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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. Semicarbazonas e tiossemicarbazonas: o amplo perfil farmacológico e usos clínicos

    OpenAIRE

    Beraldo Heloisa

    2004-01-01

    This article shows that thiosemicarbazones, semicarbazones and their metal complexes can exhibit target selectivity along with a wide pharmacological profile. Complexes of thiosemicarbazones with cytotoxic or antitumoral activity are presented, some of which show activity against cisplatinum-resistant cells. The inhibition mechanism of the enzyme ribonucleoside diphosphate reductase (RDR), involved in DNA syntheses, by alpha(N)-heterocyclic thiosemicarbazones is discussed. The encouraging res...

  3. Semicarbazonas e tiossemicarbazonas: o amplo perfil farmacológico e usos clínicos

    Directory of Open Access Journals (Sweden)

    Beraldo Heloisa

    2004-01-01

    Full Text Available This article shows that thiosemicarbazones, semicarbazones and their metal complexes can exhibit target selectivity along with a wide pharmacological profile. Complexes of thiosemicarbazones with cytotoxic or antitumoral activity are presented, some of which show activity against cisplatinum-resistant cells. The inhibition mechanism of the enzyme ribonucleoside diphosphate reductase (RDR, involved in DNA syntheses, by alpha(N-heterocyclic thiosemicarbazones is discussed. The encouraging results of clinical trials with the RDR inhibitor 3-aminopyridine-2-carboxaldehyde thiosemicarbazone ("Triapine" against rapidly growing tumors are outlined. Examples are also given of thiosemicarbazones with antiviral and antimicrobial activity. The possible applications of semicarbazones as anticonvulsants with low toxicity and good therapeutic index are presented.

  4. 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)

  5. Semicarbazonas e tiossemicarbazonas: o amplo perfil farmacológico e usos clínicos Semicarbazones and thiosemicarbazones: their wide pharmacological profile and clinical applications

    OpenAIRE

    Heloisa Beraldo

    2004-01-01

    This article shows that thiosemicarbazones, semicarbazones and their metal complexes can exhibit target selectivity along with a wide pharmacological profile. Complexes of thiosemicarbazones with cytotoxic or antitumoral activity are presented, some of which show activity against cisplatinum-resistant cells. The inhibition mechanism of the enzyme ribonucleoside diphosphate reductase (RDR), involved in DNA syntheses, by alpha(N)-heterocyclic thiosemicarbazones is discussed. The encouraging res...

  6. Antitumor compounds from marine actinomycetes.

    OpenAIRE

    Salas, José A.; Carmen Méndez; Carlos Olano

    2009-01-01

    Chemotherapy is one of the main treatments used to combat cancer. A great number of antitumor compounds are natural products or their derivatives, mainly produced by microorganisms. In particular, actinomycetes are the producers of a large number of natural products with different biological activities, including antitumor properties. These antitumor compounds belong to several structural classes such as anthracyclines, enediynes, indolocarbazoles, isoprenoides, macrolides, non-ribosomal pept...

  7. Cytokines and antitumor immunity.

    Science.gov (United States)

    Müller, Ludmila; Pawelec, Graham

    2003-06-01

    Currently, the notion of immunosurveillance against tumors is enjoying something of a renaissance. Even if we still refuse to accept that tumors arising in the normal host are unable to trigger an immune response because of the lack of initiation ("danger") signals, there is no doubt that the immune system can be manipulated experimentally and by implication therapeutically to exert anti-tumor effects. For this activity to be successful, the appropriate cytokine milieu has to be provided, making cytokine manipulation central to immunotherapy. On the other hand, the major hurdle currently preventing successful immunotherapy is the ability of tumors to evolve resistant variants under the pressure of immune selection. Here, too, the cytokine milieu plays an essential role. The purpose of this brief review is to consider the current status of the application of cytokines in facilitating antitumor immunity, as well their role in inhibiting responses to tumors. Clearly, encouraging the former but preventing the latter will be the key to the effective clinical application of cancer immunotherapy. PMID:12779349

  8. DAS performance analysis

    International Nuclear Information System (INIS)

    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

  9. DAS performance analysis

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Antitumor Immunity and Dietary Compounds

    Directory of Open Access Journals (Sweden)

    Annalise R. Smith

    2013-12-01

    Full Text Available The mechanisms by which natural dietary compounds exert their antitumor effects have been the focus of a large number of research efforts in recent years. Induction of apoptosis by inhibition of cell proliferative pathways is one of the common means of cell death employed by these dietary compounds. However, agents that can activate an antitumor immune response in addition to a chemotherapeutic effect may be useful adjuvants or alternative therapies for the treatment of cancer. The focus of this review is to highlight representative dietary compounds, namely Withania somnifera, Panax ginseng, curcumin and resveratrol with special emphasis on their antitumor immune mechanism of action. Each of these dietary compounds and their sources has a history of safe human use as food or in herbal medicine traditions, potentially making them ideal therapeutics. Here we report the recent advances in the cellular immune mechanisms utilized by these compounds to induce antitumor immunity. Taken together, these findings provide a new perspective for exploiting novel dietary compounds as chemoimmunotherapeutic anti-cancer agents.

  11. Ribonucleases and their antitumor activity

    Czech Academy of Sciences Publication Activity Database

    Matoušek, Josef

    2001-01-01

    Roč. 129, č. 3 (2001), s. 175-191. ISSN 1532-0456 R&D Projects: GA ČR GA523/01/0114; GA AV ČR KSK5052113 Keywords : angiogenin * antitumor * ribonuclease Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.930, year: 2001

  12. Das problemzentrierte Interview

    OpenAIRE

    Witzel, Andreas

    2000-01-01

    Das problemzentrierte Interview (PZI) ist ein theoriegenerierendes Verfahren, das den vermeintlichen Gegensatz zwischen Theoriegeleitetheit und Offenheit dadurch aufzuheben versucht, dass der Anwender seinen Erkenntnisgewinn als induktiv-deduktives Wechselspiel organisiert. Entsprechende Kommunikationsstrategien zielen zum einen auf die Darstellung der subjektiven Problemsicht. Zum anderen werden die angeregten Narrationen durch Dialoge ergänzt, die Resultat ideenreicher und leitfadengestützt...

  13. ANTITUMOR EFFECT OF SNAKE VENOMS

    Directory of Open Access Journals (Sweden)

    R. J. DA SILVA

    1996-01-01

    Full Text Available The search for biological antitumor agents has been pursued for over half a century. Snake venom has been shown to possess a wide spectrum of biological activities. The objectives of the present review are to evaluate the existing controversies on this subject published in a number of papers and to propose probable explanations for the phenomena observed. We reported our results obtained in a study, in which we evaluated the action of the venoms of Crotalus durissus terrificus and Bothrops jararaca on Ehrlich ascites tumor cells. We noticed an important antitumor effect, mainly with Bothrops jararaca venom, as well as an increase in the functional activity of macrophages. We also observed an increase in the number of mononuclear and polymorphonuclear cells with Bothrops jararaca venom. Considering these findings, we postulate that both Bothrops jararaca and Crotalus durissus terrificus venoms can act directly on tumor cells. In addition, we propose an indirect mechanism, based on the stimulation of the inflammatory response, to inhibit tumor growth and to promote its rejection.

  14. O marketing das cidades

    OpenAIRE

    Almeida, Clarinda da Costa

    2004-01-01

    O Marketing das Cidades, é uma área de aplicação do Marketing, com crescente importância para o desenvolvimento e crescimento de cidades, regiões, países, no limite de qualquer lugar. É o processo de gestão que é desenvolvido nas cidades para atender à satisfação das necessidades e desejos de indivíduos e organizações. Assim pretende-se, neste artigo, descrever e analisar o uso e a importância das ferramentas de marketing no desenvolvimento das cidades, através da elaboração de um modelo p...

  15. Das personalisierte Genom

    OpenAIRE

    Streubel B

    2012-01-01

    Im Jahr 2001 gelang nach langjährigen, multinationalen Bemühungen die erfolgreiche Entschlüsselung des menschlichen Genoms. Das Jahr 2008 gilt als Startpunkt der personalisierten Genomanalysen, da hier erstmals das Genom einer Person, nämlich des Entdeckers der chemischen DNA-Struktur, James Watson, vollständig sequenziert wurde. Ein wesentlicher Unterschied zur Genomsequenzierung im Jahr 2001 war hierbei, dass im Gegensatz zu der konventionellen Sangersequenzierung eine neue Sequenziert...

  16. Das Variationsproblem der Elastostatik

    OpenAIRE

    Schimmöller, Heinrich

    1989-01-01

    Das Variationsproblem der Elastostatik Ausgangspunkt der Arbeit sind die Differentialgleichungen des linear-elastischen Kontinuums und die daraus folgenden NAVIER'schen Gleichungen. Als Randbedingungen werden allgemeine gemischte Randbedingungen formuliert. Zunächst werden der Energiesatz der Elastizitätstheorie, die Formänderungsarbeit und das Gesamtpotential abgeleitet. Der einfache Denkansatz der Variation der Verschiebungen, gleichbedeutend mit dem Prinzip der virtuellen Verschiebu...

  17. 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

  18. Das berufliche und das private Geschlecht

    Directory of Open Access Journals (Sweden)

    Almut Sülzle

    2006-07-01

    Full Text Available Jutta Wergen untersucht Geschlechterkonstruktionen in Männerberufen, indem sie Frauen befragt, die als Lkw-Fahrerinnen, als Binnenschifferinnen und als Bus- bzw Straßenbahnfahrerinnen im öffentlichen Nahverkehr arbeiten. Dabei kann sie zeigen, dass diese Berufe sehr unterschiedliche Kontexte für Geschlechterarrangements zur Verfügung stellen, von traditioneller Arbeitsteilung bis zur Umkehrung derselben. Der Kern der Erkenntnis dieser Arbeit, das sei hier schon vorweggenommen, ist bestechend und zugleich faszinierend einfach: die Trennung in ein „professionelles“ und ein „privates“ Geschlecht.

  19. Antitumoral activity of marine organism

    International Nuclear Information System (INIS)

    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

  20. Das Risiko der Landschaft

    Directory of Open Access Journals (Sweden)

    Mosé Ricci

    2012-08-01

    Full Text Available Die italienischen Landschaften sind in Gefahr wegen der immer zunehmenden Umweltschaeden, und es ist noetig, ueber diese Notstandlage, die nicht allen bewusst ist, nachzudenken. Wir leben in einen zweideutigen Zustand, in welchem theoretisch alle die Unversehrtheit des Landes verteidigen, aber dann einen Lebensstil fuehren, der nicht die Systeme der Umwelt und der Landschaft schuetzt. Achgeben auf das Risiko der Landschaft hat eine doppelte Bedeutung, fuer das kollektive Gewissen und fuer die Regelung des Territoriums. Die Analyse der Gefahr fuer die Landschaft, der Kompetenz der Forschung ueber den Kulturschatz Italiens, hat die Unterstuetzung der “Carta del rischio del ministero per i beni e le attività culturali”. Um diese in Kraft treten zu lassen, ist es noetig, das Landschaftsgut aus Vermoegensanschauungen zu definieren, so wie in der Europaischen Konvention und aus Juristischer Sicht vorgesehen ist. In dieser Optik kann die Planung und Aenderung des Territoriums als Punkt der Risikokontrolle angesehen werden.

  1. Das Reflektierende Team

    DEFF Research Database (Denmark)

    Lorensen, Marlene Ringgaard; Gaarden, Marianne

    2015-01-01

    dazu hat Marlene Ringgaard Lorensen das Potenzial des von außen kommenden, dezidiert ›andersartigen‹ Beitrags der Hörenden für die dialogische Predigt im Rückgriff auf Theorien von Mikhail Bakhtin analysiert. Als theologische Grundfigur steht hinter der Arbeit im reflektierenden homiletischen Team also...

  2. 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 properti...

  3. Natural glycoconjugates with antitumor activity.

    Science.gov (United States)

    La Ferla, Barbara; Airoldi, Cristina; Zona, Cristiano; Orsato, Alexandre; Cardona, Francisco; Merlo, Silvia; Sironi, Erika; D'Orazio, Giuseppe; Nicotra, Francesco

    2011-03-01

    Cancer is one of the major causes of death worldwide. As a consequence, many different therapeutic approaches, including the use of glycosides as anticancer agents, have been developed. Various glycosylated natural products exhibit high activity against a variety of microbes and human tumors. In this review we classify glycosides according to the nature of their aglycone (non-saccharidic) part. Among them, we describe anthracyclines, aureolic acids, enediyne antibiotics, macrolide and glycopeptides presenting different strengths and mechanisms of action against human cancers. In some cases, the glycosidic residue is crucial for their activity, such as in anthracycline, aureolic acid and enediyne antibiotics; in other cases, Nature has exploited glycosylation to improve solubility or pharmacokinetic properties, as in the glycopeptides. In this review we focus our attention on natural glycoconjugates with anticancer properties. The structure of several of the carbohydrate moieties found in these conjugates and their role are described. The structure–activity relationship of some of these compounds, together with the structural features of their interaction with the biological targets, are also reported. Taken together, all this information is useful for the design of new potential anti-tumor drugs. PMID:21120227

  4. "Das Boot ist voll"

    OpenAIRE

    Pagenstecher, Cord

    2012-01-01

    Die Geschichte des Visuellen erforschte Cord Pagenstecher bereits in verschiedenen Arbeiten mit Blick auf Migration. Im hier vorliegenden Artikel befasst er sich konkret mit der visuellen Verarbeitung des Motivs „Das Boot ist voll. . . “. Es taucht über einige Jahrzehnte hinweg als Synonym für die angeblich von Flüchtlingen überflutete Bundesrepublik in den Printmedien auf. Die Flüchtlinge rassistisch, fremdenfeindlich karikierenden Titel von Zeitschriften werden mit der Zeit auch in Tag...

  5. Das Interview als Beziehungsraum

    OpenAIRE

    Tietel, Erhard

    2000-01-01

    Am Beispiel einer schwierigen Interviewbeziehung wird gezeigt, daß und in welcher Weise das Beziehungsgeschehen im Interview sowie die Verwendung des Beziehungsraums des Interviews durch den Befragten entscheidende heuristische Hinweise zum Aufspüren und Verstehen latenter Aspekte des Forschungsthemas geben können. Die im Interview stattfindende Reduktion des potentiell triadischen Beziehungsraums auf dyadisch-geschlossene Beziehungsebenen und der weitgehende Verlust des eigenen Spielraums un...

  6. Wozu all das Theater?

    OpenAIRE

    Ronke, Astrid

    2005-01-01

    Die vorliegende Arbeit untersucht theoretische und praktische Grundlagen und Implikationen von Drama und Theater als eine Unterrichtsmethode für den Fremdsprachenunterricht, speziell für den DaF(Deutsch als Fremdsprache)Unterricht in Amerika. Vor dem Hintergrund schwankender Einschreibezahlen für das Fach Deutsch, dem Desinteresse an Fremdsprachen und dem Fehlen nationaler Fremdsprachennormen für die Hochschulbildung in den USA, wird eine Unterrichtsmethode vorgestellt, die durch ihren ganzhe...

  7. Antitumor effects of electrochemical treatment

    Institute of Scientific and Technical Information of China (English)

    Héctor Manuel Camué Ciria; Maraelys Morales González; Lisset Ortíz Zamora; Luis Enrique Bergues Cabrales; Gustavo Victoriano Sierra González; Luciana Oliveira de Oliveira; Rodrigo Zanella

    2013-01-01

    Electrochemical treatment is an alternative modality for tumor treatment based on the application of a low intensity direct electric current to the tumor tissue through two or more platinum electrodes placed within the tumor zone or in the surrounding areas.This treatment is noted for its great effectiveness,minimal invasiveness and local effect.Several studies have been conducted worldwide to evaluate the antitumoral effect of this therapy.In all these studies a variety of biochemical and physiological responses of tumors to the applied treatment have been obtained.By this reason,researchers have suggested various mechanisms to explain how direct electric current destroys tumor cells.Although,it is generally accepted this treatment induces electrolysis,electroosmosis and electroporation in tumoral tissues.However,action mechanism of this alternative modality on the tumor tissue is not well understood.Although the principle of Electrochemical treatment is simple,a standardized method is not yet available.The mechanism by which Electrochemical treatment affects tumor growth and survival may represent more complex process.The present work analyzes the latest and most important research done on the electrochemical treatment of tumors.We conclude with our point of view about the destruction mechanism features of this alternative therapy.Also,we suggest some mechanisms and strategies from the thermodynamic point of view for this therapy.In the area of Electrochemical treatment of cancer this tool has been exploited very little and much work remains to be done.Electrochemical treatment constitutes a good therapeutic option for patients that have failed the conventional oncology methods.

  8. Primary Screeningof Substanceswith Potential Antitumor Activity

    OpenAIRE

    А.Kh. Khasenova; Sh.Zh.Daurenbekova

    2015-01-01

    A primary screening of antitumor substances was carried out among strains of actinomycetes isolated from the samples of natural substrates of arid zones in the Ile-Balkhash region. Antitumor properties of actinomycetes against Staphylococcus aureus209Р(S. aureus 209P) and its mutants UF-2 and UF-3 were studied using the agar block technique. The diameter of growth inhibition zone was measured after incubation of the test microorganisms at a temperature of 37 °C for 24 hours. 16...

  9. Durch das Leben lernen

    OpenAIRE

    Waßmann, Ingolf; Versick, Daniel; Thomanek, Anja; Tavangarian, Djamshid

    2014-01-01

    Web 2.0 und soziale Netzwerke gaben erste Impulse für neue Formen der Online-Lehre, welche die umfassende Vernetzung von Objekten und Nutzern im Internet nachhaltig einsetzen. Die Vielfältigkeit der unterschiedlichen Systeme erschwert aber deren ganzheitliche Nutzung in einem umfassenden Lernszenario, das den Anforderungen der modernen Informationsgesellschaft genügt. In diesem Beitrag wird eine auf dem Konnektivismus basierende Plattform für die Online-Lehre namens “Wiki-Learnia” präsentiert...

  10. Das personalisierte Genom

    Directory of Open Access Journals (Sweden)

    Streubel B

    2012-01-01

    Full Text Available Im Jahr 2001 gelang nach langjährigen, multinationalen Bemühungen die erfolgreiche Entschlüsselung des menschlichen Genoms. Das Jahr 2008 gilt als Startpunkt der personalisierten Genomanalysen, da hier erstmals das Genom einer Person, nämlich des Entdeckers der chemischen DNA-Struktur, James Watson, vollständig sequenziert wurde. Ein wesentlicher Unterschied zur Genomsequenzierung im Jahr 2001 war hierbei, dass im Gegensatz zu der konventionellen Sangersequenzierung eine neue Sequenziertechnologie, die so genannte massive Parallelsequenzierung, zur Verfügung stand, die diese personalisierte Genomanalyse erst ermöglichte. Während die Entschlüsselung des menschlichen Genoms in den Jahren 1990–2001 mehrere Milliarden Dollar kostete, sind die Kosten für Genomuntersuchungen mittlerweile dermaßen gefallen, dass die neuen Technologien bereits in die Routinelabordiagnostik Einzug gehalten und dabei neue Möglichkeiten, z. B. bei der non-invasiven Pränataltestung, eröffnet haben.

  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. DNA Modifications by Novel Antitumor Platinum Drugs

    Czech Academy of Sciences Publication Activity Database

    Brabec, Viktor

    Kiev : National Taras Shevchenko University, 2001, s. SC-L3. [NATO Advanced Research Workshop Autumn School: Frontiers in Molecular-Scale Science and Technology of Fullerene, Nanotube, Nanosilicon and Biopolymer (DNA, Protein) Multifunctional Nanosystems. Kiev (UA), 09.09.2001-12.09.2001] Institutional research plan: CEZ:AV0Z5004920 Keywords : DNA * antitumor * platinum drugs Subject RIV: BO - Biophysics

  13. Das kann ich aber auch!

    OpenAIRE

    Vollmer, Wolfgang

    2007-01-01

    In der Fotografie als reproduktiver Kunst und reproduktiver Technik existiert eine Vielzahl besonderer Umgangs- und Aneignungsformen im Kopieren originaler Bildideen. Das Spektrum reicht von der kreativen Nachstellung bis zum Plagiat. Fotografie ist das einzige Medium, das diese Bandbreite von Möglichkeiten in der Gegenüberstellung von Original und Kopie nutzen kann. Wolfgang Vollmer, Kölner Fotograf und Autor mehrerer Künstlerbücher, die sich kreativ mit Nachbildung und Fortführung von Ikone...

  14. Hypoxia-targeting antitumor prodrugs and photosensitizers

    International Nuclear Information System (INIS)

    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 λex=365 nm, while being quite stable in the dark. The photoactivation mechanism was also clarified by means of nanosecond laser flash photolysis. (authors)

  15. Synthesis and Evaluation of the Anti-corrosion Activity of Thiosemicarbazide and Thiosemicarbazone 4-N-(p-methoxyphenyl Substituted [Síntese e Avaliação da Atividade Anticorrosiva de Tiossemicarbazida e Tiossemicarbazona 4-N-(p-metóxifenil Substituídas

    Directory of Open Access Journals (Sweden)

    Danilo Sousa-Pereira

    2013-08-01

    Full Text Available The anti-corrosion activity of 1-phenyl-4-(p-methoxyphenyl-thiosemicarbazide (1and cinnamaldehyde-4-(p-methoxyphenyl-thiosemicarbazone (2 compounds against the corrosion of AISI 1020 carbon steel in 1 molL-1 HCl solution was evaluated by potentiodynamic polarization and electrochemical impedance spectroscopy (EIS at different inhibitor concentrations. The relationship between molecular structure and inhibitory efficiency was evaluated by molecular modeling. The polarization curves indicate that both compounds act as mixed inhibitors. Nyquist diagrams show that the charge transfer resistance increases when the inhibitor concentration rises; consequently, increasing the inhibitoryefficiency. The theoretical results were supported by the experimental data. All techniques used showed that thiosemicarbazone (2 is a more potent inhibitor than thiosemicarbazide (1.

  16. 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.

  17. Antitumor Activities of Metal Oxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Maria Pilar Vinardell

    2015-06-01

    Full Text Available Nanoparticles have received much attention recently due to their use in cancer therapy. Studies have shown that different metal oxide nanoparticles induce cytotoxicity in cancer cells, but not in normal cells. In some cases, such anticancer activity has been demonstrated to hold for the nanoparticle alone or in combination with different therapies, such as photocatalytic therapy or some anticancer drugs. Zinc oxide nanoparticles have been shown to have this activity alone or when loaded with an anticancer drug, such as doxorubicin. Other nanoparticles that show cytotoxic effects on cancer cells include cobalt oxide, iron oxide and copper oxide. The antitumor mechanism could work through the generation of reactive oxygen species or apoptosis and necrosis, among other possibilities. Here, we review the most significant antitumor results obtained with different metal oxide nanoparticles.

  18. First synthesis of antitumoral dasyscyphin B

    OpenAIRE

    Akhaouzan, Ali; Fern??ndez, Antonio; Mansour, Ahmed I.; ??lvarez, Esteban; Haid??ur, Ali; ??lvarez-Manzaneda, Ram??n; Chahboun, Rachid; ??lvarez-Manzaneda, Enrique

    2013-01-01

    The first synthesis of dasyscyphin B, an antitumoral metabolite obtained from the ascomycete Dasyscyphus niveus, has been achieved starting from commercial abietic acid. The key steps of the synthetic sequence are the diastereoselective ??-methylation of a ketoaldehyde, followed by an intramolecular aldol condensation and the further Diels???Alder cycloaddition of a dienol ester. The procedure reported will allow the synthesis of related metabolites functionalized in the A ring.

  19. The antitumor activity of the fungicide ciclopirox

    OpenAIRE

    Zhou, Hongyu; Shen, Tao; Luo, Yan; Liu, Lei; Chen, Wenxing; Xu, Baoshan; Han, Xiuzhen; Pang, Jia; Rivera, Chantal A; Huang, Shile

    2010-01-01

    Ciclopirox olamine (CPX) is a synthetic antifungal agent clinically used to treat mycoses of the skin and nails. Here we show that CPX inhibited tumor growth in human breast cancer MDA-MB-231 xenografts. To unveil the underlying mechanism, we further studied the antitumor activity of CPX in cell culture. The results indicate that CPX inhibited cell proliferation and induced apoptosis in human rhabdomyosarcoma (Rh30), breast carcinoma (MDA-MB231), and colon adenocarcinoma (HT-29) cells in a co...

  20. Impact of antitumor therapy on nutrition

    International Nuclear Information System (INIS)

    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

  1. Structural Antitumoral Activity Relationships of Synthetic Chalcones

    OpenAIRE

    Cesar Echeverria; Juan Francisco Santibañez; Oscar Donoso-Tauda; Escobar, Carlos A.; Rodrigo Ramirez-Tagle

    2009-01-01

    Relationships between the structural characteristic of synthetic chalcones and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with synthetic 2’-hydroxychalcones resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated reactivity indexes and the adiabatic electron affinities using the DFT method including solvent effects, suggest a structure-activity relationship between the Chalcones structure and the apoptosis in Hep...

  2. Antitumor action of bovine seminal ribonuclease

    International Nuclear Information System (INIS)

    Unlike the bovine pancreatic ribonuclease (RNase A), bovine seminal ribonuclease (BS RNase) displays various biological activities; including antitumor activity, immunosuppressivity, spermatogenicity and embryo-toxicity. To learn more about its antitumor effect we tested BS RNase on the growth of 16 cell lines derived from patients with various hematological malignancies. The cells of lymphoid origin were generally more susceptible to BS RNase, administered in the range of concentrations from 2 to 100 μg/ml, than the myeloid ones. RNase A used at the same concentrations did not exert any inhibitory effect. The inhibitory effect of BS RNase persisted in cultured cells three times wash in complete medium and cell re-cultivation in fresh medium free of BS RNase. Four cell lines were very little sensitive (KG-1 and U-937) or resistant (JOK and NAMALWA) to BS RNase regardless of their origin. The in vivo antitumor effect of BS RNase was tested on human prostate carcinoma transplanted to athymic nude mice. The daily dose of BS RNase (0.25 mg/20 g) was administered for three weeks except weekends (15 doses) by three different ways (intraperitoneally - i.p., subcutaneously - s.c. and intratumorally - i.t.). Whereas i.p. administration was ineffective, s.c. administration significantly reduced size of the tumors and i.t. administration abolished half of the tumors in treated mice. The average of treated mice decreased during the experiment by 10-15%. (author)

  3. Hat das Internet ein Programm?

    OpenAIRE

    Coy, Wolfgang

    1998-01-01

    Hat das Internet ein Programm? Ist der Papst katholisch? Natürlich hat das Internet Millionen Programme - solche, die es nutzt und solche die man per FTP - File Transfer Protocol auf die eigene Maschine herunter laden kann und solche, die sich unbemerkt auf der Festplatte festsetzen. Letztere heißen Viren, Würmer oder trojanische Pferde. Aber das sind natürlich Programme im Sinne der Informatik, nicht im Sinne der broadcast media. Im amerikanisch-englischen Sprachraum, dem die...

  4. Antitumor activity of polyacrylates of noble metals in experiment

    OpenAIRE

    Larisa A. Ostrovskaya; David B. Korman; Natalia V. Bluhterova; Margarita M. Fomina; Valentina A. Rikova; Claudia A. Abzaeva; Larisa V. Zhilitskaya; Nina O. Yarosh

    2014-01-01

    The aim of this research has been the study of the antitumor activity of polymetalacrylate derivatives containing in their structure noble metals. Metallic derivatives of polyacrylic acid were not previously tested as antitumor agents.The antitumor activity of polyacrylates, containing argentum (argacryl), aurum (auracryl) and platinum (platacryl) against experimental models of murine solid tumors (Lewis lung carcinoma and Acatol adenocarcinoma) as well as acute toxicity have been studied. It...

  5. Das Museum Plagiarius in Solingen

    OpenAIRE

    Helmenstein, Caroline

    2009-01-01

    "Das Original ist links zu sehen, das Plagiat rechts." Dieses Konzept liegt der Ausstellung von über 250 scheinbaren Zwillingen im Solinger Museum Plagiarius zugrunde. Ziel des Museums ist es, den Besuchern anschaulich die Bandbreite von Nachahmungen, Fälschungen und Raubkopien vor Augen zu führen und sie für die immensen Schäden zu sensibilisieren, die durch die Missachtung geistigen Eigentums entstehen.

  6. IDENTIDADE DAS PESSOAS E DAS ORGANIZAÇÕES

    Directory of Open Access Journals (Sweden)

    Iris Barbosa Boulart

    2008-11-01

    Full Text Available Resumo Este artigo aborda a questão da identidade no interior das organizações: identidade das pessoas, que são diferentes umas das outras e identidade das organizações, que são marcadas por suas particularidades e sua cultura. São analisadas as abordagens de autores como Erik Erikson, Georges Herbert Mead, Peter Berger e Luckman, assim como Erving Goffman no caso da identidade das pessoas. A identidade organizacional é abordada principalmente na perspectiva de Edgar Schein, que, no Brasil, tem como seguidor o grupo liderado por Maria Tereza Leme Fleury, da Universidade de São Paulo. A parte final do artigo tece considerações sobre as mudanças advindas da globalização e do desenvolvimento da tecnologia da informação e suas conseqüências para a identidade das pessoas e das organizações. Palavras-chave: identidade pessoal, identidade organizacional, identidade no trabalho, socialização organizacional. Abstract This article deals with the issue of identity within organizations: people’s identity, that are different from one another and the identity of the organizations, which are marked by their peculiarities and culture. The approaches of authors such as Erik Erikson, Georges Herbert Mead, Peter Berger and Luckman are analyzed, as well as Erving Gooffman’s approach to people’s identity. The organizationa l identity is approched mainly through Edgar Schein’s perspective, which has the group leaded by Maria Tereza Leme Fleury, from Universidade Federal de Sao Paulo, as a follower in Brazil. The final part of this article makes comments on the changes brought about globalization and information technology development and their consequences for the identity of people and organizations. Key-words: personal identity, organizational identity, work identity, organizational socialization.

  7. Antitumor Immunity Induced after α Irradiation

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Gorin

    2014-04-01

    Full Text Available Radioimmunotherapy (RIT is a therapeutic modality that allows delivering of ionizing radiation directly to targeted cancer cells. Conventional RIT uses β-emitting radioisotopes, but recently, a growing interest has emerged for the clinical development of α particles. α emitters are ideal for killing isolated or small clusters of tumor cells, thanks to their specific characteristics (high linear energy transfer and short path in the tissue, and their effect is less dependent on dose rate, tissue oxygenation, or cell cycle status than γ and X rays. Several studies have been performed to describe α emitter radiobiology and cell death mechanisms induced after α irradiation. But so far, no investigation has been undertaken to analyze the impact of α particles on the immune system, when several studies have shown that external irradiation, using γ and X rays, can foster an antitumor immune response. Therefore, we decided to evaluate the immunogenicity of murine adenocarcinoma MC-38 after bismuth-213 (213Bi irradiation using a vaccination approach. In vivo studies performed in immunocompetent C57Bl/6 mice induced a protective antitumor response that is mediated by tumor-specific T cells. The molecular mechanisms potentially involved in the activation of adaptative immunity were also investigated by in vitro studies. We observed that 213Bi-treated MC-38 cells release “danger signals” and activate dendritic cells. Our results demonstrate that α irradiation can stimulate adaptive immunity, elicits an efficient antitumor protection, and therefore is an immunogenic cell death inducer, which provides an attractive complement to its direct cytolytic effect on tumor cells.

  8. Antitumor activity of the immunomodulatory lead Cumaside.

    Science.gov (United States)

    Aminin, D L; Chaykina, E L; Agafonova, I G; Avilov, S A; Kalinin, V I; Stonik, V A

    2010-06-01

    A new immunomodulatory lead Cumaside that is a complex of monosulfated triterpene glycosides from the sea cucumber Cucumaria japonica and cholesterol possesses significantly less cytotoxic activity against sea urchin embryos and Ehrlich carcinoma cells than the corresponding glycosides. Nevertheless Cumaside has an antitumor activity against different forms of experimental mouse Ehrlich carcinoma in vivo both independently and in combination with cytostatics. The highest effect occurs at a treatment once a day for 7 days before the tumor inoculation followed by Cumaside treatment once a day for 7 days. Prophylactic treatment with Cumaside and subsequent therapeutic application of 5-fluorouracil suppressed the tumor growth by 43%. PMID:20227525

  9. PARP1 Inhibitors: antitumor drug design

    OpenAIRE

    MALYUCHENKO N.V.; Kotova, E. Yu.; Kulaeva, O. I.; Kirpichnikov, M P; STUDITSKIY V.M.

    2015-01-01

    The poly (ADP-ribose) polymerase 1 (PARP1) enzyme is one of the promising molecular targets for the discovery of antitumor drugs. PARP1 is a common nuclear protein (1–2 million molecules per cell) serving as a “sensor” for DNA strand breaks. Increased PARP1 expression is sometimes observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. The PARP1 expression level is a prognostic indicator and is associated with a poor survival prognosis. There is evidence that high PA...

  10. PARP1 INHIBITORS: ANTITUMOR DRUG DESIGN

    OpenAIRE

    MALYUCHENKO N.V.; KOTOVA E. YU.; Kulaeva, O. I.; Kirpichnikov, M P; STUDITSKIY V.M.

    2015-01-01

    The poly (ADP-ribose) polymerase 1 (PARP1) enzyme is one of the promising molecular targets for the discovery of antitumor drugs. PARP1 is a common nuclear protein (1-2 million molecules per cell) serving as a “sensor” for DNA strand breaks. Increased PARP1 expression is sometimes observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. The PARP1 expression level is a prognostic indicator and is associated with a poor survival prognosis. There is evidence that high PA...

  11. Vicenistatin, a novel 20-membered macrocyclic lactam antitumor antibiotic.

    Science.gov (United States)

    Shindo, K; Kamishohara, M; Odagawa, A; Matsuoka, M; Kawai, H

    1993-07-01

    A new antitumor antibiotic vicenistatin was isolated from the culture broth of Streptomyces sp. HC34. The structure of vicenistatin was elucidated by NMR spectral analysis. Vicenistatin exhibited antitumor activity against human colon carcinoma Co-3 in the xenograft model. PMID:8360102

  12. 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.

  13. The antitumor activity of the fungicide ciclopirox.

    Science.gov (United States)

    Zhou, Hongyu; Shen, Tao; Luo, Yan; Liu, Lei; Chen, Wenxing; Xu, Baoshan; Han, Xiuzhen; Pang, Jia; Rivera, Chantal A; Huang, Shile

    2010-11-15

    Ciclopirox olamine (CPX) is a synthetic antifungal agent clinically used to treat mycoses of the skin and nails. Here, we show that CPX inhibited tumor growth in human breast cancer MDA-MB-231 xenografts. To unveil the underlying mechanism, we further studied the antitumor activity of CPX in cell culture. The results indicate that CPX inhibited cell proliferation and induced apoptosis in human rhabdomyosarcoma (Rh30), breast carcinoma (MDA-MB231) and colon adenocarcinoma (HT-29) cells in a concentration-dependent manner. By cell cycle analysis, CPX induced accumulation of cells in G(1)/G(0) phase of the cell cycle. Concurrently, CPX downregulated cellular protein expression of cyclins (A, B1, D1 and E) and cyclin-dependent kinases (CDK2 and CDK4) and upregulated expression of the CDK inhibitor p21(Cip1), leading to hypophosphorylation of retinoblastoma protein. CPX also downregulated protein expression of Bcl-xL and survivin and enhanced cleavages of Bcl-2. Z-VAD-FMK, a pan-caspase inhibitor, partially prevented CPX-induced cell death, suggesting that CPX-induced apoptosis of cancer cells is mediated at least in part through caspase-dependent mechanism. The results indicate that CPX is a potential antitumor agent. PMID:20225320

  14. Teologia e estudo das escrituras

    Directory of Open Access Journals (Sweden)

    Rabuske, Irineu J.

    2007-01-01

    Full Text Available A revalorização da sagrada escritura, no âmbito da Igreja Católica, enseja uma reflexão sobre a relação entre a teologia e o estudo das sagradas escrituras. Ponto de partida para esta reflexão é o nº 24 do documento Dei Verbum, no Concílio Ecumênico Vaticano II: ". . . o estudo das Sagradas Escrituras seja como que a alma da Sagrada Teologia".

  15. Brexit: Droht das Auseinanderbrechen Europas?

    OpenAIRE

    Peters, Dirk

    2016-01-01

    Der Brexit ist da. Droht jetzt die Erosion, Implosion oder gar Explosion der EU, das Ende des Friedensprojekts Europa? Droht, wie Premierminister Cameron in seiner Kampagne gewarnt hatte, eine langfristige Gefährdung der britischen und europäischen Sicherheit?

  16. Onconase: A ribonuclease with antitumor activity

    Directory of Open Access Journals (Sweden)

    Małgorzata Zwolińska

    2010-02-01

    Full Text Available Onconase (ranpirnase is a homologous protein obtained from [i]Rana pipiens [/i]frog eggs. The activity of onconase, and particularly its antitumor effect, is strictly connected with ribonuclease (RN-ase activity. Onconase induces cell death through the decomposition of inner cellular RNA, inhibition of protein synthesis, and inhibition of cell growth and proliferation and it also specifically triggers tumor cell apoptosis. A very important mechanisms of its cytotoxicity is also its antioxidant activity. The results of preclinical trials demonstrated a high activity of onconase against tumor cells, also those resistant to cytostatics. Moreover, onconase showed synergic activity with other commonly used anticancer drugs. Several clinical trials were performed on patients suffering from kidney, breast, and pancreatic cancers. Most recently a phase III study of onconase in patients with mesothelioma was completed. There are also ongoing phase I and II clinical trials with non-small-cell lung cancer (NSCLC.

  17. Das Aussterben einer unbekannten Nutzungsart

    OpenAIRE

    Herb, Ulrich

    2007-01-01

    Zum 1. Januar 2008 tritt ein neues Urheberrechtsgesetz (UrhG) in Kraft. Es bringt neben zahlreichen Veränderungen etwa beim elektronischen Kopienversand en passant auch eine recht wenig beachtete Änderung: Wissenschaftliche Verlagen erhalten die Rechte zur Onlinepublikation von Dokumenten, die zwischen 1966 und 1995 bei ihnen erschienen sind. Vielleicht noch wichtiger: Damit verlieren die Autoren auch das Recht, die Texte selbst auf ihre Homepage zu stellen. Es sei denn, sie werden aktiv und ...

  18. Das Burning-Mouth-Syndrom

    OpenAIRE

    Ettlin, Dominik; Lukic, Nenad

    2014-01-01

    Anhaltendes Brennen im Mundbereich ohne dokumetierbare Ursache kann die Lebensqualität beeinträchtigen und zu frustrierenden Arzt- bzw. Zahnarztbesuchen führen. Die Gründe des primären Mundbrennens sind noch weitgehend unklar und werden erforscht. Wegen der Schmerzlokalisation kommt der Zahnmedizin eine zentrale diagnostische und therapeutische Rolle zu. Der Beitrag beleuchtet das aktuelle Wissen zum Thema und gibt Hinweise zur Behandlung betroffener Patienten.

  19. Pornografie – Was ist das ?

    OpenAIRE

    Corinna Rückert

    2010-01-01

    Die Diskussionen über das kulturelle und mediale Phänomen ‚Pornografie‘ zeichnen sich oft durch Unkenntnis des Betrachtungsgegenstands und definitorischer Ungenauigkeiten aus. Der vorliegende Text benennt Irrtümer und Vorurteile und liefert einen Beitrag zu einer wissenschaftlich nachvollziehbaren Definitionsgrundlage als Basis für weitere Diskussionen. Die nachfolgenden Überlegungen sind eine Kurzzusammenfassung der Dissertation von Corinna Rückert: ...

  20. Das k-Box-Produkt

    OpenAIRE

    Elser, Stefan

    2011-01-01

    Ziel dieser Doktorarbeit ist es, bekannte und oft verwendete Eigenschaften des Tychonow-Produkts in analoger Form für das k-Box-Produkt zu beweisen, was bisher noch nicht geschehen ist, und die Verbindung zwischen der Infinitären Kombinatorik und der Topologie zu vertiefen. In der Infinitären Kombinatorik, ein Zweig der modernen Mengenlehre, bedient man sich gerne topologischer Begriffe, um einerseits Ergebnisse zu verdeutlichen und um andererseits den sehr abstrakten kombinatorischen Be...

  1. Synthesis of Olaparib Derivatives and Their Antitumor Activities

    Institute of Scientific and Technical Information of China (English)

    LOU Xi-yu; YANG Xuan; DING Yi-li; WANG Jian-jun; YAN Qing-yan; HUANG Xian-gui; GUO Yang-hui

    2013-01-01

    A series of Olaparib derivatives was synthesized,and their structures were confirmed by 1H NMR,MS and elemental analysis.Their antitumor activities on breast cancer susceptbility gene 1/2(BRCA1/2)-deficient cancer cell lines including HCC1937,Capan-1 and MDA-MB-436 were evaluated.The antitumor activity of compound Olaparib-1 was better than the positive control Olaparib in BRCAl-deficient cell line HCC1937.

  2. Synthesis and Antitumor Activities In Vitro of Solanesylpiperazinotriamine

    Institute of Scientific and Technical Information of China (English)

    Chao Pie WANG; Jian Hong WANG; Ying GAN; Zhi Yong CHEN; Gang Jun DU; Jin ZHAO

    2006-01-01

    A series of novel antitumor agents-the solanesylpiperazinotriamine derivatives were designed and synthesized, their structures were confirmed by IR, 1H-NMR, MS, and element analysis. The preliminary tests showed that at low micromolar concentrations these compounds exhibited obvious toxicity on tumor cells in vitro, and the synergistic effect on clinical antitumor agent indicated that at noncytotoxic concentrations they also evidently enhanced the curative effect of vincristine.

  3. 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.

  4. Advanced nanocarriers for an antitumor peptide

    International Nuclear Information System (INIS)

    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

  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 activity of chemical modified natural compounds

    Directory of Open Access Journals (Sweden)

    Marilda Meirelles de Oliveira

    1991-01-01

    Full Text Available Search of new activity substances starting from chemotherapeutic agents, continously appears in international literature. Perhaps this search has been done more frequently in the field of anti-tumor chemotherapy on account of the unsuccess in saving advanced stage patients. The new point in this matter during the last decade was computer aid in planning more rational drugs. In near future "the accessibility of supercomputers and emergence of computer net systems, willopen new avenues to rational drug design" (Portoghese, P. S. J. Med. Chem. 1989, 32, 1. Unknown pharmacological active compounds synthetized by plants can be found even without this eletronic devices, as tradicional medicine has pointed out in many contries, and give rise to a new drug. These compounds used as found in nature or after chemical modifications have produced successful experimental medicaments as FAA, "flavone acetic acid" with good results as inibitors of slow growing animal tumors currently in preclinical evaluation for human treatment. In this lecture some international contributions in the field of chemical modified compounds as antineoplasic drugs will be examined, particularly those done by Brazilian researches.

  7. Das Ehrenamt im Technischen Hilfswerk

    OpenAIRE

    Oesterling, Carina

    2005-01-01

    Das Ehrenamt hat sowohl in der Forschung als auch in der Politik seit Ende der 1980er Jahre zunehmend an Bedeutung gewonnen. Durch ökonomische und soziale Veränderungen, insbesondere die Reduktion staatlicher Leistungen, rückten Wohlfahrts- und Interessenverbände, Bürger- und Umweltinitiativen, Stiftungen und nichtstaatliche Organisationen verstärkt ins öffentliche Interesse. Damit einher ging die Diskussion um freiwillige, unentgeltliche Tätigkeit und die Personen, die diese Tätigkeiten ausü...

  8. Das Naturschutzgebiet Stockberg bei Ottbergen

    OpenAIRE

    Häcker, Stefan

    2005-01-01

    Der Stockberg liegt nördlich der Ortschaft Ottbergen (Stadt Höxter) am Südrand des Herbremer Holzes, das Bestandteil eines zusammenhängenden Waldgebietes zwischen Höxter und Brakel ist. Der geologische Untergrund besteht aus Unterem Muschelkalk, dessen harte Gesteinsschichten der Verwitterung standhalten und den Grund für die steile Hangbildung zum Tal der Nethe darstellen. Während die Kuppe des Berges sowie die westlich und südöstlich exponierten Hänge waldbedeckt sind und forstlich genutzt ...

  9. Der Weg ist das Ziel

    OpenAIRE

    Schellenberg, Alexandra

    2011-01-01

    Wie entsteht ein Kunstwerk? Was passiert, bevor es ein Kunstwerk ist? Wie kann eine Idee Gestalt annehmen? Woher bezieht der Künstler überhaupt seine Inspirationen? All diesen Fragen kann der wissbegierige Besucher in der Ausstellung „Kunst im Werden. Skizzen, Projekte und Arbeitsbücher“ nachgehen, für die vom 24. Juni bis zum 22. Oktober 2011 das Buchmuseum der Sächsischen Landesbibliothek – Staats- und Universitätsbibliothek Dresden seine Türen öffnen wird.

  10. Crotalus durissus terrificus venom as a source of antitumoral agents

    Directory of Open Access Journals (Sweden)

    MA Soares

    2010-01-01

    Full Text Available The basic knowledge on neoplasms is increasing quickly; however, few advances have been achieved in clinical therapy against tumors. For this reason, the development of alternative drugs is relevant in the attempt to improve prognosis and to increase patients' survival. Snake venoms are natural sources of bioactive substances with therapeutic potential. The objective of this work was to identify and characterize the antitumoral effect of Crotalus durissus terrificus venom (CV and its polypeptide, crotoxin, on benign and malignant tumors, respectively, pituitary adenoma and glioblastoma. The results demonstrated that CV possess a powerful antitumoral effect on benign (pituitary adenoma and malignant (glioblastoma multiforme tumors with IC50 values of 0.96 ± 0.11 µg/mL and 2.15 ± 0.2 µg/mL, respectively. This antitumoral effect is cell-cycle-specific and dependent on extracellular calcium, an important factor for crotoxin phospholipase A2 activity. The CV antitumoral effect can be ascribed, at least partially, to the polypeptide crotoxin that also induced brain tumor cell death. In spite of the known CV nephrotoxicity and neurotoxicity, acute treatment with its antitumoral dose established in vitro was not found to be toxic to the analyzed animals. These results indicate the biotechnological potential of CV as a source of pharmaceutical templates for cancer therapy.

  11. Antitumor activity of polyacrylates of noble metals in experiment

    Directory of Open Access Journals (Sweden)

    Larisa A. Ostrovskaya

    2014-08-01

    Full Text Available The aim of this research has been the study of the antitumor activity of polymetalacrylate derivatives containing in their structure noble metals. Metallic derivatives of polyacrylic acid were not previously tested as antitumor agents.The antitumor activity of polyacrylates, containing argentum (argacryl, aurum (auracryl and platinum (platacryl against experimental models of murine solid tumors (Lewis lung carcinoma and Acatol adenocarcinoma as well as acute toxicity have been studied. It is found that the polyacrylates of noble metals are able to inhibit tumor growth up to 50-90% in comparison with the control. Auracryl induced the inhibition of the Lewis lung carcinoma and Acatol adenocarcinoma by 80 and 90% in comparison with the control, results recommending it for further advanced preclinical studies.

  12. Synthesis and antitumor activity of novel 10-amino acids ester homocamptothecin analogues

    Institute of Scientific and Technical Information of China (English)

    Liang You; Wan Nian Zhang; Zhen Yuan Miao; Wei Guo; Xiao Ying Che; Wen Ya Wang; Chun Quan Sheng; Jiang Zhong Yao; Ting Zhou

    2008-01-01

    Nine racemic homocamptothecin derivatives were synthesized and in vitro antitumor activities were evaluated by standard MTT method.The results showed that some of the compound had higher antitumor activity than iritecan.

  13. 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. PMID:26742746

  14. Synergistic antitumor activity of gemcitabine combined with triptolide in pancreatic cancer cells

    OpenAIRE

    QIAO, ZHIXIN; He, Min; HE, MU; Li, Weijing; WANG, XUANLIN; Wang, Yanbing; KUAI, QIYUAN; Li, Changlan; REN, SUPING; Yu, Qun

    2016-01-01

    Pancreatic cancer is a fatal human malignancy associated with an exceptionally poor prognosis. Novel therapeutic strategies are urgently required to treat this disease. In addition to immunosuppressive activity, triptolide possesses strong antitumor activity and synergistically enhances the antitumor activities of conventional chemotherapeutic drugs in preclinical models of pancreatic cancer. The present study investigated the antitumor effects of triptolide in pancreatic cancer cells, either...

  15. Das berufliche und das private Geschlecht Gender: Professional and Private

    Directory of Open Access Journals (Sweden)

    Almut Sülzle

    2006-07-01

    Full Text Available Jutta Wergen untersucht Geschlechterkonstruktionen in Männerberufen, indem sie Frauen befragt, die als Lkw-Fahrerinnen, als Binnenschifferinnen und als Bus- bzw Straßenbahnfahrerinnen im öffentlichen Nahverkehr arbeiten. Dabei kann sie zeigen, dass diese Berufe sehr unterschiedliche Kontexte für Geschlechterarrangements zur Verfügung stellen, von traditioneller Arbeitsteilung bis zur Umkehrung derselben. Der Kern der Erkenntnis dieser Arbeit, das sei hier schon vorweggenommen, ist bestechend und zugleich faszinierend einfach: die Trennung in ein „professionelles“ und ein „privates“ Geschlecht.Jutta Wergen examines gender constructions in traditionally male careers by interviewing women who work as truck drivers, ship captains, and bus and tram drivers in public transportation. In doing so she can show that these careers provide very different contexts for gender arrangements, from traditional division of work to its reversal. The core of the realization of this study-this is anticipated here-is fascinating and amazingly simple: the division between a “professional” and a “private” gender.

