The increase in ASMC mass is a major structural change described in airway remodeling in asthma. This increase has been attributed to ASMC hyperplasia and hypertrophy. The distance between ASMC and the epithelium is reduced suggesting expansion of the muscle bundle towards the epithelium. Recent studies have suggested a role of epithelial derived chemokines in ASMC migration toward the epithelium. We hypothesized that chemokines (Eotaxin, RANTES, MIP-1alpha and IL-8) can directly influence ASMC mass by increasing the rate of proliferation or enhancing survival. ASMCs were exposed to different concentrations of eotaxin, RANTES, IL-8 or MIP-1alpha. To test for proliferation, stimulated ASMC were pulsed with 3H-thymidine or stained with BrdU and then analyzed with flow cytometry. Apoptosis was measured using Annexin V and flow cytometry. Expression of phosphorylated p42/p44 and MAPKinases was assessed by Western analysis. In a concentration-dependent manner, chemokines such as Eotaxin, RANTES, IL-8 and MIP-lalpha increased ASMCs 3H-thymidine incorporation and DNA synthesis. Eotaxin, RANTES and IL-8 decreased the number of apoptotic ASMCs compared to the matched controls. A significant increase in phosphorylated p42/p44 MAPKs was seen after treating ASMCs with RANTES and eotaxin. We conclude that chemokines might contribute to airway remodeling by increasing the number of ASMCs.

Cancer has been a disease, which has generated intense research interest for many years. Misexpression of two oncoproteins, TAL 1 and LMO 1, has been found to help induce a particular type of leukemia, called T-cell acute lymphoblastic leukemia (T-ALL). Presently, it is not completely understood how these proteins induce leukemogenesis or what other cellular proteins they interact with to drive this progression. In this study, a series of experiments were conducted to identify downstream targets of TALI and LMO1. Using retroviral gene transfer, both genes were introduced, either singly or in combination, into a murine T-cell line called AKR-DP-603. Empty vectors were introduced as controls. In order to assay the effects of TALI and LMO I expression on expression of other proteins, a series of Western blots were completed on all populations of engineered cells. It was determined that there were differences in expression of Bcl-2 and p16 as indicated by differences in band intensities on the blots. This is important because it implies an effect on protein levels by TAL 1 and LMO 1. However, there were no differences in protein expression levels for Bax or cyclin D1. This suggests that TAL1 and LMOI do not have any regulatory effects on these proteins. In addition, apoptotic assays were completed on all populations of cells. The results of both a TUNEL assay and ethidium bromide/acridine orange staining protocol showed TAL1- and LMO1expressing cells to have an increase in cell survival under starvation conditions and a lower frequency of apoptosis. Statistical analysis verified significant difference in the apoptosis assays. The data suggests an up-regulation of anti-apoptotic proteins. The finding of this research allow a clearer understanding of the process of leukemogenesis and may lead to a development of better cancer treatments. / Department of Biology

The overall objective of this work was to assess the suitability of poly(3-octylthiophene) (P3OT) to sustain MC3T3-E1 osteoblast attachment and growth. The central hypothesis was that specific P3OT film properties (i.e., thickness, film preparation conditions, and level of doping) are able to regulate osteoblast functions (i.e., attachment and proliferation). Discrete and combinatorial techniques were utilized to prepare and characterize thin films of P3OT, a semiconductor in its undoped state, and to study its interaction with MC3T3-E1 osteoblasts. In this work we demonstrate that P3OT is a suitable surface to sustain MC3T3-E1 attachment and proliferation with no observed cytotoxicity. We show that P3OT has an effect on MC3T3-E1 attachment and proliferation as area, circularity, and proliferation ratio are significantly different for P3OT compared to control surfaces. We also demonstrate that P3OT doping and film preparation conditions have an effect on osteoblast attachment and proliferation but that thickness over a low and high range does not affect osteoblast functions. This work is significant because it contributes to the growing area of conducting polymers in biomedical applications and establishes P3OT as a potential cell substrate that sustains MC3T3-E1 attachment and promotes high levels of cell proliferation.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2008. / Vita. Bibliography: p. 174-213.

