3 in cervical cancer cells.

  15. Structure and Antitumor and Immunomodulatory Activities of a Water-Soluble Polysaccharide from Dimocarpus longan Pulp

    Science.gov (United States)

    Meng, Fa-Yan; Ning, Yuan-Ling; Qi, Jia; He, Zhou; Jie, Jiang; Lin, Juan-Juan; Huang, Yan-Jun; Li, Fu-Sen; Li, Xue-Hua

    2014-01-01

    A new water-soluble polysaccharide (longan polysaccharide 1 (LP1)) was extracted and successfully purified from Dimocarpus longan pulp via diethylaminoethyl (DEAE)-cellulose anion-exchange and Sephacryl S-300 HR gel chromatography. The chemical structure was determined using Infrared (IR), gas chromatography (GC) and nuclear magnetic resonance (NMR) analysis. The results indicated that the molecular weight of the sample was 1.1 × 105 Da. Monosaccharide composition analysis revealed that LP1 was composed of Glc, GalA, Ara and Gal in a molar ratio of 5.39:1.04:0.74:0.21. Structural analysis indicated that LP1 consisted of a backbone of →4)-α-d-Glcp-(1→4)-α-d-GalpA-(1→4)-α-d-Glcp-(1→4)-β-d-Glcp-(1→ units with poly saccharide side chains composed of →2)-β-d-Fruf-(1→2)-l-sorbose-(1→ attached to the O-6 position of the α-d-Glcp residues. In vitro experiments indicated that LP1 had significantly high antitumor activity against SKOV3 and HO8910 tumor cells, with inhibition percentages of 40% and 50%, respectively. In addition, LP1 significantly stimulated the production of the cytokine interferon-γ (IFN-γ), increased the activity of murine macrophages and enhanced B- and T-lymphocyte proliferation. The results of this study demonstrate that LP1 has potential applications as a natural antitumor agent with immunomodulatory activity. PMID:24663085

  16. Antitumor activity of pan-HER inhibitors in HER2-positive gastric cancer.

    Science.gov (United States)

    Yoshioka, Takahiro; Shien, Kazuhiko; Namba, Kei; Torigoe, Hidejiro; Sato, Hiroki; Tomida, Shuta; Yamamoto, Hiromasa; Asano, Hiroaki; Soh, Junichi; Tsukuda, Kazunori; Nagasaka, Takeshi; Fujiwara, Toshiyoshi; Toyooka, Shinichi

    2018-04-01

    Molecularly targeted therapy has enabled outstanding advances in cancer treatment. Whereas various anti-human epidermal growth factor receptor 2 (HER2) drugs have been developed, trastuzumab is still the only anti-HER2 drug presently available for gastric cancer. In this study, we propose novel treatment options for patients with HER2-positive gastric cancer. First, we determined the molecular profiles of 12 gastric cancer cell lines, and examined the antitumor effect of the pan-HER inhibitors afatinib and neratinib in those cell lines. Additionally, we analyzed HER2 alteration in 123 primary gastric cancers resected from Japanese patients to clarify possible candidates with the potential to respond to these drugs. In the drug sensitivity analysis, both afatinib and neratinib produced an antitumor effect in most of the HER2-amplified cell lines. However, some cells were not sensitive to the drugs. When the molecular profiles of the cells were compared based on the drug sensitivities, we found that cancer cells with lower mRNA expression levels of IGFBP7, a tumor suppressor gene that inhibits the activation of insulin-like growth factor-1 receptor (IGF-1R), were less sensitive to pan-HER inhibitors. A combination therapy consisting of pan-HER inhibitors and an IGF-1R inhibitor, picropodophyllin, showed a notable synergistic effect. Among 123 clinical samples, we found 19 cases of HER2 amplification and three cases of oncogenic mutations. In conclusion, afatinib and neratinib are promising therapeutic options for the treatment of HER2-amplified gastric cancer. In addition to HER2 amplification, IGFBP7 might be a biomarker of sensitivity to these drugs, and IGF-1R-targeting therapy can overcome drug insensitiveness in HER2-amplified gastric cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  17. Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines.

    Science.gov (United States)

    Massi, Paola; Vaccani, Angelo; Ceruti, Stefania; Colombo, Arianna; Abbracchio, Maria P; Parolaro, Daniela

    2004-03-01

    Recently, cannabinoids (CBs) have been shown to possess antitumor properties. Because the psychoactivity of cannabinoid compounds limits their medicinal usage, we undertook the present study to evaluate the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines. The addition of CBD to the culture medium led to a dramatic drop of mitochondrial oxidative metabolism [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide test] and viability in glioma cells, in a concentration-dependent manner that was already evident 24 h after CBD exposure, with an apparent IC(50) of 25 microM. The antiproliferative effect of CBD was partially prevented by the CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethylbicyclo[2,2,1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; SR2) and alpha-tocopherol. By contrast, the CB1 cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716; SR1), capsazepine (vanilloid receptor antagonist), the inhibitors of ceramide generation, or pertussis toxin did not counteract CBD effects. We also show, for the first time, that the antiproliferative effect of CBD was correlated to induction of apoptosis, as determined by cytofluorimetric analysis and single-strand DNA staining, which was not reverted by cannabinoid antagonists. Finally, CBD, administered s.c. to nude mice at the dose of 0.5 mg/mouse, significantly inhibited the growth of subcutaneously implanted U87 human glioma cells. In conclusion, the nonpsychoactive CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent.

  18. Gut Microbiota Promotes Obesity-Associated Liver Cancer through PGE2-Mediated Suppression of Antitumor Immunity.

    Science.gov (United States)

    Loo, Tze Mun; Kamachi, Fumitaka; Watanabe, Yoshihiro; Yoshimoto, Shin; Kanda, Hiroaki; Arai, Yuriko; Nakajima-Takagi, Yaeko; Iwama, Atsushi; Koga, Tomoaki; Sugimoto, Yukihiko; Ozawa, Takayuki; Nakamura, Masaru; Kumagai, Miho; Watashi, Koichi; Taketo, Makoto M; Aoki, Tomohiro; Narumiya, Shuh; Oshima, Masanobu; Arita, Makoto; Hara, Eiji; Ohtani, Naoko

    2017-05-01

    Obesity increases the risk of cancers, including hepatocellular carcinomas (HCC). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram-positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment. LTA enhances the senescence-associated secretory phenotype (SASP) of hepatic stellate cells (HSC) collaboratively with an obesity-induced gut microbial metabolite, deoxycholic acid, to upregulate the expression of SASP factors and COX2 through Toll-like receptor 2. Interestingly, COX2-mediated prostaglandin E 2 (PGE 2 ) production suppresses the antitumor immunity through a PTGER4 receptor, thereby contributing to HCC progression. Moreover, COX2 overexpression and excess PGE 2 production were detected in HSCs in human HCCs with noncirrhotic, nonalcoholic steatohepatitis (NASH), indicating that a similar mechanism could function in humans. Significance: We showed the importance of the gut-liver axis in obesity-associated HCC. The gut microbiota-driven COX2 pathway produced the lipid mediator PGE 2 in senescent HSCs in the tumor microenvironment, which plays a pivotal role in suppressing antitumor immunity, suggesting that PGE 2 and its receptor may be novel therapeutic targets for noncirrhotic NASH-associated HCC. Cancer Discov; 7(5); 522-38. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 443 . ©2017 American Association for Cancer Research.

