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Jermany, Joanne Lorna. "Biosynthesis and maturation of the prohormone convertases PC3 and PC2." Thesis, University of Aberdeen, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295620.
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The prohormone convertases PC2 and PC3 are members of the highly conserved subtilisin-like serine protease superfamily. Targeted to the regulated secretory pathway of neuroendocrine cells they are involved in the proteolytic processing of a number of co-secreted polypeptides. To investigate the nature of their biosynthesis, maturation and possible interaction with the neuroendocrine polypeptide 7B2, a series of mutants were constructed and translated in a novel cell-free in vitro translation/translocation system derived from Xenopus eggs. It was shown that PC3 undergoes rapid (T1/2<10min), autocatalytic maturation, optimally at pH7, in a calcium-independent manner, from an 88kDa proform to an 80kDa mature form, in a proteolytic reaction occurring carboxy-terminal to RSKR83. This indicates the endoplasmic reticulum as the sub-cellular location for PC3 maturation in vivo. Conversely, PC2 matures optimally at pH5.5 in an autocatalytic reaction dependent on millimolar calcium. It was demonstrated that mutation of the PC2 unique oxyanion aspartate282 to asparagine increased its optimal processing pH requirements from acidic to neutral, in a reaction still dependent on millimolar calcium. This infers that the oxyanion aspartate of PC2 influences the pH at which the protease matures. In vitro the role of the neuroendocrine precursor 7B2 in PC2 biosynthesis was shown to be two-fold and pH-dependent. At acidic pH, pro-7B2 acted as an inhibitor of pro-PC2 maturation, whereas under neutral pH conditions pro-7B2 was seen to markedly enhance pro-PC2 maturation. Neither precursor nor mature 7B2 were shown to interact with the PC2 oxyanion mutant, pro- or mature PC3 in vitro. This is consistent with the proposed view that 7B2 specifically interacts with PC2 in the regulated secretory pathway and the association is dependent upon the nature of the PC2 oxyanion aspartate residue.
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Rose, Douglas, Leonard Brian Cross, and Ivy A. Click. "The Patient-Centered Care Committee (PC3)." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/6396.
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Piassi, Amanda Resende. "Análise de pulsações magnéticas Pc3 e Pc4 na região da Anomalia Magnética do Atlântico Sul." Instituto Nacional de Pesquisas Espaciais (INPE), 2018. http://urlib.net/sid.inpe.br/mtc-m21c/2018/05.02.17.17.
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O Campo Magnético Terrestre apresenta algumas características específicas no continente sul-americano, incluindo uma região onde se observa uma diminuição significativa em sua intensidade. Essa região é chamada de Anomalia Magnética do Atlântico Sul (SAMA), na qual uma aproximação do cinturão interno de radiação resulta em significativa precipitação de partículas energéticas na atmosfera. Essa precipitação de partículas aumenta a condutividade elétrica em grande parte da ionosfera sul-americana, produzindo efeitos aeronômicos peculiares. Este trabalho teve como objetivo estudar os efeitos da SAMA nas pulsações geomagnéticas Pc3 e Pc4 registradas por magnetômetros de núcleo saturado operados pelo Programa de Estudo e Monitoramento Brasileiro do Clima Espacial(EMBRACE) e pela rede global INTERMAGNET em diferentes estações magnéticas terrestres. Os dados foram utilizados para avaliar efeitos produzidos durante períodos geomagneticamente calmos e perturbados no ano de 2015. Exceto por um resultado anômalo observados para as Pc3 durante um período calmo no equinócio de outono(março), possivelmente associado ao aumento no conteúdo eletrônico total, as amplitudes das pulsações mostraram uma amplificação consistente na SAMA, sendo o maior fator de amplificação observado próximo da região central da anomalia. Um modelo genérico é sugerido como fonte das pulsações, o qual inclui a geração de ondas superficiais por instabilidades de plasma nos limites de alta latitude da magnetosfera diurna, a propagação dessas ondas pelas linhas de campo geomagnético até latitudes polares e o subsequente vazamento das correntes geradas em direção a latitudes mais baixas por um guia de ondas terra-ionosfera. A transmissão horizontal desses campos polares pela SAMA é influenciada por variações da condutividade ionosférica e gera pulsações geomagnéticas com amplitudes diferentes em função da distância ao centro da anomalia.The Earths magnetic field presents some specific characteristics in the South American continent, including a region where a significant decrease in intensity is observed. This region is called the South Atlantic Magnetic Anomaly (SAMA), at which an approximation of the internal radiation belt results in enhanced precipitation of energetic particles into the atmosphere. This particle precipitation increases the electrical conductivity in much of the South American ionosphere, producing peculiar aeronomic effects. This work aimed to study the effects of SAMA on Pc3 and Pc4 magnetic pulsations recorded by fluxgate magnetometers operated by the Brazilian Studies and Monitoring of Space Weather (EMBRACE) and by the INTERMAGNET global network in different ground stations. The data were used to evaluate effects produced during magnetically quiet and disturbed periods in the year 2015. Except for an anomalous result observed for Pc3 during a quiet interval at the March equinox, possibly associated with the increase in Total Electronic Content, pulsation amplitudes showed a consistent amplification in SAMA, being the largest amplification factors observed near the central region of the anomaly. A generic model is suggested as the source of the pulsations, which includes the generation of surface waves by plasma instabilities at the dayside high-latitude magnetosphere boundary, the propagation of these waves through magnetic field lines until polar latitudes and the subsequent leakage of the currents toward lower latitudes by an Earthionosphere waveguide. The horizontal transmission of these polar fields through the SAMA is influenced by variations of ionospheric conductivity and generates ground geomagnetic pulsations with different amplitude as a function of the distance to the center of the anomaly.
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Scougall, Kathleen. "Maturation of pro-hormone convertases PC2 and PC3 and their interaction with the neuroendocrine protein 7B2." Thesis, University of Aberdeen, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301302.
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The activation of many pro-hormones occurs through cleavage at pairs of basic residues and is mediated by two serine proteases, PC2 and PC3. Like their substrates, they are also synthesised as inactive precurors (pro-PC2 and pro-PC3). Maturation is autocatalytic and requires removal of the N-terminal pro-peptide. Pro-PC3 matures within the endoplasmic reticulum (ER), whereas maturation of pro-PC2 proceeds within the later compartments of the Golgi network (TGN)/secretory vesicle (SV) and is thought to be regulated by 7B2. In this study the molecular basis for the differences in the maturation location and the interaction with 7B2 was examined by performing domain swap and site directed mutagenesis experiments. The mutant constructs were analysed within an in vitro cell free system. The results suggest that the oxyanion hole residue (Asp310) of pro-PC2 restricts maturation to a late secretory compartment and is important for the interaction with 7B2. Mutation of this residue to resemble that of PC3 (Asp310Ans), altered pro-PC2 maturation from a TGN/SV like environment to an ER like environment. Maturation of pro-PC2, but not pro-PC3, was shown to be inhibited by 7B2. Residue Asp310 of PC2 was necessary to mediate this interaction. When a similar mutant of PC3 was created to resemble PC2 (Asn309Asp), this residue was not sufficient to alter the maturation profile of pro-PC3 nor was it able to confer 7B2 sensitivity. The pro-region of PC2 was sufficient to alter maturation of PC3 from the ER-like compartment to a TGN/SV-like compartment, but was not able to confer 7B2 sensitivity onto PC3. This study also demonstrated that a basic cluster (HHKQQ88) of pro-PC2 was important for delaying maturation to a late compartment and that the residue Phe104, was important for efficient maturation. Mutational analysis of pro-7B2 revealed that a region within residues 1-151 was important for the interaction with pro-PC2.
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Davoodpour, Padideh. "2-ME-Induced Apoptotic Signalling in Prostate Cancer PC3 Cells." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis: Univ.-bibl. [distributör], 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6136.
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Lotz, Stefanus Ignatius. "Empirical modelling of the solar wind influence on Pc3 pulsation activity." Thesis, Rhodes University, 2012. http://hdl.handle.net/10962/d1005249.
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Geomagnetic pulsations are ultra-low frequency (ULF) oscillations of the geomagnetic field that have been observed in the magnetosphere and on the Earth since the 1800’s. In the 1960’s in situ observations of the solar wind suggested that the source of pulsation activity must lie beyond the magnetosphere. In this work the influence of several solar wind plasma and interplanetary magnetic field (IMF) parameters on Pc3 pulsations are studied. Pc3 pulsations are a class of geomagnetic pulsations with frequency ranging between 22 and 100 mHz. A large dataset of solar wind and pulsation measurements is employed to develop two empirical models capable of predicting the Pc3 index (an indication of Pc3 intensity) at one hour and five minute time resolution, respectively. The models are based on artificial neural networks, due to their ability to model highly non-linear interactions between dependent and independent variables. A robust, iterative process is followed to find and rank the set of solar wind input parameters that optimally predict Pc3 activity. According to the parameter selection process the input parameters to the low resolution model (1 hour data) are, in order of importance, solar wind speed, a pair of time-based parameters, dynamic solar wind pressure, and the IMF orientation with respect to the Sun-Earth line (i.e. the cone angle). Input parameters to the high resolution model (5 minute data) are solar wind speed, cone angle, solar wind density and a pair of time-based parameters. Both models accurately predict Pc3 intensity from unseen solar wind data. It is observed that Pc3 activity ceases when the density in the solar wind is very low, even while other conditions are favourable for the generation and propagation of ULF waves. The influence that solar wind density has on Pc3 activity is studied by analysing six years of solar wind and Pc3 measurements at one minute resolution. It is suggested that the pause in Pc3 activity occurs due to two reasons: Firstly, the ULF waves that are generated in the region upstream of the bow shock does not grow efficiently if the solar wind density is very low; and secondly, waves that are generated cannot be convected into the magnetosphere because of the low Mach number of the solar wind plasma due to the decreased density.
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Santos, Geyza Spigoti. "Avaliação do efeito radiomodificador da própolis em células de ovário de hamster chinês (CHO-K1) e em células tumorais de próstata (PC3), irradiadas com CO-60." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/85/85131/tde-26082011-100451/.
