We hypothesized that lymph node involvement in minor salivary gland cancers is associated with clinical and pathological factors commonly available to the clinician after a typical initial workup. Our aim was to identify these factors using a dataset that allowed us to compile the largest series of minor salivary gland cancers in the published literature. Using this dataset we also aimed to characterize the distribution of histological types by primary site, identify the predictors of the use of external beam radiation therapy and neck dissection, and examine the effect of lymph node involvement on survival. Using the SEER database, we identified 2667 minor salivary gland cancers with known lymph node status from 1988 to 2004. Univariate and multivariate analyses were conducted to identify factors associated with the use of neck dissection, the use of external beam radiation therapy, and the presence of cervical lymph node metastases. Kaplan Meier survival curves were constructed to examine the effect of lymph node involvement on survival. 426 (16.0%) patients had neck nodal involvement. Factors associated with neck nodal involvement on univariate analysis included increasing age, male gender, increasing tumor size, high tumor grade, T3-T4 stage, adenocarcinoma or mucoepidermoid carcinomas, and pharyngeal site of primary malignancy. On multivariate analysis, four statistically significant factors were identified, which included male gender, T3-T4 stage, pharyngeal site of primary malignancy, and high-grade adenocarcinoma or high-grade mucoepidermoid carcinomas. The proportions (and 95% confidence intervals) of patients with lymph node involvement for those with 0, 1, 2, 3 and 4 of these prognostic factors were 0.02 (0.01-0.03), 0.09 (0.07-0.11), 0.17 (0.14-0.21), 0.41 (0.33-0.49), and 0.70 (0.54-0.85) respectively. Grade was a significant predictor of metastasis for adenocarcinoma and mucoepidermoid carcinoma but not for adenoid cystic carcinoma. Overall survival was significantly worse at 5, 10, and 15 years for patients with lymph node involvement on presentation. A prognostic index using the four clinicopathological factors listed above can effectively differentiate patients into risk groups of nodal metastasis. The precision of this index is subject to the limitations of SEER data and it should be validated in further clinical studies.

No description available.

Nosso laboratório investiga os mecanismos moleculares que promovem o estabelecimento de padrões de expressão gênica regulados no desenvolvimento em eucariotos superiores. Como modelo, utilizamos o gene de pufe de DNA BhC4-1, que é amplificado e expresso de modo regulado na glândula salivar e na glândula protorácica no final do quarto estadio larval de B. hygida. Estudos funcionais em D. melanogaster resultaram na identificação de módulos cis-reguladores (MCRs) na região promotora do gene BhC4-1. O MCR de glândula anelar de 67 bp (-253/-187), promove a expressão de BhC4-1-lacZ na glândula anelar a partir do final do desenvolvimento embrionário. O MCR de glândula salivar de 129 bp (-186/-58), dirige a expressão do transgene nas glândulas salivares de prépupas. A glândula anelar é o principal órgão endócrino larval e em D. melanogaster é o resultado da fusão das glândulas protorácicas (responsáveis pela síntese de hormônios esteroides), corpus allatum (síntese de hormônio juvenil) e corpus cardiacum (glândula neuroendócrina). Neste trabalho foram obtidas 12 linhagens independentes transformadas com uma construção que contém o fragmento (-253/+40) do promotor do gene de pufe de DNA BhC4-1 clonado à montante do gene repórter GFP. O genótipo destas linhagens foi validado utilizando-se Southern blots. Inicialmente as 12 linhagens obtidas foram analisadas quanto ao padrão de expressão de GFP em larvas de terceiro estadio e em prépupas 2 horas. Em conjunto, esta análise revelou que o padrão de expressão de GFP é bastante variável nestas linhagens. A análise do padrão de expressão da proteína repórter foi estendida em duas linhagens representativas da série (- 253/+40)/GFP. Nestas linhagens a expressão de GFP é inicialmente detectada na glândula salivar durante o estágio de prépupa e na glândula anelar a partir do terceiro estadio larval. Diferentemente do anteriormente observado em linhagens (-253/+40)/lacZ, nestas linhagens não detectamos a expressão de GFP em tempos do desenvolvimento anteriores ao terceiro estadio larval. Experimentos de interação gênica revelaram que na ausência do fator de transcrição br, a expressão de GFP é mantida na glândula anelar e abolida na glândula salivar de larvas de terceiro estadio. Os resultados dos experimentos de interação gênica corroboram dados anteriores que indicavam que o conjunto de fatores de transcrição que regulam a expressão de BhC4-1-lacZ na glândula anelar é distinto daquele que promove a expressão do gene na glândula salivar. As linhagens obtidas neste trabalho constituem uma ferramenta a ser utilizada na caracterização de fatores de transcrição tecido-específicos que regulam o gene BhC4-1 na glândula anelar e/ou na glândula salivar a partir do final do desenvolvimento larval. / Our laboratory investigates the molecular mechanisms that promote the establishment of developmentally