  19. In vitro and in vivo antitumor effects of chloroquine on oral squamous cell carcinoma

    Science.gov (United States)

    Jia, Lihua; Wang, Juan; Wu, Tong; Wu, Jinan; Ling, Junqi; Cheng, Bin

    2017-01-01

    Chloroquine, which is a widely used antimalarial drug, has been reported to exert anticancer activity in some tumor types; however, its potential effects on oral squamous cell carcinoma (OSCC) remain unclear. The present study aimed to explore the effects and possible underlying mechanisms of chloroquine against OSCC. MTT and clonogenic assays were conducted to evaluate the effects of chloroquine on the human OSCC cell lines SCC25 and CAL27. Cell cycle progression and apoptosis were detected using flow cytometry. Autophagy was monitored using microtubule-associated protein 1A/1B-light chain 3 as an autophagosomal marker. In order to determine the in vivo antitumor effects of chloroquine on OSCC, a CAL27 xenograft model was used. The results demonstrated that chloroquine markedly inhibited the proliferation and the colony-forming ability of both OSCC cell lines in a dose- and time-dependent manner in vitro. Chloroquine also disrupted the cell cycle, resulting in the cell cycle arrest of CAL27 and SCC25 cells at G0/G1 phase, via downregulation of cyclin D1. In addition, chloroquine inhibited autophagy, and induced autophagosome and autolysosome accumulation in the cytoplasm, thus interfering with degradation; however, OSCC apoptosis was barely affected by chloroquine. The results of the in vivo study demonstrated that chloroquine effectively inhibited OSCC tumor growth in the CAL27 xenograft model. In conclusion, the present study reported the in vitro and in vivo antitumor effects of chloroquine on OSCC, and the results indicated that chloroquine may be considered a potent therapeutic agent against human OSCC. PMID:28849182

  20. In vitro antitumor actions of extracts from endemic plant Helichrysum zivojinii

    Directory of Open Access Journals (Sweden)

    Matić Ivana Z

    2013-02-01

    Full Text Available Abstract Background The aim of this research was to determine the intensity and mechanisms of the cytotoxic actions of five extracts isolated from the endemic plant species Helichrysum zivojinii Černjavski & Soška (family Asteraceae against specific cancer cell lines. In order to evaluate the sensitivity of normal immunocompetent cells implicated in the antitumor immune response, the cytotoxicity of extracts was also tested against healthy peripheral blood mononuclear cells (PBMC. Methods The aerial parts of the plants were air-dried, powdered, and successively extracted with solvents of increasing polarity to obtain hexane, dichloromethane, ethyl-acetate, n-butanol and methanol extracts. The cytotoxic activities of the extracts against human cervix adenocarcinoma HeLa, human melanoma Fem-x, human myelogenous leukemia K562, human breast adenocarcinoma MDA-MB-361 cells and PBMC were evaluated by the MTT test. The mode of HeLa cell death was investigated by morphological analysis. Changes in the cell cycle of HeLa cells treated with the extracts were analyzed by flow cytometry. The apoptotic mechanisms induced by the tested extracts were determined using specific caspase inhibitors. Results The investigated Helichrysum zivojinii extracts exerted selective dose-dependent cytotoxic actions against selected cancer cell lines and healthy immunocompetent PBMC stimulated to proliferate, while the cytotoxic actions exerted on unstimulated PBMC were less pronounced. The tested extracts exhibited considerably stronger cytotoxic activities towards HeLa, Fem-x and K562 cells in comparison to resting and stimulated PBMC. It is worth noting that the cytotoxicity of the extracts was weaker against unstimulated PBMC in comparison to stimulated PBMC. Furthermore, each of the five extracts induced apoptosis in HeLa cells, through the activation of both intrinsic and extrinsic signaling pathways. Conclusion Extracts obtained from the endemic plant Helichrysum

  1. In vitro antitumor actions of extracts from endemic plant Helichrysum zivojinii.

    Science.gov (United States)

    Matić, Ivana Z; Aljančić, Ivana; Žižak, Željko; Vajs, Vlatka; Jadranin, Milka; Milosavljević, Slobodan; Juranić, Zorica D

    2013-02-18

    The aim of this research was to determine the intensity and mechanisms of the cytotoxic actions of five extracts isolated from the endemic plant species Helichrysum zivojinii Černjavski & Soška (family Asteraceae) against specific cancer cell lines. In order to evaluate the sensitivity of normal immunocompetent cells implicated in the antitumor immune response, the cytotoxicity of extracts was also tested against healthy peripheral blood mononuclear cells (PBMC). The aerial parts of the plants were air-dried, powdered, and successively extracted with solvents of increasing polarity to obtain hexane, dichloromethane, ethyl-acetate, n-butanol and methanol extracts. The cytotoxic activities of the extracts against human cervix adenocarcinoma HeLa, human melanoma Fem-x, human myelogenous leukemia K562, human breast adenocarcinoma MDA-MB-361 cells and PBMC were evaluated by the MTT test. The mode of HeLa cell death was investigated by morphological analysis. Changes in the cell cycle of HeLa cells treated with the extracts were analyzed by flow cytometry. The apoptotic mechanisms induced by the tested extracts were determined using specific caspase inhibitors. The investigated Helichrysum zivojinii extracts exerted selective dose-dependent cytotoxic actions against selected cancer cell lines and healthy immunocompetent PBMC stimulated to proliferate, while the cytotoxic actions exerted on unstimulated PBMC were less pronounced. The tested extracts exhibited considerably stronger cytotoxic activities towards HeLa, Fem-x and K562 cells in comparison to resting and stimulated PBMC. It is worth noting that the cytotoxicity of the extracts was weaker against unstimulated PBMC in comparison to stimulated PBMC. Furthermore, each of the five extracts induced apoptosis in HeLa cells, through the activation of both intrinsic and extrinsic signaling pathways. Extracts obtained from the endemic plant Helichrysum zivojinii may represent an important source of novel potential

  2. Plasticity of gamma delta T cells: impact on the anti-tumor response

    Directory of Open Access Journals (Sweden)

    Virginie eLafont

    2014-12-01

    Full Text Available The tumor immune microenvironment contributes to tumor initiation, progression and response to therapy. Among the immune cell subsets that play a role in the tumor microenvironment, innate-like T cells that express T cell receptors composed of gamma and delta chains (gamma delta T cells are of particular interest. gamma delta T cells can contribute to the immune response against many tumor types (lymphoma, myeloma, melanoma, breast, colon, lung, ovary and prostate cancer directly through their cytotoxic activity and indirectly by stimulating or regulating the biological functions of other cell types required for the initiation and establishment of the anti-tumor immune response, such as dendritic cells and cytotoxic CD8+ T cells. However, the notion that tumor-infiltrating gamma delta T cells are a good prognostic marker in cancer was recently challenged by studies showing that the presence of these cells in the tumor microenvironment was associated with poor prognosis in both breast and colon cancer. These findings suggest that gamma delta T cells may also display pro-tumor activities. Indeed, breast tumor-infiltrating gamma deltaT cells could exert an immunosuppressive activity by negatively regulating DC maturation. Furthermore, recent studies demonstrated that signals from the microenvironment, particularly cytokines, can confer some plasticity to gamma delta T cells and promote their differentiation into gamma delta T cells with regulatory functions. This review focuses on the current knowledge on the functional plasticity of gamma delta T cells and its effect on their anti-tumor activities. It also discusses the putative mechanisms underlying gamma delta T cell expansion, differentiation and recruitment in the tumor microenvironment.

  3. Triclosan treatment decreased the antitumor effect of sorafenib on hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Wu M

    2018-05-01

    Full Text Available Man Wu,1,2 Guanren Zhao,2 Xiaomei Zhuang,1 Tianhong Zhang,1 Ce Zhang,2 Wenpeng Zhang,1 Zhenqing Zhang1 1State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing, China; 2Department of Pharmacy, The 309th Hospital of PLA, Beijing, China Background: Triclosan is a widely applied antimicrobial agent which affects the endocrine system and homeostasis; it may also promote the cirrhosis and hepatocellular carcinoma (HCC growth in a mice model. The exact roles of triclosan in regulating human hepatocellular carcinoma development and treatment remain unknown. Methods: MHCC97-H, a highly aggressive HCC cell line, was treated with indicated concentration of triclosan or sorafenib. The expression of drug-resistance genes was examined by qPCR. The clearance or metabolism of sorafenib was determined by liquid chromatograph-mass spectrometer/mass spectrometer (LC-MS/MS. MTT assay was used to examine the MHCC97-H cell proliferation. Nude mice were used to exam the anti-tumor effect of sorafenib on subcutaneous and intrahepatic growth of MHCC97-H cells. Results: In the present study, triclosan could induce the expression of drug-resistance genes in MHCC97-H cells (a highly aggressive HCC cell line, accelerate the clearance of sorafenib, and attenuate the anti-proliferation effect of this molecular targeted agent in MHCC97-H cells. Triclosan decreased the antitumor effect of sorafenib on subcutaneous and intrahepatic growth of MHCC97-H in nude mice. Conclusion: By discovering the fact that triclosan treatment enhances sorafenib resistance in HCC cells, this work suggests exposure of triclosan is detrimental to HCC patients during chemotherapy. Keywords: HCC, triclosan, sorafenib resistance, drug clearance 

  4. Antitumor efficacy of conventional anticancer drugs is enhanced by the vascular targeting agent ZD6126

    International Nuclear Information System (INIS)

    Siemann, Dietmar W.; Rojiani, Amyn M.

