Submitted by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2015-01-23T16:14:44Z No. of bitstreams: 5 lopes.pdf: 4584389 bytes, checksum: 490508b2570ae9d7329524ffc42068ef (MD5) license_url: 52 bytes, checksum: 3d480ae6c91e310daba2020f8787d6f9 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) license.txt: 2109 bytes, checksum: aa477231e840f304454a16eb85a9235f (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2015-02-10T10:36:20Z (GMT) No. of bitstreams: 5 lopes.pdf: 4584389 bytes, checksum: 490508b2570ae9d7329524ffc42068ef (MD5) license_url: 52 bytes, checksum: 3d480ae6c91e310daba2020f8787d6f9 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) license.txt: 2109 bytes, checksum: aa477231e840f304454a16eb85a9235f (MD5) / Made available in DSpace on 2015-02-10T10:36:20Z (GMT). No. of bitstreams: 5 lopes.pdf: 4584389 bytes, checksum: 490508b2570ae9d7329524ffc42068ef (MD5) license_url: 52 bytes, checksum: 3d480ae6c91e310daba2020f8787d6f9 (MD5) license_text: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) license.txt: 2109 bytes, checksum: aa477231e840f304454a16eb85a9235f (MD5) Previous issue date: 2013 / A presente disserta??o consiste em dois artigos cient?ficos, sendo um artigo original e outro de revis?o. Em um dos artigos, os autores fizeram uma revis?o da literatura sobre c?ncer e pr?polis, abordando a carcinog?nese experimental induzida quimicamente pelo 9,10-dimetil-1,2-benzantraceno (DMBA), a composi??o qu?mica da pr?polis e seus efeitos quimiopreventivos. O objetivo do artigo de pesquisa foi avaliar a rea??o tecidual da mucosa lingual de hamsters, submetida ? aplica??o di?ria e alternada de DMBA e extrato etan?lico de pr?polis (EEP) de uma apresenta??o comercial. Materiais e m?todos: 60 hamsters foram divididos em tr?s grupos, com dois per?odos experimentais, 13 e 20 semanas. A borda lateral da l?ngua foi submetida ? aplica??o t?pica, di?ria e alternada de DMBA 0,5 % e EEP 30 % (grupo EEP, n = 20), DMBA 0,5 % e extrato aquoso de pr?polis (EAP) (grupo EAP, n = 20), DMBA 0,5 % e soro fisiol?gico (grupo DMBA, n = 20). Realizou-se an?lise da ocorr?ncia dos tipos de altera??es cl?nicas e histol?gicas. Mensurou-se a ?rea e volume das altera??es cl?nicas, a ocorr?ncia das altera??es estruturais (AE) e citol?gicas (AC) do tecido epitelial escamoso com atipias e a ?rea histol?gica dos carcinomas de c?lulas escamosas (CCE). Para a an?lise estat?stica, aplicaram-se os testes ANOVA, qui-quadrado, Kruskal-Wallis e Mann-Whitney. Resultados: Para todas as vari?veis analisadas, n?o houve diferen?as significativas na compara??o entre os grupos nos dois tempos experimentais. Em 13 semanas ocorreu uma ?nica les?o de CCE no grupo EEP. Em 20 semanas, a maior ocorr?ncia de CCE tamb?m foi no grupo EEP. Conclus?o: o EEP, com teor alco?lico de 30 %, favoreceu a rea??o tecidual da inicia??o e da promo??o da carcinog?nese, por mecanismos ainda n?o elucidados. / ABSTRACT This dissertation consists of two papers, the first one is a review and the second is an original paper. In the first article, the authors reviewed the literature on cancer and propolis, addressing experimental carcinogenesis, chemically induced by 9,10-dimethyl-1,2-benzanthracene (DMBA), the chemical composition of propolis and its chemopreventive effects. The aim of the research paper was to evaluate the?tissue response?of tongue mucosa of hamsters, subjected to daily and alternating application of ethanolic extract of propolis (EEP) of a commercial presentation. Materials and methods: 60 hamsters were divided into three groups, and two experimental periods, 13 and 20 weeks. The lateral edge of the tongue underwent daily and alternate topical application of DMBA 0.5% and 30% EEP (EEP group, n = 20), DMBA and 0.5% aqueous extract of propolis (EAP) (EAP group; n = 20), and DMBA 0.5%?saline (DMBA?group, n =?20). The occurrence of types of clinical and histological changes was analysed. The area and volume of clinical changes, the occurrence of structural (AE) and cytological (CA) changes of squamous epithelial tissue with atypia and the histological area of squamous cell carcinoma (SCC) were measured. For statistical analysis, ANOVA, chi-square and Kruskal-Wallis and Mann-Whitney test were applied. Results: For all variables, there were no significant differences when comparing the groups in the two experimental periods. In 13 weeks, a single lesion of SCC in EEP group was observed. At 20 weeks, the highest occurrence of SCC was also in the group EEP. Conclusion: the EEP, with an alcohol content of 30% favored tissue reaction of initiation and promotion of carcinogenesis by mechanisms not yet elucidated.

