published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

published_or_final_version / Surgery / Master / Master of Medical Sciences

published_or_final_version / Surgery / Master / Master of Surgery

This study evaluated the effects of a partial glossectomy on: (1) tongue velocity, movement range, and height during speech and (2) vowel production. Videofluoroscopy and cine-MRI of single German words were used to study pre- and postoperative tongue movement in seven glossectomees. Postoperative principal component analyses demonstrated reduced complexity of lingual movement. For the videofluoroscopic data, four of the five patients exhibited reduced postoperative tongue velocity, while one patient exhibited a postoperative increase. Patients produced the words with a slower speech rate after the surgery. The mean differences between pre- and postoperative average tongue height and movement range were small and variable. The cine-MRI data did not indicate a change in postoperative tongue movement range and height. The acoustic results indicated that the vowel /u/ was produced with a more neutral tongue position, postoperatively. The present study demonstrated how tongue movement can be analyzed quantitatively based on videofluorospcopy and cine-MRI.

This study evaluated the effects of a partial glossectomy on: (1) tongue velocity, movement range, and height during speech and (2) vowel production. Videofluoroscopy and cine-MRI of single German words were used to study pre- and postoperative tongue movement in seven glossectomees. Postoperative principal component analyses demonstrated reduced complexity of lingual movement. For the videofluoroscopic data, four of the five patients exhibited reduced postoperative tongue velocity, while one patient exhibited a postoperative increase. Patients produced the words with a slower speech rate after the surgery. The mean differences between pre- and postoperative average tongue height and movement range were small and variable. The cine-MRI data did not indicate a change in postoperative tongue movement range and height. The acoustic results indicated that the vowel /u/ was produced with a more neutral tongue position, postoperatively. The present study demonstrated how tongue movement can be analyzed quantitatively based on videofluorospcopy and cine-MRI.

 Squamous cell carcinoma of the tongue has a low survival rate, with cure rate reduced by half if cervical lymph node metastasis is present. Standard treatment regimen includes surgical resection of the tumor, radiotherapy and chemotherapy. These treatment modalities, however, can result in irreversible side effects including loss of form and function of the tongue. So far, there is no efficient treatment regime targeting migration and invasion of tongue carcinoma. Curcumin is a natural polyphenol extracted from Curcuma longa. Recent studies indicated that curcumin is a potential anti-cancer agent. The anticancer effects have been demonstrated in numerous cancers including lung cancer, liver cancer, breast cancer, prostate cancer and melanoma. In head and neck cancers, the number studies is limited and its inhibitory effects in migration and invasion is rarely explored. To explore the global expression changes in tongue cancer, we used microarray to evaluate the genes responsive to curcumin treatment and focused on genes related to migration and invasion of tongue cancer cell line HN21B. The genes down-regulated by curcumin were validated in HN21B and two other tongue cancer cell line CAL27 and HN96 using qRT-PCR, Western blotting and immunostaining. The identified genes were quantified in tongue carcinoma tissues to examine whether it was up-regulated in human tongue tissues. Scratch wound assay and radial-migration assay were used to assess the degree of inhibition on migration. Adhesion and invasion assays were also performed to assess the adhesion and invasion ability. Transcriptomic analyses showed that MMP-10 was 2.36 fold down-regulated in HN21B in response to curcumin. Curcumin treatment resulted in down-regulation of MMP-10 gene in all the 3 tongue carcinoma cell lines at mRNA and protein levels. Out of 24 tongue carcinoma cases, 55% tumor tissue had obvious up-regulation of MMP-10 expression in comparison with the normal counterpart. Adhesion, migration and invasion ability of tongue carcinoma cell lines was significantly reduced upon IC50 of curcumin treatment in all TSCC cell lines. In conclusion, our results indicated that curcumin could reduce migration, adhesion and invasion in tongue carcinoma cells partly through reducing MMP-10 expression. Further investigations are warranted to explore the potential therapeutic use of curcumin to inhibit migration and invasion of tongue carcinoma cells. / published_or_final_version / Surgery / Master / Master of Philosophy