    2002-01-01

    Purpose: The present report reviews the preclinical data on combined chemotherapy/vascular targeting agent treatments. Basic principles are illustrated in studies evaluating the antitumor efficacy of the vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) when combined with the anticancer drug cisplatin in experimental rodent (KHT sarcoma) and human renal (Caki-1) tumor models. Methods and Materials: C3H/HeJ and NCR/nu-nu mice bearing i.m. tumors were injected i.p. with ZD6126 (0-150 mg/kg) or cisplatin (0-20 mg/kg) either alone or in combination. Tumor response to treatment was assessed by clonogenic cell survival. Results: Treatment with ZD6126 was found to damage existing neovasculature, leading to a rapid vascular shutdown. Histologic evaluation showed dose-dependent morphologic damage of tumor cells within a few hours after drug exposure, followed by extensive central tumor necrosis and neoplastic cell death as a result of prolonged ischemia. ZD6126 doses that led to pathophysiologic effects also enhanced the tumor cell killing of cisplatin when administered either 24 h before or 1-24 h after chemotherapy. In both tumor models, the administration of a 150 mg/kg dose of ZD6126 1 h after a range of doses of cisplatin resulted in an increase in tumor cell kill 10-500-fold greater than that seen with chemotherapy alone. In contrast, the inclusion of the antivascular agent did not increase bone marrow stem cell toxicity associated with this anticancer drug. Conclusion: The results obtained in the KHT and Caki-1 tumor models indicate that ZD6126 effectively enhanced the antitumor effects of cisplatin therapy. These findings are representative of the marked enhancements generally observed when vascular targeting agents are combined with chemotherapy in solid tumor therapy

  5. [Synthesis of a supermolecular nanoparticle γ-hy-PC/Ada-Dox and its antitumor activity].

    Science.gov (United States)

    Li, Yong-bin; Wang, Kai; Hu, Tian-nan; Wang, Qi-wen; Hu, Qi-da; Zhou, Jun; Hu, Xiu-rong; Tang, Gu-ping

    2012-11-01

    To synthesize a (2-Hydroxypropyl)-γ-cyclodextrin-polyethylenimine/adamantane-conjugated doxorubicin (γ-hy-PC/Ada-Dox) based supramolecular nanoparticle with host-guest interaction and to identify its physicochemical characterizations and antitumor effect. A novel non-viral gene delivery vector γ-hy-PC/Ada-Dox was synthesized based on host-guest interaction. 1H-NMR, NOESY, UV-Vis, XRD and TGA were used to confirm the structure of the vector. The DNA condensing ability of complexes was investigated by particle size, zeta potential and gel retardation assay. Cytotoxicity of complexes was determined by MTT assay in BEL-7402 and SMMC-7721 cells. Cell wound healing assay was performed in HEK293 and BEL-7404 cells. The transfection efficiency was investigated in HEK293 cells. H/E staining and cell uptake assay was performed in BEL-7402 cells. The structure of γ-hy-PC/Ada-Dox was characterized by 1H-NMR, NOESY, UV-Vis, XRD, TGA. The drug loading was 0.5% and 5.5%. Gel retardation assay showed that γ-hy-PC was able to completely condense DNA at N/P ratio of 2; 0.5% and 5.5% γ-hy-PC/Ada-Dox was able to completely condense DNA at N/P ratio of 3 and 4,respectively. The cytotoxicity of polymers was lower than that of PEI25KDa. The transfection efficiency of γ-hy-PC was higher than that of γ-hy-PC/Ada-Dox at N/P ratio of 30 in HEK293 cells; and the transfection efficiency was decreasing when Ada-Dox loading was increasing. Cell uptake assay showed that γ-hy-PC/Ada-Dox was able to carry drug and FAM-siRNA into cells. The novel vector γ-hy-PC/Ada-Dox has been developed successfully, which has certain transfection efficiency and antitumor activity.

  6. Supramolecular nanoparticles generated by the self-assembly of polyrotaxanes for antitumor drug delivery

    Directory of Open Access Journals (Sweden)

    Liu R

    2012-10-01

    Full Text Available Rong Liu,1,2,* Yusi Lai,1,* Bin He,1 Yuan Li,1 Gang Wang,1 Shuang Chang,1 Zhongwei Gu1 1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China; 2Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China*These authors contributed equally to this paperAbstract: A new approach of fabricating supramolecular nanoparticles generated by self-assembly polyrotaxanes for antitumor drug delivery has been reported. Cinnamic-acid-modified poly(ethylene glycol chains were threaded in a-cyclodextrins to form polyrotaxanes. The polyrotaxanes self-assembled supramolecular nanoparticles. The morphology of the nanoparticles was changed from nanovesicle to micelle after the antitumor drug, doxorubicin, was loaded. The release profile of the drug-loaded nanoparticles was investigated, and it was found that the sustaining release time could last for 32 hours. The drug-loaded nanoparticles were co-cultured with mouse 4T1 breast cancer cells with a drug concentration of 10 µg/mL; the cell survival rate was 3.3% after a 72-hour incubation. In an in vivo study of breast cancer in a mouse model, the drug-loaded nanoparticles were injected in the tail veins of mice with a dose of 5 mg/kg body weight. The tumor inhibition rate of drug-loaded nanoparticles was 53%, which was better than that of doxorubicin hydrochloride. The cardiac toxicity of doxorubicin was decreased greatly after the encapsulation into supramolecular polyrotaxane nanoparticles.Keywords: polyrotaxane, self-assembly, nanoparticle, doxorubicin, supermolecular

  7. Antitumor activity of vorinostat-incorporated nanoparticles against human cholangiocarcinoma cells.

    Science.gov (United States)

    Kwak, Tae Won; Kim, Do Hyung; Jeong, Young-Il; Kang, Dae Hwan

    2015-09-26

    The aim of this study is to evaluate the anticancer activity of vorinostat-incorporated nanoparticles (vorinostat-NPs) against HuCC-T1 human cholangiocarcinoma cells. Vorinostat-NPs were fabricated by a nanoprecipitation method using poly(DL-lactide-co-glycolide)/poly(ethylene glycol) copolymer. Vorinostat-NPs exhibited spherical shapes with sizes Vorinostat-NPs have anticancer activity similar to that of vorinostat in vitro. Vorinostat-NPs as well as vorinostat itself increased acetylation of histone-H3. Furthermore, vorinostat-NPs have similar effectiveness in the suppression or expression of histone deacetylase, mutant type p53, p21, and PARP/cleaved caspase-3. However, vorinostat-NPs showed improved antitumor activity against HuCC-T1 cancer cell-bearing mice compared to vorinostat, whereas empty nanoparticles had no effect on tumor growth. Furthermore, vorinostat-NPs increased the expression of acetylated histone H3 in tumor tissue and suppressed histone deacetylase (HDAC) expression in vivo. The improved antitumor activity of vorinostat-NPs can be explained by molecular imaging studies using near-infrared (NIR) dye-incorporated nanoparticles, i.e. NIR-dye-incorporated nanoparticles were intensively accumulated in the tumor region rather than normal one. Our results demonstrate that vorinostat and vorinostat-NPs exert anticancer activity against HuCC-T1 cholangiocarcinoma cells by specific inhibition of HDAC expression. Thus, we suggest that vorinostat-NPs are a promising candidate for anticancer chemotherapy in cholangiocarcinoma. Graphical abstract Local delivery strategy of vorinostat-NPs against cholangiocarcinomas.

