Evaluation of the immunomodulatory activity of thalidomide on tumor-associated macrophages in the 4T1 murine metastatic breast cancer model / [Avaliação do efeito imunomodulador da talidomida em macrófagos associados a tumores no modelo murino de câncer de mama metastático 4T1]

The present work evaluated the immunomodulatory effect of thalidomide (Thal) at different doses on tumor-associated macrophages (TAMs) using a mouse model of human breast cancer. Mice were inoculated with 4T1 cells in the left flank and treated with Thal once a day at concentrations of 50, 100, and 150mg/kg body weight from the 5th day until the 28th day of tumor inoculation. The tumors were sized, proliferation index and TAMs count were evaluated in primary tumors and metastatic lungs. In addition, the metastasis rate was evaluated in the lungs. Thal at 150mg/kg significantly decreased tumor growth, proliferation index, and TAMs infiltration in primary tumors. Conversely, a higher number of TAMs and lower proliferation index were observed in metastatic lungs in mice treated with 150mg/kg of Thal. Furthermore, Thal at 150mg/kg significantly decreased the metastatic nodules in the lungs. Our findings demonstrated that Thal treatment considerably decreased the primary tumor and lung metastasis in mice associated with different TAM infiltration effects in these sites.(AU)

No presente trabalho, foi avaliado o efeito imunomodulador de diferentes doses de talidomida em macrófagos associados ao tumor (TAMs), em um modelo murino de câncer de mama. Camundongos foram inoculados com células 4T1, na região do flanco esquerdo, e tratados com talidomida, uma vez ao dia, nas doses de 50, 100 e 150mg/k, por massa corporal, do quinto dia ao 28º dia de inoculação tumoral. Os tumores foram medidos, o índice de proliferação celular e a contagem de TAMs foram avaliados nos tumores primários e nos pulmões com metástases. Além disso, a taxa de metástases pulmonares também foi avaliada. A talidomida na dose de 150mg/kg diminuiu significativamente o crescimento tumoral, o índice de proliferação celular e a infiltração de TAMs nos tumores primários. Por outro lado, maior número de TAMs e menor índice de proliferação celular foram observados nos pulmões metastáticos, em camundongos tratados com 150mg/kg de talidomida. Ademais, a talidomida na dose de 150mg/kg diminuiu significativamente os nódulos metastáticos nos pulmões. Os resultados demonstraram que o tratamento com talidomida diminuiu o crescimento tumoral e as metástases pulmonares em camundongos, associado com diferentes efeitos na infiltração de TAMs nesses locais.(AU)

Suplementação com imunoestimulante em cadelas com neoplasia mamária maligna: aspectos hematológicos e bioquímicos / Immunostimulant supplementation for bitches with malignant mammary tumor: hematological and biochemical aspects

Os alimentos funcionais têm sido empregados como adjuvantes no tratamento do câncer de mama. Neste estudo avaliaram-se as respostas hematológicas e bioquímicas clínicas à ação de um alimento funcional administrado a cadelas com diagnóstico de neoplasia mamária maligna. Após a mastectomia, 16 cadelas foram divididas em dois grupos: suplementadas (S) e não suplementadas (NS) com um composto comercial contendo Saccharomyces cerevisiae, mananoligossacarídeos e nutracêuticos. Ambos grupos receberam tratamento quimioterápico com doxorrubicina e carboplatina, alternadamente, em intervalos de 21 dias, por oito sessões, totalizando 168 dias de tratamento. As avaliações clínicas e laboratoriais foram realizadas nos momentos de aplicação do tratamento. Os resultados dos perfis hematológico (hemograma, leucograma e plaquetograma) e bioquímico sérico (ureia, creatinina, albumina, bilirrubina total e direta, alanina aminotransferase, fosfatase alcalina e gama glutamiltransferase - GGT) foram analisados pelo teste de Kruskall Wallis. No grupo S comprovou-se elevação do peso corporal e não foram observados transtornos gastrointestinais ou outros sinais de alteração clínica ao longo do tratamento. Diferentemente no grupo NS, ocorreu perda de peso e alterações clínicas, como diarreia e vômito. No quadro hematológico, constatou-se leucopenia por linfopenia no grupo de cadelas NS e preservação do valores dentro dos parâmetros considerados normais para a espécie no grupo S. Dentre todas as variáveis da bioquímica clínica, constatou-se apenas a elevação da atividade sérica da GGT nos animais do grupo NS, sem alterações no grupo S. Conclui-se que cadelas com neoplasia mamária quando suplementadas com com alimento funcional imunoestimulante apresentam melhor condição clínica, hematológica e dos níveis bioquímicos, particularmente da GGT.(AU)

