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- ItemSomente MetadadadosLabeling index in pituitary adenomas evaluated by means of MIB-1: is there a prognostic role? A critical review(Maney Publishing, 2010-12-01) Pires de Aguiar, Paulo Henrique; Aires, Rogerio; Laws, Edward R.; Isolan, Gustavo Rassier; Logullo, Angela [UNIFESP]; Patil, Chirag; Katznelson, Laurence; Universidade de São Paulo (USP); Santa Casa de Londrina Hosp; Brigham & Womens Hosp; Univ Fed Rio Grande do Sul; Universidade Federal de São Paulo (UNIFESP); Stanford UnivObjective: the present article presents an overview of the literature, and analyses the methods and the primary questions related to assessment of proliferation index using the Ki-67/MIB-1 labeling index in pituitary adenomas. Although atypical adenomas are characterized by their atypical morphological features by an elevated mitotic index, a Ki-67 (MIB-1) labeling index greater than 3% and extensive nuclear staining for p53, use of the proliferation index (LI) of pituitary adenomas in assessing the degree of tumor aggressiveness is a controversial topic in the literature, and there are disparate results involving many studies.Methods: A review of literature was carried out to correlate the role of Ki-67 LI and its correlation with clinical findings, tumor size, invasiveness, recurrence, adenoma subtype, adenoma doubling time, and pituitary carcinomas is addressed. Results: the prognosis cannot be predicted on the basis of the Ki-67 LI alone. Although there is no direct relation between Ki-67 LI and some of these variables and controversial data were found regarding some topics, our review justify the use of Ki-67 in the analysis of pituitary adenomas as an additional information for clinical decision.Conclusion: Although assessment of proliferative may be helpful in predicting subsequent tumor recurrence or invasiveness, there are many other important and as yet unidentified factors pituitary tumors. It is clear that further research is needed to clarify these molecular mechanisms to predict those with a potentially poor clinical outcome.
- ItemSomente MetadadadosLysosomal exocytosis: An important event during invasion of lamp deficient cells by extracellular amastigotes of Trypanosoma cruzi(Elsevier B.V., 2009-06-26) Gaspar, Emanuelle Baldo [UNIFESP]; Mortara, Renato Arruda [UNIFESP]; Andrade, Luciana O.; Silva, Claudio Vieira da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Uberlândia (UFU); Dept MorfolTrypanosoma cruzi is an obligate intracellular organism in vertebrate hosts. Lysosomes are involved in parasite invasion. LAMP-1 and LAMP-2 are the most abundant glycoproteins of the lysosomal membrane. This Study is the first report on the invasion of T. cruzi extracellular amastigotes (EA) in single LAMP-1 or LAMP-2 knockouts, respectively, or in two independent LAMP-1/2 double-knockout cell lines. When compared to their respective wild type clones, the EA show higher infectivity in LAMP-2 knockouts, but no difference was seen ill LAMP-1 knockout cells. Similarly, EA invasion rate was higher for one of the double knockout clones but not for the other. Higher lysosomal exocytosis Correlated with a higher invasion rate and early lysosomal market acquisition. These findings suggest that lysosomal exocytosis is important to EA cell invasion. Also, phagolysosome maturation in knockout cell lines differed from previous results revealing that EA enter cells by a mechanism other than receptor-mediated phagocytosis. (C) 2009 Elsevier Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Ocorrência e caracterização de eventos de invasão de linhagens celulares cultivadas in vitro por amostras de Escherichia coli enteropatogênica (EPEC) atípica(Universidade Federal de São Paulo (UNIFESP), 2009-03-25) Yamamoto, Denise [UNIFESP]; Gomes, Tania Aparecida Tardelli [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Enteropathogenic Escherichia coli (EPEC) produce attaching/effacing (A/E) lesions on eukaryotic cells mediated by the outer membrane adhesin Intimin. EPEC are subgrouped into typical (tEPEC) and atypical (aEPEC). We have recently demonstrated that aEPEC strain 1551-2 (serotype O non-typable, non-motile) invades HeLa cells by a process dependent on the expression of intimin subtype omicron. In this study, we evaluated whether aEPEC strains expressing other intimin subtypes are also invasive using the quantitative gentamicin protection assay. We also evaluated whether aEPEC invade intestinal differentiated T84 cells. Five of six strains invaded HeLa and T84 cells in a range of 13.3%-20.9% and 5.8%-17.8%, respectively, of the total cellassociated bacteria. The strains studied were significantly more invasive than prototype tEPEC strain E2348/69 (1.4% and 0.5% in HeLa and T84 cells, respectively). aEPEC strain 1551-2 was also tested in differentiated Caco-2 cells, resulting in an invasion index similar to that obtained in T84 cells (7.5%±1.7%). This strain was also significantly more invasive than prototype tEPEC strain E2348/69 (1.8%±0.6%). Invasiveness of T84 cells was confirmed by transmission electron microscopy. We also showed that invasion of HeLa cells by aEPEC 1551-2 depended on actin filaments, but not on microtubules. In addition, infection of non-differentiated monolayers and disruption of tight junctions enhanced its invasion efficiency in T84 cells, suggesting preferential invasion via a non-differentiated surface. In summary, aEPEC strains may invade intestinal cells in vitro with varying efficiencies and independently of the intimin subtype.