  8. Activation of the Unfolded Protein Response Contributes toward the Antitumor Activity of Vorinostat

    Directory of Open Access Journals (Sweden)

    Soumen Kahali

    2010-01-01

    Full Text Available Histone deacetylase (HDAC inhibitors represent an emerging class of anticancer agents progressing through clinical trials. Although their primary target is thought to involve acetylation of core histones, several nonhistone substrates have been identified, including heat shock protein (HSP 90, which may contribute towards their antitumor activity. Glucose-regulated protein 78 (GRP78 is a member of the HSP family of molecular chaperones and plays a central role in regulating the unfolded protein response (UPR. Emerging data suggest that GRP78 is critical in cellular adaptation and survival associated with oncogenesis and may serve as a cancer-specific therapeutic target. On the basis of shared homology with HSP family proteins, we sought to determine whether GRP78 could serve as a molecular target of the HDAC inhibitor vorinostat. Vorinostat treatment led to GRP78 acetylation, dissociation, and subsequent activation of its client protein double-stranded RNA-activated protein-like endoplasmic reticulum kinase (PERK. Investigations in a panel of cancer cell lines identified that UPR activation after vorinostat exposure is specific to certain lines. Mass spectrometry performed on immunoprecipitated GRP78 identified lysine-585 as a specific vorinostat-induced acetylation site of GRP78. Downstream activation of the UPR was confirmed, including eukaryotic initiating factor 2α phosphorylation and increase in ATF4 and C/EBP homologous protein expression. To determine the biologic relevance of UPR activation after vorinostat, RNA interference of PERK was performed, demonstrating significantly decreased sensitivity to vorinostat-induced cytotoxicity. Collectively, these findings indicate that GRP78 is a biologic target of vorinostat, and activation of the UPR through PERK phosphorylation contributes toward its antitumor activity.

  9. Evaluation of tetrazolium-based semiautomatic colorimetric assay for measurement of human antitumor cytotoxicity

    International Nuclear Information System (INIS)

    Heo, D.S.; Park, J.G.; Hata, K.; Day, R.; Herberman, R.B.; Whiteside, T.L.

    1990-01-01

    A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based colorimetric assay was developed and compared with 51Cr release from different adherent tumor cell targets (human squamous cell carcinoma lines of the head and neck established in our laboratory, melanoma, and colorectal carcinoma) using 5-7-day human lymphokine-activated killer cells and monocyte-depleted peripheral blood lymphocytes as effectors. With adherent tumor cell targets, MTT colorimetry was more sensitive than the 51Cr release assay in measuring the antitumor activity of effectors: median, 4385 (range, 988-8144) versus median, 1061 (range, 582-7294) lytic units (the number of effector cells required to lyse 20% of 5 x 10(3) targets)/10(7) effectors (P less than 0.01). Background effects (without effector cells) were comparable in 4-h assays (9% versus 10%) between MTT colorimetry and 51Cr release. In 24-h assays, MTT colorimetry showed higher antitumor activity (70-100% versus 40-60% lysis at 1:1 effector:target cell ratio) but lower background effects (6% versus 38%) than 51Cr release assay. Thus, MTT colorimetry was more sensitive, did not use radiolabeled targets, required fewer effector cells, and was easier, less expensive, and better adaptable to serial monitoring of effector cell function in cancer patients. This colorimetric assay is especially well suited to adherent tumor cell targets. The use of adherent tumor cell monolayers, as opposed to trypsinized single cell suspensions, provides an opportunity to measure interactions of effector cells with enzymatically unaltered solid tumor targets. Because of the greater sensitivity of the colorimetric assay, the transformation of MTT data into lytic units, as commonly used for 51Cr release assays, required an adjustment to avoid the extrapolation based on the exponential fit equation

  10. Ukrain, a plant derived semi-synthetic compound, exerts antitumor effects against murine and human breast cancer and induce protective antitumor immunity in mice.

    Science.gov (United States)

    Bozeman, E N; Srivatsan, S; Mohammadi, H; Daniels, D; Shashidharamurthy, R; Selvaraj, P

    2012-12-01

    Despite the recent advances in anti-cancer therapies, breast cancer accounts for the highest percentage of estimated new cases among female cancer patients. The anti-cancer drug Ukrain, a plant-derived semi-synthetic compound, has been shown to be effective in a variety of tumor models including colon, brain, ovarian, melanoma and lymphoma. However, the direct cytotoxic effects of Ukrain have yet to be investigated in breast cancer models. Herein, we investigated the in vitro and in vivo cytotoxicity of Ukrain using murine (4T07 and TUBO) and human (SKBR-3) breast cancer cell lines. Cells were treated with varying concentrations of Ukrain for up to 72 h and analyzed for viability by trypan blue exclusion, apoptosis by intracellular caspase 3 and Annexin V staining, and proliferative potential by a clonogenic assay. Female BALB/c mice were challenged subcutaneously (s.c.) with 4T07-RG cells and administered 5 mg/kg or 12.5 mg/kg body weight Ukrain intravenously (i.v.) on the same day and 3 days later. Protective immune responses were determined following re-challenge of tumor-free mice 35 days post primary challenge. Ukrain exposure induced apoptosis in a dose and time-dependent manner with 50 µg/mL Ukrain leading to >50% cell death after 48 h exposure for all three breast cancer cell lines. Ukrain administration (12.5 mg/kg) led to significant inhibition of 4T07 tumor growth in vivo and sustained protective anti-tumor immunity following secondary challenge. Our findings demonstrate the in vitro and in vivo cytotoxic effects of Ukrain on breast cancer cells and may provide insight into designing Ukrain-based therapies for breast cancer patients.

  11. Dialética das relações raciais

    Directory of Open Access Journals (Sweden)

    Octavio Ianni

    2004-04-01

    Full Text Available AS RELAÇÕES raciais estão enraizadas na vida social de indivíduos, grupos e classes sociais. As desigualdades sociais frequentemente se manifestam nos estereótipos e nas intolerâncias, polarizadas em torno de etnias, assim como gênero e outras diversidades sociais como as de gênero, religiosas e outras. Em síntese, a dinâmica das diversidades e das desigualdades "fabrica" continua e reiteradamente as intolerâncias e preconceitos.RACIAL relationships are rooted in the social life of individuals, groups and social classes. Social inequalities often manifest themselves in stereotypes and intolerance, polarized around ethnicities and other social diversities such as gender, religion etc. In brief, the dynamics of diversity and inequality continuously and reiteratively "manufactures" intolerance and bigotry.

  12. Samuel Barnsley Pessoa e os determinantes sociais das endemias rurais

    Directory of Open Access Journals (Sweden)

    Gilberto Hochman

    2015-02-01

    Full Text Available O artigo analisa os principais aspectos da trajetória, das ideias e da atuação acadêmica e política de Samuel Barnsley Pessoa (1898-1976. Indica que a atuação de Samuel Pessoa deve ser compreendida também a partir da sua militância comunista e ressalta que uma das contribuições originais de seus trabalhos foi o estabelecimento da relação entre estrutura agrária e endemias rurais, entre latifúndio e doença e a adesão a um projeto de transformação da sociedade brasileira.

  13. Estudo das ausências da equipe de enfermagem

    Directory of Open Access Journals (Sweden)

    Janaina Haidê Rodrigues Belem

    1998-12-01

    Full Text Available As ausências dos elementos da equipe de enfermagem comprometem a organização do trabalho causando sobrecarga dessa equipe, e queda na qualidade da assistência de enfermagem. O presente estudo caracteriza o tipo e distribuição das ausências da equipe de enfermagem em um hospital geral de grande porte, propondo um índice de Segurança Técnica para cobertura das ausências a partir da realidade investigada. Foram estudadas 8 tipos de ausências entre previstas e não previstas. O maior número de tipos de ausências encontradas foram aquelas referentes à ausências previstas, em seqüência encontramos licença maternidade representando o maior número de ausências não previstas.