Functional foods have been used as adjuvant for breast cancer treatment of bitches. The aim of the present study was to evaluate hematological and clinical biochemistry response in female dogs diagnosed with malignant mammary tumors and supplemented with functional food. After the mastectomy, 16 bitches were divided into two groups: supplemented (S) and none supplemented (NS) with a commercial product of Saccharomyces cerevisiae, mannanoligosaccharides and nutraceuticals. Chemotherapy with doxorubicin and carboplatin was performed alternately at intervals of 21 days for eight sessions during 168 days of treatment. Clinical and laboratorial assessments was made at the treatment moments. The results of the hemogram (erythrogram, leukogram and platelet count) and serum biochemistry (urea, creatinine, albumin, total and direct bilirubin, alanine aminotransferase, alkaline phosphatase and gamma glutamyltransferase - GGT) were analyzed by Kruskal Wallis test. In the S group, increase body weight was observed, but gastrointestinal disorders or other clinical disorders were not detected over the treatment. In the NS group, loss of weight and clinical disorders were observed. All hematology parameters were normal in the S group; however, leukopenia and lymphopenia were detected in the bitches of the NS group. Among all the clinical biochemistry parameters tested, only serum GGT was increased in the NS group, with no changes in the S group. In conclusion, female dogs with mammary tumor supplemented with immunostimulant functional food have better clinical condition, they demonstrate normal levels of hematological and biochemical exams, particularly GGT.(AU)

Tarantula cubensis extract alters the degree of apoptosis and mitosis in canine mammary adenocarcinomas

In the present study, 13 clinical cases of canine mammary adenocarcinoma were evaluated in order to understand the effect of Tarantula cubensis extract (TCE) on tumor tissue. Punch biopsies were taken from the tumors before treatment with TCE. Subcutaneous injections of TCE were administered three times at weekly intervals (3 mL per dog). Between days 7 and 10 after the third injection, the tumor masses were extirpated by complete unilateral mastectomy. Pre- and post-treatment tumor tissues were immunohistochemically assessed. The expression of B-cell lymphoma 2 (Bcl-2) was found to be higher in pre-treatment compared to post-treatment tissues (p 0.05). The apoptotic index was determined to be low before treatment and increased during treatment. These results suggest that TCE may be effective for controlling the local growth of canine mammary adenocarcinoma by regulating apoptosis.

[Effects of dietary gamma-linolenic acid and docosahexaenoic acid with paclitaxel on the treatment of mice mammary carcinoma]

Breast cancer is one of the most important causes of death in women. One of the various gene expression involved in breast cancer is human epidermal growth factor receptor 2 [HER2/neu] gene expression increases. Factors of dietary affect on regulation of hormone secretion and the rate of breast cancer. One of these factors is amount and type of fats in diet. Gamma-linolenic acid [GLA] and Docosahexaenoic acid [DHA] are members of poly unsaturated fatty acids. In this study, effects of dietary GLA and DHA alone or together with paclitaxel on treatment of mice mammary carcinoma has been evaluated. Thirty female balb/c mice were divided in six groups randomly. Carcinomatous mass induced by tumor implantation method. Spontaneous breast adenocarcinoma of mice were used as tumor stock. The tumors of these mice were removed aseptically, dissected into 0.5 cm3 pieces. These pieces were transplanted subcutaneously into their right flank. GLA and DHA added to the mice diet two week prior to tumor implantation. At the end of intervention, tumors were removed and HER2 gene expression was measured. The weight of animal and tumor volume measured weekly. It was not significant change in the weight of animals that consumed DHA and DHA with taxol. Tumor volume in those groups that received corn oil with taxol [P<0.01], DHA [P<0.05] and DHA with taxol [P<0.001] showed significant decrease in comparison with control group. HER2 gene expression in DHA with taxol decreased significantly in comparison with control group [P<0.05]. Consumption of DHA oil with taxol causes decrease the volume of carcinoma mass. The future studies with large number of sample is needed to support this finding.

