Multiple Sclerosis (MS) is an autoimmune demyelination disease of the central nervous system (CNS). The traditional immunotherapies so far have not been able to stop the progression of the disease. Galanin (GAL) is an inducible neuropeptide. It has diverse regulatory effects in the nervous. The expression of galanin is induced by the administration of estrogen and is increased during pregnancy in rodents. In women with MS, pregnancy has a protective effect associated with significant remission of MS symptoms during the second and third trimester. In this study, using the cuprizone (CPZ) demyelination model of MS I demonstrated that GAL has a pronounced neuroprotective effect on demyelination and remyelination, with estrogen the protection was further enhanced. Moreover, I also found differential activation of GAL receptors in the demyelination and remyelination processes. These results suggest GAL alone or combined with estrogen might introduce next generation strategies for the treatment of MS.

Multiple Sclerosis (MS) is an autoimmune demyelination disease of the central nervous system (CNS). The traditional immunotherapies so far have not been able to stop the progression of the disease. Galanin (GAL) is an inducible neuropeptide. It has diverse regulatory effects in the nervous. The expression of galanin is induced by the administration of estrogen and is increased during pregnancy in rodents. In women with MS, pregnancy has a protective effect associated with significant remission of MS symptoms during the second and third trimester. In this study, using the cuprizone (CPZ) demyelination model of MS I demonstrated that GAL has a pronounced neuroprotective effect on demyelination and remyelination, with estrogen the protection was further enhanced. Moreover, I also found differential activation of GAL receptors in the demyelination and remyelination processes. These results suggest GAL alone or combined with estrogen might introduce next generation strategies for the treatment of MS.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 148-168).

Orientador: Carlos Rossa Junior / Banca: Alexandra Ivo de Medeiros / Banca: Luis Carlos Spolidorio / Banca: Ricardo Della Coletta / Banca: Roseanas Almeida Freitas / Resumo: Carcinoma espinocelular de cabeça e pescoço (HNSCC, squamous cell carcinoma of the head and neck) é uma neoplasia caracterizada mais comumente por invasão local/regional de prognóstico sombrio quando diagnosticada em estágios avançados e uma característica imunossupressão local ou sistêmica associada. A taxa de sobrevivência em casos avançados é inferior à de câncer de mama ou próstata, e seu tratamento usualmente causa morbidade severa. A resposta ao tratamento é altamente variável mesmo entre pacientes em estágios iniciais da doença e apesar do tratamento implementado seguir o padrão de cuidados vigente. Assim, há grande necessidade de identificar biomarcadores que indiquem um fenótipo agressivo e possa proporcionar informações de utilidade no desenvolvimento de novas terapias específicas. Nossa hipótese foi de que produtos secretados por células de HNSCC ou o contato direto das mesmas com células imunológicas podem induzir uma modulação no sentido de causar a evasão do tumor da resposta imune. Observamos que a literatura mostra diversos trabalhos onde células tumorais exercem efeito imunossupressor em diversos tipos celulares da resposta imune. O estímulo de PBMC com meio condicionado (CM) de células de HNSCC induziu uma diminuição na proliferação, bem como modulou a polarização para fenótipos anti-inflamatórios e em co-cultura de HNSCC e PBMC, o tratamento prévio com CM das PBMC conferiu vantagem às células tumorais. Por último avaliamos um possível biomarcador, a galanin... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Squamous cell carcinoma of head and neck (HNSCC) is a cancer characterized commonly by local/regional invasion of poor prognosis when diagnosed in advanced stages and are associated with local or systemic immunosuppression. The survival rate for advanced cases is below the breast or prostate cancer, and treatment usually causes severe morbidity. The response to the treatment is highly variable among patients even in the early stages of the disease, despite the treatment implemented following the current standard care. Thus, there is great need to identify biomarkers that indicate an aggressive phenotype and can provide useful information on the development of new target therapies. Our hypothesis was that secreted products by HNSCC cells or direct contact with immune cells can induce a modulation in order to cause tumor evasion of the immune response. We note that the literature shows several studies where tumor cells exert immunosuppressive effect in different cell types of the immune response. The stimulation of PBMC with conditioned medium (CM) of HNSCC cells induced a decrease in proliferation, and modulates a polarization toward anti-inflammatory phenotypes and in co-culture of HNSCC and PBMC pre-treatead with CM caused advantage to tumor cells. Finally we evaluate a possible biomarker, galanin, in modulating the immune response. The absence of galanin induced higher levels of proliferation as well a more bias towards proinflammatory phenotypes. Increase of galanin expres... (Complete abstract click electronic access below) / Doutor

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 8 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2006. / Härtill 4 uppsatser.

Orientador: Carlos Rossa Júnior / Resumo: Os macrófagos representam uma das principais pontes entre imunidade inata e adaptativa e estão presentes em grande número tanto no estroma circundando tumores sólidos quanto no interior da massa tumoral (TAMs, tumor-associated macrophages), onde podem representar até 50% da massa da lesão. Nos carcinomas espinocelulares de cabeça e pescoço (HNSCC), TAMs apresentam predominantemente o perfil M2 (pró-tumoral), e a quantidade de TAMs é inversamente relacionada ao prognóstico. A efetividade do tratamento não-cirúrgico (quimio/radioterapia ou imunoterapia) dos tumores sólidos é diretamente relacionada à indução de morte das células neoplásicas. No processo de reparo, as células apoptóticas são removidas por fagocitose por outros tipos celulares, num processo denominado eferocitose. Embora seja um processo importante para o reparo e homeostasia tecidual, a eferocitose pode afetar o fenótipo dos macrófagos, favorecendo a polarização para o perfil M2, associado à progressão de HNSCC. A galanina é um peptídeo de 29 aminoácidos amplamente distribuída no organismo e com amplo espectro de efeitos biológicos. A expressão constitutiva de galanina por células de OSCC está associada à maior agressividade do tumor e tem sido estudado como marcador prognóstico de agressividade do tumor e também como um possível alvo terapêutico de HNSCC. O objetivo do presente trabalho é determinar a influência dos produtos secretados pelas células de carcinoma espinocelular de cabeça e pescoço, bem como da ga... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Macrophages are a major link between innate and adaptive immunity and are present both in the surrounding stroma and within various solid tumors (when they are denominated tumor-associated macrophages, TAMs), where these cells may represent up to 50% of the tumor mass. In head and neck squamous cell carcinomas (HNSCC), TAMs are predominantly of the M2 phenotype and the prognosis is inversely correlated with their abundance. The effectiveness of non-surgical treatment of solid tumors (chemotherapy/radiotherapy) is directly related to the induction of neoplasic cell death. In the repair process, apoptotic/dead cells must be removed by phagocytosis by other cell types (particularly macrophages), in a process called efferocytosis. Although this is a critical step in the repair and reestablishment of tissue homeostasis, efferocytosis itself may affect the phenotype of macrophages, skewing the cells towards an M2 phenotype, which is deemed as a 'pro-tumoral' phenotype. Galanin is a 29 aminoacid peptide of 29 produced by various cell types and with a broad spectrum of biological effects. The constitutive expression of galanin by head and neck cancer cells is associated with the increased of tumor aggressiveness and has been proposed as a biomarker of tumor aggressiveness and also as a possible therapeutic target in HNSCC. Thus, the goal of the present study was to determine the role of secreted products from head and neck cancer cells, and of galanin independently, on macrophage phe... (Complete abstract click electronic access below) / Mestre

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 261-288).

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.