  14. Impacto das Competências de Equipes sobre o Desempenho

    Directory of Open Access Journals (Sweden)

    Katia Puente-Palacios

    2018-03-01

    Full Text Available Resumo As competências para o trabalho têm sido tradicionalmente compreendidas como atributos de indivíduos; entretanto, estudos mais recentes tornam pertinente defender a sua ocorrência como atributos coletivos. O objetivo deste estudo foi demonstrar que competências individuais podem transformar-se em competências coletivas e, nesse nível, predizer o desempenho da equipe. A testagem empírica foi realizada em 51 aeródromos brasileiros, totalizando 106 equipes (entre 3 e 32 integrantes. Instrumentos respondidos pelos membros focaram nas competências enquanto os respondidos pelos lideres indagaram sobre o desempenho das equipes. Os resultados revelaram que as competências coletivas explicam aproximadamente 20% do desempenho das equipes. Disso depreende-se que as competências podem se manifestar como atributos coletivos que predizem resultados de equipes de trabalho.

  15. Peran Industri Dan Produk Tekstil Pada Kelestarian Sumberdaya Lingkungan Perairan DAS Citarum

    OpenAIRE

    sudradjat, ade

    2002-01-01

    Telah diketahui bahwa sebagian besar industri yang beroperasi di DAS Citarum adalah industri tekstil, yang sebagian besar belum mengolah limbahnya dengan baik dan membuangnya ke DAS Citarum. Oleh karena itulah maka tidak mengherankan jika keberadaan industri- industri tekstil tersebut sering dinyatakan sebagai salah satu penyebab utama tercemarnya kualitas lingkungan perairan DAS Citarum.Untuk mengetahui dengan benar tentang peran industri tekstil di DAS Citarum maka paper ini disusun. Paper ...

  16. PERAN INDUSTRI DAN PRODUK TEKSTIL PADA KELESTARIAN SUMBERDAYA LINGKUNGAN PERAIRAN DAS CITARUM

    OpenAIRE

    sudradjat, ade

    2011-01-01

    Telah diketahui bahwa sebagian besar industri yang beroperasi di DAS Citarum adalah industri tekstil, yang sebagian besar belum mengolah limbahnya dengan baik dan membuangnya ke DAS Citarum. Oleh karena itulah maka tidak mengherankan jika keberadaan industri- industri tekstil tersebut sering dinyatakan sebagai salah satu penyebab utama tercemarnya kualitas lingkungan perairan DAS Citarum.Untuk mengetahui dengan benar tentang peran industri tekstil di DAS Citarum maka paper ini disusun. Paper ...

  17. As possibilidades e os limites das identidades múltiplas

    Directory of Open Access Journals (Sweden)

    Daniela do Carmo Kabengele

    2014-07-01

    Full Text Available Este artigo procura pensar a dinâmica da identidade a partir das possíveis identidades múltiplas que se inscrevem em uma pessoa, por um lado, e discute os limites da atualização dessas identidades em contextos específicos, por outro. O argumento é de que a identidade pode ser entendida como posicionamento, mas deve-se notar, especialmente, os feixes de forças presentes no contexto social.

  18. Enterprise Risk Management : Das COSO-ERM-Framework

    OpenAIRE

    Ruud, Flemming; Sommer, Katerina

    2006-01-01

    Das Enterprise Risk Management (ERM) ist ein wichtiges Element der Corporate Governance. Es kann Unternehmen bei der Zielerreichung unterstützen, indem es hilft, Chancen und Risiken zu erkennen und geeignete Massnahmen zu ergreifen. Die Weiterentwicklung des Internal-Control-Framework zu einem Enterprise-Risk-Management-Framework, dessen Grund sätze, Ziele und Komponenten, dessen Nutzen und Grenzen sowie die Unterschiede zum ursprünglichen COSO-ICFramework ist Gegenstand dieser Ausführunge...

  19. Entrprise Risk Management : Das COSO-ERM-Framework

    OpenAIRE

    Ruud, Flemming; Sommer, Katerina

    2006-01-01

    Das Enterprise Risk Management (ERM) ist ein wichtiges Element der Corporate Governance. Es kann Unternehmen bei der Zielerreichung unterstützen, indem es hilft, Chancen und Risiken zu erkennen und geeignete Massnahmen zu ergreifen. Die Weiterentwicklung des Internal-Control-Framework zu einem Enterprise-Risk-Management-Framework, dessen Grund sätze, Ziele und Komponenten, dessen Nutzen und Grenzen sowie die Unterschiede zum ursprünglichen COSO-ICFramework ist Gegenstand dieses Artikels.

  20. Geschwisterbeziehungen in der Verarbeitung sexueller Traumatisierung: Der Film "Das Fest"

    OpenAIRE

    Sohni, Hans

    2001-01-01

    Filme reizen als Gegenstand psychoanalytischer Kunstinterpretation durch ihre strukturelle Nähe zum "szenischen Verstehen" und bereichern unsere Einsicht in menschliche Beziehungen. Der Film "Das Fest" lohnt wegen seiner besonderen ästhetischen Form und wegen seiner Aussage zur Geschwisterbeziehung. Nach filmjournalistischer Einschätzung zeigt er die Demontage der bürgerlichen Gesellschaft und die Reinszenierung destruktiver Gewalt. In der Interpretation dieses Beitrags führt der Film dagegen...

  1. Das polyzystische Ovarialsyndrom: Im Spannungsfeld von Hormonen und Stoffwechsel

    Directory of Open Access Journals (Sweden)

    Wehr E

    2010-01-01

    Full Text Available Das polyzystische Ovarialsyndrom (PCOS ist eine komplexe Erkrankung und betrifft mindestens 5–10 % aller Frauen. Es ist charakterisiert durch Hyperandrogenismus (klinisch und/oder biochemisch, Oligo- oder Anovulation und polyzystische Ovarien. In der Pathogenese spielt neben der Hyperandrogenämie und der abnormen Gonadotropinsekretion die Insulinresistenz eine zentrale Rolle. Ein genetischer Hintergrund des PCOS wird vermutet, neben verschiedenen Kandidatengenen werden auch genomweite Assoziationsstudien neue Kenntnisse bringen, um in Zukunft sowohl Diagnose als auch Therapie des PCOS zu vereinfachen. Das PCOS bringt ein hohes metabolisches Risiko mit sich, ca. die Hälfte aller betroffenen Frauen ist adipös, viele leiden an Insulinresistenz, Glukosetoleranzstörungen und Diabetes mellitus Typ 2. Weiters sind viele Frauen mit PCOS von unerfülltem Kinderwunsch, Hirsutismus, Akne und androgenetischer Alopezie betroffen. Vor allem Adipositas und Hirsutismus führen zu einer starken psychischen Belastung betroffener Frauen, das Suizidrisiko ist deutlich erhöht. Zur exakten Diagnose des PCOS bedarf es einer genauen Anamnese und körperlichen Untersuchung mit anthropometrischen Messungen und Hirsutismus-Score. Ein Hormonstatus mit Bestimmung von Androgenen ist unerlässlich, ein LHRH-Test kann weitere diagnostische Hinweise liefern. Weiters sollten zur metabolischen Abklärung ein oraler Glukosetoleranztest, eine Messung der Körperfettverteilung und die Bestimmung eines Lipidstatus erfolgen. Therapeutisch ist vor allem bei adipösen Frauen eine Lebensstilintervention am wichtigsten, zusätzlich kommen Insulinsensitizer und orale Kontrazeptiva zum Einsatz. Zusammenfassend ist das PCOS eine extrem häufige Erkrankung mit komplexen Folgen und bedarf einer konsequenten, interdisziplinären individuellen Therapie bei betroffenen Frauen.

  2. O RETORNO POR EMPREGADO COMO INDICADOR DE DESEMPENHO DAS EMPRESAS

    Directory of Open Access Journals (Sweden)

    Francisca Soraia Ferreira Leite

    2013-12-01

    Full Text Available Com as transformações no ambiente de negócios, os ativos intangíveis, potencialmente gerados pelo capital intelectual, ganharam importância. Este estudo tem como objetivo analisar e testar uma métrica alternativa de avaliação de desempenho que leva em conta os recursos humanos da empresa: o Retorno por Empregado (RE. Uma pesquisa exploratória foi realizada através do estudo de caso de três empresas com ações negociadas na BM&FBOVESPA no período 2006-2009. A partir das demonstrações financeiras das empresas, foram medidos seus desempenhos pelas métricas tradicionais, Retorno sobre Ativo e Retorno sobre Patrimônio Líquido, e pelo RE. O valor das ações de cada empresa foi usado como referência para criação de valor. Um estudo empírico complementar apontou que a correlação entre o RE e o preço das ações foi mais alta e significativa do que a correlação entre os indicadores tradicionais para a empresa mais intensiva em capital intelectual. Para as empresas intensivas em capital físico e em mão de obra, os indicadores de desempenho tradicionais apresentaram correlação mais alta. Sugere-se que a métrica alternativa seja um importante índice para empresas intensivas em capital intelectual. Reforça-se que tal medida de desempenho corporativo, que incorpora o efeito da força de trabalho intelectual, é uma contribuição importante à literatura sobre intangíveis.