regulated gene expression patterns in metazoans. As a model, we employ the BhC4-1 DNA puff gene, which is amplified and expressed in a regulated manner in the salivary gland and in the prothoracic gland at the end of the fourth larval instar in B. hygida. Functional studies in D. melanogaster resulted in the identification of cis-regulatory modules (CRMs) in the BhC4-1 promoter region. The 67 bp (-253/-187) ring gland CRM drives BhC4-1-lacZ expression in the ring gland from late embryonic development. The 129 bp (-186/-58) CRM salivary gland drives transgene expression in the prepupal salivary glands. The ring gland is the major endocrine organ, and comprises the prothoracic glands (synthesis of ecdysteroid hormones), corpus allatum (synthesis of juvenile hormone) and corpus cardiacum (neuroendocrine gland). In this work, 12 independent lines transformed with a construct containing the BhC4-1 promoter fragment (- 253/+40) cloned upstream of the reporter gene GFP were obtained. The genotype of each line was validated using Southern blots. Initially, the 12 obtained lines were analyzed to investigate the pattern of GFP expression in the third instar larvae and in the 2 hours prepupae. This initial screening revealed that the pattern of GFP expression is highly variable in these lines. The developmental pattern of GFP expression was extended in two representative (- 253/+40)/GFP lines. In these lines, GFP expression is initially detected in the larval and prepupal salivary glands and in ring gland third instar. Differently from previously observed in (-253/+40)/lacZ lines, in these lines we did not detect GFP expression at developmental times prior to the third larval instar. Gene interaction experiments revealed that in the absence of the br transcription factor, GFP expression is maintained in the ring gland and abolished in the salivary gland of third instar larvae. The results of gene interaction experiments corroborate previous data indicating the set of transcription factors that regulate BhC4-1-lacZ expression in the ring gland is distinct from that which promotes gene expression in salivary glands. The lines obtained in this work constitute a tool to characterize the tissue-specific transcription factors that regulate BhC4-1 gene in the ring gland and/or in the salivary gland from the end of the larval development.

Orientador: Pablo Agustin Vargas / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-20T06:52:13Z (GMT). No. of bitstreams: 1 Fonseca_FelipePaiva_M.pdf: 2031852 bytes, checksum: 891d082818e43f0fa54efa8553fba38c (MD5) Previous issue date: 2012 / Resumo: Tumores de glândulas salivares correspondem à cerca de 3 a 6% de todos os tumores de cabeça e pescoço, apresentando uma ampla variação quanto à freqüência dos diferentes tipos histológicos e seus respectivos cursos clínicos. Desta forma, a determinação de novos marcadores moleculares que estejam relacionados com o comportamento biológico destas neoplasias se faz necessário e o uso da técnica de tissue microarray (TMA) ou micro-arranjo tecidual representa uma ferramenta altamente eficaz para a identificação destes marcadores. Sendo assim, o objetivo do presente estudo é avaliar as características clinicopatológicas de 493 neoplasias de glândulas salivares e descrever os princípios técnicos de construção de blocos de micro-arranjo tecidual, assim como suas vantagens e desvantagens para o estudo destes tumores. Para isto, os prontuários de um centro de patologia médica e de um centro de patologia oral compreendidos entre os anos de 2001 e 2011 foram revisados e os dados clinico patológicos coletados, enquanto que a construção dos blocos de TMA foi realizada por meio de equipamento manual de arranjo tecidual em matriz, onde três áreas tumorais representativas foram selecionadas e incluídas no bloco receptor. Após a obtenção dos resultados, foi observado que o adenoma pleomórfico e o carcinoma mucoepidermóide representaram as neoplasias benigna e maligna de glândulas salivares mais freqüentes e após a construção de 12 blocos de TMA foi possível obter boa representatividade utilizando-se cilindros de 1,0, 2,0 ou 3,0 mm, especialmente em neoplasias sólidas. Portanto, a distribuição dos tumores de glândulas salivares na amostra estudada está de acordo com os achados relatados anteriormente na literatura e a técnica de TMA apresenta-se como uma metodologia de alto rendimento e baixo custo no estudo de tumores de glândulas salivares / Abstract: Salivary gland tumors account for 3 to 6% of the head and neck tumors, with a broad variation in the incidence of their different histological subtypes and their respective clinical courses. For this reason, the determination of new molecular markers truly associated to the biological behavior of these neoplasias becomes necessary and the use of tissue microarray (TMA) technique represents a high-throughput laboratory tool for identifying such markers. The aim of the present study is to evaluate the clinic-pathological features of 493 salivary gland neoplasias and to describe the technical principles for construction of TMA blocks, as well as their advantages and disadvantages regarding the study of salivary gland tumors. For this, medical charts of a general pathology service and of an oral