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Abstract The Walker-256 tumor is an important experimental model that allow the development of therapies as the biological behavior of this tumor is similar that occur in humans. In front of the above considerations, the aim of this study was to describe the experimental model of Walker-256 tumor, identify the implantations sites as well as define a usual quantity of tumoral cells to induce the ascitic and solid tumor, according to the specialized literature. Were selected 45 articles using the keyword "Walker-256 tumor", free available. Were possible to observe that 58% (n=26) of the studies inoculate the tumor cells in the animals flank 33% (n = 15) in the tibia bone, 7% (n = 3) in the femur and 2% (n = 1) in the paw. The major quantitates of cells used were 8 x 107 (20%), 1 x 105 (13%), 1 x 106 (11%) and 2 x 107 (11%). After that, the site commonly used to inoculate was the flank and quantitate still a controversy, being 1x105 and 8x107 the concentrations more used.

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PURPOSE: To evaluate the antitumor activity of alcoholic extracts of green tea (Camella sinensis). METHODS: Four groups of six Wistar rats were inoculated intramuscularly with 10(6) Walker tumor cells/mL. During 10 days, the animals received by gavage either 0.9% saline solution (Group I; negative control), solution containing 20 mg/Kg of tamoxifen (Group II; positive control), solution containing 0.07 g/Kg alcoholic extract of C. sinensis (Group III), or solution containing 0.14 g/Kg alcoholic extract of C. sinensis (Group IV). Following euthanasia on the tenth day, the tumor, liver, kidneys and spleen were excised and weighed, and tumor volume and tumor growth inhibition were quantified. RESULTS: The average weight of the animals was greater in Group IV than in Group II (p=0.0107). Tumor weight was smaller in Group IV than in Group I (p=0.0062), but did not differ from Group II. Tumor volume was smaller in Groups II and IV than in Group I (p=0.0131). Tumor growth inhibition was observed in Groups II (44.67% ± 32.47), III (16.83% ± 53.02) and IV (66.4% ± 25.82) (p>0.05). The groups did not differ with regard to the weight of the excised organs. CONCLUSION: Alcoholic extracts of green tea have antitumor activity.

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PURPOSE: To evaluate the development of Walker 256 tumor in male Wistar rats treated with tacrolimus using an experimental kidney tumor model. METHODS: 40 male Wistar rats were divided into four groups: Tumor group (TU) (n=10), Tacrolimus-Tumor group (TT) (n=10), Tacrolimus group (TC) (n=10) and Control group (C) (n=10). Treatment with tacrolimus was performed in groups TT and TC. Under anesthesia, the right kidney of each animal of TU and TT was accessed through a supraumbilical incision and inoculated with a 0.1mL solution containing 2x10(6) tumor cells (Walker 256 carcinosarcoma tumor cells). Group TC was treated with a saline solution. All the animals of groups TC and TT were treated with tacrolimus (5mg/kg/day) by gavage for 15 days. TU group animals received saline by gavage for 15 days. On the 15th postoperative day, all animals were submitted to euthanasia and blood sampling for analysis of serum creatinine (Cr) and blood urea nitrogen (BUN). Abdominal gross examination was performed, the right kidney removed and prepared for histological analysis by hematoxylin-eosin staining. The resulting data were submitted to statistical analysis by ANOVA. RESULTS: Statistical significance was found when comparing creatinine level between groups TU, TT and TC -TT group culminated with a marked increased in creatinine levels (Cr=1.013 ± 0.3028 mg/mL), TU group (Cr=0.5670 ± 0.03536 mg/dL) P=0.00256, TC group (Cr =0.711 ± 0.1653 mg/mL) P= 0.02832. Statistical significance was found when comparing BUN levels in TT group (71.32 ± 17.14 mg/mL), compared with TU group (45.83 ± 5.046 mg/dL), P=0.000318. There were no statistically significant differences between groups TT and TC (61.23 ± 9.503 mg/mL) P=0.7242. Histological analysis showed a poor evolution in TT group with multiple foci of hemorrhage and cortical invasion by the Walker tumor. CONCLUSION: The Tacrolimus-treated group developed a more aggressive tumor and a drug-related nephrotoxic effect.(AU)

