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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Top quark spin correlations and leptonic forward-backward asymmetries at D0

Head, Timothy January 2013 (has links)
The top quark is the heaviest fundamental particle. Its correspondingly short lifetime implies that it will decay before top flavoured hadrons can form. This provides an opportunity to study the properties of a quark without the effects of hadronisation, which is unique in the standard model.Using data recorded by the D0 experiment at the Fermilab Tevatron collider, and corresponding to \unit[5.4]{fb^{-1}} of proton-antiproton collisions two analyses of the production and decay mechanism of top quarks are presented in this thesis. In the standard model the directions of the spin of top quarks produced in pairs by the strong interaction are expected to be correlated. In the first analysis, the strength of the correlation is extracted from the angles of the two leptons in the top quark and antiquark rest frames, yielding a correlation strength C=0.10\pm0.45. This is in agreement with the NLO QCD prediction within two standard deviations, but also in agreement with the no correlation hypothesis.In the second analysis, forward-backward asymmetries in top quark-antiquark production are measured using the charged leptons from top quark decays. We find that the angular distributions of \ell^{\mathrm{-}} relative to antiprotons and \ell^{+} relative to protons are in agreement with each other. Combining the two distributions and correcting for detector acceptance we obtain the forward-backward asymmetry \al=\left(5.8\pm5.1\mathrm{(stat)}\pm1.3\mathrm{(syst)}\right)\%, compared to the standard model prediction of \al\mathrm{(predicted)}=\left(4.7\pm0.1\right)\%.
2

An experimental investigation of solid helium mixtures

Kingsley, Christopher John January 1997 (has links)
No description available.
3

Search for Supersymmetry in the Jets + Met + TAUS Final State Using the CMS Detector at the LHC

Montalvo, Roy Joaquin 02 October 2013 (has links)
In this dissertation results are presented from a search for the pair production of heavy colored particles (gluinos, squarks) in R-parity conserving supersymmetric models, in which the lightest supersymmetric particle is a stable and neutral object. The search was performed for events with at least two tau leptons, two highly energetic jets and large missing transverse momentum in the final state on a data sample of proton-proton collisions at sqrt(s) = 7 TeV. The data sample was collected by the Compact Muon Solenoid detector at the Large Hadron Collider in 2011, and it corresponds to an integrated luminosity of 5fb^−1. The tau isolation variable was optimized for this search. The number of events corresponding to standard model processes in the final selection was estimated to be 7.49 ± 0.74 using background estimation techniques based on data. Nine observed events are found to be in agreement with the standard model prediction, and exclusion limits on gluino mass are obtained in the context of supersymmetric models at the 95% confidence level.
4

Genotoxicity and cytotoxicity of zinc oxide and titanium dioxide in HEp-2 cells.

Osman, Ilham F., Baumgartner, Adolf, Anderson, Diana, Cemeli, Eduardo, Fletcher, Jonathan N. January 2010 (has links)
Yes / Aims: The rapidly growing industrial and medical use of nanomaterials, especially zinc oxide and titanium dioxide, has led to growing concerns about their toxicity. Accordingly, the intrinsic genotoxic and cytotoxic potential of these nanoparticles have been evaluated. Materials & methods: Using a HEp-2 cell line, cytotoxicity was tested along with mitochondrial activity and neutral red uptake assays. The genotoxic potential was determined using the Comet and the cytokinesis-blocked micronucleus assays. In addition,tyrosine phosphorylation events were investigated. Results & conclusion: We found concentration- and time-dependent cytotoxicity and an increase in DNA and cytogenetic damage with increasing nanoparticle concentrations. Mainly for zinc oxide, genotoxicity was clearly associated with an increase in tyrosine phosphorylation. Our results suggest that both types of nanoparticles can be genotoxic over a range of concentrations without being cytotoxic. / Embargo ended 3/11/ 2011
5