  16. Herausforderungen fuer das Requirements Engineering eingebetteter Systeme

    OpenAIRE

    Andreas Fleischmann; Eva Geisberger; Markus Pister

    2016-01-01

    Abstract: In diesem Bericht werden in kompakter Form die spezifischen Problemstellungen und Herausforderungen bei der Entwicklung Eingebetteter Systeme aufgezeigt und die entsprechenden Anforderungen an das Requirements Engineering definiert. Der Bericht ist Teilergebnis des REFOCUS Projekts am Lehrstuhl von Professor Broy, in dem eine durchgehende Methodik fuer das Requirements Engineering Eingebetteter Systeme entworfen wird.

  17. Monstro Simile - Das Ende der Mitbestimmung

    OpenAIRE

    Michael Adams

    2004-01-01

    Prof. Dr. Michael Adams, Universität Hamburg, kommentiert das Urteil des Europäischen Gerichtshofes, das Unternehmen ermöglicht, ausländische Rechtsformen zu wählen und dann deren Sitz nach Deutschland zu verlegen.

  18. 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

  19. Antitumor effect of magnetite nanoparticles in cat mammary adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Sincai, Mariana [Cell Biology-Histology Department, Faculty of Veterinary Medicine, Calea Aradului no.119, Timisoara 19000 (Romania)]. E-mail: msincai@yahoo.com; Ganga, Diana [Cell Biology-Histology Department, Faculty of Veterinary Medicine, Calea Aradului no.119, Timisoara 19000 (Romania); Ganga, Marius [Private Veterinary Practice, Timisoara (Romania); Argherie, Diana [Cell Biology-Histology Department, Faculty of Veterinary Medicine, Calea Aradului no.119, Timisoara 19000 (Romania); Bica, Doina [Laboratory of Magnetic Fluids, Center for Fundamental and Advanced Technical Research, Romanian Academy-Timisoara Branch (Romania)

    2005-05-15

    The antitumor effect of a magnetic fluid was studied after direct inoculation into cat mammary tumors. An external magnetic field was used to retain the nanoparticles in the tumor tissue. After 2 month, the mammary tumor regressed very much in size and the microscopic exam revealed that the tumor cells massively endocytosed magnetic nanoparticles and entered in lysis process.

  20. Antitumor effect of magnetite nanoparticles in cat mammary adenocarcinoma

    International Nuclear Information System (INIS)

    The antitumor effect of a magnetic fluid was studied after direct inoculation into cat mammary tumors. An external magnetic field was used to retain the nanoparticles in the tumor tissue. After 2 month, the mammary tumor regressed very much in size and the microscopic exam revealed that the tumor cells massively endocytosed magnetic nanoparticles and entered in lysis process

  1. Encapsulation of antitumor drug methotrexate in liposome vesicles

    International Nuclear Information System (INIS)

    Liposome vesicles containing antitumor drug methotrexate (MTX) were prepared. MTX was labelled by the tritium ion beam method. After purification by TLC, the specific radioactivity of 3H-MTX was 1.19 GBq/mmol with radiochemical purity orver 95%. Under various forming conditions of liposome vesicles, the efficiency of encapsulation was 21-53%

  2. The early antitumor immune response is necessary for tumor growth

    OpenAIRE

    Parmiani, Giorgio; Maccalli, Cristina

    2012-01-01

    Early events responsible of tumor growth in patients with a normal immune system are poorly understood. Here, we discuss, in the context of human melanoma, the Prehn hypothesis according to which a weak antitumor immune response may be required for tumor growth before weakly or non-immunogenic tumor cell subpopulations are selected by the immune system.

  3. Jacalin-Activated Macrophages Exhibit an Antitumor Phenotype

    Science.gov (United States)

    Danella Polli, Cláudia; Pereira Ruas, Luciana; Chain Veronez, Luciana; Herrero Geraldino, Thais; Rossetto de Morais, Fabiana; Roque-Barreira, Maria Cristina; Pereira-da-Silva, Gabriela

    2016-01-01

    Tumor-associated macrophages (TAMs) have an ambiguous and complex role in the carcinogenic process, since these cells can be polarized into different phenotypes (proinflammatory, antitumor cells or anti-inflammatory, protumor cells) by the tumor microenvironment. Given that the interactions between tumor cells and TAMs involve several players, a better understanding of the function and regulation of TAMs is crucial to interfere with their differentiation in attempts to skew TAM polarization into cells with a proinflammatory antitumor phenotype. In this study, we investigated the modulation of macrophage tumoricidal activities by the lectin jacalin. Jacalin bound to macrophage surface and induced the expression and/or release of mainly proinflammatory cytokines via NF-κB signaling, as well as increased iNOS mRNA expression, suggesting that the lectin polarizes macrophages toward the antitumor phenotype. Therefore, tumoricidal activities of jacalin-stimulated macrophages were evaluated. High rates of tumor cell (human colon, HT-29, and breast, MCF-7, cells) apoptosis were observed upon incubation with supernatants from jacalin-stimulated macrophages. Taken together, these results indicate that jacalin, by exerting a proinflammatory activity, can direct macrophages to an antitumor phenotype. Deep knowledge of the regulation of TAM functions is essential for the development of innovative anticancer strategies. PMID:27119077

  4. Pornografie – Was ist das ?

    Directory of Open Access Journals (Sweden)

    Corinna Rückert

    2010-03-01

    Full Text Available Die Diskussionen über das kulturelle und mediale Phänomen ‚Pornografie‘ zeichnen sich oft durch Unkenntnis des Betrachtungsgegenstands und definitorischer Ungenauigkeiten aus. Der vorliegende Text benennt Irrtümer und Vorurteile und liefert einen Beitrag zu einer wissenschaftlich nachvollziehbaren Definitionsgrundlage als Basis für weitere Diskussionen. Die nachfolgenden Überlegungen sind eine Kurzzusammenfassung der Dissertation von Corinna Rückert: Frauenpornographie. Pornographie von Frauen für Frauen. Eine kulturwissenschaftliche Studie. Frankfurt am Main 2000.Discussions on the cultural and media phenomenon of “pornography” often stand out in their lack of knowledge about the object under consideration and their imprecisely defined terminology. The text at hand points out confusions and prejudices and also contributes to the creation of a scholarly and comprehensible foundation for establishing a definition that can serve as a basis for further discussion. The following considerations provide a short summary of Corinna Rückert’s dissertation: Frauenpornographie. Pornographie von Frauen für Frauen. Eine kulturwissenschaftliche Studie. Frankfurt am Main 2000 [Female Pornography. Pornography by Women for Women. A Cultural Study].

  5. 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

  6. Antitumor activity of fermented noni exudates and its fractions.

    Science.gov (United States)

    Li, Jinhua; Chang, Leng-Chee; Wall, Marisa; Wong, D K W; Yu, Xianzhong; Wei, Yanzhang

    2013-01-01

    Noni has been extensively used in folk medicine by Polynesians for over 2000 year. Recent studies have shown that noni has a wide spectrum of therapeutic activities including inhibition of angiogenesis, anti-inflammatory effects and anti-cancer activities. Intraperitoneal (i.p.) injection of fermented noni exudates (fNE) were previously found to induce significant tumor rejection in a S180 mouse sarcoma tumor model, while natural killer (NK) cells were demonstrated to be markedly involved in fNE-induced antitumor activity. In this study, fNE was partitioned into three fractions and their antitumor effects were examined using i.p. injection or as water supplement. The in vivo animal study results showed that when delivered by i.p. injection, n-butanol fraction of fNE (BuOH) effectively rejected (100%) tumor challenge and eradicated existing tumors (75%). When delivered as a water supplement, 62.5% of the mice receiving the n-butanol or ethyl acetate fractions resisted tumor cells. The tumor-resistant mice effectively rejected more and higher doses of tumor challenge, indicating that the immune system was activated. The findings confirm those of an earlier study showing fNE to have anti-tumor activity and demonstrating that the n-butanol fraction of fNE contains active antitumor components, to be further identified. More importantly, the antitumor effect of fNE and its fractions as water supplements renders a significant potential for identifying novel and powerful new dietary products for cancer prevention. PMID:24649140

  7. 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.

  8. Das Ende der Geschichte im Internet

    OpenAIRE

    Jochum, Uwe

    2001-01-01

    Gedächtnis muß sich auf Orte verlassen können, an denen sich der Inhalt des zu Merkenden mit einer Stelle im Kontext alles anderen Gewußten verbinden kann. Das gilt zumal für das kulturelle Gedächtnis. Indem das Internet auf diese "lokalistische Struktur von Gedächtnis" verzichten zu können meint, bedroht es die Funktionsfähigkeit des kulturellen Gedächtnisses und damit von Geschichte überhaupt.

  9. Das "ultimative Informationsbeschaffungssystem" World Wide Web

    OpenAIRE

    Oberthür, Petra

    1996-01-01

    Das Internet, entstanden aus dem militärischen ARPANET, hat sich zu einem weltumspannenden Computernetz entwickelt. Von den traditionellen Internetdiensten wie EMail oder FTP gingen die Entwicklungen hin zu ansprechenderen Informationssystemen und interaktiven Diensten. Seit Einführung des WWW hat das Internet einen enormen Zuwachs an Anwendern erfahren. Dieser rasante Erfolg des WWW bereitet jedoch auch Probleme, da es nicht dafür ausgelegt war, solch große Datenmengen und komplexe Anwendung...

  10. Media Control. Wer kontrolliert das Internet?

    OpenAIRE

    Coy, Wolfgang

    1996-01-01

    Neue Techniken stoßen im allgemeinen nicht auf einen rechts- und regelfreien Raum, wenngleich sie neue Interpretationen oder auch Veränderungen, Anpassungen und Neufassungen der bestehenden Regeln erfordern. Das Internet ist unter militärischer Vorgabe im akademischen Raum entstanden: Offene Rechnernetze, die durch eine gemeinsame Protokollsuite verbunden sind, vor allem durch das TCP/IP Protokoll. Ziel dieses asynchronen, datenpaketvermittelten Dienstes ist es, auch unter starken Störungen e...

  11. Pemetaan Tingkat Bahaya Erosi di DAS Ular

    OpenAIRE

    Fergina, Sukma Gika

    2015-01-01

    Drainage Basin (DAS) Ular is Das Priority I or flood-prone watershed restored. Flooding is an event where the puddles on the flat area around the river as a result of the overflow of the river water is not able to be accommodated by the river. Poor drainage systems and critical watershed conditions coupled with high rainfall factors resulted in the discharge of water in the river rises. To anticipate and reduction disadvantages flooding problem effect, needed handle with important the most...

  12. Welche Kinder haben Einfluss auf das Scheidungsrisiko?

    OpenAIRE

    Breitenbach, Andrea

    2010-01-01

    In der Scheidungsforschung werden Kinder als ein zentraler Einflussfaktor der Ehestabilität thematisiert. Je nachdem welches Kindschaftsverhältnis oder Charakteristikum von Kindern vorliegt, ist mit der Erhöhung oder Verminderung der Ehestabilität zu rechnen. Zum Beispiel wird nach der Familienökononmie, durch das Vorhandensein von unehelichen Kindern in einer Ehe die Ehestabilität vermindert, während eheliche Kinder das Scheidungsrisiko reduzieren. In den meisten Untersuchungen der Scheidung...

  13. Das (Wieder-)Erfinden von Interviewverfahren : Kommentar zu "Das existenzielle Interview"

    OpenAIRE

    Mey, Günter

    2005-01-01

    Mit Blick auf das narrative und das problemzentrierte Interview als zwei prominente Interviewverfahren und ergänzt um Anmerkungen zum episodischen, themenzentrierten und personzentrierten Interview erfolgt die Auseinandersetzung mit dem "existenziellen Interview", das Reiner Seidel als neue Methode für den Themenbereich "Biographie" vorschlägt. Vor dem Hintergrund eingeführter und elaborierter Interviewverfahren wird angemahnt, dass mit dem existenziellen Interview kein erkennbar eigens...

  14. Separation, antitumor activities, and encapsulation of polypeptide from Chlorella pyrenoidosa.

    Science.gov (United States)

    Wang, Xiaoqin; Zhang, Xuewu

    2013-01-01

    Chlorella pyrenoidosa is a unicellular green algae and has been a popular foodstuff worldwide. However, no reports on the antitumor peptides from such a microalgae are available in the literature. In this study, using low-temperature high-pressure extraction, enzymatic hydrolysis, ion exchange, and gel filtration chromatography, we separated a polypeptide that exhibited inhibitory activity on human liver cancer HepG2 cells, and named the polypeptide CPAP (C. pyrenoidosa antitumor polypeptide). Furthermore, the micro- and nanoencapsulation of CPAP were investigated by using two methods: complex coacervation and ionotropic gelation. The in vitro release tests revealed that CPAP was well preserved against gastric enzymatic degradation after micro/nanoencapsulation and the slowly controlled release in the intestine could be potentially achieved. These results suggest that CPAP may be a useful ingredient in food, nutraceutical, and pharmaceutical applications. PMID:23606619

  15. Synthesis of lapachol analogues with possible antitumoral activity

    International Nuclear Information System (INIS)

    The lapachol is presented as a hydroxynaphthoquinone and, like many naphthoquinones, has had diverse biological activity, such as antiparasitic, antimicrobial, antifungal and anticancer even. The lateral alkyl chain has been an important factor in the activity of the 2-hydroxy-l,4-naphthoquinone. The synthesis of analogous compounds to lapachol is presented, by alkylating C3 of 2-hydroxy-l,4-naphthoquinone (lawsone) by tertiary carbocations, secondary and benzilic. Several methodologies of synthesis were used to achieve products formed, the reactions have presented yields moderate to good. The derivatives were characterized by spectroscopic methods (UV, IR, 1H-NMR, 13C-NMR), mass spectrometry and high-resolution melting points. Antitumor activity tests were performed in three cell lines, the results obtained have showed that some of the synthesized compounds, can become seeded in future research for the evaluation of the antitumor activity of other analogues lapachol. (author)

  16. [Research progress on anti-tumor effect of Huaier].

    Science.gov (United States)

    Yang, Ai-lin; Hu, Zhong-dong; Tu, Peng-fei

    2015-12-01

    Huaier (Trametes robiniophila) has been widely used as an adjuvant drug for cancer treatment in China. The anti-cancer effect of Huaier extract has been confirmed in liver cancer, lung cancer, breast cancer, ovarian cancer, gastric cancer, and so on. The main mechanisms by which Huaier exerts an anti-neoplastic effect include inhibition of the growth and proliferation of cancer cells, induction of apoptosis of cancer cells, suppression of angiogenesis, inhibition of the invasion and migration of cancer cells, regulation of oncogenes and tumor suppressor genes expression, improving immunity, and reversal of drug resistance in cancer cells. In order to provide references for further study and clinical application on anti-tumor effect of Huaier, the latest research progress on anti-tumor effect of Huaier in recent years is summarized in this paper. PMID:27245026

  17. Esperamicins, a class of potent antitumor antibiotics: mechanism of action.

    OpenAIRE

    Long, B H; Golik, J; Forenza, S; Ward, B; Rehfuss, R; Dabrowiak, J C; Catino, J J; Musial, S T; Brookshire, K W; Doyle, T W

    1989-01-01

    The esperamicins represent a class of antitumor antibiotics characterized by an unusual chemical core structure and extremely potent cytotoxicity. The mechanism by which these drugs produce cytotoxicity was investigated and found to be related to the formation of single- and double-strand DNA breaks. Using five structurally related analogs, we defined a structure-activity relationship for cytotoxicity in various eukaryotic and DNA-repair-deficient prokaryotic cell lines, for DNA breakage in a...

  18. Crotalus durissus terrificus venom as a source of antitumoral agents

    OpenAIRE

    MA Soares; PB Pujatti; CL Fortes-Dias; Antonelli, L.; RG Santos

    2010-01-01

    The basic knowledge on neoplasms is increasing quickly; however, few advances have been achieved in clinical therapy against tumors. For this reason, the development of alternative drugs is relevant in the attempt to improve prognosis and to increase patients' survival. Snake venoms are natural sources of bioactive substances with therapeutic potential. The objective of this work was to identify and characterize the antitumoral effect of Crotalus durissus terrificus venom (CV) and its polypep...

  19. Tumor necrosis factor-alpha antitumor and immunomodulatory effects

    OpenAIRE

    Scheringa, Marcel

    1991-01-01

    textabstractIn the first part of this thesis we examined the possibilities of using the cytokine tumor necrosis factor-alpha (TNFcx) for the latter aproach. Although multiple studies have been performed regarding the antitumor action of TNFcx, it is still not clear whether TNFcx has sufficient potential to be used as immunotherapeutic agent in vivo. In this part of this thesis an answer to this important question is given Whereas cancer immunotherapy might benefit from immunostimulation with ...

  20. Antitumor Activity of Monoterpenes Found in Essential Oils

    OpenAIRE

    2014-01-01

    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 ...

  1. Synthesis and antitumor activity of novel podophyllotoxin derivatives

    Institute of Scientific and Technical Information of China (English)

    Ming Zhao; Min Feng; Shu Fang Bai; Yuan Zhang; Wen Chao Bi; Hong Chen

    2009-01-01

    In order to find compounds with superior bioactivity and overcoming multidrug resistance, a novel series of 4β-N-substituted podophyllotoxin derivatives were synthesized and evaluated as potential antitumor agents. Seven novel podophyllotoxin derivatives were synthesized by linking 4β-amino-4-deoxypodophyllotoxin with alcohols through maleic acid and tested against K562 and K562/A02 using MTT assay in vitro.

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

    Directory of Open Access Journals (Sweden)

    Ismael Samudio

    2010-08-01

    Full Text Available Metformin is a synthetic biguanide first described in the 1920´s as a side product of the synthesis of N,N-dimethylguanidine. Like otherrelated biguanides, metformin displays antihyperglycemic properties, and has become the most widely prescribed oral antidiabetic medicinearound the world. Intriguing recent evidence suggests that metformin has chemopreventive and direct antitumor properties, and severalongoing clinical studies around the world are using this agent alone or in combination with chemotherapeutic schemes to determineprospectively its safety and efficacy in the treatment of human cancer. Notably, immune activating effects of metformin have recently beendescribed, and may support a notion put forth in the 1950s that this agent possessed antiviral and antimalarial effects. However, how theseeffects may contribute to its observed antitumor effects in retrospective studies has not been discussed. Mechanistically, metformin has beenshown to activate liver kinase B1 (LKB1 and its downstream target AMP-activated kinase (AMPK. The activation of AMPK has beenproposed to mediate metformin´s glucose lowering effect, although recent evidence suggests that this agent can inhibit electron transport inhepatocyte mitochondria resulting in AMPK-independent inhibition of hepatic gluconeogenesis. Likewise, albeit activation of AMPK andthe resulting inhibition of the mammalian target of rapamycin (mTOR signaling have been suggested to mediate the antitumor effects ofmetformin, AMPK-independent growth inhibitory properties of this agent in tumor cells have also been described. Here we present a briefreview of the signaling, metabolic, and immune effects of metformin and discuss how their interplay may orchestrate the antitumor effectsof this agent. In addition, we provide the rationale for a compassionate use study of metformin in combination with metronomic chemotherapy.

  3. Anti-tumor Action and Clinical Application of Proteasome Inhibitor

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yong-ming; YU Mei-xia; LONG Hui; HUANG Shi-ang

    2008-01-01

    Ubiquitin-proteasome pathway mediates the degradation of cell protein,and cell cycle,gene translation and expression,antigen presentation and inflammatory development.Proteasome inhibitor Call inhibit growth and proliferation of tumor cell,induce apoptosis and reverse multipledrug resistance of tumor cell,increase the sensitivity of other chemomerapeutic drugs and radiotherapy,and is a novel class of potent anti-tumor agents.

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

    International Nuclear Information System (INIS)

    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)

  5. Pharmacology and therapeutic applications of enediyne antitumor antibiotics.

    Science.gov (United States)

    Shao, Rong-Guang

    2008-01-01

    The natural compounds that interfere with cellular DNA such as enediyne antitumor antibiotics might be important chemotherapeutic agents for the treatment of cancer. In this article, the pharmacology and anticancer activity of the enediyne antitumor agents that are approved for clinical use and undergoing pre-clinical or clinical evaluation are reviewed. Most enediyne compounds have shown potent activity against the proliferation of various cancer cells, including cells that display resistance to other chemotherapeutic drugs. Enediyne derivatives, such as an immunoconjugate composed of an enediyne compound and monoclonal antibody, reveal stronger activity and selectivity for human cancer cells. The mechanism underlying the anticancer activity of these enediyne antitumor agents may mainly lie in their generation of DNA double-strand breaks. Increasing evidence shows that the enediyne-induced DNA double-strand breaks can engage the activation of DNA damage response proteins, arresting cell cycle progression and eventually leading to apoptotic cell death. Continued investigation of the mechanisms of action and development of new enediyne derivatives and conjugates may provide more effective therapeutics for cancer treatments. PMID:20021423

  6. Functional and mechanistic analysis of telomerase: An antitumor drug target.

    Science.gov (United States)

    Chen, Yinnan; Zhang, Yanmin

    2016-07-01

    The current research on anticancer drugs focuses on exploiting particular traits or hallmarks unique to cancer cells. Telomerase, a special reverse transcriptase, has been recognized as a common factor in most tumor cells, and in turn a distinctive characteristic with respect to non-malignant cells. This feature has made telomerase a preferred target for anticancer drug development and cancer therapy. This review aims to analyze the pharmacological function and mechanism and role of telomerase in oncogenesis; to provide fundamental knowledge for research on the structure, function, and working mechanism of telomerase; to expound the role that telomerase plays in the initiation and development of tumor and its relationship with tumor cell growth, proliferation, apoptosis, and related pathway molecules; and to display potential targets of antitumor drug for inhibiting the expression, reconstitution, and trafficking of the enzyme. We therefore summarize recent advances in potential telomerase inhibitors for antitumor including natural products, synthetic small molecules, peptides and proteins, which indicate that optimizing the delivery method and drug combination could be of help in a combinatorial drug treatment for tumor. More extensive understanding of the structure, biogenesis, and mechanism of telomerase will provide invaluable information for increasing the efficiency of rational antitumor drug design. PMID:27118336

  7. Antitumor effects of the benzophenanthridine alkaloid sanguinarine: Evidence and perspectives.

    Science.gov (United States)

    Gaziano, Roberta; Moroni, Gabriella; Buè, Cristina; Miele, Martino Tony; Sinibaldi-Vallebona, Paola; Pica, Francesca

    2016-01-15

    Historically, natural products have represented a significant source of anticancer agents, with plant-derived drugs becoming increasingly explored. In particular, sanguinarine is a benzophenanthridine alkaloid obtained from the root of Sanguinaria canadensis, and from other poppy Fumaria species, with recognized anti-microbial, anti-oxidant and anti-inflammatory properties. Recently, increasing evidence that sanguinarine exibits anticancer potential through its capability of inducing apoptosis and/or antiproliferative effects on tumor cells, has been proved. Moreover, its antitumor seems to be due not only to its pro-apoptotic and inhibitory effects on tumor growth, but also to its antiangiogenic and anti-invasive properties. Although the precise mechanisms underlying the antitumor activity of this compound remain not fully understood, in this review we will focus on the most recent findings about the cellular and molecular pathways affected by sanguinarine, together with the rationale of its potential application in clinic. The complex of data currently available suggest the potential application of sanguinarine as an adjuvant in the therapy of cancer, but further pre-clinical studies are needed before such an antitumor strategy can be effectively translated in the clinical practice. PMID:26798435

  8. Antitumor effects of the benzophenanthridine alkaloidsanguinarine: Evidence and perspectives

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Historically, natural products have represented a significantsource of anticancer agents, with plant-deriveddrugs becoming increasingly explored. In particular,sanguinarine is a benzophenanthridine alkaloid obtainedfrom the root of Sanguinaria canadensis , and from otherpoppy Fumaria species, with recognized anti-microbial,anti-oxidant and anti-inflammatory properties. Recently,increasing evidence that sanguinarine exibits anticancerpotential through its capability of inducing apoptosisand/or antiproliferative effects on tumor cells, has beenproved. Moreover, its antitumor seems to be due notonly to its pro-apoptotic and inhibitory effects on tumorgrowth, but also to its antiangiogenic and anti-invasiveproperties. Although the precise mechanisms underlyingthe antitumor activity of this compound remain notfully understood, in this review we will focus on themost recent findings about the cellular and molecularpathways affected by sanguinarine, together withthe rationale of its potential application in clinic. Thecomplex of data currently available suggest the potentialapplication of sanguinarine as an adjuvant in the therapyof cancer, but further pre-clinical studies are neededbefore such an antitumor strategy can be effectivelytranslated in the clinical practice.

  9. 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.

  10. Antitumor efficacy of vaccinia virus-modified tumor cell vaccine

    International Nuclear Information System (INIS)

    The antitumor efficacies of vaccinia virus-modified tumor cell vaccines were examined in murine syngeneic MH134 and X5563 tumor cells. UV-inactivated vaccinia virus was inoculated i.p. into C3H/HeN mice that had received whole body X-irradiation at 150 rads. After 3 weeks, the vaccines were administered i.p. 3 times at weekly intervals. One week after the last injection, mice were challenged i.p. with various doses of syngeneic MH134 or X5563 viable tumor cells. Four methods were used for preparing tumor cell vaccines: X-ray irradiation; fixation with paraformaldehyde for 1 h or 3 months; and purification of the membrane fraction. All four vaccines were effective, but the former two vaccines were the most effective. A mixture of the membrane fraction of untreated tumor cells and UV-inactivated vaccinia virus also had an antitumor effect. These results indicate that vaccine with the complete cell structure is the most effective. The membrane fraction of UV-inactivated vaccinia virus-absorbed tumor cells was also effective. UV-inactivated vaccinia virus can react with not only intact tumor cells but also the purified membrane fraction of tumor cells and augment antitumor activity

  11. A study on recent tendency of anti-tumor herbal acupuncture

    OpenAIRE

    Yoo Hwa-Seung; Lee Yong-Yeon; Cho Jung-Hyo; Lee Yeon-Weol; Son Chang-Gue; Cho Chong-Kwan; Hwang Kyu-Jeong

    2001-01-01

    Objectives: The purpose of this study is to develop and activate anti-tumor herbal acupuncture for cancer patients in South Korea. Methods: We investigated some literatures on anti-tumor herbal acupuncture which is used in South Korea and China, and made diagrams. Results: The results are summarized as follows. Anti-tumor herbal acupuncture is one of the traditional oriental medical method which is effective for cancer patients. In domestic studies, most of herb materials are belong to ...

  12. A Recent Study of Anti-tumor Herbal Acupuncture in Korea

    OpenAIRE

    Hwa-Seung Yoo; Sun-hwi Bang; Chong-Kwan Cho

    2006-01-01

    Objectives : This systematic review summarizes the existing evidence on anti-tumor herbal acupuncture in South Korea. Methods : Literature searches were conducted in four databases. All studies of anti-tumor herbal acupuncture which has been published in South Korea until May, 2006 were included. Data were extracted according to pre-defined criteria by two independent reviewers. Results : We found 73 papers related to anti-tumor herbal acupuncture in South Korea. Seventy of seventy-thre...

  13. Interaction between antitumor drug and silver nanoparticles:combined fluorscence and surface enhanced Raman scattering study

    Institute of Scientific and Technical Information of China (English)

    Jing Yang; Hong Wang; Zhuyuan Wang; Xuebin Tan; Chunyuan Song; Ruohu Zhang; Jin Li; Yiping Cui

    2009-01-01

    Optical methods and MTT method are used to characterize the antiproliferation effect of antitumor drug 9-aminoacridine (9AA) with and without silver nanoparticles.Intracellular surface enhanced Raman scat tering (SERS) spectra and fluorescent spectra of 9AA indicate the form of 9AA adsorbed on the surface of silver nanoparticles.Although both silver nanoparticles and antitumor drug can inhibit the growth of Hela cells,silver nanoparticles can slow down the antiproliferation effect on Hela cells at low concentration of antitumor drugs.Our experimental results suggest that silver nanoparticles may serve as slow-release drug carriers,which is important in antitumor drug delivery.

  14. Wem gehört das Wasser?

    OpenAIRE

    Hettich, Peter

    2010-01-01

    Der Mensch besteht zum Grossteil aus Wasser. Daher ist auch Wasser das wichtigste Lebensmittel des Menschen. Doch trotz dieser Bedeutung, ist der Umgang mit Wasser meist sehr gedankenlos. Während ein Grossteil der Menschheit keinen Zugang zu sauberem Wasser hat, wird in den Industrieländern das verfügbare Wasser teilweise verschwendet oder durch chemische Aufbereitung verändert. Neben den absehbaren klimatischen Veränderungen im Zusammenhang mit dem hohen CO2- Ausstoss der Menschheit, wird de...

  15. Maurice Merleau-Ponty und das Smartphone

    OpenAIRE

    Lisker, Mareike

    2015-01-01

    In dieser Arbeit wird untersucht, inwiefern die Leibphänomenologie Maurice Merleau-Pontys uns helfen kann, moderne Phänomene der Digitalität und ihre Beziehung zu uns als Mensch zu verstehen. Theoretische Einbettung für die Phänomene wie beispielsweise das Smartphone bietet das Konzept des Ubiquitous Computing sowie die Angebotstheorie James Jerome Gibsons. Zentral für die Arbeit ist der Begriff des Körperschemas, den Merleau-Ponty entwickelt. Mit dessen Hilfe wird dafür argumentiert, dass d...

  16. Mapeamento das competências chave

    OpenAIRE

    Teixeira, João Ferreira

    2016-01-01

    Com este trabalho pretendemos desenvolver um projeto de intervenção no âmbito do Mapeamento de Competências, a implementar na Amorim & Irmãos, SA, a Entidade Acolhedora do Projeto. O diagnóstico realizado à Função Recursos Humanos permitiu identificar como potencial de intervenção o Mapeamento de Competências Chave. As Competências Chave são fundamentais para a operacionalização da missão e visão das organizações. Nos contextos de atuação global das empresas prevalec...

  17. Synergistic Antitumor Efficacy of Oncolytic Adenovirus Combined with Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    LI Yue-min; QIAN Qi-jun; SONG San-tai; JIANG Ze-fei; ZHANG Qi; QU Yi-mei; SU Chang-qing; ZHAO Chuan-hua; LI Zhi-qiang; GE Fei-jiao

    2007-01-01

    Objective: Chemotherapy is an effective means of treating breast cancer, and cancer-specific replicative adenovirus is also a promising antitumor agent in recent years. Our investigation aims to demonstrate that CNHK300 can mediate selective antitumor efficacy and produce synergistic cytotoxicity with chemotherapy on HER-2 over-expressing breast cancer. Methods: We engineered the telomerase-dependent replicative adenovirus CNHK300 by placing the E1A gene under the control of the human hTERT promoter. By analysis of E1A expression, we proved the fidelity of hTERT promoter in adenovirus genome and the selective expression of E1A in telomerase-positive breast cancer cells but not in normal fibroblast cells. By proliferation test, we further showed efficient replication of CNHK300 in breast cancer cells with apparently attenuated proliferation in normal fibroblast cells. Finally, we demonstrated by MTT methods that CNHK300 virus caused potent cytolysis and produced synergistic cytotoxicity with chemotherapy in breast cancer cells with attenuated cytotoxicity on normal cells. Results: In this virus, the E1A gene is successfully placed under the control of the human hTERT promoter. CNHK300 virus replicated as efficiently as the wild-type adenovirus and caused intensive cell killing in HER-2 over-expressing breast cancer cells in vitro. In contrast, telomerase-negative normal fibroblast cells, which expressed no hTERT activity, were not able to support CNHK300 replication. Combined treatment of CNHK300 with paclitaxel improved cytotoxicity on cancer cells. Conclusion: We conclude that CNHK300 can produce selective antitumor efficacy and enhance the in vitro response of chemotherapy on HER-2 overexpressing breast cancer.

  18. Glycosylated antitumor ether lipids: activity and mechanism of action.

    Science.gov (United States)

    Arthur, Gilbert; Bittman, Robert

    2014-05-01

    Glycosylated antitumor ether lipids (GAELs) are distinguished from the alkyllysophospholipids or alkylphosphocholines classes of antitumor ether lipids (AEL) by the presence of a sugar moiety. Non-phosphorus GAELs, the subject of this review, have a sugar moiety in place of the phosphobase found in alkyllysophospholipids. Analogues of non-phosphorus GAELs with glucose, maltose, arabinose, or disaccharide moieties have been synthesized. Non-phosphorus GAELs with monosaccharides have cytotoxic and antiproliferative effects against cancer cells derived from a wide range of tissues, including drug resistant cell lines. The most active compound of this group to date is 1-O-hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (11), which displays in vitro activity similar to or greater than that of ET-18-OCH3, the AEL "gold" standard. While the detailed molecular mechanism of action of non-phosphorus GAELs is not known, the data indicate that non-phosphorus GAELs are taken up by endocytosis and incorporated into early endosomes. The presence of non-phosphorus GAELs perturbs the maturation of the endocytic vesicles, resulting in the formation of large acidic vacuoles. Cell death appears to be the result of the release of cathepsins from the vacuoles into the cytosol and subsequent activation of a death pathway that is independent of the mitochondria and independent of apoptosis. The ability of these GAELs to kill cells via an apoptosis-independent mechanism makes them prime candidates for development of effective compounds against chemo-resistant tumors and cancer stem cells. The disaccharide-linked GAELs do not have cytotoxic activity but rather inhibit cancer cell motility due to the ability of the compounds to block specific calcium-activated potassium channels in cells. The antitumor activities displayed by these experimental compounds augurs well for their eventual development into clinically useful agents for cancer treatment. PMID:24628233

  19. NMR studies on antitumor drug candidates, berberine and berberrubine

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Young Wook; Jung, Jin Won; Kang, Mi Ran; Chung, In Kwon; Lee, Weon Tae [Yonsei Univ., Seoul (Korea, Republic of)

    2002-03-01

    Berberine and berberrubine, which display antitumor activity, have also demonstrated distinct enzyme-poisoning activities by stabilizing topoisomerase II-DNA cleavable complexes. The protoberberine berberrubine differs in chemical structure with berberine at only one position, however, it shows a prominent activity different from berberine. Solution structures of berberine and berberrubine determined by NMR spectroscopy are similar, however, the minor structural rearrangement has been observed near 19 methoxy or hydroxyl group. We suggest that the DNA cleavage activities of topoisomerase II poisons could be correlated with both chemical environments and minor structural change together with hydrophobicity of interacting side chains of drugs with DNA molecules.

  20. [Polyacrylates of noble metals as potential antitumor drugs].

    Science.gov (United States)

    Ostrovskaia, L A; Voronkov, M G; Korman, D B; Bliukhterova, N V; Fomina, M M; Rykova, V A; Abzaeva, K A; Zhilitskaia, L V

    2014-01-01

    The antitumor activity of polyacrylates of the noble metals containing argentum (argacryl), aurum (auracryl) and platinum (platacryl) has been studied using experimental murine solid tumor models (Lewis lung carcinoma and Acatol adenocarcinoma). It has been found that polyacrylates of the noble metals are capable of inhibiting tumor development by 50-90% compared to control. Auracryl that inhibites the growth of Lewis lung carcinoma and Acatol adenocarcinoma by 80 and 90%, respectively, compared to control is the most efficient among the tested compounds and can be recommended for the further profound preclinical studies. PMID:25707247

  1. Synthesis and antitumor activity of tetrahydrocarbazole hybridized with dithioate derivatives.

    Science.gov (United States)

    El-Nassan, Hala Bakr

    2015-04-01

    The present study reported the synthesis of tetrahydrocarbazoles hybridized with dithioate derivatives. Three series were synthesized namely alkyl dithiocarbonates (4a-d), heterocyclic dithiocarbamates (6a-g) and dialkyl dithiocarbamate (7). The synthesized compounds were tested in vitro on human breast adenocarcinoma cell line (MCF7) and the human colon tumor cell line (HCT116). Most of the synthesized compounds exploited potent antitumor activity, especially compound 6f [4-chlorophenylpiperazine derivative], which showed cytotoxic activity against MCF7 superior to doxorubicin with IC50 value of 7.24 nM/mL. PMID:24899376

  2. THEORETICAL STUDY OF PODOPHYLLOTOXIN AND QUINOLONE ANALOGUES AS ANTITUMOR DRUGS

    Institute of Scientific and Technical Information of China (English)

    何峰; 戴颖仪; 朱孝峰; 黄爱东; 张翎; 颜少平; 刘宗潮

    2002-01-01

    Objective: To study the active sites of podophyllotoxin derivatives. Methods: Some podophyllotoxin derivatives were analyzed by quantum and mechanics method. Results: Some information was given according to the calculation results about HOMO and LUMO electron density. The C-4 position is the position for effective modification. The B ring and E ring are important active centers. Conclusion: The hole of positive charge in B ring easily combines with an acceptor within the molecular. Some quinolones with similar electronic construction to podophyllotoxin may have antitumor activity.

  3. Tumor Regulatory T Cells Potently Abrogate Antitumor Immunity1

    OpenAIRE

    Liu, Zuqiang; Kim, Jin H.; Falo, Louis D.; You, Zhaoyang

    2009-01-01

    Treg from mice bearing a breast tumor were elevated (tumor Treg). In vitro, whereas tumor Treg ability to inhibit tumor-primed CD4+ T cell activity is comparable to Treg from naïve mice (naïve Treg), only tumor Treg suppress naïve CD8+ T cell activation and DC function. Neither tumor Treg nor naïve Treg can suppress antitumor immunity at the effector phase of the immune response induced by adoptively-transferred tumor-primed CD4+ T cells. This is consistent with the observation that, in this ...

  4. GHRSST-14 DAS-TAG Report

    Science.gov (United States)

    Armstrong, Edward; Piolle, Jean Francois

    2013-01-01

    The DAS-TAG provides the informatics and data management expertise in emerging information technologies for the GHRSST community. It provides expertise in data and metadata formats and standards, fosters improvements for GHRSST data curation, experiments with new data processing paradigms, and evaluates services and tools for data usage. It provides a forum for producer and distributor data management issues and coordination.

  5. Physik gestern und heute Das Eiskalorimeter

    Science.gov (United States)

    Heering, P.

    2003-07-01

    Kalorimetrische Messungen gehören heute zum experimentellen Standardrepertoire im Bereich der Thermodynamik und der physikalischen Chemie. Das erste Gerät für derartige Messungen entwickelten Ende des 18. Jahrhunderts die französischen Wissenschaftler Antoine Laurent Lavoisier und Pierre Simon de Laplace.

  6. Das DLR_School_Lab Oberpfaffenhofen

    OpenAIRE

    Schüttler, Tobias; Hausamann, Dieter

    2011-01-01

    Das DLR_School_Lab Oberpfaffenhofen ist eines von derzeit neun Schullaboren des Deutschen Zentrums für Luft- und Raumfahrt und ein typischer außerschulischer Lernort, der für eine Verkleinerung der MINT-Lücke sorgen soll.

  7. Das Urheberrecht prallt auf die remix generation

    Directory of Open Access Journals (Sweden)

    Christian Berger

    2011-03-01

    Full Text Available LehrerInnen sind ehrenhafte Menschen, die sich bemühen, keine Rechtsverstöße zu machen. Allerdings macht das geltende Urheberrecht dies sehr schwer. Die nächste Generation hat da ohnehin schon eine ganz andere Praxis. Eigentlich beginnt es oftmals ganz harmlos und mensch selbst hat dabei weder böse Hintergedanken noch kommerzielle Interessen. Eine Lehrerin möchte ein Arbeitsblatt herstellen. Schnell mal ins Internet und ein geeignetes Foto zur Illustration suchen. Download öffnen und … naja, eigentlich könnte ich da doch schnell noch eine Kleinigkeit dazu ergänzen, dann würde das optimal passen. Gesagt, getan. Im Bildbearbeitungsprogramm ist die Sache in fünf Minuten erledigt. Reinkopieren ins Arbeitsblatt. Fertig. Morgen noch in der Schule ausdrucken und kopieren. Den SchülerInnen gefällt das und sie sind motiviert, das Blatt auszufüllen. Die Lehrerin hat allerdings eine Rechtsverletzung begangen und wäre dafür auch gerichtlich verfolgbar.

  8. Tricot e o Dia das Comadres

    OpenAIRE

    Melo, Helena Sousa

    2014-01-01

    Neste artigo aborda-se a matemática existente nos trabalhos de tricot; a aritmética modular e a geometria das transformações, nomeadamente as simetrias. Apresenta-se um exemplo prático com a execução da fita de Mobius.

  9. Staatliche Eingriffe in das System der Mindestentgelte

    Czech Academy of Sciences Publication Activity Database

    Štefko, Martin

    Wien: Verlag des ÖGB, 2013 - (Löschnigg, G.), s. 266-279. (Internationales und vergleichendes Arbeits- und Sozialrecht. 4). ISBN 978-3-7035-1635-1. [Staatliche Eingriffe in das System der Mindestentgelte im internationalen Vergleich. Graz (AT), 11.10.2012-12.10.2012] Institutional support: RVO:68378122 Keywords : minimum wage * collective agreement * social partners Subject RIV: AG - Legal Sciences

  10. Prophylactic Antitumor Effect of Mixed Heat Shock Proteins/Peptides in Mouse Sarcoma

    Directory of Open Access Journals (Sweden)

    Yu Wang

    2015-01-01

    Conclusions: Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors. This mHSP/P vaccine exerted greater antitumor effects than did HSP70, HSP60, or tumor lysates alone.

  11. Synthesis and in vitro antitumor activity of new butenolide-containing dithiocarbamates.

    Science.gov (United States)

    Wang, Xiao-Juan; Xu, Hai-Wei; Guo, Lin-Lin; Zheng, Jia-Xin; Xu, Bo; Guo, Xiao; Zheng, Chen-Xin; Liu, Hong-Min

    2011-05-15

    Three series of butenolide-containing dithiocarbamates were designed and synthesized. Their anti-tumor activity in vitro was evaluated. Among them compound I-14 exhibited broad spectrum anti-cancer activity against five human cancer cell lines with IC(50) dithiocarbamate side chains on the C-3 position of butenolide was crucial for anti-tumor activity. PMID:21486694

  12. Antitumor activity of levan polysaccharides from selected microorganisms.

    Science.gov (United States)

    Yoo, Sang-Ho; Yoon, Eun Ju; Cha, Jaeho; Lee, Hyeon Gyu

    2004-04-01

    Levans were isolated from the cultures of Gluconoacetobacter xylinus (G-levan; Mw = 40,000), Microbacterium laevaniformans (M; Mw = 710,000), Rahnella aquatilis (R; Mw = 380,000), and Zymomonas mobilis (Z; Mw = 570,000). The levans were composed mainly of fructose residues when analyzed by TLC and HPLC, and their main backbones were beta-(2,6)-linkages with beta-(2,1)-branches by GC-MS and NMR. In the in vitro antitumor activity test of the levans against eight different tumor cell lines, relatively stronger activity was observed from the SNU-1 and HepG2. The M- (52.54-62.05%) and R-levan (52.15-58.58%) showed the significantly high activity against SNU-1, while M-levan showed the highest (49.93-61.82%) activity against HepG2. During the in vivo analysis of inhibitory activity of the levans against Sarcoma-180 growth, M-, R- and Z-levans showed strong antitumor activity (average 66%) but G-levan (42%) had significantly lower activity. PMID:15178007

  13. ANTITUMOR EFFECTS OF MONOCLONAL ANTIBODY FAB′ FRAGMENT CONTAINING IMMUNOCONJUGATES

    Institute of Scientific and Technical Information of China (English)

    刘小云; 甄永苏

    2002-01-01

    Objective.Using monoclonal antibody (mAb) Fab′ fragment to develop mAb immunoconjugates for cancer. Methods.Fab′ fragment of mAb 3A5 was prepared by digestion of the antibody with pepsin and then reduced by dithiothreitol (DTT),while Fab′ fragment of mAb 3D6 was obtained by digestion of the antibody with ficin and subsequently reduced by β mercaptoethanol.The conjugation between Fab′ fragment and pingyangmycin (PYM),an antitumor antibiotic,was mediated by dextran T 40.Immunoreactivity of Fab′ PYM conjugates with cancer cells was determined by ELISA,and the cytotoxicity of those conjugates to cancer cells was determined by clonogenic assay.Antitumor effects of the Fab′ PYM conjugates were evaluated by subcutaneously transplanted tumors in mice. Results.The molecular weight of Fab′ fragment was approximately 53 kD,while the average molecular weight of Fab′ PYM conjugate was 170 kD.The Fab′ PYM conjugates showed immunoreactivity with antigen relevant cancer cells and selective cytotoxicity against target cells.Administered intravenously,Fab′ PYM conjugates were more effective against the growth of tumors in mice than free PYM and PYM conjugated with intact mAb. Conclusion.Fab′ PYM conjugate may be capable of targeting cancer cells and effectively inhibiting tumor growth,suggesting its therapeutic potential in cancer treatment.

  14. Antitumor activity of C-phycocyanin from Arthronema africanum (Cyanophyceae

    Directory of Open Access Journals (Sweden)

    Elena Gardeva

    2014-10-01

    Full Text Available Pure C-phycocyanin (C-PC was isolated from Arthronema africanumto evaluate its potential antitumor effects in vivo and in vitro. Experimental myeloid Graffi tumor in hamsters was used as a model. The cell proliferation assay showed that C-PC treatment, at concentration of 100 µg mL-1 for 24 h, significantly inhibited the growth of Graffi tumor cells (51.4% viability. Agarose gel electrophoresis of the genomic DNA of treated cells displayed time-and concentration-dependent fragmentation pattern, typical for apoptosis. Apoptotic process was related to the increase in cellular manganese and copper/zinc superoxide dismutases and glutathione reductase activities, coupled with a low catalase activity. In vivo C-PC administration (5.0 mg kg-1 body weight suppressed the tumor transplantability and growth, while the mean survival time of the tumor-bearing hamsters was increased. The results revealed promising antitumor activities of A. africanum C-PC and suggested the potential of this natural biliprotein pigment for future pharmacological and medical applications. The study provided new data on the mechanism of the C-PC induced apoptosis in which the imbalance of antioxidant enzymes that favoured hydrogen peroxide accumulation might play a leading role.

  15. Antitumor effect of sonodynamically activated pyrrolidine tris-acid fullerene

    Science.gov (United States)

    Iwase, Yumiko; Nishi, Koji; Fujimori, Junya; Fukai, Toshio; Yumita, Nagahiko; Ikeda, Toshihiko; Chen, Fu-shin; Momose, Yasunori; Umemura, Shin-ichiro

    2016-07-01

    In this study, the sonodynamically induced antitumor effect of pyrrolidine tris-acid fullerene (PTF) was investigated. Sonodynamically induced antitumor effects of PTF by focused ultrasound were investigated using isolated sarcoma-180 cells and mice bearing ectopically-implanted colon 26 carcinoma. Cell damage induced by ultrasonic exposure was enhanced by 5-fold in the presence of 80 µM PTF. The combined treatment of ultrasound and PTF suppressed the growth of the implanted colon 26 carcinoma. Ultrasonically induced 2,2,6,6-tetramethyl-4-piperidone-1-oxyl (4oxoTEMPO) production in the presence and absence of PTF was assessed, and it was shown that 80 µM PTF enhanced 4oxoTEMPO production as measured by ESR spectroscopy. Histidine, a reactive oxygen scavenger, significantly reduced cell damage and 4oxoTEMPO generation caused by ultrasonic exposure in the presence of PTF. These results suggest that singlet oxygen is likely to be involved in the ultrasonically induced cell damage enhanced by PTF.

  16. Replicase-based plasmid DNA shows anti-tumor activity

    Directory of Open Access Journals (Sweden)

    Weiss Richard

    2011-03-01

    Full Text Available Abstract Background Double stranded RNA (dsRNA has multiple anti-tumor mechanisms. Over the past several decades, there have been numerous attempts to utilize synthetic dsRNA to control tumor growth in animal models and clinical trials. Recently, it became clear that intracellular dsRNA is more effective than extracellular dsRNA on promoting apoptosis and orchestrating adaptive immune responses. To overcome the difficulty in delivering a large dose of synthetic dsRNA into tumors, we propose to deliver a RNA replicase-based plasmid DNA, hypothesizing that the dsRNA generated by the replicase-based plasmid in tumor cells will inhibit tumor growth. Methods The anti-tumor activity of a plasmid (pSIN-β that encodes the sindbis RNA replicase genes (nsp1-4 was evaluated in mice with model tumors (TC-1 lung cancer cells or B16 melanoma cells and compared to a traditional pCMV-β plasmid. Results In cell culture, transfection of tumor cells with pSIN-β generated dsRNA. In mice with model tumors, pSIN-β more effectively delayed tumor growth than pCMV-β, and in some cases, eradicated the tumors. Conclusion RNA replicase-based plasmid may be exploited to generate intracellular dsRNA to control tumor growth.

