Influência de contaminante ambiental em tumor de mama em cadela

Mammary cancer is a multifactorial disease that is believed to be caused by genetic and environmental factors. Among the environmental factors, pyrethroids appear to be able to participate in carcinogenesis through several mechanisms, and have been shown to be associated to mammary tumors in canines. In order to investigate the possible rule of pyrethroid on DNA lesion in mammary tissue we compare the comet assay results between mammary tumor bearing dogs with and without pyrethroid associated to the peri mammary adipose tissue or the tumor itself. The pyrethroids presence was assessed by High Performance Liquid Chromatography (HPLC) and the DNA damage was assessed by the comet assay as previously described. Despite of correlation between DNA damage and tumor histologic aggressiveness, association between the severity of DNA damage and different types of mammary carcinoma was not found. Although pyrethroids were present in 22% of tumors and peritumoral adipose tissue, no difference in the degree DNA damage between the exposed and non exposed cells to pyrethroids were found. As future perspectives for this work, our group will evaluate the relationship of pyrethroids presence in tumors with its angiogenic potential. Angiogenesis evaluation will be based on presence of vascular endothelial growth factor (VEGF) in the tumor cells, and microvessel counts

Planejamento e síntese de novo candidato a fármaco útil para o tratamento de tumores sólidos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Caracterização de anticorpos anti-idiotípicos e anti-anti-idiotípicos de BEVACIZUMAB

Propomos avaliar o potencial de uma abordagem imunoterápica que tem o fator de crescimento do endotélio vascular (VEGF) como alvo. A angiogênese é necessária para nutrir o tumor e propicia sua metastatização. Sabe-se que VEGF é produzido pela maioria dos tumores sólidos metastatizantes. A eficiência do anticorpo anti-VEGF, BEVACIZUMAB, já foi demonstrada. Entretanto, efeitos adversos limitam sua utilização em alguns casos e, com base na teoria da rede idiotípica e na experiência do grupo com anticorpos anti-idiotípicos (anti-Id ou AB2), anticorpos AB2 capazes de mimetizar VEGF foram obtidos. Assim, com o objetivo de explorar o rationale, dois anticorpos monoclonais (MAb) anti-Id de Bevacizumab, 10.D7 e 3.E3, foram produzidos em nosso laboratório. O controle da purificação de anticorpos foi feito através da avaliação do material purificado em géis de poliacrilamida. Immunoblots comprovaram a especificidade do reconhecimento do idiotipo de Bevacizumab pelos MAbs anti-Id. Foi mostrado que os AB2 obtidos se ligam a moléculas da superfície de células endoteliais, que expressam receptores de VEGF, sugerindo que esses anticorpos mimetizam VEGF. Entretanto, não foi possível verificar inibição do crescimento dessas células quando cultivadas em presença desses MAbs. Será necessária a otimização dos protocolos utilizados para uma avaliação mais definitiva. Uma vez demonstrada a atividade anti-idiotípica dos AB2 in vitro, 10.D7 e 3.E3 foram utilizados como imunógenos em camundongos Balb/c, com o objetivo de avaliar a resposta AB3 ou anti-anti-Id. Por meio de ensaio imunoenzimático (ELISA) indireto foi verificada a presença de anticorpos anti-anti-Id ligantes de VEGF nos soros dos camundongos imunizados. Os animais imunizados com o MAb 10.D7 responderam melhor do que os imunizados com 3.E3. Anticorpos IgG purificados dos soros desses animais reconheceram VEGF em ensaios imunoenzimáticos. Foram então selecionados os ...

Determinação de fatores angiogênicos e anti-angiogênicos em plasma de gestantes portadoras de pré-eclâmpsia precoce e tardia

Changes in circulating angiogenic factors have been implicated in the pathogenesis of preeclampsia. Thus, evaluation of angiogenesis agonist and antagonist factors is of greater importance to understand the mechanisms responsible for this disorder. The objective of the present study was to evaluate whether circulating angiogenic and anti-angiogenic factors may differentiate early-onset from late-onset preeclampsia. The study was conducted in 86 women with preeclampsia diagnosed in the third trimester of pregnancy. Preeclampsia was classified according to the onset of clinical manifestation in early-onset (before 34 weeks of gestation; n=31) or in late-onset (from 34 weeks of gestation on; n=55) preeclampsia. Serum was obtained from the patients in the moment of the diagnosis and assayed for placental growth factor (PlGF), vascular endothelial growth factor (VEGF), soluble Endoglin (sEng) and soluble form of vascular endothelial growth factor receptor (sVEGFR-1) determination by enzyme-linked immunosorbent assay. The results showed that early-onset preeclampsia was characterized by significant lower levels of PlGF (median 38.3 vs 123.5 pg/mL) and VEGF (median 23.1 vs 35.3 pg/mL) in serum as well as by higher serum levels of sEng (median 54.7 vs 42.1 pg/mL) and sVEGFR-1 (median 5211.0 vs 4657.6 pg/mL) compared with late-onset preeclampsia. In this study serum levels of angiogenic and anti-angiogenic factors prove useful in differentiating early-onset from late-onset preeclampsia in the third trimester of pregnancy. Therefore, these findings suggest that angiogenic factors determination may indicate that early- and late-onset preeclampsia have different pathophysiology

