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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
41

Genes, Proteins and Metabolites in the Interaction of Strawberry and Fungal Pathogen

Nagpala, Ellaine Grace <1985> January 1900 (has links)
Colletrotrichum acutatum and Botrytis cinerea are among the major fungal pathogens of Fragaria spp. Both pathogens could infect strawberry fruits during the fruit’s early developing stage and remain quiescent until ripening. In strawberry, a fruit ontogenic resistance to pathogen infection was described and correlated with fungal quiescence during the unripe stages of the fruit. Due to the period of fungal quiescence, the management of anthracnose and gray mould diseases becomes more complex as symptoms only manifest in ripe fruits. To identify the underlying component in the ontogenic resistance of strawberry fruits, transcriptomic and metabolomic approaches were used. White and red fruits of strawberry were artificially inoculated with C. acutatum and B. cinerea. Transcriptome profile of B. cinerea infected fruits exhibited a general up-regulation of defense-related genes in white fruits after 24 h of infection. Meanwhile, accumulation of phenolic compounds such as proanthocyanidins, catechins and the ellagitannin casuarictin was also observed in white fruits after 48 h of interacting with C. acutatum and B. cinerea. The acquisition of these findings could provide a benchmark to further investigate the interaction of strawberry against pathogens with latent infection. Hence, a strawberry transformation was performed to study the mechanism of a gene encoding for a mannose-binding lectin protein which was previously identified to be correlated with the resistance of white strawberry fruits to C. acutatum. The regeneration system utilized in the transformation is also discussed.
42

Caracterización de los pacientes hospitalizados por primera vez por exacerbación de la Enfermedad Pulmonar Obstructiva Crónica

Balcells Vilarnau, Eva, 1967- 20 January 2016 (has links)
Introducción: Hay poca información sobre la primera hospitalización por exacerbación de la Enfermedad Pulmonar Obstructiva Crónica (EPOC), a pesar de ser un evento importante en la historia natural de esta enfermedad. El objetivo de esta tesis fue estudiar el perfil clínico de los pacientes hospitalizados por primera vez por una exacerbación de la EPOC, con especial atención a la comorbilidad psicológica y su relación con la calidad relacionada con la salud de la vida (CVRS), y también investigar el grado y las características del infradiagnóstico de la EPOC, en este momento. Métodos: El estudio incluyó una amplia muestra de pacientes hospitalizados por primera vez por exacerbación de la EPOC (2004-2006). Un total de 342 pacientes fueron ampliamente caracterizados con variables sociodemográficas, clínicas y funcionales. Se evaluó la asociación entre ansiedad, depresión o ambos, y la CVRS, después de ajustar por posibles factores de confusión y se identificaron factores modificadores del efecto de esta asociación. Se investigaron las características y el pronóstico (rehospitalizaciones y mortalidad) de los pacientes con EPOC no diagnosticada. Resultados: (1) los pacientes con EPOC tenían un amplio espectro de gravedad, con una proporción importante de pacientes con EPOC leve a moderada, y de fumadores activos; más de un tercio de pacientes tenían EPOC no diagnosticada; (2) los pacientes con EPOC no diagnosticada tenían una enfermedad menos grave y menor riesgo de rehospitalización en comparación con los pacientes con EPOC conocida; (3) este estudio mostró una asociación significativa entre ansiedad, depresión, o ambas y deterioro de la CVRS; los factores clínicamente relevantes que afectaron a la magnitud de esta asociación fueron la situación laboral, la gravedad de la EPOC, y la presencia de comorbilidades. Conclusiones: La presente tesis es el primer estudio que describe las características de una muestra amplia y representativa de pacientes hospitalizados por primera vez por exacerbación de la EPOC; la tesis enfatiza que esta primera hospitalización abre una ventana de oportunidad para el diagnóstico de la EPOC y el inicio de un tratamiento adecuado. / Introduction: There is little information about the first hospitalisation for an exacerbation of Chronic Obstructive Pulmonary Disease (COPD), although it is an important event in the natural history of this disease. The aim of this thesis was to study the clinical profile of patients hospitalised for the first time for an exacerbation of COPD, with special attention to the psychological comorbidity and their relationship to health related quality of life (HRQoL), and also to investigate the extent and characteristics of underdiagnosis of COPD, at this time. Methods: The study included a large sample of patients hospitalised for the first time for an exacerbation of COPD (2004-2006). A total of 342 patients were extensively characterised using sociodemographic, clinical and functional variables. We evaluated the association between anxiety, depression or both, and HRQoL, after adjusting for potential confounders and identified effect modifiers of this association. We also investigated the characteristics and prognosis (re-hospitalisations and mortality) of patients with undiagnosed COPD. Results: (1) COPD patients had a wide range of severity, with a large proportion of patients with mild-to-moderate COPD, and current smokers; more than one third of patients had undiagnosed COPD; (2) undiagnosed COPD patients had less severe disease and lower risk of re-hospitalisation when compared with patients with known COPD; (3) this study showed a significant association between anxiety, depression, or both conditions and impaired HRQoL; clinically relevant factors modifying the magnitude of this association included work status, COPD severity, and the presence of comorbidities. Conclusions: The present thesis is the first study that describes the characteristics of a large and representative sample of patients hospitalised for the first time for an exacerbation of COPD. The thesis emphasizes that this first hospitalisation opens a window of opportunity for the COPD diagnosis and the initiation of appropriate therapy.
43