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Nestas últimas décadas, investigações sobre compostos naturais, efetivos, não tóxicos, com potencial radioprotetor vêm despertando um grande interesse em consonância com a utilização crescente de vários tipos de radiação ionizante nas mais diversas finalidades. Entre eles a própolis uma resina coletada pelas abelhas (Apis mellifera), vem sendo apontada como promissora por apresentar uma série de características biológicas vantajosas, por exemplo, anti-inflamatória, antimicrobiana, antitumoral, imunomoduladora, antioxidante e também scavenger de radicais livres. O presente estudo teve como objetivo principal, averiguar efeito da própolis brasileira procedente de Rio Grande do Sul (AF 08) em células de ovário de hamster Chinês (CHO-K1) e em células tumorais de próstata (PC3), irradiadas com 60Co. Para tanto, foram utilizados três principais parâmetros interligados entre si: indução de micronúcleo, viabilidade celular e morte clonogênica. A escolha destes parâmetros se justifica pelo seu significado biológico, além do fato de serem prontamente observáveis e mensuráveis em células irradiadas. Os dados citogenéticos obtidos, mostraram um efeito radioprotetor da própolis (5 - 100 μg/ml) na indução de dano ao DNA em ambas as linhagens celulares, irradiadas com doses de 1 - 4 Gy. No entanto, o ensaio de citotoxicidade mostrou um efeito antiproliferativo pronunciado da própolis (50 - 400 μg/ml) em células PC3 irradiadas com 5 Gy. As curvas de sobrevida obtidas foram ajustadas satisfatoriamente pelo modelo linear-quadrático, cujo componente foi mais alto em células CHO-K1. Quanto à capacidade clonogênica, as células PC3 mostraram-se mais radiossensíveis que as células CHO-K1 nas doses mais altas da curva de sobrevida. A própolis, nas concentrações de 30 - 100 μg/ml, não influenciou no potencial clonogênico das células PC3, visto que, as curvas de sobrevida associadas ou não com a própolis, mostraram perfis similares, ao passo que o tratamento combinado em células CHO-K1 exibiu um efeito estimulador da proliferação. Os dados obtidos in vitro mostraram um potencial uso da própolis AF-08, como uma substância natural e não tóxica, na prevenção contra os efeitos danosos da radiação ionizante, nas doses e nas concentrações analisadas.In the last decades, it has been given a great interest to investigations concerning natural, effective, nontoxic compounds with radioprotective potential together with the increasing utilization of different types of ionizing radiation for various applications. Among them propolis, a resinous compound produced by honeybees (Apis mellifera), has been considered quite promising, since it presents several advantageous biological characteristics, i. e., anti-inflammatory, antimicrobial, anticarcinogenic, antioxidant and also free radical scavenging action. The purpose of the present study was to evaluate the effect of Brazilian propolis, collected in the State of Rio Grande do Sul, on Chinese hamster ovary (CHO-K1) and human prostate cancer (PC3) cells, irradiated with 60Co radiation. For this purpose, three interlinked parameters were analyzed: micronucleus induction, cell viability and clonogenic death. The choice of these parameters was justified by their biological significance, in addition to the fact that they are readily observable and measurable in irradiated cells. The cytogenetic data obtained showed a radioprotective effect of propolis (5-100 μg/ml) in the induction of DNA damage for both cell lines, irradiated with doses of 1 - 4 Gy. The cytotoxicity assay, however, showed a prominent antiproliferative effect of propolis (50 - 400 μg/ml) in PC3 cells irradiated with 5 Gy. The survival curves obtained were adequately fitted by a linear-quadratic model, where the coefficient was higher in CHO-K1 cells. Concerning the clonogenic capacity, PC3 cells were more radiosensitive than CHO-K1 cells at the higher doses of the survival curve. Propolis at the concentrations of 30 - 100 μg/ml, did not influence the clonogenic potential of PC3 cells, since the survival curves, associated or not with propolis, were found similar, although the combined treatment in CHO-K1 cells exhibited a stimulating proliferative effect. The data obtained in vitro showed a potential use of propolis AF-08, a natural and nontoxic compound, in the prevention against the adverse effect of ionizing radiation, at the doses and concentrations here analyzed.
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Zanandrea, Ademilson. "Estudos de micropulsacoes geomagneticas PC3-5 em latitudes muito baixas, no Brasil." Instituto Nacional de Pesquisas Espaciais (INPE), 1998. http://urlib.net/sid.inpe.br/deise/1999/10.14.15.11.
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Neste estudo, procurou-se compreender os mecanismos de geracao e modos de propagacao de micropulsacoes Pc3-5, em latitudes muito baixas e equatoriais. Usou-se dados simultaneos observados com uma cadeia de 10 estacoes geomagneticas. no territorio brasileiro, dispondo de magnetometros ""fluxgate"" de alta sensibilidade. Utilizou-se o metodo de estimacao espectral por multiplas janelas, baseado na Transformada Rapida de Fourier (FFT), para obter os espectros de potencia, parametros de polarizacao e fase das micropulsacoes. Observou-se um aumento na ocorrencia das pulsacoes Pc3-5 altamente polarizadas, atingindo o maximo proximo ao meio-dia local (14:00 e 15:00 UT) nas estacoes mais proximas ao equador magnetico. Os espectros dinamicos mostraram a ocorrencia de 81 eventos simultaneos de pulsacoes Pc3-4 com alto grau de polarizacao, principalmente durante o dia. Os eventos diurnos mostraram um aumento de 3,2 vezes na densidade de potencia polarizada para as pulsacoes observadas nas estacoes proximas do equador magnetico em comparacao com as mais distantes. As fases das pulsacoes mostraram atrasos entre 48' e 62' nas estacoes equatoriais em relacao as mais distantes. Estes efeitos estao relacionados ao aumento da condutividade ionosferica e da intensidade de eletrojato equatorial. As curvas de densidade de potencia polarizada para as 10 estacoes mostraram um comportamento identico, com picos maximos ocorrendo na mesma frequencia. Isto esta possivelmente relacionado ao modo de oscilacao global da cavidade plasmasferica. A elipticidade mostrou-se quase-linear, com eixo maior na direcao norte-sul, devido ao fato de que as oscilacoes poloidais das linhas de campo magneticas sao quase desacopladas. A amplitude da componente norte-sul mostrou-se maior que a oeste-leste. Estes resultados sao uma evidencia de que o mecanismo da ressonancia das linhas de campo nao explica as micropulsacoes Pc3-4 observadas em latitudes muito baixas e equatoriais. O aumento na ocorrencia de eventos Pc3-4 durante o dia., com maximo proximo ao meio-dia local e presenca predominante do modo poloidal (compressional), esta provavelmente associado com a propagacao da onda compressional, proveniente da instabilidade ion-ciclotronica na regiao da frente de choque, que se propaga na magnetosfera em baixas latitudes. A propagacao desta onda pode excitar o modo compressional aprisionado ou o modo global compressional. O fenomeno resultante, das oscilacoes forcadas das linhas de campo na plasmasfera, e o mais provavel mecanismo fonte das pulsacoes Pc3-4 em latitudes muito baixas e equatoriais.This study is aimed at the understanding of source mechanisms and propagation modes of Pc3-5 micropulsations at very low and equatorial latitudes. It used simultaneous data measured with a chain of 10 geomagnetic stations in Brazil using high sensitive °uxgate magnetometers. Multiple tapered spectral estimation method based on Fast Fourier Transforms (FFT) was used to obtain micropulsation power spectra, polarization parameters and phases. It was observed an increase on the occurrence of highly polarized Pc3-5 pulsations, reaching maxima close to local noon (14:00 and 15:00 UT) in the stations nearest to the magnetic equator. The dynamic spectra showed the occurrence of 81 simultaneous events of Pc3-4 pulsations with high degree of polarization, mainly during daytime. The diurnal events showed increases in the polarized power density of 3,2 times for pulsations observed at stations close to the magnetic equator in comparison to the more distant ones. The phase of the pulsations observed at station close of the magnetic equator showed a delay of 48± and 62± in relation to the most distant one. This e®ects is clearly related to the increase of ionospheric conductivity and equatorial electrojet intensity. The polarized power density curves for all the 10 stations showed a similar behaviour, the maximum peaks occurring at same frequency. This may indicate a possible link to the plasmaspheric cavity global oscillation mode. The ellipticity was quase-linear, with the arger axis in the north-south direction, due to the fact that the poloidal mode is almost uncoupled from the oscillation of magnetic ¯eld lines. The amplitude of north-south component is much larger than the west-east one. These results could be an evidence that field line resonance mechanism does not explain Pc3-5 micropulsations observed at very low and equatorial latitudes. The increase in the occurrence of Pc3-4 diurnal events is probably associated with incoming compressional waves resulted from bow shock ion cyclotron instabilities that propagate in the magnetosphere at low latitudes. The propagation of the compressional waves may excite the trapped compressional mode or the compressional global mode. The resulting phenomenon, field lines forced oscillations in the plasmasphere, may be a possible source mechanism for Pc3-4 pulsations at very low latitudes.
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Bugiel, Steven. "β1 Integrin Regulates PC3 Prostate Cancer Cell Phenotypes in part via Regulation of Matricellular SPARC." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34785.
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We have shown herein that β1 integrin stably depleted PC3 sub-clonal cells confer a trend towards increased survival of mice compared to β1 integrin expressing counterparts when tested in an intracardial bone metastasis model. Therefore, we sought to investigate novel factors that mediate β1 integrin-dependent cellular migration and three dimensional growth of prostate cancer PC3 cells in vitro. We show herein that depletion of β1 integrin using siRNA directed techniques results in increased SPARC protein expression. We further show that suppression of SPARC by β1 integrin appears to occur through a JNK dependent mechanism. Moreover, siRNA mediated depletion of β1 integrin results in impaired sphere formation in 3D BME assays. This was mediated in part by the increased production of SPARC. β1 integrin-depleted cells also diminished the enhanced migration of cells on the predominant bone matrix, collagen I. Concomitant SPARC depletion in β1 integrin-depleted cells did not rescue this enhanced migration. These findings suggests that the role of β1 integrin in mediating 3D growth of PC3 cells occurs at least in part through the suppression of SPARC protein expression.
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Andrews, Natalie M. "Beta1 integrin modulates the anchorage independent growth, invasion and migration of prostate cancer cell line PC3." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28850.
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Integrins provide mechanical continuity between the extra- and intracellular environments. Upon binding to extracellular matrix (ECM), integrins interact with downstream effectors to promote cell adhesion, proliferation and migration. In contrast to its well-known role in adhesion, we have found that beta 1 integrin is also involved in the anchorage independent (AI) growth of prostate tumor cells. In concurrence with our previous findings, stable depletion of beta1 integrin in PC3 cells using an shRNA approach resulted in the complete inability of cells to form colonies in soft agarose, while adherent monolayer growth remained unaffected. In order to address the mechanism for beta1 integrin dependent AI growth, we examined the expression and localization of beta-catenin and E-cadherin, both of which are known to modulate AI growth. Migration and invasion through matrigel were found to be impeded by depletion of beta1 integrin. A qPCR array identified potential downstream targets that could be altered as a result of beta1 integrin depletion, these were further examined in all cell lines and it was found that TGFbeta1 is reduced in shITGB1 expressing cells. Taken together, these findings suggest a role for both beta1 integrin in driving anchorage independent growth and invasion of cancer cells.
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Hwang, Ji Hui. "The effects of acute exercise and aging on the growth of prostate cancer cells." Thesis, Queensland University of Technology, 2019. https://eprints.qut.edu.au/130703/2/Ji_Hui_Hwang_Thesis.pdf.
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This study investigated the effects on exercise and ageing on prostate cancer cell growth. Blood serum was collected before and after exercise from older and younger adults and tested in a cell culture model using prostate cancer cells. Expanding upon previous research by others that was conducted in young adults only, the results of this study suggest that exercise increases the cancer-inhibitory effects of serum from older adults.
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Hassanieh, Sarah. "CO-ADMINISTRATION OF SILDENAFIL POTENTIATES DOXORUBICIN-INDUCED APOPTOSIS IN PROSTATE CANCER: THE ROLE OF NF-kappaB." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1655.
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Our recent studies have shown that that erectile dysfunction (ED) drugs including Sildenafil (Viagra), Vardenafil (Levitra) and Tadalafil (Cialis) enhance killing of several types of cancer cells by anticancer drug, Doxorubicin (DOX). We observed increased cell death by apoptosis in response to the combined treatment with ED drugs and DOX. However, the mechanism of such enhancement of cell death by combined treatment of ED drugs and DOX is not fully understood. Nuclear factor-κB (NF-κB) is an oxidant-sensitive transcription factor that plays a critical role in the immediate-early activation of a multitude of genes that have been documented to play critical role in programmed cell death (apoptosis). NF-κB activation has been shown to block apoptosis and its inhibition improves existing anti-oncogenic therapy such as chemotherapy. In the present study, we tested the hypothesis whether combined treatment of prostate cancer cells, PC3, with Sildenafil plus DOX would attenuate the activation of NFκB by inhibiting translocation of the p65 and p50 subunits to the nucleus and by phosphorylation of cytosolic IκB In addition, we investigated the effect of DOX and DOX plus Sildenafil on the expression of BCL family of proteins which play critical role in apoptosis. We treated PC3 cells with 1.5 μM DOX with or without 10 µM Sildenafil for 6 hours and 72 hours. The nuclear translocation of p65 and p50 and expression of BCL family of proteins was determined by western blot analysis. Our results show that combined treatment of DOX and Sildenafil significantly reduced the nuclear translocation of p65 and p50 as compared with DOX alone (P < 0.05). This correlated with the significant reduction in the expression of Bcl-2, BclxL and phosphorylation of BAD. These data provide an important mechanism by which Sildenafil treatment augments the apoptotic potential of DOX in PC3 cancer cells.