  3. Das Archiv der Familie Szwojnicki aus Borkłojnie

    Directory of Open Access Journals (Sweden)

    Andrzej Mycio

    2017-11-01

    Full Text Available 2004 erwarb die Universitätsbibliothek in Thorn einen kleinen Bestand, das Privatarchiv der Familie Szwojnicki, die bis zum Zweiten Weltkrieg ihre Landgüter in Borkłojnie in der Republik Litauen inne hatte. Die von den nacheinander folgenden Familienvertretern gesammelten Materialien, die sich bis zum heutigen Tag bewährten, erlauben die wichtigsten Schicksale dieser Familie wiederherzustellen. Die Szwojnickis waren eine Familie der Landesbeamten. Im 19. Jahrhundert waren ihre Landgüter in Borkłojnie ein Hort, wo die polnischen Truppen während des Januaraufstandes unterstützt, geschützt und versorgt wurden. Die Landgüter wurden von 1897 bis zum Ende des Zweiten Weltkrieges von Zygmunt Szwojnicki verwaltet. In der Zwischenkriegszeit bemühte er sich aktiv um die Bewahrung der nationalen Identität der in der Republik Litauen lebenden Polen. 1946 wurde er zusammen mit anderen Polen in den polnischen Staat umgesiedelt. Das ganze Familienarchiv Szwojnickis ist einer der kleineren Archivbestände, die in der Universitätsbibliothek in Thorn aufbewahrt werden. Dazu gehörten insgesamt 12 Inventareinheiten. Das älteste Dokument in diesem Bestand stammt aus dem Jahr 1531, das jüngste aus dem Jahr 1946. Die erhaltenen Archivalien entstanden also innerhalb von über 400 Jahren. Sie schildern die Schicksale der Familie Szwojnicki und ihrer Landgüter in Borkłojnie. Der Archivbestand der Familie Szwojnicki ist ein typisches Beispiel von Familienakten des nicht so wohlhabenden polnischen Adels, der die Gebiete Litauens bewohnte. Es bewährten sich vor allem die Urkunden, die von den Ansprüchen der Familie auf den Adelstitel sowie auf die Landgüter zeugen, darüber hinaus: Matrikelakten, Testamente, Finanzurkunden sowie biografische Materialien in Bezug auf den letzten Eigentümer Zygmunt Szwojnicki.

  4. Kohapärimuslik luule nädalalehes Das Inland / Die Sagendichtung in der Wochenschrift Das Inland

    Directory of Open Access Journals (Sweden)

    Liina Lukas

    2012-01-01

    Full Text Available Das spätromantische Interesse für Ortsüberlieferungen, angeregt von den “Deutschen Sagen” (1816–1818 der Brüder Grimm, blühte im Baltikum in den 1830er und 1840er Jahren auf und gipfelte – im estnischen Sprachgebiet – in der zweisprachigen Ausgabe des estnischen Nationalepos “Kalevipoeg” / “Kalew’s Sohn” (1857–1861, dem Friedrich Reinhold Kreutzwald seine Endgestalt gab, aber das von mehreren Sammlern und Bearbeitern geprägt wurde. Literarische Bearbeitungen von Volkssagen fanden schnell ihren Weg in Zeitungen und Zeitschriften, in Gedichtbände und Anthologien – oft in modischer Balladenform, die dem mythisch-romantischen Inhalt der Volkssage am besten zu entsprechen schien. Die Blütezeit der Sagendichtung im Baltikum sind die 1840er Jahre, als vor allem in der Zeitschrift „Das Inland“ mehrere dichterischen Bearbeitungen estnischer und lettischer Volkssagen erschienen (von Heinrich Blindner, Otto Dreistern, Eduard Pabst, Minna von Mädler, Theodor Rutenberg, Robert Falck, P. Otto u. a. 1845 erschien hier das nach einer Sage von Friedrich Robert Faehlmann verfasste Gedicht „Koit und Hämarik / Morgenroth und Abendroth“ von Minna von Mädler – fünf Jahre vor der Fassung von Friedrich Reinhold Kreutzwalds estnischsprachiger Ballade „Koit ja Hämarik“. Zwischen 1831 und 1836 verfasste Friedrich Reinhold Kreutzwald seine deutschsprachigen Balladen, von denen „Die Belagerung von Bewerin im Jahre 1207“ 1846 im „Inland“ gedruckt wurde. Das Jahr 1846 kann als „Balladenjahr“ der Zeitschrift bezeichnet werden. Die eigentliche Domäne der deutschbaltischen (lyro-epischen Dichtung ist die historische Ballade, die fußend auf baltischen Chroniken und Familiengeschichten zumeist von Ruinen alter Schlösser und den sie einst bewohnenden historischen Personen und deren Heldentaten berichtet. Doch schon im Jahre 1847 kann man im Inland die Kritik gegenüber diesem Balladenboom vernehmen, u.a. mit dem

  5. Contribuição das incubadoras tecnológicas na internacionalização das empresas incubadas

    Directory of Open Access Journals (Sweden)

    Raquel Engelman

    2013-03-01

    Full Text Available Neste trabalho, teve-se como propósito verificar como as incubadoras tecnológicas brasileiras contribuem para a internacionalização das empresas incubadas no ponto de vista dos gestores das incubadoras. Para atender a esse propósito, desenvolveu-se um modelo que, além de oferecer suporte à pesquisa, possa servir de base para estudos e ações sobre internacionalização de empresas de base tecnológica incubadas. O modelo foi elaborado a partir da literatura sobre as duas áreas de interesse do trabalho. De um lado, foram abordadas referências sobre internacionalização de empresas, fazendo-se um levantamento sobre os fatores que influenciam sua internacionalização, principalmente micro e pequenas empresas de base tecnológica; de outro, foram estudados aspectos sobre o processo de incubação de empreendimentos tecnológicos, bem como as ações e os serviços disponibilizados pelas incubadoras. A pesquisa descritiva foi realizada com 40 incubadoras tecnológicas brasileiras (50% da população e que atenderam aos seguintes critérios: estar em efetiva operação há um tempo superior a dois anos e com pelo menos uma empresa graduada. A partir de questionários identificou-se que 40% das incubadoras da amostra possuem programa formal voltado para a internacionalização das incubadas e 60% das incubadoras têm empresas que iniciaram processo de internacionalização. Os resultados apontaram uma relação positiva entre incubação e internacionalização. A pesquisa forneceu indicações de ações e serviços que são efetivos na internacionalização das empresas.