OS CONSENSOS PARA PESQUISA DE AUTOANTICORPOS EM CÉLULAS HEp-2 (FAN HEp-2): IMPLANTAÇÃO DAS DIRETRIZES NOS LABORATÓRIOS CLÍNICOS BRASILEIROS

Silva, Glaucielen Gomes da 08 March 2017 (has links)
Submitted by admin tede (tede@pucgoias.edu.br) on 2017-04-27T14:19:15Z No. of bitstreams: 1 GLAUCIELEN GOMES DA SILVA.pdf: 1992448 bytes, checksum: 7764de752332d80cd64fa3e7a9e1b7a1 (MD5) / Made available in DSpace on 2017-04-27T14:19:16Z (GMT). No. of bitstreams: 1 GLAUCIELEN GOMES DA SILVA.pdf: 1992448 bytes, checksum: 7764de752332d80cd64fa3e7a9e1b7a1 (MD5) Previous issue date: 2017-03-08 / The search for autoantibodies in HEp-2 cells represents a relevant tool for diagnostic assistance in the investigation of autoimmune diseases, especially rheumatic diseases. This methodology, over the last years, underwent by intense process of improvement and standardization with the accomplishment of the Brazilian Consensus. The objective of this study was to evaluate the implantation of recommendations in the clinical laboratories that perform the methodology, 16 years after the accomplishment of the I Brazilian Consensus on ANA in HEp-2 cells. A research was conducted for the laboratories between February and October 2016. The laboratories were invited to answer questions that dealt with the guidelines of the Consensus, addressing technical aspects, quality control, reading of the slides, issuance of reports and educational programs. The study counted on the participation of 53 laboratories that jointly realize an estimate of 300,000 ANA by month. It has been identified that several medical specialties request the examination, and different professionals are responsible for the technical procedure and reading of the fluorescence slides. Consensus recommendations are being followed by all laboratories, in absolute by 58.5% of the laboratories. Regarding the technical procedure, 83.1% of the participants are screening at a 1:80 dilution and the title depletion, recommended by consensus, is being adopted by all participants. It was evidenced that 39.6% of the participants use more than one brand of kit and that 22.6% performs titration of the conjugate to each new kit and different lamp powers are used in laboratories with a predominance of 100 Watts. Regarding the reading of the slides, 94.3% stated that they observed the four cell compartments, 92.5% said to classify the chromosome metaphase plate negative or positive and 32.1% of the participants did not affirm to observe the cells in all phases of the cycle. In the issue of reports, 13.2% of the laboratories admitted to reporting only the name of the standard followed by the title, not presenting the descriptive report and 24.5% of the participants do not use education and quality control programs. Most laboratories were able to identify representative images of sets of patterns. The results presented here demonstrate consistent advances from the implementation of the ANA Consensus in Brazil, but also evidence the need for actions to implement continuing education programs. / A pesquisa de autoanticorpos em células HEp-2 tem auxiliado no diagnóstico na investigação de doenças autoimunes especialmente as reumáticas. Tal metodologia, ao longo dos últimos anos, passou por um intenso processo de aperfeiçoamento e padronização com a realização do Consenso Brasileiro. O presente trabalho teve como objetivo avaliar, 16 anos após a realização do I Consenso Brasileiro de FAN em Células HEp-2, a implantação das recomendações nos laboratórios clínicos que realizam a metodologia. Foi realizada uma pesquisa direcionada aos laboratórios entre fevereiro e outubro de 2016. Os laboratórios foram convidados a responder um questionário sobre as diretrizes do Consenso, abordando aspectos técnicos, controle de qualidade, leitura das lâminas, emissão de laudos e programas educativos. O estudo contou com a participação de 53 laboratórios que, em conjunto, realizam uma estimativa de 300.000 FAN/mês. Foi identificada uma heterogeneidade em especialidades médicas solicitantes do teste e profissionais responsáveis pelo procedimento técnico e leitura das lâminas de fluorescência. As recomendações do Consenso estão sendo seguidas em sua totalidade por 58,5% dos laboratórios. Em relação ao procedimento técnico, 83,1% dos participantes fazem triagem com diluição 1:80 e o esgotamento de título, recomendado pelo Consenso, está sendo adotado por todos os participantes. Evidenciou-se que 39,6% dos participantes utilizam mais de uma marca de kit e que 22,6% realiza a titulação do conjugado a cada nova kit, e diferentes potências de lâmpadas são utilizadas nos laboratórios com predomínio das de 100 Watts. Em relação à leitura das lâminas, 94,3% afirmam observar os quatro compartimentos celulares, 92,5% afirmam classificar a placa metafásica cromossômica em negativa ou positiva e 32,1% dos participantes não afirmaram observar as células em todas as fases do ciclo celular. Na emissão de laudos, 13,2% dos laboratórios admitiram relatar somente o nome do padrão seguido pelo título, não apresentando o laudo descritivo e 24,5% dos participantes não utilizam programas de educação e controle de qualidade. A maioria dos laboratórios foi capaz de identificar imagens representativas de grupos de padrões. Os resultados aqui apresentados demonstram consistentes avanços a partir da implantação do Consenso de FAN no Brasil, porém, evidenciam também a necessidade de ações para implementação dos programas de educação continuada.
6