La stérilisation des espèces aquacoles est recherchée en aquaculture pour remédier aux problèmes de reproduction intempestive et risques de pollution génétique de la reproduction des poissons d'élevage échappés avec des espèces endémiques. Nous avons cherché à caractériser certains des mécanismes mis en jeu lors d'une stérilisation induite par de fortes températures chez une espèce de poissons thermosensible d'intérêt majeur en aquaculture, le tilapia du Nil, Oreochromis niloticus. L'effet d'une température élevée de 37°C sur le développement gonadique a été étudié pendant la différenciation sexuelle chez des alevins et pendant la maturation sexuelle chez des juvéniles, provenant de descendances mixtes (XXXY) et monosexes femelles (XX) /mâles (XY). L'analyse immunohistochimique de la protéine vasa montre que des traitements à 37°C provoquent une diminution du nombre de cellules germinales (CG) qui résulte d'une augmentation du taux d'apoptose et/ou d'une réduction du taux de prolifération de ces cellules, aboutissant à une stérilité partielle et transitoire ou complète et permanente. L'expression du gène vasa, marqueur des CG, est inhibée dans les gonades des poissons traités à 37°C pendant un minimum de 60 jours ; ceci est corrélé avec la réduction du nombre de CG dans ces gonades. La baisse du niveau d'expression des gènes cyp19a1a et amh, respectivement marqueurs de cellules somatiques femelles et mâles, suggère que la température de 37°C affecte également le nombre ou la fonctionnalité des cellules de la granulosa chez les femelles et de Sertoli chez les mâles. Un traitement de 60 jours est nécessaire pour induire de tels effets et semble impacter préférentiellement les gonades femelles. Ce travail confirme que les fortes températures induisent une réduction du nombre de CGs, en modifiant la balance entre les taux d'apoptose et de prolifération cellulaire, conduisant à des stérilités partielles ou totales. / The sterilization of farmed fishes is searched in aquaculture to remedy in the problems of inconvenient reproduction and risk of genetic pollution of reproduction of escaped farmed fishes into the natural environment with endemic species. We characterized some of the mechanisms involved during induced-sterilization by high temperatures in the Nile tilapia, Oreochromis niloticus, a thermosensitive species of major interest in fish farming. The effect of 37°C-elevated temperature on gonadal development was studied during sexual differentiation in fry and during sexual maturation in juvenile, from mix-sexed (XX/XY), all-genetic female (XX) and male (XY) progenies. The immunochemistry analysis of vasa protein shows that 37°C-treatment causes germ cell (CGs) decrease, resulting from an increase of apoptosis rate and/or reduction of cell proliferation, leading to partial and transitory or complete and permanent sterilization.This work confirms that high temperatures induce a decrease of germ cell number, modifying the balance between rates of cell apoptosis and cell proliferation, leading to partial or complete sterilization.The expression profile of vasa gene, marker of germ cells, is inhibited in gonads of fish treated at least during 60 days at 37°C ; that is correlated with the reduction of germ cell number. The reduction of expression levels of cyp19a1a and amh genes, respectively markers of female and male somatic cells, suggests that the 37°C-temperature also affects the number or function of granulosa cells in females and Sertoli cells in males. A treatment of 60 days is necessary to induce such effects and seems to impact preferentially female gonads.