OBJETIVO: Avaliar as alterações na evolução do carcinosarcoma 256 de Walker, inoculado no rim de ratos Wistar, sob tratamento imunossupressor com o tacrolimus. MÉTODOS: Foram utilizados 40 ratos Wistar, machos divididos em quatro grupos de 10: grupo Tumor (TU), Tumor-Tacrolimus (TT), Tacrolimus (TC) e Controle (C). Os ratos dos grupos TU e TT foram inoculados com 0,1 mL de solução contendo 2x10(6) células do tumor de Walker no parênquima do rim direito. Os dos grupos TC e TT receberam tratamento com tacrolimus na dose de 5mg/kg de peso, via gavagem orogástrica durante 15 dias. Os ratos do grupo TU receberam solução salina isotônica pH 7,2. Ao 15º dia de evolução, todos foram submetidos à eutanásia. Amostras de sangue eram coletadas para dosagem de creatinina (Cr) e uréia (Ur) e posteriormente realizada nefrectomia para avaliação histológica. RESULTADOS: As dosagens séricas de creatinina foram maiores no grupo TT (Cr = 1,013±0,3028 mg/mL), que diferiu significantemente dos grupos TU (Cr=0,5670 ± 0,03536 mg/dL) com p=0,00256 e do TC (Cr=0,711 ± 0,1653 mg/mL) com p=0,02832. As dosagens séricas de uréia foram maiores no grupo TT (71,32 ± 17,14 mg/mL), que diferiu significantemente do grupo TU (45,83 ± 5,046mg/dL) com p=0,000318, mas comparado ao grupo TC (61,23 ± 9,503 mg/mL) não houve diferença significante (p=0,7242). No inventário da cavidade abdominal dos grupos TU e TT, observou-se presença macroscópica de tumor em todos os rins direitos; não foram evidenciadas efusões ascíticas, formação de bridas ou metástases tumorais em outros órgãos ou tecidos adjacentes aos rins direitos. CONCLUSÃO: O tacrolimus exerceu efeito nefrotóxico e induziu exacerbação do crescimento do tumor de Walker 256, quando implantado no rim de ratos Wistar.(AU)

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Cancer anemia is classified as an anemia of chronic diseases, although it is sometimes the first symptom of cancer. Cancer anemia includes a hemolytic component, important in the terminal stage when even transfused cells are rapidly destroyed. The presence of a chronic component and the terminal complications of the illness limit studies of the hemolytic component. A multifocal model of tumor growth was used here to simulate the terminal metastatic dissemination stage (several simultaneous inoculations of Walker 256 cells). The hemolytic component of anemia began 3-4 days after inoculation in 100% of the rats and progressed rapidly thereafter: Hb levels dropped from 14.9 +/- 0.02 to 8.7 +/- 0.06 from days 7 to 11 ( approximately 5 times the physiologically normal rate in rats) in the absence of bleeding. The development of anemia was correlated (r2 = 0.86) with the development of other systemic effects such as anorexia. There was a significant decrease in the osmotic fragility of circulating erythrocytes: the NaCl concentration causing 50% lysis was reduced from 4.52 +/- 0.06 to 4.10 +/- 0.01 (P<0.01) on day 7, indicating a reduction in erythrocyte volume. However, with mild metabolic stress (4-h incubation at 37oC), the erythrocytes showed a greater increase in osmotic fragility than the controls, suggesting marked alteration of erythrocyte homeostasis. These effects may be due to primary plasma membrane alterations (transport and/or permeability) and/or may be secondary to metabolic changes. This multifocal model is adequate for studying the hemolytic component of cancer anemia since it is rapid, highly reproducible and causes minimal animal suffering.

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Cancer anemia is classified as an anemia of chronic diseases, although it is sometimes the first symptom of cancer. Cancer anemia includes a hemolytic component, important in the terminal stage when even transfused cells are rapidly destroyed. The presence of a chronic component and the terminal complications of the illness limit studies of the hemolytic component. A multifocal model of tumor growth was used here to simulate the terminal metastatic dissemination stage (several simultaneous inoculations of Walker 256 cells). The hemolytic component of anemia began 3-4 days after inoculation in 100 percent of the rats and progressed rapidly thereafter: Hb levels dropped from 14.9 +/- 0.02 to 8.7 +/- 0.06 from days 7 to 11 (~5 times the physiologically normal rate in rats) in the absence of bleeding. The development of anemia was correlated (r2 = 0.86) with the development of other systemic effects such as anorexia. There was a significant decrease in the osmotic fragility of circulating erythrocytes: the NaCl concentration causing 50 percent lysis was reduced from 4.52 +/- 0.06 to 4.10 +/- 0.01 (P<0.01) on day 7, indicating a reduction in erythrocyte volume. However, with mild metabolic stress (4-h incubation at 37§C), the erythrocytes showed a greater increase in osmotic fragility than the controls, suggesting marked alteration of erythrocyte homeostasis. These effects may be due to primary plasma membrane alterations (transport and/or permeability) and/or may be secondary to metabolic changes. This multifocal model is adequate for studying the hemolytic component of cancer anemia since it is rapid, highly reproducible and causes minimal animal suffering.