Pesquisa de autoanticorpos contra antígenos intracelulares, em células HEp-2, em Goiânia Goiás / Research on autoantibodies against intracellular antigens in HEp-2 cells, in Goiânia Goiás

RÊGO, Jozelia 17 December 2009 (has links)
Made available in DSpace on 2014-07-29T15:25:24Z (GMT). No. of bitstreams: 1 tese Jozelia rego.pdf: 289983 bytes, checksum: 81f90ad780122cbecb664ab66f6306c0 (MD5) Previous issue date: 2009-12-17 / Autoimmune diseases are a clinical syndrome caused by the activation of T and/or B cells. They are multifactorial in nature and characterized by the presence of autoantibodies directed against cellular components. These autoantibodies can act as diagnostic markers or as predictors for these diseases. The ANA test is a very useful tool in the investigation of autoimmune diseases. OBJECTIVES: a) establishing a correlation between clinical diagnoses and fluorescence patterns in ANA tests on HEp-2 cells; b) determining the frequency of fluorescence patterns; c) establishing a correlation between clinical diagnosis and fluorescence titers; d) establishing possible correlations of changes in fluorescence patterns. CASES AND METHODS: All the ANA requests sent to the Immunorheumatology Laboratory of the Teaching Hospital of the Federal University of Goias, from January / 2000 to December / 2007 were analyzed and those with positive results were selected. For the ANA research, the investigator used the IFI technique and HEp-2 cells as substrate. To classify the fluorescence patterns decision trees proposed by the Brazilian Consensus for Standardization of ANA in HEp-2 cells were used. RESULTS: Among the 8,631 ANA requests, 1,167 presented positive results (13,52%). These positive tests were divided into two groups: Group I (tests requested in one occasion) and Group II (tests requested in more than one occasion). In Group I, nuclear patterns were more prevalent (89,41%). Speckled nuclear patterns were seen more frequently (78,81%), with special notice to fine speckled nuclear patterns (32,74%), coarse speckled nuclear patterns (29,86%) and fine dense speckled nuclear patterns (9,79%). Among the clinical diagnoses, rheumatic autoimmune diseases were the most prevalent (59,87%) and they correlated mostly with speckled nuclear patterns. A positive ANA was noted in 216 cases (34,67%) of non-immune conditions and in 22 cases (3,53%) of undetermined diagnosis. Cases with moderate (1:160) and high (1:640 and > 1:640) titers presented a high association with autoimmune diseases (54,25%; 73,23%; 83,91%, respectively). In Group II, the analytic clinical diagnosis and fluorescence titer factors showed a significant association with the change in the fluorescence pattern. CONCLUSIONS: 1) ANA was found to be positive in autoimmune (61,80%) and in non-autoimmune diseases (34,67%). 2) The most frequently found positive ANA correlation was seen with a diagnosis of lupus erythematosus (38,04%), mainly with coarse speckled nuclear pattern (32,91%), fine speckled nuclear pattern (25,73%), homogeneous nuclear pattern (19,40%) and fine dense speckled nuclear pattern (10,12%). 3) Nuclear patterns were more frequently found (89,41%), and among them, speckled patterns were prevalent (78,81%). 4) Low titers can be found in rheumatic autoimmune diseases and, therefore, can not be interpreted as an exclusion criteria for autoimmune disease, as long as there are clinical indications. 5) High titers can be found in non-autoimmune diseases and, therefore, can not be interpreted as specific to autoimmune diseases. 6) When the ANA test was requested in more than one occasion for the same patient, the clinical diagnosis (especially SLE) and the fluorescence titer (1:40 and 1:160) showed an association with the change of the fluorescence pattern. 