O objetivo do presente estudo foi avaliar os efeitos dos consumos agudo e crônico de etanol, da sua cessação e do co-tratamento com vitamina E em parâmetros de estresse oxidativo na mucosa e na atividade proliferativa no epitélio lingual de ratos. Após realizar-se uma revisão de literatura, observou-se que o acúmulo de acetaldeído (um metabólito do etanol), o polimorfismo das enzimas que metabolizam o álcool e o estresse oxidativo poderiam ser mecanismos envolvidos na patogênese do dano pelo álcool na mucosa bucal, sendo o estresse oxidativo escolhido como tema do estudo. Uma amostra de 48 ratos Wistar, fêmeas, com 3 meses, foram divididos em 6 grupos (álcool, álcool cessação, álcool vitamina E, controle, tween e vitamina E). O grupo tween recebeu solução de 5% de Tween 80 (veículo da vitamina E) por meio de gavagem enquanto os outros animais receberam solução salina. Após 14 dias os animais foram anestesiados e uma biópsia foi realizada no centro do dorso da língua. Esse material foi utilizado para análise do efeito do consumo agudo de etanol e do co-tratamento com vitamina E em parâmetros de estresse oxidativo (TBARS, grupos carbonil, atividade das enzimas antioxidantes superóxido dismutase-SOD e catalase-CAT e relação SOD/CAT). Após 60 dias de experimento, os animais do grupo álcool cessação tiveram o álcool substituído por água. Após 120 dias, os animais foram mortos e as línguas foram removidas. Esse material foi utilizado para a avaliação de parâmetros de estresse oxidativo (TBARS, grupos carbonil, SOD, CAT e relação SOD/CAT, imunoconteúdos da CAT e do Nrf2), da atividade proliferativa (AgNORS) e da possível relação entre ambos. Os animais submetidos ao tratamento agudo com álcool mostraram redução dos níveis de TBARS. A atividade da CAT foi mais alta no grupo álcool vitamina E após o tratamento agudo. O consumo crônico de etanol induziu aumento da atividade proliferativa no epitélio do ventre da língua quando comparado ao grupo controle. Esse efeito foi atenuando pela cessação do consumo. Além disso, houve aumento da atividade da CAT e diminuição dos níveis de TBARS nesse grupo. O grupo álcool vitamina E mostrou maior atividade proliferativa em relação ao grupo vitamina E e maior atividade da SOD, indicando que o co-tratamento com vitamina E não teve efeito protetor nos tecidos linguais. Conclui-se que o aumento da proliferação relacionado ao álcool no epitélio lingual não está associado ao estresse oxidativo. Uma vez que o dano provocado pelo álcool foi revertido, é possível sugerir que o álcool atua como um promotor de câncer bucal. / The aim of the present study was to evaluate the effects of acute and chronic alcohol consumption, alcohol consumption cessation and vitamin E cotreatment on rats tongue mucosa oxidative stress parameters and on tongue epithelium proliferative activity. After to conduce a literature review it was observed that acetaldehyde accumulation (an alcohol metabolite), the polimorphism of alcohol metabolization enzymes and oxidative stress could be mechanisms related to pathogenesis of alcohol damage in oral mucosa, and the former was choosen for the study. Forty-eight Wistar rats, female, 3 months-old were separated into 6 groups (alcohol, alcohol cessation, alcohol vitamin E, control, vitamin E, tween, vitamin E). The tween group received 5% tween 80 (vitamin E vehicle) by gavage, and the other animals received saline. At day 14, the animals were anesthetized and a biopsy was performed on tongue dorsum. In this sample, it was evaluated the acute alcohol consumption and vitamin cotreatment effects on oxidative stress parameters (thiobarbituric acid reactive substances-TBARS, carbonyl groups, superoxide dismutase activity-SOD and catalase activity-CAT and SOD/CAT ratio). After 60 days, 40% (v/v) ethyl alcohol was replaced with water in the alcohol cessation group. Vitamin E was given by gavage to animals in the alcohol/vitamin E and vitamin E groups. After 4 months, the animals were killed and the tongue was removed. Cell proliferation rate was evaluated using AgNOR quantification in histological sections. Oxidative stress parameters (TBARS, carbonyl groups, SOD and CAT, CAT and Nrf2 immunocontent) were quantified in tongue homogenates as well as the association between oxidative parameters and cell proliferation. The animals subjected to acute alcohol treatment showed TBARS decrease. SOD activity was lower and CAT activity was higher in alcohol and vitamin E group after acute treatment. Chronic alcohol consumption induced increase in cell proliferation rates of ventral tongue epithelium when compared to the Control group. This effect was attenuated after alcohol cessation. In addition, an imbalance of superoxide dismutase and catalase activities and decrase in TBARS were found in this group. The alcohol/vitamin E group showed higher proliferation rate than the Vitamin E group, suggesting that vitamin E cotreatment had no protective effects on the tongue tissues. It was concluded that the alcohol-related cell proliferation increase in tongue epithelium is not associated to oxidative stress parameters. Since the alcohol damage was reversible, it is possible to suggest that alcohol acts as an oral cancer promoter.