  17. Replicase-based plasmid DNA shows anti-tumor activity

    International Nuclear Information System (INIS)

    Double stranded RNA (dsRNA) has multiple anti-tumor mechanisms. Over the past several decades, there have been numerous attempts to utilize synthetic dsRNA to control tumor growth in animal models and clinical trials. Recently, it became clear that intracellular dsRNA is more effective than extracellular dsRNA on promoting apoptosis and orchestrating adaptive immune responses. To overcome the difficulty in delivering a large dose of synthetic dsRNA into tumors, we propose to deliver a RNA replicase-based plasmid DNA, hypothesizing that the dsRNA generated by the replicase-based plasmid in tumor cells will inhibit tumor growth. The anti-tumor activity of a plasmid (pSIN-β) that encodes the sindbis RNA replicase genes (nsp1-4) was evaluated in mice with model tumors (TC-1 lung cancer cells or B16 melanoma cells) and compared to a traditional pCMV-β plasmid. In cell culture, transfection of tumor cells with pSIN-β generated dsRNA. In mice with model tumors, pSIN-β more effectively delayed tumor growth than pCMV-β, and in some cases, eradicated the tumors. RNA replicase-based plasmid may be exploited to generate intracellular dsRNA to control tumor growth

  18. Electroporation: A New Approach Enhancing Antitumor Effects of Cytoxan

    Institute of Scientific and Technical Information of China (English)

    Yang Kong(杨孔); Yue Bisong; Wang Zishu; Zou Fangdong; Zhao Ermi; Wang Baoyi; Zhang Hong

    2003-01-01

    Electrochemotherapy (ECT) is a novel cancer treatment in which electric pulses (Eps) inducing cell membrane pored (electroporation) are used as a means of delivering antitumor drugs to the cytoplasm of cancer cells. In vitro, with scan electromicroscope (SEM) and Trypan blue staining examination, the best parameter of Eps of electroporation is studied by the S-180 cells exposed to EP with various voltages, pulses , capacitance. The best parameter of EP of electroporation is 600V/cm, 6 pulses, 10 μF. In the in vivo study, ECT is studied with the Cytoxan (CTX) injected directly into the tumor followed immediately by a local EP at the tumor site. Four parameters, which include the tumor inhibitory ratio, the curing ratio and the vas capillare of tumor, the tumor's histopathological characteristics are determined and compared among the ECT group, the control group, the EP-only group and the drug-only group. The results indicate that the antitumor effect of CTX is significantly enhanced by electroporation.

  19. [Primary research on anti-tumor activity of panaxadiol fatty acid esters].

    Science.gov (United States)

    Zhang, Chun-Hong; Zhang, Lian-Xue; Li, Xiang-Gao; Gao, Yu-Gang; Liu, Ya-Jing

    2006-11-01

    For making use of Ginseng resources and finding new anti-tumor drugs, the anti-tumor activity of three kinds of new panaxadiol fatty acid ester derivates: 3beta-acetoxy panaxadiol (I), 3beta-palmitic acid aceloxy panaxadiol (II), 3beta-octadecanoic acid aceloxy panaxadiol (Ill) and panaxaiol were compared through the method of cell stain and counting. Tumor cell was Vero cell line. Positive control was 5-FU. Blank was RPM11640 culture medium. Negative control was RPM11640 culture medium and the solvent for subjected drugs. The result showed that compound I had the strongest anti-tumor activity, second was panaxadiol, II and III had the same and the weakest antitumor activity. Furthermore, the anti-tumor activities of panaxadiol fatty acid ester derivates showed positive correlation with subjects' concentrations, but no relationship with molecular weight of fatty acid. PMID:17228662

  20. Das Repertory-Grid-Interview als Methode kooperativen Forschungshandelns

    OpenAIRE

    Dick, Michael

    2006-01-01

    Ausgehend von einer Kritik an der Ausrichtung der Methodenausbildung in der Psychologie (in Deutschland) werden die Gegenstandsangemessenheit und die Kooperationsförderlichkeit von Methoden als Kriterien methodischer Professionalität betont. Anschließend wird das Repertory-Grid-Interview als Verfahren vorgestellt, das beiden Kriterien gerecht wird. Das rezensierte Lehrbuch sowie die damit korrespondierende Software stellen eine geeignete Einführung in das Verfahren dar, setzen allerdings eine...

  1. Das naturwissenschaftliche Labor als Ort der "Verdichtung" von Gesellschaft

    OpenAIRE

    Knorr-Cetina, Karin D.

    1988-01-01

    ZieI der vorliegenden Arbeit ist es zu zeigen, daß sich das herrschende ,,Feindbild" des Sozialen als dasjenige, das wissenschaftliche Resultate "venureinigt" und von außen infiltriert, bei Betrachtung der Forschungspraxis der Naturwissenschaften nicht aufrecht erhalten läßt. Das naturwissenochaflliche Labor zeigt sich vielmehr als ein Ort, an dem gesellschaftliche Praktiken für epistemiosche Zwecke instrumentalisiert und in Apparaturen der Erkenntnisfabrikation transfonniert werden: das Labo...

  2. Chemical composition and antitumor activity of different wild varieties of Moroccan thyme Composição química e atividade antitumoral de diferentes variedades selvagens de tomilho Marroquino

    Directory of Open Access Journals (Sweden)

    Abdeslam Jaafari

    2007-12-01

    analisados. De um modo geral, os constituintes principais da composição química das populações de tomilho morroquinas foram carvacrol, timol, borneol e p-cimeno. A quantidade desses componentes pode ser de 85%, 42%, 59%, e 23%, respectivamente. Em adição, os óleos essenciais bem como dois produtos puros (carvacrol e timol foram testados quanto à sua atividade antitumoral contra mastocitoma da linhagem P815. Enquanto todos esses produtos mostraram efeito citotóxico dependente da dose, o carvacrol foi o mais citotóxico quando comparado aos outros. Interessantemente, quando estes produtos foram testados contra células mononucleares sangüíneas periféricas humanas normais, mostraram efeito proliferativo em vez de citotóxico.

  3. Das morgendliche Brückenritual

    Science.gov (United States)

    Sander, Oliver

    Es wäre für Mediziner sehr interessant zu wissen, was für Kräfte genau in den menschlichen Knien wirken. Klar ist, dass sie recht groß sein müssen. Das Gewicht eines erwachsenen Mannes beträgt ca. 80 kg. Wenn davon je die Hälfte auf einem Bein ruht hat man schon mindestens 400 Newton pro Knie, beim Laufen, Springen, oder Treppensteigen noch viel mehr. Man will es aber noch viel genauer wissen. Die Kondylen, das sind die Kontaktflächen in den Knien, sind nicht eben. Es gibt dort Unregelmäßigkeiten, und die Kräfte konzentrieren sich dort. An einzelnen Stellen können die Kräfte dann noch viel höher sein.

  4. RESPONSABILDIADE SOCIAL E AMBIENTAL DAS EMPRESAS

    OpenAIRE

    MONTEIRO, RENATO PEREIRA; MONTEIRO, RENATA PEREIRA BENDER

    2015-01-01

    Nas últimas duas décadas a discussão acerca da responsabilidade social e ambiental (RSA) das empresas têm crescido, bem como o entendimento da sociedade de que as empresas devem ter um papel de protagonistas, assim como os governos devem buscar um padrão de atuação responsável social e ambientalmente. A globalização dos negócios e da informação gerou um novo ambiente de atuação das empresas muito mais competitivo e de pressão dos diversos stakeholders. Questiona-se sua atuação e seu impacto e...

  5. DAS: Intelligent Scheduling Systems for Shipbuilding

    OpenAIRE

    Lee, Jae Kyu; Lee, Kyoung Jun; Hong, June Seok; Kim, Wooju; Kim, Eun Young; Choi, Soo Yeoul; Kim, Ho Dong; Yang, Ok Ryul; Choi, Hyung Rim

    1995-01-01

    Daewoo Shipbuilding Company, one of the largest shipbuilders in the world, has experienced great deal of trouble with the planning and scheduling of its production process. To solve the problems, from 1991 to 1993, Korea Advanced Institute of Science and Technology (KAIST) and Daewoo jointly conducted the Daewoo Shipbuilding Scheduling (das) Project. To integrate the scheduling expert systems for shipbuilding, we used a hierarchical scheduling architecture. To automate the dynamic spatial lay...

  6. Forschung Frankfurt : das Wissenschaftsmagazin. 2012, Nr. 1

    OpenAIRE

    2012-01-01

    Schwerpunkt: Gefäßforschung. Inhalt: Vorwort ... », Kompakt * Paul Ehrlich-Preis für Zellbiologen und Nachwuchspreis für Diabetes-Forscherin * Ausgezeichnet: Leibniz-Preis für Rainer Forst * Biologischer Nanomotor mit Hybridantrieb entdeckt Forschung intensiv * Thrombose-Forschung. Wenn das Blut in den Adern stockt [Eva-Maria Siefert] * Sauerstoffradikale. Schutz oder Schaden für die Gefäße? [Ralf Brandes und Katrin Schröder] * Fettstoffwechsel ...

  7. Legitimation allein durch Entwicklung? : Das Beispiel Ruanda

    OpenAIRE

    Stroh, Alexander

    2007-01-01

    "In Ruanda soll 2008 zum zweiten Mal nach dem Genozid (1994) ein Teil des Parlaments gewählt werden. Eine Debatte um die Bedeutung der Qualität dieser Wahlen für die weitere Entwicklungszusammenarbeit ist noch nicht erkennbar. Obgleich sich global ein allgemeiner Zusammenhang zwischen Demokratie und Entwicklungszuwendungen etabliert hat, wird die autokratische Herrschaft in Ruanda von Geberseite akzeptiert. Das Land erhält gegenwärtig so viel Entwicklungshilfe wie nie zuvor in Friedenszeiten....

  8. Das Übertragungsverhalten von Synchronriemengetrieben

    OpenAIRE

    Librentz, Roy

    2006-01-01

    Die Verkürzung von Produktentwicklungszeiten in der Antriebstechnik erfordert zunehmend den Einsatz von leistungsfähigen Simulationswerkzeugen. Die Basis für eine realitätsnahe Modellbildung liegt in der Kenntnis der wesentlichen, das Übertragungsverhalten bestimmenden Wirkmechanismen. Bezogen auf den im Rahmen der vorliegenden Dissertation betrachteten Synchronriementrieb finden die essentiellen Vorgänge im Riemen-Scheibe-Kontakt statt. Deshalb wurden diese Vorgänge mittels gezielter experim...

  9. Das Christentum, eine Religion der Gewalt?

    OpenAIRE

    Vinnai, Gerhard

    2009-01-01

    "Das Christentum ist seinem Selbstverständnis nach eine Liebesreligion, aber seine Geschichte ist nicht zuletzt auch eine Geschichte der Gewalt. Der Text versucht diesen Widerspruch zu erklären. Er untersucht mit den Mitteln der Analytischen Sozialpsychologie, ausgehend vom Text der Bibel, was in dieser Religion der Ausübung von Gewalt entgegenkommen kann." (Autorenreferat) "in its self-image the Christianity is a religion of love, but its history itself is a history of violence too....

  10. Documentos escolares: impactos das novas tecnologia

    Directory of Open Access Journals (Sweden)

    Flávia Obino Corrêa Werle

    2012-07-01

    Full Text Available  Reflexões acerca das mudanças proporcionadas pelas novas tecnologias na gestão, escrituração e arquivos escolares e das alterações normativas referentes a escrituração e arquivo. Descrição e análise da diferenciação documental tornando corno objeto formas de registro e comunicação do aproveitamento dos alunos pelas escolas aos pais e à sociedade ­livros de atas de aproveitamento, relatórios impressos, boletim semanal de comportamento, boletins de aproveitamento dos alunos para comunicação mensal ou bimestral aos pais, até boletins digitalizados que trafegam eletronicamente entre a escola e os pais, disponíveis em página web das escolas.Palavras-chave: história das instituições educativas; arquivos de instituições educativas; digitalização de documentos.   Abstract Reflections about the changes provided by new technologies to the administration, book­keeping and school archives and the normative alterations referring to book-keeping and archives. The description and analysis of the documental differentiation taking as an object ways of registry and communication to the parents and society of results of the pupils - book of registration of the progress, printed reports, weekly bulletin of behavior, bulletins of progress of the pupils for the monthly or bimestrial communication to the parents, as well as digitalized bulletins which can travel electronically between the school and the parents, available on web pages of the schools. Keywords: history of the educational institutions, archives of the educational institutions, digitalization of documents. 

  11. Finding New Tricks for Old Drugs: Tumoricidal Activity of Non-Traditional Antitumor Drugs.

    Science.gov (United States)

    Zhang, Fangrong; Li, Min; Wang, Junling; Liang, Xi; Su, Yujie; Wang, Wei

    2016-06-01

    Chemotherapy, a traditional method, plays an important role in tumor therapy. Currently, common clinical antitumor drugs have several defects like poor efficacy, side effects, etc. Furthermore, developing new antitumor drugs takes a long time and requires many resources. Recent studies have found that oldies are newbies for the oncologist, such as flavonoid, metformin, aspirin, etc. These non-traditional antitumor drugs (NTADs) are widely used in management of non-cancer diseases, which gained FDA approval for treatment of patients. Increasingly, studies about antitumor action of NTADs have attracted many researchers' interests. A giant amount of studies showed a decrease in cancer incidence in NTAD-treated patients. Several reports outlined a direct inhibitory effect of NTADs on cancer cell growth and antitumoral actions. This review summarized the research progress on antitumor effects of ten NTADs. Retrospective and meta-analyses of trials also showed that these NTADs had preventive effects against cancer in vitro and in vivo. These drugs represent a promising option for cancer treatment, which have clear benefits including clinical safety, obvious curative effect, and saving medical and health resources. Judged from previous reports, future studies will yield valuable data about the profitable effects of these drugs. With a better understanding of its mechanisms of antitumor activity, NTADs may become available for combination with chemotherapy or targeted therapy in clinic. PMID:27032934

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

    International Nuclear Information System (INIS)

    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

  13. Gene Therapy of Cancer: Induction of Anti-Tumor Immunity

    Institute of Scientific and Technical Information of China (English)

    ChengQian; JesusPrieto

    2004-01-01

    Many malignancies lack satisfactory treatment and new therapeutic options are urgently needed. Gene therapy is a new modality to treat both inherited and acquired diseases based on the transfer of genetic material to the tissues. Different gene therapy strategies against cancers have been developed. A considerable number of preclinical studies indicate that a great variety of cancers are amenable to gene therapy. Among these strategies, induction of anti-tumor immunity is the most promising approach. Gene therapy with cytokines has reached unprecedented success in preclinical models of cancer. Synergistic rather than additive effects have been demonstrated by combination of gene transfer of cytokines/chemokines, costimulatory molecules or adoptive cell therapy. Recent progress in vector technology and in imaging techniques allowing in vivo assessment of gene expression will facilitate the development of clinical applications of gene therapy, a procedure which may have a notorious impact in the management of cancers lacking effective treatment. Cellular & Molecular Immunology. 2004;1(2):105-111.

  14. Telomerase:a novel target of antitumor agents

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Telomerase activity was found to be high in various human cancers, but absent in most normal tissues. Its expression pattern made it a novel target for antitumor agents. Several strategies against telomerase were presented in this review. Targeting the telomerase RNA component by oligonucleotide/ribozyme was considered to be one of the most hopeful approaches. Some progresses were made in this area, such as the use of PANs and 2- 5A antisense compounds. The relationships among telomerase activity and cell differentiation, signal transduction, oncogene, tumor suppressor gene as well as cell cycle modulation also provided a series of valuable ideas in designing anti-telomerase drugs for cancer therapy. In conclusion, although there is still a long way in understanding the mechanism and regulation of telomerase, the advance of studies on telomerase has allowed the development of numerous strategies for the treatment of cancer.

  15. Synthesis and antitumor activity of natural compound aloe emodin derivatives.

    Science.gov (United States)

    Thimmegowda, Naraganahalli R; Park, Chanmi; Shwetha, Bettaswamigowda; Sakchaisri, Krisada; Liu, Kangdong; Hwang, Joonsung; Lee, Sangku; Jeong, Sook J; Soung, Nak K; Jang, Jae H; Ryoo, In-Ja; Ahn, Jong S; Erikson, Raymond L; Kim, Bo Y

    2015-05-01

    In this study, we have synthesized novel water soluble derivatives of natural compound aloe emodin 4(a-j) by coupling with various amino acid esters and substituted aromatic amines, in an attempt to improve the anticancer activity and to explore the structure-activity relationships. The structures of the compounds were determined by (1) H NMR and mass spectroscopy. Cell growth inhibition assays revealed that the aloe emodin derivatives 4d, 4f, and 4i effectively decreased the growth of HepG2 (human liver cancer cells) and NCI-H460 (human lung cancer cells) and some of the derivatives exhibited comparable antitumor activity against HeLa (Human epithelial carcinoma cells) and PC3 (prostate cancer cells) cell lines compared to that of the parent aloe emodin at low micromolar concentrations. PMID:25323822

  16. Vaccines against Human Carcinomas: Strategies to Improve Antitumor Immune Responses

    Directory of Open Access Journals (Sweden)

    Claudia Palena

    2010-01-01

    Full Text Available Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultimately will reduce tumor burden by tipping the balance from a protumor to an antitumor immune environment. This review discusses common mechanisms that govern immune cell activation and tumor immune escape, and some of the current strategies employed in the field of cancer vaccines aimed at enhancing activation of tumor-specific T-cells with concurrent reduction of immunosuppression.

  17. A mathematical model of the dynamics of antitumor laser immunotherapy

    Science.gov (United States)

    Dawkins, Bryan A.; Laverty, Sean M.

    2014-02-01

    We use a mathematical model to describe and predict the population dynamics of tumor cells, immune cells, and other immune components in a host undergoing laser immunotherapy treatment against metastatic cancer. We incorporate key elements of the treatment into the model: a function describing the laser-induced primary tumor cell death and parameters capturing the role and strength of the primary immunoadjuvant, glycated chitosan. We focus on identifying conditions that ensure a successful treatment. In particular, we study the patient response (i.e., anti-tumor immune dynamics and treatment outcome) in two different but related mathematical models as we vary quantitative features of the immune system (supply, proliferation, death, and interaction rates). We compare immune dynamics of a `baseline' immune model against an `augmented' model (with additional cell types and antibodies) and in both, we find that using strong immunoadjuvants, like glycated chitosan, that enhance dendritic cell activity yields more promising patient outcomes.

  18. Study on the Interaction between Antitumor Drug Daunomycin and DNA

    Institute of Scientific and Technical Information of China (English)

    CHENG Gui-Fang; ZHAO Jie; TU Yong-Hua; HE Pin-Gang; FANG Yu-Zhi

    2005-01-01

    A detection of anthracycline antitumor drug daunomycin (DNR) reacting with DNA in simulate metabolism in vitro has been made. It was found that DNR could react with DNA to form DNR-DNA adducts. The adduct compositions of DNR with fish sperm DNA and thermally denaturated DNA were determined. The equilibrium association constant K of DNR with fish sperm DNA is 1.98 × 105 L/mol and that of DNR with denaturated DNA is 2.29 × 104 L/mol. Semiquinone free radicals, metabolic products of DNR, can destroy both fish sperm DNA and its thermally denaturated DNA. It is verified by hyperchromic effect increase observed in UV spectrum and AFM experiments. The mechanism of DNA degradation has also been investigated. Results obtained allow one to explain the reason of side effect of anthracycline drug and give the way to depress, which were of clinical significance.

  19. Antitumor effect of metformin in esophageal cancer: in vitro study.

    Science.gov (United States)

    Kobayashi, Mitsuyoshi; Kato, Kiyohito; Iwama, Hisakazu; Fujihara, Shintaro; Nishiyama, Noriko; Mimura, Shima; Toyota, Yuka; Nomura, Takako; Nomura, Kei; Tani, Joji; Miyoshi, Hisaaki; Kobara, Hideki; Mori, Hirohito; Murao, Koji; Masaki, Tsutomu

    2013-02-01

    Recent studies suggest that metformin, which is a member of the biguanide family and commonly used as an oral anti-hyperglycemic agent, may reduce cancer risk and improve prognosis of numerous types of cancer. However, the mechanisms underlying the antitumor effect of metformin on esophageal cancer remain unknown. The goal of the present study was to evaluate the effects of metformin on the proliferation of human ESCC in vitro, and to study changes in the expression profile of microRNAs (miRNAs), since miRNAs have previously been associated with the antitumor effects of metformin in other human cancers. The human ESCC cell lines T.T, KYSE30 and KYSE70 were used to study the effects of metformin on human ESCC in vitro. In addition, we used miRNA array tips to explore the differences between miRNAs in KYSE30 cells with and without metformin treatment. Metformin inhibited the proliferation of T.T, KYSE30 and KYSE70 cells in vitro. Metformin blocked the cell cycle in G0/G1 in vitro. This blockade was accompanied by a strong decrease of G1 cyclins, especially cyclin D1, as well as decreases in cyclin-dependent kinase (Cdk)4, Cdk6 and phosphorylated retinoblastoma protein (Rb). In addition, the expression of miRNAs was markedly altered with the treatment of metformin in vitro. Metformin inhibited the growth of three ESCC cell lines, and this inhibition may have involved reductions in cyclin D1, Cdk4 and Cdk6. PMID:23229592

  20. Deprivation of human natural killer cells and antitumor immune response

    Directory of Open Access Journals (Sweden)

    Vyacheslav Ogay

    2014-01-01

    Full Text Available Introduction: Cell-based immunotherapy has been given increased attention as a treatment for cancer. Human natural killer (NK cells are resident lymphocyte populations. They exhibit potent antitumor activity without human leukocyte antigen matching and without prior antigen exposure. They also are a promising tool for immunotherapy of solid and hematologic cancers. However, most cancer patients do not have enough NK cells to induce an effective antitumor immune response. This demonstrates a need for a source of NK cells that can supplement the endogenous cell population. Material and methods: In this study, we derived induced pluripotent stem cells (iPSCs from peripheral blood T-lymphocytes using Sendai virus vectors. Results: Generated iPSCs exhibited monoclonal T cell receptors (TCR rearrangement in their genome, a hallmark of mature terminally differentiated T cells. These iPSCs were differentiated into NK cells using a two-stage coculture system: iPSCs into hematopoietic CD34+ cells with feeder cells M210-B4 (ATCC, USA and CD34+ cells into mature NK cells with AFT024 cells (ATCC, USA. Our results showed that iPSC-derived NK cells expressed CD56, CD16, NKp 44 and NKp 46, possessed high cytotoxic activity  and produced high level of interferon-γ. Conclusion: Based on our data, derivation of NK cells from induced pluripotent stem cells should be considered in the treatment of oncologic diseases.This would allow for the development of cell therapy for cancer using immunologically compatible NK cells derived from iPSCs. This may contribute to a more efficient treatment of oncologic diseases in addition to traditional cancer treatment.

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

    International Nuclear Information System (INIS)

    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 2x106 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

  2. The Anti-Oxidant and Antitumor Properties of Plant Polysaccharides.

    Science.gov (United States)

    Jiao, Rui; Liu, Yingxia; Gao, Hao; Xiao, Jia; So, Kwok Fai

    2016-01-01

    Oxidative stress has been increasingly recognized as a major contributing factor in a variety of human diseases, from inflammation to cancer. Although certain parts of signaling pathways are still under investigation, detailed molecular mechanisms for the induction of diseases have been elucidated, especially the link between excessive oxygen reactive species (ROS) damage and tumorigenesis. Emerging evidence suggests anti-oxidant therapy can play a key role in treating those diseases. Among potential drug resources, plant polysaccharides are natural anti-oxidant constituents important for human health because of their long history in ethnopharmacology, wide availability and few side effects upon consumption. Plant polysaccharides have been shown to possess anti-oxidant, anti-inflammation, cell viability promotion, immune-regulation and antitumor functions in a number of disease models, both in laboratory studies and in the clinic. In this paper, we reviewed the research progress of signaling pathways involved in the initiation and progression of oxidative stress- and cancer-related diseases in humans. The natural sources, structural properties and biological actions of several common plant polysaccharides, including Lycium barbarum, Ginseng, Zizyphus Jujuba, Astragalus lentiginosus, and Ginkgo biloba are discussed in detail, with emphasis on their signaling pathways. All of the mentioned common plant polysaccharides have great potential to treat oxidative stress and cancinogenic disorders in cell models, animal disease models and clinical cases. ROS-centered pathways (e.g. mitochondrial autophagy, MAPK and JNK) and transcription factor-related pathways (e.g. NF-[Formula: see text]B and HIF) are frequently utilized by these polysaccharides with or without the further involvement of inflammatory and death receptor pathways. Some of the polysaccharides may also influence tumorigenic pathways, such as Wnt and p53 to play their anti-tumor roles. In addition, current

  3. An Investigation on a Novel Anti-tumor Fusion Peptide of FSH33-53-IIKK

    Science.gov (United States)

    Yang, Runlin; Liu, Ping; Pan, Donghui; zhang, Pengjun; Bai, Zhicheng; Xu, Yuping; Wang, Lizhen; Yan, Junjie; Yan, Yongjun; Liu, Xingdang; Yang, Min

    2016-01-01

    A novel fusion peptide FSH33-53-IIKK was designed and expected to combine the follicle stimulating hormone receptor (FSHR) targeting and tumor toxicity. In vitro and in vivo study showed the anti-tumor activity of FSH33-53-IIKK was enhanced compared to that of IIKK only. FSH33-53-IIKK could inhibit the growth of tumor via apoptosis and autophagy pathways. In summary, combining the tumor marker-target peptide and anti-tumor peptide together may be an efficient way to search for better anti-tumor candidates. PMID:27313792

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

    OpenAIRE

    Andreza P. Mendonça; Paulo de T. B. Sampaio; Francisco de A. C. Almeida; Raissa F. Ferreira; Juliene M. Novais

    2015-01-01

    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...

  5. Therapie der IPP - Ist das Messer besser?

    Directory of Open Access Journals (Sweden)

    Breuer G

    2009-01-01

    Full Text Available Die Induratio penis plastica (IPP, auch als M. de LaPeyronie bekannt, ist eine erworbene Erkrankung des fibromatösen Formenkreises. Klinisch imponiert sie als derber Plaque der dorsalen penilen Tunica albuginea. Es kommt zur Deviation des Penisschaftes während der Erektion, so kann die Kohabitation vollständig verhindert werden. Die IPP verläuft in einer Früh- und einer Spätphase. Sind in der Frühphase noch die medikamentöse Therapieoption (Kalium-Paraminobenzoat, Potaba® sowie die extrakorporale Stoßwellentherapie (ESWT möglich, um die Deviationsprogression und die Schmerzhaftigkeit positiv zu beeinflussen, ist die Spätphase durch einen fixierten, zumeist kalzifizierten Plaque gekennzeichnet. Es stehen in diesem Stadium zur symptomatischen Therapie lediglich operative Therapien zur Verfügung, die in der überwiegenden Anzahl zur Verkürzung des Penisschaftes führen und in der Regel nicht-resorbierbares Nahtmaterial einbringen (z. B. OP nach Schroeder/Essed, OP nach Nesbith. Alternativen mit Inzision/Teilresektion des Plaques mit zum Teil umfangreicher Transplantatchirurgie (z. B. Venen-Patch sind aufwendig und komplikationsreich. Die hier vorgestellte komplette Exzision des dokumentierten Plaques und nachfolgende Defektdeckung durch ein Kollagenvlies (TachoSil®, das mit einer Thrombin- und Fibrinogenkomponente beschichtet ist, stellt ein Verfahren dar, das komplikationsarm die weitestgehende Vermeidung der Schaftverkürzung, das zeiteffektive Decken des Gewebsdefekts sowie die Kombination von Blutstillung und druckstabilem Tunikaersatz in sich vereint.

  6. 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...

  7. Die Parlamentswahlen und das Referendum in Belarus'

    OpenAIRE

    Ott, Alexander

    1995-01-01

    Von allen europäischen Staaten sind in Belarus das Streben nach Selbständigkeit und die nationale Volksidentität am wenigsten ausgeprägt. Die früher 'sowjetischste' aller Sowjetrepubliken befindet sich in einer tiefen Identitätskrise. Im Unterschied zu Rußland und der Ukraine hat Belarus keine Antikommunismus- und Souveränitätswelle erlebt. Der Transformationsprozeß hat in der Republik noch nicht begonnen. Die Dominanz Rußlands, seiner Kultur, Sprache und Wirtschaft ist in Belarus allgegenwär...

  8. Das „unsägliche Verbrechen“

    Directory of Open Access Journals (Sweden)

    Angela Koch

    2006-03-01

    Full Text Available Gesa Danes Untersuchung zur Vergewaltigung in Literatur und Recht ist eine präzise Analyse literarischer „Vergewaltigungsfälle“ vor dem jeweiligen zeitgenössischen rechtlichen Hintergrund. Im Vordergrund der Betrachtung stehen Texte von Barockautoren wie Grimmelshausen, Lohenstein oder Calderón de la Barca sowie von Schriftsteller/-innen des ausgehenden 18. und 19. Jahrhunderts wie Wagner, Goethe, Kleist, Lessing oder Hahn-Hahn. Diese Texte hat Dane auf deren anthropologische Konzeptionen von Ehre, Scham und Schande und auf das Tabu des Sprechens über sexuelle Gewalt befragt.

  9. 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

  10. Das Ehegattensplitting im Widerstreit der Argumente

    Directory of Open Access Journals (Sweden)

    Sabine Berghahn

    2008-07-01

    Full Text Available Der von Barbara Seel herausgegebene Sammelband beschäftigt sich u. a. aus familienpolitischer Sicht mit den Pro- und Contra-Argumenten zu der in Deutschland geltenden Ehegattenbesteuerung. Der Band ist interdisziplinär angelegt und stellt einen Überblick her, der auch für Expert/-innen noch neue Gesichtspunkte enthält. Als Gesamttendenz zeigt sich ein Plädoyer für eine individualisierende Reform. Zu einem ähnlichen Ergebnis kommt Britta Dietrich in ihrer schmalen Abhandlung, in der sie – knapp und kaum erkenntnisfördernd – die juristische Debatte über das Ehegattensplitting nachzeichnet.

  11. 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.

  12. Para politizar o mundo das coisas

    OpenAIRE

    Thiago Machado Balbi

    2014-01-01

    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, ...

  13. 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.

  14. A controladoria no contexto atual das empresas

    OpenAIRE

    Aliciane Aparecida Novello; Reginaldo A. de Oliveira; Ardinete Rover

    2005-01-01

    A literatura existente sobre percorre caminhos que nem sempre proporcionam o entendimento imediato ou a solução para as dificuldades surgidas durante o desenvolvimento dessa função dentro das organizações, como a apresentação dos conceitos básicos e de exemplos objetivos para a solução deles. Acredita-se que se pode transcrever sobre o tema de forma ainda sucinta por se tratar de uma área razoavelmente nova, que permite ser desmistificada. Controles bem feitos, baseados em informações de boa ...

  15. Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms

    Institute of Scientific and Technical Information of China (English)

    Zhi-bin LIN; Hui-na ZHANG

    2004-01-01

    Ganoderma lucidum (G lucidum) is a medicinal fungus with a variety of biological activities. It has long been used as a folk remedy for promotion of health and longevity in China and other oriental countries. The most attractive character of this kind of medicinal fungus is its immunomodulatory and anti-tumor activities. Large numbers of studies have shown that G lucidum modulate many components of the immune system such as the antigen-presenting cells, NK cells, T and B lymphocytes. The water extract and the polysaccharides fraction of G lucidum exhibited significant anti-tumor effect in several tumor-bearing animals mainly through its immunoenhancing activity. Recent studies also showed that the alcohol extract or the triterpene fraction of G lucidum possessed antitumor effect, which seemed to be related to the cytotoxic activity against tumor cells directly. Preliminary study indicated that antiangiogenic effect may be involved antitumor activity of G lucidum.

  16. Plant-derived triterpenoids and analogues as antitumor and anti-HIV agents†

    OpenAIRE

    Kuo, Reen-Yen; Qian, Keduo; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung

    2009-01-01

    This article reviews the antitumor and anti-HIV activities of naturally occurring triterpenoids, including the lupane, ursane, oleanane, lanostane, dammarane, and miscellaneous scaffolds. Structure–activity relationships of selected natural compounds and their synthetic derivatives are also discussed.

  17. Synthesis and Antitumor Activity of C-2/C-10 Modified Analogues of Docetaxel

    Institute of Scientific and Technical Information of China (English)

    Wei Shuo FANG; Hong Yan LIU; Qi Cheng FANG

    2005-01-01

    Four 10-propionyl docetaxel analogues (11a-d) with 2α-amido substituents were prepared, and their antitumor activity against three solid tumor cell lines and their drug-resistant counterparts were determined.

  18. A review about the development of fucoidan in antitumor activity: Progress and challenges.

    Science.gov (United States)

    Wu, Lei; Sun, Jing; Su, Xitong; Yu, Qiuli; Yu, Qiuyang; Zhang, Peng

    2016-12-10

    Fucoidan is composed of l-fucose, sulfate groups and one or more small proportions of d-xylose, d-mannose, d-galactose, l-rhamnose, arabinose, glucose, d-glucuronic acid and acetyl groups in different kinds of brown seaweeds. Many reports have demonstrated that fucoidan has antitumor activities on various cancers. However, until now, few reviews have discussed the antitumor activity of fucoidan and few reports have summarized detailed molecular mechanisms of its actions and antitumor challenges of fucoidan specially. In this review, the antitumor signaling pathway mechanisms related to fucoidan are elucidated as much detail as possible. Besides, the factors affecting the anticancer effects of fucoidan, the structural characteristics of fucoidan with anticancer activities and the challenges for the further development of fucoidan are also summarized and evaluated. The existing similar and different conclusions are summarized in an attempt to provide guidelines to help further research, and finally contribute to go into market as chemotherapeumtics. PMID:27577901

  19. 5α-reductase inhibitors, antiviral and anti-tumor activities of some steroidal cyanopyridinone derivatives.

    Science.gov (United States)

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

    2012-01-01

    We herein report the 5α-reductase inhibitors, antiviral and anti-tumor activities of some synthesized heterocyclic cyanopyridone and cyanothiopyridone derivatives fused with steroidal structure. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All the compounds, except 3b, were interestingly less toxic than the reference drug (Prednisolone(®)). Seventeen heterocyclic derivatives containing a cyanopyridone or cyanothiopyridone rings fused to a steroidal moiety were synthesized and screened for their 5α-reductase inhibitors, antiviral and anti-tumor activities comparable to that of Anastrozole, Bicalutamide, Efavirenz, Capravirine, Ribavirin, Oseltamivir and Amantadine as the reference drugs. Some of the compounds exhibited better 5α-reductase inhibitors, antiviral and anti-tumor activities than the reference drugs. The detailed 5α-reductase inhibitors, antiviral and anti-tumor activities of the synthesized compounds were reported. PMID:22057085

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

    OpenAIRE

    Svetla Angelova; Zlatina Gospodinova; Maria Krasteva; Georgi Antov; Valentin Lozanov; Tsanko Markov; Stefan Bozhanov; Elena Georgieva; Vanio Mitev

    2013-01-01

    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 o...

  1. Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents–A drug repurposing strategy

    OpenAIRE

    Chia-Hsien Wu; Li-Yuan Bai; Ming-Hsui Tsai; Po-Chen Chu; Chang-Fang Chiu; Michael Yuanchien Chen; Shih-Jiuan Chiu; Jo-Hua Chiang; Jing-Ru Weng

    2016-01-01

    Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo. Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents. This effort culminated in A4 [10-(3-(piperazin-1-yl)propyl)-2-(trifluoromethyl)-10H-phenothiazine] which exhibited multi-fold higher apoptosis-inducing activity than the pa...

  2. Efficient microwave irradiation enhanced stereoselective synthesis and antitumor activity of indolylchalcones and their pyrazoline analogs

    Indian Academy of Sciences (India)

    Magdy A H Zahran; Hanan F Salama; Yasmin G Abdin; Amira M Gamal-Eldeen

    2010-07-01

    2-Aryl-1-indole-3-carbaldehyde derivatives underwent Claisen-Schmidt condensation with acetophenone derivatives under microwave irradiation condition compared with the conventional heating to afford excellent yields of trans substituted indolylchalcones which subjected to condensation reaction with phenylhydrazine to afford their indolylpyrazoline analogs. The antitumor activity of the synthesized compounds was examined and evaluated against human hepatocellular carcinoma cell line (Hep-G2) as well as the half maximal inhibitory concentration (IC50). Most of them showed high potent antitumor activity.

  3. Myeloid-Derived Suppressor Cells and anti-tumor T cells: a complex relationship

    OpenAIRE

    Monu, Ngozi R.; Frey, Alan B.

    2012-01-01

    Myeloid-Derived Suppressor Cells (MDSC) are immature myeloid cells that are potent inhibitors of immune cell function and which accumulate under conditions of inflammation, especially cancer. MDSC are suggested to promote the growth of cancer by both enhancement of tumor angiogenesis and metastasis and also inhibition of antitumor immune responses. The presence of deficient and/or defective antitumor adaptive and innate immune responses, coincident with accumulation of MDSC in lymphoid organs...

  4. Medicinal Plants Used as Antitumor Agents in Brazil: An Ethnobotanical Approach

    OpenAIRE

    Joabe Gomes de Melo; Ariane Gaspar Santos; Elba Lúcia Cavalcanti de Amorim; Silene Carneiro do Nascimento; Ulysses Paulino de Albuquerque

    2011-01-01

    In this study, we describe the medicinal plants that have been reported to be antitumor agents and that have been used in ethnobotanic research in Brazil to answer the following questions: what is the abundance of plants reported to be antitumor in Brazil? Have the plant species used for tumor treatment in traditional Brazilian medicine been sufficiently examined scientifically? Our analysis included papers published between 1980 and 2008. A total of 84 medicinal plant species were reported t...

  5. The antitumor effect of locoregional magnetic cobalt ferrite in dog mammary adenocarcinoma

    International Nuclear Information System (INIS)

    The endocytosis of nanosized magnetic particles by tumor cells led to numerous tests to establish the use of this phenomenon in antitumor therapy. The direct antitumor effect of a biocompatible cobalt-ferrite-based magnetic fluid directly inoculated in bitch mammary tumors was studied. A direct correlation between tumor cell lysis and cobalt ferrite was established in tumors. Massive endocytosis of magnetic particles was observed 1 h after the contact of magnetic fluid with tumor cells

  6. Das abdominelle Aortenaneurysma: Indikation - Therapie - Ergebnisse

    Directory of Open Access Journals (Sweden)

    Gollackner B

    2006-01-01

    Full Text Available Das abdominelle Aortenaneurysma (AAA zeigte in den vergangenen zwei Jahrzehnten eine deutliche Zunahme. Kommt es zu einer Ruptur, beträgt die Mortalität trotz Notfalleingriff 50 %. In der elektiven Situation konnte die Mortalität auf unter 3 % reduziert werden. Ursache für ein AAA ist in 95 % eine Degeneration der Aortenwand. Aufgrund der erhöhten Rupturgefahr stellen asymptomatische AAA ab 5,5 cm und symptomatische AAA immer dann, wenn es der Allgemeinzustand des Patienten erlaubt, eine Operationsindikation dar. Der Ultraschall dient der Diagnosesicherung und eignet sich gut zur Verlaufsbeobachtung. Vor jeder Operation ist eine CT durchzuführen. Die Komorbidität vieler Patienten erhöht das Operationsrisiko und verkürzt auch die Lebenserwartung nach erfolgreicher OP. Diese Patienten sollten einer endovaskulären Stentimplantation zugeführt werden. Die offene Operation bleibt der goldene Standard zur Behandlung eines AAA bei jüngeren Patienten mit geringen Risikofaktoren. Die endovaskuläre Therapie eröffnet so eine Möglichkeit, bei sonst inkurablen ASAIV-Patienten doch interventionell interdisziplinär aktiv zu werden.

  7. 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.

  8. Deep Astrometric Standards (DAS) and Galactic Structure

    CERN Document Server

    Platais, I; Zacharias, N

    2005-01-01

    The advent of next-generation imaging telescopes such as LSST and Pan-STARRS has revitalized the need for deep and precise reference frames. The proposed weak-lensing observations with these facilities put the highest demands on image quality over wide angles on the sky. It is particularly difficult to achieve a sub-arcsecond PSF on stacked images, where precise astrometry plays a key role. Current astrometric standards are insufficient to achieve the science goals of these facilities. We thus propose the establishing of a few selected deep (V=25) astrometric standards (DAS). These will enable a reliable geometric calibration of solid-state mosaic detectors in the focal plane of large ground-based telescopes and make a substantial contribution to our understanding of stellar populations in the Milky Way. In this paper we motivate the need for such standards and discuss the strategy of their selection and acquisition and reduction techniques. The feasibility of DAS is demonstrated by a pilot study around the o...

  9. Os arredores das cidades romanas de Portugal

    Directory of Open Access Journals (Sweden)

    de Alarcão, Jorge

    1999-12-01

    Full Text Available The author has considered in previous papers three levels of Roman urban settlements: capital towns, vici and castella (Romanized hill-forts or villages; and «casais» or very small farm-houses. In the present paper, he considers the landscape on the outskirts of four Roman capital towns of Portugal and distinguishes three different landscapes: the first, with middle and small farms, sometimes, a villa; the second, with villages around the town, at some distance; finally, the villae in a centuriated landscape.[pt] O autor distinguiu, em anteriores trabalhos, três níveis de aglomerados populacionais —capitais de civitates, vici e castella/aldeias— e três níveis de estabelecimentos rurais— villae, granjas e casais. Neste artigo examina os arredores das cidades romanas de Portugal e distingue três tipos de paisagem: uma composta por granjas e casais, eventualmente algumas villae; outra, por aldeias, mais ou menos distantes umas das outras; e uma terceira, composta de villae num território centuriado.

  10. 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.

  11. DASMiner: discovering and integrating data from DAS sources

    OpenAIRE

    Vasconcelos Ana; Veiga Diogo; Deus Helena; Akdemir Caner; Almeida Jonas

    2009-01-01

    Abstract Background DAS is a widely adopted protocol for providing syntactic interoperability among biological databases. The popularity of DAS is due to a simplified and elegant mechanism for data exchange that consists of sources exposing their RESTful interfaces for data access. As a growing number of DAS services are available for molecular biology resources, there is an incentive to explore this protocol in order to advance data discovery and integration among these resources. Results We...

  12. Das naturwissenschaftliche Labor als Ort der "Verdichtung" von Gesellschaft

    OpenAIRE

    Cetina, Karin Knorr

    1988-01-01

    Ziel der vorliegenden Arbeit ist es zu zeigen, daß sich das herrschende 'Feindbild' des Sozialen als dasjenige, das wissenschaftliche Resultate 'verunreinigt' und von außen infiltriert, bei Betrachtung der Forschungspraxis der Naturwissenschaften nicht aufrecht erhalten läßt. Das naturwissenschaftliche Labor zeigt sich vielmehr als ein Ort, an dem gesellschaftliche Praktiken für epistemische Zwecke instrumentalisiert und in Apparaturen der Erkenntnisfabrikation transformiert werden: da...

  13. Wie die Wirtschaftsberichterstattung der Medien das Konsumentenvertrauen lenkt

    OpenAIRE

    Sophie Wörsdorfer

    2005-01-01

    In der Konjunkturbeobachtung haben Stimmungsindikatoren, wie das Geschäftsklima oder das Konsumentenvertrauen, große öffentliche Bedeutung erlangt. An deren Analyse knüpfen sich die Erwartungen, Anhaltspunkte für das zukünftige Verhalten der Wirtschaftsakteure zu gewinnen. Allerdings besteht weitgehend Unklarheit darüber, wie die Konsumenten bzw. Unternehmer zu ihren Einschätzungen gelangen. Der vorliegende Beitrag untersucht exemplarisch die Rolle der Wirtschaftsberichterstattung der Medien ...

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

    International Nuclear Information System (INIS)

    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

  15. Doxycycline potentiates antitumor effect of cyclophosphamide in mice

    International Nuclear Information System (INIS)

    Cyclophosphamide (CPA) is a widely used chemotherapeutic drug in neoplasias. It is a DNA and protein alkylating agent that has a broad spectrum of activity against variety of neoplasms including breast cancer. The therapeutic effectiveness of CPA is limited by the high-dose hematopoietic, renal, and cardiac toxicity that accompanies the systemic distribution of liver-derived activated drug metabolites. The present study examines the potential of combining well-tolerated antibiotic doxycycline (DOX) with CPA and understanding the mechanism of cell killing. Interestingly, we found that DOX significantly enhances the tumor regression activity of CPA on xenograft mice model bearing MCF-7 cells. DOX also potentiates MCF-7 cell killing by CPA in vitro. In presence of DOX (3 μg/ml), the IC50 value of CPA decreased significantly from 10 to 2.5 mM. Additional analyses indicate that the tumor suppressor p53 and p53-regulated proapoptotic Bax were upregulated in vivo and in vitro following CPA treatment in combination with DOX, suggesting that upregulation of p53 may contribute to the enhancement of antitumor effect of CPA by DOX. Furthermore, downregulation of antiapoptotic Bcl-2 was observed in animals treated with CPA and CPA plus DOX when compared to untreated or DOX-treated groups. Our results raise the possibility that this combination chemotherapeutic regimen may lead to additional improvements in treatment of breast cancer

  16. Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Paraskar, Abhimanyu; Soni, Shivani; Basu, Sudipta; Srivats, Shyam; Roy, Rituparna Sinha; Sengupta, Shiladitya [BWH-HST Center for Biomedical Engineering, Harvard Medical School, 65 Landsdowne street, Cambridge, MA 02139 (United States); Amarasiriwardena, Chitra J; Lupoli, Nicola, E-mail: ssengupta2@partners.org [Channing Laboratory, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, 65 Landsdowne street, Cambridge, MA 02139 (United States)

    2011-07-01

    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{sub 50} = 0.77 {+-} 0.11 {mu}M comparable to that of free cisplatin (IC{sub 50} = 0.44 {+-} 0.09 {mu}M). 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.

  17. Antitumor constituents from the leaves of Carya cathayensis.

    Science.gov (United States)

    Cao, Xu-Dong; Ding, Zhi-Shan; Jiang, Fu-Sheng; Ding, Xing-Hong; Chen, Jian-Zhen; Chen, Su-Hong; Lv, Gui-Yuan

    2012-01-01

    This study aimed to find cytotoxic chemical constituents from Carya cathayensis leaves (LCC) by using various chromatographic procedures. Identification of the chemical constituents was carried out by various spectroscopic techniques and classical chemical methods. The cytotoxic activity of the constituents was assayed on HeLa and HepG2 cell lines by staining with 3-(4,5-dimethylthiahiazol-2-y1)-2,5-di-phenytetrazolium bromide (MTT). Six flavanoids, namely (1) pinostrobin, (2) pinostrobin chalcone, (3) wogonin, (4) cardamonin, (5) alpinetin and (6) tectochrysin were identified from this species. Compounds 2-6 were isolated from this kind of plant for the first time. MTT results showed that wogonin has a moderate cytotoxic activity with IC(50) values of 17.03 ± 2.41 and 44.23 ± 3.87 µM against HeLa and HepG2 cell lines, respectively. According to the correlation of primary the structure and activity, 8-methoxy substituent in these flavones may be a major factor of the antitumor activity. PMID:22007794

  18. GMCSF-armed vaccinia virus induces an antitumor immune response.

    Science.gov (United States)

    Parviainen, Suvi; Ahonen, Marko; Diaconu, Iulia; Kipar, Anja; Siurala, Mikko; Vähä-Koskela, Markus; Kanerva, Anna; Cerullo, Vincenzo; Hemminki, Akseli

    2015-03-01

    Oncolytic Western Reserve strain vaccinia virus selective for epidermal growth factor receptor pathway mutations and tumor-associated hypermetabolism was armed with human granulocyte-macrophage colony-stimulating factor (GMCSF) and a tdTomato fluorophore. As the assessment of immunological responses to human transgenes is challenging in the most commonly used animal models, we used immunocompetent Syrian golden hamsters, known to be sensitive to human GMCSF and semipermissive to vaccinia virus. Efficacy was initially tested in vitro on various human and hamster cell lines and oncolytic potency of transgene-carrying viruses was similar to unarmed virus. The hGMCSF-encoding virus was able to completely eradicate subcutaneous pancreatic tumors in hamsters, and to fully protect the animals from subsequent rechallenge with the same tumor. Induction of specific antitumor immunity was also shown by ex vivo co-culture experiments with hamster splenocytes. In addition, histological examination revealed increased infiltration of neutrophils and macrophages in GMCSF-virus-treated tumors. These findings help clarify the mechanism of action of GMCSF-armed vaccinia viruses undergoing clinical trials. PMID:25042001

  19. Über Theatermetaphorik und das Standardgehirn

    Directory of Open Access Journals (Sweden)

    Katharina Piechocki

    2004-07-01

    Full Text Available Der Sammelband KörperKonzepte/Concept du corps dokumentiert die Ergebnisse der gleichnamigen, von der Schweizerischen Gesellschaft für Frauen- und Geschlechterforschung im März 2001 an der Universität in Basel organisierten Konferenz. Die Herausgeberinnen betonen in ihrem Vorwort den internationalen und interdisziplinären Charakter des Bandes und sehen in ihrem Anliegen, sowohl kultur- als auch naturwissenschaftliche theoretische Ansätze zu verbinden, einen Vorteil gegenüber einer „ausschließlich kulturwissenschaftliche[n] Perspektive“ (S. 12. Das in drei Teile gegliederte Buch beschäftigt sich mit „Sichtweisen und Lesarten“, „Kulturhistorische[n] Zugänge[n]“ und stellt im letzten Teil „Fragen an die Lebenswissenschaften“.

