Teses em Oncologia e Ciências Médicas (Doutorado) - PPGOCM/NPO
URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/9481
O Doutorado Acadêmico iniciou-se em 2011 e pertence ao Programa de Pós-Graduação em Oncologia e Ciências Médicas (PPGOCM) integra o Núcleo de Pesquisas em Oncologia (NPO) da Universidade Federal do Pará (UFPA).
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Item Acesso aberto (Open Access) Análise de citocinas no soro de pacientes com câncer gástrico(Universidade Federal do Pará, 2017-08-16) HAGE, Pedro Antônio Mufarrej; CALCAGNO, Danielle Queiroz; http://lattes.cnpq.br/1326603355062154Despite the reduction in the worldwide incidence of gastric cancer, this neoplasm remains the second largest cause of cancer death in the world. Late diagnosis occurs mainly due to the absence of symptoms or the presence of non-specific symptoms in the early stages of the disease. In this case, few effective therapeutic options are available, resulting in high rates of morbidity and mortality. The continuous study of new strategies for the early diagnosis, definition of the prognosis and identification of new therapeutic methods is of great interest in this neoplastic type. In the present study was quantified inflammatory proteins candidate to biomarkers in the serum of 19 patients with gastric adenocarcinoma before surgical resection and 13 healthy individuals as control. The methodology used for quantification of proteins was the MAGPIX system and panels of cancer biomarkers inventoried by the manufacturer (Bio-Plex Pro Human Pro-Cytokine, Chemokine and Growth Factors). In the comparison between patients with gastric adenocarcinoma and control group was observed the levels of IL-1β, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-12, IL-15, G-CSF, GM-CSF, IFN-γ, MIP1α, RANTES and VEGF were higher in serum of gastric adenocarcinoma patients. According clinicopathological characteristics, was observed elevated levels of IL-5, IL-7, IL-10 and IL-17A in diffuse-type gastric adenocarcinoma in relation intestinal-type. In addition, the association of the expression of the cytokines studied with overall survival (OS) and relapse-free survival (PFS) were performed using the KM Plotter Online Tool. Overexpression of G-CSF, GM-CSF and VEGF in tumor was associated with lower OS and PFS of gastric cancer patients. However, the overexpression of IL-10 was associated only with PFS. Thus, we can conclude that the IL-1β, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-12, IL-15, G-CSF, GM-CSF, IFN-γ, MIP1α, RANTES and VEGF cytokines are potential biomarkers of gastric cancer, and diffuse-type adenocarcinoma can related to a greater inflammatory response than intestinal-type. Survival analysis suggests that elevated levels of IL-10, G-CSF, GM-CSF and VEGF in serum are potential biomarkers of prognosis in gastric cancerpatients.Item Acesso aberto (Open Access) Distribuição tecidual, neuroproteção e efeitos anti-inflamatórios do conjugado LDE/metotrexato após isquemia cortical induzida por microinjeções de endotelina 1 em ratos adultos(Universidade Federal do Pará, 2017-04-05) PEREIRA, Edmundo Luís Rodrigues; BURBANO, Rommel Mario Rodriguéz; http://lattes.cnpq.br/4362051219348099; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072Ischemic stroke is one of the leading causes of morbidity and mortality in adults worldwide. Currently, there is only a single pharmacological therapy available to treat such neural disorder, using a high-cost thrombolytic agent, which must be administered within 4 hours of the onset of symptoms, but with a significant risk of transforming the initially oligoemic area into a catastrophic cerebral haemorrhage. In the last decades, nanoparticles with high affinity for certain types of tissues and specially configured with an enhanced diffusibility through biological barriers, have been employed as vehicles to carry therapeutic agents. Among these, the novel liposomal nanoparticle LDE conjugated to the agent methotrexate (cLDE / MTX) has been successfully tested in several experimental models of inflammation, with promising results. Considering that modulation of the inflammatory process that accompanies cerebral infarction is of prognostic significance, the present study investigated the effects of cLDE / MTX upon an experimental model of cerebral ischemia induced by the vasoconstrictor agent endothelin-1 (ET-1) in the cerebral cortex of adults rats. During the first phase of the study, the behavior of tritiated LDE particles (LDE3H+) concerning the blood-brain barrier (BBB), once injected through the caudal vein, was evaluated in either sham animals (N = 18) and animals submited to ET-1 injection (80pMol / Μl) directly into the frontal cortex (N = 5). Further, the anti-inflammatory and neuroprotective effects of cLDE / MTX (1 mg / kg), also injected by caudal vein, were investigated in ischemic animals (N = 5), with the control group (N = 5) receiving only free LDE. All animals were perfused with 0.9% saline and 4% paraformaldehyde 7 days after ischemic induction. Histopathological findings were evaluated by staining with cresyl violet and immunohistochemistry for adult neuronal bodies (anti-NeuN), astrocytes (anti-GFAP) and microglia (anti-Iba1). The results showed that LDE3H+ positively crosses BBB in both sham animals and ischemic animals, and that cLDE / MTX treatment, despite the fact that it reduces not the total area of primary infarction, was able to considerably reduces microglial activation phenomenon at the center of the lesion, inducing as well a significant neuronal preservation at the periphery of the infarction, when compared to the control animals, injected only with unconjugated LDE (P <0.01). At last, the astrocytosis phenomena usually encountered in cerebral ischemia remained unchanged. The results indicate that cLDE / MTX is a promising anti-inflammatory and neuroprotective agent in such experimental model of ischemic stroke. Future studies are desirable in order to increase knowledge about these outcomes, including in animal models with longer survivals.