pathology service from 2001 to 2011 were reviewed and the clinic-pathological data acquired, whereas TMA blocks were constructed using a manual tissue arrayer by selecting three representative neoplastic areas to be included in the recipient block. Following the acquisition of the results, it was observed that pleomorphic adenoma and mucoepidermoid carcinoma represented the most frequent benign and malignant neoplasias, respectively, and that after the building of 12 TMA blocks it was possible to obtain high representative cores by using 1.0, 2.0 and 3.0 mm cylinders, especially in solid neoplasias. Hence, the distribution of salivary gland tumors in the sample studied is in agreement with the findings reported previously in the literature and the TMA technique presents as a high-throughput and low-cost methodology in salivary gland tumors study / Mestrado / Patologia / Mestre em Estomatopatologia

The heterogeneity of salivary gland neoplasms have made classification and prognostication of these tumours sometimes difficult, and the in­troduction of techniques, such as enzyme and carbohydrate histochemis­try and electron microscopy have only to a certain extent increased our knowledge in these respects. In the present study immunohistochemical methods have been used to identify intermediate filament proteins (IFP) in normal fetal and adult parotid glands, as well as in salivary neo­plasms. The intermediate filaments (IF) make up the cytoskeleton in eucaryotic cells. Epithelial tissue contains IF composed of different cytokeratins (CK 1-19) whilst mesenchymal tissue generally contains IF composed of vimentin, and the IFP pattern is very stable even during cell transformation. It would thus be possible to further clarify the histogenesis of salivary neoplasms by identifying IFP, in addition the IFP pattern would probably be useful in tumour typing. Furthermore, ultrastructural cytochemical studies, microspectorphotometry on nuclear DNA as well as enzyme secretory studies of certain tumour types were carried out, in order to further characterize the biology of salivary neoplasms. The immunohistochemical investigations showed that in normal parotid tissue, the different cell types differed in IFP expression: acinar cells express mainly CK 18 and myoepithelial cells mainly CK 17 and 19, whilst duct cells contained a broad range of CK. Vimentin could in ad­dition to CK be detected in myoepithelial cells and basal cells of ex­cretory ducts. Fetal parotid cells showed a similar CK pattern as mature duct cells. In addition, vimentin could be found in some basal cells of the terminal tubules of the fetal glands. Salivary neoplasms could be divided into three types with regard to their IFP pattern:  Acinic cell carcinomas showed a CK-pattern similar to normal acinar cells but a co-expression of CK and vimentin was present in some cells.  Adenoid cystic carcinomas, mixed tumours and basal cell adenomas showed a CK-pattern of normal duct or myoepithelial cells. The peri­pheral cells were also vimentin positive. 3. Mucoepidermoid carcinomas and adenocarcinomas had a similar CK-pattern as duct cells, and no tu­mour cells contained vimentin. This indicates that typing of IFP may be useful for subgrouping of salivary neoplasms. By stereological measurements, the cells of acinic cell carcinomas were found to be very similar to normal parotid acinar cells. Furthermore, they contained amylase and after stimulation by norepiphrine a secre­tory response was induced, with a rise in intracellular cAMP as well as a release of amylase. By single cell measurements of nuclear DNA con­tent, no difference was found between acinic cell carcinomas with de­finite metastasis and those without recurrence, both in paraffin sec­tions and cytological smears. / digitalisering@umu.se

A thesis on Head and neck cancer focusing on dose planning, salivary gland carcinoma and Single nucleotide polymorphism. For dose planning PET/CT (Positron emissions tomography/computed tomography) with tracer gave more precise information in comparison dose planning with CT. More primary tumours and metastases were found with the acetate tracer than with glucose tracer. Acetate PET/CT also showed larger volume of tumours attributed to lipid metabolism. In a retrospective study salivary gland cancer 5-year overall survival (OS) was 53 %. Salivary gland carcinoma consists of many histopathological groups, the two largest groups being mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ASCC). For ACC, having the best 5-year OS, it was 70 percent. Facial palsy, advanced stage disease, lymph node metastases worsened prognosis. ACC and polymorphous low grade carcinoma (PLGA) expressed c-myc and cyclin D1 to a larger extent than MEC. In squamous cell carcinoma of the head and neck we examined the occurrence of Single Nucleotide polymorphism, SNP. We found that the SNPs in male and female patients differed from each other. In male patients the SNPs were associated with immune response while in female patients the association was to SNPs concerning inflammation. This means that different pathways were engaged in cancer development for men and women. We also found that the SNPs in patients were different from those expressed in the healthy controls.