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Friedrich, Beate. "Cathepsine B, H, L und ihre Inhibitoren im Gewebe und in Zellkulturen der Prostata." Doctoral thesis, [S.l.] : [s.n.], 1999. http://deposit.ddb.de/cgi-bin/dokserv?idn=957675186.
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Kahmann, Cindy. "Quantifizierung von DNA-Schäden an adhaerenten Zelllinien nach Bestrahlung mit 188 Re- bzw. Röntgenstrahlung unter Zugabe von Methimazol, Nicotinamid und Perchlorat durch den Comet Assay." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2008. http://nbn-resolving.de/urn:nbn:de:bsz:14-ds-1219154119996-02487.
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Martins, Thiago Martino. "Avaliação da ação antitumoral in vitro da pterocarpanoquinona LQB 118 e estudo de alguns mecanismos de ação." Universidade do Estado do Rio de Janeiro, 2013. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=9423.
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Conselho Nacional de Desenvolvimento Científico e TecnológicoTem sido descrito que o acúmulo de mutações em proto-oncogenes e genes supressores de tumor contribui para o direcionamento da célula à carcinogênese. Na maioria dos casos de câncer, as células apresentam proliferação descontrolada devido a alterações na expressão e/ou mutações de ciclinas, quinases dependentes de ciclinas e/ou inibidores do ciclo celular. Os tumores sólidos figuram entre o tipo de câncer mais incidente no mundo, sendo a quimioterapia e/ou hormônio-terapia, radioterapia e cirurgia os tratamentos mais indicados para estes tipos de tumores. Entretanto, o tratamento quimioterápico apresenta diversos efeitos colaterais e muitas vezes é ineficaz. Portanto, a busca por novas moléculas capazes de conter a proliferação destas células e com baixa toxicidade para o organismo se faz necessário. Este trabalho teve por objetivo avaliar a ação antitumoral in vitro de um novo composto sintético, a pterocarpanoquinona LQB118, sobre algumas linhagens tumorais humanas de alta prevalência e estudar alguns dos seus mecanismos de ação. As linhagens tumorais estudadas neste trabalho foram os adenocarcinomas de mama (MCF7) e próstata (PC-3), e carcinoma de pulmão (A549). A citotoxicidade foi avaliada pelo ensaio do MTT e a proliferação celular pela contagem de células vivas (exclusão do corante azul de tripan) e análise do ciclo celular (citometria de fluxo). A expressão gênica foi avaliada por RT-PCR e a apoptose foi avaliada por condensação da cromatina (microscopia de fluorescência-DAPI), fragmentação de DNA (eletroforese) e marcação com anexina V (citometria de fluxo). Das linhagens tumorais testadas, a de próstata (PC3) foi a que se mostrou mais sensível ao LQB 118, e em função deste resultado, os demais experimentos foram realizados com esta linhagem tumoral. O efeito citotóxico do LQB 118 se mostrou tempo e concentração dependente. Esta substância inibiu a proliferação celular e prejudicou a progressão do ciclo celular, acumulando células nas fases S e G2/M. Buscando esclarecer os mecanismos desta ação antitumoral, demonstrou-se que o LQB 118 inibe a expressão do mRNA do fator de transcrição c-Myc e das ciclinas D1 e B1, e induz a apoptose de tais células tumorais. Em suma, o LQB 118 é capaz de inibir a proliferação das células tumorais de próstata, alterando a expressão do mRNA de alguns genes reguladores do ciclo celular, resultando em interrupção do ciclo celular e indução de apoptose, indicando este composto como um potencial candidato a futuro medicamento no tratamento do câncer de próstata.
It has been reported that accumulation of mutation on proto-oncogenes and tumor suppressor genes directs cells to carcinogenesis. In most described cancer, cells display uncontrolled proliferation due to altered expression or mutations of cyclins, cyclin-dependent kinases and cell cycle inhibitors. The solid tumors are the most common cancer type in world. Chemotherapy and/or hormone-therapy, radiotherapy and surgery are the suitable treatment for this disease. However, chemotherapy has been shown several side effects and often ineffective. Therefore, the search for new molecules with antitumoral activity low cytotoxicity is needed. The aim of this work was to evaluate the in vitro antitumoral effects of a new synthetic compound, the pterocarpanquinone LQB 118, on tumor cell lines of high prevalence in the world and to study some mechanisms of action. Tumor cell lines of breast (MCF7), lung (A549) and prostate (PC3) were cultivated at RPMI medium with 10% of serum fetal bovine. The cytotoxicity was evaluated by MTT assay and the cell proliferation by cell counting (trypan blue exclusion) and cell cycle analysis (flow cytometry). Apoptosis was evaluated by chromatin condensation (fluorescence microscopy with DAPI), DNA fragmentation (electrophoresis) and annexin-V and iodide propidium staining. Gene expression was studied by RT-PCR. As LQB 118 (5 g/ml) induced cytotoxic effect mainly on prostate tumor cells, further experiments were then performed only with this tumor cell line. The LQB 118 cytotoxic effects were time and concentration-dependent. Furthermore, this substance inhibited cell proliferation and promoted cell cycle arrest, increasing cell number in S and G2/M phases. Studying the mechanisms of the LQB 118 antitumoral action, it was demonstrated that this substance inhibited the mRNA expression of the transcription factor c-Myc, cyclin D1 and cyclin B1 and also induced apoptosis of PC3. Concluding, LQB 118 impairs prostate tumor cells proliferation due to altered mRNA expression of some cell cycle regulator genes, resulting in cell cycle arrest and apoptosis induction, suggesting this compound as a good candidate for a future drug in prostate cancer treatment.
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Kommagani, Ramakrishna. "DIFFERENTIAL REGULATION OF VITAMIN D RECEPTOR (VDR) BY p53, p63 AND p73." Wright State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=wright1239687284.
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Osorio, Rojas Luis Alfredo. "Efecto del factor transcripcional SNAIL1 sobre las propiedades proliferativas, migratorias e invasivas en las líneas celulares de cáncer prostático LNCaP y PC3." Tesis, Universidad de Chile, 2014. http://repositorio.uchile.cl/handle/2250/145065.
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Magister en biomedicina celular y molecularEn Chile la incidencia y mortalidad del cáncer de próstata (CaP) está aumentado, siendo actualmente la segunda causa de muerte por cáncer en hombres. Durante la progresión tumoral las células epiteliales disminuyen sus moléculas de adhesión, polaridad, posicionamiento, reordenan su citoesqueleto y aumentan sus capacidades migratorias e invasivas. Todos estos cambios se conocen bajo el concepto de Transición Epitelio-Mesénquima (TEM). La TEM se caracteriza por el aumento de ciertos factores transcripcionales, tales como SNAIL1, que reprime genes característicos de un fenotipo epitelial, como E-cadherina, y aumenta indirectamente la expresión de genes que promueven el fenotipo mesenquimático. Se propone que el factor transcripcional SNAIL1 disminuye la proliferación y aumenta las capacidades migratorias e invasivas en líneas celulares de CaP. Para ello se trabajó con las líneas celulares LNCaP y PC3 con expresión ectópica y silenciamiento de SNAIL1 obtenidas mediante el uso de vectores lentivirales. Se caracterizó la expresión de marcadores de TEM mediante PCR en tiempo real, western blot e inmunofluorescencia. Además, se analizó la sobrevida mediante MTS; proliferación utilizando anticuerpos contra PCNA y Ki-67; migración a través de placas con poros de 8 μm (que permiten el paso de células) e invasividad mediante cámaras de membranas cubiertas con una capa de membrana basal. Complementariamente se determinó la apoptosis mediante un kit que contiene un sustrato que es modificado por las caspasas 3 y 7. Se determinó que ambas líneas celulares de CaP con sobreexpresión y silenciamiento de SNAIL1 la proliferación y sobrevida disminuyen. Sin embargo, la sobreexpresión de SNAIL1 disminuye la apoptosis respecto a las células con silenciamiento de la expresión de éste gen, en las cuales aumenta la muerte celular. Respecto a las capacidades migratorias e invasivas, aumentaron sólo en las células con sobreexpresión de SNAIL1 y disminuyeron en las células con silenciamiento. En conclusión, células de CaP con sobreexpresión de SNAIL1 exhibieron características fenotípicas tipo TEM, mientras que el silenciamiento de éste represor transcripcional condujo a las células a un fenotipo tipo epitelial con la disminución de características mesenquimales como la migración e invasión.
FONDECYT No 1110269
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Holmquist, Markus. "Analys av apoptos hos Docetaxel- och manganbehandlade prostatacancerceller." Thesis, Högskolan Kristianstad, Sektionen för lärande och miljö, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:hkr:diva-16981.
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Prostatacancer är idag den vanligaste cancerformen i Sverige, och drygt 10 000 män årligen blir diagnosticerade med sjukdomen. En obotlig variant med dödlig utgång är kastrationsresistent prostatacancer som behandlas primärt med Docetaxel. Tumörcellerna utvecklar dock med tiden resistens mot cytostatikan, och det föreligger därför ett stort behov av att utveckla kombinationsbehandlingar med Docetaxel som grund. Mangan har i flera studier visat sig kunna inducera apoptos hos olika celltyper, och är därför intressant som ett möjligt komplement till Docetaxelbehandling. Syftet med studien var att analysera apoptos hos prostatacancerceller från cellinjen PC3 som exponerats för Docetaxel i kombination med mangan. Cellerna odlades och behandlades med Docetaxel i kombination med mangan under 24, 48 och 72 timmar. Analys av apoptos utfördes med flödescytometer efter infärgning med Annexin V och propidiumjodid. Beroende på cellernas tillstånd färgas de in i olika kombinationer och kan därmed detekteras som tidigt respektive sent apoptotiska, eller som nekrotiska. Resultaten visade på en ökning av apoptos hos kombinationsbehandlade celler, men ingen signifikant skillnad förelåg i jämförelse med obehandlade celler. Ytterligare försök bör därför upprepas med ökad koncentration av Docetaxel i kombination med olika koncentrationer av mangan, och även med andra prostatacancer cellinjer såsom DU145 och LnCaP. Dessutom bör analyser av apoptotiska markörer genomföras, i syfte att bekräfta apoptos.
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Sanmukh, Swapnil Ganesh. "Caracterização da interação dos bacteriofagos T4, M13, e MS2 com células epiteliais prostáticas tumoriais (LNCaP e PC3) ativação das vias de proliferação, sobrevivência e morte celular. /." Botucatu, 2018. http://hdl.handle.net/11449/154970.