  20. 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.

  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. Avaliação do potencial anticorrosivo de tiossemicarbazonas solubilizadas em microemulsão

    Directory of Open Access Journals (Sweden)

    Elaine Cristina M. de Moura

    2013-01-01

    Full Text Available In this paper, thiosemicarbazones 4-N-cinnamoyl-thiosemicarbazone (CTSC, 4-N-(2'-methoxycinnamoyl-thiosemicarbazone (MCTSC, and 4-N-(4'-hydroxy-3'-methoxybenzoyl- thiosemicarbazone (HMBTSC were solubilized in an oil-in-water (O/W microemulsion system (ME_OCS, forming systems CTSC_ME_OCS, MCTSC_ME_OCS and HMBTSC_ME_OCS. The effectiveness of these systems in the process of inhibiting AISI 1020 carbon steel corrosion was evaluated in a saline solution (NaCl 0.5%, using a galvanostatic method. The tested thiosemicarbazones showed higher inhibitory effects (85.7% for CTSC_ME_OCS, 84.0% for MCTSC_ME_OCS, and 83.3% for HMBTSC_ME_OCS. The surfactant OCS (dissolved in H2O and the ME_OCS system showed lower efficacies, with 71.0% for OCS and 74.0% for ME_OCS system.

  3. O impacto da adoção das IPSAS no relato financeiro das autarquias

    OpenAIRE

    Cunha, Ana Maria Valente da

    2011-01-01

    O International Public Sector Accounting Standadrs Board (IPSASB) emite normas de contabilidade para o setor público que se denominam, International Public Sector Accounting Standards (IPSAS). Estas normas constituem adaptações das International Financial Reporting Standards (IFRS), emitidas pelo International Accounting Standards Board (IASB). O IPSASB tem vindo a desenvolver esforços no sentido da harmonização contabilística a nível mundial e, nesse sentido, conseguiu j...

  4. Das Aufdecken des Inzests als emanzipatorischer Akt - Noch einmal: "Das Fest" von Thomas Vinterberg

    OpenAIRE

    Hirsch, Mathias

    2003-01-01

    Der dänische Film "Das Fest" wird unter dem Aspekt der typischen Dynamik der Inzestfamilie untersucht. Die Aufdeckung des Inzests ist Zentrum der Handlung dieses Films; sie wird nicht etwa als Ausdruck der Aggression aufgrund der sekundären Identifikation mit dem Aggressor oder als der Rache verstanden, sondern vielmehr als Emanzipationsbestrebung, sich nämlich aus der Opferidentität (primäre Identifikation mit dem Aggressor) und der verleugnenden Kollaboration trennen zu wollen. Damit verbun...

  5. Acetylated starch nanocrystals: Preparation and antitumor drug delivery study.

    Science.gov (United States)

    Xiao, Huaxi; Yang, Tao; Lin, Qinlu; Liu, Gao-Qiang; Zhang, Lin; Yu, Fengxiang; Chen, Yuejiao

    2016-08-01

    In this study, we developed a new nanoparticulate system for acetylated starch nanocrystals (ASN) using broken rice. ASN with different degrees of substitution (DS) of 0.04, 0.08 and 0.14 were prepared using acetic anhydride as acetylating agent through reaction with starch nanocrystals (SN). The resulting ASN were investigated for the capability to load and release doxorubicin hydrochloride (DOX), and the antitumor activities of DOX-loaded SN and DOX-loaded ASN were evaluated as potential drug delivery systems for cancer therapy. Cellular uptake and cytotoxicity of nanocrystals and the DOX-loaded nanocrystals were investigated using fluorescence microscopy and a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. Compared with acetylated starches (AS) and native starches (NS), ASN with DS 0.14 loaded up to 6.07% of DOX with a higher loading efficiency of 91.1% and had steadier drug-release rates. Toxicity analysis using the rat hepatocytes model suggested that ASN was biocompatible and could be used for drug delivery. Furthermore, ASN were taken up by cancer cells in vitro and significantly enhanced the cytotoxicity of DOX against HeLa human cervical carcinoma cells. The IC50 value of DOX-loaded ASN-DS 0.14 was 3.8μg/mL for 24h of treatment, which was significantly lower than that of free DOX (21μg/mL). These results indicate that the prepared ASN using broken rice is a promising vehicle for the controlled delivery of DOX for cancer therapy. PMID:27156696

  6. Antitumoral Effect of L. inermis in Mice with EAC

    Directory of Open Access Journals (Sweden)

    Mehmet Ozaslan

    2009-01-01

    Full Text Available In recent years, prophylactic usage of natural products and tendency to resort to alternative medicine has increased rapidly. Henna (Lawsonia sp. has been used not only cosmetically but also medicinally in Turkish population. Among the studies of henna’s antifungal, anti-microbial, tuberculostatic and antitumoral effects come on the science. In this study, we planned to research the effect of Lawsonia inermis that is an oxidant agent against development of cancer, by constituting peritonitis carcinomatous with Ehrlich ascites cells. The animals were divided to three groups and Lawsonia inermis extract and tap water were given to mice for 5 days. After 5 days, all of animals were decapitated by cervical dislocation and their liver tissues were sampled to measure reduced glutathione (GSH level. Mean Survival Time (MST and Average Survival Time (AST were calculated; peritoneal liquid pH was measured; Ehrlich Ascites Carcinoma (EAC cells were counted with hemocytometer. At the result, the longest life period was detected on the group which was given 10 mg/kg/day Lawsonia inermis. In group 2 and 3 which were given Lawsonia inermis following to forming Ehrlich ascites carcinoma, total number of cancer cell decreased. The scaled pH levels belonging to group 2 and 3 changed into alkaline compared to that of group1 (pH = 6.2. Glutathione levels of liver tissue were determined to decrease in group 2 and 3 in comparison with group1. In conclusion, Lawsonia inermis may lead cells to apoptosis related to deficiency in detoxification of intracellular radicals.

  7. Herceptin-geldanamycin immunoconjugates: pharmacokinetics, biodistribution, and enhanced antitumor activity.

    Science.gov (United States)

    Mandler, Raya; Kobayashi, Hisataka; Hinson, Ella R; Brechbiel, Martin W; Waldmann, Thomas A

    2004-02-15

    The efficacy of monoclonal antibodies (mAbs) as single agents in targeted cancer therapy has proven to be limited. Arming mAbs with a potent toxic drug could enhance their activity. Here we report that conjugating geldanamycin (GA) to the anti-HER2 mAb Herceptin improved the activity of Herceptin. The IC(50)s of the immunoconjugate H-GA were 10-200-fold lower than that of Herceptin in antiproliferative assays, depending on the cell line. The H-GA mode of action involved HER2 degradation, which was partially lactacystin sensitive and thus proteasome dependent. The linkage between GA and Herceptin remained stable in the circulation, as suggested by the pharmacokinetics of Herceptin and conjugated GA, which were almost identical and significantly different from that of free GA. Tumor uptake of Herceptin and H-GA were similar (52 +/- 7 and 43 +/- 7% of the initial injected dose per gram tissue, respectively; P = 0.077), indicating no apparent damage attributable to conjugation. Therapy experiments in xenograft-bearing mice consisted of weekly i.p. doses, 4 mg/kg for 4 months. H-GA showed a greater antitumor effect than Herceptin because it induced tumor regression in 69% of the recipients compared with 7% by Herceptin alone. Median survival time was 145 days as opposed to 78 days, and 31% of the recipients remained tumor free 2 months after therapy was terminated versus 0% in the Herceptin group. Enhancement of Herceptin activity could be of significant clinical value. In addition, the chemical linkage and the considerations in therapeutic regimen described here could be applied to other immunoconjugates for targeted therapy of a broad spectrum of cancers. PMID:14973048

  8. 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.

  9. Pedagogical Basis of DAS Formalism in Engineering Education

    Science.gov (United States)

    Hiltunen, J.; Heikkinen, E.-P.; Jaako, J.; Ahola, J.

    2011-01-01

    The paper presents a new approach for a bachelor-level curriculum structure in engineering. The approach is called DAS formalism according to its three phases: description, analysis and synthesis. Although developed specifically for process and environmental engineering, DAS formalism has a generic nature and it could also be used in other…

  10. Das Konzept des Foregrounding in der modernen Textverarbeitungspsychologie

    OpenAIRE

    Holt, Nadine van; Groeben, Norbert

    2005-01-01

    Das Konzept des "Foregrounding" in der modernen Textverarbeitungspsychologie wird als Manifestation der gestaltpsychologischen Figur-Grund-Unterscheidung angesehen. Durch Ausdifferenzierung verschiedener Bezugsdimensionen von Vorder- und Hintergrund können sowohl basale Mikroprozesse des Textverstehens als auch anspruchsvolle literarische Rezeptionen als Varianten einer Figur-Grund-Unterscheidung beim Lesen rekonstruiert werden. Für das literarische Foregrounding stellt die Unterscheidung von...

  11. Design of a Dynamic Arm Support (DAS) for gravity compensation

    NARCIS (Netherlands)

    Kramer, Gijs; Römer, GertWillem R.B.E.; Stuyt, Harry J.A.

    2007-01-01

    The Dynamic Arm Support, or briefly the Das, is a new medical device that serves to compensate for lost arm function of the severely disabled. The target group suffers from insufficient muscle force to move its arms over the usual Range of Motion (RoM). The purpose of the Das is to assist its user d

  12. Vox humana mit Tieren : zu den Gedichten "Das brennende Haus"

    OpenAIRE

    Chiarloni, Anna

    2010-01-01

    Anna Chiarloni analysiert und interpretiert exemplarisch und vergleichend einzelne Gedichte bzw. Gedichtausschnitte aus Günter Herburgers 1991 erschienen Lyrikband "Das brennende Haus": "Späte Schicht", "Die Mole", "Anglunipe", "Heimkehr", "Mein Newton", "Die Zigeunerin", "Die Kopenhagener Deutung", "Rückkehr", "Das Versteck", "Grönland", "Die imaginäre Haltestelle", "Heimweh", "Tee", "Lied" und "Einstand".

  13. DASMiner: discovering and integrating data from DAS sources

    Directory of Open Access Journals (Sweden)

    Vasconcelos Ana

    2009-01-01

    Full Text Available Abstract Background DAS is a widely adopted protocol for providing syntactic interoperability among biological databases. The popularity of DAS is due to a simplified and elegant mechanism for data exchange that consists of sources exposing their RESTful interfaces for data access. As a growing number of DAS services are available for molecular biology resources, there is an incentive to explore this protocol in order to advance data discovery and integration among these resources. Results We developed DASMiner, a Matlab toolkit for querying DAS data sources that enables creation of integrated biological models using the information available in DAS-compliant repositories. DASMiner is composed by a browser application and an API that work together to facilitate gathering of data from different DAS sources, which can be used for creating enriched datasets from multiple sources. The browser is used to formulate queries and navigate data contained in DAS sources. Users can execute queries against these sources in an intuitive fashion, without the need of knowing the specific DAS syntax for the particular source. Using the source's metadata provided by the DAS Registry, the browser's layout adapts to expose only the set of commands and coordinate systems supported by the specific source. For this reason, the browser can interrogate any DAS source, independently of the type of data being served. The API component of DASMiner may be used for programmatic access of DAS sources by programs in Matlab. Once the desired data is found during navigation, the query is exported in the format of an API call to be used within any Matlab application. We illustrate the use of DASMiner by creating integrative models of histone modification maps and protein-protein interaction networks. These enriched datasets were built by retrieving and integrating distributed genomic and proteomic DAS sources using the API. Conclusion The support of the DAS protocol allows that

  14. A study on recent tendency of anti-tumor herbal acupuncture

    Directory of Open Access Journals (Sweden)

    Yoo Hwa-Seung

    2001-12-01

    Full Text Available Objectives: The purpose of this study is to develop and activate anti-tumor herbal acupuncture for cancer patients in South Korea. Methods: We investigated some literatures on anti-tumor herbal acupuncture which is used in South Korea and China, and made diagrams. Results: The results are summarized as follows. Anti-tumor herbal acupuncture is one of the traditional oriental medical method which is effective for cancer patients. In domestic studies, most of herb materials are belong to action of cooling&detoxification(25.0% and strengthening body resistance(46.4% which are proved to have effects of anti-tumor, immune activation and preventing tumor. In China, point injection therapy are used for improving symptoms of cancer patients and healing tumor. Also herbal intravenous injection is used for combination of chinese traditional and western cancer therapy and treating cancer patients variously. Conclusions: From the above results, it is expected that anti-tumor herbal acupuncture is useful to improve clinical symptoms and quality of life(QOL of cancer patients. Also we must develop new progressive methods of point injection and herbal intravenous injection for treating cancer patients, and advance clinical studies and trials.

  15. ANTITUMOR EFFECT OF SARCNU IN A 06-METHYLGUANINE-DNA METHYLTRANSFERASE POSITIVE HUMAN GLIOMA XENOGRAFT MODEL

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To assess whether novel analogue of nitrosoureas, 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), has antitumor effect to 06-methylguanine-DNA methyltransferase (MGMT) positive tumors in vivo. Methods: MGMT positive human glioma cell line SF-767 xenografts in nude mice were treated with SarCNU. The antitumor efficacy of SarCNU was compared with the results of 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment with or without 06-benzylguanine (06-BG) preadministration. Results: Since the SF-767 is MGMT strongly positive, BCNU treatment alone did not result in a satisfactory anticancer effect. As expected, 06-BG by depleting MGMT activity, significantly enhanced BCNU antitumor efficacy (p<0.001). More interestingly, SarCNU treatment alone had a better antitumor effect than 06-BG plus BCNU treatment (F=51.7, p=0.00036). Conclusion: Since SarCNU enters cells via extraneuronal monoamine transporter (EMT), the enhanced antitumor activity of SarCNU in this MGMT positive human tumor xenograft model may be due to the presence of EMT in SF-767.SarCNU may be used as an alternative treatment for MGMT positive tumors, specifically for tumors expressing EMT.

  16. Establishment of antitumor memory in humans using in vitro-educated CD8+ T cells.

    Science.gov (United States)

    Butler, Marcus O; Friedlander, Philip; Milstein, Matthew I; Mooney, Mary M; Metzler, Genita; Murray, Andrew P; Tanaka, Makito; Berezovskaya, Alla; Imataki, Osamu; Drury, Linda; Brennan, Lisa; Flavin, Marisa; Neuberg, Donna; Stevenson, Kristen; Lawrence, Donald; Hodi, F Stephen; Velazquez, Elsa F; Jaklitsch, Michael T; Russell, Sara E; Mihm, Martin; Nadler, Lee M; Hirano, Naoto

    2011-04-27

    Although advanced-stage melanoma patients have a median survival of less than a year, adoptive T cell therapy can induce durable clinical responses in some patients. Successful adoptive T cell therapy to treat cancer requires engraftment of antitumor T lymphocytes that not only retain specificity and function in vivo but also display an intrinsic capacity to survive. To date, adoptively transferred antitumor CD8(+) T lymphocytes (CTLs) have had limited life spans unless the host has been manipulated. To generate CTLs that have an intrinsic capacity to persist in vivo, we developed a human artificial antigen-presenting cell system that can educate antitumor CTLs to acquire both a central memory and an effector memory phenotype as well as the capacity to survive in culture for prolonged periods of time. We examined whether antitumor CTLs generated using this system could function and persist in patients. We showed that MART1-specific CTLs, educated and expanded using our artificial antigen-presenting cell system, could survive for prolonged periods in advanced-stage melanoma patients without previous conditioning or cytokine treatment. Moreover, these CTLs trafficked to the tumor, mediated biological and clinical responses, and established antitumor immunologic memory. Therefore, this approach may broaden the availability of adoptive cell therapy to patients both alone and in combination with other therapeutic modalities. PMID:21525398

  17. Experimental research on effects of a new Traditional Chinese medicine on antitumor metastases

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective: To study the efficacy and mechanism of AT-1 a new compound (an aqueous agent extracted from a Traditional Chinese herb with antiplatelet efficacy) on antitumor metastases in mice. Methods: AT-1,a compound extracted from a Traditional Chinese herb, was prepared by our lab. C57BL/6 female mice, which were transplanted H22 liver cancer cells, received the agent. The tumor nodules, the pulmonary metastasis rate and tumor cell proliferation activity were tested. The tumor cells were exposed to different concentrations of AT-1, and then the condition of the tumor proliferations were tested. Results: High and middle dosages of AT-1 inhibited both the lymphatic and blood systemic tumor pulmonary metastases significantly, but had no effect on inhibition of the tumor cell proliferation in vitro. Conclusion:The major antitumor actions of AT-1 may be on antitumor metastases, and the compounnd may be a new candidate for antitumor metastases agent. More study of the mechanism and action of AT1 on antitumor metastases and the actions are still being done deeply.

  18. Comparative antitumor and anti-proliferative activities of Hippophae rhamnoides L. leaves extracts

    Directory of Open Access Journals (Sweden)

    Javid Ali

    2015-03-01

    Full Text Available Objective: To evaluate the antitumor and anti-proliferative activities of methanol, aqueous, acetone, ethyl acetate, ethanol, chloroform and n-hexane extracts of Hippophae rhamnoides leaves. Methods: Antitumor activities were evaluated by using the antitumor potato disc assay by using inoculums (Agrobacterium tumefaciens with three different concentrations of test samples (10, 100 and 1 000 mg/L. Anti-proliferative activity was evaluated by the given method of methyl thiazolyl tetrazolium assay. The concentrations of the extract ranging from 0.039 to 10 mg/mL were tested against HeLa cells. Results: Highest tumors inhibition activity (60.9% and 55.8% was shown by methanol and ethanol extracts, with EC50 values of 424.41 and 434.61 mg/L respectively. At 10 mg/mL, The highest cell inhibition 75.61% was observed in methanol extract and the lowest 36.59% were calculated in n-hexane extract. The difference in tumor and cell inhibition (% may be due to the different concentration of active compounds responsible for antitumor and anti-proliferative activities. All extracts have considerable level of tumor and cell inhibitiory effect in a dose dependent manner. Conclusions: Our finding showed that Hippophae rhamnoides leaves are a potent natural source of antitumor and antiproliferative agent.

  19. Paracetamol Supplementation Does Not Alter The Antitumor Activity and Lung Toxicity of Bleomycin

    Directory of Open Access Journals (Sweden)

    Ghada M. Suddek

    2014-01-01

    Full Text Available Bleomycin (BLM is well known by its antitumor activity both in vitro and in vivo. However, pulmonary fibrosis has been considered the dose limiting toxicity of the drug. Hyperpyrexia following injection of BLM was reported thus, paracetamol is sometimes administered with BLM as antipyretic drug. Actually, paracetamol was found to interfere with cytotoxicity of some drugs. This study was conducted to investigate the effect of paracetamol administration on the antitumor and lung toxicity of BLM. The antitumor activity was evaluated both in vitro and in vivo using Ehrlich ascites carcinoma (EAC cells. Paracetamol did not alter the antitumor effect of BLM in vitro or in vivo. The lung toxicity of BLM was evidenced by decrease in the body weight, increase in the lung/body weight ratio, decrease in the response of pulmonary arterial rings to 5-hydroxytryptamine (5-HT and increase in the contractility of tracheal smooth muscles induced by acetylcholine (ACh. The toxicity was also confirmed biochemically by marked increases in hydroxyproline and lipid peroxidation in rat lung and the decrease in reduced glutathione (GSH level. Pretreatment with paracetamol did not significantly change lipid peroxidation, GSH level, percent survival of rats or the response of pulmonary arterial rings and tracheal smooth muscles to 5-HT and ACh respectively. The results of the present study indicated that paracetamol neither modified the antitumor effect of BLM nor changed drug-induced lung toxicity.

  20. 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.

  1. Cytotoxic and antitumor activities of a polypore macrofungus, Phellinus rimosus (Berk) Pilat.

    Science.gov (United States)

    Ajith, T A; Janardhanan, K K

    2003-02-01

    Cytotoxic and antitumor activities of ethyl acetate, methanol and aqueous extracts of a wood inhabiting polypore macrofungus, Phellinus rimosus (Berk) Pilat. were studied. Ethyl acetate and methanol extracts showed in vitro cytotoxic activity against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines. The aqueous extract did not exhibit cytotoxicity against the tested cell lines. All the three extracts were highly effective in inhibiting growth of solid tumor induced by DLA cell line in mice. However, the antitumor activity of ethyl acetate extract was higher than that of methanol and aqueous extracts. The ethyl acetate extract was also effective in preventing the EAC induced ascites tumor development in mice. The antitumor activity of all the three extracts against solid tumor at a dose of 50 mg/kg (p.o.) was comparable to the clinically used standard reference drug, cisplatin (4 mg/kg, i.p.). Pre-treatment of the extracts was also effective in inhibiting the tumor growth induced by DLA cell lines. The experimental results revealed that ethyl acetate extract of P. rimosus possessed significant antitumor activity. The findings thus suggest the potential use of this mushroom as antitumor agent. PMID:12648809

  2. Das Metabolische Syndrom und die Eizelle

    Directory of Open Access Journals (Sweden)

    Blüher M

    2009-01-01

    Full Text Available Der Begriff Metabolisches Syndrom beschreibt eine individuelle Häufung von Risikofaktoren für kardiovaskuläre Erkrankungen und Typ-2-Diabetes. Zu diesen Risikofaktoren gehören: viszerale Adipositas, erhöhte Glukose- und Triglyzeridplasmaspiegel, niedrige HDL-Cholesterin-Spiegel, Hypertonie, sowie ein proinflammatorischer und prothrombotischer Status. An der Entwicklung des Metabolischen Syndroms sind genetische Faktoren, Verhaltensmuster, Lebensgewohnheiten und Umwelteinflüsse und deren Wechselwirkung beteiligt. Die auslösenden Faktoren des Metabolischen Syndroms wie beispielsweise eine fettreiche Ernährung können auch Eizellen schädigen und zum medizinischen Problem der Infertilität bei einer Gruppe adipöser Frauen beitragen. Außerdem tritt das Metabolische Syndrom sehr häufig gemeinsam mit dem Syndrom der Polyzystischen Ovarien (PCOS auf. Das PCOS ist die häufigste endokrinologische Erkrankung geschlechtsreifer Frauen, unter der in Deutschland etwa 1 Million Frauen leiden. Nach neueren Definitionen liegt ein PCOS vor, wenn 2 der Kriterien polyzystische Ovarien, Oligo- oder Anovulation und klinische oder laborchemische Zeichen eines Hyperandrogenismus, nach Ausschluss anderer endokriner Erkrankungen erfüllt sind. Die Insulinresistenz des PCOS führt kompensatorisch zu einer vermehrten Insulinfreisetzung. Die so entstehende Hyperinsulinämie verstärkt die vorbestehende Hyperandrogenämie, einerseits durch direkte Steigerung der ovariellen Androgenproduktion, andererseits durch vermehrte hypophysäre LH-Freisetzung, die am Ovar ebenfalls zu einer gesteigerten Hormonproduktion führt. Bei PCOS-Patientinnen scheinen nicht nur die absolute Menge zugeführter Kalorien, sondern die Zusammensetzung der Nahrung, körperliche Aktivität und insbesondere genetische Faktoren den Zusammenhang zum Metabolischen Syndrom zu erklären. Lebensstilveränderungen, die kalorische Restriktion und erhöhte körperliche Aktivität einschließen, aber

  3. XPath Query Completeness Verification Algorithms in DAS

    Directory of Open Access Journals (Sweden)

    Xiaoyuan Bao

    2010-10-01

    Full Text Available With the development in the application environment of database management system, the related technologies such as data management and data access have become more and more complex and the cost of maintenance has been more and more expensive. The problems that how to enable enterprises to focus on their expert areas and outsource the unfamiliar enterprise information systems to others, thus to save a lot of resources but receive the same quality of services, are widely concerned by the database research and application areas. Database as a service (DAS, which means that enterprises outsource the database system to some database service providers (DSP who manage the massive data and provide high-quality data management service becomes an important application in nowadays. To enjoy services provided by a third party, we need to ensure the correctness and completeness of query results. This paper pospose an algorithm which provides an authentication method for the  query results returned from a possible malicous server on which database is outsourced and query is evaluated. The basic idea is to build some Merkle hash trees twice to verify the correctness and completeness of the query results. We have demonstrated the effectiveness of our method in experiments.

  4. Zinc protoporphyrin IX, a heme oxygenase-1 inhibitor, demonstrates potent antitumor effects but is unable to potentiate antitumor effects of chemotherapeutics in mice

    International Nuclear Information System (INIS)

    HO-1 participates in the degradation of heme. Its products can exert unique cytoprotective effects. Numerous tumors express high levels of HO-1 indicating that this enzyme might be a potential therapeutic target. In this study we decided to evaluate potential cytostatic/cytotoxic effects of zinc protoporphyrin IX (Zn(II)PPIX), a selective HO-1 inhibitor and to evaluate its antitumor activity in combination with chemotherapeutics. Cytostatic/cytotoxic effects of Zn(II)PPIX were evaluated with crystal violet staining and clonogenic assay. Western blotting was used for the evaluation of protein expression. Flow cytometry was used to evaluate the influence of Zn(II)PPIX on the induction of apoptosis and generation of reactive oxygen species. Knock-down of HO-1 expression was achieved with siRNA. Antitumor effects of Zn(II)PPIX alone or in combination with chemotherapeutics were measured in transplantation tumor models. Zn(II)PPIX induced significant accumulation of reactive oxygen species in tumor cells. This effect was partly reversed by administration of exogenous bilirubin. Moreover, Zn(II)PPIX exerted potent cytostatic/cytotoxic effects against human and murine tumor cell lines. Despite a significant time and dose-dependent decrease in cyclin D expression in Zn(II)PPIX-treated cells no accumulation of tumor cells in G1 phase of the cell cycle was observed. However, incubation of C-26 cells with Zn(II)PPIX increased the percentage of cells in sub-G1 phase of the cells cycle. Flow cytometry studies with propidium iodide and annexin V staining as well as detection of cleaved caspase 3 by Western blotting revealed that Zn(II)PPIX can induce apoptosis of tumor cells. B16F10 melanoma cells overexpressing HO-1 and transplanted into syngeneic mice were resistant to either Zn(II)PPIX or antitumor effects of cisplatin. Zn(II)PPIX was unable to potentiate antitumor effects of 5-fluorouracil, cisplatin or doxorubicin in three different tumor models, but significantly

  5. Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice

    Science.gov (United States)

    Barakat, Waleed; Elshazly, Shimaa M.; Mahmoud, Amr A. A.

    2015-01-01

    Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg) against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg). Untreated mice developed a palpable solid tumor after 13 days. Unlike fluorouracil, spirulina at the investigated two dose levels failed to exert any protective effect. In addition, spirulina did not potentiate the antitumor effect of fluorouracil when they were administered concurrently. Interestingly, their combined administration resulted in a dose-dependent increase in mortality. The present study demonstrates that spirulina lacks antitumor effect against this model of solid Ehrlich carcinoma and increased mortality when combined with fluorouracil. However, the implicated mechanism is still elusive. PMID:26366170

  6. Design, synthesis and biological evaluation of new rhodacyanine analogues as potential antitumor agents

    Institute of Scientific and Technical Information of China (English)

    Yang Xiong Li; Xin Zhai; Wei Ke Liao; Wu Fu Zhu; Ying He; Ping Gong

    2012-01-01

    In an attempt to develop potent antitumor agents,new rhodacyanine analogues containing the pyridinium ring (5a-5h),the isoquinolinium ring (6a-6c) and the quinolinium ring (7a-7e) linked to the rhodanine ring via N-N covalent bond were designed,synthesized and evaluated for antitumor activity against human lung cancer cell line (H460) by MTT assay in vitro.Most of the tested compounds showed enhanced antitumor activity with IC50 values ranging from 0.006 to 9.2 μmol/L as compared to the lead compound MKT-077.Among them,the most promising compound 7d (IC50 =0.006 μmol/L) was 216.7 times more active than MKT-077 (IC50 =1.3 μmol/L).The preliminary structure-activity relationship of the target compounds was discussed.

  7. ANTITUMOR AQCTIVITY OF REGIONAL ADMINISTRATION OF A-NK CELLS IN VIVO

    Institute of Scientific and Technical Information of China (English)

    GAO Jun; WANG Zhi-hua; ZHANG Zhi-bin; YANG Hong

    2006-01-01

    Objective: To observe the proliferation of A-NK in vitro and antitumor activity in vivo. Methods: The growth curve of A-NK and NA-NK cells was drawn in vitro. In the rat model, we compared the regional administration of A-NK-/IL-2 with the systemic administration. Results: The expansion of A-NK cells reached to climax on day 10 in the culture, increased 16.08 folds compared with the only 3.36 folds for NA-NK cells. In the rat model, we found that the regional administration of A-NK/IL-2 was better than systemic administration or administration of NA-NK/IL-2 not only in tumor infiltration and antitumor response, but also in the survival rate of rats (P<0.05). Conclusion: A-NK cells is a new immune effecter cells with high expansibility and high antitumor activity in vivo and in vitro.

  8. Experimental research on the in vitro antitumor effects of Crataegus sanguinea.

    Science.gov (United States)

    Sun, Jianling; Gao, Guolan; Gao, YuLian; Xiong, LiJuan; Li, Xiaoying; Guo, Jihong; Zhang, Yueming

    2013-09-01

    Crataegus sanguinea is a wild plant, which has been widely grown in the north and south of the Tianshan mountains in Xinjiang. In order to explore their anti-cancer properties, edible wild plants from Xinjiang have been tested for their antitumor properties. We used Ames tests, mouse bone marrow polychromatic erythrocytes micronucleus tests, and tumor cells cultured in vitro to study the anti-mutagenic and anti-tumor effects of C. sanguinea extract. We have shown that C. sanguinea has anti-mutagenic effect, but no mutagenicity. Cell culture in vitro experiments show that there is no inhibition of growth or increase in cell death on normal mouse fibroblasts, but a stronger inhibition of cell growth and an increase in cell death of Hep-2 and MGC-803 tumor cells. The results of this study illustrate that C. sanguinea extract has both anti-mutagenic and anti-tumor effects. PMID:23423688

  9. Enhancement of Antitumor Effect of Tegafur/Uracil (UFT) plus Leucovorin by Combined Treatment with Protein-Bound Polysaccharide, PSK, in Mouse Models

    Institute of Scientific and Technical Information of China (English)

    Ryoji Katoh; Mitsuru Ooshiro

    2007-01-01

    We evaluated the antitumor effect of combined therapy with tegafur/uracil (UFT) plus leucovorin (LV) (UFT/LV)and protein-bound polysaccharide, PSK, in three mouse models of transplantable tumors. UFT/LV showed antitumor effect against Meth A sarcoma, and the antitumor effect was enhanced when PSK given concomitantly.UFT/LV showed antitumor effect to Lewis lung carcinoma and PSK alone also showed antitumor effect at high dose, but a combination of UFT/LV and PSK resulted in no enhanced antitumor effect. Colon 26 carcinoma was weakly responsive to UFT/LV, and no enhancement of antitumor effect was found even PSK was used in combination. In conclusion, while the effect of PSK varies depending on tumor, combined use of UFT/LV and PSK may be expected to augment the antitumor effect.

  10. Comparative Analysis of the Biosynthetic Gene Clusters and Pathways for Three Structurally Related Antitumor Antibiotics Bleomycin, Tallysomycin and Zorbamycin†

    OpenAIRE

    Galm, Ute; Wendt-Pienkowski, Evelyn; Wang, Liyan; Huang, Sheng-Xiong; Unsin, Claudia; Tao, Meifeng; Coughlin, Jane M.; Shen, Ben

    2011-01-01

    The biosynthetic gene clusters for the glycopeptide antitumor antibiotics bleomycin (BLM), tallysomycin (TLM), and zorbamycin (ZBM) have been recently cloned and characterized from Streptomyces verticillus ATCC15003, Streptoalloteichus hindustanus E465-94 ATCC31158, and Streptomyces flavoviridis ATCC21892, respectively. The striking similarities and differences among the biosynthetic gene clusters for the three structurally related glycopeptide antitumor antibiotics prompted us to compare and...

  11. NKT cells as an ideal anti-tumor immunotherapeutic

    Directory of Open Access Journals (Sweden)

    Shin-ichiro eFujii

    2013-12-01

    Full Text Available Human NKT cells are characterized by their expression of an invariant T cell antigen receptor (TCR  chain variable region encoded by a V24J18 rearrangement. These NKT cells recognize -galactosylceramide (-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-, 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 -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- production had significantly prolonged median survival times (MST of 29.3 Mo 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 wks after the combination therapy of -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 -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 one 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- in vitro and in vivo

  12. Anti-tumor immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

    2009-06-01

    Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp

  13. Molecular interactions between nucleic acids and antitumor substances by Raman and NMR spectroscopy.

    Science.gov (United States)

    Bertoluzza, A; Fagnano, C; Tosi, R; Tugnoli, V; Morelli, M A; Barbarella, G

    1986-01-01

    1-Methyladenosine (1-MeAdo) and protonated 1-Methyladenosine (1-MeAdo.H+) were chosen as a model to study the molecular interactions between the carcinogen dimethylsulphate (DMS) and the base adenine, and the interactions between the antitumoral electrophilic cis-diamminedichlorophatinum (II) (cis-Pt) and the methylation product of the base, respectively. Raman and multinuclear NMR studies show the molecular perturbations caused by the carcinogen on the base and those of the antitumoral substance on the reaction product base-carcinogen. PMID:3813493

  14. Anti-tumor targeted drug delivery systems mediated by aminopeptidase N/CD13

    Directory of Open Access Journals (Sweden)

    Xun Wang

    2011-08-01

    Full Text Available Aminopeptidase N (APN/CD13 is a transmembrane glycoprotein, which is overexpressed on tumor neovascular endothelial cells and most tumor cells, where it plays an important role in tumor angiogenesis. Peptides containing the Asn-Gly-Arg (NGR motif can specifically recognize APN/CD13 allowing them to act as tumor-homing peptides for the targeted delivery of anti-tumor drugs to tumor neovascular endothelial cells and tumor cells. This article reviews the literature and recent developments related to APN/CD13, its role in tumor growth and some anti-tumor drug delivery systems containing NGR peptides designed to target APN/CD13.

  15. Synthesis and antitumor evaluation of fluoroquinolone C3 fused heterocycles (Ⅱ): From triazolothiadiazines to pyrazolotriazoles

    Institute of Scientific and Technical Information of China (English)

    Guo Qiang Hu; Wen Long Huang; Li Li Hou; Yong Yang; Lei Yi; Song Qiang Xie; Guo Qiang Wang; Nan Nan Duan; Tie Yao Chao; Xiao Yi Wen

    2011-01-01

    To further expand an effective modified route for the shift from an antibacterial fluoroquinolone (FQ) to an antitumor FQ, two series of title compounds based on an isostere of the FQ C3 carboxylic group with two fused heterocyclic rings, [l,2,4]triazolo[3,4-6][l,3,4]thiadiazine and pyrazolo[5,l-c][l,2,4]triazole, respectively, were designed and synthesized starting from the current antibacterial FQs, and their in vitro antitumor activity against L1210, CHO cell lines were evaluated via their respective IC50 values.

  16. Enhancement of antitumor vaccine in ablated hepatocellular carcinoma by high-intensity focused ultrasound

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate whether tumor debris created by high-intensity focused ultrasound(HIFU)could trigger antitumor immunity in a mouse hepatocellular carcinoma model. METHODS:Twenty C57BL/6J mice bearing H22 hepatocellular carcinoma were used to generate antitumor vaccines.Ten mice underwent HIFU ablation,and the remaining 10 mice received a sham-HIFU procedure with no ultrasound irradiation.Sixty normal mice were randomly divided into HIFU vaccine,tumor vaccine and control groups.These mice were immunized w...

  17. Pure Multiplicative Noises Induced Population Extinction in an Anti-tumor Model under Immune Surveillance

    International Nuclear Information System (INIS)

    The dynamical characters of a theoretical anti-tumor model under immune surveillance subjected to a pure multiplicative noise are investigated. The effects of pure multiplicative noise on the stationary probability distribution (SPD) and the mean first passage time (MFPT) are analysed based on the approximate Fokker-Planck equation of the system in detail. For the anti-tumor model, with the multiplicative noise intensity D increasing, the tumor population move towards to extinction and the extinction rate can be enhanced. Numerical simulations are carried out to check the approximate theoretical results. Reasonably good agreement is obtained.

  18. Auswirkungen eines dreiachsigen Spannungszustandes auf das Verformungsverhalten und das Rissinitiierungsverhalten von Gruppenfehlstellen

    OpenAIRE

    Weichert, Christina

    2004-01-01

    Während des Erstarrungsprozesses von großen Schmiedestücken ist die Entstehung von Fehlstellen (nichtmetallische Einschlüsse) und Inhomogenitäten nicht vollständig vermeidbar. Daher ist es erforderlich, Kriterien zur Beurteilung der Zulässigkeit von Fehlstellen zu erarbeiten. Zum Auffinden und zur Größenbestimmung der Fehlergrößen im Inneren der Schmiedestücke wird die Ultraschallprüfung angewandt. Zur Ermittlung von Oberflächenfehlern dient die Magnetpulverrissprüfung. Das Ziel dieser Arbeit...

  19. UMA REVISÃO DAS TEORIAS SOBRE A ESTRUTURA DE CAPITAIS DAS EMPRESAS

    OpenAIRE

    Jorge, Susana Margarida Faustino; Armada, Manuel José da Rocha

    2000-01-01

    Passados quarenta anos sobre a publicação do polémico artigo, em que Modigliani e Miller (1958) demonstraram não existir uma estrutura óptima para os capitais das empresas, defendendo assim que o valor de mercado e custo de capital destas eram independentes da sua estrutura de financiamento, a controvérsia em torno destas considerações subsiste. Depois destes autores, rnuitos outros estudaram o assunto, desenvolvendo urn conjunto diverso de teorias sobre a estrutura de capitais, nas quais ...

  20. The role of radiotherapy for the induction of antitumor immune responses; Die Rolle der Strahlentherapie bei der Induktion von Antitumor-Immunantworten

    Energy Technology Data Exchange (ETDEWEB)

    Multhoff, G. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Klinik fuer Strahlentherapie und Radiologische Onkologie, Experimentelle Radioonkologie; Helmholtz-Zentrum Muenchen (HMGU) (Germany). Klinische Kooperationsgruppe: ' Angeborene Immunantwort in der Tumorbiologie' ; Gaipl, U.S. [Universitaetsklinikum Erlangen (Germany). Strahlenklinik/Radioonkologie, Strahlen-Immunbiologie; Niedermann, G. [Universitaetsklinikum Freiburg (Germany). Klinik fuer Strahlenheilkunde, Sektion fuer Klinische und Experimentelle Strahlenbiologie

    2012-11-15

    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.

  1. Responsabilidade Social Corporativa: estudo comparativo das normas socioambientais

    OpenAIRE

    Francisco Roberto Pinto; Dorelland Ponte Lima; Marcelle Colares Oliveira; Leonel Gois Lima Oliveira

    2007-01-01

    A utilização de normas socioambientais visa dar maior credibilidade às práticas de Responsabilidade Social Corporativa (RSC). Neste estudo, levantaram-se os seguintes questionamentos: Quais as características das normas socioambientais existentes quanto à avaliação do processo produtivo, das relações com a comunidade, das relações com os empregados e dependentes? Quais os aspectos convergentes e divergentes dessas características no tocante à integração dos sistemas de gestão da RSC propugnad...

  2. Das Zentralinstitut für Seelische Gesundheit

    OpenAIRE

    Meyer-Lindenberg, Andreas; Schredl, Michael

    2015-01-01

    Wer sich beim Ski-Fahren das Bein bricht, wird von Freunden und Kollegen umsorgt, bei seelischen Problemen halten die meisten immer noch unwillkürlich Abstand zum Patienten. Dagegen hat die Universität Heidelberg schon früh ein Zeichen gesetzt: Das Zentralinstitut für Seelische Gesundheit (ZI) wurde mitten in die Mannheimer Innenstadt gesetzt. Das funktioniert seit 40 Jahren erstaunlich gut, wie Campus Reporter Nils Birschmann im Gespräch mit Prof. Andreas Meyer-Lindenberg und Prof. Michael S...

  3. Musgos urbanos do recanto das Emas, Distrito Federal, Brasil

    OpenAIRE

    Câmara Paulo Eduardo; Teixeira Rodrigo; Lima Jaqueline; Lima Janaina

    2003-01-01

    Fruto da ocupação desordenada de Brasília, o Recanto das Emas é uma das mais recentes cidades criadas no entorno da capital. Localizada a 25,8km do Plano Piloto, conta com área de 101.476km². O Recanto das Emas foi criado em 1993 e hoje conta com população de aproximadamente 100.000 habitantes. Foram selecionados vários pontos de coleta procurando abranger toda a cidade e diferentes áreas. Foram encontrados relativamente poucos representantes da brioflórula, com predomínio de espécies ruderai...

  4. Reengenharia do processo de reclamações das lojas

    OpenAIRE

    Pereira, Ana Maria Nogueira

    2015-01-01

    Num contexto global de incerteza, as cadeias de abastecimento mais ágeis e os clientes com mais exigências manifestam uma constante preocupação com a melhoria contínua da eficiência das operações logísticas. O presente projeto foi desenvolvido na empresa Sonae Modelo Continente Hipermercados, S.A, uma das duas principais empresas do retalho da grande distribuição alimentar em Portugal. Sendo a logística um fator chave de sucesso, uma das atividades críticas de uma empresa...

  5. Neurobiologia das emoções Neurobiology of the emotions

    OpenAIRE

    Vanderson Esperidião-Antonio; Marilia Majeski-Colombo; Diana Toledo-Monteverde; Glaciele Moraes-Martins; Juliana José Fernandes; Marjorie Bauchiglioni de Assis; Rodrigo Siqueira-Batista

    2008-01-01

    CONTEXTO: A "natureza" das emoções é um dos temas arcaicos do pensamento ocidental, sendo tematizada em diferentes manifestações da cultura como a arte, a religião, a filosofia e a ciência, desde tempos imemoriais. Nos últimos anos, o avanço das neurociências possibilitou a construção de hipóteses para a explicação das emoções, especialmente a partir dos estudos envolvendo o sistema límbico. OBJETIVOS: Apresentar uma discussão atualizada acerca da neurobiologia dos processos relativos às emoç...

  6. Schriften eines Unbequemen. Das Prosawerk von Kay Hoff

    OpenAIRE

    Wörther, Thomas

    2008-01-01

    Der 1924 in Neustadt in Holstein geborene, heute in Berlin lebende, Kay Hoff hat in seiner mehr als 50 Jahre andauernden Schriftstellerkarriere seinen Ruf als unbequemer, das heißt gesellschaftliche und politische Missstände unmissverständlich tadelnder, Autor häufig in Werk und Wirken unter Beweis gestellt. Leben und Schaffen des promovierten Germanisten zeigen sich geprägt durch das, was er selbst bezeichnet als seinen „wichtigsten Lebenseinschnitt [...]: das Kriegsende 1945.“ So gehören Ve...

  7. Aspectos pouco comuns da morfologia das plantas superiores.

    OpenAIRE

    Oliveira, José N. B.

    1991-01-01

    A importância do estudo da Morfologia das Plantas Superiores resulta, em grande parte, do facto do seu conhecimento estar na base da identificação das espécies, contribuir significativamente para a interpretação das relações filogenéticas e ainda constituir o ponto de partida para os estudos da morfo-funcionalidade. Muito embora a moderna Sistemática procure cada vez mais fundamentar-se também noutras áreas científicas, a Morfologia continua a ser o ramo científico mais importante para a Sist...

  8. 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)

  9. Musgos urbanos do recanto das Emas, Distrito Federal, Brasil Urban mosses from Recanto das Emas, Distrito Federal, Brazil

    OpenAIRE

    Paulo Eduardo Câmara; Rodrigo Teixeira; Jaqueline Lima; Janaina Lima

    2003-01-01

    Fruto da ocupação desordenada de Brasília, o Recanto das Emas é uma das mais recentes cidades criadas no entorno da capital. Localizada a 25,8km do Plano Piloto, conta com área de 101.476km². O Recanto das Emas foi criado em 1993 e hoje conta com população de aproximadamente 100.000 habitantes. Foram selecionados vários pontos de coleta procurando abranger toda a cidade e diferentes áreas. Foram encontrados relativamente poucos representantes da brioflórula, com predomínio de espécies ruderai...

  10. Wann wird die Demokratie erwachsen? Kinder und das Wahlrecht

    Directory of Open Access Journals (Sweden)

    Lecce, Steven

    2012-12-01

    Full Text Available Dieser Artikel untersucht, ob es moralisch vertretbar ist, Kindervon Wahlen auszuschließen. Letztendlich gibt es starke Spannungen zwischen den egalitären Annahmen der Demokratie und unserem offensichtlichen Unwillen, Kindern das Wahlrecht zuzugestehen. Solange kein plausibler Grund für die ungleiche Behandlungvon Erwachsenen und Kindern gefunden wird, muss die anhaltende politische Vorenthaltung des Wahlrechts von unseren jüngsten Bürgern als das bezeichnet werden, was sie ist: soziale Ungerechtigkeit. Der Artikel beginnt mit der Darstellung einiger konzeptionellerSchwierigkeiten, die im Verhältnis Kindheit – Demokratie aufkommen. Anschließend untersucht er zwei sehr unterschiedliche Demokratieansätze und ihre Bedeutung für das Kinderwahlrecht: Prozeduralismus und das vermeintliche Kinderrecht auf eine offene Zukunft.

  11. DAS: a data management system for instrument tests and operations

    CERN Document Server

    Frailis, Marco; Zacchei, Andrea; Lodi, Marcello; Cirami, Roberto; Pasian, Fabio; Trifoglio, Massimo; Bulgarelli, Andrea; Gianotti, Fulvio; Franceschi, Enrico; Nicastro, Luciano; Conforti, Vito; Zoli, Andrea; Smart, Ricky; Morbidelli, Roberto; Dadina, Mauro

    2014-01-01

    The Data Access System (DAS) is a metadata 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 Syste...

  12. Das Interne Audit und die Erwartungen der Stakeholder

    OpenAIRE

    Ruud, Flemming

    2014-01-01

    Trotz seiner relativ jungen Geschichte hat der Berufsstand des internen Audits in der Vergangenheit steigende Popularität und viele Veränderungen erfahren. Als Managementfunktion diente das interne Audit früher vor allem zur Überprüfung von Finanzberichten. Getrieben durch die Globalisierung, die Professionalisierung des Berufsstands sowie durch regulatorische Änderungen erweiterte sich das Aufgabenspektrum über die Jahre hinweg. Aufgrund der zunehmenden Bedeutung der internen Steuerung und K...

  13. Determinantes da estrutura de capital das empresas familiares portuguesas

    OpenAIRE

    Correia, Telma

    2003-01-01

    O presente estudo visa identificar os determinantes da estrutura de capital das empresas familiares portuguesas. Pretende-se testar o poder explicativo dos principais determinantes identificados pelas várias teorias da estrutura de capital no comportamento financeiro das empresas familiares e, identificar outros determinantes com base nas suas especificidades. A investigação incide sobre um conjunto de empresas familiares portuguesas que se constituíram como associados fundadores da As...

  14. Besteuerung des Nichts: Steuerarbitrage und das schwindende Aufkommen bei Kapitaleinkommensteuern

    OpenAIRE

    Schindler, Dirk

    2002-01-01

    In einem Ein-Perioden-Modell werden die Auswirkungen des deutschen Steuerrechts zur Kapitalbesteuerung auf das Kapitalmarktgleichgewicht untersucht. Dabei modellieren wir sowohl einen Unternehmenssektor, der der K¨orperschaftsteuer unterliegt, als auch Privatinvestoren, die einkommensteuerpflichtig sind. Es zeigt sich, daß weder lokale Steuerarbitrage noch Steuerclientele auftreten. Erweitert man das Modell um Aktien und Finanzderivate verschwindet die Steuerbasis f¨ur Kapitalertragsteuern im...

  15. Das Phosphatidylinositol-Transfer-Protein PITPnm2 in humanen Thrombozyten

    OpenAIRE

    Kramer, Daniel

    2013-01-01

    Die Analyse des Phosphoproteoms in ruhenden und in aktivierten humanen Plättchen führte zur Identifikation des PITPnm2-Proteins. Dieses Protein wird bei einer Stimulation von Thrombozyten mit dem Prostazyklinanalogon Iloprost phosphoryliert. Diese Ergebnisse gaben Anlass zu weiteren Untersuchungen zum Vorkommen und zur Funktion dieses Proteins in Thrombozyten. In der Arbeit wurde gezeigt, dass das PITPnm2-Protein das einzige Protein der PITP-Familie ist, welches in humanen Thrombozyten exprim...