Expressão gênica de MMP-2 e 9, TIMP-1 e 2, ATM, TP53, VEGF, COX-2 e CDH-1 no TVT canino

Pós-graduação em Medicina Veterinária - FCAV

Fator de crescimento do endotélio vascular e do transportador de glicose 1 em cães com ceratose actínica e carcinoma de células escamosas

Pós-graduação em Medicina Veterinária - FCAV

Neovascularization after ischemic injury: evaluation with 99mTc-HYNIC-RGD

Purpose: Angiogenesis involves many mediators including integrins, and the tripeptide RGD is a target amino acid recognition sequence for many of them. Hindlimb ischemia is a simple and convenient animal model however standardization of the injection procedures in the devascularized and control limb is lacking, thus rendering difficult the interpretation of results. The aim of this investigations was to evaluate neovascularization in a hindlimb murine model by means of 99mTc-HYNIC-ß-Ala-RGD. Methods: 99mTc-HYNIC-RGD analog was prepared using coligands. Ischemia was induced in Wistar rats by double- ligation of the common femoral artery. Radiolabeled RGD was injected after 2h, as well as 1, 3, 5, 7, 10 and 14 days. Uptake was evaluated by planar imaging and biodistribution studies. Results: The highest ratio between ischemia and control was achieved at the 7th day (2.62 ± 0.95), with substantial decrease by the 14th day. For pertechnetate the 7th day ratio was 0.87 ± 0.23. Scintigraphic image confirmed different uptakes. Conclusion: 99mTc-HYNIC-RGD analog concentrated in ischemic tissue by the time of widespread angiogenesis and pertechnetate confirmed reduction in blood flow. In this sense, the protocol can be recommended for ischemic models.

Doppler and Elastography as complementary diagnostic methods for mammary neoplasms in female cats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos anti-inflamatório e antitumoral dos constituintes de Qualea grandiflora no tumor de Ehrlich

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Interação de fibroblastos associados ao câncer em co-cultura com linguagens tumorias mamárias e a resposta terapêutica em o uso da melatonina

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Investigação da ação da proteína anexina A1 sobre o processo de angiogênese induzido pelo fator de crescimento do endotélio vascular: modelos experimentais in vivo e in vitro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos preventivos do treinamento físico na expressão das proteínas Cox-2 e Vegf de ratos tratados com dexametasona

Dexamethasone is a synthetic glucocorticoid widely used to treat allergic and inflammatory processes. This drug is used in three main situations, are used to contain acute or chronic inflammatory processes, or like immunosuppressive drug's. In these cases the patient will receive high doses for a chronic period and, therefore, has a much greater chance of adverse side effects, such as hypertension, diabetes and dyslipidemia. Dexamethasone promotes deleterious effects on the arachidonic acid pathway, when administered in high doses, because it is a potent anti-inflammatory drug. We recently demonstrated that dexamethasone significantly reduces the protein expression of vascular endothelial growth factor (VEGF) in both skeletal muscle and heart, but the mechanisms involved remain unclear. Meanwhile, exercise has been shown to be effective against high blood pressure, diabetes and dyslipidemia, promoting, among other factors, the increase in VEGF and angiogenesis. One possible explanation for these effects would be the creation of new vessels mediated by inflammation, or by the stimulation of the formation of products of the metabolism of arachidonic acid (AA), such as prostaglandin E2 (PGE2) and VEGF, by increasing the stimulation of the enzymes cyclooxygenase 1 and 2 (COX-1 and COX-2). Little is known about the preventive effects of training on the action of dexamethasone in the arachidonic acid pathway. Therefore, the aim of this study was to determine whether aerobic exercise training, performed before and concomitant treatment with dexamethasone, was able to prevent the effects of the dexamethasone in the protein expression of COX-2 and VEGF. For this, we used young Wistar rats (n = 40) which were randomly divided into 4 groups: sedentary control (SC), sedentary and treated with dexamethasone (SD), trained control (TC) and trained and treated with dexamethasone (TD). These rats performed aerobic exercise training, 60% of maximum capacity, 5

Modulação da atividade das interleucinas 17B e 25 associadas à melatonina como indutores de apoptose em cultivo celular de neoplasias mamárias

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Desenvolvimento e avaliação de um sistema de liberação sustentada de gentamicina em biomembranas de látex natural

Pós-graduação em Biociências - FCLAS