- ItemAcesso aberto (Open Access)Respiratory epithelial cells: more than just a physical barrier to fungal infections(MDPI, 2022-05-24) Barros, Bianca Carla Silva Campitelli; Almeida, Bruna Rocha; Barros, Débora Tereza Lucas [UNIFESP]; Toledo, Marcos Sergio [UNIFESP]; Suzuki, Erika [UNIFESP]; http://lattes.cnpq.br/3545915337077337; http://lattes.cnpq.br/1449454874275064; http://lattes.cnpq.br/0670710968392309; http://lattes.cnpq.br/3304493420272173; http://lattes.cnpq.br/3308810633774571The respiratory epithelium is highly complex, and its composition varies along the conducting airways and alveoli. In addition to their primary function in maintaining the respiratory barrier and lung homeostasis for gas exchange, epithelial cells interact with inhaled pathogens, which can manipulate cell signaling pathways, promoting adhesion to these cells or hosting tissue invasion. Moreover, pathogens (or their products) can induce the secretion of chemokines and cytokines by epithelial cells, and in this way, these host cells communicate with the immune system, modulating host defenses and inflammatory outcomes. This review will focus on the response of respiratory epithelial cells to two human fungal pathogens that cause systemic mycoses: Aspergillus and Paracoccidioides. Some of the host epithelial cell receptors and signaling pathways, in addition to fungal adhesins or other molecules that are responsible for fungal adhesion, invasion, or induction of cytokine secretion will be addressed in this review.
- ItemSomente MetadadadosRole of Interleukin 8 in Uterine Natural Killer Cell Regulation of Extravillous Trophoblast Cell Invasion(W B Saunders Co Ltd, 2010-07-01) De Oliveira, L. G. [UNIFESP]; Lash, G. E.; Murray-Dunning, C.; Bulmer, J. N.; Innes, B. A.; Searle, R. F.; Sass, N. [UNIFESP]; Robson, S. C.; Newcastle Univ; Universidade Federal de São Paulo (UNIFESP)Background: Extravillous trophoblast cell (EVT) invasion of maternal tissues is critical for successful pregnancy. Decidual factors, including uterine natural killer (uNK) and T cell derived cytokines play a role in regulating this process. Interleukin (IL) 8 has been implicated as a regulator of EVT invasion.Hypothesis: uNK cell stimulation of EVT invasion is associated with IL-8 levels.Methods: CD8+, total decidual and CD56+ uNK cells (8-10 and 12-14 weeks gestational age) were cultured. IL-8 mRNA and protein levels were determined. IL-8 receptors (IL-8RA and IL-8RB) were localised in first trimester placental bed biopsies. the effect of IL-8 IL-8 neutralising antibodies and CD8+ T cell or uNK cell supernatants IL-8 neutralising antibodies on EVT invasion was assessed. EVT secreted levels of MMP-2, MMP-9, uPA, PAI-1 and PAI-2 were assessed by substrate zymography or Western Blot.Results: High levels of IL-8 protein and mRNA were detected in all samples. IL-8RA and IL-8RB were expressed by EVT. Exogenous IL-8 stimulated EVT invasion in a paracrine manner. uNK cell supernatants, but not CD8+ cell supernatants, stimulated EVT invasion. IL-8 neutralising antibody partially abrogated this uNK cell stimulated invasion. IL-8 increased levels of secreted MMP-2, but did not alter any of the other proteases or protease inhibitors tested.Conclusion: uNK cell stimulation of EVT invasion is partially mediated by IL-8. Unstimulated CD8+ T cells do not alter EVT invasion despite secreting similar levels of IL-8 as uNK cells. (C) 2010 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosUpdate on Thin Melanoma: Outcome of