  16. Das Potential von Social Business in Österreich

    OpenAIRE

    Vandor, Peter; Millner, Reinhard; Moder, Clara Maria; Schneider, Hanna; Meyer, Michael

    2015-01-01

    Der vorliegende Bericht stellt die Ergebnisse einer im Frühjahr 2015 durchgeführten Studie zum Thema "Das Potential von Social Business in Österreich" vor. Basierend auf einer systematischen Literaturrecherche, der Auswertung von Sekundärdatensätzen und einer ExpertInnenbefragung (n=18), werden die derzeitige Bedeutung und das zukünftige Potential von Social Businesses analysiert. (authors' abstract)

  17. Deutschland und das Völkerrecht nach der Wiedervereinigung

    OpenAIRE

    Krieger, Heike

    2011-01-01

    Inhalt: - I. Das Ende des Kalten Krieges und die internationale Neuausrichtung Deutschlands - II. Schaffung neuer Handlungsspielräume für die auswärtige Gewalt - II.1. Anpassung verfassungsrechtlicher Standards an internationale Verpflichtungen: Internationale Strafgerichtsbarkeit und Art. 16 Abs. 2 S. 1 GG - II.2. Auslegung von verfassungsrechtlichen Standardsfür sicherheitspolitische Handlungsspielräume - III. Begrenzung und Kontrolle der Einwirkung völkerrechtlicher Normen auf das innersta...

  18. Konferenz-Management über das WWW

    OpenAIRE

    Müller, Uwe

    2002-01-01

    Der folgende Artikel beschäftigt sich mit einem datenbankbasierten Verwaltungssystem für wissenschaftliche Konferenzen, das seine Funktionalität für sämtliche Benutzergruppen über eine WWW-Schnittstelle zur Verfügung stellt. Das System ist in seiner jetzigen Ausprägung als Prototyp für die Compstat2002 in Berlin entwickelt worden, bietet aber auch weiterreichende Konfigurations- und Einstellungsmöglichkeiten.

  19. DAS: a data management system for instrument tests and operations

    OpenAIRE

    Frailis, Marco; Sartor, Stefano; Zacchei, Andrea; Lodi, Marcello; Cirami, Roberto; Pasian, Fabio; Trifoglio, Massimo; Bulgarelli, Andrea; Gianotti, Fulvio; Franceschi, Enrico; Nicastro, Luciano; Conforti, Vito; Zoli, Andrea; Smart, Ricky; Morbidelli, Roberto

    2014-01-01

    The Data Access System (DAS) is a metadata 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 applica...

  20. EVOLUÇÃO DAS ORGANIZAÇÕES POR MEIO DAS ABORDAGENS INSTITUCIONAL, ECOLOGIA DAS ORGANIZAÇÕES E EQUILÍBRIO PONTUADO

    OpenAIRE

    Ana Clarissa Santos

    2013-01-01

    Dentro do paradigma funcionalista, caracterizado pelo objetivismo filosófico e pela sociologia da manutenção do status quo, a teoria institucional e da ecologia das organizações são amplamente estudadas para explicar por que as organizações podem ser, paradoxalmente, tão diferentes e tão semelhantes. A teoria da ecologia das organizações defende que existe grande diferença entre as organizações e, com o passar do tempo, aquelas mais adaptadas são selecionadas pelo ambiente. Isso faz com que a...

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. Synthesis and anti-tumor activity of all-trans retinoic acid derivatives

    Institute of Scientific and Technical Information of China (English)

    Juan Shen; Jing Bo Shi; Fei Hu Chen; Yuan Wang; Jing Jing Ruan; Yua Huang

    2009-01-01

    A series of retinoate and retinamide derivatives were designed, synthesized, and their anti-tumor activities were investigated in NB4 by MTT and flow cytometry assays (FCM). All compounds showed cytotoxicity, especially compounds 1a and 1d exhibited a higher cytotoxicity than other derivatives and all-traus retinoic acid (ATRA). Furthermore, compound ld could induce NB4 cell lines differentiation efficiently.

  6. 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

  7. Stereospecific Synthesis of the Skeleton of the Antitumor Marine Natural Product Et-743

    Institute of Scientific and Technical Information of China (English)

    LIU Zhan-Zhu; TANG Ye-Feng; WANG Ye; CHEN Shi-Zhi

    2003-01-01

    @@ Ecteinascidin 743 (Et-743) is an exceedingly potent antitumor agent isolated from the marine tunicate Ecteinascidia turbinate. As its structurally simplified version, Phthalascidin was found to retain the cytotoxicity of the natural product. Their novel structures, impressive biological activities and difficult availabilities conspire to render the attractive targets for total synthesis.

  8. Expression property and antitumor effect of pEgr-angiostatin induced by ionizing radiation

    International Nuclear Information System (INIS)

    Objective: To study on the expression and antitumor effect of pEgr-angiostatin induced with ionizing radiation. Methods: Mouse angiostatin cDNA was amplified with RT-PCR. The pEgr-angiostatin recombinant plasmid was constructed and was then transfected into B16 cells with liposome. The cells were irradiated and the expression of angiostatin mRNA in B16 cells was detected. Finally, the antitumor effect of pEgr-angiostatin was studied. Results: The sequence of mouse angiostatin cDNA was identical to reported. Egr-1 promoter and angiostatin cDNA was inserted correctly into expression vector. The expression property of pEgr-angiostatin was examined by ionizing radiation. The gene-therapy with pEgr-angiostatin showed remarkably antitumor effect. Conclusion: Mouse angiostatin cDNA had been cloned successfully in the study. The expression property and the antitumor effect of pEgr-angiostatin are induced by ionizing radiation. This result provides the basis for multi-gene-radiotherapy of tumor

  9. Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents-A drug repurposing strategy.

    Science.gov (United States)

    Wu, Chia-Hsien; Bai, Li-Yuan; Tsai, Ming-Hsui; Chu, Po-Chen; Chiu, Chang-Fang; Chen, Michael Yuanchien; Chiu, Shih-Jiuan; Chiang, Jo-Hua; Weng, Jing-Ru

    2016-01-01

    Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo. Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents. This effort culminated in A4 [10-(3-(piperazin-1-yl)propyl)-2-(trifluoromethyl)-10H-phenothiazine] which exhibited multi-fold higher apoptosis-inducing activity than the parent compound in oral cancer cells. Compared to trifluoperazine, A4 demonstrated similar regulation on the phosphorylation or expression of multiple molecular targets including Akt, p38, and ERK. In addition, A4 induced autophagy, as evidenced by increased expression of the autophagy biomarkers LC3B-II and Atg5, and autophagosomes formation. The antitumor activity of A4 also related to production of reactive oxygen species and adenosine monophosphate-activated protein kinase. Importantly, the antitumor utility of A4 was extended in vivo as it, administrated at 10 and 20 mg/kg intraperitoneally, suppressed the growth of Ca922 xenograft tumors. In conclusion, the ability of A4 to target diverse aspects of cancer cell growth suggests its value in oral cancer therapy. PMID:27277973

  10. Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents–A drug repurposing strategy

    Science.gov (United States)

    Wu, Chia-Hsien; Bai, Li-Yuan; Tsai, Ming-Hsui; Chu, Po-Chen; Chiu, Chang-Fang; Chen, Michael Yuanchien; Chiu, Shih-Jiuan; Chiang, Jo-Hua; Weng, Jing-Ru

    2016-01-01

    Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo. Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents. This effort culminated in A4 [10-(3-(piperazin-1-yl)propyl)-2-(trifluoromethyl)-10H-phenothiazine] which exhibited multi-fold higher apoptosis-inducing activity than the parent compound in oral cancer cells. Compared to trifluoperazine, A4 demonstrated similar regulation on the phosphorylation or expression of multiple molecular targets including Akt, p38, and ERK. In addition, A4 induced autophagy, as evidenced by increased expression of the autophagy biomarkers LC3B-II and Atg5, and autophagosomes formation. The antitumor activity of A4 also related to production of reactive oxygen species and adenosine monophosphate-activated protein kinase. Importantly, the antitumor utility of A4 was extended in vivo as it, administrated at 10 and 20 mg/kg intraperitoneally, suppressed the growth of Ca922 xenograft tumors. In conclusion, the ability of A4 to target diverse aspects of cancer cell growth suggests its value in oral cancer therapy. PMID:27277973

  11. 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

  12. 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. PMID:2191767

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

    International Nuclear Information System (INIS)

    Maghemite (γ-Fe2O3) 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-Fe2O3 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-Fe2O3 nanoparticles showed higher antitumor and antimetastatic activities than commercial CuFe2O4 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

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

    International Nuclear Information System (INIS)

    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. 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. 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. 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 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

  16. Antimicrobial, antitumor and brine shrimp lethality assay of Ranunculus arvensis L. extracts.

    Science.gov (United States)

    Bhatti, Muhammad Zeeshan; Ali, Amjad; Saeed, Asma; Saeed, Ahmad; Malik, Salman Akbar

    2015-05-01

    To investigate the antitumor activity, brine shrimp lethality assay, antibacterial and antifungal activity of Methanol Extract (ME), Water Extract (WE), Acetone Extract (AE), Chloroform Extract (CE), Methanol-Water Extract (MWE), Methanol-Acetone Extract (MAE), Methanol-Chloroform Extract (MCE) of Ranunculus arvensis (L.). Antitumor activity was evaluated with Agrobacterium tumefaciens (At10) induced potato disc assay. Cytotoxicity was evaluated with brine shrimp lethality assay. Antibacterial activity was evaluated with six bacterial strains including Escherichia coli, Enterobacter aerogenes, Bordetella bronchiseptica, Klebsiella pneumoniae, Micrococcus luteus and Streptococcus anginosus and antifungal screening was done against five fungal strains including Aspergillus niger, A. flavus, A. fumigates, Fusarium solani and Mucor species by using disc diffusion method. Best antitumor activity was obtained with ME and WE, having highest IC50 values 20.27 ± 1.62 and 93.01 ± 1.33μg/disc. Brine shrimp lethality assay showed LC50 values of AE, MAE and ME were obtained as 384.66 ± 9.42μg/ml, 724.11 ± 8.01μg/ml and 978.7 ±8.01 μg/ml respectively. WE of R. arvensis revealed weak antimicrobial result against the tested microorganisms. On the other hand, the antifungal activity of the plant extracts was found to be insignificant. These findings demonstrate that extracts of R. arvensis possesses significant antitumor activity. Further extensive study is necessary to assess the therapeutic potential of the plant. PMID:26004705

  17. ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis

    Science.gov (United States)

    Cubillos-Ruiz, Juan R.; Silberman, Pedro C.; Rutkowski, Melanie R.; Chopra, Sahil; Perales-Puchalt, Alfredo; Song, Minkyung; Zhang, Sheng; Bettigole, Sarah E.; Gupta, Divya; Holcomb, Kevin; Ellenson, Lora H.; Caputo, Thomas; Lee, Ann-Hwee; Conejo-Garcia, Jose R.; Glimcher, Laurie H.

    2015-01-01

    SUMMARY Dendritic cells (DCs) are required to initiate and sustain T cell-dependent anti-cancer immunity. However, tumors often evade immune control by crippling normal DC function. The endoplasmic reticulum (ER) stress response factor XBP1 promotes intrinsic tumor growth directly, but whether it also regulates the host anti-tumor immune response is not known. Here we show that constitutive activation of XBP1 in tumor-associated DCs (tDCs) drives ovarian cancer (OvCa) progression by blunting anti-tumor immunity. XBP1 activation, fueled by lipid peroxidation byproducts, induced a triglyceride biosynthetic program in tDCs leading to abnormal lipid accumulation and subsequent inhibition of tDC capacity to support anti-tumor T cells. Accordingly, DC-specific XBP1 deletion or selective nanoparticle-mediated XBP1 silencing in tDCs restored their immunostimulatory activity in situ and extended survival by evoking protective type 1 anti-tumor responses. Targeting the ER stress response should concomitantly inhibit tumor growth and enhance anti-cancer immunity, thus offering a unique approach to cancer immunotherapy. PMID:26073941

  18. Function of Helper T Cells in the Memory CTL-mediated Anti-tumor Immunity

    Institute of Scientific and Technical Information of China (English)

    高丰光; GermainJ.P.Fernendo; 刘文军

    2004-01-01

    Abstract To investigate the role of CD4+ helper T (Th) cells in the memory CTL-mediated anti-tumor immunity, the RAG-1 gene knock out mice were adoptively transferred with OT-1 cells to generate the memory CTL, the C57B1/6 mice immunized with the epitope peptide of OVA specific Th cells and with different adjuvants were adopfively transferred with these memory-CTLs, and then the animals were challenged with tumor cells EGT. It was found that although the simple immunization of mice with the epitope peptide of the OVA specific Th cells could generate more effect CTL, but this effect was not so strong enough to resist completely the challenges with tumor cells. Nevertheless, the memory CTL-mediated anti-tumor immune effect required the helps of Th1 and Th2 cells. The cross-regulation between Thl and Th2 cells seemed to be beneficial for the host to generate more effector CTL for mounting an efficient anti-tumor response. It concluded that the interaction between Thl and Th2 cells might be more important than the single subset of Th cells in the memory CTL-mediated anti-tumor immune response. More attention should be paid in this regard for the future studies.

  19. Camelliin B and nobotanin I, macrocyclic ellagitannin dimers and related dimers, and their antitumor activity.

    Science.gov (United States)

    Yoshida, T; Chou, T; Haba, K; Okano, Y; Shingu, T; Miyamoto, K; Koshiura, R; Okuda, T

    1989-11-01

    Camelliin B and nobotanin I, dimeric hydrolyzable tannins of a new class having macrocyclic structures, were isolated from Camellia japonica and Heterocentron roseum, respectively. Nobotanin G and H of the structures related to nobotanin I, were also obtained from H. roseum. Camelliin B and also woodfordin C, a macrocyclic dimer from Woodfordia fruticosa, exhibited marked host-mediated antitumor activities. PMID:2632067

  20. 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: 3.444, year: 2014

  1. A novel cationic lipid with intrinsic antitumor activity to facilitate gene therapy of TRAIL DNA.

    Science.gov (United States)

    Luo, Cong; Miao, Lei; Zhao, Yi; Musetti, Sara; Wang, Yuhua; Shi, Kai; Huang, Leaf

    2016-09-01

    Metformin (dimethylbiguanide) has been found to be effective for the treatment of a wide range of cancer. Herein, a novel lipid (1,2-di-(9Z-octadecenoyl)-3-biguanide-propane (DOBP)) was elaborately designed by utilizing biguanide as the cationic head group. This novel cationic lipid was intended to act as a gene carrier with intrinsic antitumor activity. When compared with 1,2-di-(9Z-octadecenoyl)-3-trimethylammonium-propane (DOTAP), a commercially available cationic lipid with a similar structure, the blank liposomes consisting of DOBP showed much more potent antitumor effects than DOTAP in human lung tumor xenografts, following an antitumor mechanism similar to metformin. Given its cationic head group, biguanide, DOBP could encapsulate TNF-related apoptosis-inducing ligand (TRAIL) plasmids into Lipid-Protamine-DNA (LPD) nanoparticles (NPs) for systemic gene delivery. DOBP-LPD-TRAIL NPs demonstrated distinct superiority in delaying tumor progression over DOTAP-LPD-TRAIL NPs, due to the intrinsic antitumor activity combined with TRAIL-induced apoptosis in the tumor. These results indicate that DOBP could be used as a versatile and promising cationic lipid for improving the therapeutic index of gene therapy in cancer treatment. PMID:27344367

  2. Enhanced Antitumor Efficacy and Reduced Toxicity of Docetaxel Loaded Estradiol Functionalized Stealth Polymeric Nanoparticles

    DEFF Research Database (Denmark)

    Jain, Sanyog; Spandana, Gollapalli; Agrawal, Ashish Kumar; Kushwah, Varun; Thanki, Kaushik

    2015-01-01

    antitumor efficacy in DMBA induced rat model demonstrated significant reduction in tumor volume in comparison with the plain counterpart (PLGA-NPs) and a marketed formulation, Taxotere. Moreover, the safety of the estradiol functionalized PLGA NPs was confirmed by hepato- and nephrotoxicity studies....

  3. Antitumoral materials with regenerative function obtained using a layer-by-layer technique

    Directory of Open Access Journals (Sweden)

    Ficai D

    2015-03-01

    Full Text Available Denisa Ficai,1 Maria Sonmez,1,2 Madalina Georgiana Albu,2 Dan Eduard Mihaiescu,1 Anton Ficai,1 Coralia Bleotu3 1Faculty of Applied Chemistry and Material Science, Politehnica University of Bucharest, 2Leather and Footwear Research Institute, National Research and Development Institute for Textiles and Leather, 3Stefan S Nicolau Institute of Virology, Romanian Academy, Bucharest, Romania Abstract: A layer-by layer technique was successfully used to obtain collagen/hydroxyapatite-magnetite-cisplatin (COLL/HAn-Fe3O4-CisPt, n=1–7 composite materials with a variable content of hydroxyapatite intended for use in the treatment of bone cancer. The main advantages of this system are the possibility of controlling the rate of delivery of cytostatic agents, the presence of collagen and hydroxyapatite to ensure more rapid healing of the injured bone tissue, and the potential for magnetite to be a passive antitumoral component that can be activated when an appropriate external electromagnetic field is applied. In vitro cytotoxicity assays performed on the COLL/HAn-Fe3O4-CisPt materials obtained using a layer-by layer method confirmed their antitumoral activity. Samples with a higher content of hydroxyapatite had more antitumoral activity because of their better absorption of cisplatin and consequently a higher amount of cisplatin being present in the matrices. Keywords: multifunctional materials, antitumoral activity, scaffold, bone grafts

  4. Hydrogels in endovascular embolization Part V. Antitumor agent methotrexate-containing p(HEMA)

    Czech Academy of Sciences Publication Activity Database

    Horák, Daniel; Gumargalieva, K. Z.; Zaikov, G. E.; Artsis, M. I.; Madyuskina, L. L.

    Hauppauge : Nova Science Publishers, 2010 - (Shishkina, L.; Zaikov, G.; Goloschapov, A.), s. 39-50 ISBN 978-1-60741-861-0 Institutional research plan: CEZ:AV0Z40500505 Keywords : antitumor agent * hydrogels * p(HEMA) Subject RIV: CD - Macromolecular Chemistry

  5. 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

  6. TRAF1/C5 but Not PTPRC Variants Are Potential Predictors of Rheumatoid Arthritis Response to Anti-Tumor Necrosis Factor Therapy

    Directory of Open Access Journals (Sweden)

    Helena Canhão

    2015-01-01

    Full Text Available Background. The aim of our work was to replicate, in a Southern European population, the association reported in Northern populations between PTPRC locus and response to anti-tumor necrosis factor (anti-TNF treatment in rheumatoid arthritis (RA. We also looked at associations between five RA risk alleles and treatment response. Methods. We evaluated associations between anti-TNF treatment responses assessed by DAS28 change and by EULAR response at six months in 383 Portuguese patients. Univariate and multivariate linear and logistic regression analyses were performed. In a second step to confirm our findings, we pooled our population with 265 Spanish patients. Results. No association was found between PTPRC rs10919563 allele and anti-TNF treatment response, neither in Portuguese modeling for several clinical variables nor in the overall population combining Portuguese and Spanish patients. The minor allele for RA susceptibility, rs3761847 SNP in TRAF1/C5 region, was associated with a poor response in linear and logistic univariate and multivariate regression analyses. No association was observed with the other allellic variants. Results were confirmed in the pooled analysis. Conclusion. This study did not replicate the association between PTPRC and the response to anti-TNF treatment in our Southern European population. We found that TRAF1/C5 risk RA variants potentially influence anti-TNF treatment response.

  7. Encapsulation of cisplatin in long-circulating and pH-sensitive liposomes improves its antitumor effect and reduces acute toxicity

    Directory of Open Access Journals (Sweden)

    Leite EA

    2012-10-01

    Full Text Available Elaine A Leite,1,2 Cristina M Souza,3 Álvaro D Carvalho-Júnior,1,2 Luiz GV Coelho,4 Ângela MQ Lana,5 Geovanni D Cassali,3 Mônica C Oliveira11Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 2Departamento de Farmácia, Faculdade de Ciências Biológicas e da Saúde, Universidade Federal dos Vales do Jequitinhonha e Mucuri, Diamantina, Minas Gerais, Brazil; 3Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 4Departamento de Clínica Médica, Instituto Alfa de Gastroenterologia, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; 5Departamento de Zootecnia, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, BrazilAbstract: Cisplatin (CDDP is one of the most effective and potent anticancer drugs used as first-line chemotherapy against several solid tumors. However, the severe side effects and its tendency to provoke chemoresistance often limit CDDP therapy. To avoid these inconveniences, the present study's research group developed long-circulating and pH-sensitive liposomes containing CDDP (SpHL-CDDP. The present study aimed to evaluate the antitumor effect and toxicity of SpHL-CDDP, as compared with that of free CDDP, and long-circulating and non-pH-sensitive liposomes containing CDDP (NSpHL-CDDP, after their intravenous administration in solid Ehrlich tumor-bearing mice. Antitumor activity was evaluated by analysis of tumor volume and growth inhibition ratio, serum vascular endothelial growth factor (VEGF levels, and histomorphometric and immunohistochemical studies. Body weight variation and the histological examination of bone marrow and kidneys were used as toxicity indicators. A significant reduction in the tumor volume and a higher tumor growth inhibition ratio was

  8. 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

  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. 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.

  11. 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

  12. Preimmunization of donor lymphocytes enhances antitumor immunity of autologous hematopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    Lymphopenia-induced homeostatic proliferation (HP) of T cells following autologous hematopoietic stem cell transplantation (HSCT) skews the T-cell repertoire by engaging tumor-associated antigens (TAAs), leading to an induction of antitumor immunity. Here, as the tumor-reactive lymphocytes preferentially proliferate during the condition of HP, we examined whether the priming of a donor lymphocytes to TAAs could enhance HP-induced antitumor immunity in autologous HSCT recipients. First, to examine whether the tumor-bearing condition of donor influences the antitumor effect of HSCT, the lymphocytes isolated from CT26 tumor-bearing mice were infused into lethally irradiated mice. The growth of tumors was substantially suppressed in the mice that received HSCT from a tumor-bearing donor compared with a naïve donor, suggesting that a fraction of donor lymphocytes from tumor-bearing mice are primed in response to TAAs and remain responsive upon transplantation. We previously reported that type I interferon (IFN) maturates the dendritic cells and promotes the priming of T cells. We then investigated whether the further priming of donor cells by IFN-α can strengthen the antitumor effect of HSCT. The intratumoral IFN-α gene transfer significantly increased the number of IFN-γ-positive lymphocytes in response to CT26 cells but not the syngeneic lymphocytes in donor mice. The infusion of primed donor lymphocytes markedly suppressed the tumor growth in recipient mice, and cured 64% of the treated mice. Autologous HSCT with the infusion of primed donor lymphocytes is a promising strategy to induce an effective antitumor immunity for solid cancers

  13. 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

  14. Melphalan antitumor efficacy and hepatotoxicity: the effect of variable infusion duration in the hepatic artery.

    Science.gov (United States)

    Rothbarth, Joost; Woutersen, Ruud A; Sparidans, Rolf W; van de Velde, Cornelis J H; Mulder, Gerard J

    2003-06-01

    The optimum conditions (duration and concentration) of a fixed dose, intra-arterial melphalan infusion in relation to its antitumor effect and toxicity in the liver were investigated in a rat colon tumor model (CC531) of liver metastases. We studied the difference in tumor and liver uptake, as well as antitumor effect and hepatotoxicity after 5- and 20-min hepatic arterial infusion (HAI) of a fixed melphalan dose. Melphalan content in perfusate, liver, and tumor tissue was analyzed by high-performance liquid chromatography. The antitumor effect and hepatotoxicity in rats treated either systemically or with 5- and 20-min HAI, with a fixed dose melphalan (4.4 micromol), were assessed 2 weeks after treatment. No difference in melphalan content of tumor/liver tissue or antitumor effect was observed between rats treated with 5- and 20-min HAI. Hepatotoxicity was strongly affected by perfusion duration/concentration, however. Rats treated with 5-min HAI weighed significantly less, and liver toxicity parameters were significantly increased compared with those of all other groups; eight of nine rats showed severe cholangiofibrosis. Body weights and liver toxicity parameters of the rats treated with 20-min HAI were not statistically different from the control group. In conclusion, duration of HAI with 4.4 micromol of fixed dose melphalan did not affect tumor uptake and antitumor effect, but the resulting increase in melphalan concentration had major impact on hepatobiliary toxicity. Therefore, in a clinical setting, caution should be taken when infusion duration and concentration of melphalan are changed. PMID:12606622

  15. APLICAÇÃO DAS MACROTENDÊNCIAS NO GERENCIAMENTO DAS MARCAS CONTEMPORÂNEAS

    Directory of Open Access Journals (Sweden)

    Janiene dos Santos e Silva

    2010-02-01

    Full Text Available A investigação das tendências comportamentais e suas possíveis manifestações nos cenários de consumo é fundamental para as marcas definirem suas estratégias mercadológicas e construírem vínculos mais duradouros com seus consumidores. Existem diversas empresas fornecedoras de metodologias de pesquisa que sistematizam essas tendências, disponibilizando-as para uso dos profissionais de marketing e branding. A proposta do presente artigo é associar as tendências atuais no gerenciamento de marcas e os comportamentos emergentes na sociedade, resultado do contexto sociocultural, econômico e político. Trata-se, portanto, de um texto predominantemente teórico, ainda que expresse a pesquisa documental realizada junto aos institutos de pesquisa no país que atuam no segmento de tendências comportamentais.

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

    International Nuclear Information System (INIS)

    Irradiation of spore-endotoxin mixtures from Bacillus thuringiensis cultures at 254 nm (60 μW cm-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). (author)

  17. 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.

  18. Anti-tumor effect and influence of Gekko gecko Linnaeus on the immune system of sarcoma 180-bearing mice.

    Science.gov (United States)

    You, Qi; Han, Shiyu; Zhang, Yuanlong; Zheng, Jianhua

    2009-01-01

    Gekko gecko Linnaeus (GgL) is an extract used in traditional Chinese medicine. In the present study, we examined the anti-tumor activity of GgL and its effect on the immune system of mice. Sarcoma 180-bearing mice were used as the animal model, and cisplatin was applied as the positive control drug. The mice were randomly divided into six groups, and each group was treated with a different drug or drug concentration. The effects of GgL were evaluated based on its anti-tumor activity and prolongation of the lifespan, the lymphocyte transformation rate and pathological changes observed in the tumors. The results suggest that GgL has anti-tumor activities and up-regulates the immune system in a dose-dependent manner. This study provides original data related to the anti-tumor and immune up-regulating function of GgL. PMID:21475868

  19. Tratamento farmacológico das psicoses na epilepsia

    OpenAIRE

    Guarnieri Ricardo; Hallak Jaime Eduardo Cecílio; Walz Roger; Velasco Tonicarlo Rodrigues; Alexandre Júnior Veriano; Terra-Bustamante Vera Cristina; Wichert-Ana Lauro; Sakamoto Américo Ceiki

    2004-01-01

    A epilepsia é uma das causas mais comuns de incapacidade funcional. Comorbidades psiquiátricas, como as psicoses, estão freqüentemente associadas à epilepsia. Psicoses na epilepsia (PNE) requerem tratamento farmacológico mais cuidadoso, levando-se em conta a propensão dos antipsicóticos (AP) em provocar crises convulsivas e o risco de interação farmacocinética com as drogas antiepilépticas (DAE). Após uma breve descrição da classificação e das principais características clínicas das PNE, fora...

  20. Das Metabolische Syndrom - Beginn des "Tödlichen Quartetts"?

    Directory of Open Access Journals (Sweden)

    Toplak H

    2005-01-01

    Full Text Available Das Metabolische Syndrom (MetSy ist heute der entscheidende Risikofaktor der Sklerose der großen Gefäße und damit verantwortlich für die Mehrzahl der Todesfälle – auch in Österreich. Die Definition des MetSy wurde in den letzten Jahren einem leichten Wandel unterzogen. Die Klassifikationen (vor allem WHO und NCEP-ATP-III nähern sich marginal unterschiedlich entweder via Insulinresistenz oder Fettverteilung an den Menschen, und sind daher naturgemäß in Grenzfällen nicht 100 % deckungsgleich, obwohl die meisten "schwerer betroffenen" Patienten dann in beiden Schemata als MetSy klassifiziert werden. Wir haben gelernt, daß die androide Adipositasform und damit das viszerale Fett zentraler Triggerfaktor des MetSy ist und auch zahlreiche neuere makrovaskuläre Risikofaktoren, wie Akutphasenproteine, Entzündungsmediatoren und prokoagulatorische Zustände, beeinflußt. Die oft erst später hinzutretende Blutzuckerstoffwechselstörung bis hin zum Diabetes mellitus Typ II selbst verursacht mehrheitlich zusätzlich die Mikroangiopathien. Das "Tödliche Quartett" ist verwandt mit der NCEP-Definition des MetSy, es wurde ihm als Folge der "Upper Body Obesity" und des assoziierten Risikoclusters (Glukosetoleranzstörung, Hypertriglyzeridämie und Hypertonie der vaskuläre Tod angelastet. Das "Tödliche Quartett" ist dem MetSy also verwandt und eher als sein Vollbild zu verstehen, das naturgemäß damit zuerst auftreten kann. Die neuesten aktuellen IDF-Richtlinien 2005 (IDF Consensus worldwide definition of the metabolic syndrome in clinical practice gehen noch einen Schritt weiter und nehmen den Bauchumfang auf niedrigerem Level als bisher (Mann 94 und Frau 80 cm als unabdingbaren Parameter in die Klassifikation des MetSy auf, die anderen beiden Risikofaktoren sind variabel. Das entspricht auch den Grundlinien des Autors.

  1. Antitumor effect of sFlt-1 gene therapy system mediated by Bifidobacterium Infantis on Lewis lung cancer in mice

    OpenAIRE

    Zhu, H; Z. Li; Mao, S.; Ma, B.; S. Zhou; Deng, L.; Liu, T; Cui, D.; Zhao, Y.; He, J.; C. Yi; Huang, Y.

    2011-01-01

    Soluble fms-like tyrosine kinase receptor (sFlt-1) is a soluble form of extramembrane part of vascular endothelial growth factor receptor-1 (VEGFR-1) that has antitumor effects. Bifidobacterium Infantis is a kind of non-pathogenic and anaerobic bacteria that may have specific targeting property of hypoxic environment inside of solid tumors. The aim of this study was to construct Bifidobacterium Infantis-mediated sFlt-1 gene transferring system and investigate its antitumor effect on Lewis lun...

  2. Fibronectin-mediated Calmette-Guerin bacillus attachment to murine bladder mucosa. Requirement for the expression of an antitumor response.

    OpenAIRE

    Kavoussi, L R; Brown, E J; Ritchey, J K; Ratliff, T L

    1990-01-01

    Adjuvant intravesical Calmette-Guerin bacillus (BCG) is an effective treatment for superficial bladder cancer. The mechanisms by which BCG mediates antitumor activity are not known. We investigated the initial interaction of BCG with the bladder mucosa to determine whether binding was essential for the development of antitumor activity. Herein, we show that bladder urothelial disruption induced by acrolein, adriamycin, or electrocautery resulted in BCG binding in areas of urothelial damage. B...

  3. Ang-2/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival

    OpenAIRE

    Kloepper, Jonas; Riedemann, Lars; Amoozgar, Zohreh; Seano, Giorgio; Susek, Katharina; Yu, Veronica; Dalvie, Nisha; Amelung, Robin L.; Datta, Meenal; Song, Jonathan W.; Askoxylakis, Vasileios; Taylor, Jennie W.; Lu-Emerson, Christine; Batista, Ana; Kirkpatrick, Nathaniel D.

    2016-01-01

    Improving survival of patients with glioblastoma (GBM) using antiangiogenic therapy remains a challenge. In this study we show that dual blockade of angiopoietin-2 and vascular endothelial growth factor delays tumor growth and enhances survival benefits through reprogramming of tumor-associated macrophages toward an antitumor phenotype as well as by pruning immature tumor vessels. The antitumor immunomodulatory potential of this dual blockade supports clinical testing of this approach for GBM...

  4. Politische Bildung und das Web 2.0

    OpenAIRE

    Heike Schaumburg

    2011-01-01

    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 s...

  5. Benjamin revisited. Das Kunstwerk im Zeitalter der digitalen Medien

    OpenAIRE

    Sauer, Martina

    2011-01-01

    Hat das Werk eines Künstlers mit seiner technischen Reproduzierbarkeit bzw. der Tatsache, dass es womöglich ausschließlich als ein flüchtiges, wegklickbares Objekt existiert überhaupt noch den Status eines Kunstwerks? Es sind nicht die technischen Möglichkeiten, seien es analoge oder digitale, so lässt sich im Anschluss an die Relektüre von Benjamins für die Medientheorie grundlegenden Aufsatz aufzeigen, die das Kunstwerk ausmachen, sondern dessen Möglichkeit durch Brüche ("Chockwirkungen") s...

  6. O modelo de financiamento das Forças Armadas

    OpenAIRE

    Mata, João

    2013-01-01

    Num contexto de grandes dificuldades económico-financeiras que afetam atualmente o país, a escassez dos recursos disponíveis trás à luz do dia a discussão sobre as funções do Estado, nela se inserindo a questão da sustentabilidade das próprias Forças Armadas (FFAA). O presente estudo pretende assim analisar o modelo de financiamento das FFAA portuguesas, tendo por objetivo identificar eventuais deficiências e lacunas e propor alterações que contribuam para criar um modelo mais equilibrado ...

  7. Impacto da crise no consumo das famílias

    OpenAIRE

    Duarte, Daniela Alexandra Oliveira

    2014-01-01

    Este estudo pretende estudar as áreas do consumo mais relevantes no quotidiano das famílias portuguesas. Deste modo, pretende-se analisar as alterações ocorridas nos hábitos das famílias perante alterações do rendimento recorrentes da crise internacional, dado que esta está a ter grandes impactos nas famílias portuguesas devido às medidas de restrição orçamental implementadas pelo governo. A classificação dos diferentes tipos de consumo de acordo com os trabalhos de Engel e Pasinetti pode ...

  8. Modelos de democracia na era das transições

    OpenAIRE

    Ribeiro, Adelia Maria Miglievich; Coutinho, George Gomes

    2006-01-01

    O artigo reúne perspectivas acerca da democracia contemporânea, seus desafios e possibilidades, de quatro importantes autores vinculados, em suas especificidades, à chamada teoria crítica. Ellen Wood, Jürgen Habermas, Boaventura de Sousa Santos e Claus Offe são convocados para a terefa de esclarecimento do polissêmico conceito de democracia e expressar a crise mesma do fenômeno que se busca nomear, portanto, das idéias de representação e de participação, das relações entre o político e o econ...

  9. Das molekulare Unbewusste : Bemerkung zum Anti-Ödipus

    OpenAIRE

    Schäfer, Armin

    2012-01-01

    Gilles Deleuze und Félix Guattari haben ein polemisches Buch geschrieben, das seinen Gegner im Titel benennt: Anti-Ödipus. Kapitalismus und Schizophrenie. Man fände kein Ende, wenn man allen seinen Bezügen zur Psychoanalyse nachgehen wollte. Als es 1972 herauskommt, wird es als Rück fall hinter deren Errungenschaften kritisiert. André Green zieht einen Vergleich mit Sigmunds Freuds voranalytischen Schriften: [...] Worauf der Vergleich aus ist, ist ein Tertium comparationis, das in der Rolle d...

  10. Harry Potter - das Trauma als Motor der psychischen Entwicklung

    OpenAIRE

    Subkowski, Peter

    2004-01-01

    In den Harry Potter-Bänden wird exemplarisch die psychische Entwicklung eines traumatisierten Jungen von der frühen verinnerlichten Mutterliebe über das massive Verlusttrauma zur Zeit der analen Phase und der kumulativen Traumatisierung durch die Vernachlässigung und das Gequältwerden bei seinen Verwandten dargestellt. Über die Identifikation mit seinem Vater und anderen Ersatzvätern erwirbt sich Harry Potter schließlich Selbstvertrauen und gewinnt neue Freunde. Harry durchläuft dab...

  11. Partial purification of a Bacillus licheniformis levansucrase producing levan with antitumor activity.

    Science.gov (United States)

    Dahech, Imen; Belghith, Karima Srih; Belghith, Hafedh; Mejdoub, Hafedh

    2012-10-01

    The extracellular fructosyltransferase (FTase) of a novel strain of Bacillus licheniformis capable of producing fructooligosaccharides (FOS) and a polysaccharide type levan was obtained and partially purified. The purification was achieved by ammonium sulfate precipitation, DEAE cellulose and gel filtration chromatographies. The enzyme was partially purified as determined by SDS-PAGE, and the specific activity reached was 67.5, representing a purification factor of 177 and yield of 40%. Levan was isolated from the cultures of B. licheniformis. The levan was composed mainly of fructose residues when analyzed by TLC after acid hydrolysis and NMR analysis. In a previous study, the levan produced exhibited a hypoglycemiant activity. The present paper deals with the study of the antitumor and anti-cytotoxic effect of levan produced by B. licheniformis strain. In the in vitro antitumor activity test of levan against some tumor cell lines, relatively the significantly high activity was observed against the HepG(2). PMID:22579870

  12. Antitumor and immunomodulatory activity of water-soluble polysaccharide from Inonotus obliquus.

    Science.gov (United States)

    Fan, Liuping; Ding, Shaodong; Ai, Lianzhong; Deng, Kequan

    2012-10-01

    The medicinal mushroom Inonotus obliquus has been used as a folk remedy for a long time in Russia and East-European countries to treat gastrointestinal cancer, cardiovascular disease and diabetes. In our study, a water-soluble polysaccharide (ISP2a) was successfully purified from I. obliquus by DEAE-Sepharose CL-6B and Sepharose CL-6B column chromatography. In vivo ISP2a had not only shown antitumor activity, but also could significantly enhance the immune response of tumor-bearing mice. In addition, ISP2a significantly enhanced the lymphocyte proliferation and increased the production of TNF-α. Results of these studies demonstrated that ISP2a had a potential application as natural antitumor agent with immunomodulatory activity. PMID:22840014

  13. Preconditioning Vaccine Sites for mRNA-Transfected Dendritic Cell Therapy and Antitumor Efficacy.

    Science.gov (United States)

    Batich, Kristen A; Swartz, Adam M; Sampson, John H

    2016-01-01

    Messenger RNA (mRNA)-transfected dendritic cell (DC) vaccines have been shown to be a powerful modality for eliciting antitumor immune responses in mice and humans; however, their application has not been fully optimized since many of the factors that contribute to their efficacy remain poorly understood. Work stemming from our laboratory has recently demonstrated that preconditioning the vaccine site with a recall antigen prior to the administration of a dendritic cell vaccine creates systemic recall responses and resultantly enhances dendritic cell migration to the lymph nodes with improved antitumor efficacy. This chapter describes the generation of murine mRNA-transfected DC vaccines, as well as a method for vaccine site preconditioning with protein antigen formulations that create potent recall responses. PMID:27076169

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

    Directory of Open Access Journals (Sweden)

    Giovanni Zummo

    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.

  15. 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

  16. An investigation on the anti-tumor properties of FSH33-53-Lytic

    International Nuclear Information System (INIS)

    A new designed hybrid peptide FSH33-53-Lytic was synthesized and expected to combine the follicle stimulating hormone receptor (FSHR) targeting and tumor cell membranes disintegration. Through in vitro and vivo study, no significant enhancement on anti-tumor activity was shown compared with Lytic peptide only. We also prepared 18F-Al-NOTA-MAL-FSH33-53-Lytic and use microPET image to observe the FSHR targeting of FSH33-53-Lytic. No accumulation in the tumor may explain the failure of FSH33-53-Lytic on cancer therapy. In summary, microPET image can provide more accurate and visible information for screening new anti-tumor agents. (author)

  17. Enhanced antitumor effect and mechanism of chemotherapy combined with low dose radiation

    International Nuclear Information System (INIS)

    It is well known that whole body irradiation (WBI) with low dose X-rays could improve the function of the immunological system and the antitumor efficacy of local large dose irradiation. In order to study the adjuvant effect of WBI with low dose on the tumor suppressive effect of chemotherapy, 6 hours before mitomycin C or cyclophosphamide I.P. administration, WBI with 75 mGy was given to C57BL/6 mice bearing Lewis Lung carcinoma. It was found that WBI with 75 mGy X-rays could markedly enhanced the suppressive effect of chemotherapy on tumor and significantly increase some immunological parameters related to tumor killing. The results suggested that WBI with 75 mGy X-rays could reduce the immunological damage of tumor-bearing mice caused by chemotherapy and enhance the antitumor efficacy of cytotoxic agents

  18. Green synthesis and characterization of gold nanoparticles using extract of anti-tumor potent Crocus sativus

    Science.gov (United States)

    Vijayakumar, R.; Devi, V.; Adavallan, K.; Saranya, D.

    2011-12-01

    In the present study, we have explored anti-tumor potent Crocus sativus (saffron) as a reducing agent for one pot size controlled green synthesis of gold nanoparticles (AuNps) at ambient conditions. The nanoparticles were characterized using UV-vis, scanning electron microscope (SEM), high resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD) and FTIR analysis. The prepared AuNPs showed surface Plasmon resonance centered at 549 nm with average particle size of 15±5 nm. Stable, spherical and triangular crystalline AuNPs with well-defined dimensions were synthesized using anti-tumor potent Crocus sativus (saffron). Crystalline nature of the nanoparticles is confirmed from the HR-TEM, SAED and SEM images, and XRD patterns. From the FTIR spectra it is found that the biomolecules are responsible for capping in gold nanoparticles.

  19. Anticancer and Antitumor Potential of Fucoidan and Fucoxanthin, Two Main Metabolites Isolated from Brown Algae

    Directory of Open Access Journals (Sweden)

    Soheil Zorofchian Moghadamtousi

    2014-01-01

    Full Text Available Seaweed is one of the largest producers of biomass in marine environment and is a rich arsenal of active metabolites and functional ingredients with valuable beneficial health effects. Being a staple part of Asian cuisine, investigations on the crude extracts of Phaeophyceae or brown algae revealed marked antitumor activity, eliciting a variety of research to determine the active ingredients involved in this potential. The sulfated polysaccharide of fucoidan and carotenoid of fucoxanthin were found to be the most important active metabolites of brown algae as potential chemotherapeutic or chemopreventive agents. This review strives to provide detailed account of all current knowledge on the anticancer and antitumor activity of fucoidan and fucoxanthin as the two major metabolites isolated from brown algae.

  20. ANTITUMOR ACTIVITY OF METHANOLIC EXTRACT OF TERMINALIA CATAPPA LEAVES AGAINST EHRLICH ASCITES INDUCED CARCINOMA IN MICE

    Directory of Open Access Journals (Sweden)

    Saroja M

    2011-12-01

    Full Text Available Terminalia catappa belongs to the family combretaceae and is popularly known as badam.It is a well known herb in Ayurvedic system of medicine The aim of the present study is to evaluate the effect of methanolic extract of leaves of Terminalia catappa against Ehrlich ascetic Lymphoma (ELA in Swiss albino mice.The tumor was induced in mice by intraperitoneal injection of ELA cells (1X106cells/mice. Methanolic extract of Terminalia catappa was administered to the experimental animals at a dose of 75µg/kg/day after 24 h of tumor inoculation. The antitumor effect of extract was evaluated by assessing in vitro cytotoxicity, increase in lifespan, hematological parameters and liver enzymes. The methanolic extract brought back the altered levels of the hematological parameters and liver enzymes. Thus the present study revealed that methanolic extract of Terminalia catappa possessed significant antitumor activity.

  1. Enhanced antitumor reactivity of tumor-sensitized T cells by interferon alfa

    Energy Technology Data Exchange (ETDEWEB)

    Vander Woude, D.L.; Wagner, P.D.; Shu, S.; Chang, A.E. (Univ. of Michigan, Ann Arbor (USA))

    1991-03-01

    Tumor-draining lymph node cells from mice bearing the methylcholanthrene-induced MCA 106 tumors can be sensitized in vitro to acquire antitumor reactivity. We examined the effect of interferon alfa on the function of cells that underwent in vitro sensitization in adoptive immunotherapy. Interferon alfa increased the antitumor reactivity of in vitro sensitized cells in the treatment of MCA 106 pulmonary metastases. This effect was evident in irradiated mice, indicating that a host response to the interferon alfa was not required. Interferon alfa treatment increased class I major histocompatibility complex antigen expression on tumor cells and increased their susceptibility to lysis by in vitro sensitized cells. These results suggest that interferon alfa enhancement of adoptive immunotherapy was mediated by its effect on tumor cells. Interferon alfa may be a useful adjunct to the adoptive immunotherapy of human cancer.

  2. EXPERIMENT STUDIES OF ANTITUMOR PROLIFERATION AND METASTASIS OF A NEW CHINESE HERB AT-1

    Institute of Scientific and Technical Information of China (English)

    曲迅; 郑广娟; 杨美香; 周文; 赵丽霞

    2003-01-01

    Objective: To study the effects of a new Chinese herb AT-1 on the tumor cell proliferation and metastasis in vitro. Methods: Tumor cell proliferation activity was tested by MTT. The ability of tumor cell invasion and migration was assayed by counting the number of tumor cells going throw matrigel. The expression changes of CD44 genes in PG cells treated with AT-1 were tested by FACS. Results: Compared with the control, the proliferation activity of the cells treated with the At-1 was restrained. The invasion and migration ability of PG cells and the expression of the cell adherence related gene CD44 was decreased treatment with AT-1. Conclusion: AT-1 is a new antitumor proliferation and metastasis agent. Its antitumor metastasis effect might be achieved by decreasing the expression of the cell adherence-associate gene CD44.

  3. The antitumor efficiency of combined electrochemotherapy and single dose irradiation on a breast cancer tumor model

    International Nuclear Information System (INIS)

    The aim of this study was to investigate the antitumor effectiveness of electrochemotherapy with cisplatin combined with suboptimal radiotherapy doses. Tumor radiosensitization was evaluated on large invasive ductal carcinoma tumors in Balb/C mice. Tumors of an average volume of 630 mm3 were treated with cisplatin, electric pulses, radiotherapy, electrochemotherapy, alone as well as in appropriate combinations. Tumors were irradiated with Cobalt-60 γ-rays at doses 3 Gy and 5 Gy in combination with electrochemotherapy using cisplatin. Controls included each of the treatments alone as well as the combination of the radiotherapy with electric pulses alone or with cisplatin alone. Antitumor effectiveness was evaluated by tumor growth delay, tumor-doubling time, inhibition ratio and the objective response rates. As anticipated, electrochemotherapy was more effective than the treatment with cisplatin alone or the application of the electric pulses alone. When treatments were combined with tumor irradiation at either 3 or 5 Gy, the combination with electrochemotherapy was more effective: at 5 Gy, 2 animals out of 8 were in complete remission 100 days later. In general the higher 5 Gy dose of γ-radiation was more effective than the lower one of 3 Gy. The results of our study demonstrate that irradiation doses, 3 Gy or 5 Gy, increase the antitumor effectiveness of electrochemotherapy with cisplatin on invasive ductal carcinoma tumors. Good antitumor results were achieved in experimental tumors with a size comparable to clinical lesions, demonstrating that this three-modality combined treatment is useful for the treatment of large lesions even at sub-optimal radiotherapy doses

  4. Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity

    OpenAIRE

    Aaes, Tania Løve; Kaczmarek, Agnieszka; Delvaeye, Tinneke; De Craene, Bram; De Koker, Stefaan; Heyndrickx, Liesbeth; Delrue, Iris; Taminau, Joachim; Wiernicki, Bartosz; De Groote, Philippe; Garg, Abhishek; Leybaert, Luc; Grooten, Johan; Bertrand, Mathieu J. M.; Agostinis, Patrizia

    2016-01-01

    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 ...

  5. In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

    OpenAIRE

    Nogueira, Daniele R.; Tavano, Lorena; Mitjans Arnal, Montserrat; Pérez Muñoz, Lourdes; Infante Martínez-Pardo, Ma. Rosa; Vinardell Martínez-Hidalgo, Ma. Pilar

    2013-01-01

    Nanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from Nα,Nε-dioctanoyl lysine with an inorgan...

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

    OpenAIRE

    2014-01-01

    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...

  7. Crocin Exhibits Antitumor Effects on Human Leukemia HL-60 Cells In Vitro and In Vivo

    OpenAIRE

    Yan Sun; Hui-Juan Xu; Yan-Xia Zhao; Ling-Zhen Wang; Li-Rong Sun; Zhi Wang; Xiu-Fang Sun

    2013-01-01

    Crocin is a carotenoid of the saffron extract that exhibits antitumor activity against many human tumors. However, the effects of crocin on HL-60 cells in vivo have not been evaluated. This study aimed to examine the effects of crocin on HL-60 cells in vitro and in vivo and investigate the underlying mechanisms. HL-60 cells were treated by crocin, and cell proliferation, apoptosis, and cell cycle profiles were examined by MTT assay, AO/EB staining, and flow cytometry, respectively. Furthermor...