Contribution of vascular resident mesenchymal stromal cells to abdominal aortic aneurysm pathogenesis: increased MMP-9 expression and ineffective immunomodulation

Ciavarella, Carmen <1986> 12 May 2015 (has links)
Background. Ageing and inflammation are critical for the occurrence of aortic diseases. Extensive inflammatory infiltrate and excessive ECM proteloysis, mediated by MMPs, are typical features of abdominal aortic aneurysm (AAA). Mesenchymal Stromal Cells (MSCs) have been detected within the vascular wall and represent attractive candidates for regenerative medicine, in virtue of mesodermal lineage differentiation and immunomodulatory activity. Meanwhile, many works have underlined an impaired MSC behaviour under pathological conditions. This study was aimed to define a potential role of vascular MSCs to AAA development. Methods. Aortic tissues were collected from AAA patients and healthy donors. Our analysis was organized on three levels: 1) histology of AAA wall; 2) detection of MSCs and evaluation of MMP-9 expression on AAA tissue; 3) MSC isolation from AAA wall and characterization for mesenchymal/stemness markers, MMP-2, MMP-9, TIMP-1, TIMP-2 and EMMPRIN. AAA-MSCs were tested for immunomodulation, when cultured together with activated peripheral blood mononuclear cells (PBMCs). In addition, a co-colture of both healthy and AAA MSCs was assessed and afterwards MMP-2/9 mRNA levels were analyzed. Results. AAA-MSCs showed basic mesenchymal properties: fibroblastic shape, MSC antigens, stemness genes. MMP-9 mRNA, protein and enzymatic activity were significantly increased in AAA-MSCs. Moreover, AAA-MSCs displayed a weak immunosuppressive activity, as shown by PBMC ongoing along cell cycle. MMP-9 was shown to be modulated at the transcriptional level through the direct contact as well as the paracrine action of healthy MSCs. Discussion. Vascular injury did not affect the MSC basic phenotype, but altered their function, a increased MMP-9 expression and ineffective immunmodulation. These data suggest that vascular MSCs can contribute to aortic disease. In this view, the study of key processes to restore MSC immunomodulation could be relevant to find a pharmacological approach for monitoring the aneurysm progression.
44

Fusariosi della spiga dell'orzo: eziologia e caratterizzazione di fusaria produttori di micotossine / Fusarium head blight on barley: etiology and characterization of Fusaria producers of mycotoxins