Made available in DSpace on 2015-07-22T20:50:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-10-27. Added 1 bitstream(s) on 2015-08-11T03:25:30Z : No. of bitstreams: 1 Publico-00376a.pdf: 1954101 bytes, checksum: ab9812845158d2c4c296f255d1304dac (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:30Z : No. of bitstreams: 2 Publico-00376a.pdf: 1954101 bytes, checksum: ab9812845158d2c4c296f255d1304dac (MD5) Publico-00376b.pdf: 1910033 bytes, checksum: 3104d18a155b521c486f36410aae2b4c (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:30Z : No. of bitstreams: 3 Publico-00376a.pdf: 1954101 bytes, checksum: ab9812845158d2c4c296f255d1304dac (MD5) Publico-00376b.pdf: 1910033 bytes, checksum: 3104d18a155b521c486f36410aae2b4c (MD5) Publico-00376c.pdf: 1815310 bytes, checksum: ed9fd0e797e536bfb039209f57c2ba21 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:30Z : No. of bitstreams: 4 Publico-00376a.pdf: 1954101 bytes, checksum: ab9812845158d2c4c296f255d1304dac (MD5) Publico-00376b.pdf: 1910033 bytes, checksum: 3104d18a155b521c486f36410aae2b4c (MD5) Publico-00376c.pdf: 1815310 bytes, checksum: ed9fd0e797e536bfb039209f57c2ba21 (MD5) Publico-00376d.pdf: 1673355 bytes, checksum: 0f8e3c112d9bf024a9c7e52fb4859991 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:31Z : No. of bitstreams: 5 Publico-00376a.pdf: 1954101 bytes, checksum: ab9812845158d2c4c296f255d1304dac (MD5) Publico-00376b.pdf: 1910033 bytes, checksum: 3104d18a155b521c486f36410aae2b4c (MD5) Publico-00376c.pdf: 1815310 bytes, checksum: ed9fd0e797e536bfb039209f57c2ba21 (MD5) Publico-00376d.pdf: 1673355 bytes, checksum: 0f8e3c112d9bf024a9c7e52fb4859991 (MD5) Publico-00376e.pdf: 1965795 bytes, checksum: 373c9589bb7d477fe5d31f7838237e5b (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:31Z : No. of bitstreams: 6 Publico-00376a.pdf: 1954101 bytes, checksum: ab9812845158d2c4c296f255d1304dac (MD5) Publico-00376b.pdf: 1910033 bytes, checksum: 3104d18a155b521c486f36410aae2b4c (MD5) Publico-00376c.pdf: 1815310 bytes, checksum: ed9fd0e797e536bfb039209f57c2ba21 (MD5) Publico-00376d.pdf: 1673355 bytes, checksum: 0f8e3c112d9bf024a9c7e52fb4859991 (MD5) Publico-00376e.pdf: 1965795 bytes, checksum: 373c9589bb7d477fe5d31f7838237e5b (MD5) Publico-00376f.pdf: 1677823 bytes, checksum: d93d3b40f2c273e474e7fef525f351c8 (MD5) / E2F1 pertence a uma família de fatores de transcrição e possui papel central no controle da expressão de genes relacionados à regulação da proliferação celular, pois ativa genes que participam da síntese de DNA. A atividade de E2F1 é regulada por meio da proteína pRB que, quando fosforilada por quinases associadas à ciclinas (Ciclinas/CDK) libera este fator de transcrição, promovendo assim a proliferação. A disfunção da complexa via de regulação da divisão celular pode acarretar em proliferação exacerbada, sendo a superexpressão de E2F1 bastante comum em diferentes tipos de tumores. Este fenômeno pode ser o principal fator para a alta proliferação de células tumorais. Desta forma, a inibição da atividade de E2F1 através de RNA de interferência (RNAi) pode ser promissora como tratamento para a diminuição da proliferação de células de melanoma. Assim sendo, objetiva-se neste trabalho inativar por RNAi o gene E2f1 em células B16mCAR, derivadas de melanoma de C57BL/6 e que superexpressam o receptor CAR, e averiguar os efeitos de sua ausência na proliferação celular, tanto in vitro como in vivo. / E2F1 belongs to a family