  8. Synthesis and biological evaluation of some polymethoxylated fused pyridine ring systems as antitumor agents.

    Science.gov (United States)

    Rostom, Sherif A F; Hassan, Ghada S; El-Subbagh, Hussein I

    2009-10-01

    A series of 3,5-bis(arylidene)-4-piperidones like chalcone analogues carrying variety of methoxylated aryl groups, pyrazolo[4,3-c]pyridines, pyrido[4,3-d]pyrimidines, and pyrido[3,2-c]pyridines, carrying an arylidene moiety, and some pyrano[3,2-c]pyridines, like flavone and coumarin isosteres, were synthesized and screened for their in-vitro antitumor activity at the National Cancer Institute (NCI, USA). The tested compounds 7, 9, 10, 12, 13, 15, 17, and 19 exhibited a broad spectrum of antitumor activity. Compounds belonging to the pyrazolo[4,3-c]pyridine series proved to be more active than those of the pyrido[3,2-c]pyridine and pyrano[3,2-c]pyridine analogues, in which the monomethoxylated derivatives showed better antitumor activity when compared with their corresponding dimethoxylated congeners. Compound 7 is considered to be the most active member identified in this study with a broad spectrum of activity against 22 different tumor cell lines belonging to the nine subpanels employed, and a particular effectiveness against the breast cancer T-47D cell line (GI 54.7%). The pyrano[3,2-c]pyridine heterocyclic system 19 proved to be the most active antitumor agent among the six-membered fused pyridines, with variable activity against 18 different tumor cell lines, and special activity against the non-small cell lung cancer Hop-92 and ovarian cancer OVCAR-4 cell lines (GI values 63.9 and 48.5%, respectively). PMID:19714673

  9. Prophylactic Antitumor Effect of Mixed Heat Shock Proteins/Peptides in Mouse Sarcoma

    Institute of Scientific and Technical Information of China (English)

    Yu Wang; Shu-Yun Liu; Mei Yuan; Yu Tang; Quan-Yi Guo; Xue-Mei Cui; Xiang Sui

    2015-01-01

    Background:To develop a vaccine-based immunotherapy for sarcoma,we evaluated a mixture of heat shock proteins (mHSPs) as a vaccine for sarcoma treatment in a mouse model.Heat shock protein/peptides (HSP/Ps) are autoimmune factors that can induce both adaptive and innate immune responses;HSP/Ps isolated from tumors can induce antitumor immune activity when used as vaccines.Methods:In this study,we evaluated the effects of mHSP/Ps on prophylactic antitumor immunity.We extracted mHSP/Ps,including HSP60,HSP70,GP96,and HSP l 10,from the mouse sarcoma cell lines S 180 and MCA207 using chromatography.The immunity induced by mHSP/Ps was assessed using flow cytometry,ELISPOT,lactate dehydrogenase release,and enzyme-linked immunosorbent assay.Results:Of S180 sarcoma-beating mice immunized with mHSP/Ps isolated from S180 cells,41.2% showed tumor regression and long-term survival,with a tumor growth inhibition rate of 82.3% at 30 days.Of MCA207 sarcoma-bearing mice immunized with mHSP/Ps isolated from MCA207 cells,50% showed tumor regression and long-term survival with a tumor growth inhibition rate of 79.3%.All control mice died within 40 days.The proportions of natural killer cells,CD8+,and interferon-γ-secreting cells and tumor-specific cytotoxic T-lymphocyte activity were increased in the immunized group.Conclusions:Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors.This mHSP/P vaccine exerted greater antitumor effects than did HSPT0,HSP60,or tumor lysates alone.

  10. 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.

  11. Anticancer and Antitumor Potential of Fucoidan and Fucoxanthin, Two Main Metabolites Isolated from Brown Algae

    OpenAIRE

    Soheil Zorofchian Moghadamtousi; Hamed Karimian; Ramin Khanabdali; Mahboubeh Razavi; Mohammad Firoozinia; Keivan Zandi; Habsah Abdul Kadir

    2014-01-01

    Seaweed is one of the largest producers of biomass in marine environment and is a rich arsenal of active metabolites and functional ingredients with valuable beneficial health effects. Being a staple part of Asian cuisine, investigations on the crude extracts of Phaeophyceae or brown algae revealed marked antitumor activity, eliciting a variety of research to determine the active ingredients involved in this potential. The sulfated polysaccharide of fucoidan and carotenoid of fucoxanthin were...

  12. Supramolecular nanoparticles generated by the self-assembly of polyrotaxanes for antitumor drug delivery

    OpenAIRE

    Liu R; Lai YS; He B; Li Y; Wang G; Chang S; Gu Z

    2012-01-01

    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(ethy...

  13. CYP24A1 Inhibition Enhances the Antitumor Activity of Calcitriol

    OpenAIRE

    Muindi, Josephia R.; Yu, Wei-Dong; Ma, Yingyu; Engler, Kristie L.; Kong, Rui-Xian; Trump, Donald L.; Johnson, Candace S.

    2010-01-01

    High systemic exposures to calcitriol are necessary for optimal antitumor effects. Human prostate cancer PC3 cells are insensitive to calcitriol treatment. Therefore, we investigated whether the inhibition of 24-hydroxylase (CYP24A1), the major calcitriol inactivating enzyme, by ketoconazole (KTZ) or RC2204 modulates calcitriol serum pharmacokinetics and biologic effects. Dexamethasone (Dex) was added to minimize calcitriol-induced hypercalcemia and as a steroid replacement for the KTZ inhibi...

  14. ESR of copper and iron complexes with antitumor and cytotoxic properties.

    OpenAIRE

    Antholine, W E; Kalyanaraman, B.; Petering, D H

    1985-01-01

    The relatively few iron and copper metal complexes which have been examined in cells and tissues for their redox properties, radical generation properties, and antitumor activity are discussed for studies which utilized electron spin resonance spectroscopy (ESR). A common property of a number of metal complexes, which include bleomycin, adriamycin, and thiosemicarbazones described in this review, is that they are readily reduced by thiol compounds and oxidized by oxygen or reduced species of ...

  15. Lovastatin potentiates antitumor activity and improves hemorheology in lewis lung carcinoma in C57 mice

    Institute of Scientific and Technical Information of China (English)

    Tian-luoLEI; Xue-junLI

    2004-01-01

    AIM: Lovastatin is commonly used in the clinic to treat hypercholesterolemia. The aim of the present studies was to investigate whether lovastatin had an antitumor activity on lewis lung carcinoma and evaluate whether lovastatin had a direct effect on hemorheology in tumor model. METHODS: The C57 mice which with lewis lung carcinoma were treated with lovastatin at concentrations of 10, 20, and 40 mg/kg ig for 21 d. We exam-

  16. The Potential of Intralesional Rose Bengal to Stimulate T-Cell Mediated Anti-Tumor Responses

    OpenAIRE

    Maker, Ajay V; Prabhakar, Bellur; Pardiwala, Krunal

    2015-01-01

    Rose Bengal (RB) is a red synthetic dye that was initially used in the garment industry and has been used safely for decades as a corneal stain by ophthalmologists. Antineoplastic properties of RB have also been observed, though the mechanism of action remained to be elucidated. Recently, interest in RB as a therapeutic cancer treatment has increased due to significant anti-tumor responses with direct tumor injection in human clinical trials for metastatic melanoma. In these patients, there h...

  17. 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

  18. Anti-tumor activity of calcitriol: pre-clinical and clinical studies.

    Science.gov (United States)

    Trump, Donald L; Hershberger, Pamela A; Bernardi, Ronald J; Ahmed, Sharmilla; Muindi, Josephia; Fakih, Marwan; Yu, Wei-Dong; Johnson, Candace S

    2004-05-01

    1,25-Dihydroxycholecalciferol (calcitriol) is recognized widely for its effects on bone and mineral metabolism. Epidemiological data suggest that low Vitamin D levels may play a role in the genesis of prostate cancer and perhaps other tumors. Calcitriol is a potent anti-proliferative agent in a wide variety of malignant cell types. In prostate, breast, colorectal, head/neck and lung cancer as well as lymphoma, leukemia and myeloma model systems calcitriol has significant anti-tumor activity in vitro and in vivo. Calcitriol effects are associated with an increase in G0/G1 arrest, induction of apoptosis and differentiation, modulation of expression of growth factor receptors. Glucocorticoids potentiate the anti-tumor effect of calcitriol and decrease calcitriol-induced hypercalcemia. Calcitriol potentiates the antitumor effects of many cytotoxic agents and inhibits motility and invasiveness of tumor cells and formation of new blood vessels. Phase I and II trials of calcitriol either alone or in combination with carboplatin, taxanes or dexamethasone have been initiated in patients with androgen dependent and independent prostate cancer and advanced cancer. Data indicate that high-dose calcitriol is feasible on an intermittent schedule, no dose-limiting toxicity has been encountered and optimal dose and schedule are being delineated. Clinical responses have been seen with the combination of high dose calcitriol+dexamethasone in androgen independent prostate cancer (AIPC) and apparent potentiation of the antitumor effects of docetaxel have been seen in AIPC. These results demonstrate that high intermittent doses of calcitriol can be administered to patients without toxicity, that the MTD is yet to be determined and that calcitriol has potential as an anti-cancer agent. PMID:15225831

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

    OpenAIRE

    Lin-Tao Han; Ying Fang; Ming-Ming Li; Hong-Bing Yang; Fang Huang

    2013-01-01

    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 sapon...

  20. Metabolic inhibition of galectin-1-binding carbohydrates accentuates anti-tumor immunity

    OpenAIRE

    Cedeno-Laurent, Filiberto; Opperman, Matthew; Barthel, Steven R.; Hays, Danielle; Schatton, Tobias; Zhan, Qian; He, Xiaoying; Matta, Khushi L.; Supko, Jeffrey G; Frank, Markus H; Murphy, George F.; Dimitroff, Charles J

    2011-01-01

    Galectin-1 (Gal-1) has been shown to play a major role in tumor immune escape by inducing apoptosis of effector leukocytes and correlating with tumor aggressiveness and disease progression. Targeting the Gal-1 – Gal-1 ligand axis, thus, represents a promising cancer therapeutic approach. Here, to test the Gal-1-mediated tumor immune evasion hypothesis and demonstrate the importance of Gal-1-binding N-acetyllactosamines in controlling the fate and function of anti-tumor immune cells, we treate...

  1. Anti-inflammatory, antioxidant and antitumor activities of ingredients of Curcuma phaeocaulis Val

    OpenAIRE

    Hou, Yan; Lu, Chuan-li; Zeng, Qiao-Hui; Jiang, Jian-Guo

    2015-01-01

    Curcuma phaeocaulis Val. is used in Chinese Pharmacopoeia as health food and folk medicine for removing blood stasis, alleviating pain and tumor therapy. This research was aimed to explore and compare three main bioactivities including anti-oxidant, antitumor and anti-inflammatory activities between the ethanol extract of C. Phaeocaulis and its fractions using different in vitro models. Firstly, 70 % ethanol was used to extract C. Phaeocaulis, and then the crude extract was re-extracted, resu...

  2. Antitumor activity and pharmacokinetics of podophyllotoxin incorporated into solid lipid nanoparticles

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    To evaluate the antitumor activity and pharmacokinetics of podophyllotoxin(PPT) incorporated into solid lipid nanoparticles(SLN),Kunming mice inoculated with flesh tumor were used as animal model.The mice received a single daily intraperitoneal injection of PPT in 20% ethanol(5 mg/kg) and PPT-SLN(5 mg/kg in PPT) for 3 weeks.Gross tumor volumes,body weight and clinical observations were recorded daily.The mice were sacrificed for 24 h after the last administration,and the tumor inhibition rate was calculated with the tumor weight.For the pharmacokinetics research,the mice were treated with intraperitoneal injection of PPT(10 mg/kg) and PPT-SLN(10 mg/kg in PPT).Blood samples were collected at different time to determine the PPT concentration in plasma by HPLC.Blood drug level-time curve was made and pharmacokinetic parameters were calculated.As a result of drug administration,the tumor volume and weight of the mice injected with PPT-SLN were significantly restrained compared with mice treated with PPT or negative control.The tumor inhibition rate of 58.13% showed a significant antitumor activity of PPT-SLN.At the same time,the increased weight gain of the mice injected with PPT-SLN suggested a reduced toxicity of PPT in SLN.Pharmacokinetics study displayed a higher blood concentration,a prolonged circulation time,and an increased bioavailability of PPT-SLN compared with those of PPT.Our results demonstrated that PPT-SLN could optimize pharmacokinetics,enhance antitumor activity and attenuate toxicity,so it has a promising prospect for the application in anti-tumor treatment.

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

    International Nuclear Information System (INIS)

    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.)

  4. Actividad antimicrobiana y antitumoral de la variabilina y sus enantiomeros aislados de ircinia felix

    OpenAIRE

    Salama, Ahmen; Gamboa Estrada, Marlen; Pinzón Orjuela, Mauricio

    2008-01-01

    El presente trabajo muestra un amplio espectro antimicrobiano para la variabilina y sus enantiomeros siendo activos contra los microorganismos Gram (+) Micrococcus luteus, Staphylococcus aureus y Bacillus subtilis y los microorganismos Gram (-) Pseudomonas sp, Enterobacter aerogenes y Escherichia coli. Los compuestos no mostraron actividad contra los hongos Aspergillus tamari, Aspergillus niger y Penicillium sp, en las concentraciones ensayadas. El efecto antitumoral en disco de zanahoria se ...

  5. Alkyl Caffeates Improve the Antioxidant Activity, Antitumor Property and Oxidation Stability of Edible Oil

    OpenAIRE

    Wang, Jun; Gu, Shuang-Shuang; Pang, Na; Wang, Fang-Qin; Pang, Fei; Cui, Hong-Sheng; Wu, Xiang-Yang; Wu, Fu-An

    2014-01-01

    Caffeic acid (CA) is distributed widely in nature and possesses strong antioxidant activity. However, CA has lower solubility in non-polar media, which limits its application in fat-soluble food. To increase the lipophilicity of natural antioxidant CA, a series of alkyl caffeates were synthesized and their antioxidant and antitumor activities were investigated. The antioxidant parameters, including the induction period, acid value and unsaturated fatty acid content, of the alkyl caffeates in ...

  6. Anti-tumor targeted drug delivery systems mediated by aminopeptidase N/CD13

    OpenAIRE

    Xun Wang; Bin Wang; Qiang Zhang

    2011-01-01

    Aminopeptidase N (APN)/CD13 is a transmembrane glycoprotein, which is overexpressed on tumor neovascular endothelial cells and most tumor cells, where it plays an important role in tumor angiogenesis. Peptides containing the Asn-Gly-Arg (NGR) motif can specifically recognize APN/CD13 allowing them to act as tumor-homing peptides for the targeted delivery of anti-tumor drugs to tumor neovascular endothelial cells and tumor cells. This article reviews the literature and recent developments rela...

  7. OX40 engagement and chemotherapy combination provides potent antitumor immunity with concomitant regulatory T cell apoptosis

    OpenAIRE

    Hirschhorn-Cymerman, Daniel; Rizzuto, Gabrielle A.; Merghoub, Taha; Cohen, Adam D.; Avogadri, Francesca; Lesokhin, Alexander M.; Weinberg, Andrew D.; Wolchok, Jedd D; Houghton, Alan N.

    2009-01-01

    Expansion and recruitment of CD4+ Foxp3+ regulatory T (T reg) cells are mechanisms used by growing tumors to evade immune elimination. In addition to expansion of effector T cells, successful therapeutic interventions may require reduction of T reg cells within the tumor microenvironment. We report that the combined use of the alkylating agent cyclophosphamide (CTX) and an agonist antibody targeting the co-stimulatory receptor OX40 (OX86) provides potent antitumor immunity capable of regressi...

  8. Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity

    OpenAIRE

    Ostrand-Rosenberg, Suzanne

    2010-01-01

    Myeloid-derived suppressor cells (MDSC) accumulate in most cancer patients and experimental animals with cancer. They accumulate in response to pro-inflammatory mediators and they use a variety of mechanisms to block both innate and adaptive antitumor immunity. Because of their critical role in obstructing immune responses, MDSC are a strategic obstacle to immunotherapies that require activation of the host’s cell-mediated and innate immune responses. Following a brief description of the fact...

  9. 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

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

    OpenAIRE

    Chen, Gaimin; Gong, Rudong

    2016-01-01

    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 prep...

  11. Rag2-/-;gammac-/- immunodeficient mice, a new preclinical model to study antitumor approaches

    OpenAIRE

    Antognoli, Agnese

    2010-01-01

    Animal models have been relevant to study the molecular mechanisms of cancer and to develop new antitumor agents. Anyway, the huge divergence in mouse and human evolution made difficult the translation of the gained achievements in preclinical mouse based studies. The generation of clinically relevant murine models requires their humanization both concerning the creation of transgenic models and the generation of humanized mice in which to engraft a functional human immune system, and reprodu...

  12. Alopecia secondary to anti-tumor necrosis factor-alpha therapy *

    OpenAIRE

    Ribeiro, Lara Beatriz Prata; Rego, Juliana Carlos Gonçalves; Estrada, Bruna Duque; Bastos, Paula Raso; Piñeiro Maceira, Juan Manuel; Sodré, Celso Tavares

    2015-01-01

    Biologic drugs represent a substantial progress in the treatment of chronic inflammatory immunologic diseases. However, its crescent use has revealed seldom reported or unknown adverse reactions, mainly associated with anti-tumor necrosis factor (anti-TNF). Psoriasiform cutaneous reactions and few cases of alopecia can occur in some patients while taking these drugs. Two cases of alopecia were reported after anti-TNF therapy. Both also developed psoriasiform lesions on the body. This is the s...

  13. Pure multiplicative stochastic resonance of anti-tumor model with seasonal modulability

    OpenAIRE

    Zhong, Wei-Rong; Shao, Yuan-Zhi; He, Zhen-Hui

    2006-01-01

    The effects of pure multiplicative noise on stochastic resonance in an anti-tumor system modulated by a seasonal external field are investigated by using theoretical analyses of the generalized potential and numerical simulations. For optimally selected values of the multiplicative noise intensity quasi-symmetry of two potential minima and stochastic resonance are observed. Theoretical results and numerical simulations are in good quantitative agreement.

  14. Selective Antitumor Activity of Ibrutinib in EGFR-Mutant Non–Small Cell Lung Cancer Cells

    OpenAIRE

    Gao, Wen; Wang, Michael; Wang, Li; Lu, Haibo; Wu, Shuhong; Dai, Bingbing; Ou, Zhishuo; Zhang, Liang; Heymach, John V.; Gold, Kathryn A.; Minna, John ,; Roth, Jack A.; Hofstetter, Wayne L.; Swisher, Stephen G.; Fang, Bingliang

    2014-01-01

    Ibrutinib, which irreversibly inhibits Bruton tyrosine kinase, was evaluated for antitumor activity in a panel of non–small cell lung cancer (NSCLC) cell lines and found to selectively inhibit growth of NSCLC cells carrying mutations in the epidermal growth factor receptor (EGFR) gene, including T790M mutant and erlotinib-resistant H1975 cells. Ibrutinib induced dose-dependent inhibition of phosphor-EGFR at both Y1068 and Y1173 sites, suggesting ibrutinib functions as an EGFR inhibitor. Survi...

  15. Synthesis and antitumor evaluation of novel sulfonylcycloureas derived from nitrogen mustard.

    Science.gov (United States)

    Cheloufi, H; Belhani, B; Ouk, T S; Zerrouki, R; Aouf, N-E; Berredjem, M

    2016-05-01

    A new series of sulfonylcycloureas derivatives have been synthesized and evaluated in vitro for their antitumor activity against four cancer cell lines (A431, Jurkat, U266, and K562). These compounds were prepared by the condensation of several sulfonamides (2a-m) with ethyl bis(2-chloroethyl)carbamate (1a). The relative cytotoxicity of these new derivatives in comparison to chlorambucil is reported. PMID:26597910

  16. Pharmaceutical development and manufacturing of a parenteral formulation of a novel antitumor agent, VNP40101M

    OpenAIRE

    Krishna, Gopal; Hodnick, William F.; Lang, Wengsheng; Lin, Xu; Karra, Srinivasa; Mao, John; Almassian, Bijan

    2001-01-01

    The objective of this study was to develop and manufacture a stable parenteral formulation for Phase I clinical trials of VNP40101M (1,2-Bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(2-methylamino)carbonyl] hydrazine), a novel antitumor agent. The solubility and stability of the drug was determined. Solubility studies suggested that VNP40101M exhibited poor aqueous solubility but showed appreciable solubility in nonaqueous solvents. The aqueous solubility of the drug could not be increased by adj...

  17. CCL21/IL21-armed oncolytic adenovirus enhances antitumor activity against TERT-positive tumor cells.

    Science.gov (United States)

    Li, Yang; Li, Yi-Fei; Si, Chong-Zhan; Zhu, Yu-Hui; Jin, Yan; Zhu, Tong-Tong; Liu, Ming-Yuan; Liu, Guang-Yao

    2016-07-15

    Multigene-armed oncolytic adenoviruses are capable of efficiently generating a productive antitumor immune response. The chemokine (C-C motif) ligand 21 (CCL21) binds to CCR7 on naïve T cells and dendritic cells (DCs) to promote their chemoattraction to the tumor and resultant antitumor activity. Interleukin 21 (IL21) promotes survival of naïve T cells while maintaining their CCR7 surface expression, which increases their capacity to transmigrate in response to CCL21 chemoattraction. IL21 is also involved in NK cell differentiation and B cell activation and proliferation. The generation of effective antitumor immune responses is a complex process dependent upon coordinated interactions of various subsets of effector cells. Using the AdEasy system, we aimed to construct an oncolytic adenovirus co-expressing CCL21 and IL21 that could selectively replicate in TERTp-positive tumor cells (Ad-CCL21-IL21 virus). The E1A promoter of these oncolytic adenoviruses was replaced by telomerase reverse transcriptase promoter (TERTp). Ad-CCL21-IL21 was constructed from three plasmids, pGTE-IL21, pShuttle-CMV-CCL21 and AdEasy-1 and was homologously recombined and propagated in the Escherichia coli strain BJ5183 and the packaging cell line HEK-293, respectively. Our results showed that our targeted and armed oncolytic adenoviruses Ad-CCL21-IL21 can induce apoptosis in TERTp-positive tumor cells to give rise to viral propagation, in a dose-dependent manner. Importantly, we confirm that these modified oncolytic adenoviruses do not replicate efficiently in normal cells even under high viral loads. Additionally, we investigate the role of Ad-CCL21-IL21 in inducing antitumor activity and tumor specific cytotoxicity of CTLs in vitro. This study suggests that Ad-CCL21-IL21 is a promising targeted tumor-specific oncolytic adenovirus. PMID:27157859

  18. CpG Oligodeoxynucleotide1826 combined with radioresistant cancer cell vaccine confers significant antitumor effects.

    Science.gov (United States)

    Zhuang, X B; Xing, N; Zhang, Q; Yuan, S J; Chen, W; Qiao, T K

    2015-01-01

    Immunotherapy is a hot issue in cancer research over the years and tumor cell vaccine is one of the increasing number of studies. Although the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. CpG Oligodeoxynucleotides (CpG ODNs), synthetic oligonucleotides containing a cytosine-phosphate-guanine(CpG) motif, was shown to enhance immune responses to a wide variety of antigens. In this study, we generated the radioresistant Lewis lung cancer cell by repeated X-ray radiation and inactivated it as a whole tumor cell vaccine to enhance the immunogenicity of tumor cell vaccine. Mice were subcutaneously immunized with this inactivated vaccine combined with CpG ODN1826 and then inoculated with autologous Lewis lung cancer (LLC) to estimate the antitumor efficacy. The results showed that the radioresistant tumor cell vaccine combined with CpG ODN1826 could significantly inhibit tumor growth, increased survival of the mice and with 20% of the mice surviving tumor free in vivo compared with the unimmunized mice bearing LLC tumor. A significant increase of apoptosis was also observed in the tumor prophylactically immunized with vaccine of inactivated radioresistant tumor cell plus CpG ODN1826. The potent antitumor effect correlated with higher secretion levels of tumor necrosis factor-alpha(TNF-α) and lower levels of interleukin-10(IL-10) concentration in serum. Furthermore, the results suggested that the antitumor mechanism was probably depended on the decreased level of programmed death ligand-1(PD-L1) which plays an important role in the negative regulation of immune response by the inhibition of tumor antigen-specific T cell activation. These findings clearly demonstrated that the radioresistant tumor cell vaccine combined with CpG ODN1826 as an appropriate adjuvant could induce effective antitumor immunity in vivo. PMID:26458317

  19. Radionuclide imaging of primary renal-cell carcinoma by I-131-labeled antitumor antibody

    International Nuclear Information System (INIS)

    A goat antibody against human renal-cell carcinoma reacted on immunofluorescence with renal-cell carcinomas from 20 patients, but not with normal adult human tissues, including kidney. After i.v. administration the I-131-linked antibody showed preferential tumor localization in six of seven patients with primary renal carcinoma. Labeled antitumor antibodies may have the specificity for tumor imaging that current radiopharmaceuticals lack

  20. Preparation and Sonodynamic Antitumor Effect of Protohemin-Conjugated Multiwalled Carbon Nanotubes Functionalized with Carboxylic Group.

    Science.gov (United States)

    Wang, Chuan-Jin; Li, Wei

    2016-05-01

    Preclinical Research Sonodynamic therapy (SDT) is a cutting edge approach to treating cancer that involves necrosis and/or apoptosis. Multiwalled carbon nanotubes functionalized with carboxylic groups (MWCNTs-COOH) due their physicochemical structure represent a novel drug delivery system in the field of nanomedicine. The purpose of the research reported in this paper was to increase the antitumor potency and reduce the potential side effects of protohemin (Ph), a sonosensitizer for SDT, which was noncovalently encapsulated into MWCNTs-COOH (MWCNTs-Ph). The Ph loading efficiency in MWCNTs-COOH carrier was determined as approximately 68.8% (w/w). The growth inhibition rate of MWCNTs-Ph (Ph: 180 μg/mL) was approximately 95 ± 8.5%, whereas Ph-F (Ph: 180 μg/mL) inhibited 58 ± 4.5% of tumor cell. Ph (Ph: 180 μg/mL) alone had no antitumor effect in HepG-2 cells using ultrasound treatment at 1.0 MHz and 0.5 W/cm(2) for 100 s. Assessment of the antitumor effects of MWCNTs-Ph and Ph-F at day 11 after SDT showed that he tumor inhibition ratio for MWCNTs-Ph (6.18 × 10(-2) g·kg(-1) ·d(-1) ) was 82.8%, twice that of Ph-F (6.18 × 10(-2) g·kg(-1) ·d(-1) ) ay 41.8%. In conclusion, MWCNTs-Ph had increased antitumor efficiency and also decreased potential side effects. Drug Dev Res 77 : 152-158, 2016. © 2016 Wiley Periodicals, Inc. PMID:27029561

  1. EVOLUÇÃO DAS ORGANIZAÇÕES POR MEIO DAS ABORDAGENS INSTITUCIONAL, ECOLOGIA DAS ORGANIZAÇÕES E EQUILÍBRIO PONTUADO

    Directory of Open Access Journals (Sweden)

    Ana Clarissa Santos

    2013-01-01

    Full Text Available Dentro do paradigma funcionalista, caracterizado pelo objetivismo filosófico e pela sociologia da manutenção do status quo, a teoria institucional e da ecologia das organizações são amplamente estudadas para explicar por que as organizações podem ser, paradoxalmente, tão diferentes e tão semelhantes. A teoria da ecologia das organizações defende que existe grande diferença entre as organizações e, com o passar do tempo, aquelas mais adaptadas são selecionadas pelo ambiente. Isso faz com que as empresas se mantenham mais semelhantes, seja, simplesmente, pela própria seleção, seja pela busca da uniformidade àquelas que são bem sucedidas. Essa é a ideia central da teoria institucional, em que a existência dos isomorfismos coercitivo, mimético e normativo padroniza as organizações. Ocorrendo uma mudança importante no ambiente, o ciclo reinicia, havendo uma nova seleção e a consequente busca do isomorfismo. Finalmente, pode-se observar que uma teoria complementa a outra, gerando um ciclo para a existência das organizações, que não podem ser vistas como excludentes.

  2. USING OF C60 FULLERENE COMPLEXES WITH ANTITUMOR DRUGS IN CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    S. V. Prylutska

    2014-06-01

    Full Text Available The literature data and own research results concerning antitumor effect in vitro and in vivo of C60 fullerene and its derivatives, cytostatics, and conjugated systems on their basis, which enable the practical application of C60 in combined chemotherapy for treatment efficacy improving of malignant tumors are generalized. The mechanism of antitumor action of C60 fullerene in combined treatment with cytostatics is based on antioxidant properties of its molecule, thereby reducing toxic side effects of traditional drugs in a body and ability to their transport purposefully into the target cells. The unique structure of C60 enables to modify its surface with chemotherapeutic drugs. Under combined action of the "fullerene C60-chemotherapy drug" conjugate the anti-tumor effects enhancement is observed both in vitro and in vivo, namely quantity reduction of viable tumor cells, tumor reduction etc. Furthermore, protective effects of fullerene C60 and derivatives relatively toxic effects of chemotherapeutic agents in a body were observed. Conjugate auxesis empowers it to be kept longer in a cell and prolong the duration of drug action. Ability of fullerene C60 to selective accumulation provides its using for target drug delivery.

  3. Folate-conjugated beta-cyclodextrin-based polymeric micelles with enhanced doxorubicin antitumor efficacy.

    Science.gov (United States)

    Zhang, Lu; Lu, Jiafei; Jin, Yangmin; Qiu, Liyan

    2014-10-01

    In order to enhance the antitumor effects of doxorubicin (DOX), a novel micellar vector with high DOX loading and tumor targeting function based on folate-conjugated amphiphilic copolymer folate-poly(ethylene glycol)-poly(d,l-lactide)-β-cyclodextrin (FA-PEL-CD) was constructed. Cytotoxicity and cellular uptake experiments were performed in HeLa, KB, and A549 cell lines expressing different amounts of folate receptors in order to evaluate the targeting effect of the folate modification. The antitumor experiments performed in a KB cell-xenografted nude mouse model showed that the treatment with 10mg/kg DOX loaded FA-PEL-CD micelles achieved approximately 86% of tumor growth inhibition compared to the control. Ex vivo fluorescence imaging experiments and histological examination confirmed that folate modification can enhance the antitumorigenesis efficacy and reduce the cardiotoxicity of DOX. These results suggest that FA-PEL-CD copolymer-based micelles are promising nanocarriers for targeted doxorubicin delivery, with improved antitumor efficacy and reduced toxicity in normal tissues. PMID:25058857

  4. Cloning and biological activity of an anti-tumor peptide of Tumstatin

    Institute of Scientific and Technical Information of China (English)

    WANG Shujing; LIU Yan; LIN Xuesong; FU Xue; XU Jianyong; LIU Xinghan

    2007-01-01

    To obtain an anti-tumor peptide of Tumstatin and detect its biological activity,the nucleotide sequence encoding 185-203 amino acids (19peptide) of Tumstatin was synthesized and inserted into the fusion protein vector pTYB2.After identification by sequencing and restriction endonucleases,the recombined vector was transformed into BL-21 (DE3) E.coli competent cells.Transformed E.coli BL-21 (DE3) were induced by isopropyl-β-thiogalactopyranoside (IPTG),and then expressed.By 1,4-dithiothreitol (DTT)reduction,the soluble 19peptide was obtained from a chitin affinity chromatograph.The biological activity of 19peptide was determined by 3-[4,5-dimethylthiazol-2-y1]-2,5-diphenytetrazolium bromide (MTT) assay,cell growth curve,the effect of the ascitic fluid transfevent H22 hepatoma on mice and via histopathological slices.The purified 19peptide directly inhibited proliferation and migration of murine B16 melanoma cells,SMMC-7721hepatoma carcinoma cells and human umbilical vein endothelial cells (HUVEC).The tumor inhibition rate of mice ascitic fluid transfevent H22 hepatoma was 48.46%.Histopathological slices showed that it could promote tumor tissue necrosis and decrease the density of blood vessels.With higher anti-tumor activity,19peptide has the potential to become a novel,potent anti-tumor agent.

  5. Anti-Tumor Activity of a Novel Protein Obtained from Tartary Buckwheat

    Directory of Open Access Journals (Sweden)

    Huiyuan Yao

    2010-12-01

    Full Text Available TBWSP31 is a novel antitumor protein that was isolated from tartary buckwheat water-soluble extracts. The objective of this paper was to investigate the anti-proliferative effects of TBWSP31 on breast cancer Bcap37cells and to explore its possible mechanism. After treatment of Bcap37 cells with TBWSP31, typical apoptotic morphological changes were observed by inverted microscopy and scanning electron microscopy (SEM, such as detachment from the culture plate, change to a round shape, cell shrinkage, the absence of obvious microvilli, plasma membrane blebbing, and formation of apoptotic bodies. Cell-cycle analysis revealed that treatment with TBWSP31 resulted in a G0/G1 arrest and prevented the cells from growing from G0/G1 phase to S phase, which was most prominent at 48 h. The expression of bcl-2 and Fas were detected quantitatively by FCM, which showed that TBWSP31 induced-apoptosis may be involved with the participation of Fas and bcl-2. These results suggest that TBWSP31 is a potential antitumor compound and that apoptosis induced by TBWSP31 is a key antitumor mechanism.

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

    Directory of Open Access Journals (Sweden)

    ClaireVanpouille-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.

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

    International Nuclear Information System (INIS)

    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

  8. Antimicrobial and antitumor activities of chitosan from shiitake stipes, compared to commercial chitosan from crab shells.

    Science.gov (United States)

    Chien, Rao-Chi; Yen, Ming-Tsung; Mau, Jeng-Leun

    2016-03-15

    Chitosan was prepared by alkaline N-deacetylation of chitin obtained from shiitake stipes and crab shells and its antimicrobial and antitumor activities were studied. Chitosan from shiitake stipes and crab shells exhibited excellent antimicrobial activities against eight species of Gram positive and negative pathogenic bacteria with inhibition zones of 11.4-26.8mm at 0.5mg/ml. Among chitosan samples, shiitake chitosan C120 was the most effective with inhibition zones of 16.4-26.8mm at 0.5mg/ml. In addition, shiitake and crab chitosan showed a moderate anti-proliferative effect on IMR 32 and Hep G2 cells. At 5mg/ml, the viability of IMR 32 cells incubated with chitosan was 68.8-85.0% whereas that of Hep G2 cells with chitosan was 60.4-82.9%. Overall, shiitake chitosan showed slightly better antimicrobial and antitumor activities than crab chitosan. Based on the results obtained, shiitake and crab chitosan were strong antimicrobial agents and moderate antitumor agents. PMID:26794761

  9. Antitumor and antimicrobial activities of endophytic fungi from medicinal parts of Aquilaria sinensis

    Institute of Scientific and Technical Information of China (English)

    Jin-long CUI; Shun-xing GUO; Pei-gen XIAO

    2011-01-01

    The purpose of this study was to isolate and characterize endophytic fungi from the stem tissue which can produce fragrant ingredients in Aquilaria sinensis (also called agarwood) to determine their antitumor and antimicrobial activities. Twenty-eight fungal endophytes were isolated from agarwood by strict sterile sample preparation and were classified into 14 genera and 4 taxonomic classes (Sordariomycetes, Dothideomycetes, Saccharomycetes, and Zygomycetes) based on molecular identification. Of the 28 isolates, 13 (46.4%) showed antimicrobial activity against at least one of the test strains by the agar well diffusion method, and 23 isolates (82.1%) displayed antitumor activity against at least one of five cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay. The diameters of inhibition zones of YNAS07, YNAS14, HNAS04, HNAS05, HNAS08, and HNAS11 were equal to or higher than 14.0 mm against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, B. subtilis, Aspergillus fumigatus, and B. subtilis, respectively. The inhibition rates of YNAS06, YNAS08, and HNAS06 were not less than 60% to 293-T, 293-T, and SKVO3 cells, respectively. These results suggest that the endophytic fungi associated with agarwood will provide us with not only useful micro-ecological information, but also potential antimicrobial and antitumor agents.

  10. Osthole promotes anti-tumor immune responses in tumor-bearing mice with hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Lurong; Jiang, Guorong; Yao, Fei; Liang, Guoqiang; Wang, Fei; Xu, Heng; Wu, Yan; Yu, Xiao; Liu, Haiyan

    2015-06-01

    Osthole, a natural coumarin derivative, has been shown to have anti-tumor and anti-inflammatory activity. However, the effect of osthole on anti-tumor immune responses in tumor-bearing mice has not yet been reported. In the present study, osthole treatment did not affect the weight and the coefficient of thymus and spleen in tumor-bearing mice with hepatocellular carcinoma (HCC). However, osthole administration significantly elevated the proportion and number of the splenic CD8(+) T cells, the proportion of CD4(+) T and CD8(+) T cells in tumor tissues, and the levels of IL-2 and TNF-α in the serum of HCC tumor-bearing mice. Our results suggested that osthole could promote the activation of the tumor-infiltrating CD4(+) T and CD8(+) T cells, and elevate the proportion of CD4(+) and CD8(+) effector T cells. Osthole treatment also significantly decreased the proportion of CD4(+)CD25(+)Foxp3(+) regulatory T cells in the spleen. Taken together, osthole could enhance the T cell mediated anti-tumor immune responses in the tumor-bearing mice with HCC. PMID:25975579

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

    International Nuclear Information System (INIS)

    Objective: To study the anti-tumor effect of a recombinant plasmid expressing human interleukin-12 (pEGFP-CIIL- 12) in vivo and in vitro. Methods: We transduct the recombinant gene (pEGFP-CIIL-12) to liver cancer cell HepG2 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 VX2 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-ClIL-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)

  12. 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. PMID:26152290

  13. Synthesis and anti-tumor activity evaluation of rhein-aloe emodin hybrid molecule.

    Science.gov (United States)

    Yuan, Ye-Fei; Hu, Xiang-Yu; He, Ying; Deng, Jia-Gang

    2012-02-01

    To improve the anti-tumor effects of rhein and aloe-emodin, a rhein-aloe-emodin hybrid molecule (RH-AE) was synthesized from rhein and aloe-emodin in the presence of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP). Chemical and spectroscopic methods, such as 1H and 13C NMR spectroscopy, and HR-ESIMS were used for the structure identification of RH-AE. Using the cell counting kit-8 (CCK-8) assay, the in vitro anti-tumor effects were compared between RH-AE, rhein and aloe-emodin on human hepatoma HepG2, human nasopharyngeal carcinoma CNE, human lung cancer NCI-H460, human ovarian cancer SK-OV-3, and human cervical cancer Hela cells. The results showed that the half inhibitory concentration (IC50) of RH-AE on HepG2, CNE, NCI-H460, SK-OV-3, and Hela cells were significantly lower than those of rhein and aloe-emodin. This showed that RH-AE has a better in vitro anti-tumor effect than rhein and aloe-emodin. PMID:22474959

  14. Study on the Antitumor Effects of Low-energy Laser Irradiation Combined with Cyclophosphamide

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Systematic experiments about the antitumor effects of low-energy laser irradiation combined with the traditional antitumor medicine of cyclophosphamide were conducted using the experimental model of mouse S180 ascites sarcoma.The three groups of tumor bearing mice were irradiated upon the inner corners with the dosages of 11.00,14.67 and 22.00 J*cm-2 LELI respectively,and injected with CYT intraperitoneally to observe the changes of the survival time,the ascites growth speed,and the kinetic changes of immune functions.The survival times of the three groups of CYT/LELI combination were obviously longer than those of the tumor and CYT control groups.Correspondingly,the amounts of ascites,tumor cells densities and total tumor cells in CYT/LELI groups decreased significantly,while the death ratio of the tumor cells increased.Comparatively,the group of 22.00 J*cm-2 LELI combined with CYT showed the most ideal antitumor effects,and the life prolongation ratio was up to 53.20%.

  15. Synergistic antitumor efficacy of combined DNA vaccines targeting tumor cells and angiogenesis.

    Science.gov (United States)

    Yin, Xiaotao; Wang, Wei; Zhu, Xiaoming; Wang, Yu; Wu, Shuai; Wang, Zicheng; Wang, Lin; Du, Zhiyan; Gao, Jiangping; Yu, Jiyun

    2015-09-18

    To further enhance the antitumor efficacy of DNA vaccine, we proposed a synergistic strategy that targeted tumor cells and angiogenesis simultaneously. In this study, a Semliki Forest Virus (SFV) replicon DNA vaccine expressing 1-4 domains of murine VEGFR2 and IL12 was constructed, and was named pSVK-VEGFR2-GFc-IL12 (CAVE). The expression of VEGFR2 antigen and IL12 adjuvant molecule in 293T cells in vitro were verified by western blot and enzyme-linked immune sorbent assay (ELISA). Then CAVE was co-immunized with CAVA, a SFV replicon DNA vaccine targeting survivin and β-hCG antigens constructed previously. The antitumor efficacy of our combined replicon vaccines was evaluated in mice model and the possible mechanism was further investigated. The combined vaccines could elicit efficient humoral and cellular immune responses against survivin, β-hCG and VEGFR2 simultaneously. Compared with CAVE or CAVA vaccine alone, the combined vaccines inhibited the tumor growth and improved the survival rate in B16 melanoma mice model more effectively. Furthermore, the intratumoral microvessel density was lowest in combined vaccines group than CAVE or CAVA alone group. Therefore, this synergistic strategy of DNA vaccines for tumor treatment results in an increased antitumor efficacy, and may be more suitable for translation to future research and clinic. PMID:26253468

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

    Science.gov (United States)

    Cassinelli, Giuseppe

    2016-06-01

    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. PMID:27103205

  17. Antitumor activities and immunomodulatory of rice bran polysaccharides and its sulfates in vitro.

    Science.gov (United States)

    Wang, Li; Li, Yulin; Zhu, Lidan; Yin, Ran; Wang, Ren; Luo, Xiaohu; Li, Yongfu; Li, Yanan; Chen, Zhengxing

    2016-07-01

    Polysaccharides purified from rice bran show antitumor activity against tumor cells, yet the mechanism of this action remains poorly understood. To address this issue, our study evaluated the effect of rice bran polysaccharides on mouse melanoma cell line B16, and Raw264.7 macrophages. Rice bran polysaccharides (RBP) failed to inhibit B16 cell growth in vitro. However, Raw264.7 macrophages treated by RBP enhancement of cytotoxic effects. The cytotoxicity was confirmed by the stimulation of nitric oxide (NO) production and tumor necrosis factor-α (TNF-α) secretion on Raw264.7 macrophages in a dose-dependent manner. RBP2, a fraction of RBP, notably enhanced the inhibition of B16 cells and boosted the immunepotentiation effect compared with RBP. To further enhance the inhibition of B16 cell growth, sulfated polysaccharides (SRBP) was derived using the chlorosulfonic acid-pyridine method. SRBP2 was found to suppress B16 cell growth, reduce B16 cell survival and stimulate NO and TNF-α production. However, SRBP2 displayed a cytotoxic effect on Raw264.7 macrophages. These results suggest that the antitumor activity of RBP and RBP2 is mediated mainly through the activation of macrophages. SRBP2 exerts its antitumor activity by inducing apoptosis in tumor cells and the secretion of NO and TNF-α. PMID:27064087

  18. Current development of Pd(II) complexes as potential antitumor agents.

    Science.gov (United States)

    Gao, Enjun; Liu, Cong; Zhu, Mingchang; Lin, Huakuan; Wu, Qiong; Liu, Lei

    2009-03-01

    Research has proven that the most effective and widely used metal-containing chemotherapy anticancer drugs are cisplatin ([cis-PtCl(2)(NH(3))(2)]) and many platinum complexes, however, these compounds have significant disadvantages including poor water solubility and serious side effects. Thus researches in order to overcome these shortcomings have never interrupted. Many non-platinum complexes have been synthesized and tested, in which some palladium complexes show significant antitumor activity in normal tumor cells and lower resistance of tumor cells to clinical treatments as well as lower side effects. Mononuclear palladium complexes with aromatic N-containing ligands, amino acid ligands, S-donor ligands, and P-containing ligands have respective qualities and properties due to the different structures and properties of the ligands; some dinuclear palladium complexes possess interesting steric structures and good antitumor activity; a try to modify natural medicines with Pd(2+) leads the research to a new route. In this review, medicinal chemistry, the development status and interactions of palladium complexes with DNA are discussed in order to provide guidance and determine structure and antitumor activity relationships for continuing studies of these systems. PMID:19275527

  19. Transcytosis, Antitumor Activity and Toxicity of Staphylococcal Enterotoxin C2 as an Oral Administration Protein Drug

    Science.gov (United States)

    Zhao, Wenbin; Li, Yangyang; Liu, Wenhui; Ding, Ding; Xu, Yingchun; Pan, Liqiang; Chen, Shuqing

    2016-01-01

    Staphylococcal enterotoxin C2 (SEC2) is a classical superantigen (SAg), which can tremendously activate T lymphocytes at very low dosage, thus exerting its powerful antitumor activity. As an intravenous protein drug and a bacterial toxin, SEC2 has some limitations including poor patient compliance and toxic side effects. In this research, we devoted our attention to studying the antitumor activity and toxicity of SEC2 as a potential oral administration protein drug. We proved that His-tagged SEC2 (SEC2-His) could undergo facilitated transcytosis on human colon adenocarcinoma (Caco-2) cells and SEC2-His was detected in the blood of rats after oral administration. Furthermore, oral SEC2-His caused massive cytokine release and immune cell enrichment around tumor tissue, leading to inhibition of tumor growth in vivo. Meanwhile, although SEC2-His was dosed up to 32 mg/kg in mice, no significant toxicity was observed. These data showed that SEC2 can cross the intestinal epithelium in an immunologically integral form, maintaining antitumor activity but with reduced systemic toxicity. Therefore, these results may have implications for developing SEC2 as an oral administration protein drug. PMID:27322320

  20. Antitumor activity of the novel multi-kinase inhibitor EC-70124 in triple negative breast cancer.

    Science.gov (United States)

    Cuenca-López, María Dolores; Serrano-Heras, Gemma; Montero, Juan Carlos; Corrales-Sánchez, Verónica; Gomez-Juarez, Mónica; Gascón-Escribano, Maria José; Morales, Jorge Carlos; Voisin, Veronique; Núñez, Luz Elena; Morís, Francisco; Bader, Gary D; Pandiella, Atanasio; Ocaña, Alberto

    2015-09-29

    Disseminated triple negative breast cancer (TNBC) is an incurable disease with limited therapeutic options beyond chemotherapy. Therefore, identification of druggable vulnerabilities is an important aim. Protein kinases play a central role in cancer and particularly in TNBC. They are involved in many oncogenic functions including migration, proliferation, genetic stability or maintenance of stem-cell like properties. In this article we describe a novel multi-kinase inhibitor with antitumor activity in this cancer subtype. EC-70124 is a hybrid indolocarbazole analog obtained by combinatorial biosynthesis of Rebeccamycin and Staurosporine genes that showed antiproliferative effect and in vivo antitumoral activity. Biochemical experiments demonstrated the inhibition of the PI3K/mTOR and JAK/STAT pathways. EC-70124 mediated DNA damage leading to cell cycle arrest at the G2/M phase. Pathway analyses identified several deregulated functions including cell proliferation, migration, DNA damage, regulation of stem cell differentiation and reversion of the epithelial-mesenchymal transition (EMT) phenotype, among others. Combination studies showed a synergistic interaction of EC-70124 with docetaxel, and an enhanced activity in vivo. Furthermore, EC-70124 had a good pharmacokinetic profile. In conclusion these experiments demonstrate the antitumor activity of EC-70124 in TNBC paving the way for the future clinical development of this drug alone or in combination with chemotherapy. PMID:26314846

  1. Verification of antitumor effect in vivo using nanosecond pulsed streamer discharge

    Science.gov (United States)

    Yonetamari, Kenta; Shirakawa, Yuki; Akiyama, Taketoshi; Mizuno, Kazue; Ono, Ryo

    2015-09-01

    Cancer treatment using plasma has intensively studied these days. In this work, antitumor effect by nanosecond pulsed streamer discharge was investigated. Nanosecond pulsed streamer plasma was used as a plasma source, which can generate stable streamer discharge by using a nanosecond pulsed power supply. The rod electrode of 3 mm diameter is made of copper. Its end is formed into a semispherical shape of 1.5 mm curvature. The electrode is inserted into a quartz tube (inner diameter: 4 mm, thickness: 1 mm) concentrically, so any gas can be introduced. B16F10 cells were selected to perform in vivo antitumor study. These cells were injected under the skin of leg of mice to make cancer tumor. One week later from injections, plasma was applied to the cancer tumor. Mice were randomly assigned into three groups which were one control group and two plasma treatment groups. In the control group, mice were not treated. In the plasma treatment groups, plasma with dry N2 and wet O2 as a working gas were irradiated for 5 consecutive days. Processing time was 10 min and the gap distance between the electrode and tumor was 4 mm. After 5 days plasma treatment, antitumor effect was observed. The result indicates that the streamer discharge has a potential for cancer treatment.

  2. Epistasis between MicroRNAs 155 and 146a during T Cell-Mediated Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Thomas B. Huffaker

    2012-12-01

    Full Text Available An increased understanding of antitumor immunity is necessary for improving cell-based immunotherapies against human cancers. Here, we investigated the roles of two immune system-expressed microRNAs (miRNAs, miR-155 and miR-146a, in the regulation of antitumor immune responses. Our results indicate that miR-155 promotes and miR-146a inhibits interferon γ (IFNγ responses by T cells and reduces solid tumor growth in vivo. Using a double-knockout (DKO mouse strain deficient in both miR-155 and miR-146a, we have also identified an epistatic relationship between these two miRNAs. DKO mice had defective T cell responses and tumor growth phenotypes similar to miR-155−/− mice. Further analysis of the T cell compartment revealed that miR-155 modulates IFNγ expression through a mechanism involving repression of Ship1. Our work reveals critical roles for miRNAs in the reciprocal regulation of CD4+ and CD8+ T cell-mediated antitumor immunity and demonstrates the dominant nature of miR-155 during its promotion of immune responses.

  3. 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.