Giannini, Marta <1982> January 1900 (has links)
FHB dell’orzo è una malattia dall’eziologia complessa causata da specie fungine tossigene appartenenti al genere Fusarium in grado di compromettere interi raccolti. La predominanza di una specie di Fusarium rispetto ad un’altra dipende principalmente dal clima. Con i cambiamenti climatici in corso si sta assistendo ad una modificazione delle popolazioni fungine e per questo risulta fondamentale monitorare le specie fungine presenti in una determinata coltura, onde prevenire micotossicosi per l’uomo ed animali. Da analisi micologiche su granella di orzo proveniente da varie regioni italiane F. graminearum, F. poae e F. tricinctum sono risultate le specie più presenti. Prove in ambiente controllato hanno consentito di mettere a punto una scala fitopatometrica per la valutazione di FHB. Tale scala risulta pratica e facilmente applicabile ed è stata utilizzata per le prove di campo. In queste prove oltre a FHB sono stati valutati altri parametri quali produzione e contaminazione da micotossine. Il contenuto di micotossina Deossinivalenolo è correlata alla frequenza di F. graminearum su granella. I dati produttivi delle tesi inoculate non sono apparsi significativamente distinti dalle tesi non inoculate, facendo dedurre che granella contaminata da micotossina possa facilmente ritrovarsi nelle derrate alimentari, in quanto le cariossidi infette, solo lievemente più leggere di quelle sane. vengono ugualmente raccolte e commercializzate con serie conseguenze per l’industria mangimistica e alimentare. Con il presente lavoro si è dimostrato per la prima volta che per effetto della colonizzazione di culmi di piante di orzo da parte di tre specie Fusarium, responsabili sia della fusariosi del piede che della spiga, la micotossina DON può traslocare dalla base delle piante fino alla spiga, mentre la presenza dei funghi è rilevata da alte concentrazioni fino al secondo nodo. Da questo emerge che la presenza di Fusarium a livello basale contribuisce alla contaminazione della granella, oltre a quella dovuta ad FHB. / Fusarium head blight (FHB) is a barley disease with a complex etiology which is caused by different toxigenic Fusarium species able to compromise the whole crop yield. Climatic conditions establish the predominance of one Fusarium species respect to the others. With the climate change in progress we are attending to a modification of fungal populations that evidence the importance of monitoring the presence of fungal species in the crop, to prevent mycotoxicosis, dangerous for humans and animals. Mycological analysis in barley kernel from different Italian regions has shown that F. graminearum, F. poae and F. tricinctum are the main species. A phytopathometric scale to evaluate FHB was set up in controlled conditions. That scale, practical and easy to use, was used in field trials, where FHB, yield and mycotoxin contamination were evaluated. Mycotoxin DON content was correlated to F. graminearum frequency. Yield data of inoculated plots were not significant respect to the not inoculated ones, this implies that it is easy to find kernel contaminated by mycotoxins in food and feed, because infected grains are slightly lighter than those not infected and they are harvested and commercialized as well with serious consequences to public safety. For the first time on barley, with this study it was shown that after culm colonization of the plant by three toxigenic Fusarium spp., able to cause both FHB and FCR, DON mycotoxin can be transferred from the bottom to the head, whereas the presence of the fungi was with high level until the second node. This means that presence of Fusarium at base level contributes to the kernel contamination, additionally to FHB.
45

From Drosophila to Humans: MYC-Mediated Clone Competition as an Evolutionary Trait of Tumor Progression

Di Giacomo, Simone <1984> January 1900 (has links)
Cell competition describes the result of a mechanism of fitness comparison undertaken by cells inhabiting the same tissue, that leads to the elimination of the weakest cells and, in the physiology, to the formation of a homogeneous organ. Over the years, many molecules have been identified that are involved in cell competition and among them MYC oncoprotein: from Drosophila to mammals, cell populations characterised by higher expression of MYC induce apoptotic death of the neighbours, allowing the fittest to acquire an advantage in space occupancy. My work defined the presence of markers of MYC-mediated cell competition in primary and secondary human carcinomas and demonstrated through experiments in human cancer cell lines that MYC modulation is per se sufficient to induce competitive behaviours in both genetically distant and identical cells. Noteworthy, MYC under-regulation in the fittest cell line is sufficient to undermine its competitive status, suggesting a role for MYC-mediated cell competition in the selective growth of tumour clones and, as a consequence, in cancer evolution. In addition, I was able to demonstrate a functional cooperation between MYC and p53 in this phenomenon. The data obtained in the Drosophila model, where MYC over-expressing and MYC knock-down clones have been induced within a growing tumour, suggest that MYC-mediated cell competition is normally at work in these malignant cells, and it shapes cancer evolution through the elimination of the less fit cells (with lower levels of MYC) and the expansion of the most performant ones (with higher levels of MYC), demonstrating an evolutionary role played in defining the composition and the size of the final mass.
46