7) A correct valuation of the ANA test should associate information from positive results to the clinical history and the physical examination of the patient when they are suggestive of an autoimmune disease, most notably, of rheumatic autoimmune diseases / As doenças autoimunes são síndromes clínicas causadas pela ativação de células T e/ou B, de origem multifatorial, caracterizadas pela presença de autoanticorpos dirigidos contra componentes celulares. Os autoanticorpos podem atuar como marcadores diagnósticos ou como marcadores preditores destas doenças. O teste de FAN é um exame útil na investigação de doenças autoimunes. OBJETIVOS: a) verificar a correlação entre os diagnósticos clínicos e os padrões de fluorescência na pesquisa de FAN em células HEp-2; b) determinar a freqüência dos padrões de fluorescência; c) verificar a correlação entre os diagnósticos clínicos e os títulos de fluorescência; d) verificar as possíveis correlações da mudança dos padrões de fluorescência. CASUÍSTICA E MÉTODOS: Foram analisadas todas as solicitações de FAN encaminhadas ao Laboratório de Imuno-Reumatologia do Hospital das Clínicas da Universidade Federal de Goiás, durante o período de jan./ 2000 a dez./ 2007, e selecionadas as solicitações com resultados positivos. A pesquisa do FAN foi realizada pela técnica de IFI, utilizando-se como substrato células HEp-2. Para a classificação dos padrões de fluorescência utilizou-se as árvores de classificação definidas pelo I Consenso Nacional para padronização dos laudos de FAN em células HEp-2. RESULTADOS: Das 8631 solicitações de FAN, 1167 apresentaram resultados positivos (13,52%). Os testes positivos foram divididos em dois grupos: Grupo I (exames solicitados em uma ocasião) e Grupo II (exames solicitados em mais de uma ocasião). No Grupo I, os padrões encontrados em maior freqüência foram os nucleares (89,41%). Os padrões nucleares pontilhados foram observados em maior freqüência (78,81%), destacando-se os padrões nuclear pontilhado fino (32,74%), nuclear pontilhado grosso (29,86%) e nuclear pontilhado fino denso (9,79%). Dentre os diagnósticos clínicos descritos, as doenças autoimunes reumáticas foram observadas em maior freqüência (59,87%) e correlacionaram-se, principalmente, com os padrões nucleares pontilhados. FAN positivo foi observado em 216 casos (34,67%) de situações não-autoimunes e em 22 casos (3,53%) de diagnóstico não definido. Os casos com títulos moderados (1:160) e elevados (1:640 e > 1:640) apresentaram maior associação com enfermidades autoimunes (54,25%; 73,23%; 83,91%, respectivamente). No Grupo II, os fatores analíticos diagnóstico clínico e título de fluorescência mostraram associação significativa com a mudança do padrão de fluorescência. CONCLUSÕES: 1) A positividade do teste de FAN foi observada em doenças autoimunes (61,80%) e em doenças não-autoimunes (34,67%). 2) A correlação mais freqüente do FAN positivo foi observada com o diagnóstico de lupus eritematoso (38,04%), principalmente com os padrões nuclear pontilhado grosso (32,91%), nuclear pontilhado fino (25,73%), nuclear homogêneo (19,40%) e nuclear pontilhado fino denso (10,12%). 3) Os padrões nucleares foram observados em maior freqüência (89,41%), sendo os pontilhados os mais comuns (78,81%). 4) Títulos baixos podem ser encontrados em doenças autoimunes reumáticas e, portanto, não devem ser interpretados como critério para exclusão de doença autoimune, desde que exista suspeita clínica. 5) Títulos altos podem ser encontrados em doenças não-autoimunes e, portanto, não devem ser interpretados como específicos de doença autoimune. 6) Quando o teste de FAN foi solicitado em mais de uma ocasião, para o mesmo paciente, o diagnóstico clínico (principalmente de LES) e o título de fluorescência (1:40 e 1:160) mostraram associação com a mudança do padrão de fluorescência. 7) A valorização correta do teste de FAN deve associar as informações fornecidas pelo resultado positivo à história clínica e exame físico do paciente, quando sugestivos de doença autoimune, principalmente de doenças autoimunes reumáticas.
7