  4. CCR4 is critically involved in effective antitumor immunity in mice bearing intradermal B16 melanoma.

    Science.gov (United States)

    Matsuo, Kazuhiko; Itoh, Tatsuki; Koyama, Atsushi; Imamura, Reira; Kawai, Shiori; Nishiwaki, Keiji; Oiso, Naoki; Kawada, Akira; Yoshie, Osamu; Nakayama, Takashi

    2016-08-01

    CCR4 is a major chemokine receptor expressed by Treg cells and Th17 cells. While Treg cells are known to suppress antitumor immunity, Th17 cells have recently been shown to enhance the induction of antitumor cytotoxic T lymphocytes. Here, CCR4-deficient mice displayed enhanced tumor growth upon intradermal inoculation of B16-F10 melanoma cells. In CCR4-deficient mice, while IFN-γ+CD8+ effector T cells were decreased in tumor sites, IFN-γ+CD8+ T cells and Th17 cells were decreased in regional lymph nodes. In wild-type mice, CD4+IL-17A+ cells, which were identified as CCR4+CD44+ memory Th17, were found to be clustered around dendritic cells expressing MDC/CCL22, a ligand for CCR4, in regional lymph nodes. Compound 22, a CCR4 antagonist, also enhanced tumor growth and decreased Th17 cells in regional lymph nodes in tumor-bearing mice treated with Dacarbazine. In contrast, CCR6 deficiency did not affect the tumor growth and the numbers of Th17 cells in regional lymph nodes. These findings indicate that CCR4 is critically involved in regional lymph node DC-Th17 cell interactions that are necessary for Th17 cell-mediated induction of antitumor CD8+ effector T cells in mice bearing B16 melanoma. PMID:27132989

  5. 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.

  6. 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.

  7. Application of metabolomics to investigate the antitumor mechanism of flavopiridol in MCF-7 breast cancer cells.

    Science.gov (United States)

    Shao, Xiaojian; Gao, Dan; Wang, Yini; Jin, Feng; Wu, Qin; Liu, Hongxia

    2016-07-01

    Flavopiridol is reported to have potent antitumor effects by inhibition of cyclin-dependent kinases (CDKs). However, most studies of flavopiridol focus on specific genes and kinases, so the antitumor mechanism needs further elucidation at the metabolic level. In the present study, an UPLC/Q-TOF MS metabolomics approach was used to investigate its antiproliferative effects on MCF-7 breast cancer cells. Comparing flavopiridol-treated MCF-7 cells with vehicle control, 21 potential biomarkers involved in five metabolism pathways were identified. Two pathways involving glutathione metabolism and glycerophospholipid metabolism showed that glutathione (GSH) and phosphatidylcholines (PCs) levels were reduced while their oxidized products oxidized glutathione (GSSG) and lysophosphatidylcholines (LysoPCs) were greatly increased. Further investigation showed an apparent accumulation of reactive oxygen species (ROS) and a decrease in mitochondrial membrane potential (MMP). Thus, we suggest that oxidative stress was provoked in MCF-7 cells to reduce the GSH and PCs levels and cause mitochondria lesions. Moreover, cell cycle analysis showed that flavopiridol blocked cells at G1 stage, which was consistent with the depletion of spermidine and spermine that are believed to promote cancer progression. Taking these together, we concluded that flavopiridol could induce oxidative stress and cell cycle arrest, which finally lead to cell apoptosis in MCF-7 cells. This study provides a new strategy for studying the antitumor mechanism of flavopiridol, which could be used for its further improvement and application. PMID:27208856

  8. Kulturelle Identität und Differenz : das Jüdische und das Christliche in Heinrich Heines "Rabbi von Bacherach"

    OpenAIRE

    Sonkwé Tayim, Constantin

    2010-01-01

    Der vorliegende Aufsatz will im Fragment "Der Rabbi von Bacherach" von Heinrich Heine, erschienen 1840, die Problematik der kulturellen Hybridität am Beispiel der Protagonisten Rabbi Abraham und Ritter Don Isaak Abarbanel diskutieren. Meine Überlegungen gehen dahin zu zeigen, dass Heine in diesem Fragment das Christliche und das Jüdische so dargestellt hat, dass die Möglichkeit einer binären Trennung zwischen beiden Räumen unmöglich wird. Aus seiner Inszenierung des Dialogs zwischen dem ansch...

  9. A perspectiva relacional das redes sociais no contexto das políticas públicas participativas

    OpenAIRE

    Andrés Burgos Delgado; Diana Rocío Rodríguez Triana; Doris Aleida Villamizar Sayago

    2013-01-01

    Este trabalho analisa as políticas públicas desde a perspectiva relacional das redes sociais, apresentando os principais aspectos metodológicos e conceituais embasados na abordagem da policy network, de modo a contribuir para o debate sobre participação, democracia e políticas públicas, desde o reconhecimento da importância das relações sociais. Explora-se o cenário deste conceito visando incrementar o entendimento de como atores, em diferentes posições institucionais, se relacionam e, como a...

  10. Responsabilidade Social Corporativa: estudo comparativo das normas socioambientais

    Directory of Open Access Journals (Sweden)

    Francisco Roberto Pinto

    2007-05-01

    Full Text Available A utilização de normas socioambientais visa dar maior credibilidade às práticas de Responsabilidade Social Corporativa (RSC. Neste estudo, levantaram-se os seguintes questionamentos: Quais as características das normas socioambientais existentes quanto à avaliação do processo produtivo, das relações com a comunidade, das relações com os empregados e dependentes? Quais os aspectos convergentes e divergentes dessas características no tocante à integração dos sistemas de gestão da RSC propugnados nas normas socioambientais? Trata-se de um estudo exploratório, com abordagem qualitativa, em que se realizou pesquisa bibliográfica e documental, e análise comparativa do conteúdo dos documentos pesquisados. As normas estudadas foram SA 8000, AA 1000, ISO 14001, NBR 16001 e ISO 26000, esta ainda em fase de elaboração. Concluiu-se que as normas apresentam semelhanças quanto ao processo produtivo, relação com a comunidade e integração dos sistemas de gestão, sendo recomendável a aplicação complementar das mesmas.

  11. 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"

  12. Musgos urbanos do recanto das Emas, Distrito Federal, Brasil

    Directory of Open Access Journals (Sweden)

    Câmara Paulo Eduardo

    2003-01-01

    Full Text Available Fruto da ocupação desordenada de Brasília, o Recanto das Emas é uma das mais recentes cidades criadas no entorno da capital. Localizada a 25,8km do Plano Piloto, conta com área de 101.476km². O Recanto das Emas foi criado em 1993 e hoje conta com população de aproximadamente 100.000 habitantes. Foram selecionados vários pontos de coleta procurando abranger toda a cidade e diferentes áreas. Foram encontrados relativamente poucos representantes da brioflórula, com predomínio de espécies ruderais. A divisão Bryophyta conta com 10 espécies e sete famílias, destacandose a família Bryaceae com três espécies. Barbula indica (Hook. Spreng. é citada pela primeira vez para a região Centro-Oeste. Os resultados explicam-se pelo pouco tempo de existência da cidade, que conta com poucos substratos para fixação das populações de briófitas e não permitiram ainda o estabelecimento de nova cobertura vegetal.

  13. Impacto dos investimentos no desempenho das empresas brasileiras.

    Directory of Open Access Journals (Sweden)

    Graziela Fortunato

    2012-08-01

    Full Text Available Este artigo objetiva verificar como o desempenho das empresas de capital aberto, com ações negociadas na Bolsa de Valores de São Paulo entre os anos de 1998 e 2007, é influenciado pelos investimentos de capital realizados pelas empresas. Trabalhos que investigam como os investimentos realizados pelas empresas afetam seu desempenho não são encontrados com facilidade e frequência na literatura (LI, 2004. Os trabalhos encontrados em publicações nacionais concentram-se em analisar o impacto da divulgação dos investimentos nas cotações das ações em bolsa, através da técnica de estudo de eventos (ANTUNES; PROCIANOY, 2003; FAMÁ; LUCCHESI, 2005; LYRA; OLINQUEVICTH, 2007; MCCONNELL; MUSCARELLA, 1985, havendo uma lacuna nas pesquisas sobre os investimentos realizados. Espera-se, por meio deste trabalho, reduzir a lacuna existente ao verificar o impacto dos investimentos do desempenho das empresas por meio de dados de painel. A técnica de análise de regressão em painel foi utilizada numa amostra de 508 empresas. Foram adotadas como proxys para o desempenho das empresas o valor de mercado e o lucro operacional (Ebit. Os resultados encontrados indicam que, pela métrica do mercado, os investimentos influenciam positivamente o desempenho das empresas; no entanto, pela métrica contábil, não há evidências da existência de relação. Os resultados obtidos sugerem, ainda, que as conclusões dos trabalhos de Lyandres, Sun e Zhang (2008 e Titman, Wei e Xie (2004 não são verificadas nas empresas brasileiras, visto que não se encontrou relação negativa entre os investimentos e o desempenho das empresas. Com esses resultados, espera-se fornecer subsídios que auxiliem tanto a construção de cenários para precificação e valuation das empresas, como também uma orientação da qualidade da decisão de investimentos por parte de seus gestores.

  14. A noção de das Ding em Jacques Lacan The notion of das Ding in Jacques Lacan

    Directory of Open Access Journals (Sweden)

    Ariana Lucero

    2009-01-01

    Full Text Available O presente artigo visa explicitar como se deu a apropriação lacaniana da noção de das Ding a partir do Projeto de uma psicologia de Freud ([1895] 1995. Além disso, buscaremos mostrar em que medida das Ding pode esclarecer aspectos importantes da obra de Lacan como, por exemplo, a relação do infante com o Outro, bem como o estatuto deste último; e a questão da tradução do termo Vorstellungsrepräsentanz por representante-da-representação.The present article aims to explicit the Lacanian usage of the notion of das Ding extracted from Freud's ([1895] 1995 Entwurf einer Psychologie. We will also try to show at what point das Ding can clarify important aspects of Lacan's work, such as the relationship of the infant with the Other, as well as the statute of the latter; and the question of the translation of the term Vorstellungsrepräsentanz to presentation-of-representation.

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

    Science.gov (United States)

    Fox, Barbara A; Sanders, Kiah L; Rommereim, Leah M; Guevara, Rebekah B; Bzik, David J

    2016-07-01

    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 control the

  16. Synthesis and Anti-tumor Evaluation of B-ring Modified Caged Xanthone Analogues of Gambogic Acid%Synthesis and Anti-tumor Evaluation of B-ring Modified Caged Xanthone Analogues of Gambogic Acid

    Institute of Scientific and Technical Information of China (English)

    李想; 张晓进; 汪小涧; 李念光; 林昌军; 高原; 于卓沁; 郭青龙; 尤启冬

    2012-01-01

    Gambogic acid (GA, 1), the most prominent member of Garcinia natural products, has been reported to be a promising anti-tumor agent. Previous studies have suggested that the planar B ring and the unique 4-oxa-tricyclo- [4.3.1.03.7]dec-2-one caged motif were essential for anti-tumor activity. To further explore the structure-activity relationship (SAR) of caged Garcinia xanthones, two new series of B-ring modified caged GA analogues 13a-13e and 15a-lge were synthesized utilizing a Claisen/Diel-Alder cascade reaction. Subsequently, these compounds were evaluated for their in vitro antitumor activities against A549, MCF-7, SMMC-7721 and BGC-823 cancer cell lines by MTT assay. Among them, 13b-13e exhibited micromolar inhibition against several cancer cell lines, being approximately 2-4 fold less potent in comparison to GA. SAR analysis revealed that the peripheral gem-dimethyl groups are essential for maintaining antitumor activity and substituent group on C1 position of B-ring has a significant effect on potency, while modifications at C-2, C-3 and C-4 positions are relatively tolerated. These findings will enhance our understanding of the SAR of Garcinia xanthones and lead to the development of simplified analogues as potential anti-tumor agents.

  17. Wer liest schon das "Kleingedruckte"? Urheberrecht bei Audioproduktion im Unterricht

    Directory of Open Access Journals (Sweden)

    Christian Berger

    2015-03-01

    Full Text Available Gesetze gelten, ob mensch diese kennt oder auch nicht kennt. Dieser Beitrag ist keine juristische Abhandlung sondern bietet praxisbezogene Wegweiser für LehrerInnen durch den juristischen Dschungel des Urheberrechtes und die Schaffung einer Basis für eine Verbreitung der schulischen Medienproduktionen ... Aus dem Alltag der SchülerInnen und LehrerInnen ist die Nutzung des Internets nicht mehr wegzudenken. Es ist also nicht überraschend, dass zahlreiche Audioproduktionen aus dem Unterricht im Internet zu finden sind. Weniger bekannt sind die rechtlichen Rahmenbedingungen, die hier zu beachten sind. Auf Webseiten findet man Nutzungsbedingungen für die Inhalte oftmals nur nach längerem Suchen – wenn überhaupt. Wenn aber da nicht zu lesen ist, in welcher Art die Inhalte der Webseite zu nutzen sind, dann ist außer dem Lesen, Ansehen, Anhören und Speichern auf dem eigenen Rechner nichts ohne Rückfrage bei den InhaberInnen der Seiten gestattet. Das Urheberrecht soll die Werke der kreativ Schaffenden vor unerlaubter Nutzung schützen und ihnen die Möglichkeit offen lassen, ihre Werke oder auch nur die Nutzung derselben zu verkaufen. Nun werden Sie sagen, dass es doch ganz normal sei in unserer kapitalistischen Gesellschaft, dass Werke zu Waren und am Marktplatz gehandelt werden. Aber ganz so klar und einfach ist das nicht, denn im Markt spielen noch mehr Beteiligte mit, die ebenfalls verdienen wollen. Nun werden Sie einwenden, dass die Schule eben kein Marktplatz sei und der Unterricht doch ganz andere Ziele verfolge. Richtig. Allerdings beinhaltet das derzeitige Urheberrecht hier keine Ausnahmeregelungen. Es gibt allerdings auch keine einfachen allgemeinen Regelungen, sondern viele Einzelfälle, die ihre Besonderheiten haben und unterschiedlich abzuhandeln sind. Konkret geht es um drei Bereiche der Gesetzgebung: das Urheberrecht, das Medienrecht und Schutzbestimmungen im "Persönlichkeitsrecht". Hier ist gleich einmal anzumerken, dass ein

  18. Growth inhibitory effect of triple anti-tumor gene transfer using Semliki Forest virus vector in glioblastoma cells.

    Science.gov (United States)

    Lee, Jong-Soo; Lee, Jun-Han; Poo, Haryoung; Kim, Mi-Suk; Lee, Seung-Hoon; Sung, Moon-Hee; Kim, Chul-Joong

    2006-03-01

    The gene delivery of multiple tumor suppressors can provide an efficient tumor therapy in the case of malignant human glioblastomas containing multiple genetic alteration and inactivation. As such, the current study presents a new delivery system that can simultaneously express three anti-tumor genes using a Semliki Forest virus (SFV) vector in the expectation of combined or synergistic effects of angiogenesis inhibition by angiostatin and apoptosis induction by p53, PTEN and the rSFV particle itself. Recombinant SFV (rSFV) containing three anti-tumor genes (rSFV-Agt/p53/PTEN) were found to efficiently transduce and express each anti-tumor gene in glioblastoma cells. In addition, rSFV-Agt/p53/PTEN also resulted in a more effective induction of apoptosis in vitro and inhibition of tumor growth in nude mice when compared with other rSFVs containing only one or two anti-tumor genes. Accordingly, the current results demonstrate that a triple anti-tumor gene transfer using an rSFV vector would be a powerful strategy for regional cancer gene therapy. PMID:16465369

  19. Kooperation und Asymmetrie : das Entwicklungsprofil eines betrieblichen Ost-West-Projekts

    OpenAIRE

    Dörr, Gerlinde; Kessel, Tanja

    2001-01-01

    "Das vorliegende Papier befaßt sich mit einer transnationalen Unternehmenskooperation. Rekonstruiert wird das Entwicklungsprofil der Kooperation der beiden Automobilhersteller Skoda und Volkswagen, das durch das Ineinandergreifen der beiden aktuellen Tendenzen von Transformation und Globalisierung geprägt ist. Als für den Kooperationserfolg entscheidend zeigte sich nicht nur der von Volkswagen geleistete beträchtliche Know-how- und Managementtransfer an den tschechischen Standort, sondern auc...

  20. Kooperation und Asymmetrie: Das Entwicklungsprofil eines betrieblichen Ost-West-Projekts

    OpenAIRE

    Dörr, Gerlinde; Kessel, Tanja

    2002-01-01

    Das vorliegende Papier befaßt sich mit einer transnationalen Unternehmenskooperation. Rekonstruiert wird das Entwicklungsprofil der Kooperation der beiden Automobilhersteller Skoda und Volkswagen, das durch das Ineinandergreifen der beiden aktuellen Tendenzen von Transformation und Globalisierung geprägt ist. Als für den Kooperationserfolg entscheidend zeigte sich nicht nur der von Volkswagen geleistete beträchtliche Know-how- und Managementtransfer an den tschechischen Standort, sondern auch...

  1. Das Common Warehouse Metamodel - ein Referenzmodell für Data-Warehouse-Metadaten

    OpenAIRE

    Melchert, Florian; Schwinn, Alexander; Herrmann, Clemens

    2003-01-01

    Der vorliegende Beitrag beschreibt das Vorgehen zur Realisierung eines integrierten Metadatenmanagements im Data-Warehouse-Projekt einer Schweizer Universalbank. Untersucht wurde insbesondere, inwieweit das Common Ware­house Metamodell der Object Management Group geeignet ist, als Referenzmodell für die Metadatenbasis herangezogen zu werden. Nach einem Überblick über das Referenzmodell werden das Vorgehen zu seiner Anwendung sowie die dabei identifizierten Stärken und Schwächen beschrieben....

  2. 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.

  3. 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.

  4. Culturas das Ciências Naturais Cultures of Natural Sciences

    OpenAIRE

    Maria Margaret Lopes

    2005-01-01

    Este artigo apresenta subsídios para o ensino de História das Ciências, considerando particularmente o campo da História da História Natural e das Ciências Naturais. Sem ser uma revisão completa da historiografia desses campos de conhecimento sobre o mundo natural, retoma alguns traços gerais desses longos processos de definição de campos disciplinares que se configuram desde a Renascença até o final do século XVIII. Considera diversas tradições culturais e historiográficas que contribuíram p...

  5. 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

  6. 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.

  7. Der Einfluss von Relaxin auf das Wachstum von Mammakarzinomen

    OpenAIRE

    Habla, Christiane

    2010-01-01

    Brustkrebs ist die häufigste Krebstodesursache bei Frauen in den Industrienationen mit einer jährlich ansteigenden Neuerkrankungsrate (Senn und Niederberger 2002). Durch vorangegangene Untersuchungen wurde bereits deutlich, dass das Peptidhormon Relaxin unter in vitro Bedingungen maßgeblich zur Tumorprogression von Mammakarzinomen beiträgt (Binder et al. 2002). Die vorliegende Arbeit hat untersucht, ob Relaxin diese Wirkung auch in vivo auf Mammakarzinome ausübt. Relaxin ist...

  8. Internationalization strategy of Água das Pedras to Dubai

    OpenAIRE

    Mendonça, Mafalda Vaz Pinto Furtado de

    2013-01-01

    Água das Pedras is the leading brand of sparkling water in Portugal, with 140 years of history, and detains the consumer preference in the domestic market. Pedras wants to explore growing opportunities leveraging its competitive advantage and experience. The work project presents an expansion to the Dubai market, a region where 1L of petrol is cheaper than 1L of bottled water1. Entering in the premium segment, the foreign market promises a growing demand with high margins.

  9. Das Polenbild in Deutschland – Entstehung und Gegenwart

    OpenAIRE

    Gatzke, Niels

    2012-01-01

    Der Artikel beschreibt die Entstehung des deutschen Polenbildes, die Veränderungen im Polenbild durch polnische Zuwanderung nach Deutschland Ende des 19. Jahrhunderts, Polen als "Feindbild" der Zwischenkriegszeit und beleuchtet die Reaktionen in der DDR auf das Entstehen der Solidarność. Ebenso werden die heutige Wahrnehmung Polens, anhand der Begriffe Distanz, Sympathie und Akzeptanz betrachtet. Dabei zeigt sich, dass es zur Überwindung der Vorurteile und Stereotype eine gesellschaftliche Au...

  10. Marx, Mead und das Konzept widersprüchlicher Praxis

    OpenAIRE

    Müller, Horst

    1983-01-01

    Die 'praxiswissenschaftliche' Interpretation von Meads Theorie wendet sich gegen deren 'intersubjektivitätstheoretische' Vereinnahmung und führt ihre kohärente Kerngestalt vor. Der Untersuchung liegt ein Fragespektrum zugrunde, das sich von der Handlungs- und Erkenntnis- bis zur Evolutionstheorie erstreckt. Auf allen konstitutionstheoretischen Ebenen enthüllen sich Konvergenzen zwischen Meads universalistischer Theorie und dem praxiszentrierten Marxismus. Es kristallisiert sich 'widers...

  11. Schwerelose Gefahr für das Immunsystem

    OpenAIRE

    Ullrich, O

    2009-01-01

    Forscher der Universität Zürich und die Schweizer Luftwaffe arbeiten gemeinsam an einem der Hauptprobleme der bemannten Raumfahrt – dem Einfluss der Schwerelosigkeit auf das Immunsystem. Die Luftwaffe ist im Projekt gleich doppelt vertreten: Einerseits gehört Berufsmilitärpilot Marc Studer dem Forschungsteam an und andererseits hat der Lufttransportdienst des Bundes (LTDB) den Transport der zu erforschenden Zellen übernommen.

  12. Das non-neuronale cholinerge System des Kolons der Ratte

    OpenAIRE

    Bader, Sandra

    2014-01-01

    Acetylcholin ist nicht nur ein Neurotransmitter, sondern wird auch in einer Reihe von nicht-neuronalen Zellen, v. a. solchen mit Barriere- oder Abwehrfunktion, gefunden. Zum Beispiel wird das Schlüsselenzym für die Acetylcholinsynthese, die Cholinacetyltransferase (ChAT), bei verschiedenen Säugern vom Kolonepithel exprimiert. Diese Zellen setzen, bei mukosaler Stimulation durch Propionat, Acetylcholin nach basolateral frei. Propionat ist eine kurzkettige Fettsäure, die physiologischerweise im...

  13. 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.

  14. Das PORTAL www.informationskompetenz.de – Analyse, Bewertung, Perspektiven

    OpenAIRE

    Grünleitner, Karin

    2012-01-01

    Diese Bachelorarbeit befasst sich mit dem Portal http://www.informationskompetenz.de/, das als Gemeinschaftsprojekt bibliothekarischer Arbeitsgemeinschaften zur Vermittlung von Informationskompetenz der regionalen und überregionalen Kooperation von Bibliotheken in Deutschland dienen soll. Neben einem Glossar, Standards und Erklärungen sowie Präsenzen der beteiligten Bundesländer stellt es insbesondere eine Datenbank zur Sammlung und zum Austausch von Materialien zu diesem Thema bereit. Nach e...

  15. Informationskompetenz 2.0 und das Verschwinden des Nutzers

    OpenAIRE

    Hapke, Thomas

    2007-01-01

    Ausgehend von einer sich wandelnden Rolle des Nutzers von Informationssystemen im Web 2.0 wird das Konzept Informationskompetenz kritisch hinterfragt. Fünf Thesen zur Informationskompetenz 2.0, verbunden mit Anregungen auf weiterführende Literatur, schlagen einen Perspektivwechsel der in deutschen Bibliotheken vorherrschenden Sicht auf Informationskompetenz hin zu einem ganzheitlicheren Verständnis von Informations- und Lernprozessen vor. Starting from the changing role of the user in info...

  16. Das Aerosol-Ionenfallen-Massenspektrometer (AIMS) : Aufbau, Charakterisierung und Feldeinsatz

    OpenAIRE

    Fachinger, Johannes Richard Werner

    2012-01-01

    Um die in der Atmosphäre ablaufenden Prozesse besser verstehen zu können, ist es wichtig dort vorhandene Partikel gut charakterisieren zu können. Dazu gehört unter anderem die Bestimmung der chemischen Zusammensetzung der Partikel. Zur Analyse insbesondere organischer Partikel wurde dazu in einer früheren Promotion das Aerosol-Ionenfallen-Massenspektrometer (AIMS) entwickelt.Im Rahmen dieser Arbeit wurden Entwicklungsarbeiten durchgeführt, um die Charakteristiken des Prototypen zu verbessern ...

  17. Marketing und Sales Performance Measurement : Das Beispiel Dell

    OpenAIRE

    Freyer, Achim; Kurzmann, Heike

    2008-01-01

    Die Fähigkeit eines Unternehmens Leistungsnachweise von Marketing- und Verkaufsmassnahmen zu erbringen, wird bei Dell als Grundvoraussetzung für den wirtschaftlichen Erfolg angesehen. Die RAD ("Retention Akquisition Development")-Matrix ist ein Vorzeigebeispiel für ein Kennzahlencockpit, welches als Kontrollinstrument dient, mit dem Ziel, Zusammenhänge zwischen Marktaktivitäten und Marktleistung transparent zu machen. Zusätzlich ermöglicht das Cockpit eine proaktive Steuerung zukünftiger Mark...

  18. Das Atelier als Spiegelbild des Künstlers

    OpenAIRE

    Jooss, Birgit

    2009-01-01

    Das Künstleratelier als Raum des Kunstschaffenden spiegelte von Anbeginn auch dessen Habitus wieder. Neben der Werkstatt-Funktion kann ein Atelier zahlreiche weitere Aufgaben erfüllen und durch die Inszenierung zum Spiegelbild seines Nutzers werden. Im Aufsatz werden die unterschiedlichen Selbstinszenierungs-Strategien der drei Künstler Franz von Lenbach, Franz von Stuck und Max Liebermann analysiert. Es wird verdeutlicht, dass Ausstattung und Lichtinszenierung des jeweiligen Ateliers verblüf...

  19. Einfluss produktionsbezogener Kommunikation auf das Verbrauchervertrauen in (Bio-)Lebensmittel

    OpenAIRE

    Kriege-Steffen, Astrid

    2015-01-01

    Untersuchungsgegenstand in der vorliegenden Arbeit ist der Einfluss von Vertrauen in Lebensmittel auf den Kaufentscheidungsprozess und die Bedeutung von produktionsbezogener Kommunikation auf das Verbrauchervertrauen. Die Entscheidungsgründe für oder gegen bestimmte Lebensmittel wurden bereits in einigen Studien untersucht. Dabei werden beispielsweise die Bedeutung des Preises, des Gesundheitswertes und des Tier- und Umweltschutzes erfasst. Ebenso werden Ängste der Konsumenten in Bezug au...

  20. 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.

  1. 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...

  2. Der physikalische Raum und das Apriori methodologischer Normen

    OpenAIRE

    Carrier, Martin; Pasternack, Gerhard

    1987-01-01

    Die Klärung des Problems des Apriori in der physikalischen Geometrie verlangt einen Umweg. Es ist zuerst die Frage zu diskutieren, ob die physikalische Geometrie überhaupt bestimmt [und nicht vielmehr willkürlich] ist, bzw. wodurch sie bestimmt ist. Erst in einem zweiten Schritt kann dann das Problem in Angriff genommen werden, ob sich unter den Bedingungen dieser Bestimmtheit apriorische Elemente auffinden lassen.

  3. Regionale Innovationsnetzwerke und Unternehmensverhalten: das Beispiel InnoRegio

    OpenAIRE

    Rainer Voßkamp

    2004-01-01

    Das Bundesministerium für Bildung und Forschung (BMBF) hat mit dem Förderprogramm InnoRegio 23 regionale Innovationsnetzwerke (InnoRegios) in Ostdeutschland initiiert. Im vorliegenden Bericht wird erläutert, welche wesentlichen Wirkungen von der Netzwerkbildung und der Bearbeitung gemeinsamer Innovationsprojekte in den InnoRegios auf die Wettbewerbsfähigkeit der Unternehmen und der Regionen erwartet und wie sie identifiziert und gemessen werden können. Eingebettet werden diese Überlegungen u ...

  4. Das Zuschauspiel : lebendige Körper im Theater

    OpenAIRE

    Proske, Margrit

    2001-01-01

    Theaterformen, die Präsenz, Ereignis und Erfahrung privilegieren, involvieren die Zuschauer in besonderer Weise als Teilhabende. Das Theaterpublikum agiert als pluraler Körper, als kommunizierende Körper unter anderen, die eine Aufführung mitschaffen. Erarbeitet wird eine Theorie des Zuschauens, die die lebendig erlebende, körperliche Wahrnehmung integriert. Die dezentrierte Begriffsstruktur (Derrida) erweitert den Diskursrahmen. Der Körper kann nun umfassend als offener und zu...

  5. Erigeron sumatrensis, das Sumatra-Berufkraut, in Frankfurt am Main

    OpenAIRE

    Buttler, Karl Peter

    2007-01-01

    Erigeron sumatrensis ist seit 1981 in Frankfurt am Main als Neophyt bekannt. Das gegenwärtige Verbreitungsmuster deutet darauf hin, dass die Art sich langsam ausbreitet. Um ihr Erkennen zu erleichtern, wird ein Bestimmungsschlüssel für die in Europa vorkommenden annuellen Adventivarten der Sektion Conyza beigegeben, ergänzt durch einige Anmerkungen zu noch offenen taxonomischen Fragen. Für drei Herkünfte aus Frankreich wurde die hexaploide Chromosomenzahl 2n = 54 ermittelt.

  6. Anamnesen des Undarstellbaren. Zum Widerstreit um das Vergessen(e)

    OpenAIRE

    Tholen, Georg Christoph

    1997-01-01

    Zwischen Erinnern und Vergessen: Risse im Verstehen Shoah - Holocaust - Ausschwitz: Drei Passwörter für das stets unvollständige Begreifen der nationalsozialistischen Massenvernichtung, die als jeweils bevorzugtes Schibboleth die Grenzen des Verstehens markieren und zugleich verdecken. Denn indem mit ihnen die bleibende Unzugänglichkeit eines einmaligen Zivilisationsbruchs definiert und datiert werden soll, ist zugleich eine Aporie zwischen Datum und dem, was sich diesem entzieht, gegeben. Di...

  7. 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.

  8. An NGR-integrated and enediyne-energized apoprotein shows CD13-targeting antitumor activity.

    Science.gov (United States)

    Zheng, Yan-Bo; Shang, Bo-Yang; Li, Yi; Zhen, Yong-Su

    2013-03-01

    Targeting and inhibiting angiogenesis is a promising strategy for treatment of cancer. NGR peptide motif is a tumor-homing peptide, which could bind with CD13 expressed on tumor blood vessels. Lidamycin is a highly potent antitumor antibiotic, which is composed of an apoprotein (LDP) and an active enediyne chromophore (AE). Here, an NGR-integrated and enediyne-energized apoprotein composed of cyclic NGR peptide and lidamycin was developed by a two-step procedure. Firstly, we prepared the fusion protein composed of NGR peptide and LDP by recombinant DNA technology. Then, AE was reloaded to the fusion protein to get NGR-LDP-AE. Our experiments showed that NGR-LDP could bind to CD13-expressing HT-1080 cells, whereas the recombinant LDP (rLDP) showed weak binding. NGR-LDP-AE exerted highly potent cytotoxicity to cultured tumor cells in vitro. In vivo antitumor activity was evaluated in murine hepatoma 22 (H22) model and human fibrosarcoma HT-1080 model. At the tolerable dose, NGR-LDP-AE and lidamycin inhibited H22 tumor growth by 94.8 and 66.9%, and the median survival time of the mice was 62 and 37 days, respectively. In the HT-1080 model, NGR-LDP-AE inhibited tumor growth by 88.6%, which was statistically different from that of lidamycin (74.5%). Immunohistochemical study showed that NGR-LDP could bind to tumor blood vessels. Conclusively, these results demonstrate that fusion of LDP with CNGRC peptide delivers AE to tumor blood vessels and improves its antitumor activity. PMID:23206754

  9. Preparation, characterization, and evaluation of antitumor effect of Brucea javanica oil cationic nanoemulsions.

    Science.gov (United States)

    Liu, Ting-Ting; Mu, Li-Qiu; Dai, Wei; Wang, Chuan-Bang; Liu, Xin-Yi; Xiang, Da-Xiong

    2016-01-01

    The purpose of this study was to prepare Brucea javanica oil cationic nanoemulsions (BJO-CN) with BJO as drug as well as oil phase and chitosan as cationic inducer, to explore the practical suitability of using cationic nanoemulsions for oral delivery of mixed oil, and to test its bioavailability and antitumor effect. BJO-CN was prepared by chitosan solution stirring method and then characterized physicochemically. The obtained BJO-CN had a spherical morphology with a positive zeta potential of 18.9 mV and an average particle size of 42.36 nm, showing high colloidal stability. The drug loading of BJO-CN was 91.83 mg·mL(-1), determined by high-performance liquid chromatography with precolumn derivatization. Pharmacokinetic studies revealed that, compared with BJO emulsion (BJO-E) (the dosage of BJO-CN and BJO-E was equal to 505 mg·kg(-1), calculated by oleic acid), BJO-CN exhibited a significant increase in the area under the plasma drug concentration-time curve over the period of 24 hours and relative bioavailability was 1.6-fold. Furthermore, the antitumor effect of BJO-CN in the orthotopic mouse model of lung cancer was evaluated by recording the median survival time and the weight of lung tissue with tumor, hematoxylin and eosin staining, and immunohistochemical technique. Results of anticancer experiments illustrated that, even though the administrated dosage in the BJO-CN group was half of that in the BJO-E group, BJO-CN exhibited similar antitumor effect to BJO-E. Moreover, BJO-CN had good synergistic effect in combination therapy with vinorelbine. These results suggested that cationic nanoemulsions are an effective and promising delivery system to enhance the oral bioavailability and anticancer effect of BJO. PMID:27330293

  10. Biodegradable nanoassemblies of piperlongumine display enhanced anti-angiogenesis and anti-tumor activities

    Science.gov (United States)

    Liu, Yuanyuan; Chang, Ying; Yang, Chao; Sang, Zitai; Yang, Tao; Ang, Wei; Ye, Weiwei; Wei, Yuquan; Gong, Changyang; Luo, Youfu

    2014-03-01

    Piperlongumine (PL) shows an inhibitory effect on tumor growth; however, lipophilicity has restricted its further applications. Nanotechnology provides an effective method to overcome the poor water solubility of lipophilic drugs. Polymeric micelles with small particle size can passively target tumors by the enhanced permeability and retention (EPR) effect, thus improving their anti-tumor effects. In this study, to improve the water solubility and anti-tumor activity of PL, PL encapsulated polymeric micelles (PL micelles) were prepared by a solid dispersion method. The prepared PL micelles showed a small particle size and high encapsulation efficiency, which could be lyophilized into powder, and the re-dissolved PL micelles are homogenous and stable in water. In addition, a sustained release behavior of PL micelles was observed in vitro. Encapsulation of PL into polymeric micelles could increase the cytotoxicity, cellular uptake, reactive oxygen species (ROS) and oxidized glutathione (GSSG), and reduce glutathione (GSH) levels in vitro. Encapsulation of PL into polymeric micelles enhanced its inhibitory effect on neovascularization both in vitro and in vivo. Compared with free PL, PL micelles showed a stronger inhibitory effect on the proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs). Additionally, in a transgenic zebrafish model, embryonic angiogenesis was inhibited by PL micelles. Furthermore, PL micelles were more effective in inhibiting tumor growth and prolonging survival in a subcutaneous CT-26 murine tumor model in vivo. Therefore, our data revealed that the encapsulation of PL into biodegradable polymeric micelles enhanced its anti-angiogenesis and anti-tumor activities both in vitro and in vivo.

  11. Anti-inflammatory, antioxidant and antitumor activities of ingredients of Curcuma phaeocaulis Val.

    Science.gov (United States)

    Hou, Yan; Lu, Chuan-Li; Zeng, Qiao-Hui; Jiang, Jian-Guo

    2015-01-01

    Curcuma phaeocaulis Val. is used in Chinese Pharmacopoeia as health food and folk medicine for removing blood stasis, alleviating pain and tumor therapy. This research was aimed to explore and compare three main bioactivities including anti-oxidant, antitumor and anti-inflammatory activities between the ethanol extract of C. Phaeocaulis and its fractions using different in vitro models. Firstly, 70 % ethanol was used to extract C. Phaeocaulis, and then the crude extract was re-extracted, resulting in petroleum ether (EZ-PE), ethyl acetate (EZ-EA), and water fractions (EZ-W), respectively, and then a series of index was detected. Results showed that all the extracts had medium DPPH radical scavenging activity when the concentration was 200 μg/ml and their DPPH radical scavenging activity was in a concentration-dependent manner. The extracts except ethanol extract of C. Phaeocaulis had almost no cytotoxicity to the survival of RAW264.7 cell when the concentration reached 80 μg/ml, and all of them had medium inhibitory effect on nitrite release. Extracts of C. Phaeocaulis had medium intensity antitumor activity, EZ-PE and EZ-EA fractions significantly inhibited the proliferation of four tumor cells (SMMC-7721 cell lines, HepG-2 cell lines, A549 cell lines and Hela cell lines). C. Phaeocaulis had antioxidant and anti-inflammatory activities, which did not carry out centralized phenomenon when re-extracted. EZ-PE and EZ-EA were active antitumor sites of C. Phaeocaulis. PMID:26648822

  12. 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

    2014-04-01

    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. PMID:24368211

  13. 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.

  14. Inhibition of colony stimulating factor-1 receptor improves antitumor efficacy of BRAF inhibition

    International Nuclear Information System (INIS)

    Malignant melanoma is an aggressive tumor type that often develops drug resistance to targeted therapeutics. The production of colony stimulating factor 1 (CSF-1) in tumors recruits myeloid cells such as M2-polarized macrophages and myeloid derived suppressor cells (MDSC), leading to an immune suppressive tumor milieu. We used the syngeneic mouse model of BRAFV600E-driven melanoma SM1, which secretes CSF-1, to evaluate the ability of the CSF-1 receptor (CSF-1R) inhibitor PLX3397 to improve the antitumor efficacy of the oncogenic BRAF inhibitor vemurafenib. Combined BRAF and CSF-1R inhibition resulted in superior antitumor responses compared with either therapy alone. In mice receiving PLX3397 treatment, a dramatic reduction of tumor-infiltrating myeloid cells (TIM) was observed. In this model, we could not detect a direct effect of TIMs or pro-survival cytokines produced by TIMs that could confer resistance to PLX4032 (vemurafenib). However, the macrophage inhibitory effects of PLX3397 treatment in combination with the paradoxical activation of wild type BRAF-expressing immune cells mediated by PLX4032 resulted in more tumor-infiltrating lymphocytes (TIL). Depletion of CD8+ T-cells abrogated the antitumor response to the combination therapy. Furthermore, TILs isolated from SM1 tumors treated with PLX3397 and PLX4032 displayed higher immune potentiating activity. The combination of BRAF-targeted therapy with CSF-1R blockade resulted in increased CD8 T-cell responses in the SM1 melanoma model, supporting the ongoing evaluation of this therapeutic combination in patients with BRAFV600 mutant metastatic melanoma. The online version of this article (doi:10.1186/s12885-015-1377-8) contains supplementary material, which is available to authorized users

  15. A novel oncolytic herpes simplex virus type 2 has potent anti-tumor activity.

    Directory of Open Access Journals (Sweden)

    Qian Zhao

    Full Text Available Oncolytic viruses are promising treatments for many kinds of solid tumors. In this study, we constructed a novel oncolytic herpes simplex virus type 2: oHSV2. We investigated the cytopathic effects of oHSV2 in vitro and tested its antitumor efficacy in a 4T1 breast cancer model. We compared its effect on the cell cycle and its immunologic impact with the traditional chemotherapeutic agent doxorubicin. In vitro data showed that oHSV2 infected most of the human and murine tumor cell lines and was highly oncolytic. oHSV2 infected and killed 4T1 tumor cells independent of their cell cycle phase, whereas doxorubicin mainly blocked cells that were in S and G2/M phase. In vivo study showed that both oHSV2 and doxorubicin had an antitumor effect, though the former was less toxic. oHSV2 treatment alone not only slowed down the growth of tumors without causing weight loss but also induced an elevation of NK cells and mild decrease of Tregs in spleen. In addition, combination therapy of doxorubicin followed by oHSV2 increased survival with weight loss than oHSV2 alone. The data showed that the oncolytic activity of oHSV2 was similar to oHSV1 in cell lines examined and in vivo. Therefore, we concluded that our virus is a safe and effective therapeutic agent for 4T1 breast cancer and that the sequential use of doxorubicin followed by oHSV2 could improve antitumor activity without enhancing doxorubicin's toxicity.

  16. Annonaceous acetogenins nanosuspensions stabilized by PCL–PEG block polymer: significantly improved antitumor efficacy

    Directory of Open Access Journals (Sweden)

    Hong JY

    2016-07-01

    Full Text Available Jingyi Hong,1,* Yanhong Li,1,2,* Yijing Li,1 Yao Xiao,1,2 Haixue Kuang,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 2School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, People’s Republic of China *These authors contributed equally to this work Abstract: Annonaceous acetogenins (ACGs have shown superior antitumor activity against a variety of cancer cell lines, but their clinical application has been limited by their poor solubility. In this study, ACGs-nanosuspensions (NSps were successfully prepared by a precipitation ultrasonic method using monomethoxypoly (ethylene glycol2000–poly (ε-caprolactone2000 (mPEG2000–PCL2000 as a stabilizer. The resultant ACGs-NSps had a mean particle size of 123.2 nm, a zeta potential of -20.17 mV, and a high drug payload of 73.68%. ACGs-NSps were quite stable in various physiological solutions, and they exhibited sustained drug release. Compared to free drug, ACGs-NSps exhibited stronger cytotoxicity against 4T1, MCF-7, and HeLa cells. An in vivo real-time biodistribution investigation after labeling with 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide, a noninvasive near-infrared fluorescence probe, demonstrated that ACGs-NSps could effectively accumulate in tumor. An in vivo antitumor activity study in 4T1 tumor-bearing mice revealed that ACGs-NSps achieved much better therapeutic efficacy than the traditional dosage form (oil solution even at 1/10 of the dose (74.83% vs 45.53%, P<0.05, demonstrating that NSp was a good dosage form for ACGs to treat cancer. Keywords: annonaceous acetogenins, mPEG2000–PCL2000, near–infrared fluorescence, biodistribution, antitumor efficacy

  17. Antitumor effects of interleukin-18 gene-modified hepatocyte cell line on implanted liver carcinoma

    Institute of Scientific and Technical Information of China (English)

    冷建杭; 张立煌; 姚航平; 曹雪涛

    2003-01-01

    Objective To investigate the antitumor effects of intrasplenically transplanted interleukin-18 (IL-18) gene-modified hepatocytes on murine implanted liver carcinoma.Methods Embryonic murine hepatocyte cell line (BNL-CL2) was transfected with a recombinant adenovirus encoding IL-18 and used as delivery cells for IL-18 gene transfer. Two cell lines, BNL-LacZ and BNL-CL2, were used as controls. One week after intrasplenic injection of C26 cells (colon carcinoma line), tumor-bearing syngeneic mice underwent the intrasplenic transplantation of IL-18 gene-modified hepatocyte cell line and were divided into treatment group (BNL IL-18) and control groups (BNL-LacZ and BNL-CL2 ). Two weeks later, the serum levels of IL-18, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) in the implanted liver carcinoma-bearing mice were assayed, the cytotoxicity of murine splenic cytotoxic T-lymphocytes (CTLs) was measured, and the morphology of the hepatic tumors was studied to evaluate the antitumor effects of the approach. Results In the treatment group, the serum levels of IL-18, IFN-γ, TNF-α and NO increased significantly. The splenic CTL activity increased markedly (P<0.01) , accompanied by a substantial decrease in tumor volume and the percentage of tumor area and prolonged survival of liver carcinomo-being mice.Conclusions In vivo IL-18 expression by ex vivo manipulated cells with IL-18 recombinant adenovirus is able to exert potent antitumor effects by inducing a predominantly T-cell-helper type 1 (Th1) immune response. Intrasplenic transplantation of adenovirus-mediated IL-18 gene-modified hepatocytes could be used as a targeting treatment for implanted liver carcinoma.

  18. Characterization and Anti-tumor Activity of Giycopeptides from Ganoderma sinensis

    Institute of Scientific and Technical Information of China (English)

    GAO Yang; JIANG Ru-zhi; CHEN Ying-hong; LUO Hao-ming; XU Duo-duo; GAO Qi-pin

    2009-01-01

    The water-soluble part(GS) of Ganoderma sinense Zhao, Xu et Zhang was divided into high molecu-Iar(GS-H) and low molecular(GS-L) parts by Cellulose Super Filtration, and GS was also fractionated into four frac-tions, GS-1, 2, 3, and 4 by ethanol precipitation according to their molecular weights. Chemical analysis shows that GS and GS-I, 2, 3, 4 were complexes of polysaccharide and peptide. The fractions with molecular weights over 4000, GS-1, 2, 3, and GS-H show anti-tumor activities, however, the fractions with molecular weights lower than 4000,GS-4, and GS-L have no anti-tumor activity, indicating that the anti-tumor activity of Ganoderma Sinensis was caused by glucopeptides with molecular weight ranging from 4000 to 20000. Two purified glucopeptides, GS-6b and GS-7b were obtained from GS-H by ion-exchange and gel-permeation chromatography. Their molecular weights, glycosidic linkages, and configurations were detected by means of IR spectrum, sugar composition analysis, and me-thylation analysis. The polysaccharide parts of GS-6b and GS-7b had glucan backbone consisting of β-1→3 Glc, and side chain containing glucosyl, mannosyl, fueosyl, xylosyl, galactosyl, and glucuronic acid residues attached on 1-2,1-4, 1-6 positions of the backbone of GS-6b, or 1-6, 1-4 positions of the backbone of GS-7b. The peptide parts in GS-6b and GS-7b were composed of 10 kinds of amino acids, including Asp, Ser, Arg, Gly, Thr, Pro, Ala, Val, Met, and Lys.

  19. Assessment of the antitumor potential of Bithionol in vivo using a xenograft model of ovarian cancer.

    Science.gov (United States)

    Ayyagari, Vijayalakshmi N; Johnston, Nancy A; Brard, Laurent

    2016-07-01

    In terms of the concept of 'drug repurposing', we focused on pharmaceutical-grade Bithionol (BT) as a therapeutic agent against ovarian cancer. Our recent in-vitro study provides preclinical data suggesting a potential therapeutic role for BT against recurrent ovarian cancer. BT was shown to cause cell death by caspases-mediated apoptosis. The present preliminary study further explores the antitumor potential of pharmaceutical-grade BT in an in-vivo xenograft model of human ovarian cancer. Nude Foxn1 mice bearing SKOV-3 human ovarian tumor xenografts were treated with titrated doses of BT and the therapeutic efficacy of pharmaceutical BT was determined using bioluminescence imaging. BT-induced changes in cell proliferation and apoptosis were evaluated by Ki-67 immunochemical staining and TUNEL assay. The effect of BT on autotaxin levels in serum, ascitic fluid, and tumor tissue was assessed by colorimetric and western blot techniques. BT treatment did not show antitumor potential or enhanced survival time at any of the doses tested. No apparent signs of toxicity were observed with any of the doses tested. Immunohistological analysis of tumor sections did not indicate a significant decrease in cellular proliferation (Ki-67 assay). An increase in apoptosis (by TUNEL assay) was observed in all BT-treated mice compared with vehicle-treated mice. Although BT did not show significant antitumor activity in the present study, the ability of BT to induce apoptosis still makes it a promising therapeutic agent. Further confirmatory and optimization studies are essential to enhance the therapeutic effects of BT. PMID:27058706

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

    Institute of Scientific and Technical Information of China (English)

    Arzu Birinci Yildirim; Fatma Pehlivan Karakas; Arzu Ucar Turker

    2013-01-01

    Objective: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. Methods: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. Results: 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

  1. 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.

  2. Histopathologic observation of anti-tumor effect of bleomycin and irradiation on cancers of tongue

    International Nuclear Information System (INIS)

    Nine cases of squamous cell carcinoma of the tongue were treated by either intramuscular or local injections of total 60 to 200 mg of Bleomycin (BLM), and 7 cases by total doses of 1,200 to 5,320 rads of irradiation, followed by surgical removal of primary neoplasm. The histologic examination was do ne focussing on the antitumor effect of both treatments. In the cases with keratinizing component more than 25 % in the biopsy specimens, the earliest change due to BLM was vacuolar degeneration of proliferating cells either at the base of superficial cancer epithelia or at the periphery of invading cancer foci. When the proliferating cancer cells disappeared, an appearance of invading cancer foci resembled to that of ectopic islands of normal squamous epithelium. These foci of differentiated squamous cell carcinoma gradually underwent morphological change into the so-called cancer pearls. Finally, the cancer pearls degenerated, leaving foreign bodies consisting of concreted keratin. The stromal reaction was characterized by the formation of granulation tissues accompanying significant numbers of foreign body giant cells. In the cases of lingual carcinoma with poor squamous differentiation, these processes were indistinct. Instead, the proliferating anaplastic cancer cells were markedly reduced and the remaining cancer cells transformed into large bizarre cells, probably at degenerative stage. On the histologic level, irradiation showed essentially similar antitumor effect to BLM, except for the rapid formation of concreted keratin bodies accompanying more abundant foreign body giant cells and the presence of irregular granulation tissues at different stages. We concluded that both BLM and irradiation had a powerful antitumor action on squamous cell carcinoma of the tongue. (J.P.N.)