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Orientador: Sergio Luis FelisbinoResumo: O câncer de próstata (PCa) é o segundo tipo de câncer mais frequente e tem a segunda maior taxa de morbidade e mortalidade entre os homens. A cultura de células prostáticas LNCaP e PC3 tem sido utilizada para investigar possíveis alvos e vias de sinalização celular importantes para o crescimento e progressão do CaP. Trabalhos anteriores do nosso laboratório demonstraram que a presença de fibronectina no meio de cultura altera significativamente o padrão de expressão gênica dessas células. Também, bacteriófagos recentemente usados como agentes terapêuticos no tratamento de vários tipos de câncer, diretamente ou portadores de moléculas antitumorais, incluindo câncer de próstata, foram relatados. Estudos anteriores mostraram que bacteriófagos podem interagir com proteínas de membrana de células de mamíferos, incluindo integrinas que reconhecem sequências de RGD em proteínas virais, bem como fibronectina e outras moléculas da matriz extracelular. O objetivo deste projeto foi caracterizar a interação de três bacteriófagos com as duas linhagens celulares epiteliais prostáticas LNCaP e PC3. Estas duas linhas celulares foram cultivadas em seus meios de cultura, nos quais foram adicionados bacteriófagos com concentrações definidas. As células foram coletadas após 24 horas de tratamento. A expressão gênica de genes relacionados as vias integrinas ITGA5, ITGAV, ITGB1, ITGB3, ITGB5, AKT, PI3K, MAPK1, MAPK3, HSP27, HSP90, receptor de androgênio AR, STAT3, PGC1A foi analisada por qPCR. A a... (Resumo completo, clicar acesso eletrônico abaixo)
Doutor
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SANTOS, GEYZA S. "Avaliação do efeito radiomodificafor da própolos em células de ovário de hamster chinês (CHO-K1) e em células tumorais de próstata (PC3), irradiadas com CO-60." reponame:Repositório Institucional do IPEN, 2011. http://repositorio.ipen.br:8080/xmlui/handle/123456789/10003.
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Made available in DSpace on 2014-10-09T12:33:42Z (GMT). No. of bitstreams: 0Made available in DSpace on 2014-10-09T14:04:00Z (GMT). No. of bitstreams: 0
Dissertação (Mestrado)
IPEN/D
Instituto de Pesquisas Energéticas e Nucleares - IPEN-CNEN/SP
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Billant, Olivier. "Utilisation de la levure S. cerevisiae pour déchiffrer les mécanismes de l'effet dominant-négatif affectant la famille de gènes suppresseurs de tumeurs p53, p63 et p73." Thesis, Brest, 2016. http://www.theses.fr/2016BRES0055/document.
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P53 est un gène suppresseur de tumeur ubiquitaire qui empêche la prolifération de cellules malignes chez l’humain. En réponse à des dommages à l’ADN ou à des stress cellulaires, p53 entraine l’arrêt du cycle cellulaire et initie la réparation des lésions du génome. Si ces réparations échouent, p53 déclenche alors la mort de la cellule endommagée par apoptose. De plus, p53 présente une forte homologie avec deux autres gènes suppresseurs de tumeur : p63 et p73. Ces trois protéines forment une famille de facteurs de transcription qui protège l’organisme contre le développement de tumeurs. Ce système de défense est enrichi par les multiples isoformes de p53, p63 et p73 dont les rôles sont encore mal décrits. La neutralisation de la fonction de suppression de tumeur de p53, p63 et p73 est un mécanisme clef du développement tumoral auquel participent les mutants hotspots de p53 ainsi que certaines isoformes de p53, p63 et p73 par un effet dominant-négatif. Toutefois, de nombreuses zones d’ombre limitent notre compréhension de ce phénomène. Tout d’abord, l’identification des membres de la famille de p53 impliqués dans l’effet dominant-négatif reste incomplète. Ensuite, les mécanismes responsables de l’effet dominant-négatif sont débattus, suite notamment à l’émergence d’une nouvelle hypothèse impliquant un mécanisme de type prion. Enfin, l’effet dominant-négatif de la famille de p53 pourrait également être mis en cause dans d’autres types de pathologies comme les syndromes développementaux associés à des mutations de p63. Au cours de cette thèse, j’ai étudié l’impact fonctionnel des mutations hotspots de p53 ainsi que celui des principales isoformes de la famille de p53 sur l’activité transcriptionnelle des isoformes actives de p53, p63 et p73. En utilisant comme modèle d’étude un eucaryote simple, la levure S. cerevisiae, nous avons pu démontrer que l’effet dominant-négatif des mutants et isoformes de la famille de p53 repose sur la formation d’hétéro-tétramères entre formes actives et inactives de ces protéines et n’implique pas de mécanisme de type prion. De plus nos travaux ont montré que certains mutants de p53 interfèrent avec les isoformes actives de p63 et p73 par un mécanisme partiellement basé sur la tétramérisation. En outre, nos résultats préliminaires suggèrent que les mutants de p63 impliqués dans les syndromes développementaux EEC, ADULT et NSCL1 exercent également un effet dominant-négatif similaire à celui des mutants de p53. L’identification des mécanismes de l’effet dominant-négatif observé au sein de la famille de p53 permet d’envisager de nouvelles cibles thérapeutiques tant dans les cancers que dans certaines maladies rares du développement humainP53 is a ubiquitous tumor suppressor gene that prevents damaged cells from proliferating. Following DNA damage or cellular stress, p53 induces a cell cycle arrest and initiates an attempt to repair the lesions. If the repair fails, p53 triggers the apoptosis of the cell. p53 shares a high homology with two other tumor suppressor genes: p63 and p73. Together they form a family of transcription factors, which are actively protecting the organism from tumor development. This defense network is enriched by multiple N-terminal and C-terminal isoforms of p53, p63 and p73. The loss of p53, p63 and p73 tumor suppression function is a key step of cancer progression. Mutants of p53 and isoforms of p53, p63 and p73 often exhibit a dominant-negative behavior resulting in the loss of p53 tumor suppression activity. However, the extent of the dominant-negative effect within p53 family remains unclear. The mechanisms behind the dominant-negative effect are also debated due to the recent emergence of a prion-like hypothesis. Finally, the dominant-negative effect of p53 family members could be involved in other pathologies such as p63-related developmental syndromes During this PhD, I studied the functional consequences of hotspot mutations of p53 and of the main isoforms of the p53 family on the transcriptional activity of p53, p63 and p73. Using the naïve eukaryotic model S. cerevisiae we have demonstrated that the dominant-negative effect of mutants and isoforms of the p53 family relies on the formation of hetero-tetramers between functional and non-functional members of the family but not on a prion-like mechanism. In addition, certain p53 mutants are able to interfere with p63 and p73 isoforms though a mechanism that is only partially based on tetramerization. Of note, we obtained preliminary results suggesting that mutants of p63, which are involved in EEC, ADULT and NSCL1 developmental syndromes, behave like dominant-negative hotspot mutants of p53. The identification of the mechanisms of the dominant-negative effect occurring within p53 family could lead to new therapeutic targets both in cancer and in rare developmental syndromes.1 EEC : ectrodactyly, ectodermal dysplasia and cleft lip/palate syndrome, ADULT : acro-dermato-ungual-lacrimal-tooth syndrome, NSCL : non-syndromic cleft lip
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Smolczyk, Yara [Verfasser], and Jörg [Akademischer Betreuer] Reichrath. "p53, Hautpigmentierung und Vitamin D : Untersuchungen zur Assoziation der Genvarianten (SNPs) von Mitgliedern der p53-Familie (p53, p63, p73) und der 25-Hydroxyvitamin- D-Serumkonzentration / Yara Smolczyk ; Betreuer: Jörg Reichrath." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2017. http://d-nb.info/1173163158/34.
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Damm, Friederike [Verfasser], Rainer [Akademischer Betreuer] Engers, and Reza [Akademischer Betreuer] Ahmadian. "Funktionelle Relevanz des Tiam 1 / Rac 3-Signalwegs für die Progression des Prostatakarzinoms: Eine in vitro-Untersuchung am Beispiel der hormonresistenten Prostatakarzinomzelllinie PC3 / Friederike Damm. Gutachter: Rainer Engers ; Reza Ahmadian." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2014. http://d-nb.info/1051734657/34.
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Vayssade, Muriel. "Implication de p53 et de ses homologues, p73 et p63 dans la chimiosensibilité des cellules de cancer du sein." Paris 6, 2002. http://www.theses.fr/2002PA066362.
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Huang, Vera. "Interactions of p53 and p73 with human promoters." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2007. http://wwwlib.umi.com/cr/ucsd/fullcit?p3283559.
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Thesis (Ph. D.)--University of California, San Diego, 2007.Title from first page of PDF file (viewed November 21, 2007). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Silva, Lara Marques Loureiro. "ASPP2 regulating p63/p73 and Notch pathways in tumourigenesis." Master's thesis, Universidade de Aveiro, 2012. http://hdl.handle.net/10773/10878.
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Mestrado em Biotecnologia MolecularNa pele surgem dois dos tipos mais comuns de cancro epitelial, o carcinoma basocelular (BCC) e o carcinoma escamoso da pele (SCC). Neste trabalho, investigámos como ASPP2, membro da família de proteínas que interage com a família p53, pode afectar a tumurigénese da pele. Estudou-se a regulação por ASPP2 das vias de sinalização envolvidas na homeostasia normal do tecido epitelial, tais como as vias de p63 e Notch. A activação anormal de ΔNp63 no epitélio é uma causa conhecida para o surgimento do SCC e os nossos resultados indicam que a ASPP2 é importante a limitar a expressão de ΔNp63 no epitélio diferenciado, prevenindo a proliferação das células na pele. Para além disso, observámos que ASPP2 coopera com vias de sinalização pró-diferenciação, tais como as de Notch e p73. Os nossos resultados mostram um possível mecanismo pelo qual a expressão de p63 pode ser regulada na pele e sugerem um novo modelo para a formação espontânea de SCC.
The skin is where two of the most common types of epithelial cancer, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), arise. In this work, we have investigated how ASPP2, a member of a family of proteins that interact with the p53 family, can affect skin tumourigenesis. We analysed the regulation of ASPP2 in pathways involved in the normal homeostasis of the epithelium, such as the p63 and Notch. Aberrant or misplaced activation of ΔNp63 in the epithelium is a known initiating cause for SCC and our results indicate that ASPP2 is important in limiting ΔNp63 expression in the differentiated epithelium, preventing cell proliferation in the skin. Additionally, we found that ASPP2 can cooperate with skin pro-differentiation pathways, such as Notch and p73. Overall, our results indicate a possible mechanism by which p63 expression can be regulated in the skin, and provide a new model for the spontaneous formation of SCC.
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Chisholm, A. M. "Oxford City PCG and PCT : a case study of collaboration." Thesis, Oxford Brookes University, 2007. http://radar.brookes.ac.uk/radar/items/c8b866a0-5bf4-b06a-dcfd-3d59e8093840/1.
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In 1997 the New Labour government instigated a period of radical reform for the National Health Service, a key element of which was the establishment across England of Primary Care Groups (PCGs), which subsequently became Primary Care Trusts (PCTs). These were local statutory governance bodies with responsibility to deliver and develop primary care and to improve the health of their local population: complex functions requiring collaboration with a range of organisations and agencies. The central aim of this study was to investigate whether and how PCG/Ts developed and facilitated collaboration within primary care, and between it and other NHS and non-NHS bodies, and to identify factors which enabled and inhibited collaboration. Using a theoretical framework which draws on a critical realist tradition, an approach was adopted to the analysis of organisational change which was attentive not only to rational, incremental processes of change but which took into account the political, cultural and economic context in which PCG/Ts operated. A key element of this context was the strong resemblance between New Labour's prominent `third way' discourse of collaboration and the defining characteristics of a network mode of governance: trust, loyalty, reciprocity and voluntariness. Inductive and deductive approaches were combined to test and develop theory about the interactions between context and organisational form, using multiple qualitative methods within a longitudinal nested case study. The study demonstrated that the locality-wide base of PCG/Ts, their explicit health improvement remit, budgetary arrangements and the presence of clinicians on their governing bodies were aspects of their organisational forms which equipped them to facilitate collaboration. However, over time, certain contradictions became apparent in New Labour's approach to organising the NHS which undermined many of the PCG/T's collaborative processes. This thesis argues that the alignment of the third way discourse with a network mode of governance exemplified 'symbolic politics. ' What was presented as a rational response to complex social problems and fragmentation of public services, was in fact largely a pragmatic political manoeuvre designed to distance itself from the perceived failure of previous administrations' hierarchy and market modes of governance.