Neste estudo avaliou-se os efeitos do diabetes mellitus (DM) sobre dois sistemas: glândula parótida de ratos e células cultivadas in vitro. Foram avaliados respectivamente a composição da matriz extracelular e a migração de células expostas a elevada concentração de glicose. Na parótida observou-se aumento de colágenos III, IV e V, laminina e fibronectina, mediado por TGFb2. Em células isoladas observou-se que a glicose dificultou a polarização celular, reduziu a velocidade e direcionalidade de migração, reduziu a persistência e estabilidade das protrusões celulares e a maturação de adesões. Estas alterações estão relacionadas à ativação da GTPase Rac1, dependente de estresse oxidativo. Este estudo sugere, pela primeira vez, que: 1) a hipofunção salivar pode envolver um espessamento da lâmina basal de capilares e parênquima por mecanismos previamente observados em outros orgãos-alvo de complicações diabéticas e 2) que a glicose exerce um efeito direto sobre a migração celular, fator que pode contribuir para a cicatrização deficiente em indivíduos diabéticos. / In this study we evaluated the effects of DM on two different systems: the rat parotid gland and in vitro cultured cells. Extracellular matrix composition and the migratory behavior of cells exposed to a high glucose concentration (HG) were evaluated, respectively. In the parotid, DM led to an increase in collagens III, IV and V, laminin and fibronectin, through a TGFb2-dependent mechanism. In cultured cells, HG impaired cell polarization, reduced migration velocity and directionality, reduced the persistence and stability of protrusive cellular processes, as well as adhesion maturation. These effects were related to Rac1 GTPase activation, dependent on the oxidative stress promoted by HG. This study suggests, for the first time, that: 1) salivary hypofunction in DM might involve the thickening of capillary and parenchyma basal lamina, through mechanisms already described in other target organs for diabetic complications and 2) that glucose directly impairs cell migration, and this effect may contribute to the chronic wound healing observed in diabetic patients.