  6. Clinical applications of Ga-67 DFO-DAS-fibrinogen

    International Nuclear Information System (INIS)

    Iio, Masahiro; Ohtake, Tohru; Nishikawa, Junichi; Watanabe, Toshiaki; Yasuhara, Hiroshi; Ohashi, Shigenobu; Takayama, Yutaka; Tada, Yusuke; Shirakawa, Motoaki

    1987-01-01

    Ga-67 DFO-DAS-fibrinogen scanning was performed in 15 patients to detect fresh arterial thrombus. Seven patients were preoperative cases of aortic aneurysm and eight were postoperative cases of graft bypass. Scanning was performed on the first and second days after the injection. Nine of 13 grafts in eight cases were visualized by 67 Ga-DFO-DAS-fibrinogen scan. Velour Dacron grafts were more strongly visualized compared with woven Dacron or Goatex. In three patients with aortic aneurysm in whom fresh thrombus was identified by operative findings, arterial thrombus was clearly visualized by 67 Ga-DFO-DAS-fibrinogen scan, whereas in three other patients with aortic aneurysm, thrombus was not visualized, although it was identified by other examinations. In one case, a marked accumulation was observed in the abdominal aorta, although no arterial thrombus was found at operation. This was thought to be an accumulation in a blood pool because it decreased on the second day. We think it important to observe the relative changes of accumulation. (author)

  7. "Doidas e putas”: usos das categorias travesti e transexual

    Directory of Open Access Journals (Sweden)

    Bruno Cesar Barbosa

    Full Text Available Neste artigo discuto os usos das categorias travesti e transexual com base em trabalho de campo realizado entre 2008 e 2009 com participantes das reuniões denominadas Terças Trans. A questão central que norteou a análise foi como as diferentes pessoas observadas utilizavam categorias relacionadas a identidades sexuais e de gênero e como acionavam e articulavam diversas associações convencionais nesse processo para produzir sentidos e diferenças acerca destas categorias. Embora as convenções do discurso médico sejam referências centrais para a definição de corpos, subjetividades e identidades das pessoas pesquisadas, foi possível observar também uma variedade de reelaborações e deslocamentos de sentidos. Procuro desenvolver o argumento de que travesti e transexual são categorias performativas, e que tal performatividade não se esgota apenas em enunciados de gênero e sexualidade, mas também pode ser expressa por meio de articulações contingentes que remetem a diferenças de classe, cor/raça e geração.

  8. UMA VISÃO GERAL SOBRE A INTERNET DAS COISAS

    Directory of Open Access Journals (Sweden)

    Gustavo Marin Suppi

    2017-02-01

    Full Text Available No decorrer dos anos, a tecnologia computacional tem evoluído, com os dispositivos móveis abriu um imenso leque de possibilidades de sistemas que visam facilitar a vida de toda a sociedade. Na Internet das Coisas, a conexão não se limita a esses dispositivos, mas a qualquer objeto no ambiente, desde torneiras até sinaleiras, onde formam uma estrutura de rede guiada por troca de informações, onde sensores captam informações do meio e enviam para dispositivos que as processam. Por meio de uma revisão de literatura, o objetivo foi coletar dados sobre essa nova infraestrutura, proporcionando ao leitor uma visão geral, expondo os principais pontos mencionados pelos autores dos artigos pesquisados. Concluiu-se que o objetivo da Internet das Coisas é de fato revolucionar o meio de como usamos a internet, desde a conectividade até a distribuição da informação, porém, para tal, será necessário fortes estudos em relação a segurança das informações obtidas dos usuários.

  9. Politische Bildung und das Web 2.0

    Directory of Open Access Journals (Sweden)

    Heike Schaumburg

    2011-08-01

    Full Text Available Aktuell erhält die Diskussion um die Rolle des Internet in der Politischen Bildung neuen Auftrieb durch die Entwicklung der sogenannten Web-2.0- Technologien, die im Vergleich zum Web 1.0 ein erheblich grösseres Potenzial zur Mitgestaltung politischer Inhalte und Prozesse und bzw. zur Partizipation bieten, aber auch neue Möglichkeiten der Kommunikation und Vernetzung eröffnen. In der vorliegenden Studie wird der Frage nachgegangen, inwieweit das Internet und speziell das Web 2.0 in der Lage sind, die in die Technik gesetzten Hoffnungen zu erfüllen. Dabei wird zunächst ausgelotet, welche Potenziale das Web 2.0 für die Politische Bildung mit Blick auf ihre didaktische Gestaltung bieten könnte. Im Anschluss daran wird auf der Basis einer Analyse des Internet-Angebots der traditionellen Anbieter Politischer Bildung (Bundes- und Landeszentralen für Politische Bildung, politische Stiftungen sowie von Internetportalen im Bereich Politische Bildung festgestellt, welche Verbreitung Web-2.0-Angebote gegenwärtig besitzen. Schliesslich wird auf der Grundlage einer Nutzerbefragung an knapp 300 Teilnehmern virtueller politischer Bildungsangebote einer politischen Stiftung der Frage nachgegangen, wie Web-2.0-Angebote in der Politischen Bildungsarbeit aus Nutzersicht beurteilt werden.

  10. A leitura das obras completas em contexto escolar no Quebec

    Directory of Open Access Journals (Sweden)

    Olivier Dezutter

    2017-06-01

    Full Text Available No Quebec, as recentes reformas curriculares testemunham as elevadas exigências quanto ao número de obras completas a serem lidas no período de formação pré-universitária, e dedicam uma grande liberdade aos professores para a seleção dos títulos. Fundamentamo-nos aqui sobre os resultados de uma vasta pesquisa para estabelecer a situação das exigências dos professores em matéria de leitura das obras, das finalidades associadas a esta prática e do corpus escolhido. Os professores do primário e do secundário visam ao desenvolvimento do prazer da leitura; aqueles do colegial, à constituição de uma cultura literária de base: a primeira centra-se na literatura quebequense enquanto a segunda leva em consideração o patrimônio francês.

  11. Alternativas técnicas para o controle das alterações dimensionais das resinas acrílicas em prótese total

    OpenAIRE

    GOMEZ Tomas; MORI Matsuyoshi; CORRÊA Gerson de Arruda; MATSON Edmir

    1998-01-01

    Os autores propõem uma nova técnica para diminuição dos problemas provenientes das alterações dimensionais das resinas acrílicas utilizadas na confecção das próteses totais. Com essa proposta, conseguiu-se praticamente eliminar essas alterações dimensionais tão prejudiciais às próteses totais.

  12. O \\"reino das plantas\\" nos livros didáticos de ciências: análise das imagens

    OpenAIRE

    Rená Manoel de Souza e Silva

    2017-01-01

    As imagens sempre desempenharam papel fundamental na compreensão do conhecimento científico e, portanto, também nos livros didáticos de ciências. Porém, pesquisas têm mostrado que as imagens não são transparentes; por isso, defendemos a fundamental compreensão dos professores em relação ao uso das imagens no processo de ensino-aprendizagem, e na orientação da leitura e no uso desse recurso como suporte das atividades pedagógicas. Esta pesquisa analisou as imagens presentes nos livros didático...

  13. Tendências temporais e espaciais da qualidade das águas superficiais da sub-bacia do Rio das Velhas, estado de Minas Gerais

    OpenAIRE

    Trindade, Ana Laura Cerqueira; Almeida, Katiane Cristina de Brito; Barbosa, Pedro Engler; Oliveira, Sílvia Maria Alves Corrêa

    2016-01-01

    RESUMO Este artigo apresenta uma análise da tendência temporal e espacial da qualidade das águas superficiais da sub-bacia do Rio das Velhas, inserida na bacia do Rio São Francisco, em Minas Gerais, Brasil. Foram analisados 16.625 dados coletados no período de 2002 a 2011 pelo programa de monitoramento de qualidade das águas superficiais efetuado pelo Instituto Mineiro de Gestão das Águas (Igam). Testes estatísticos, multivariados e não paramétricos foram utilizados para avaliar 11 variáveis ...

  14. A DESIGUALDADE AMBIENTAL EM RIO DAS OSTRAS-RJ, BRASIL

    Directory of Open Access Journals (Sweden)

    Juliana Higa Bellini

    2016-12-01

    Full Text Available Este artigo analisou a desigualdade ambiental em Rio das Ostras-RJ por meio do mapeamento das condições adequadas de habitação, baseada nos índices de abastecimento de água, de esgotamento sanitário, de alfabetização, de renda, de disposição do lixo e de presença de vegetação, oriundos do Censo IBGE de 2010 e de imagens de satélite Cbers-2b e Landsat-5, de 2008. Os índices foram ponderados pelo método Analitic Hierarchy Process e agregados no software ArcGis 10.0, construindo o índice de desigualdade ambiental. O município de Rio das Ostras foi selecionado por apresentar um elevado crescimento populacional entre 2000 e 2010, seguido de um significativo crescimento econômico derivado da exploração de petróleo e gás na Bacia de Campos. Nesse sentido, tornou-se importante verificar se o crescimento populacional e econômico vinha acompanhando de condições de habitação adequadas para toda a população. O resultado expôs a presença de desigualdade ambiental em Rio das Ostras, afetando principalmente a população de menor renda, com maiores porcentagens de analfabetos e localizados no limite da área urbanizada e na área rural, cujas áreas apresentaram deficiência na oferta de serviços e infraestrutura. Concluiu-se que a distribuição condições adequadas de habitação avaliada por este trabalho não é homogênea e segue a lógica de valorização da terra urbana para o processo de especulação imobiliária em Rio das Ostras. A presença da desigualdade ambiental também representa dificuldades na garantia da sustentabilidade urbana, com diversas áreas desprovidas de condições de habitação em que, por isso, acabam por impactar o meio ambiente.