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BARBERO, PIERRE. "Les convertases de pro-hormones pc1, pc2 et pc5-a : maturation des precurseurs polypeptidiques et adressage dans la voie regulee de secretion des cellules eucaryotes." Nice, 1999. http://www.theses.fr/1999NICE5296.
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L'obtention de molecules bioactives issues d'un precurseur polypeptidique inactif necessite de nombreuses etapes de maturation post-traductionnelle. Parmi ces etapes, le clivage endoproteolytique au niveau de motifs basiques permet la liberation des peptides du precurseur. Les enzymes realisant cette proteolyse des precurseurs hormonaux polypeptidiques sont qualifiees de pro-hormones convertases (pcs). Actuellement, huits pcs ont ete identifiees et seules pc1, pc2 et pc5-a sont specifiques de la voie regulee de secretion des cellules neuroendocrines. La neurotensine (nt) et la neuromedine n (nn), deux peptides apparentes aux fonctions de type neurotransmetteur/neuromodulateur dans le snc et de type hormonale dans la peripherie, sont synthetises au sein d'un precurseur commun le pro-nt/nn. Le pro-nt/nn est mature de facon differente selon les tissus, engendrant la nt et la nn libres dans le snc, et la nt et des formes intermediaires de maturation (bignt et bignn) dans la peripherie. Nos travaux revelent que pc1, pc2 et pc5-a maturent le pro-nt/nn avec des profils de maturation differents. Pc1 engendre un profil semblable au profil intestinal, de plus, elle est colocalisee avec le pro-nt/nn dans l'intestin de souris. Pc5-a mature le pro-nt/nn avec un profil similaire a celui observe dans la glande surrenale qui se trouve etre riche en pc5. En revanche, pc2 qui engendre une maturation complete du pro-nt/nn avec liberation des peptides nt et nn libres, serait l'enzyme de maturation cerebrale de ce precurseur. De plus, sa colocalisation avec le pro-nt/nn dans l'intestin de rat pourrait rendre compte du profil particulier observe avec l'apparition de nn libre en quantite importante dans ce tissu. Enfin, nous avons montre que la proteine 7b2 qui se lie specifiquement a pc2 est essentielle a l'activation de cette pc en assurant son orientation correcte vers la voie regulee de secretion ou elle peut alors pleinement jouer son role d'enzyme de maturation. Un mecanisme d'adressage plus general via des sequences presentes dans le domaine carboxy-terminal des pcs pourrait rendre compte de la localisation intracellulaire specifique de pc1, pc2 et pc5-a.
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Gangnon, Françoise. "Contribution à l'identification des enzymes impliquées dans la maturation des précurseurs de neuropeptides : caractérisation des prohormone-convertases PC1, PC2 et PC5-A chez la grenouille." Rouen, 2002. http://www.theses.fr/2002ROUES025.
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Les prohormone-convertases (PCs) sont des protéases à sérine de type subtilisine qui clivent les précurseurs des hormones peptidiques et des neuropeptides, généralement, au niveau de doublets basiques, pour générer des peptides actifs. Parmi ces enzymes, seules PC1, PC2 et PC5-A sont adressées vers la voie régulée de sécrétion et, de fait, interviendraient dans la maturation des pro-neuropeptides. Dans le cadre d'un programme d'identification de nouveaux neuropeptides chez la grenouille, nous avons cloné les ADNc codant PC1, PC2 et PC5-A chez cet amphibien. Les trois convertases ont été hautement conservées au cours de l'évolution. Elles sont présentes dans le SNC et en périphérie. Les transcrits de PC1, PC2 et PC5-A de grenouille sont abondamment exprimés dans des régions cérébrales où la présence de différents neuropeptides a déjà été établie. Ces résultats sont en faveur d'un rôle majeur joué par ces enzymes dans la maturation des précurseurs de neuropeptidesProhormone-convertases (PCs) are subtilisin-like serine proteases responsible for the proteolytic cleavage of pro-hormones and pro-neuropeptides, that generally occurs at dibasic sites. Among the different PCs characterized to date, only PC1, PC2 and PC5-A are sorted towards the regulated secretory pathway, suggesting that these three convertases may be involved in the processing of neuropeptide precursors. As part of a program of identification of novel regulatory peptides in the brain of the frog, conducted in our laboratory, we have cloned frog PC1, PC2 and PC5-A cDNAs. The three convertases have been highly conserved during evolution. The tissue distribution of frog PCs revealed that PC1, PC2 and PC5-A are present both in the CNS and in peripheral organs. The frog PCs mRNAs are actively expressed in brain nuclei which contain various regulatory peptides, supporting the view that these enzymes are involved in the processing of neuropeptide precursors
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Gillardin, Pierre. "Régulation épigénétique et protéique de p73 dans le Myélome Multiple." Thesis, Nantes, 2017. http://www.theses.fr/2017NANT1037/document.
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Les anomalies de TP53, que sont la délétion génique associée ou non à des mutations somatiques, demeurent un facteur de résistance au traitement dans le Myélome Multiple (MM) malgré l’introduction de nouveaux agents thérapeutiques. Pour contourner les anomalies de TP53, nous avons étudié la possibilité d’activer p73, un membre de la famille de p53, qui n’est pas fréquemment muté dans les cancers. Nous avons étudié l’expression, la méthylation et la régulation de TP73 dans une collection de lignées de MM sauvages ou déficientes pour p53. Nous montrons que TP73 est rarement exprimé et surtout dans les lignées TP53 sauvage. Nous avons étudié la méthylation de l’ilot CpG situé en amont du gène par MS-PCR et montré que l’absence d’expression correspond à son hyperméthylation, qui peut néanmoins être réversée par la décitabine, un inhibiteur de la méthylation. Malgré l’augmentation d’expression de TP73, la décitabine ne permet pas une expression protéique significative de p73. Pour étudier la régulation de p73, nous avons utilisé des agents alkylants, des inhibiteurs de MDM2 et du protéasome. Nous montrons que les nutlin3a et MG132, ne stabilisent pas p73 mais diminuent son expression constitutive. Les agents alkylants induisent une augmentation de p73 mais uniquement dans les lignées TP53 sauvage et l’extinction de p53 par ARN interférence inhibe cette régulation. Dans les lignées déficientes pour p53, la décitabine augmente l’expression génique mais le melphalan ne permet pas de stabilisation de la protéine. L’ensemble de nos résultats montre que TP73 n’apparaît pas être un bon candidat pour contourner les anomalies de TP53TP53 deficiency remains a major adverse event in Multiple Myeloma despite therapeutic progresses. p73, a member of p53 family, is very rarely mutated and has been poorly studied in myeloma. Using human myeloma cell lines with different TP53 status, we assessed methylation, expression and regulation of TP73. We report that TP73 is silenced by methylation and that decitabine increases its expression, which remains however insufficient for significant protein expression. Alkylating drugs increase expression of TP73 only in TP53wt cells and fail to synergize with decitabine in p53 deficient cells. On the other hand, MG132 and nutlin-3a don’t stabilize p73 in response to in TP53wt p73 positive cell lines. TP73 does not appear as a promising target for bypassing p53 deficiency in Multiple Myeloma
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Bertagnolli, Angélica Cavalheiro. "Expressão de p63 e p53 em tumores mamários mistos de cadelas." Universidade Federal de Santa Maria, 2006. http://repositorio.ufsm.br/handle/1/10165.
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Conselho Nacional de Desenvolvimento Científico e TecnológicoThe p63 protein is expressed in the nuclei of the mammary myoepithelial cells and has synergisms or antagonisms with p53 tumor suppressor protein. The immunohistochemistry expression of p63 was studied for access the role of myoepithelial cells in histogenesis of the mixed tumors. Additionally, the possible association between p63 and p53 for access the biological aspects of this tumors was evaluated. Four specimens of the normal gland, 20 benign mixed tumors, 35 carcinomas in mixed tumors and 11 tubulopapilary carcinomas were evaluated. Myoepithelial cells forming layers periductals/periacinars continuous were reactive for protein p63 in normal gland and in benign mixed tumor. The carcinomas in mixed tumors and 72.7% (8/11) tubulopapilary carcinomas were reactive for p63. In the mixed tumors star and spindle shaped cells were reactive for p63. The p53 protein was expressed in 20.0% (4/20), 28.6% (10/35) and 36.7% (4/11), benign mixed tumors, carcinoma in mixed tumors and tubulopapilary carcinomas, respectively. There was not relation between p63 and p53 expression in none type of tumor. The present study point the participation of the mioepithelial cells in the histogenesis of the mixed tumors. The decrease in p63 expression in the basal myoepithelial cells of the carcinomas may be important for tumoral progression.
A proteína p63 é expressa no núcleo das células mioepiteliais da mama e apresenta funções sinérgicas ou antagonistas com a proteína de supressão tumoral p53. A expressão imuno-histoquímica de p63 foi estudada para acessar o papel das células mioepiteliais na histogênese dos tumores mistos. Adicionalmente, avaliou-se a possível relação entre expressão imuno-histoquímica de p63 e p53 com a finalidade de obter informações sobre a biologia desses tumores. Quatro amostras de mama normais, 20 tumores mistos benignos, 35 carcinomas em tumores mistos e 11 carcinomas tubulopapilares foram avaliados. Células mioepiteliais, formando camadas periductais/periacinares contínuas, foram imunoreativas para p63 na mama normal e nos tumores mistos benignos. Todos os carcinomas em tumores mistos e 72,7% (8/11) dos carcinomas tubulopapilares foram reativos para p63. A reatividade para p63 foi superior nos tumores mistos benignos quando comparada com os carcinomas. Nos tumores mistos, células mioepiteliais com formato fusiforme e estrelado, presentes no estroma mucinoso também foram reativas para p63. A proteína p53 foi expressa em 20,0% (4/20), 28,6% (10/35) e 36,4% (4/11) dos tumores mistos benignos, carcinomas em tumores mistos e carcinomas tubulopapilares, respectivamente. Não houve relação entre a expressão de p53 e p63 nos diferentes tipos tumorais. O presente estudo evidenciou a participação das células mioepiteliais na histogênese dos tumores mistos. A diminuição da expressão de p63 nas células mioepiteliais que compõem a camada basal dos carcinomas pode ser um evento importante para a progressão tumoral.
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Lusson, Juliette. "Clonage de la pro-protéine convertase PC5 et étude du rôle des motifs structuraux conservés de PC1 et de PC2 dans l'activation et l'adressage de ces convertases." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0024/NQ33049.pdf.
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Santos, Mónica Cristina Barão Costa. "PCT e PCR no apoio ao diagnóstico de sépsis no recém-nascido." Master's thesis, Universidade de Aveiro, 2012. http://hdl.handle.net/10773/10891.