an International Workshop(Lippincott Williams & Wilkins, 2016) Mihic-Probst, Daniela; Shea, Chris; Duncan, Lyn; de la Fouchardiere, Arnaud; Landman, Gilles [UNIFESP]; Landsberg, Jennifer; ven den Oord, Joost; Lowe, Lori; Cook, Martin G.; Yun, Sook Jung; Clarke, Loren; Messina, Jane; Elder, David E.; Barnhill, Raymond L.The following communication summarizes the proceedings of a 1-day Workshop of the International Melanoma Pathology Study Group, which was devoted to thin melanoma. The definitions and histologic criteria for thin melanoma were reviewed. The principal differential diagnostic problems mentioned included the distinction of thin melanoma from nevi, especially from nevi of special site, irritated nevi, inflamed and regressing nevi, and dysplastic nevi. Histologic criteria for this analysis were discussed and the importance of clinico-pathologic correlation, especially in acral sites, was emphasized. Criteria for the minimal definition of invasion were also discussed. In addition, a new technique of m-RNA expression profiling with 14 genes was presented and facilitated the distinction of thin melanomas from nevus in histologically obvious cases. However, for particular nevi, it was not obvious why the results indicated a malignant lesion. Despite many molecular and other ancillary investigations, Breslow thickness remains the most important prognostic factor in thin melanoma. The prognostic significance of radial (horizontal) and vertical growth phases, Clark level, regression, and mitotic rate were also discussed. Because of the increasing frequency of thin melanomas, there is a great need to develop more refined predictors of thin melanomas with worse clinical outcome.
- ItemSomente MetadadadosUpdate on Thin Melanoma: Outcome of an International Workshop(Lippincott Williams & Wilkins, 2016) Mihic-Probst, Daniela; Shea, Chris; Duncan, Lyn; de la Fouchardiere, Arnaud; Landman, Gilles [UNIFESP]; Landsberg, Jennifer; ven den Oord, Joost; Lowe, Lori; Cook, Martin G.; Yun, Sook Jung; Clarke, Loren; Messina, Jane; Elder, David E.; Barnhill, Raymond L.; Universidade Federal de São Paulo (UNIFESP)The following communication summarizes the proceedings of a 1-day Workshop of the International Melanoma Pathology Study Group, which was devoted to thin melanoma. The definitions and histologic criteria for thin melanoma were reviewed. The principal differential diagnostic problems mentioned included the distinction of thin melanoma from nevi, especially from nevi of special site, irritated nevi, inflamed and regressing nevi, and dysplastic nevi. Histologic criteria for this analysis were discussed and the importance of clinico-pathologic correlation, especially in acral sites, was emphasized. Criteria for the minimal definition of invasion were also discussed. In addition, a new technique of m-RNA expression profiling with 14 genes was presented and facilitated the distinction of thin melanomas from nevus in histologically obvious cases. However, for particular nevi, it was not obvious why the results indicated a malignant lesion. Despite many molecular and other ancillary investigations, Breslow thickness remains the most important prognostic factor in thin melanoma. The prognostic significance of radial (horizontal) and vertical growth phases, Clark level, regression, and mitotic rate were also discussed. Because of the increasing frequency of thin melanomas, there is a great need to develop more refined predictors of thin melanomas with worse clinical outcome.