A comparative membrane surface analysis between two human hepatocarcinoma cell lines ( SK-HEP-1 and Hep G2 cells ) using Atomic Force Microscope

Li, I-Ting 03 September 2010 (has links)
Atomic force microscopy (AFM) can be used to acquire high-resolution topographical images of surfaces, but has the additional capability of detecting the local nanometer scale mechanical properties. For these reasons, it becomes a standard research tool in the surface science recently. In this paper, we used AFM to measure the several properties of two different human hepatocellular carcinoma cell lines, Hep G2 ( known as well differentiated and more highly carcinomatous hepatoma cell lines ) and SK-HEP-1 ( known as poorly differentiated and more lightly carcinomatous hepatoma cell lines ) cells fixed on the glass substrate, which including the surface morphology and the relationship between the cantilever deflections and loading forces ( force curve ). Considered the heterogeneous characteristics of the cell surface, the preferred experimental method is to make pixel-by-pixel force curves in a designated area ( force map ) , both adhesion forces and elasticity associated with different locations on the cell surfaces will be obtained. Finally, we use Hertzian model to calculate Young's modulus of Hep G2 and SK-HEP-1 respectively. Based on these results, we can understand the surface properties of two human hepatocarcinoma cell lines with different differentiated stage. The results showed the difference of the morphology, height, cell migration, degree of cell aggregation, roughness, elasticity, adhesive force of two cells. SK-HEP-1 cell has the wide distance of the folds, better cell migration, homogeneous properties of elasticity. It can be assumed that the SK-HEP-1 cells have a dense network structure of actin filaments under the cell membrane like branches (branched networks); Hep G2 cell has the narrow distance of the folds, poor cell migration, heterogeneous properties of elasticity. It can be assumed that the Hep G2 cells have the individual actin filaments and cross-linked network structure of actin filaments under the cell membrane. The above results can be speculated that the elastic properties of the membrane surface will be influenced of actin filaments.
8

Développement d’un algorithme de suivi de particules pour l’ILC : outils de surveillance de qualité de données en ligne / Particle flow algorithm development for the ILC experiment : Online data quality monitoring tools