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Ratos receberam implante de células tumorais (Walker 256) sendo sacrificados 7-21 dias mais tarde. Nesses animais verificou-se queda substancial dos níveis circulantes de T3 e T4 (15-60 por cento) e aumento dos de rT3 (1-3,7 vezes), caracterizando a síndrome do T3 baixo. Estas alteraçöes apresentaram alta correlaçäo estatística com o peso do tumor (1,2-25g; p<05 para T4, T3 e rT3) e em menor grau com o tempo de evoluçäo do tumor (7-21 dias; p<0,05 para T4 e T3). A atividade das enzimas lipogênicas, málica (EM) e glicose-6-fosfato desidrogenase (G-6P-D), no fígado e coraçäo desses animais apresentou diminuiçäo que beirou o limite da significância estatística [EM(17-29 por cento) e G-6-33)], dependendo do tempo de evoluçäo e do tecido estudado. Nesses mesmos animais, a atividade da enzima mitocondrial oxidativa alfa-glicerolfosfato desidrogenase (alfa-GPD), entretanto, apresentou diminuiçäo bastante maior (27-53 por cento) e sempre estatisticamente significativa. A injeçäo de dose saturante de T3 (100µg/100g de peso corporal, i.p.) em ratos portadores de tumor de Walker, 24h antes do scrifício, resultou em estimulaçäo das enzimas EM (1,7-3,3 vezes) e G-6P-D(33-150 por cento), maior que a observada nos respectivos animais controle. Entretanto, a induçäo na atividade da alfa-GPD mitocondrial causada pelo T3, embora, näo foi maior que a observada nos animais controle. Finalmente, a infusäo de doses fisológicas de T3(300ng/100g de peso corporal/dia), por 5 dias, através do implante subcurâneo de mini-bomba osmótica em ratos portadores de tumor, resultou em normalizaçäo da EM e G-6P-D em ambos os tecidos e num aumento significativo de alfa-GPD mitocondrial, embora näo suficiente para atingir a normalizaçäo. Esses resultados indicam que, ao contrário do que se poderia esperar, enzimas envolvidas em diferentes vias metabólicas (lipogênese e fosforilaçäo oxidativa) respondem de forma diferente às alteraçöes desencadeadas na síndrome do T3 baixo e a administraçäo de T3, sugerindo a existência de diferentes mecanismos adaptativos desencadeados nos tecidos alvo dos hormônios tireoideanos durante a instalaçäo dessa sídrome

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O tumor maligno é capaz de interferir com os valores do peso da carcaça, da albumina sérica e dos testes de hipersensibilidade, o mesmo acontecendo com a desnutriçäo. Procurando distinguir os efeitos dos dois fenômenos, ratos Wistar adultos foram submetidos a diferentes manipulaçöes nutricionais em associaçäo com o implante de células de carcinomassarcoma de Walker 256 (TU). Seis grupos de animais normais com resposta positiva ao Keyhole Limpet hemocyanin (KLH) foram estudados. Três grupos de ratos portadores de tumor foram submetidos a diferentes esquemas nutricionais: dieta aprotéica antes e depois do implante tumoral (grupo DDT); dieta aprotéica antes do implante, seguindo-se dieta normal (grupo DNT); dieta normal ao longo de todo o experimento (grupo NNT). Grupos controles sem tumor receberam os mesmos tratamentos nutricionais, constituindo os grupos DDC, DNC e NNC. O peso corpóreo dos ratos e da massa tumoral em evoluçäo foram determinados diariamente; os testes KLH foram realizados periodicamente e a albumina sérica foi dosada no dia do sacrifício dos animais. Os resultados indicam que o tumor maligno produz acentuadas modificaçöes na resposta imunológica; a desnutriçäo é responsável por anergia e perda de peso . Quando ambas as condiçöes estäo presentes, ocorrem pertubaçöes mais acentuadas. A realimentaçäo (grupos DNC e DNT) foi capaz de restabelecer o peso corpóreo e a resposta ao KLK, tanto nos ratos normais, quanto nos portadores de tumor, mas prejuízo subseqüente ocorreu em ratos portadores do tumor, depois da primeira semana de desenvolvimento tumoral. Conclui-se que o câncer potencializa os efeitos da desnutriçäo sobre o peso corpóreo e a resposta imunológica, com recuperaçäo temporária após adequada realimentaçäo

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