Análise da evolução e características de um Serviço de Anatomia Patológica Bucal durante o período de 37 anos. Checagem, revisão e atualização diagnóstica. / ANALYSIS OF THE EVOLUTION AND FEATURES OF THE ANATOMY ORAL PATHOLOGY SERVICE FOR THIRTY SEVEN YEARS CHECKING, REVIEW AND DIAGNOSTIC ACTUALIZATION

Velloso, Tania Regina Grao 26 November 2001 (has links)
Análise dos arquivos do Serviço de Anatomia Patológica da Faculdade de Odontologia de Bauru, Universidade de São Paulo, desde 1963 a 2000; para estudar sua evolução e características, promovendose uma revisão e atualização dos seus arquivos e métodos. Observou-se um aumento crescente e significativo da demanda dos serviços prestados, bem como um aperfeiçoamento destes. Realizou-se uma revisão de laudos, blocos e lâminas, avaliando-se a nomenclatura das lesões se condizente com a atual; o reconhecimento de entidades clínicas novas e os erros de diagnóstico. Discutiu-se as prováveis razões para as diferenças encontradas e concluiu-se da necessidade de atualização constante no trabalho em grupo, bem como do estímulo constante à análise crítica dos conceitos e critérios diagnósticos em todos os momentos da prática da patologia bucal como especialidade odontológica. / Analysis of archives of the Anatomy Pathology Service of Bauru Dental School, São Paulo University, since 1963-2000 to study the evolution and characteristics, promoting a re-examination and actualization of their archives and methods. It was observed a significative increment of demand in the lending Services, and an improvement of these. It was made a revision of the report copies, blocks histologic and slides, evaluating the nomenclature of the lesions according to the nowadays; identification of new clinical entities and diagnostic errors. It was discuss the provable reasons of the found differences and conclude the necessity of a continue actualization in the work of group, and the constant incentivation to critical analysis of concepts and diagnostic criteria on every moment of practice in the oral pathology as a dental speciality.
47

Hipercementose:estudo macroscópico, estereomicroscópico, radiográfico e à microscopia eletrônica de varredura / HYPERCEMENTOSIS: MACROSCOPIC, STEREOMICROSCOPY, RADIOGRAPHIC AND SCANNING ELECTRON MICROSCOPIC STUDY

Pinheiro, Bethânia Camargo 27 September 2005 (has links)
A hipercementose é caracterizada pela formação excessiva de cemento além do limite necessário para cumprir suas funções normais resultando em espessamento anormal com alteração da forma macroscópica da raiz. Inicialmente, procedeu-se à realização do exame macroscópico e estereomicroscópico e radiográfico de 576 dentes permanentes humanos com hipercementose em espécimes pertencentes ao Departamento de Patologia da Faculdade de Odontologia de Bauru - Universidade de São Paulo. Os critérios morfológicos analisados radiograficamente foram o término do canal principal, canais secundários, acessórios, delta apical, constrição apical e observação da hipercementose e sua junção com a dentina. Selecionaram-se 28 dentes e analisaram-se seus ápices radiculares à microscopia eletrônica de varredura. Verificou-se que a progressão da hipercementose em forma de clava está diretamente associada ao fechamento gradativo das foraminas e forames apicais; a forma focal de hipercementose apresenta foraminas em sua superfície, mesmo quando lateralmente localizadas nas raízes dentárias; a hipercementose em forma de boca de manga de camisa acomete principalmente raízes residuais. Sendo assim, o clínico, nas várias especialidades, durante a escolha da técnica terapêutica, deve considerar as variações anatômicas interna e externa dos dentes portadores de hipercementose, visto que radiograficamente não é possível, com precisão e segurança, determinar essas variações e suas implicações / Hypercementosis is characterized by the excessive formation of the cementum beyond its physiological limits resulting in abnormal thickening with alteration of the macroscopic root appearance. This study analyzed 576 permanent human teeth with hypercementosis though macroscopic and stereomicroscopy means. The teeth were radiographed and some morphologic aspects were observed such as: the end of the main root canal, secondary and accessories canals, apical delta, apical constriction, hypercementosis manifestation and its junction with the dentin. Out of these specimens 28 were selected and analyzed its root apexes through scanning electron microscopy. It was verified that the progression of hypercementosis in club form is directly associated to foraminas and apical foramen obstruction; the focal form of hypercementosis presents foraminas in its surface, even they are sidelong located in its dental roots; the hypercementosis in "shirt mouth sleeve form" attacks mainly residual roots. Based in these findings it must be considered during dental practice a proper therapeutic technique and also the teeth's anatomical variations due to hypercementosis, since it is not possible with accuracy and safety to determine radiographically, the anatomical modifications and its implications
48

