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Master's Dissertation
DOI
10.11606/D.10.2006.tde-05012007-103648
Document
Author
Full name
Luiz Roberto Biondi
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2006
Supervisor
Committee
Mariano, Mario (President)
Dagli, Maria Lucia Zaidan
Jericó, Marcia Marques
Title in Portuguese
Influência do hipotireoidismo na progressão do melanoma experimental
Keywords in Portuguese
B16F10
Camundongos
Hipotireoidismo
Melanoma
Propiltiouracil
Abstract in Portuguese
Este trabalho teve por objetivo avaliar os efeitos do hipotireoidismo experimental induzido mediante utilização da droga propiltiouracil ou por tireoidectomia actínica, utilizando-se Iodo131, sobre o crescimento tumoral local e potencial metastático do melanoma murino, cepa B16F10 em camundongos C57BL6. O trabalho constituiu-se de dois experimentos distintos: 1. Influência do hipotireoidismo sobre o crescimento local e sobrevida, mediante indução do hipotireoidismo com propiltiouracil (PTU) a 0,05% na água de bebida e inoculação de células B16F10 por via subcutânea. 2. Influência do hipotireoidismo sobre o potencial metastático, onde os animais foram submetidos aos seguintes tratamentos: água (CTRL_M); indução do hipotireoidismo com propiltiouracil a 0,05% na água de bebida (PTU_M); indução do hipotireoidismo com iodo131 (I131_M) e do hipertireoidismo com L-tiroxina a 0,00005% na água de bebida (T4_M) e posterior inoculação de células B16F10, por via intravenosa. No experimento 1, os parâmetros avaliados consistiram na medida do volume tumoral e taxa de sobrevida. Os volumes tumorais variaram de 1,8 mm³ a 10.673,1 mm³. Na média diária dos volumes tumorais, o menor valor foi de 1,6 mm³ enquanto o maior volume obtido foi de 8140,9 mm³. A análise estatística das médias dos volumes, mediante teste de T não pareado, não indicou diferença significativa entre os grupos CTRL_L (controle) e PTU_L (tratado), com p = 0,795 para o teste de T e p = 0,5759 para o teste de F, para um intervalo de confiança de 95%. A média da sobrevida foi de 22 dias para o grupo CTRL_L e 21 dias para o grupo PTU_L. A analise estatística dos dados de sobrevida seguiu o Teste de Mantel-Haensze, não havendo diferença significativa na evolução da sobrevida entre os grupos, com p = 0,752 para um intervalo de confiança de 95%. No experimento 2, o parâmetro avaliado consistiu no número de nódulos metastáticos mediante contagem dos nódulos na superfície dos pulmões dos animais, após eutanásia. A distribuição de nódulos tumorais pulmonares apresentou média de 32 nódulos para o grupo CTRL_M; 91 nódulos para o grupo PTU_M; 23 nódulos para o grupo T4_M e 77 nódulos para o grupo I131_M. Houve diferença estatisticamente significativa (p < 0,01) entre os grupos CTRL_M versus PTU_M e I131_M e entre os grupos T4_M versus PTU_M e I131_M. Não houve diferença significativa (p > 0,05) entre os grupos CTRL_M versus T4_M e entre os grupos PTU_M versus I131_M. Os estudos estatísticos foram realizados mediante Teste de Analise de Variância simples (ANOVA) e aplicação de pós-teste de Dunnett, de múltipla comparação. Concluiu-se que o hipotireoidismo não interferiu no crescimento local da cepa B16F10 do melanoma murino em camundongos C57BL6 e significativamente alterou o comportamento metastático da referida cepa nesta linhagem isogênica, favorecendo a formação de nódulos metastáticos nos animais em que este estado patológico foi induzido, quer pela utilização de droga antitireoidiana PTU, quer pela tireoidectomia actínica com I131, no entanto, a administração de L-tiroxina não acarretou o efeito contrário
Title in English
Influence of hipothyroidism on experimental melanoma progression
Keywords in English
B16F10
Hypothyroidism
Melanoma
Mouse
Propylthiouracil
Abstract in English
The aim of this study was to evaluate the effects of hypothyroidism induced by propylthiouracil or by actinic thyroidectomy, using I131, on focal and methastatic tumor growth of murine melanoma, B16F10, in mice C57BL6. The study was consisted of two different assays: 1. the influence of hypothyroidism on the focal growth and survival rate, by hypothyroidism induction with propylthiouracil (PTU) 0.05% in drinking water and subcutaneous inoculation of B16F10 and 2. the influence of hypothyroidism on the methastatic potential, were the animals underwent the followed treatments: drinking water (CTRL_L), hypothyroidism induction by propylthiouracil on 0.05% in drinking water (PTU_M group), hypothyroidism induction by I131 (I131_M group) and hypothyroidism induction by L-tiroxine on 0.00005% in drinking water (T4_M group). B16F10 cells were intravenously inoculated in all groups. On the first assay, the tumor volume was measured and the survival rate was evaluated. The tumor volumes ranged from 1.8 mm³ to 10673.1 mm³. Regarding the daily mean of tumor volumes, the lowest volume was 1.6 mm³ while the highest one was 8140.9 mm³. A statistical analysis of the tumor volumes was performed using unpaired T test and it showed no significant difference between group CTRL_L (control) and group PTU_L (treated one) (with p=0.795 on T test and p= 0.5759 on F test, using a confidence interval of 95%). The survival rate mean was 22 days on group CTRL_L and 21 days on group PTU_L. The Mantel-Haenszel (logrank) test was used for statistical analysis of these data, and there was no significant difference on the survival rate between groups CTRL_L and PTU_L (with p=0.752 and confidence interval of 95%). On the second assay, the number of methastatic nodules on the lung surface after euthanasia was evaluated. Regarding the lung nodules distribution, 32 nodules were found on group CTRL_M, 91 nodules were found on group CTRL_M, 23 on group T4_M and 77 on group I131_M. There was a statistically significant difference (p<0.01) between groups CTRL_M and PTU_M / I131_M and between groups T4_M and PTU_M / I131_M. No significant difference was observed (p>0.05) between groups CTRL_M and T4_M and between groups PTU_M and I131_M. ANOVA test was used for statistical analysis, followed by multiple comparison Dunnett?s post test. It was concluded that hypothyroidism did not have any influence on the focal growth of the murine melanoma B16F10 in mice C57BL6 and significantly did alter the methastatic behavior of that clone in this isogenic lineage, enhancing the methastatic nodules formation in the animals who were induced to this pathological condition, either by PTU or by actinic thyroidectomy, using I131; however, the administration of L-tiroxine did not show the opposite effect
 
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Publishing Date
2007-02-28
 
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