of transcription factors and plays a central role in controlling the expression of genes related to regulation of the cell-cycle progression, since it activates genes involved in DNA synthesis. The activity of E2F1 is regulated by pRB protein, that when phosphorylated by cyclin-dependent kinases cyclins (Cyclins/CDK) releases this transcription factor, thereby promoting proliferation. The dysfunction of the complex regulatory pathway of cell division can lead to excessive proliferation, which overexpression of E2F1 is quite common in different types of tumors. This phenomenon may be the main factor for the high proliferation of tumor cells. Thus, inhibition of E2F1 activity by RNA interference (RNAi) may be promising as a treatment for decreased proliferation of melanoma cells. Therefore, the purpose of this work is the inactivation of the E2f1 gene through RNAi in B16mCAR cells, derived from C57BL/6’s melanoma and overexpresses the CAR receptor, and also verifies the effects of its absence on cell proliferation in vitro and in vivo. / TEDE / BV UNIFESP: Teses e dissertações

Made available in DSpace on 2016-08-29T15:34:42Z (GMT). No. of bitstreams: 1 tese_7863_Tese_Marcelo dos Santos.pdf: 3192836 bytes, checksum: 0f6dcd43e2d9f2f7922c37d18da58333 (MD5) Previous issue date: 2014-08-29 / O câncer de cabeça e pescoço é o quarto em incidência e o quinto em mortalidade na lista das neoplasias mais frequentes no mundo. Para o ano de 2014, são estimados pouco mais de 15 mil novos casos de câncer oral e de orofaringe no Brasil. Assim como outros tumores, o câncer oral e de orofaringe é uma doença multifatorial decorrente de fatores ambientais e genéticos, envolvendo diversas alterações em mecanismos moleculares importantes para a homeostase celular. A investigação de marcadores moleculares envolvidos nesses mecanismos tem sido o objeto de estudo de muitos grupos de pesquisa, uma vez que, apesar do crescente avanço em técnicas terapêuticas, a sobrevida desses pacientes pouco tem aumentado nas ultimas décadas. É sabido que a progressão do tumor depende de que suas células adquirem algumas competências, como por exemplo, evasão da apoptose mediada pelo sistema imunológico, disfunção no controle da proliferação celular, proliferação celular facilitada pela ativação angiogênica, adaptações celulares como resposta à hipóxia tumoral, ativação do mecanismo de sobrevivência celular e modificações epigenéticas dependentes de hipóxia. Considerando sua atuação nesses mecanismos, o presente trabalho teve o objetivo de avaliar o potencial das proteínas FAS, FASL, FGFR4, LEPR, HIF1-a, NDRG1 e JMJD1a e os polimorfismos Gly388Arg no gene FGFR4 e Gln223Arg no gene LEPR, como possíveis marcadores moleculares para as características clinicopatológicas e o prognóstico de pacientes com o carcinoma epidermóide oral e de orofaringe. Nossos resultados mostraram a expressão HIF1-alpha relacionada com a recidiva local da doença e sobrevida livre de doença local nos pacientes submetidos à radioterapia pósoperatória, sendo também relacionada com a microdensidade vascular tumoral. Adicionalmente, a expressão NDRG1 foi diferente quando comparadas as amostras de tecido tumoral e margem cirurgica não tumoral, também mostrando relação com a sobrevida da doença. Com relação ao FGFR4, a expressão e o polimorfismo Gly388Arg mostraram relação com a ocorrência do óbito e com a sobrevida da doença. Contudo, apenas a expressão FGFR4 