Submitted by PPG Odontologia (odontologia-pg@pucrs.br) on 2017-10-03T13:27:09Z No. of bitstreams: 1 MARIA_NOEL__MARZANO_RODRIGUES_PETRUZZI_TES.pdf: 3641098 bytes, checksum: 3aa8ce331659fd0a8d765be0dc6f3d45 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-10-04T12:34:26Z (GMT) No. of bitstreams: 1 MARIA_NOEL__MARZANO_RODRIGUES_PETRUZZI_TES.pdf: 3641098 bytes, checksum: 3aa8ce331659fd0a8d765be0dc6f3d45 (MD5) / Made available in DSpace on 2017-10-04T12:36:41Z (GMT). No. of bitstreams: 1 MARIA_NOEL__MARZANO_RODRIGUES_PETRUZZI_TES.pdf: 3641098 bytes, checksum: 3aa8ce331659fd0a8d765be0dc6f3d45 (MD5) Previous issue date: 2017-06-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq / A late diagnosis of oral squamous cell carcinoma is related to high morbidity and mortality rates, as well as recurrence after treatment. Hence, there is an increasing interest in the validation of biological markers, chemoprevention strategies, and adjuvant treatment alternatives for combating oral cancer. The present Thesis evaluated the anticancer effect of cannabidiol (CBD) in a validated experimental murine model of oral carcinogenesis. Fifteen Fischer 344 rats were randomly divided into three groups of five animals each and subjected to a 7,12-dimethylbenzanthracene (DMBA) topical application on the ventral mucosa of their tongues, thrice a week. From the 2nd to the 12th week, they received intraperitoneally-administered vehicle (group 1), CBD 5 mg/kg (group 2), or CBD 10 mg/kg (group 3). After euthanasia, the tongues were dissected, processed and assessed by histological and immunohistochemical analysis. Group 2 and group 3 showed inhibition of severe oral epithelial dysplasia and carcinoma, and exhibited lower cell proliferation as compared to group 1. The null hypothesis was rejected when results showed statistical significance at a 0.05 level (confidence interval = 95%). In sequence are presented three manuscripts, first one regarding the original experiment and the two subsequent ones providing overall theoretical support. / O diagn?stico tardio do carcinoma espinocelular oral est? relacionado a um alto ?ndice de morbi-mortalidade e recorr?ncia ap?s o tratamento. Portanto, h? um crescente interesse na valida??o de marcadores biol?gicos que contribuam para o diagn?stico precoce, novas estrat?gias de quimiopreven??o e recursos adjuvantes para o tratamento dessa neoplasia maligna. A presente Tese centrou-se na avalia??o do efeito anticarcinog?nico do canabidiol (CBD) em um modelo experimental consagrado para a indu??o de altera??es epiteliais, com risco de malignidade, na mucosa oral de murinos. Para tanto, 15 ratos Fischer 344 foram aleatoriamente divididos em tr?s grupos, onde todos os animais tiveram o ventre de suas l?nguas expostas ao 7,12-dimetilbenzantraceno (DMBA) tr?s vezes por semana. A partir da segunda semana os grupos receberam por via intraperitoneal, ve?culo (grupo 1), 5 mg/Kg ou 10 mg/Kg de CBD (grupos 2 e 3, respectivamente). Na d?cima segunda semana ap?s o in?cio do experimento realizou-se a eutan?sia dos animais, dissec??o das l?nguas e processamento dos esp?cimes. As an?lises foram realizadas por meio das t?cnicas histol?gicas de rotina e imunoistoqu?mica. Observou-se a inibi??o do desenvolvimento de displasia oral severa e carcinoma, bem como a modula??o dos ?ndices de prolifera??o celular nos grupos 2 e 3 em rela??o ao grupo 1. A hip?tese nula p?de ser rejeitada, uma vez que os resultados obtidos apresentaram n?vel de signific?ncia de 0,05 (intervalo de confian?a = 95%). A seguir, apresentam-se tr?s artigos cient?ficos que descrevem primeiramente o experimento original desenvolvido e, em sequ?ncia, as revis?es da literatura para subsidiar a discuss?o do tema proposto.