  15. Das perguntas wittgensteinianas à pedagogia das competências: ou desmontando a caixa-preta de Perrenoud

    Directory of Open Access Journals (Sweden)

    Rafael Ferreira de Souza Mendes Pereira

    2015-03-01

    Full Text Available Este artigo faz parte de uma pesquisa de mestrado que se propõe a analisar conceitos educacionais e curriculares por meio da filosofia da linguagem elaborada por Ludwig Wittgenstein. Dessa perspectiva, examinamos alguns pressupostos teóricos da chamada pedagogia das competências e interrogamos se esse modelo pedagógico, em nome de pretensa renovação do ensino, não encorajaria a reificação de conceitos mentais concernentes ao processo de aprendizagem. Com este fim, abordamos a reformulação que essa pedagogia oferece a respeito de conceitos como aprender, saber, compreender, destacando as ambiguidades daí decorrentes. Argumenta-se que é possível obter uma leitura mais rigorosa das suas propostas de modernização pedagógica se investigarmos o uso dado a esses conceitos nos jogos de linguagem em que eles são mobilizados. Wittgenstein, na segunda fase de sua produção intelectual, mostrou como a negligência linguística à dinâmica que dá significado aos conceitos e metáforas referentes à nossa vida mental fez com que diversas filosofias assumissem um perfil metafísico. Este artigo não apenas examina como um fenômeno análogo pode ocorrer no campo pedagógico, como também defende que as ferramentas analíticas construídas por Wittgenstein podem ser usadas contra os diferentes dogmatismos pedagógicos. Desse modo, o artigo aponta vias alternativas de problematização acerca do significado das reformas dos sistemas escolares que têm buscado fundamentos naquela pedagogia.

  16. ESTUDO DAS VARIÁVEIS OPERACIONAIS E CONJUNTURAIS SOBRE O MARKET VALUE DAS EMPRESAS DE CARNES E DERIVADOS NO BRASIL

    Directory of Open Access Journals (Sweden)

    Eduardo Pozzi Lucchesi

    2015-06-01

    Full Text Available O objetivo deste trabalho é identificar as variáveis relacionadas aos aspectos operacionais e conjunturais que influenciam o Market Value das empresas do segmento de carnes e derivados listadas na BM&FBovespa, no período de 2007 a 2013. O estudo foi elaborado sob a perspectiva de dois eixos teóricos. O primeiro foi uma análise das contribuições do Market Value como um indicador útil para determinação do valor justo de mercado criado aos acionistas e, portanto, constituindo uma base sólida para mensuração do desempenho das empresas. O segundo foi a Hipótese de Mercado Eficiente que considera a eficiência da informação ou o impacto de determinadas informações na precificação dos ativos. O modelo especificado produziu resultados que ratificaram algumas hipóteses da pesquisa, tanto na significância individual, quanto no sinal de algumas variáveis independentes. Além disso, o modelo apresentou significância global, dada pelo teste F, a 5%, com um coeficiente de determinação múltiplo ajustado de 9,22%.

  17. A Chemoinformatics Approach to the Discovery of Lead-Like Molecules from Marine and Microbial Sources En Route to Antitumor and Antibiotic Drugs

    Science.gov (United States)

    Pereira, Florbela; Latino, Diogo A. R. S.; Gaudêncio, Susana P.

    2014-01-01

    The comprehensive information of small molecules and their biological activities in the PubChem database allows chemoinformatic researchers to access and make use of large-scale biological activity data to improve the precision of drug profiling. A Quantitative Structure–Activity Relationship approach, for classification, was used for the prediction of active/inactive compounds relatively to overall biological activity, antitumor and antibiotic activities using a data set of 1804 compounds from PubChem. Using the best classification models for antibiotic and antitumor activities a data set of marine and microbial natural products from the AntiMarin database were screened—57 and 16 new lead compounds for antibiotic and antitumor drug design were proposed, respectively. All compounds proposed by our approach are classified as non-antibiotic and non-antitumor compounds in the AntiMarin database. Recently several of the lead-like compounds proposed by us were reported as being active in the literature. PMID:24473174

  18. Antitumor activity of novel chimeric peptides derived from cyclinD/CDK4 and the protein transduction domain 4.

    Science.gov (United States)

    Wang, Haili; Chen, Xi; Chen, Yanping; Sun, Lei; Li, Guodong; Zhai, Mingxia; Zhai, Wenjie; Kang, Qiaozhen; Gao, Yanfeng; Qi, Yuanming

    2013-02-01

    CyclinD1/CDK4 and cyclinD3/CDK4 complexes are key regulators of the cell progression and therefore constitute promising targets for the design of anticancer agents. In the present study, the key peptide motifs were selected from these two complexes. Chimeric peptides with these peptides conjugated to the protein transduction domain 4 (PTD4) were designed and synthesized. The chimeric peptides, PTD4-D1, PTD4-D3, PTD4-K4 exhibited significant anti-proliferation effects on cancer cell lines. These peptides could compete with the cyclinD/CDK4 complex and induce the G1/S phase arrest and apoptosis of cancer cells. In the tumor challenge experiment, these peptides showed potent antitumor effects with no significant side effects. Our results suggested that these peptides could be served as novel leading compounds with potent antitumor activity.

  19. Preliminary evaluation of the encapsulation of new antidiabetic sulphonylhydrazone and antitumor N-acylhydrazone derivatives using PLGA nanoparticles

    International Nuclear Information System (INIS)

    Costa, F N; Ibiapino, A L; De Figueiredo, L P; De Castro, C E; Giacomelli, F C; Ferreira, F F; Barreiro, E J; Lima, L M; Do Amaral, D N

    2015-01-01

    It has been demonstrated the feasibly of using PLGA nanoparticles to promote the encapsulation of novel anti-diabetic sulphonylhydrazone and antitumor N-acylhydrazone derivatives. The motivation is to further demonstrate the possibility of long-term release of anti-diabetic as well as higher accumulation of the antitumor derivative by using the nanotechnology-based production. The produced nanoparticles were obtained by the nanoprecipitation method, which revealed to be effective in the encapsulation of the bioactive compounds. The determined sizes were in the range of ∼100 nm, which are supposed to be suitable for both potential applications. The preliminary experimental data demonstrated the formation of stable nanosystems and further experiments are underway in order to determine the loading content, encapsulation efficiency and release profile of the hydrophobic bioactive compounds. (paper)

  20. A pH-responsive chitosan-b-poly(p-dioxanone) nanocarrier: formation and efficient antitumor drug delivery

    International Nuclear Information System (INIS)

    Tang Daolu; Song Fei; Chen Cheng; Wang Xiuli; Wang Yuzhong

    2013-01-01

    Increasing attention has recently been paid to the fabrication of drug delivery systems with excellent cell internalization and intracellular drug release properties. In this study, an amphiphilic block copolymer of chitosan was synthesized for the first time, which can self-assemble into micelles in a neutral aqueous solution but partially disassemble in an acidic endosomal/lysosomal environment. The antitumor drug, camptothecin (CPT), was encapsulated in the cores of the micelles for tumor cell therapy. In vitro drug release studies demonstrated that the micelles presented a much faster release of CPT at pH 5.0 than at pH 7.4. Blank micelles were found to be nontoxic in preliminary in vitro cytotoxicity assays. Cell experiments showed that the CPT-loaded micelles could be effectively internalized by Hela cells and accomplished a potent antitumor cell efficacy, indicating that the chitosan-based micelles might be an attractive new platform for efficient intracellular drug delivery. (paper)