Neurofibroma isolado na região de cabeça e pescoço: considerações clínicas e histopatológicas

Marocchio, Luciana Sassa 04 June 2004 (has links)
Os neurofibromas ocorrem na região de cabeça e pescoço como lesões, isoladas ou múltiplas, freqüentemente associadas às síndromes das neurofibromatoses. O objetivo deste trabalho consistiu em avaliar os aspectos clínicos e microscópicos dos neurofibromas, particularmente a variante plexiforme, na pele da região de cabeça e pescoço e na mucosa bucal e discutir a patogênese e as condutas clínicas dessas lesões, quando de sua ocorrência isolada não associada a neurofibromatose-1 (NF-1). Nossa amostra foi selecionada a partir dos neurofibromas na região de cabeça e pescoço diagnosticados no período entre 1973 a 2003 pelos Serviços de Anatomia Patológica do Departamento de Estomatologia – Área de Patologia da Faculdade de Odontologia de Bauru/USP e do Instituto de Pesquisa Lauro de Souza Lima. Os dados demográficos e a história clínica das lesões foram obtidos pela análise do prontuário do paciente. Um total de 66 neurofibromas foram avaliados microscopicamente em coloração de rotina sendo registradas algumas características como a morfologia celular, a organização histológica da lesão, a presença e distribuição do infiltrado inflamatório, da vascularização sanguínea, bem como, a presença de mastócitos e corpúsculos táteis-like. Nossos resultados demonstraram uma maior freqüência de lesões cutâneas (81,8%) se comparadas à mucosa bucal (18,2%), manifestando-se principalmente em indivíduos do gênero feminino e na faixa etária acima de 40 anos. Uma maior ocorrência de lesões únicas, isoladas (51,2%) foi observada na pele e mucosa bucal, sendo as lesões múltiplas (37,2%) quase sempre associadas a NF-1 clinicamente comprovada em 12 pacientes (28,0%). Na boca, as lesões foram encontradas em 27,9% dos casos, sendo o local mais afetado a mucosa gengival e rebordo alveolar. Dos dois neurofibromas plexiformes observados, ambos na mucosa bucal, apenas um estava associado a NF-1. Microscopicamente, a variante difusa foi predominantemente observada sobre a plexiforme sendo encontrados inclusive corpúsculos táteis-like. Nossos resultados demonstraram que os neurofibromas isolados, particularmente a variante plexiforme, embora observados comumente na pele, podem ocorrer também na mucosa bucal sem associação com a NF-1. O comportamento clínico benigno do neurofibroma isolado na região de cabeça e pescoço e a ausência da associação com a NF-1 sugere uma natureza hamartomatosa para estas lesões, cuja patogênese precisa ser melhor investigada. / The neurofibroma occurs, in the head and neck region, as isolated or multiple lesion, frequently associated with neurofibromatosis. The aim of this study was to analyse the clinical and histopathological features of neurofibromas, particularly the plexiform type, located in the skin and in oral mucosa, and to discuss their pathogenesis as well as clinical management of isolated, sporadic lesion, unassociated with neurofibromatosis-1 (NF-1). Sixty six cases of neurofibromas from the files of Stomatology Department - Area of Pathology of the Bauru School of Dentistry and Lauro de Souza Lima Research Institute, were retrospectively reviewed. Clinical data, therapy and follow-up information were obtained from the medical records. Histopathological analysis of the neurofibromas was performed on paraffin sections routinely stained with hematoxilin-eosin. Some features such as cellular morphology, tissue organization, distribution of inflammatory infiltrate, presence of mast cells, and tactile-like bodies were investigated. The results showed a high frequency of cutaneous lesions (81,8%), as compared with those of the oral mucosa (18,2%), occurring mainly in females and patients older than 40 years. Isolated neurofibromas were found in 51.2% of patients and multiple lesions (37,2%) were often associated with the NF-1 (28.0%). In addition 27.9% of patients presented neurofibromas in the oral mucosa, being the gingival mucosa and alveolar ridge the most commonly affected sites. Only two neurofibromas (3,0%), both arising in oral mucosa, were found and one of them, was associated with the von Recklinghausen neurofibromatosis. Microscopically, diffused neurofibromas occur more frequently than the plexiform variant, and tactile-like bodies seen in both types. These results demonstrated that neurofibromas, particularly, the plexiform type, can occur in the skin and oral mucosa as a isolated lesion, not associated with the NF-1. The benign clinical behavior of the isolated, sporadic neurofibroma unassociated with neurofibromatosis, in the head and neck region, suggests a hyperplastic hamartomatous nature, whose pathogenesis needs to be further investigated
49