Sammanfattning Bakgrund: Sjögren syndrom (SS) är en globalt utbredd sjukdom som berör 0,5–1% av befolkningen, främst kvinnor i medelåldern.  Syfte: Syftet med denna litteraturöversikt var att beskriva vilka extra- och intraorala kliniska tecken som upptäcks hos patienter med SS   Metod: En allmän litteraturöversikt genomfördes. Artiklar publicerade mellan 2012–2022, med tydligt urskiljbar information om SS överensstämmande med syftet användes.  Resultat: Studier visar att patienter med SS har högre grad av oral involvering inklusive oral lichen planus, candida infektioner och angulär cheilit. Salivproduktionen kan vara nedsatt vilket orsakar hyposalivation och ger ökad risk för karies. Svullnad av spottkörtlar, nedsatt funktion i käkleder och tandslitage förekommer också.   Slutsats: Av de intraorala tecken var hyposalivation, oral candidos och angulär cheilit bland annat vanligt förekommande och extraoralt var svullnad av parotiskörtlarna vanligast. Svullna parotiskörtlar var även det vanligaste kliniska tecknet för barn med SS. Det förekom en stor variation i kliniska tecken och det är därför viktigt att fortsätta utforska sambandet mellan SS och oral påverkan för att förbättra diagnos och behandling av sjukdomen då den är svårdiagnostiserad. / Summary Title: Sjogren´s syndrome and oral health: A literature study.  Background: Sjogren´s syndrome (SS) is a globally prevalent disease affecting 0,5–1% of the population, predominantly middle-aged women.  Aim: The aim of this literature review was to describe the extra- and intraoral clinical signs detected in patients with Sjogren's syndrome.   Method: A general literature study was conducted. Articles published between 2012 and 2022 with clearly discernible information about SS consistent with the objective were included. Results: Studies show that patients with SS can have oral involvement, including oral lichen planus, candida infections and angular cheilitis. Saliva production can be reduced, which causes hyposalivation and increases the risk of dental caries. Swelling of salivary glands, reduced function of the jaw and tooth wear may also occur.   Conclusion: Among the intraoral signs, hyposalivation, oral candidosis and angular cheilitis were mostly common, and for the extraoral signs swelling of the parotid glands was the most common. There was a large variation in clinical signs and it´s important to continue to explore the relationship between SS and oral involvement to improve the diagnosis and treatment for SS of the disease as it is difficult to diagnose.

O carcinoma mucoepidermóide (CME) é o tumor mais comum entre as neoplasias malignas de glândula salivar. Recentemente, uma rara população de células com características de multipotência, autorrenovação e potencial tumorigênico, denominadas como células tronco tumorais (CTT), foi descrita no CME. As CTT são resistentes as terapias atuais, e têm sido consideradas responsáveis pela recorrência e metástase, levando a um pior prognóstico para o paciente. A descoberta de que as CTT do CME superexpressam componentes da via de sinalização mTOR, levantou a hipótese que os pacientes poderiam ser beneficiados com o uso inibidores de mTOR como terapia para eliminação das CTT. O objetivo desse estudo foi avaliar o potencial uso de inibidores de mTOR como terapia para o CME com foco em CTT, assim como, investigar o funcionamento da via de sinalização mTOR e os efeitos moleculares do tratamento com inibidores dessa via nas CTT do CME. Foi realizada imuno-histoquímica para p-mTOR e p-S6K-1 em casos de pacientes diagnosticados com CME, os resultados foram correlacionados com os dados clínicos dos pacientes e também foi realizada dupla marcação por imunofluorescência para ALDH/p-mTOR. Estudos in vitro foram realizados em 3 linhagens de CME (UM-HMC-1, -3A, -3B) e com inibidores da via de sinalização mTOR. Após exposição aos inibidores, realizou-se ensaios de western blot (proteínas da via mTOR e BMI-1), citometria de fluxo para ALDH/CD44; salisfera; e apoptose, esse último comparando com quimioterápicos utilizados atualmente. Adicionalmente, foi utilizado o silenciamento genético de mTOR para confirmar os resultados obtidos com inibidores químicos. Por fim, foram realizados ensaios in vivo com as células silenciadas e com o inibidor de mTOR tensirolimo. Os resultados evidenciaram que a via de sinalização mTOR está ativa no CME, é correlacionada com pior prognóstico clínico e está superexpressa nas CTT. O tratamento com inibidores da via mTOR levaram a diminuição da fração de CTT, devido a perda de autorrenovação e apoptose das CTT. A apoptose, junto a diminuição de p-AKT revelada por western blot, sugeriram que esteja ocorrendo inibição de mTORC2 nas CTT, um importante componente na eficácia do tratamento com inibição de mTOR no câncer. Além disso, também houve redução de vasos sanguíneos, nichos das CTT, e diminuição do crescimento tumoral com uso de inibidores ou silenciando mTOR in vivo. Coletivamente, os resultados mostraram