Navegando por Palavras-chave "Células mielóides supressoras"
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- ItemAcesso aberto (Open Access)Avaliação da evolução do tumor pulmonar experimental induzido por uretana em camundongos sedentários Santos(Universidade Federal de São Paulo (UNIFESP), 2013-02-18) Tomás, Caio Marins [UNIFESP]; Bueno, Valquiria [UNIFESP]; http://lattes.cnpq.br/1984756436508114; http://lattes.cnpq.br/6759338394343139; Universidade Federal de São Paulo (UNIFESP)Tumores “escapam” da função antitumoral pela secreção de fatores que inibem o sistema imune. Um efeito dos fatores secretados pelo tumor é o aumento das células mieloides supressoras (MDSC) que suprimem a resposta imune favorecendo assim o desenvolvimento tumoral. Buscando compreender a ação do câncer sobre as células do sistema imune, nosso grupo avaliou as mudanças quantitativas das células da resposta imune (linfócitos e mielóides supressoras) em camundongos BALB/c sedentários com câncer de pulmão induzido por um carcinógeno químico. Os camundongos foram induzidos ao câncer de pulmão pela administração de Uretana (120 dias para formação de nódulos pulmonares) e após o desenvolvimento tumoral o baço, timo, medula óssea, e o sangue foram coletados e avaliados por citometria de fluxo (T CD4, T CD8, além das MDSC - CD11b+Gr-1+). Os pulmões foram removidos para análise histológica (número e área dos nódulos tumorais). Nosso intuito foi comparar camundongos sedentários saudáveis e sedentários com câncer de pulmão induzido por Uretana quanto á quantidade de linfócitos e células mielóides supressoras em alguns órgãos linfóides (timo, medula óssea, baço) e sangue. Também avaliamos, se o possível aumento de células mielóides supressoras esteve relacionado ao aumento da área e número de nódulos pulmonares. Os resultados contribuirão para o melhor entendimento do câncer de pulmão e sua relação com a expressão de MDSC em camundongos BALB/c sedentários. Na sequência é meu interesse propor modalidades de exercício físico que possam agir sobre as células do sistema imune como terapia de restrição do desenvolvimento tumoral.
- ItemAcesso aberto (Open Access)Avaliação de células mielóides supressoras e linfócitos T em indivíduos longevos(Universidade Federal de São Paulo (UNIFESP), 2018-02-22) Alves, Amanda Soares [UNIFESP]; Bueno, Valquiria [UNIFESP]; http://lattes.cnpq.br/1984756436508114; http://lattes.cnpq.br/3901894720824067; Universidade Federal de São Paulo (UNIFESP)Modern society has been facing a major demographic revolution that is the population aging. The increase in life expectancy depends on the adjusted function of several organs and tissues in order to deal with damaging events in life time. Successful aging seems to be dependent at least in part on the adequate function of the immune system. It has been reported that aging is associated with changes in the percentage of myeloid-derived suppressor cells (MDSC) and T lymphocytes besides the impairment of T cells functions. Our aim was to evaluate young and long-living individuals according to myeloid-derived suppressor cells; T cells proliferative response, phenotype, and cytokines secretion after mitogen stimulation. Non-institutionalized both gender long-living individuals (80 years old and over; 80+) from SABE study were evaluated and compared to young students from UNIFESP (20-30 years old). Aging was associated with reduced circulating number of leukocytes in older individuals (80+). The percentage of MDSC was higher in 80+ group whereas the absolute number of these cells was not statistically different when young and 80+ individuals were compared. Aged individuals also presented higher CD4/CD8 ratio, decrease of naïve and increase of EMRA cells mainly in CD8+ compartment. Under PHA stimulus 80+ individuals presented lower proliferative capacity, and decreased expression of IL-1, IL-2, IL-6, IFN-y, and TNF-alpha. Aging is a complex, multifactorial, and heterogeneous process and based on our results it is suggested that MDSC (percentage and absolute cell number), percentage of naïve and EMRA TCD8+ cells, CD4/CD8 ratio, proliferative T cell percentage, and cytokine levels could be used as biomarkers in aging individuals to predict pathologies, to indicate interventions and to evaluate interventions' efficacy. In addition, aging population presented very heterogeneous results, reinforcing the importance of an individualized treatment for these individuals.
- ItemAcesso aberto (Open Access)Estudo da modulação das células mielóides supressoras no adenocarcinoma metastático após terapia antiangiogênica(Universidade Federal de São Paulo (UNIFESP), 2016-08-31) Chaves, Karen Cristina Barbosa [UNIFESP]; Bellini, Maria Helena [UNIFESP]; http://lattes.cnpq.br/4219112551635779; http://lattes.cnpq.br/1190409748118272; Universidade Federal de São Paulo (UNIFESP)Renal cell carcinoma (RCC), the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and resistant to radiotherapy and chemotherapy. Antiangiogenic drugs are promising and widely used in clinical, on the other hand, mechanism of evasive resistance has been seen to treatment with anti-VEGF antibody. Recent reports suggest that treatment resistance of patients with cancer is related to the presence of myeloid-derived suppressor cells. Endostatin (ES) is a fragment of collagen XVIII that mediates antiangiogenic activity, however, its mechanisms of action are unclear. In this study, we tracked Gr-1+ cells in different organs, evaluated the role of CD11b+Gr-1+ cells and their subsets during tumoral progression and examined the therapeutic potential of ES in modulating CD11b+Gr-1+ cells and their subsets as well as their immunosuppressive activities in lung metastasis. Healthy Balb/c mice were used to detect Gr-1+ cells. CCRm-bearing mice were nephrectomized on day 7 and collected metastatic lung, spleen and bone marrow after 3, 7 and 10 days. Quantification of CD11b+Gr-1+ cells and their monocytic and granulocytic subsets was performed by flow cytometry and microscopic analysis were viewed in HE staining. CCRm-bearing mice were treated with NIH/3T3-LendSN-clone 5 or with NIH/3T3-LXSN cells as a control. ES and G-CSF levels were measured by ELISA and Milliplex, respectively. Quantification of CD11b+Gr-1+ cells and their subsets was performed by flow cytometry. Gr-1+ cells magnetically separated were evaluated in vitro the nitrite levels in supernatant and arginase activity in cells by colorimetric assays. ROS production was measured in CD11b+Gr-1+ cells using the DCFDA marker by flow cytometry. Our data showed the presence of CD11b+Gr-1+ cells in the bone marrow as well as in the kidney, lung and spleen, confirming the monocytic and granulocytic morphologies In metastatic progression, saw the expansion of CD11b+Gr-1+ cells and, preferably, the granulocytic subtype in the bone marrow. Our data demonstrate the progressive accumulation of splenic CD11b+Gr-1+ cells and the opposite was seen in metastatic lungs.Gene therapy with ES reduced the number of pulmonary metastatic lesions, the number of CD11b+Gr-1+ cells and the number of granulocytic cells. G-CSF levels were also reduced and ROS production by granulocytic cells was affected after the treatment with ES. Here, we demonstrate that the metastatic progression is inversely proportional to the number of CD11b+Gr-1+ cells present in the tumor microenvironment, showing that the granulocytic subtype is involved in advanced metastasis. Treatment with ES induced relevant antitumor immune response abrogating the reduction of ROS-producing myeloid-derived suppressor cells in the metastatic local.