Estrogen receptor profiles: changes in mouse and rat mammary tumors by treatment with selective estrogen receptor modifiers

The aim of this work was to analyze the effect of estradiol [E2], medroxyprogesterone and the two selective estrogen receptor modulators [SERMs] [tamoxifen [Tam] and raloxifene [Ral]] on the estrogen receptor [ER] conformers profile performed by size exclusion HPLC in relation to hormone dependence of mammary tumors. Materials and Two types of mammary tumors were studied: tumors transplanted in BALB/c mice that are medroxyprogesterone acetate [MPA]-dependent for growth, and tumors induced in Sprague-Dawley rats by intraperitoneal injection of N-nitroso-N-methylurea [NMU]. Tumors from mice treated with MPA, E2, Tam or Ral and NMU-treated rats were analyzed and compared to that of control. The tumor conformer profiles were as follows: control and MPA-treated mice showed only one peak [oligomeric form]; E2-treated mice also showed only one peak [dimer]; Tam-treated mice showed one peak corresponding to a possible proteolytic fragment, and Ral-treated mice showed two peaks [oligomeric and a possible proteolytic fragment]. On the other hand, NMU-induced mammary tumors from rats showed three peaks [oligomeric, monomeric and proteolytic]. Our findings may indicate that SERMs affect the aggregation state of ER and thereby its ability to modulate genomic transcription mechanisms related to growth rate

Aspectos clínico e cirúrgicos do tumor mamário canino / Canine mammary neoplasia: clinical and surgical evolution

As neoplasias mamárias em cadelas representam importante parcela das neoplasias em cäes, merecendo atençäodos pesquisadores quanto ao diagnóstico, tratamento e prognóstico. No presente trabalho, 23 cadelas de várias raças ou cruzamentos, com idades entre 8 e 11 anos portadoras de neolasia mamária foram estudadas. Doze eram multíparas, 6 primíparas e 5 nulíparas. Todas eram da regiäo de Jaboticabal, SP, atendidas no Hospital Veterinário da FCAVJ-UNESP. Os animais foram avaliados clínica e radiológicamente e submetidos à punçäo aspirativa da massa anormal de tecido, com agulha fina. Dessa mesma massa foi também retirado, cirurgicamente, um fragmento para exame histopatológico. A maior incidência foi de carcinoma (52,17 porcento), seguidos por tumores mistos (17,39 porcento). Os tratamentos cirúrgicos empregados nos 23 animais foram: mastectomia regional ou mastectomia em bloco, com remoçäo de linfonodos. Quinze cadelas foram tratadas com doxorubicina, na dose de 20mg/m² e ciclofosfamida, na dose de 100mg/m², aos 7, 9 e 11 dias após o ato cirúrgico. Todos os animais tiveram evoluçäo favorável e, 12 meses após a cirurgia, 18 deles foram reavaliados, näo constatando nenhuma recidiva ou surgimento de metástase.

"In vivo" and "in vitro" antitumoral action of Larrea divaricata cav

We previously reported that aqueous extract of Larrea divaricata Cav had an antiproliferative activity upon tumoral lymphoid cells (BW 5147), without affecting normal immunity. To determine the probable mechanism of the inhibitory action of the extract upon cell growth, the participation of intracellular signals involved in the inhibition of cell proliferation, namely the activation of adenylate cyclase system was studied. The production of cyclic 3', 5 adenosine monophosphate (cAMP) in presence and absence of extract was analized. The extract increased the cAMP levels, but neither the cAMP production nor the inhibitory effect of the extract on proliferation were blocked by a beta adrenergic receptor antagonist (propranolol) or by histaminergic receptor antagonistis (cimetidine and mepyramine). So, we concluted that the antiproliferative activity of the extract of BW 5147 cells would be mediated by an increase in cAMP intracellular levels no related to the activation of the membrane receptors here studied. In parallel, the extract was administered to a pregnant rat with a spontaneous mammarian carcinoma and "in vivo"antitumoral activity was found.