que a inibição de mTOR foi capaz de agir nas CTT por mecanismos diretos (indução de apoptose e diminuição da autorrenovação) e indiretamente através da redução de angiogênese, sugerindo que o uso de inibidores de mTOR no tratamento do CME é uma estratégia molecular eficiente para a redução de CTT, e uma potencial terapia adjuvante. / Mucoepidermoid carcinoma (MEC) is the most common tumor among malignant salivary gland neoplasms. Recently, a rare population of multipotent, self-renewing, and tumorigenic cells, termed cancer stem cells (CSC), was described in MEC. CSC are resistant to current therapies, and have been considered responsible for recurrence and metastasis, leading to worse patient prognosis. The discovery that CSC from MEC overexpressed the mTOR signaling pathway raised the hypothesis that use of mTOR inhibitors as therapy for CSC elimination could benefit patients. The objective of this study was to evaluate the potential use of mTOR inhibitors as a therapy for MEC targeting CTT, as well to investigate the functioning of mTOR signaling pathway and the molecular effects of treatment with mTOR inhibitors in MEC CSC. Immunohistochemistry was performed for p-mTOR and p-S6K-1 in paraffin samples from patients diagnosed with MEC and results were correlated with clinical data, in addition, co-immunoflorescence was performed for ALDH/p-mTOR. In vitro studies were performed with 3 MEC cell lines (UM-HMC-1, -3A, -3B) and with inhibitors of the mTOR signaling pathway. After exposure to inhibitors the following assays were performed: western blot (mTOR signaling pathway proteins and BMI-1), flow cytometry for ALDH/CD44, salispheres, and apoptosis, the latter comparing with currently chemotherapeutic agents used as treatment for cancer patients. In addition, mTOR genetically silent was used to confirm results with chemical inhibitors. Finally, in vivo assays were performed with knockdown cells and with mTOR inhibitor temsirolimus treatment. Results showed that mTOR signaling pathway is active in MEC, it is correlated with worse clinical prognosis and it is overexpressed in CSC. Treatment with inhibitors of mTOR signaling pathway led to a decrease in CSC fraction, caused by loss of self-renewal and apoptosis. Apoptosis, together with the decrease in p-AKT revealed by western blot, suggest that inhibition of mTORC2, an important compound in the efficacy of mTOR inhibition for cancer treatment, is occurring. In addition, there was reduction of blood vessels, CSC niches, and decreased tumor growth using mTOR inhibitors or silencing mTOR. Collectively, results showed that inhibition of mTOR was able to act in CSC by direct mechanisms (induction of apoptosis, decreased self-renewal) and indirectly through reduction of angiogenesis, suggesting that the use of mTOR inhibitors in treatment of MEC is an efficient molecular strategy to reduce fraction of CSC, and a potential therapy.

A saliva de insetos hematófagos possui moléculas capazes de modular o sistema imune do hospedeiro. Com base na literatura a respeito das atividades presentes na saliva de Aedes aegypti, investigamos se o EGS dessa espécie era capaz de modular a EAE. Imunizamos animais C57BL/6 com MOG35-55, e realizamos um tratamento com EGS. O tratamento com EGS diminuiu a incidência da doença e provocou um atraso no aparecimento dos sinais clínicos, além de estes serem mais brandos. Observamos que a modulação se deu na fase de indução da resposta imune, não na efetora. De fato, o EGS consegue suprimir a doença por 4 vias: 1) diminuindo a expressão de MHCII, CD80 e CD86 em células dendríticas, e diminuindo a produção de citocinas responsáveis pela indução das respostas Th1/Th17; 2) induzindo células produtoras de IL-10 in vivo; 3) induzindo apoptose em linfócitos T naive; 4) induzindo células com perfil Th2 produtoras de IL-4 e IL-5. Concluímos que o EGS é capaz de atuar na supressão dos sintomas durante o curso da EAE e na inibição do início da resposta imune. / The saliva of hematophagous insects has molecules that can modulate the host immune system. Based on the literature about activities found in Aedes aegypti saliva, we investigate if SGE of this species could modulate EAE. We have immunized C57BL/6 mice with MOG35-55, and carried out a treatment with SGE. The treatment with SGE reduced the incidence of disease and caused a delay onset of clinical signs making them softer. We have observed that modulation occured in the induction phase of immune response, not in effector phase. In fact, SGE can suppress the disease by four ways: 1) decreasing the expression of MHCII, CD80 and CD86 in dendritic cells and decreasing the production of cytokines responsible for Th1/Th17 response induction; 2) inducing cells producing IL-10 in vivo; 3) inducing apopotosis in naive T lymphocytes; 4) inducing cells Th2 producing IL-4 e IL-5. We came to the conclusion that SGE can act in supressing symptoms during the course of EAE and inhibiting the beggining of autoimmune response.