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Master's Dissertation
DOI
https://doi.org/10.11606/D.17.2020.tde-11022020-163949
Document
Author
Full name
Diogo Akio Kumagai Hashimoto
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2019
Supervisor
Committee
Garcia, Sergio Britto (President)
Brunaldi, Mariângela Ottoboni
Oliveira, Enio Chaves de
Uyemura, Sergio Akira
Title in Portuguese
Efeito inibitório da lidocaína na carcinogênese experimental do cólon
Keywords in Portuguese
Antineoplásico
Carcinoma colorretal
Lidocaína
Abstract in Portuguese
Embora existam técnicas avançadas de diagnóstico que possibilitaram o tratamento em seus estágios iniciais, o Câncer de Cólon Retal (CCR) ainda encontra-se entre os mais prevalentes no Brasil e no mundo. O tratamento de CCR ainda depende primariamente da ressecção cirúrgica e, sabe-se que o período perioperatório possui grande influência em casos de recorrência tumoral. A lidocaína, um importante anestésico local amídico, tem sido relacionada a efeitos antineoplásicos, in vitro e in vivo, através de seus efeitos diretos nas células tumorais ou através de regulação dos processos neuroimunoinflamatórios. Objetivos: avaliar o potencial antioneoplásico da lidocaína intraperitoneal e intrarretal, em dois regimes terapêuticos distintos (iniciação e pós-iniciação) em lesões préneoplásicas induzidas por instilações intrarretais do carcinógeno metilnitronitrosoguanidina em camundongos. Procedimentos: Para avaliar nossa hipótese, 42 camundongos foram separados em 7 grupos de 6 animais cada, a saber: grupo M (apenas MNNG), C (apenas solução salina), L5-IR (lidocaína por 5 semanas via IR), ML1-IR (MNNG seguido por lidocaína na semana 1 via IR), ML2,5- IR (MNNG seguido por lidocaína nas semanas 2 a 5, via IR), ML1-IP (MNNG seguido por lidocaína na semana 1 via IP) e ML2,5-IP (MNNG seguido por lidocaína nas semanas 2 a 5, via IP). A avaliação da progressão das lesões foi realizada através da contagem de criptas displásicas, índice apoptótico e imunoistoquímicas de PCNA, Akt, Caspase 3 e Survivina. Conclusões: A lidocaína mostrou-se eficaz na diminuição das lesões pré-neoplásicas, com diferenças significativas entre os grupos experimentais, quando comparados ao grupo controle. Não foram identificadas diferenças significativas entre os tratamentos no período inicial e pós-inicial da carcinogênese, nem entre os regimes terapêuticos intraperitoneal e intrarretal
Title in English
Inhibitory effect of lidocaine on experimental colon carcinogenesis
Keywords in English
Antineoplastic
Colorrectal carcinoma
Lidocaine
Abstract in English
Although there are advanced diagnostic techniques that have enabled treatment in its early stages, Colon Rectal Cancer (CRC) is still among the most prevalent in Brazil and worldwide. The treatment of CRC still depends primarily on surgical resection and it is known that the perioperative period has great influence in cases of tumor recurrence. Lidocaine, an important amidic local anesthetic, has been related to antineoplastic effects in vitro and in vivo through its direct effects on tumor cells or through regulation of neuroimmune inflammatory processes. Objectives: To evaluate the antioneoplastic potential of intraperitoneal and intrarectal lidocaine in two distinct therapeutic regimens (initiation and postinitiation) in pre-neoplastic lesions induced by intrarectal instillation of the Methylnitronitrosoguanidine carcinogen in mice. Procedures: To evaluate our hypothesis, 42 mice were separated into 7 groups of 6 animals each, namely: group M (MNNG only), C (saline solution only), L5-IR (5-week lidocaine via IR), ML1- IR (MNNG followed by lidocaine at week 1 in via IR), ML2,5-IR (MNNG followed by lidocaine at weeks 2 to 5 via IR), ML1-IP (MNNG followed by lidocaine at week 1 via IP) and ML2, 5-IP (MNNG followed by lidocaine at weeks 2 to 5 via IP). The evaluation of lesion progression was performed by counting dysplastic crypts, apoptotic index and immunohistochemistry of PCNA, Akt, Caspase 3 and Survivin. Conclusions: Lidocaine was effective in reducing pre-neoplastic lesions, with significant differences between experimental groups when compared to the control group. No significant differences were identified between treatments in the initial and post-initial period of carcinogenesis, nor between intraperitoneal and intraretal therapeutic regimens
 
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Publishing Date
2020-03-17
 
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