Full textAbstract:
Mestrado em Bioquímica - Bioquímica ClínicaApesar de uma significativa diminuição nas últimas décadas, os processos infeciosos mantêm-se como uma das principais causas de mortalidade/morbilidade neonatal, um fato em parte devido à imaturidade do sistema imunológico do recém-nascido (RN) e ao crescente número de natos prematuros de reduzido peso corporal. O diagnóstico precoce de quadros de sépsis e a apropriada intervenção terapêutica representam deste modo um desafio diário em neonatologia. Dos diversos marcadores biológicos utilizados no apoio ao diagnóstico de sépsis, as proteínas de fase aguda procalcitonina (PCT) e proteína C-reactiva (PCR) têm mostrado considerável utilidade clínica. Devido à sua rápida cinética após estímulo imunológico, são considerados marcadores biológicos precoces de sépsis, permitindo uma resposta em tempo útil inferior ao tempo necessário para a identificação do agente etiológico por exame cultural. Pretendeu-se com este trabalho reavaliar a utilidade dos marcadores biológicos PCT e PCR no apoio ao diagnóstico de sépsis no RN. Adicionalmente foi também avaliada a possível correlação entre o padrão de variação dos referidos biomarcadores e a etiologia dos agentes infeciosos. O estudo baseou-se na recolha de dados relativos aos parâmetros PCT e PCR em RN com suspeita de sépsis, seguindo-se o seu tratamento e análise estatística. As amostras foram processadas no Centro Hospitalar Entre Douro e Vouga (CHEDV) dizendo respeito ao intervalo de tempo compreendido entre Janeiro de 2011 e Abril de 2012. Os resultados obtidos corroboram com outros estudos feitos para o mesmo efeito, em que a PCT e a PCR em conjugação com uma cuidadosa avaliação clínica, fornecem uma informação de grande valia no diagnóstico de sépsis no RN. Relativamente aos resultados dos exames culturais pedidos nas primeiras horas de vida dos 84 RN do estudo, 99% foram negativos e 1% foram positivos. Estes resultados sustentam crescentes dúvidas acerca da utilidade/validade dos exames culturais.
In the last recent decades, the infectious processes have been decreasing significantly; however, they are still one of the leading causes of neonatal mortality / morbidity, in part due to the immaturity of the newborn immune system and to the increasing number of premature births, whose infants are of low birth weight. Early diagnosis of sepsis and the appropriate therapeutic intervention represent, therefore, a daily challenge in neonatology units. Among all the different biological markers used to support the diagnosis of sepsis, acute phase proteins, procalcitonin (PCT) and C-reactive protein (CRP) have shown to be of considerable clinical value. Due to their rapid kinetics after immune stimulation, these molecules are considered early markers of sepsis, as they provide the needed answers earlier than the time usually needed for the identification of the etiologic agents done by culture exam. The aim of this study was to reassess the utility of the biomarkers PCT and CRP in order to help in the diagnosis of newborn sepsis. Additionally, it was also evaluated the possible correlation between the variation profile of these biomarkers and the etiology of the infectious agents. The study was based on the data collection of the PCT and CRP parameters in neonates, who were under sepsis suspicion, followed by the treatment and statistical analysis. The samples were processed in the Centro Hospitalar Entre Douro e Vouga (CHEDV), which comprise the analysed cases from January 2011 till April 2012. The results corroborate other studies done for the same effect, in which the PCT and CRP in conjunction with a careful clinical assessment, provide valuable information in the diagnosis of sepsis in neonates. In what culture test results ordered in the first 84 hours of life of infants in the study is concerned, 99% were negative and 1% was positive. These results support the growing doubts about the usefulness / validity of the cultural tests.
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Colozza, Roberto. "Repubbliche comuniste. La simbologia nazionale nel Pci e nel Pcf (1944-1953)." Doctoral thesis, Scuola Normale Superiore, 2007. http://hdl.handle.net/11384/85648.
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Beitzinger, Michaela [Verfasser], and Michael [Akademischer Betreuer] Schön. "Regulierung der Telomerase durch das p53-Homolog p73 / Michaela Beitzinger. Betreuer: Michael Schön." Würzburg : Universität Würzburg, 2006. http://d-nb.info/1099603676/34.
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Mitchell, Geoffrey C. "The p53 homolog p63 modulates acute and chronic damage in irradiated salivary glands." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/194089.
Full textAbstract:
Head and neck cancer is diagnosed in more than 50,000 Americans each year, resulting in roughly 11,000 deaths. For this disease, a typical therapeutic regimen involves cisplatin, a radiosensitizer, given alongside targeted irradiation. While technological advances such as IMRT have been useful in sparing normal tissues from radiotherapy, the salivary glands occupy much of the head and neck and surround several lymph nodes, and thus, non-diseased salivary glands are often damaged. This causes reduced salivary output, damaged oral mucosa, dysphagia, malnutrition and tooth decay. Often, these side-effects are so severe that patients discontinue treatment, however, in many cases, salivary gland damage is permanent, and treatment options are palliative. Specifically, muscarinic-cholinergic agonists are used to enhance secretion from remaining salivary cells, although due to non-specific action, these drugs have a number of ill-effects. It is clear that therapies are needed to prevent radiation-induced salivary gland damage, as well as to restore glandular function in patients who are already suffering.Previous work from our group has shown that salivary gland dysfunction results from loss of acinar cells to radiation-induced apoptosis. Importantly, a single intravenous dose of IGF1 can prevent apoptosis and preserve salivary output when given immediately prior to irradiation. Because of its broad effects, however, IGF1 may never be a viable clinical option. Instead, our goal is to identify signaling events that mediate the radioprotective effects of IGF1 downstream of Akt. Because radiation-induced apoptosis in salivary glands is p53-dependent, we assessed the contributions of the p53 homologs p63 and p73 to the DNA damage response. Here, we show that IGF1 enhances cell cycle arrest following irradiation by reducing inhibitory binding of deltaNp63 to the p21 promoter. We hypothesize that IGF1-induced cell cycle arrest may allow time for DNA repair, thus preventing apoptosis and maintaining salivary function. In addition, we indicate chronic signaling events downstream of p63 that may contribute to permanent loss of salivary function by blocking differentiation of salivary progenitor cells. Together, these results indicate that p63 may be a valid therapeutic target for both prevention of damage and restoration of function in irradiated salivary glands.
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Mondeková, Věra. "Cytotoxicita vybraných naftochinonů na prostatických buněčných liniích." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2013. http://www.nusl.cz/ntk/nusl-220038.
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This master´s thesis discusses cytotoxicity of selected naphthoquinones on prostatic cell cultures. The introductory part is dedicated to general characteristic of naphthoquinones with focus on their cytotoxicity, testing of cytotoxicity and mechanisms of cytotoxicity. This part is followed by chapters about cytotoxicity, characteristics and biological activities of selected naphthoquinones; plumbagin and naphthazarin. The last part of this thesis’ theoretical section speaks about fluorescence microscopy and its use in research of naphthoquinones cytotoxicity. The practical part is dedicated to evaluation of cytotoxical tests’ results and to analysation of pictures of cells obtained by fluorescence microscope. At the end of thesis, all finding are summarized and put in the context.
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Pozniak, Christine D. "The related p53 and p73 proteins have opposing roles in neuronal survival and apoptosis /." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38259.
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The neurotrophins support survival of many different classes of neurons during development of the nervous system. Appropriate neuronal numbers are generated as developing neurons compete for adequate amounts of neurotrophin and those that are unsuccessful die by a process of apoptosis. In addition to survival, the neurotrophins have recently been shown to regulate apoptosis by activating the p75 neurotrophin receptor at the cell surface. Therefore, the decision to live or die depends on the interplay between survival and death signals, but the underlying mechanisms mediating these events are only beginning to be elucidated. The following chapters highlight the function of two related proteins, p53 and p73, and their opposing roles in neuronal apoptosis and survival.The first chapter demonstrates that the endogenous p53 tumor suppressor protein is essential for naturally occurring death of sympathetic neurons. Blocking the function of p53 either by targeted deletion in mice or viral inhibitors can rescue sympathetic neurons from apoptosis. These results are consistent with the role of p53 following injury in postmitotic neurons, however, they also demonstrate a novel function for p53 during nervous system development.
The next experiments define a role for the p53 related protein, p73, in sympathetic neuron development. P73 exists as both pro and anti-apoptotic isoforms with the latter being predominantly expressed in the nervous system. Here I report that the anti-apoptotic p73 protein (DeltaNp73) is essential for sympathetic neuron survival during development and that one of its main targets is p53.
The final section examines the role of DeltaNp73 in the CNS. Cortical neurons die at a rapid and continuous rate in the absence of DeltaNp73. We also identify p73 at a position downstream of PI3 kinase, a major survival protein important for many types of neurons. Finally, we demonstrate that p73 overexpression can protect neurons from DNA damage induced death.
Together these studies have identified novel and opposing roles for the p53 family members in developing and mature neurons of the central and peripheral nervous systems.
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Pei, Lim-cho Steven, and 貝念祖. "Role(s) of p53/p63 in chondrocyte re-differentiation upon activation of ER stress." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hdl.handle.net/10722/198926.
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Endoplasmic Reticulum (ER) stress signal is a cellular response to various insults including
abnormal protein folding load, activating the unfolded protein response. Under severe ER stress,
apoptosis will occur in most cell types. Interestingly, this does not happen in a disease model for
Metaphyseal chondrodysplasia type Schmid (MCDS), where ER stress was activated in the
hypertrophic zone of the growth plate where mutant collagen X proteins that cannot be folded
correctly is expressed. Instead of normal progression from proliferating chondrocytes (PCs) to
hypertrophic chondrocytes (HCs) and conversion to bone, HCs in MCDS mice undergo
re-differentiation to PCs as a survival strategy due to an activation of ER stress. Transcription
factors are known to be important in regulating differentiation. p53 family members, as
transcription factors, are known to play important roles in developmental processes including
cellular reprogramming, thus, we hypothesize that the ectopic expression of key transcription
factors, p53 and TAp63, which are activated by ER stress is involved in HC re-differentiation. p53
is normally expressed in late PCs, Pre-HCs, and upper HCs, while TAp63 is expressed in PCs and
Pre-HCs suggesting they may have roles in chondrocyte differentiation. p53 activated under ER
stress in HCs are nuclear localized in MCDS mice, but did not invoke the apoptotic programme.
In this project, using quantitative analyse to study the expression level of p53 and p63 isoforms, it
was confirmed that p53 and TAp63γ are in part transcriptionally activated upon ER stress. From
functional study by inactivating p53 in MCDS mice, it was shown that p53 alone was not sufficient
to mediate re-differentiation. Given that TAp63γ isoforms is also highly upregulated upon ER
stress, and the negative regulator, ΔNp63, is downregulated, this combination of change in gene
expression also need to be considered.
Furthermore, known regulators of p53 and p63 activity such as ASPP1 and iASPP are also
differentially expressed in HCs, and are altered upon activation of ER stress favouring cell survival.