Evaluation of immuno expression of LGR5 and LGR6 in the stem cells in primary gastric cancer, lymph node metastases and histologically normal gastric mucosa / AvaliaÃÃo da imunoexpressÃo de LGR5 e LGR6 em cÃlulas-tronco no cÃncer gÃstrico primÃrio, metÃstases linfonodais e mucosa gÃstrica histologicamente normal

Adriana Estela Flores Valiente 16 February 2017 (has links)
coordenadoria de aperfeiÃoamento de pessoal de ensino superior / O cÃncer gÃstrico à a quarta neoplasia mais comum em todo o mundo e a segunda causa de mortalidade por cÃncer. Apesar do tratamento com cirurgia e quimioterapia, a sobrevida global em cinco anos de pacientes com cÃncer gÃstrico permanece baixa, uma possÃvel explicaÃÃo para menor eficÃcia da terapia à a presenÃa de cÃlulas tronco cancerosas. VÃrios marcadores, incluindo LGR5 e LGR6, tÃm sido relatados como marcadores de cÃlulas- tronco, normais e cancerosas. LGR5 e LGR6 sÃo proteÃnas transmembranas, do grupo da proteÃna G, ricas em resÃduos leucina, que participam nas vias de sinalizaÃÃo das cÃlulas e ativam fatores de transcriÃÃo relacionados com a formaÃÃo de tumores. O objetivo deste trabalho foi avaliar a imunoexpressÃo de LGR5 e LGR6 como possÃveis marcadores de cÃlulas-tronco no cÃncer gÃstrico primÃrio, metÃstases linfonodais e mucosa gÃstrica histologicamente normal, atravÃs das tÃcnicas de microarranjo tissular (tissue microarray) e imuno-histoquÃmica. O estudo, de carÃter transversal e observacional realizou-se a partir de oitenta e oito (88) peÃas de gastrectomias devido a carcinomas gÃstricos, realizadas no Hospital UniversitÃrio Walter CantÃdio, que fazem parte dos Arquivos do ServiÃo de Patologia e Medicina Legal da Universidade Federal do CearÃ. As relaÃÃes entre a expressÃo diferencial de LGR5 e LGR6 e caracterÃsticas clinico-patolÃgicas foram avaliadas pelo teste do qui-quadrado ou teste exato de Fisher. Um valor de p < 0,05 foi considerado estatisticamente significativo. Foramconsiderados positivos (a partir de relatos prÃvios) casos que apresentaram uma ou mais cÃlulas com imunomarcaÃÃo citoplasmÃtica ou membranar. LGR5 mostrou-se, neste estudo, ser um potencial biomarcador, mais caracterÃstico de cÃlulas-tronco tumorais e nÃo tumorais, do que LGR6. Ambos sÃo expressos em tecido tumoral e nÃo tumoral, com predomÃnio em mucosa histologicamente normal, em terÃo basal da espessura epitelial. LGR5 positivo predominou no histotipo difuso e LGR6 no tipo intestinal de carcinomas gÃstricos. Nos casos positivos dos dois biomarcadores, cÃlulas marcadas sÃo pouco frequentes ou raras, no total de cÃlulas da massa tumoral e da mucosa gÃstrica normal. LGR6 esteve presente no tumor gÃstrico