Ete, Rémi 08 March 2017 (has links)
Après la découverte au Large Hadron Collider (LHC) d'un boson de Higgs compatible avec celui du modèle standard, les futurs projets de collisionneurs tels que le Collisionneur Linéaire International ILC sont proposés pour succéder au LHC. Les deux détecteurs proposés pour être placés au point de collision de l'ILC, le Grand Détecteur International ILD et le Détecteur en Silicium SiD, seront des détecteurs généralistes, conçus pour permettre l'application des algorithmes de suivi de particules, principal sujet d'intérêt de cette thèse. Le calorimètre hadronique à lecture semi-digitale SDHCAL développé essentiellement à l'IPN de Lyon, fait partie des options pour le calorimètre hadronique du détecteur ILD. Les travaux effectués dans cette thèse portent sur le développement d'un algorithme de suivi de particules basé sur la topologie en arbre des gerbes hadroniques. Après une première implémentation pour le prototype du SDHCAL d'une taille d'un mètre cube, une seconde implémentation est proposée pour reconstruire les particules issues des collisions dans le détecteur ILD. A l'aide de données issues de simulations numériques, les performances physiques sont extraites. Dans le cas de la version dédiée au prototype du SDHCAL, les résultats sont comparés aux données récoltées lors des différents tests sur faisceau.En parallèle de ces travaux, un logiciel de surveillance de données en ligne générique nommé DQM4HEP a été développé. Des analyses spécifiques aux données récoltées par le prototype du SDHCAL lors des divers tests sur faisceau, ont été déployées afin de tester le logiciel / After the discovery of a Higgs boson compatible with the standard model one at the Large Hadron Collider (LHC), future project of particle colliders such as the ILC are suggested to succeed the LHC. The two detectors at the collision point, the International Large Detector (ILD) and the Silicon Detector (SiD), are generalist detectors, deigned to allow the application of particle flow algorithms, main topic of interest of this thesis.The semi-digital hadronic calorimeter (SDHCAL), mainly developped at the IPNL, is one the options for the hadronic calorimeterof the ILD detector. The researches presented in this thesis are focused on particle flow development based on the tree topology of hadronic showers. After a first implementation for the SDHCAL physics prototype, a second one is proposed to reconstruct the particles from collisions in the ILD detector. Using Monte-Carlo data samples, physics performances are extracted. In the first version case, results are compared to available test beam data recorded by the SDHCAL prototype at CERN.In parrallel of this work, a data quality monitoring framework, called DQM4HEP, has been developped. Analyzes specific to SDHCAL data taken during beam tests have been deployed in order to test the software
9

Propriedades das vari?veis antropom?tricas e laboratoriais como indicativas de doen?a hep?tica gordurosa n?o-alco?lica grave em indiv?duos com obesidade grau II e III