Thus, it would be important to evaluate the combination of TAp63 in the re-differentiation process
from conditional inactivation of p63 or in combination with p53 to gain a clearer understanding of
the contribution and relationship of these transcription factors in the survival strategy of stressed
HCs.published_or_final_version
Biochemistry
Master
Master of Philosophy
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Maia, Rodrigo Ismael Francisco [UNESP]. "Crise da esquerda comunista: políticas do PCI e do PCP sobre a união europeia." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/132429.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Questa dissertazione ha lo scopo di capire le relazione tra il Partito Comunista Italiano(PCI) e il Partito Comunista Portoghese (PCP) rispetto il processo di integrazione europeo che si è concluso con l'Unione Europea (UE), rilevando la connessione fra politica interna e estera nelle strategie dei partiti. In Italia e Portogallo, lo stabilimento della democrazia faceva parte della strategia dei due PC, i quali avevano ampie basi nelle classi lavoratrici. La tenuta della autoorganizzazione delle classi lavoratrici e la fine dei processi di agitazione sociale portarono alla normalità democratica e alla internazionalizzazione economica, liberale. Il PCI, promuovendo la sua particolare via italiana al socialismo, ha collaborato con la formazione della Comunità Economica Europea (CEE), il PCP che inizialmente la rifiutava, ha iniziato a prenderla come fonte di benefici in difesa dalla democrazia. Lo sviluppo sociale della CEE è stato disuguale e combinato, grazie al quale i paesi sono diventati parte del mercato comune mentre la frammentazione devastava il mondo del lavoro. L'isolamento è stata una prima sconfitta per i due PC nei governi nazionali, e un'altra è stata la impossibilità di andare avanti con la strategia delle riforme in direzione al socialismo. Al fallimento pratico e ideologico si è aggiunto quello politico al momento della conclusione della UE e della crisi finale della sinistra comunista internazionale, quando il PCI ha deciso per lo scioglimento e il PCP per la continuità ortodossa.
Esta dissertação tem o objetivo de compreender as relações entre o Partido Comunista Italiano (PCI) e o Partido Comunista Português (PCP) a respeito do processo de integração europeu que culminou na União Europeia (EU), destacando a conexão entre a política interna e externa nas estratégias dos partidos. Na Itália e em Portugal, a instauração do regime democrático fazia parte da estratégia dos dois PCs, os quais possuíam amplas bases nas classes trabalhadoras. O estancamento das auto-organizações das classes trabalhadoras e o fim dos processos de efervescência social levaram à normalidade democrática e à internacionalização das economias, liberalizando-as. O PCI, promovendo sua particular via italiana ao socialismo, colaborou com a formação da Comunidade Econômica Europeia (CEE), o PCP que inicialmente a recusava, passou a tomá-la como fonte de benefícios em defesa da democracia. O desenvolvimento social da CEE foi desigual e combinado, no qual os países passaram a fazer parte do mercado comum ao mesmo tempo em que a fragmentação assolava o mundo do trabalho. O isolamento foi uma primeira derrota dos dois PCs nos governos nacionais, e a outra foi a impossibilidade de avançar com a estratégia de reformas rumo ao socialismo. À falência prática e ideológica se somou a política no limiar da efetivação da UE e diante da crise terminal da esquerda comunista internacional, quando o PCI decidiu pelo desmanche e o PCP pelo prosseguimento ortodoxo.
This thesis aims to understand the relationships between the Italian Communist Party (PCI) and the Portuguese Communist Party (PCP) about the European integration process which culminated in the EU, highlighting the connection between domestic and foreign policy in strategies of the parties. In Italy and Portugal, the establishment of the democratic system was part of the strategy of the two PCs, which had broad-based in the working class. The stagnation of the selforganization of the working classes and the end of social unrest processes have led to democratic normality and the internationalization of economies, liberalizing them. The PCI, promoting their particular Italian via to socialism, collaborated with the formation of the European Economic Community (EEC), the PCP that initially refused, began to take it as a source of benefits in defense of democracy. The EEC's social development was uneven and combined, in which countries became part of the common market at the same time the fragmentation ravaged the world of work. The isolation was a first defeat of the two PCs in national governments, and the other was the impossibility to move forward with the strategy of reforms toward socialism. To the practical and ideological failure was joined the politics at the threshold of execution of the EU, in front of the terminal crisis of the international communist left, when the PCI decided for dismantle and the PCP to the orthodox continuation.
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Maia, Rodrigo Ismael Francisco. "Crise da esquerda comunista : políticas do PCI e do PCP sobre a união europeia /." Marília, 2015. http://hdl.handle.net/11449/132429.
Full textAbstract:
Orientador: Marcos Del RoioAbstract: This thesis aims to understand the relationships between the Italian Communist Party (PCI) and the Portuguese Communist Party (PCP) about the European integration process which culminated in the EU, highlighting the connection between domestic and foreign policy in strategies of the parties. In Italy and Portugal, the establishment of the democratic system was part of the strategy of the two PCs, which had broad-based in the working class. The stagnation of the selforganization of the working classes and the end of social unrest processes have led to democratic normality and the internationalization of economies, liberalizing them. The PCI, promoting their particular Italian via to socialism, collaborated with the formation of the European Economic Community (EEC), the PCP that initially refused, began to take it as a source of benefits in defense of democracy. The EEC's social development was uneven and combined, in which countries became part of the common market at the same time the fragmentation ravaged the world of work. The isolation was a first defeat of the two PCs in national governments, and the other was the impossibility to move forward with the strategy of reforms toward socialism. To the practical and ideological failure was joined the politics at the threshold of execution of the EU, in front of the terminal crisis of the international communist left, when the PCI decided for dismantle and the PCP to the orthodox continuation.
Astratto: Questa dissertazione ha lo scopo di capire le relazione tra il Partito Comunista Italiano(PCI) e il Partito Comunista Portoghese (PCP) rispetto il processo di integrazione europeo che si è concluso con l'Unione Europea (UE), rilevando la connessione fra politica interna e estera nelle strategie dei partiti. In Italia e Portogallo, lo stabilimento della democrazia faceva parte della strategia dei due PC, i quali avevano ampie basi nelle classi lavoratrici. La tenuta della autoorganizzazione delle classi lavoratrici e la fine dei processi di agitazione sociale portarono alla normalità democratica e alla internazionalizzazione economica, liberale. Il PCI, promuovendo la sua particolare via italiana al socialismo, ha collaborato con la formazione della Comunità Economica Europea (CEE), il PCP che inizialmente la rifiutava, ha iniziato a prenderla come fonte di benefici in difesa dalla democrazia. Lo sviluppo sociale della CEE è stato disuguale e combinato, grazie al quale i paesi sono diventati parte del mercato comune mentre la frammentazione devastava il mondo del lavoro. L'isolamento è stata una prima sconfitta per i due PC nei governi nazionali, e un'altra è stata la impossibilità di andare avanti con la strategia delle riforme in direzione al socialismo. Al fallimento pratico e ideologico si è aggiunto quello politico al momento della conclusione della UE e della crisi finale della sinistra comunista internazionale, quando il PCI ha deciso per lo scioglimento e il PCP per la
Resumo: Esta dissertação tem o objetivo de compreender as relações entre o Partido Comunista Italiano (PCI) e o Partido Comunista Português (PCP) a respeito do processo de integração europeu que culminou na União Europeia (EU), destacando a conexão entre a política interna e externa nas estratégias dos partidos. Na Itália e em Portugal, a instauração do regime democrático fazia parte da estratégia dos dois PCs, os quais possuíam amplas bases nas classes trabalhadoras. O estancamento das auto-organizações das classes trabalhadoras e o fim dos processos de efervescência social levaram à normalidade democrática e à internacionalização das economias, liberalizando-as. O PCI, promovendo sua particular via italiana ao socialismo, colaborou com a formação da Comunidade Econômica Europeia (CEE), o PCP que inicialmente a recusava, passou a tomá-la como fonte de benefícios em defesa da democracia. O desenvolvimento social da CEE foi desigual e combinado, no qual os países passaram a fazer parte do mercado comum ao mesmo tempo em que a fragmentação assolava o mundo do trabalho. O isolamento foi uma primeira derrota dos dois PCs nos governos nacionais, e a outra foi a impossibilidade de avançar com a estratégia de reformas rumo ao socialismo. À falência prática e ideológica se somou a política no limiar da efetivação da UE e diante da crise terminal da esquerda comunista internacional, quando o PCI decidiu pelo desmanche e o PCP pelo prosseguimento ortodoxo.
Mestre
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Goldschneider, David. "Intéractivité de p73 et p53 dans les processus d'apoptose et de différenciation du neuroblasme." Paris 11, 2004. http://www.theses.fr/2004PA11T022.
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Liu, Yue. "Regulation of p53 and p73 function by PCAF and adenovirus E1B 55-kDa oncoprotein." Thèse, Sherbrooke : Université de Sherbrooke, 2002. http://savoirs.usherbrooke.ca/handle/11143/4172.
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Gasperis, Alexia de. "Expression et fonctions biologiques de l’isoforme ΔNp63." Thesis, Lyon 1, 2011. http://www.theses.fr/2011LYO10275.
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Le gène TP63 fait partie de la famille du gène suppresseur de tumeur TP53. Il code plusieurs isoformes. L’une d’entre elles, tronquée dans la région amino-terminale et appelée ΔNp63, présente des propriétés oncogéniques. Elle est impliquée dans la progression tumorale et la chimiorésistance. Sa surexpression est fréquente dans certains types de cancers. La première partie de mes travaux a consisté à identifier les facteurs de transcription impliqués dans la régulation du promoteur de ΔNp63. J’ai montré que l’expression de cette isoforme est inhibée par p53 et activée par ΔNp63 elle-même et par la β-caténine, dans des lignées de carcinome hépatocellulaire et de carcinome épidermoïde de l’œsophage. Dans des conditions physiologiques, un des types cellulaires dans lequel ΔNp63 est exprimée est la cellule basale mammaire. Il est admis que les tumeurs mammaires dites basal-like sont issues des cellules basales. Certaines de ces tumeurs présentant une surexpression de ΔNp63, nous avons émis l’hypothèse que ΔNp63 serait impliquée dans la tumorigenèse des cellules basales. Dans la deuxième partie, j’ai montré que l’expression de ΔNp63 peut être augmentée en cultivant les cellules mammaires en présence de surnageant de fibroblastes embryonnaires humains. L’identification de facteurs solubles responsables est en cours. D’autre part, j’ai caractérisé les conséquences biologiques de cette augmentation en termes de prolifération, de motilité et de survie des cellules immatures mammaires normales et tumorales. Les plus grandes modifications observées concernent (i) l’état de différenciation, les cellules surexprimant ΔNp63 présentant un phénotype plus immature ; (ii) la balance entre migration et adhésion qui penche en faveur de cette dernière. ΔNp63 semble donc être au carrefour des mécanismes de prolifération, d’adhésion, de différenciation et de motilité, processus impliqués dans la formation et l’homéostasie des tissus, mais dont l’altération peut conduire à l’initiation et à la progression tumorale ainsi qu’à la dissémination métastatique. Mes travaux apportent des informations sur le rôle de cette protéine dans ces processus et devraient, à terme, permettre de mieux comprendre la genèse de certains cancers, en particulier les carcinomes basal-likeTP63 gene belongs to the TP53 tumor suppressor gene family. It encodes several isoforms. One of these, truncated in its amino-terminal end and called ΔNp63, displays oncogenic properties. It is involved in tumor progression and chemoresistance and is overexpressed in some tumor types. The first part of my work consisted of identifying the transcription factors involved in the regulation of the ΔNp63 promoter. I have shown that ΔNp63 expression is inhibited by p53 and activated by ΔNp63 itself and by β-catenin in hepatocellular carcinoma and esophageal squamous cell carcinoma cell lines. Under physiological conditions, one of the cell types in which ΔNp63 is expressed is the mammary basal cell. The “basal-like” mammary tumor sub-type seems to stem from basal cells. As some of these tumors exhibit overexpression of ΔNp63, we hypothesized that this isoform could be involved in the genesis of basal-like tumors. In the second part, I have shown that ΔNp63 expression can be increased in mammary cells cultivated in the presence of human embryonic fibroblast supernatant. Identifying the soluble factors responsible for this increase is in progress. In parallel, I have evaluated the biological consequences of ΔNp63 overexpression in terms of proliferation, cell motility and survival of normal and malignant immature mammary cells. The main modifications relate to (i) the differentiation status, ΔNp63-overexpressing cells exhibiting a more immature phenotype; (ii) the balance between migration and adhesion that is in favor of this latter. ΔNp63 seems to be at the crossroads of proliferation, adhesion, differentiation and motility, processes implicated in tissue formation and homeostasis, but whose alteration may lead to tumor initiation and progression and to metastatic dissemination. My work provides information on the role of this isoform in these processes and should allow better understanding of the genesis of some tumor types, in particular basal-like breast carcinomas
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Faridoni-Laurens, Laetitia. "Implication des gènes de la " Famille p53 " dans la différenciation et la carcinogenèse de l'épithélium des voies aéro-digestives supérieures (VADS)." Paris 6, 2002. http://www.theses.fr/2002PA066135.