mostrou relação com com a metástase linfonodal e a ocorrência de recidiva. O perfil FGFR4 proposto mostrou relação com a sobrevida da doença. Sobre o sistema FAS/FASL, ambas expressões mostraram relação com a ocorrência do óbito e o perfil FAS/FASL proposto foi significantemente relacionado com a sobrevida da doença. O polimorfismo Gln223Arg no gene LEPR mostrou relação com a sobrevida livre de doença e da doença específica, enquanto que a expressão LEPR mostrou relação com a metástase linfonodal. Á respeito da proteína JMJD1A, tanto a expressão nuclear quanto a citoplasmática mostraram relação com a metastase linfonodal. Contudo, apenas a expressão nuclear JMJD1A mostrou relação com a ocorrência de recidiva e com a sobrevida da doença. Em conclusão, nossos resultados sugerem que as proteínas e polimorfismos avaliados podem ser utilizados como marcadores moleculares para auxiliar na predição prognóstica de pacientes com carcinoma epidermóide oral e de orofaringe. / Head and neck cancer is the fourth in incidence and the fifth in mortality among the most frequent malignancies worldwide. For 2014, there has been estimated over 15 thousand new oral and oropharynx cancers in Brasil. Similar to other tumors, oral and oropharynx cancer is a multifactorial disease, caused by multiple environmental and genetic factors, involving alterations in molecular pathways and cellular homeostasis. The investigation of molecular markers involved in this process has been the object of my studies, especially because in spite of great advances in the molecular aspects of cancer, little progress has been made in the clinical outcome during the last decades. It is known that tumor progression depends on cellular aquisition of competences, such as apoptosis evasion, cell proliferation disregulation, angiogenic activation, cellular adaptation to hipoxia, cell survival mechanism activation and hypoxia dependent epigenetic changes. Therefore, the present work had the purpose to evaluate the potential of proteins FAS, FASL, FGFR4, LEPR, HIF1-a, NDRG1 and JMJD1a, as well as polymorphisms FGFR4 Gly388Arg and LEPR Gln223Arg, as putative molecular markers for clinicopathological tumor features or oral and oropharynx squamous cell carcinoma. Our results show that HIF1-1 expression was associated with local disease relapse and local disease-free survival in patients who undertook pos-operative radiotherapy and were also related to tumor vascular microdensity. In addition, NDRG1 expression was different in tumor tissue and non tumoral margins, but also showing an association with disease survival. FGFR4 polymorphism and expression showed a relation with death and disease survival. However, FGFR4 expression alone showed an association with lymph node metastasis and relapse. FGFR4 profile showed a relation with disease survival. FAS/FASL expression showed a correlation with death and its proposed profise was related with disease survival. LEPR Gln223Arg polymorphism was realted with disease free survival and disease specific survival, whereas LEPR expression was realted with lymph node metastasis. JMJD1A nuclear and cytoplasmic expression were related with lymph node metastasis. However, only nuclear expression was related with relapse and disease survival. In conclusion, our results suggest that proteins ans polymorphisms can be used as molecular markers to help predict prognosis in oral and oropharynx squamous cell carcinoma.

