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Avaliação da hipertermoterapia associada ao Paclitaxel, 5-Fluorouracil e 5-Fluorouracil mais Ácido Folínico no Tumor de Walker 256 implantado em estômagos de rato / Evaluation of the hyperthermotherapy associated with paclitaxel, 5-fluorouracil and 5-fluorouracil plus folinic acid on the Walker 256 tumor implanted in rat stomachs

OLIVEIRA, Paulo Ferdinando de Melo. Avaliação da hipertermoterapia associada ao Paclitaxel, 5-Fluorouracil e 5-Fluorouracil mais Ácido Folínico no Tumor de Walker 256 implantado em estômagos de rato. 2003. 235 f. Tese (Doutorado em Farmacologia) - Universidade Federal do Ceara. Faculdade de Medicina, Fortaleza, 2003. / Submitted by denise santos (denise.santos@ufc.br) on 2012-09-06T11:30:44Z
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Previous issue date: 2003 / The conventional chemotherapy drugs have not obtained success on the treatment of gastric cancer. The paclitaxel (Taxol®) showed to be effective on treating lung, breast and ovarian cancer. The 5-fluorouracil (5-FU) has shown promising results on the treatment of colon cancer. The folinic acid (Leucovorin®) reinforces the 5-FU cytotoxicity. Studies developed in Japan, United States and Europe suggest the use of chemotherapy associated with hyperthermia on the control of locally advanced disease. Objectives: Evaluate the influence of paclitaxel, 5-fluorouracil and 5-fluorouracil plus folinic acid, isolated and associated with hyperthermia, on the survival of rats with Walker 256 tumor implanted on their stomach, and observe the behavior of the original Walker 256 tumor implanted in the stomach of rats with no treatment and with the proposed chemotherapy treatments associated with hyperthermia. Methods: The Walker 256 tu-mor was implanted on the mucous layer of the rat stomach on the 3rd, 7th and 10th day after inoculation. The animals were treated with paclitaxel, 5-fluorouracil and 5-fluorourcil plus folinic acid isolated and associated with hyperthermia. Paclitaxel 25 mg/m2, 5-fluorouracil 130 mg/m2 and folinic acid 7 mg/m2 were used. The Whole-Body Hyperthermia was initiated 2 hours after the administration of the chemotherapic drugs, with 1 hour of duration. Results: The animals in-oculated with tumor showed a survival of 13.25 ± 0.53. The animals treated with Paclitaxel isolated showed a survival of 28.61 ± 0.82; 20.92 ± 1.77 and 20.07 ± 0.60 in the 3rd, 7th and 10th days, respectively, and those treated with Paclitaxel + hyperthermia showed a survival of 19.17 ± 1.20; 22.54 ± 1.47 and 17.92 ± 1.06 in the same periods. The animals treated with 5-fluorouracil isolated showed a survival of 16.16 ± 0.52; 15.57 ± 0.57 and 17.94 ± 0.46 in the 3rd, 7th and 10th days, respectively, and those treated with 5-fluorouracil + hyperthermia showed a survival of 14.45 ± 0.36; 16.36 ± 0.81 and 18.37 ± 1.86 in the same periods. The animals treated with 5-fluorouracil + folinic acid showed a survival of 14.89 ± 0.71; 16.56 ± 0.91 and 16.11 ± 0.67 in the 3rd, 7th and 10th days, respectively, and those treated with 5-fluorouracil + folinic acid + hyperthermia showed a survival of 17.60 ± 1.22; 15.42 ± 0.31 and 15.45 ± 0.39 in the same periods. Conclusions: The Walker 256 is a small cell tumor. The hyperthermia associated with chemotherapy using pacli-taxel, 5-fluorouracil and 5-fluorouracil plus folinic acid as treatment of Walker experimental tu-mor implanted in Wistar rat stomachs do not improved the survival. / As drogas quimioterápicas convencionais não têm obtido sucesso no tratamento do câncer gástrico. O paclitaxel (Taxol®) mostrou ser efetivo no tratamento dos cânceres de ovário, mama e pulmão. O 5-fluorouracil (5-FU) tem apresentado resultados promissores no tratamento do câncer de cólon. O ácido folínico (Leucovorin®) potencializa a citotoxicidade do 5-fluorouracil. Estudos desen-volvidos no Japão, Estados Unidos e Europa vêm sugerindo o uso de quimioterapia associada à hiper-termia no controle da doença localmente avançada. Objetivos: Avaliar a influência do paclitaxel, 5-fluorouracil e 5-fluorouracil mais ácido folínico, isolados e associados à hipertermia, na sobrevida de ratos com tumor de Walker 256 implantados no estômago, e observar o comportamento do tumor de Walker 256 original implantado em estômagos de rato sem tratamento e submetidos aos tratamentos quimioterápicos propostos, associados à hipertermia. Métodos: Implantou-se o tumor de Walker 256 na mucosa gástrica de rato no 3o, 7o, e 10o dias de inoculação do tumor. Os animais foram tratados com paclitaxel, 5-fluorouracil e 5-fluorouracil mais ácido folínico, isolados e associados à hipertermia. Foram administrados paclitaxel na dose de 25 mg/m2, 5-fluorouracil na dose de 130 mg/m2 e ácido folínico na dose de 7 mg/m2. A Hipertermia de Corpo Inteiro foi iniciada 2 horas após a administração dos quimioterápicos, tendo duração de 1 hora. Resultados: Os animais inoculados com tumor apresentaram uma sobrevida de 13,25 ± 0,53. Os animais tratados com Paclitaxel isolado apresentaram sobrevida de 28,61 ± 0,82; 20,92 ± 1,77 e 20,07 ± 0,60 no 3o, 7o e 10o dias, respectivamente, e aqueles trata-dos com Paclitaxel + hipertermia apresentaram sobrevida de 19,17 ± 1,20; 22,54 ± 1,47 e 17,92 ± 1,06 nos mesmos períodos. Os animais tratados com 5-fluorouracil isolado apresentaram sobrevida de 16,16 ± 0,52; 15,57 ± 0,57 e 17,94 ± 0,46 no 3o, 7o e 10o dias, respectivamente, e aqueles tratados com 5-fluorouracil + hipertermia apresentaram sobrevida de 14,45 ± 0,36; 16,36 ± 0,81 e 18,37 ± 1,86 nos mesmos períodos. Os animais tratados com 5-fluorouracil + ácido folínico apresentaram sobrevida de 14,89 ± 0,71; 16,56 ± 0,91 e 16,11 ± 0,67 no 3o, 7o e 10o dias, respectivamente, e aqueles tratados com 5-fluorouracil + ácido folínico + hipertermia apresentaram sobrevida de 17,60 ± 1,22; ±15,42 ± 0,31 e 15,45 ± 0,39 nos mesmos períodos. Conclusões: O tumor experimental de Walker 256 é um tumor de pequenas células. A hipertermia associada à quimioterapia, com paclitaxel, 5-fluorouracil, 5-fluorouracil mais ácido folínico como tratamento do tumor de Walker experimental implantado nos estômagos de rato Wistar, não melhorou a sobrevida.

Identiferoai:union.ndltd.org:IBICT/oai:www.repositorio.ufc.br:riufc/3737
Date January 2003
CreatorsOliveira, Paulo Ferdinando de Melo
ContributorsRibeiro, Ronaldo de Albuquerque, Moraes Filho , Manoel Odorico de
Source SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis
Sourcereponame:Repositório Institucional da UFC, instname:Universidade Federal do Ceará, instacron:UFC
Rightsinfo:eu-repo/semantics/openAccess

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