  3. ICD-10-GM und OPS: Neue Versionen für das Jahr 2005

    OpenAIRE

    Müller, W.

    2004-01-01

    Das Deutsche Institut für Medizinische Dokumentation und Information (DIMDI) teilt mit: Für das DRG-Vergütungssystem beginnt am 1. Januar 2005 die Konvergenzphase. Zur Vorbereitung darauf hat das DIMDI die neuen Versionen 2005 der Internationalen Klassifikation der Krankheiten (ICD-10-GM) und des Operationen- und Prozedurenschlüssels (OPS) auf seinen Internetseiten veröffentlicht.

  4. Einfluss von Konstruktion und Betriebsweise von Trinkwasserinstallationen auf das Wachstum von Mikroorganismen im Trinkwasser

    OpenAIRE

    Astitouh, F. (Fariha)

    2013-01-01

    Das Wachstumsverhalten von Biofilmen und Krankheitserregern im Wasser aus Trinkwasserinstallationen wird durch Temperatur und Stagnation beeinflusst. Die Vermeidung von „lauwarmen“ Temperaturen, die das Legionellenwachstum begünstigt, stellt höhere Anforderungen an Konstruktion und Betriebsweise von Kaltwassersystemen. Diese Arbeit analysiert Konstruktionsprinzipien von Stockwerksinstallationen auf den Einfluss auf das Wachstum von Mikroorganismen im Trinkwasser „Kalt“. Die Versuchsanlage sim...

  5. 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.

  6. Anti-tumor effect of IFNγ endostatin gene-radiotherapy in vivo and its mechanism

    International Nuclear Information System (INIS)

    Objective: To study the anti-tumor effect of pEgr-IFN γ-endostatin gene-radiotherapy in mice bearing Lewis lung carcinoma and its mechanism. Methods: The plasmids packed by liposome were injected locally into the tumors of the mice, and the tumors were irradiated with 5 Gy X-rays 36 hours later. The tumor growth rate at different times and the mean survival period of the mice were observed. Cytotoxic activity of splenic CTL, NK and TNFα secretion activity of peritoneal macrophages of the mice in various groups were evaluated 15 days after irradiation. The intratumor microvessel density was evaluated by immunohistochemical staining 10 days after irradiation. Results: The tumor growth rate of the mice in double-gene-radiotherapy group was significantly lower than that of the control group, 5 Gy X-irradiation alone group and single-gene-radiotherapy group 6-18 days after gene-radiotherapy, and the mean survival period of which was longer. The tumor growth rate in mice treated with pEgr-IFN γ-endostatin and 2.5 Gy X-ray irradiation for four times was lower significantly than that in mice treated with pEgr-IFN γ-endostatin and 10 Gy X-irradiation for once only 12-18 days after therapy, and the mean survival time of mice was longer. Cytotoxic activity of splenic CTL, NK and TNF α secretion activity of peritoneal macrophages of the mice in the double-gene-radiotherapy group were significantly higher than those in the control group, 5 Gy X-irradiation alone group and pEgr-endostatin gene-radiotherapy group 15 days after irradiation. The intratumor microvessel density of the mice in double-gene-radiotherapy group was significantly lower than that in the control group, 5 Gy X-irradiation alone group and pEgr-IFNγ gene-radiotherapy group. Conclusions: The anti-tumor effect of double-gene-radiotherapy is significantly better than that of single-gene-radiotherapy. Its mechanism is perhaps associated with the expressions of IFNγ and endostatin induced by X-ray irradiation

  7. Effect of Molecular Weight and Structure on Antitumor Activity of Oxidized Chitosan

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Various low molecular weight chitosans were prepared by oxidative degradation with H2O2, and characterized by IR, 13C-NMR and gel permeation chromatography. Their carboxylic contents increased with decrease in molecular weight (Mw). The antitumor test of the samples against sarcoma 180 tumors suggested that the water-soluble chitosan with higher Mw have higher inhibitory ratio in vivo. The introduction of carboxylic group is advantage to water-solubility of chitosan, but more acidic groups might decrease the function of amino groups of chitosan against sarcoma 180 tumor.

  8. Antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide

    Institute of Scientific and Technical Information of China (English)

    Qi-zhen CAO; Zhi-bin LIN

    2004-01-01

    AIM: To investigate the antitumor and anti-angiogenic activity of Ganoderma lucidum polysaccharides peptide (GLPP). METHODS: Antitumor effect of GLPP was observed in tumor-bearing mice in vivo. At the same time,the effects of GLPP on proliferation of tumor cells and human umbilical cord vascular endothelial cell (HUVEC)were detected by MTT assay in vitro. Subsequently, spleen lymphocytes proliferation of nude mice was stimulated by LPS or ConA. To investigate the anti-angiogenic effect of GLPP, GLPP 80 μg per disc and GLPP-treated serum 10 μL per disc were added to the chick chorioallantoic membrane (CAM) respectively in vivo. RESULTS: GLPP 50, 100, and 200 mg/kg inhibited growth of Sarcoma 180 in BALB/c mice markedly by 35.2 %, 45.2%, and 61.9%,respectively. GLPP which was directly added to the cultured medium did not inhibit PG cell proliferation in vitro;but GLPP-treated serum 50, 100, 200 mg/kg potently inhibited PG cell proliferation by 22.5%, 26.8%, and 30.3 %,respectively; and reduced the xenograft (human lung carcinoma cell PG) in BALB/c nude mice greatly in vivo by 55.5 %, 46.0 %, and 46.8 %, respectively. Lymphocytes proliferation of nude mice could be stimulated by LPS 5 mg/L but not by ConA 2.5 mg/L, indicating that GLPP could not promote the T lymphocyte proliferation and neutral red phagocytosis of peritoneal macrophages of nude mice. The CAM assay showed that GLPP and GLPP-treated serum had anti-angiogenic effect. GLPP (1, 10, and 100 mg/L) inhibited HUVEC proliferation in vitro with the inhibitory rate of 9.4 %, 15.6%, and 40.4%, respectively. CONCLUSION: GLPP has antitumor and antiangiogenic activity. The anti-angiogenesis of GLPP may be a new mechanism underlying its anti-tumor effects.

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

    International Nuclear Information System (INIS)

    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

  10. Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice

    OpenAIRE

    Deng, Liufu; LIANG, Hua; Burnette, Byron; Beckett, Michael; Darga, Thomas; Weichselbaum, Ralph R.; Fu, Yang-Xin

    2014-01-01

    High-dose ionizing irradiation (IR) results in direct tumor cell death and augments tumor-specific immunity, which enhances tumor control both locally and distantly. Unfortunately, local relapses often occur following IR treatment, indicating that IR-induced responses are inadequate to maintain antitumor immunity. Therapeutic blockade of the T cell negative regulator programmed death–ligand 1 (PD-L1, also called B7-H1) can enhance T cell effector function when PD-L1 is expressed in chronicall...

  11. Studies on Synthesis and Antitumor Activity of Phosphorylated Achyranthes bidentata Polysaccharide (P-AbPS)

    Institute of Scientific and Technical Information of China (English)

    CHEN,Xiao-Ming(陈晓明); ZHANG,Jian(张健); TIAN,Geng-Yuan(田庚元)

    2002-01-01

    The synthesis of phosphorylated Achyranthes bidentata polysaccharide (P-AbPS) was reported based on different strategies.The P-AbPS with high degree of substitution (D.S. >0.5) was obtained when phosphorus oxychloride (POCl3) was used as a phosphorylating agent and trimethyl phosphate-pyridine or dimethyl formamide was used as solvent. The influences of different solvents and reaction conditins were discussed. Thepharmacology assay shows that P-AbPS possesses antitumor activity against sarcoma 180 and Lewis lung carner in mice.

  12. 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

  13. Synthesis and Antitumor Activity of Amino Acid Ester Derivatives Containing 5-Fluorouracil

    Directory of Open Access Journals (Sweden)

    Jing Xiong

    2009-08-01

    Full Text Available A series of amino acid ester derivatives containing 5-fluorouracil were synthesized using 1-ethyl-3-(3-dimethylaminopropylcarbodiimide hydrochloride (EDC•HCl and N-hydroxybenzotriazole (HOBt as a coupling agent. The structures of the products were assigned by NMR, MS, IR etc. The in vitro antitumor activity tests against leukaemia HL-60 and liver cancer BEL-7402 indicated that (R-ethyl 2-(2-(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H-ylacetamido-3-(4-hydroxyphenyl propanoate showed more inhibitory effect against BEL-7402 than 5-FU.

  14. Antitumor activity of colloidal silver on MCF-7 human breast cancer cells

    OpenAIRE

    Franco-Molina Moisés A; Mendoza-Gamboa Edgar; Sierra-Rivera Crystel A; Gómez-Flores Ricardo A; Zapata-Benavides Pablo; Castillo-Tello Paloma; Alcocer-González Juan; Miranda-Hernández Diana F; Tamez-Guerra Reyes S; Rodríguez-Padilla Cristina

    2010-01-01

    Abstract Background Colloidal silver has been used as an antimicrobial and disinfectant agent. However, there is scarce information on its antitumor potential. The aim of this study was to determine if colloidal silver had cytotoxic effects on MCF-7 breast cancer cells and its mechanism of cell death. Methods MCF-7 breast cancer cells were treated with colloidal silver (ranged from 1.75 to 17.5 ng/mL) for 5 h at 37°C and 5% CO2 atmosphere. Cell Viability was evaluated by trypan blue exclusion...

  15. Synthesis and preliminary study on a new class anti-tumor agents--acetylthiophene thiosemicarbazone

    International Nuclear Information System (INIS)

    Six 2-acetylthiophene TSC have been synthesized and characterized by IR, MC and elemental analysis. Five of them are the first prepared compounds. The anti-tumor activities of them have been investigated. The results show that they have high inhibition to all three carcinoma cells (KB cell, HCT-8 cell and Bel 7402 cell). These ligands are labelled with 111In. The bio-distributions of six 111In ligand complexes in mice are determined. The results show that concentrating of 111In ligand complexes in blood is not apparent. Further study is needed to see the uptake of 111In ligand complexes by carcinoma cells

  16. Anti-Angiogenesis and Anti-Tumor Effect of Shark Cartilage Extract

    Institute of Scientific and Technical Information of China (English)

    王锋; 王漪涛; 谢莉萍; 张荣庆

    2001-01-01

    The effect of shark cartilage extract (SCE), purified in this laboratory, on angiogenesis in chick chorioallantoic membrane (CAM), on the activity of collagenase IV and on human umbilical vein endothelial cell (ECV-304) proliferation and apoptosis was investigated in vitro. The results showed that SCE caused a decline in CAM blood vessels and significantly prevented collagenase-induced collagenolysis. Moreover, SCE produced a dose-dependent decline in ECV-304 proliferation and altered its normal cell cycle. These results suggest that the anti-angiogenesis and anti-tumor effects of shark cartilage may be due to inhibition of endothelial cells as well as collagenolysis.

  17. Actividad antitumoral y toxicidad de (+)-curcufenol y de curcudiol aislados de la esponja marina didisus oxeata

    OpenAIRE

    Salama, Ahmed M.; Fonseca, Claudia; Renjifo, Laura

    2009-01-01

    El extracto metanólico, el extracto clorofórmico, el curcufenol y el curcudiol obtenido de la esponja fueron evaluados frente a Artemia salina obteniéndose una concentración letal media de 0.54, 5.57, 3.10 y 0.70 m g/mL, respectivamente. También se probó su actividad antitumoral mediante el bioensayo de tumorogénesis inducida por Agrobacterium tumefaciens en disco de zanahoria, produciéndose inhibición en concentraciones mayores de 60 m g/mL.

  18. Antitumor Activity of Antimicrobial Peptides Containing CisoDGRC in CD13 Negative Breast Cancer Cells

    OpenAIRE

    Hou, Lei; ZHAO, XINHAN; Wang, Pei; Ning, Qian; Meng, Min; Liu, Caigang

    2013-01-01

    Backgroud isoAsp-Gly-Arg (isoDGR) is a derivative of the Asn-Gly-Arg (NGR) motif, which is used as a targeted delivery tool to aminopeptidase N (CD13) positive cells. Recent studies have shown that cyclic isoDGR (CisoDGRC) has a more efficient affinity with αvβ3, a type of integrin that overexpresses in tumor cells. Antimicrobial peptides (AMPs) are an efficient antitumor peptide that specifically kills tumor cells. In the present study, we designed antimicrobial peptides containing the CisoD...

  19. Mecanismos moleculares involucrados en la citotoxicidad del agente antitumoral beta-lapachona.

    OpenAIRE

    Menacho-Márquez, Mauricio

    2008-01-01

    Beta-lapachona ( -lap) es un agente antitumoral que induce apoptosis selectivamente en células tumorales. El mecanismo preciso de citotoxicidad de -lap no es aún completamente comprendido. Aquí reportamos que -lap produce un retraso en la progresión del ciclo celular en la transición G1/S, aumenta la fosforilación de la quinasa de control Rad53p y disminuye la supervivencia celular en la levadura de gemación Saccharomyces cerevisiae. Además, -lap induce la fosforilación de histona H2A en l...

  20. In vitro and In vivo Evaluation of Select Kahalalide F Analogs with Antitumor and Antifungal Activities

    OpenAIRE

    Shilabin, Abbas Gholipour; Hamann, Mark T

    2011-01-01

    Kahalalide F (KF) and the regioisomer isoKF are novel anticancer drugs of marine origin and currently under clinical investigation. Here we report the synthesis of two new KF analogs with significant in vitro and in vivo antifungal and antitumor activities. The primary amine hydrogen of ornithine in KF has been replaced with 4-fluoro-3-methylbenzyl and morpholin-4-yl-benzyl via reductive N-alkylation. The TGI of these analogs using the NCI-60 cell line screening revealed promising results whe...

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

    OpenAIRE

    Luara de Sousa Monteiro; Katherine Xavier Bastos; José Maria Barbosa-Filho; Petrônio Filgueiras de Athayde-Filho; Margareth de Fátima Formiga Melo Diniz; Marianna Vieira Sobral

    2014-01-01

    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 animal...

  2. 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

  3. Neustart des LHC das Higgs-Teilchen und das Standardmodell : die Teilchenphysik hinter der Weltmaschine anschaulich erklärt

    CERN Document Server

    Knochel, Alexander

    2016-01-01

    Dieses Essential gibt eine kompakte Einführung in unser aktuelles Bild der Elementarteilchenphysik. Es legt dabei den Schwerpunkt auf Phänomene wie das Higgs-Teilchen, welche am Large Hadron Collider (LHC) erforscht werden. Der LHC am Forschungszentrum CERN bei Genf ist der leistungsfähigste Beschleuniger der Welt und läuft seit dem Frühjahr 2015 erneut mit Rekordenergie. Der Autor beschreibt, wie das sogenannte „Standardmodell der Teilchenphysik“ aufgebaut ist und wie die Experimente des LHC es durch genauere Messungen festigen und durch neue Entdeckungen revolutionieren können. Dabei werden die wichtigsten grundlegenden Begriffe erklärt: Was sind beispielsweise virtuelle Teilchen, und welche Rolle spielen sie in der Natur? Was ist eine Quantenfeldtheorie? Sind die Elementarteilchen wirklich elementar? Was ist Symmetriebrechung?

  4. Determinantes das comunicações word-of-mouth dos alunos das escolas profissionais em Portugal

    OpenAIRE

    Rodrigues, Teresa Margarida Oliveira; Ferreira, Alcina Teresa Gaspar

    2014-01-01

    Este estudo analisa o impacto da satisfação, da lealdade, da qualidade percebida, da confiança, do compromisso, do valor percebido, das emoções, da imagem corporativa e do ano frequentado na criação de comunicação word-of-mouth (WOM) positiva e negativa no contexto dos serviços de educação. O modelo de investigação foi testado numa amostra de 2787 alunos das escolas profissionais portuguesas, tendo-se concluído que as variáveis que determinam as valências positiva e negativa do WOM não são ne...

  5. Neurobiologia das emoções Neurobiology of the emotions

    Directory of Open Access Journals (Sweden)

    Vanderson Esperidião-Antonio

    2008-01-01

    Full Text Available CONTEXTO: A "natureza" das emoções é um dos temas arcaicos do pensamento ocidental, sendo tematizada em diferentes manifestações da cultura como a arte, a religião, a filosofia e a ciência, desde tempos imemoriais. Nos últimos anos, o avanço das neurociências possibilitou a construção de hipóteses para a explicação das emoções, especialmente a partir dos estudos envolvendo o sistema límbico. OBJETIVOS: Apresentar uma discussão atualizada acerca da neurobiologia dos processos relativos às emoções, demarcando suas conexões com o controle neurovegetativo. MÉTODOS: Revisão da literatura e reflexão crítica dos textos obtidos. RESULTADOS: Apresentação das principais estruturas neurais relativas às emoções, suas vias e circuitos de maior relevância, os neurotransmissores implicados, seguindo-se uma discussão sobre as principais emoções. CONCLUSÕES: Espera-se que o presente manuscrito possa contribuir à difusão de idéias sobre o sistema das emoções, as quais poderão motivar futuros estudos capazes de elucidar pontos ainda em aberto.BACKGROUND: The "nature" of emotions is one of the archaic subjects of the western thought, being the theme choice in diverse manifestations of culture - as in art, religion, philosophy and science - from time immemorial. In recent years the advances in Neurosciences have made it possible to build hypotheses to explain emotions, a possibility derived particularly from the studies involving the limbic system. OBJECTIVES: To present an updated discussion about the neurobiology of the processes relating to emotions and their connections with neurovegetative control. METHODS: Review of the literature on the subject. RESULTS: An updated account of the main neural structures related with emotions, the pathways and circuits of greater relevance as well as the regarding neurotransmitters. The neurobiological aspects of emotions are also discussed. DISCUSSION: It is expected that the present

  6. 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.

  7. Adoptive transfer of Tc1 or Tc17 cells elicits antitumor immunity against established melanoma through distinct mechanisms.

    Science.gov (United States)

    Yu, Yu; Cho, Hyun-Ii; Wang, Dapeng; Kaosaard, Kane; Anasetti, Claudio; Celis, Esteban; Yu, Xue-Zhong

    2013-02-15

    Adoptive cell transfer (ACT) of ex vivo-activated autologous tumor-reactive T cells is currently one of the most promising approaches for cancer immunotherapy. Recent studies provided some evidence that IL-17-producing CD8(+) (Tc17) cells may exhibit potent antitumor activity, but the specific mechanisms have not been completely defined. In this study, we used a murine melanoma lung-metastasis model and tested the therapeutic effects of gp100-specific polarized type I CD8(+) cytotoxic T (Tc1) or Tc17 cells combined with autologous bone marrow transplantation after total body irradiation. Bone marrow transplantation combined with ACT of antitumor (gp100-specific) Tc17 cells significantly suppressed the growth of established melanoma, whereas Tc1 cells induced long-term tumor regression. After ACT, Tc1 cells maintained their phenotype to produce IFN-γ, but not IL-17. However, although Tc17 cells largely preserved their ability to produce IL-17, a subset secreted IFN-γ or both IFN-γ and IL-17, indicating the plasticity of Tc17 cells in vivo. Furthermore, after ACT, the Tc17 cells had a long-lived effector T cell phenotype (CD127(hi)/KLRG-1(low)) as compared with Tc1 cells. Mechanistically, Tc1 cells mediated antitumor immunity primarily through the direct effect of IFN-γ on tumor cells. In contrast, despite the fact that some Tc17 cells also secreted IFN-γ, Tc17-mediated antitumor immunity was independent of the direct effects of IFN-γ on the tumor. Nevertheless, IFN-γ played a critical role by creating a microenvironment that promoted Tc17-mediated antitumor activity. Taken together, these studies demonstrate that both Tc1 and Tc17 cells can mediate effective antitumor immunity through distinct effector mechanisms, but Tc1 cells are superior to Tc17 cells in mediating tumor regression. PMID:23315072

  8. Sex differences in response to anti-tumor necrosis factor therapy in early and established rheumatoid arthritis -- results from the DANBIO registry

    DEFF Research Database (Denmark)

    Jawaheer, Damini; Olsen, Jørn; Hetland, Merete Lund

    2012-01-01

    To investigate sex differences in response to anti-tumor necrosis factor-a (TNF-a) therapy over time in early versus established rheumatoid arthritis (RA).......To investigate sex differences in response to anti-tumor necrosis factor-a (TNF-a) therapy over time in early versus established rheumatoid arthritis (RA)....

  9. Structural organization of C60 fullerene, doxorubicin, and their complex in physiological solution as promising antitumor agents

    International Nuclear Information System (INIS)

    Specific features of structural self-organization of C60 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, C60 + 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 C60 fullerene

  10. Gecko Proteins Exert Anti-Tumor Effect against Cervical Cancer Cells Via PI3-Kinase/Akt Pathway

    OpenAIRE

    Jeong, Ae-Jin; Chung, Chung-Nam; Kim, Hye-Jin; Bae, Kil Soo; Choi, Song; Jun, Woo Jin; Shim, Sang In; Kang, Tae-Hong; Leem, Sun-Hee; Chung, Jin Woong

    2012-01-01

    Anti-tumor activity of the proteins from Gecko (GP) on cervical cancer cells, and its signaling mechanisms were assessed by viable cell counting, propidium iodide (PI) staining, and Western blot analysis. GP induced the cell death of HeLa cells in a dose-dependent manner while it did not affect the viability of normal cells. Western blot analysis showed that GP decreased the activation of Akt, and co-administration of GP and Akt inhibitors synergistically exerted anti-tumor activities on HeLa...

  11. Synthesis and antitumor and antibacterial evaluation of fluoroquinolone derivatives (Ⅲ) : Mono-and bis-Schiff-bases

    Institute of Scientific and Technical Information of China (English)

    Guo Qiang Hu; Wen Long Huang; Xiao Kui Wu; Guo Qiang Wang; Nan Nan Duan; Xiao Yi Wen; Tie Yao Cao; Yin Jun; Wang Wei; Song Qiang Xie

    2012-01-01

    To further explore an efficient modified route for the shift from an antibacterial fluoroquinolone to an antitumor one,monoSchiff bases 6a-6h related to ciprofloxacin C3 carbonylhydrazone and bis-Schiff bases 4a-4h corresponding to C3/C7 carbonylhydrazone/hydrazone attached on a skeleton of ciprofloquinolone were designed and synthesized,and their in vitro antitumor activity against CHO,HL60,L1210 cells and antibacterial activity against Staphylococcus aureus and Escherichia coli were also reported.

  12. In Vitro Antitumor Activity of a Keggin Vanadium-Substituted Polyoxomolybdate and Its ctDNA Binding Properties

    OpenAIRE

    2015-01-01

    A Keggin vanadium-substituted polyoxomolybdate, K5PMo10V2O40 (PMo10V2), has been synthesized and it’s antitumor effect against Hela cells was investigated. The calf thymus DNA (ctDNA) binding ability of PMo10V2 was also evaluated by UV-Vis absorption spectra and fluorescence spectra. The identity and high purity of PMo10V2 was confirmed by elemental analysis and IR analysis. And the antitumor activity test of PMo10V2 was carried out on Hela cancer cells line by MTT assay. The results of MTT ...

  13. 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.

  14. PEGylation alleviates the non-specific toxicities of Alpha-Momorcharin and preserves its antitumor efficacy in vivo.

    Science.gov (United States)

    Deng, Nian-hua; Wang, Ling; He, Qian-chuan; Zheng, Jue-cun; Meng, Yao; Meng, Yan-Fa; Zhang, Chong-Jie; Shen, Fu-bing

    2016-01-01

    Alpha-Momorcharin (α-MMC) is a ribosome inactivating protein from Momordica charantia with anti-tumor activity. Previously, we had observed that modification of α-MMC with polyethylene glycol (PEG) could reduce toxicity, but it also reduces its anti-tumor activity in vitro. This study aims to investigate whether the metabolism-extended properties of α-MMC resulting from PEGylation could preserve its anti-tumor efficacy in vivo through pharmacokinetics and antitumor experiments. The pharmacokinetics experiments were conducted in rats using the TCA (Trichloroacetic Acid) method. Antitumor activity in vivo was investigated in murine mammary carcinoma (EMT-6) and human mammary carcinoma (MDA-MB-231) transplanted tumor mouse models. The results showed that PEGylation increased the plasma half-life of α-MMC in rats from 6.2-7.5 h to 52-87 h. When administered at 1 mg/kg, α-MMC-PEG and α-MMC showed similar anti-tumor activities in vivo, with a T/C% of 38.56% for α-MMC versus 35.43% for α-MMC-PEG in the EMT-6 tumor model and 36.30% for α-MMC versus 39.88% for α-MMC-PEG in the MDA-MB-231 tumor model (p > 0.05). Importantly, at the dose of 3 mg/kg, all the animals treated with α-MMC died while the animals treated with α-MMC-PEG exhibited only moderate toxic reactions, and α-MMC-PEG exhibited improved anti-tumor efficacy with a T/C% (relative tumor growth rate) of 25.18% and 21.07% in the EMT-6 and MDA-MB-231 tumor models, respectively. The present study demonstrates that PEGylation extends the half-life of α-MMC and alleviates non-specific toxicity, thereby preserving its antitumor efficacy in vivo, and a higher lever of dosage can be used to achieve better therapeutic efficacy. PMID:24786488

  15. 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.

  16. Anti-Tumor Effect and Anti-Inflammatory Activity of Boschniakia rossica

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the anti-tumor effect and anti-inflammatory activity of Boschniakia rossica (BR). Methods: The expression of tumor marker, GST-P, p53 and p21ras proteins in promotion stage of rat chemical hepatocarcinogenesis were examined by immunohistochemical technique ABC method. Anti-tumor effect of BR was investigated by inhibitory test on Sarcoma180. Anti-inflammatory activity of BR was tested by xylene-induced mouse ear swelling method. Results: BR-H2O extract (the H2O extract fractionated from BR-Methanol extract with CH2Cl2 and H2O) 500 mg/kg has inhibitory effect on the formation of diethylnitrosamine (DEN)-induced glutathione S-transferase placental form (GST-P) positive foci in rat liver with the expression of mutant p53 and p21ras proteins lower than those of non-treated hepatic preneoplastic lesions. BR extract showed inhibitory effect on Sarcoma180 and anti-inflammatory effect in mice by xylene-induced mouse ear swelling tests. Conclusion: BR- H2O extract exerted inhibitory effect on DEN-induced preneoplastic hepatic foci in promotion stage of rat chemical hepatocarcinogenesis and might suppress the growth of solid Sarcoma180 in mice. Both CH2Cl2 and H2O extract from BR exerted anti-inflammatory effect in mice.

  17. Purification, Characterization and Antitumor Activities of a New Protein from Syngnathus acus, an Officinal Marine Fish

    Directory of Open Access Journals (Sweden)

    Ying Peng

    2011-12-01

    Full Text Available Discovery and development of new antitumor agents from abundant marine fish are attracting an increasing interest. In the present study, we extracted and purified a novel antitumor protein Syngnathusin from the whole body of Syngnathus acus L., a precious marine fish traditionally used for tumors. Syngnathusin was comprised of 16 kinds of amino acids, mainly acidic amino acids. Its molecular weight was 67.3 kDa and its isoelectric point was 4.57. The N-terminal amino acid sequence of Syngnathusin was determined to be Lys-Arg-Asp-Leu-Gly-Phe-Val-Asp-Glu-Ile-Ser-Ala-His-Tyr and showed no significant homology with the known proteins. Syngnathusin could significantly inhibit the growth of A549 and CCRF-CEM cells. However, the obvious proliferation inhibition against human non-tumor cell lines was not observed. Flow cytometry, morphologic assessment and comet assay revealed that Syngnathusin could induce apoptosis in A549 and CCRF-CEM cells and strongly cooperated with MTX. Syngnathusin could inhibit the growth of S180 tumor transplanted in mice. Syngnathusin may be developed as a novel, selective and effective antineoplastic agent.

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

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Daniela P. [University of Sao Paulo State, UNESP, Institute of Chemistry (Brazil); Ruiz, M. Adolfina; Gallardo, Visitacion [University of Granada, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy (Spain); Zanoni, Maria Valnice B. [University of Sao Paulo State, UNESP, Institute of Chemistry (Brazil); Arias, Jose L., E-mail: jlarias@ugr.es [University of Granada, Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy (Spain)

    2011-09-15

    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 Almost-Equal-To 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 Degree-Sign 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.

  19. PROTEÍNAS DE CHOQUE TÉRMICO, MUERTE CELULAR Y RESPUESTA ANTITUMORAL

    Directory of Open Access Journals (Sweden)

    S. Fiorentino

    2007-12-01

    Full Text Available Heat shock proteins (HSP, particularly inducible HSP72 protein, have an important role generating aneffective antitumoral response as immunogenic peptide carriers or as immunostimulants, when induceactivation and maturation of dendritic cells (DC. These proteins, as molecular chaperones ATP dependant,increase cell survival under any kind of stress. Chaperone function is intrinsic of protein family HSP70structure, having a C-terminal domain that binds unfolded proteins and peptides and a N-terminal ATPasedomain that controls peptide binding pocket opening and closing. Their immunostimulant role mayantagonize with their protective activity against cell death induced by stress or cytotoxic agents. InducibleHSP70 protein is involved in carrying out these two functions, which is the purpose of this review.Furthermore, other members of HSP70 protein family could be implicated, but in different ways: inducingimmune response or promoting tumoral growth inhibiting apoptosis. Comprehension of mechanisms thatregulate both activities is crucial in developing an effective antitumoral therapy through searchingsubstances, which preserving their immunogenic potential, do not increase tumor resistance to classicalantitumoral therapy.

  20. Antitumor activity of rhein lysinate against human glioma U87 cells in vitro and in vivo.

    Science.gov (United States)

    Liu, Jin; Zhang, Ke; Zhen, Yong-Zhan; Wei, Jie; Hu, Gang; Gao, Jun-Ling; Tian, Yan-Xia; Lin, Ya-Jun

    2016-03-01

    In previous studies, we demonstrated that rhein lysinate (RHL), the salt of rhein and lysine that is easily dissolved in water, inhibited the growth of tumor cells derived from breast and ovarian cancer, hepatocellular carcinoma, cervical cancer and lung carcinoma. Based on these observations, human glioma U87 cells and a xenograft model in BALB/c nude mice were used to examine the antitumor activity of RHL against human glioma. Notably, RHL statistically significantly suppressed the growth of human glioma U87 xenografts in BALB/c nude mice. In vitro, there was a significant reduction in cell proliferation after treatment with RHL in a dose- and time-dependent manner. The overall growth inhibition was correlated with the increase in reactive oxygen species (ROS) production and cell apoptosis. The apoptosis- and cell cycle-related proteins including BAX and Bim were increased, whereas Bcl-2 and cyclin D were decreased in the RHL-treated cells. The results demonstrated that RHL is highly effective against the growth of human glioma U87 xenografts in BALB/c nude mice. The potent antitumor activity of RHL may be mediated through downregulation of Bcl-2 and cyclin D expression and upregulation of BAX and Bim expression. PMID:26707131

  1. Antitumor Activity of Garcinol in Human Prostate Cancer Cells and Xenograft Mice.

    Science.gov (United States)

    Wang, Yu; Tsai, Mei-Ling; Chiou, Li-Yu; Ho, Chi-Tang; Pan, Min-Hsiung

    2015-10-21

    Garcinol, which is isolated from fruit rinds of Garcinia indica, is a polyisoprenylated benzophenone. It has been studied for its antitumor activity by inducing apoptosis and inhibiting autophagy in human prostate cancer cells. The Bax/Bcl-2 ratio increased when garcinol was applied to PC-3 cells indicating a presence of apoptosis. Meanwhile, procaspases-9 and -3 were suppressed with attenuating PARP and DFF-45. Autophagy was inhibited through activating p-mTOR and p-PI3 Kinase/AKT by garcinol, which as a result induced the cells to apoptosis directly. In addition, the apoptosis effect of garcinol in a xenograft mouse model was also tested, suggesting a consistent result with PC-3 cell model. The tumor size was reduced more than 80 percent after the mouse accepted the garcinol treatment. Garcinol was demonstrated to have a strong antitumor activity through inhibiting autophagy and inducing apoptosis, which was discovered for the first time. Based on these findings, our data suggests that garcinol deserves further investigation as a potent chemopreventive agent. PMID:26442822

  2. High in Vitro Anti-Tumor Efficacy of Dimeric Rituximab/Saporin-S6 Immunotoxin.

    Science.gov (United States)

    Bortolotti, Massimo; Bolognesi, Andrea; Battelli, Maria Giulia; Polito, Letizia

    2016-01-01

    The anti-CD20 mAb Rituximab has revolutionized lymphoma therapy, in spite of a number of unresponsive or relapsing patients. Immunotoxins, consisting of toxins coupled to antibodies, are being investigated for their potential ability to augment Rituximab efficacy. Here, we compare the anti-tumor effect of high- and low-molecular-weight Rituximab/saporin-S6 immunotoxins, named HMW-IT and LMW-IT, respectively. Saporin-S6 is a potent and stable plant enzyme belonging to ribosome-inactivating proteins that causes protein synthesis arrest and consequent cell death. Saporin-S6 was conjugated to Rituximab through an artificial disulfide bond. The inhibitory activity of HMW-IT and LMW-IT was evaluated on cell-free protein synthesis and in two CD20⁺ lymphoma cell lines, Raji and D430B. Two different conjugates were separated on the basis of their molecular weight and further characterized. Both HMW-IT (dimeric) and LMW-IT (monomeric) maintained a high level of enzymatic activity in a cell-free system. HMW-IT, thanks to a higher toxin payload and more efficient antigen capping, showed stronger in vitro anti-tumor efficacy than LMW-IT against lymphoma cells. Dimeric HMW-IT can be used for lymphoma therapy at least for ex vivo treatments. The possibility of using HMW-IT augments the yield in immunotoxin preparation and allows the targeting of antigens with low internalization rates. PMID:27338475

  3. High in Vitro Anti-Tumor Efficacy of Dimeric Rituximab/Saporin-S6 Immunotoxin

    Directory of Open Access Journals (Sweden)

    Massimo Bortolotti

    2016-06-01

    Full Text Available The anti-CD20 mAb Rituximab has revolutionized lymphoma therapy, in spite of a number of unresponsive or relapsing patients. Immunotoxins, consisting of toxins coupled to antibodies, are being investigated for their potential ability to augment Rituximab efficacy. Here, we compare the anti-tumor effect of high- and low-molecular-weight Rituximab/saporin-S6 immunotoxins, named HMW-IT and LMW-IT, respectively. Saporin-S6 is a potent and stable plant enzyme belonging to ribosome-inactivating proteins that causes protein synthesis arrest and consequent cell death. Saporin-S6 was conjugated to Rituximab through an artificial disulfide bond. The inhibitory activity of HMW-IT and LMW-IT was evaluated on cell-free protein synthesis and in two CD20+ lymphoma cell lines, Raji and D430B. Two different conjugates were separated on the basis of their molecular weight and further characterized. Both HMW-IT (dimeric and LMW-IT (monomeric maintained a high level of enzymatic activity in a cell-free system. HMW-IT, thanks to a higher toxin payload and more efficient antigen capping, showed stronger in vitro anti-tumor efficacy than LMW-IT against lymphoma cells. Dimeric HMW-IT can be used for lymphoma therapy at least for ex vivo treatments. The possibility of using HMW-IT augments the yield in immunotoxin preparation and allows the targeting of antigens with low internalization rates.

  4. Anti-Tumor Effect of Heat Shock Protein 70-Peptide Complexes on A-549 Cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the anti-tumor immunity in vitro of heat shock protein 70-peptide complexes (HSP70-PC) from human lung cancer tissue. Methods: HSP70-PC was purified from lung tumor tissues and corresponding non-tumor lung samples with the methods of ADP-affinity chromatography, DEAE ion-exchange chromatography and Western-blot. The activation and proliferation of PBMC induced by different HSP70-PC and tumor cytotoxic reactivity to A549 cells in vitro were measured by the MTT cell proliferation assay. Results: The purified HSP70-PC had a very high purity found by SDS-PAGE and Western-blot. Human lymphocytes were sensitized efficiently by HSP70 preparation purified from lung cancer tissues and a definite cytotoxicity to A-549 cells was observed. There was significant difference with HSP70-PC purified from lung cancer, compared with the control group (P<0.001). Conclusion: High purity of HSP70-PC could be achieved from tumor tissues in this study. HSP70-PC purified from human tumor tissues can induce anti-tumor immunity in vitro mainly implemented by eliciting CTL immunity.

  5. Enhanced Anti-tumor Reactivity of Cytotoxic T Lymphocytes Expressing PD-1 Decoy

    Science.gov (United States)

    Shin, Jae Hun; Park, Hyung Bae

    2016-01-01

    Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy. PMID:27162530

  6. LJNK, an indoline-2,3-dione-based aminopeptidase N inhibitor with promising antitumor potency.

    Science.gov (United States)

    Hou, Jinning; Jin, Kang; Li, Jin; Jiang, Yuqi; Li, Xiaoyang; Wang, Xuejian; Huang, Yongxue; Zhang, Yingjie; Xu, Wenfang

    2016-07-01

    In our previous study, we found that LJNK showed potent aminopeptidase N (APN)-inhibitory activity. In the current study, we further evaluated the antitumor effects of LJNK both in vitro and in vivo. Enzyme experiments showed that LJNK showed better inhibitory activity than bestatin against APN both from human carcinoma cells' surface and from porcine kidney microsomes. In addition, LJNK could suppress rat aortic ring microvessel growth and HUVEC tubular structure formation, which showed its stronger antiangiogenesis effects than bestatin. [(3-[4,5-Dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide)] assay and clonogenic assay showed that LJNK suppressed cancer cell growth both in the short and the long term. Mice bearing H22 transplantation tumor proved its antitumor effects in vivo. Annexin V-fluorescein isothiocyanate/propidium iodide assay showed that LJNK could induce 28.1% PLC/PRF/5 cell apoptosis and the apoptotic pathway was probably identified by western blot. The above-mentioned results suggested that LJNK inhibited cell proliferation and angiogenesis, and induced apoptosis by decreasing APN activity. PMID:26872309

  7. 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.

  8. Supramolecular nanoparticles generated by the self-assembly of polyrotaxanes for antitumor drug delivery

    Science.gov (United States)

    Liu, Rong; Lai, Yusi; He, Bin; Li, Yuan; Wang, Gang; Chang, Shuang; Gu, Zhongwei

    2012-01-01

    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 α-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. PMID:23055732

  9. 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.

  10. 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.

  11. β-glucan restores tumor-educated dendritic cell maturation to enhance antitumor immune responses.

    Science.gov (United States)

    Ning, Yongling; Xu, Dongqin; Zhang, Xiaohang; Bai, Yu; Ding, Jun; Feng, Tongbao; Wang, Shizhong; Xu, Ning; Qian, Keqing; Wang, Yong; Qi, Chunjian

    2016-06-01

    Tumors can induce the generation and accumulation of immunosuppressive cells such as myeloid-derived suppressor cells (MDSCs) in a tumor microenvironment, contributing to tumor escape from immunological attack. Although dendritic cell-based cancer vaccines can initiate antitumor immune responses, tumor-educated dendritic cells (TEDCs) involved in the tolerance induction have attracted much attention recently. In this study, we investigated the effect of β-glucan on TEDCs and found that β-glucan treatment could promote the maturation and migration of TEDCs and that the suppressive function of TEDCs was significantly decreased. Treatment with β-glucan drastically decreased the levels of regulatory T (Treg) cells but increased the infiltration of macrophages, granulocytes and DCs in tumor masses, thus elicited Th1 differentiation and cytotoxic T-lymphocyte responses and led to a delay in tumor progression. These findings reveal that β-glucan can inhibit the regulatory function of TEDCs, therefore revealing a novel function for β-glucan in immunotherapy and suggesting its potential clinical benefit. β-Glucan directly abrogated tumor-educated dendritic cells-associated immune suppression, promoted Th1 differentiation and cytotoxic T-lymphocyte priming and improved antitumor responses. PMID:26773960

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

    Science.gov (United States)

    Haiyan, Gong; Lijuan, He; Shaoyu, Li; Chen, Zhang; Ashraf, Muhammad Aqeel

    2016-07-01

    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. PMID:27298587

  13. 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.

  14. An armed oncolytic adenovirus system,ZD55-gene,demonstrating potent antitumoral efficacy

    Institute of Scientific and Technical Information of China (English)

    ZI LAI ZHANG; WEI GUO ZOU; CHUN XIA LUO; BING HUA LI; JIN HUI WANG; LAN YING SUN; QI JUN QIAN; XIN YUAN LIU

    2003-01-01

    ONYXONYX-015 is an attractive therapeutic adenovirus for cancer because it can selectively replicate in tumor cells and kill them.To date,clinicaltrials of this adenovirus have demonstrated marked safety but not potent enough when it was used alone.In this paper,we put forward a novel concept of Gene-Viro Therapy strategy and in this way,we constructed an armed therapeutic onco1ytic adenovirus system,ZD55-gene,whichis not only deleted of E1B 55-kD gene similar to ONYX-015,but also armed with foreign antitumor gene.ZD55-gene exhibited similar cytopathic effects and replication Kinetics to that of ONYX-015 in vitro.Importantly,the carried gene 1s expressed and the expression level can increase with the replication of virus.Consequently,a significant antitumoral efficacy was observed when ZD55-CD/5-FU was used as an example in nude mice with subcutaneous human SW620 colon cancer.Our data demonstratedthat ZD55-gene,which utilizingthe Gene-ViroTherapy strategy,is more efficacious than each individual component in vivo.

  15. Modified chitosan thermosensitive hydrogel enables sustained and efficient anti-tumor therapy via intratumoral injection.

    Science.gov (United States)

    Jiang, Yingchun; Meng, Xuanyu; Wu, Zhenghong; Qi, Xiaole

    2016-06-25

    Thermosensitive in situ hydrogels are potential candidates to achieve intratumoral administration, nevertheless their weak mechanical strength always lead to serious drug leakage and burst. Herein, we developed a chitosan based thermosensitive hydrogel of high mechanical strength, which was modified by glutaraldehyde (GA) and polyvinyl alcohol (PVA), for intratumoral delivery of paclitaxel (PTX). The modified hydrogel system could achieve sol-gel transition at 35.79±0.4°C and exhibit a 7.03-fold greater mechanical strength compared with simple chitosan hydrogel. Moreover, the drug release of PTX loaded modified hydrogel in PBS (pH 7.4) was found to be extended to 13 days. After intratumoral administration in mice bearing H22 tumors, PTX-loaded modified hydrogels exhibited a 3.72-fold greater antitumor activity compared with Taxol(®). Overall, these modified hydrogel systems demonstrated to be a promising way to achieve efficient sustained release and enhanced anti-tumor therapy efficiency of anticancer drugs through in situ tumor injectable administration. PMID:27083815

  16. Enhanced Anti-tumor Reactivity of Cytotoxic T Lymphocytes Expressing PD-1 Decoy.

    Science.gov (United States)

    Shin, Jae Hun; Park, Hyung Bae; Choi, Kyungho

    2016-04-01

    Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy. PMID:27162530

  17. Transcriptome Profiling Reveals the Antitumor Mechanism of Polysaccharide from Marine Algae Gracilariopsis lemaneiformis

    Science.gov (United States)

    Li, Hua; Wu, Jun; Xu, Xiaoting; Sun, Xue; Zhao, Xiaodong; Xu, Nianjun

    2016-01-01

    Seaweed is one of the important biomass producers and possesses active metabolites with potential therapeutic effects against tumors. The red alga Gracilariopsis lemaneiformis (Gp. lemaneiformis) possesses antitumor activity, and the polysaccharide of Gp. lemaneiformis (PGL) has been demonstrated to be an ingredient with marked anticancer activity. However, the anticancer mechanism of PGL remains to be elucidated. In this study, we analyzed the inhibitory effect of PGL on the cell growth of 3 human cancer cell lines and found that PGL inhibited cell proliferation, reduced cell viability, and altered cell morphology in a time- and concentration-dependent manner. Our transcriptome analysis indicates that PGL can regulate the expression of 758 genes, which are involved in apoptosis, the cell cycle, nuclear division, and cell death. Furthermore, we demonstrated that PGL induced apoptosis and cell cycle arrest and modulated the expression of related genes in the A549 cell line. Our work provides a framework to understand the effects of PGL on cancer cells, and can serve as a resource for delineating the antitumor mechanisms of Gp. lemaneiformis. PMID:27355352

  18. Antitumor and immune regulation activities of the extracts of some Chinese marine invertebrates

    Institute of Scientific and Technical Information of China (English)

    ZHANG Lixin; FAN Xiao; HAN Lijun

    2005-01-01

    Extracts of 21 marine invertebrates belonging to Coelenterata, Mollusca, Annelida, Bryozoa,Echiura, Arthropoda, Echinodermata and Urochordata were screened for the studies on their antitumor and immune regulation activities. Antitumor activity was determined by MTT method and immune regulation activity was studied using T- and B-lymphocytes in mice spleen in vitro. It was found that the n-butanol part of Asterina pectinifera, the acetic ether part of Tubuaria marina, 95% ethanol extract of Acanthochiton rubrolineatus have a high inhibition rate of 96.7%, 63.9% and 50.5% respectively on tumor cell line HL-60 at the concentration of 0.063 mg/ml. The inhibition rate of the acetic ether part of Tubuaria marina on the tumor cell line A-549 is 65.4 % at concentration of 0.063 mg/mL. The 95% ethanol extract of Meretrix meretrix has so outstanding promoting effect on T-lymphocyfes that their multiplication increases 25% when the sample concentration is only 1 μg/ml. On B-lymphocytes, the 95% extract of Rapana venosa, at concentration of 100μg/ml, has a promotion percentage of 60%. On the other hand, under the condition of no cytotoxic effect, the 95% ethanol extracts of Acanthochiton rubrolineatus and Cellana toreum can reach 92% inhibition rate on T lymphocyte at concentration of 100 μg/ml, while the inhibition rate on B lymphocyte of the 95% extract of Acanthochiton rubrolineatus reaches 92% at the same concentration.

  19. Epigenetic suppression of the antitumor cytotoxicity of NK cells by histone deacetylase inhibitor valproic acid

    Science.gov (United States)

    Shi, Xiumin; Li, Min; Cui, Meizi; Niu, Chao; Xu, Jianting; Zhou, Lei; Li, Wei; Gao, Yushun; Kong, Weisheng; Cui, Jiuwei; Hu, Jifan; Jin, Haofan

    2016-01-01

    Natural killer (NK) cells play an essential role in the fight against tumor development. The therapeutic use of autologous NK cells has been exploited to treat human malignancies, yet only limited antitumor activity is observed in cancer patients. In this study, we sought to augment the antitumor activity of NK cells using epigenetic approaches. Four small molecules that have been known to promote epigenetic reprogramming were tested for their ability to enhance the activity of NK cells. Using a tumor cell lysis assay, we found that the DNA demethylating agent 5-azacytidine and vitamin C did not significantly affect the tumor killing ability of NK cells. The thyroid hormone triiodothyronine (T3) slightly increased the activity of NK cells. The histone deacetylase inhibitor valproic acid (VPA), however, inhibited NK cell lytic activity against leukemic cells in a dose-dependent manner. Pretreatment using VPA reduced IFNγ secretion, impaired CD107a degranulation, and induced apoptosis by activating the PD-1/PD-L1 pathway. VPA downregulated the expression of the activating receptor NKG2D (natural-killer group 2, member D) by inducing histone K9 hypermethylation and DNA methylation in the gene promoter. Histone deacetylase inhibitors have been developed as anticancer agents for use as monotherapies or in combination with other anticancer therapies. Our data suggest that the activity of histone deacetylase inhibitors on NK cell activity should be considered in drug development.

  20. Nanosuspension delivery of paclitaxel to xenograft mice can alter drug disposition and anti-tumor activity

    Science.gov (United States)

    Chiang, Po-Chang; Gould, Stephen; Nannini, Michelle; Qin, Ann; Deng, Yuzhong; Arrazate, Alfonso; Kam, Kimberly R.; Ran, Yingqing; Wong, Harvey

    2014-04-01

    Paclitaxel is a common chemotherapeutic agent that is effective against various cancers. The poor aqueous solubility of paclitaxel necessitates a large percentage of Cremophor EL:ethanol (USP) in its commercial formulation which leads to hypersensitivity reactions in patients. We evaluate the use of a crystalline nanosuspension versus the USP formulation to deliver paclitaxel to tumor-bearing xenograft mice. Anti-tumor efficacy was assessed following intravenous administration of three 20 mg/kg doses of paclitaxel. Paclitaxel pharmacokinetics and tissue distribution were evaluated, and differences were observed between the two formulations. Plasma clearance and tissue to plasma ratio of mice that were dosed with the nanosuspension are approximately 33- and 11-fold higher compared to those of mice that were given the USP formulation. Despite a higher tumor to plasma ratio for the nanosuspension treatment group, absolute paclitaxel tumor exposure was higher for the USP group. Accordingly, a higher anti-tumor effect was observed in the xenograft mice that were dosed with the USP formulation (90% versus 42% tumor growth inhibition). This reduction in activity of nanoparticle formulation appeared to result from a slower than anticipated dissolution in vivo. This study illustrates a need for careful consideration of both dose and systemic solubility prior utilizing nanosuspension as a mode of intravenous delivery.