Berleze, Diovanne 14 April 2011 (has links)
Made available in DSpace on 2015-04-14T13:36:00Z (GMT). No. of bitstreams: 1 461548.pdf: 554767 bytes, checksum: a8061ad380e2b55b475c03df57b4c518 (MD5) Previous issue date: 2011-04-14 / Introduction : Obesity is a pandemic disease. Obesity grade II and III often needs invasive treatment such as bariatric surgery. In these patients, comorbidities are frequent, including the nonalcoholic fatty liver disease (NAFLD), characterized by fatty infiltration of the liver of nonalcoholic etiology in individuals without other chronic liver diseases. Objectives : This study aimed to evaluate the properties of a group of anthropometric and laboratory tests according to the diagnosis of severe liver damage. Patients and Methods : We studied 845 patients with body mass index of 35 or more, with data from liver biopsy. We evaluated the properties (sensitivity, specificity, PPV, NPV, LR + and LR-) of anthropometric and laboratory, compared to the biopsy, for diagnosis of severe liver damage. The variable was dichotomized NAFLD in severe liver damage or not. Results : The prevalence of severe liver damage was 38.1% (95% CI 34.8 to 41.4). The average age of the individuals was 37.2 years and mean weight was 131.0 kg and prevalence of NAFLD was 53.3% higher in men (95% CI 47.0 to 59.7) than in women 32.1% (95% CI 28.3 to 36.9). Conclusions : Among the anthropometric variables studied, the waist / hip ratio (WHR) was the best variable to classify patients with and without severe liver damage, followed by the waist. Transaminases showed better performance than the anthropometric variables, TGP being the best, followed in order by AST and GGT. / Introdu??o : A obesidade ? hoje uma pandemia. A obesidade grau II e III, s?o graus avan?ados de obesidade, que necessitam muitas vezes de tratamento invasivo como a cirurgia bari?trica. Nestes pacientes, ? freq?ente a presen?a de comorbidades, entre elas a Doen?a Hep?tica Gordurosa N?o Alco?lica (DHGNA), caracterizada por infiltra??o gordurosa do f?gado de etiologia n?o alco?lica em indiv?duos sem outras hepatopatias cr?nicas. Objetivos : Este estudo teve como objetivo avaliar as propriedades de um grupo de testes antropom?tricos e laboratoriais em fun??o do diagnostico de dano hep?tico grave. Pacientes e M?todos : Foram estudados 845 pacientes com ?ndice de massa corporal de 35 ou mais, com dados de bi?psia hep?tica. Foram avaliadas as propriedades (sensibilidade, especificidade, valor preditivo positivo, valor preditivo negativo, likelihood ratio positivo e likelihood ratio negativo) de vari?veis antropom?tricas e laboratoriais comparadas com a bi?psia, para diagn?stico de dano hep?tico grave. A vari?vel DHGNA foi dicotomizada em dano hep?tico grave ou n?o. Resultados : A preval?ncia de dano hep?tico grave foi de 38,1% (IC95% 34,8 41,4). A m?dia de idade dos indiv?duos avaliados foi de 37,2 anos e a m?dia de peso foi de 131,0 Kg. A preval?ncia de DHGNA foi maior nos homens 53,3% (IC95% 47,0 59,7) do que nas mulheres 32,1% (IC95% 28,3 36,9) Conclus?es : Dentre as vari?veis antropom?tricas estudadas a raz?o cintura quadril (RCQ) foi a melhor vari?vel para classificar os pacientes com e sem dano hep?tico grave, seguida da cintura. As aminotransferase apresentaram melhor desempenho do que as antropom?tricas sendo a melhor a ALT seguida em ordem pela AST e a GGT.
10

Goniothalamin induces TP53-dependent and -independent apoptosis in hepatocellular carcinoma derived cells

Tsai, Cheng-Hui 15 July 2008 (has links)
The objective was to study apoptotic effects and underlying molecular mechanisms of goniothalamin (GTN) in hepatocellular carcinoma (HCC)-derived cells. The GTN that isolated from Goniothalamus amuyon, was found to possess profound cytotoxic activities against human SK-Hep1 and Hep-3B cells in vitro. The cytotoxicity of GTN/cell viability was measured by MTT assay at 570-nm absorbance and the IC50 at 72 h were determined as 7.5, 17 mM in SK-Hep1 and Hep-3B respectively. The GTN induced cell death and accumulation of reactive oxygen species in HCC-derived cells. One reactive oxygen species inhibitor, N-actylcysteine, further restored cell viabilities post-GTN treatments. Formation of £^-H2AX foci suggested that GTN-induced DNA damages were double-strand breaks. The GTN arrested cell cycle at G0/G1 by regulation of CCND, CCNE1, RB1 and E2F1 proteins in SK-Hep1, and at G2/M by regulation of CCNB1 in Hep-3B cells. The GTN-induced apoptosis in HCC-derived cells were evidenced by phosphatidylserine externalization and involved both extrinsic and intrinsic pathways in SK-Hep1 cells, but only extrinsic pathway in Hep-3B cells. In SK-Hep1 cells, GTN induced apoptosis and cell cycle arrest through TP53-mediated pathway in contrast to that of TP53/FAS mutated Hep-3B cells. Importantly, GTN was able to induce apoptosis in both TP53 wild type and TP53/FAS mutated HCC-derived cells. On the other hand, GTN was able to induce TP53 and p21WAF1/Cip1 up-regulation in SK-Hep1 and Hep-3B cells and p27Kip1 up-regulation in Hep-3B cells. These results demonstrated that GTN induced apoptosis in HCC cells through distinct signaling pathways.

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