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Cadot, Bruno. "P63alpha, membre de la famille de p53 : structure, interaction et importance du domaine SAM de p63alpha." Paris 6, 2005. http://www.theses.fr/2005PA066045.
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Ho, Daniel Kuan-te. "Mechanisms used by p73, p63 and XIAP to regulate survival and apoptosis of sympathetic neurons." Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=81341.
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Developmental neuron death is determined by the activities of pro-survival and pro-apoptotic proteins. Here, we investigate the functions of three such proteins---p73, p63 and XIAP---in cultured neonatal sympathetic neurons. p73 and p63 are members of the p53 family that exist in both full-length (TA) and truncated (DeltaN) isoforms. First, we ask whether DeltaNp73 mediates sympathetic neuron survival in p53-dependent and/or -independent fashions. Overexpression of DeltaNp73 in sympathetic neurons withdrawn from NGF prevents upregulation of the p53 targets p21waf1 and Apaf-1, induction of the BH3-only protein BimEL, and cleavage of the effector caspase-3. DeltaNp73 also promotes survival in p53-independent manner by acting upstream of p53 to decrease JNK phosphorylation. Second, we ask whether p63 functions as a pro-apoptotic molecule in a manner similar to that of p53. TAp63 levels markedly increase in sympathetic neurons withdrawn from NGF. Similar to p53, TAp63 overexpression in neurons maintained in NGF upregulates p21waf1 and Apaf-1 levels, induces caspase-3 cleavage, and does not induce BimEL levels and JNK phosphorylation. Third, we examine the role of the caspase inhibitor XIAP and ask whether XIAP is a substrate of the serine/threonine kinase Akt. XIAP rescues NGF withdrawal- and LY294002-induced apoptosis and promotes sympathetic neuron survival cooperatively with Ras. In addition, Akt associates with XIAP and phosphorylates XIAP at serine 87.
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Brar, Bhawanjit Kaur. "Studies on the processing of proenkephalin A by the prohormone converting enzymes PC1 and PC2." Thesis, University of Reading, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296696.
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Bergaglio, Cecilia. "Identités et stratégies politiques du PCI et du PCF : une comparaison entre le Triangolo Industriale en italie et la région industrielle du Rhônes - Alpes en France." Thesis, Université Grenoble Alpes (ComUE), 2015. http://www.theses.fr/2015GREAL029.
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Les objectifs du projet de recherche ont leur fondement dans la tentative de répondre à quelques questions essentielles concernant l'identité du Parti Communiste italien et du Parti Communiste français en tant que sujets politiques complexes, multiformes et dynamiques.On a d'abord crée deux laboratoires d'analyse, l'un en Italie, le deuxième en France, en tant que lieux d'observation, d'étude et de dénouement des thèmes les plus significatifs liés à l'identité, la stratégie et la culture communiste.En ce qui concerne l'Italie, on a tout naturellement choisi le Triangle Industriel qui constitue une macro zone aux caractères sociaux et économiques communs où le PCI a joué un rôle important et tout à fait différent par rapport aux autres zones sub-culturelles de la péninsule dans les années de l'après-guerre.Il m'a paru de plus en plus évident que la région Rhône-Alpes se caractérisait par des aspects économiques, sociaux, géographiques et anthropiques intéressants qui la rapprochaient au Triangle Industriel avec lequel, d'ailleurs, il existait une proximité territoriale.D'après un regard plus attentif au tissu socio-économique de la région, on s'aperçoit que les trois plus importantes villes - Grenoble, Lyon, Saint Etienne- se caractérisent par le même mélange d' « ingrédients » sur lesquels se fonde le caractère particulier des chefs-lieux du Triangle Italien. Il s'agit d'une très forte vocation industrielle, d'une société hétérogène, d'un équilibre parmi les forces politiques protagonistes du débat local (ou, au moins, pas de supériorité nette et durable de l'une par rapport aux autres), de Fédérations à même de marquer, d'une manière nette et durable, l'histoire, l'identité, la mentalité des inscrits et des électeurs, enfin d'une partie considérable de la société.Après les domaines, les temps de la recherche. La Libération, ou mieux encore, l'année 1946 s'est imposée d'une manière tout à fait naturelle comme « incipit ». Il s'agissait d'une césure chronologique évidente pour le début d'un parcours ; une date naturelle mais pas infranchissable, plutôt osmotique avec le passé des militants et des cadres qui, par leur mémoire personnelle, reviennent à la période précédant la naissance du parti.C'est un parcours long, sinueux, complexe dont on a repéré la fin, d'une manière tout à fait subjective mais bien motivée, en 1976, en ce qui concerne l'Italie et en 1978, en ce qui concerne la France. Les deux dates sont très représentatives des deux Pays et des deux partis communistes.On est bien dans les années de l'apogée après lequel va commencer la chute.Deux évènements vont caractériser ce moment : le doublement raté en Italie et la débâcle électorale en France. Il s'agit d'une histoire différente mais de là on va assister à un déclin lent et inexorable. C'est une conjoncture qui nous implique tous et qui change, irrémédiablement, la destinée de nos microcosmes.Les sources utilisées pour ce travail de recherche se divisent en trois groupes différents. Appartiennent au premier groupe les données quantitatives concernant la base militante et les Comités Fédéraux de chacune des Fédération faisant l'objet de la recherche.Un deuxième groupe de sources se compose, par contre, de la documentation officielle concernant les débats intérieurs au parti. Il s'agit de congrès, de réunions du Comité Fédéral, de rapports préparatoires, une masse de documents produits par les Fédérations qui a été tout à fait indispensable dans la reconstruction des stratégies politiques poursuivies sur les territoires.Le troisième et tout dernier groupe de sources est sans doute celui qui m'a fascinée davantage par sa richesse et par ses infinies possibilités d'interprétation et par le passage du plan quantitatif au qualitatif aussi. Il s'agit de biographies rédigées par les cadres au moment de l'inscription au parti ou bien pendant la participation à l'une de ses écolesThe aim of the research project is the attempt to answer some basic questions about the identity of the Italian and French Communist parties, considered as complex and dynamic political subjects.The first step was to select two case studies, one in Italy and one in France, as places where to observe and deal with the most meaningful themes linked to the identity, the strategies and the political communist cultures.As far as Italy is concerned, I chose the so-called Triangolo Industriale. It represents a macro-area with economic and social common features and where the Pci played an important role, different from the other sub- cultural areas of Italy in the second post-war period.I realized that the Rhône-Alpes had the economic, social, geographical and anthropic features approaching it to the Triangolo Industriale, with which also as a geographical proximity.Going deeper into the social and the economic texture of the three most important cities – Grenoble, Lyon, Saint Étienne - I discovered that they have the same mixture of “ingredients” compared to Milan, Turin and Genua: well-rooted industrial vocation, heterogeneous society, a good balance among the political forces, local communist Federations able to mark the identity, the history and the cultural of their members and the electors.The research has as starting point the year 1946. Natural chronological caesura but overcome by the memories of the militants and political leaders, which date back until the previous period to the birth of the party.It is a long and complex process lasting until 1976 for Italy and 1978 for France. These dates are extremely representative for both communist parties because they constitute the apogee moment, before the beginning of the decline. Two events characterize this moment: the failed “sorpasso” in Italy and the electoral defeat in France. It is a crucial point implying a radical change also in our two micro-cosmos.The sources used in this research can be divided in three groups: the first group is represented by the statistic data about militants and political local structures. The second is represented by the official documents of the internal party debates, useful to reconstruct the political strategies pursued in every territory.The third and last source is the one that has struck me more for the infinite interpretative possibilities and for the passage from the quantitative to the qualitative level. They are the biographies written by the communist leaders at the moment of their adhesion to the party or when they attended the political schools of the party.STAR
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Johnson, Jodi L. "The p53 family interacting pathways in carcinogenesis and cellular response to DNA damage." Oregon Health & Science University, 2007. http://content.ohsu.edu/u?/etd,628.
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Ph.D.Molecular and Medical Genetics
The objective of this study is to examine, in light of the expression of multiple p53 family member isoforms, the specific role of p73 in malignant conversion, cellular response to DNA damage, and direct or indirect cooperation with other p53 family members in a clonal model of epidermal carcinogenesis. We first focused on the role of p73 in malignant conversion. Whether sporadic or siRNA induced, loss of p73 in initiated p53+/+ keratinocytes lead to conversion to squamous cell carcinoma (SCC) in vivo which was reversible upon reconstitution of TAp73α but not ΔNp73α. Second, we investigated the cellular response to ionizing radiation (IR) in the presence and absence of p73, showing that loss of p73 at malignant conversion was associated with resistance to IR in vitro. The loss of radiation sensitivity and malignant conversion was characterized by reduced steady state DNA binding levels of transcriptionally active p63 isoforms to the p21 promoter, failure to induce specific p53 family transcriptional targets, and failure to arrest in G1. Reconstitution of TAp73α, but not ΔNp73α, increased steady state DNA binding capabilities of TAp63β, TAp63γ, and ΔNp63γ, and steady state levels of p53 family target mRNA, but did not restore cellular sensitivity to IR. We thus uncovered a functional cooperation between TA isoforms of p73 and p63 and showed that p73-mediated DNA damage response was uncoupled from its tumor suppressive role. We observed preferential DNA binding of the inhibitory ΔNp63α isoform both in vitro and invivo in SCC suggesting that in the absence of TAp73α a balance is tipped toward DNA binding of the inhibitory isoforms. Third, we studied the role of the p53 family inkeratinocyte response to UVB. Tumorigenic cells lacking p73 that were resistant to IR remained sensitive to UVB, accompanied by DNA binding of the TAp63γ isoform, suggesting that keratinocyte response to UVB is not dependent upon p73 and suggesting a hierarchy of p53 family member responses to DNA damage. Finally, we examined TAp73α interaction with the p53 family inhibitor Mdm2. Mdm2 was in complex with DNA-bound p53 family members in malignant cells, but reconstitution of cells withTAp73α correlated with removal of Mdm2 from the complex, making them more like primary keratinocytes or initiated cells. Like the initiated cells, cells expressing TAp73α were refractory to treatment with the Mdm2-p53 inhibitor Nutlin-3 while cells lacking p73 expression or expressing ΔNp73α were sensitive. Thus, we suggest that p73 may be acting as a molecular shield to keep p53 family member inhibitors, such as ΔNp63α andMdm2, at bay. Further understanding of p53 family interplay in tumor development and DNA damage response could lead to new therapies or optimization of current therapeutic strategies in solid tumors of epithelium, particularly where deregulation or loss of p63 and p73 expression is associated with increased tumor invasiveness, treatment resistance, and poor patient prognosis.