primÃrio em nÃmero de cÃlulas muito superior ao encontrado nas respectivas metÃstases linfonodais, diferenÃa nÃo observada em relaÃÃo a LGR5. Com exceÃÃo da relaÃÃo de cada biomarcador com um histotipo especÃfico, jà citada, nÃo houve relaÃÃo entre as demais variÃveis clinico-patolÃgicas e a expressÃo de LGR5 e LGR6. / Gastric cancer is the fourth most common neoplasm in the world and the second leading cause of cancer mortality. Despite the treatment with surgery and chemotherapy, the overall five-year survival of patients with gastric cancer remains low, a possible explanation for less effective therapy is the presence of cancer stem cells. Several markers, including LGR5 and LGR6, have been reported as markers of normal and cancerous stem cells. LGR5 and LGR6 are transmembrane proteins of the G protein group, rich in leucine residues, that participate in cell signaling pathways and activate transcription factors related to tumor formation. The objective of this work was to evaluate the immunoexpression of LGR5 and LGR6 as possible markers of stem cells in primary gastric cancer, lymph node metastases and histologically normal gastric mucosa through tissue microarray and immunohistochemistry techniques. The cross-sectional and observational study was carried out from eighty-eight (88) pieces of gastrectomies due to gastric carcinomas performed at the Walter CantÃdio University Hospital, which are part of the Archives of the Service of Pathology and Legal Medicine of the Federal University Of CearÃ. The relationships between LGR5 and LGR6 differential expression and clinical-pathological characteristics were assessed by the chi-square test or Fisher's exact test. A value of p <0.05 was considered statistically significant. Positive (from previous reports) were considered cases that presented one or more cells with cytoplasmic or membrane immunostaining. LGR5 was shown to be a potential biomarker, more characteristic of tumor and non-tumor stem cells, than LGR6 in this study. Both are expressed in tumoral and non-tumoral tissue, predominantly in histologically normal mucosa, in a basal third of epithelial thickness. Positive LGR5 predominated in the diffuse histotype and LGR6 in the intestinal type of gastric carcinomas. In the positive cases of the two biomarkers, marked cells are infrequent or rare, in the total cells of the tumor mass and the normal gastric mucosa.
50

L lysine in intestinal and urothelial epithelial carcinogenesis of the augmentation of bladderand ureterosigmoidostomy in female rats / L lisina na carcinogÃnese de epitÃlios intestinal e urotelial nas ampliaÃÃes vesicais e ureterosigmoidostomias em ratas