Made available in DSpace on 2014-06-11T19:31:09Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-02-23Bitstream added on 2014-06-13T18:41:47Z : No. of bitstreams: 1 denardi_ab_dr_jabo.pdf: 758766 bytes, checksum: efc4e6ede867b7e7930b46b41a712f2f (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Tendo em vista a relação da ciclooxigenase-2 (COX-2) com a progressão do câncer, este trabalho teve como objetivo investigar a expressão da atividade desta enzima com a imunorreativadade do Ki-67 , P53 e Caspase-3 no diagnóstico e prognóstico de neoplasias mamárias em cadelas. Para a realização deste estudo foram selecionadas 60 amostras de tumores mamários de cadelas. As amostras foram divididas em seis grupos, com 10 tumores em cada grupo, de acordo com a classificação histopatológica. Nos grupos adenoma, carcinoma com prognóstico bom e carcinoma com prognóstico ruim a seleção dos casos se deu pela classificação histológica e evolução clínica do tumor. Os outros 30 tumores foram representados por 10 amostras de carcinoma primário metastático, 10 de metástase pulmonar e 10 de carcinoma inflamatório. A avaliação da expressão da COX-2 (Dako, CX-294), Ki67 (Dako, M7240), P53 (Novocastra, CM1), Caspase-3 (Neomarkers, Asp175) foi conduzida por imunoistoquímica, utilizando-se a técnica de estreptoavidina-biotinaperoxidase. Em relação aos resultados houve correlação da expressão da COX-2 com o índice de proliferação celular Ki-67 no grupo dos adenomas, metástases pulmonares e carcinomas inflamatórios (P<O,05). Em todos os grupos estudados a COX-2 apresentou correlação com a proteína P53 (P<0,01). Observou-se correlação da expressão da ciclooxigenase-2 com a Caspase-3 no grupo dos carcinomas primários metastáticos e nas metástases pulmonares (P<0,05). A expressão da ciclooxigenase-2 variou de acordo com a agressividade das neoplasias mamárias nos casos de adenoma, carcinoma metastático e carcinoma não metastáticos (P<O,05). A sobrevida das pacientes com neoplasias mamária no pós-operatório está ligada à expressão da COX-2, no grupo dos adenomas, carcinoma com prognóstico bom e carcinoma com prognóstico ruim (P<O,01). / Considering the relationship between cyclooxygenase-2 (COX-2) with the cancer evolution, this study aimed to detect the expression of this enzyme with the immunoreactive of Ki-67, P53 and Caspase-3 in the diagnosis and prognostic of mammary neoplasms in bitches. Sixty mammary tumors samples were selected for the accomplishment of this study. The samples were divided into six groups, contenting 10 tumors in each group, in accordance to histopathology classification. In adenoma, good prognosis carcinoma and poor prognosis carcinoma groups the criteria for selection was made by histology classification and clinical tumor evolution. The others 30 tumors samples were represented by 10 samples of metastatic primary carcinoma, 10 of pulmonary metastases, and 10 of inflammatory carcinoma. The evaluation of the COX-2 (Dako, CX-294), Ki-67 (Dako, M7240), P53 (Novocastra, CM1), Caspase-3 (Neomarkers, Asp175) expression was achieved by immunohistochemistry, by means of streptavidine-biotine-peroxidase. About the results a positive correlation between COX-2 and the cellular proliferation index Ki-67 was found in the adenomas, pulmonary metastases, and inflammatory carcinomas groups (P<0,05). In ali studied groups the COX-2 presented correlation with P53 protein (P<O,01). There was correlation of cyclooxygenase-2 with caspase-3 in the primary metastatic carcinoma and in the pulmonary metastases group (P<0,05). The cyclooxygenase-2 expression varied in accordance with aggressiveness of mammary neoplasms in cases such adenoma, metastatic carcinoma, and non metastatic carcinoma (P<0,05). The post operative survival rate of patients with mammary neoplasms was linked to COX-2 expression in the adenomas, good prognosis carcinoma and poor prognosis carcinoma groups (P<O,01).