Alessandra Marques dos Santos 15 February 2016 (has links)
The present study evaluated the effects of L lysine in intestinal and urothelial epithelia in augmentation of bladder and ureterosigmoidostomy in rats.A total of 66 female rats 9 weeks old were split divided in to 9 experimental groups. The animals from groups: I , II and III were subjected to bladder augmentation with colon segment (AV) and treated with L lysine, celecoxib and H2O, respectively. The groups: IV, V and VI were subjected to ureterosigmoidostomy (US) treated with L lysine, celecoxib and H2O in that order. Groups: VII, VIII and IX (non- operated controls) received L lysine, celecoxib and H2O respectively. The dosage of L lysine was 150mg/ kg/ body weight and the celecoxib was 20mg/kg/ body weight. The effects of L lysine on the colon epithelium of rats subjected to US was initially evaluated by analysis Aberrant Cripts Foci (ACF) at stereostopic microscopy, after fixation with formaldehyde and staining with methylene blue. Followed by histopathological study of ureteral epithelium, colonic and bladder in all groups, stained with hematoxylin and eosin and PAS Alcian Blue. Rare ACF were found in all mice with US and compared between groups. There was no statistically significant difference between groupsOn histopathology with hematoxylin and eosin, mild to moderate hyperplasia was observed in intestinal and urothelial epithelia at the site of anastomosis in all animals submitted to cystoplasty (Groups I and III), but transitional metaplasia of the intestinal glandular epithelium was more accentuated in Group I (p=0.045). There were no inflammatory cells, dysplasia or atypia. In epithelia of the left ureter and colon of mice with US a mild inflammatory infiltrate composed of lymphocytes, moderate to severe intensity, had urothelial hyperplasia of moderate to severe intensity in all the ureters, three polyps in different ureters and inflammatory polyps in colon . There were no dysplasia or atypia. The staining with Alcian Blue, noticed an important decrease of goblet cells and mucin in colon in all operated rats. In the histopathology there is similarity in the quality and quantity of injuries. Thus, we conclude that L-Lysine did not influence the carcinogenesis of intestinal epithelia, and urothelial of rats submitted to US and AV with colon segment, at times, doses and methods evaluated.However, the L-lysine stressed the "urothelial metaplasia" in intestinal segment bladder and ureter transitional hyperplasia in rats subjected to ureterosigmoidostomies. / Avalia os efeitos da L lisina na carcinogÃnese de epitÃlios intestinal e urotelial nasampliaÃÃes vesicais e ureterossigmoidostomias em ratas. O total de 66 ratas com nove semanas de idade foi dividido em nove grupos. Os animais dos grupos I, II e III foram submetidas a ampliaÃÃo vesical com segmento de colo (AV) e tratados com L lisina, celecoxibe e H2O, respectivamente. Os do grupo IV, V e VI foram submetidos a ureterossigmoidostomia (US) e tratados com L lisina, celecoxibe e H2O nesta ordem. Os grupos VII, VIII e IX (controles nÃo operados), receberam L lisina, celecoxibe e H2O, respectivamente. A dose de L lisina foi de 150 mg/kg/peso e o celecoxibe foi de 20 mg/kg/peso. Os efeitos da L lisina no epitÃlio do colo de ratos submetidos a US foi inicialmente avaliado pela anÃlise de FCA (focos de criptas aberrantes) a microscopia estereoscÃpica apÃs fixaÃÃo com formol e coloraÃÃo pelo azul de metileno. Seguiu-se estudo histopatolÃgico dos epitÃlios ureterais, cÃlicos e vesicais em todos os grupos, corados pela hematoxilina e eosina e PAS Alcian Blue. Foram encontrados raros FCA, em todas as ratas com US e na comparaÃÃo entre os grupos. NÃo ocorreu diferenÃa estatisticamente significantes entre os grupos. No estudo histopatolÃgico, com hematoxilina e eosina de epitÃlios cÃlicos e vesicais de animais com AV, foram observados hiperplasia urotelial leve a moderada em todos os animais submetidos a cistoplastia, em regiÃo de anastomoses colovesical e maior nÃmero de animais apresentaram âmetaplasia transicionalâ em epitÃlio glandular intestinal no grupo I (p= 0,045). NÃo havia cÃlulas inflamatÃrias, displasias ou atipias. Nos epitÃlios de ureter esquerdo e colo das ratas com US, em meio a infiltrado inflamatÃrio constituÃdo por linfÃcitos, de moderada a acentuada intensidade, havia hiperplasia urotelial de moderada a acentuada, trÃs polipos em distintos ureteres e um polipo inflamatÃrio em colo. NÃo havia displasias ou atipias. Quanto à coloraÃÃo pelo Alcian Blue, notou-se importante diminuiÃÃo de cÃlulas caliciformes e de mucinas em colo, em todas as ratas operadas. Desta forma, conclui-se que a L lisina nÃo influenciou na carcinogÃnese do epitÃlio intestinal das ureterossigmoidostomias em ratas nos tempos e doses, bem como pelo mÃtodo de avaliaÃÃo de criptas aberrantes. A L lisina acentuou a âmetaplasia urotelialâ em segmento intestinal de ampliaÃÃes vesicais e a hiperplasia transicional no ureter das ratas submetidas a ureterossigmoidostomias.

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