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Estudos publicados recentemente têm sugerido uma possível associação entre câncer e doença periodontal. A avaliação do impacto da doença periodontal sobre a patogênese de câncer de língua não foi estudada até o presente momento. Para tanto, o objetivo deste trabalho foi analisar o efeito da presença de doença periodontal induzida por ligadura e o desenvolvimento experimental de câncer de língua pelo carcinógeno 4-nitroquinolina 1-óxido (4NQO) em ratos Wistar. Foram utilizados 72 ratos machos Wistar com 60 dias de idade distribuídos em três grupos experimentais: Grupo 4NQO, no qual os animais foram expostos ao uma solução de 50 ppm do carcinógeno por 140 dias; Grupo Ligadura+4NQO, no qual foi induzida a doença periodontal por meio de ligadura no segundo molar superior direito por 14 dias e, após, exposição ao 4NQO por mais 140 dias; Grupo 4NQO+Ligadura, no qual os animais foram expostos ao 4NQO por 140 dias, após os quais doença periodontal foi induzida por ligadura durante 14 dias. O peso dos animais foi monitorado ao longo do estudo. Os animais foram mortos ao final do experimento e as peças maxilares e línguas foram analisadas em relação a perda óssea alveolar e lesões histopatológicas. Cinquenta e seis animais completaram o estudo. Não houve diferenças estatisticamente significativas na perda óssea alveolar no lado que não recebeu colocação de ligaduras; no lado com ligaduras houve uma maior perda óssea nos grupos a elas expostos. Observou-se uma menor ocorrência de carcinoma bem diferenciado nos animais que apresentavam, desde o início da exposição ao carcinógeno, a presença de inflamação periodontal (p<0,05). Conclui-se que a presença de inflamação periodontal parece ter potencial de modular o processo de carcinogênese. / Recent studies have suggested a possible association between cancer and periodontal disease. The evaluation of the impact of periodontal disease on the pathogenesis of tongue cancer has not been studied up to the present moment. Therefore, the objective of this study was to analyze the effect of the presence of ligature induced periodontal disease on the experimental development of tongue cancer by the carcinogen 4-Nitroquinoline 1-Oxide (4NQO) in Wistar rats. Seventy-two 60-day-old male Wistar rats were distributed in three experimental groups: Group 4NQO, in which animals were exposed to a 50 ppm solution of the carcinogen for 140 days; Group Ligature+4NQO, in which the periodontal disease was induced by ligature in the second upper molar for 14 days and, after, the exposition to 4NQO for more 140 days; Group 4NQO+Ligature, in which the animals were exposed to 4NQO for 140 days, and, after, periodontal disease was induced for 14 days. Weight of the animals was monitored during the whole study. Animals were sacrificed at the end of the experiment and the maxillary specimens and the tongues were analyzed in relation to alveolar bone loss and histopathological alterations. Fifty-six animals completed the study. No statistically significant difference was observed in the sides without ligatures; a higher degree of bone loss was observed in the side that received ligature. There was a lower occurrence of well-differentiated squamous cell carcinoma in the animals that presented, from the beginning of the exposition to the carcinogen, the presence of periodontal inflammation (p<0,05). It may be concluded that the presence of periodontal inflammation seems to be a potential modulator of the carcinogenic process.

Estudos publicados recentemente têm sugerido uma possível associação entre câncer e doença periodontal. A avaliação do impacto da doença periodontal sobre a patogênese de câncer de língua não foi estudada até o presente momento. Para tanto, o objetivo deste trabalho foi analisar o efeito da presença de doença periodontal induzida por ligadura e o desenvolvimento experimental de câncer de língua pelo carcinógeno 4-nitroquinolina 1-óxido (4NQO) em ratos Wistar. Foram utilizados 72 ratos machos Wistar com 60 dias de idade distribuídos em três grupos experimentais: Grupo 4NQO, no qual os animais foram expostos ao uma solução de 50 ppm do carcinógeno por 140 dias; Grupo Ligadura+4NQO, no qual foi induzida a doença periodontal por meio de ligadura no segundo molar superior direito por 14 dias e, após, exposição ao 4NQO por mais 140 dias; Grupo 4NQO+Ligadura, no qual os animais foram expostos ao 4NQO por 140 dias, após os quais doença periodontal foi induzida por ligadura durante 14 dias. O peso dos animais foi monitorado ao longo do estudo. Os animais foram mortos ao final do experimento e as peças maxilares e línguas foram analisadas em relação a perda óssea alveolar e lesões histopatológicas. Cinquenta e seis animais completaram o estudo. Não houve diferenças estatisticamente significativas na perda óssea alveolar no lado que não recebeu colocação de ligaduras; no lado com ligaduras houve uma maior perda óssea nos grupos a elas expostos. Observou-se uma menor ocorrência de carcinoma bem diferenciado nos animais que apresentavam, desde o início da exposição ao carcinógeno, a presença de inflamação periodontal (p<0,05). Conclui-se que a presença de inflamação periodontal parece ter potencial de modular o processo de carcinogênese. / Recent studies have suggested a possible association between cancer and periodontal disease. The evaluation of the impact of periodontal disease on the pathogenesis of tongue cancer has not been studied up to the present moment. Therefore, the objective of this study was to analyze the effect of the presence of ligature induced periodontal disease on the experimental development of tongue cancer by the carcinogen 4-Nitroquinoline 1-Oxide (4NQO) in Wistar rats. Seventy-two 60-day-old male Wistar rats were distributed in three experimental groups: Group 4NQO, in which animals were exposed to a 50 ppm solution of the carcinogen for 140 days; Group Ligature+4NQO, in which the periodontal disease was induced by ligature in the second upper molar for 14 days and, after, the exposition to 4NQO for more 140 days; Group 4NQO+Ligature, in which the animals were exposed to 4NQO for 140 days, and, after, periodontal disease was induced for 14 days. Weight of the animals was monitored during the whole study. Animals were sacrificed at the end of the experiment and the maxillary specimens and the tongues were analyzed in relation to alveolar bone loss and histopathological alterations. Fifty-six animals completed the study. No statistically significant difference was observed in the sides without ligatures; a higher degree of bone loss was observed in the side that received ligature. There was a lower occurrence of well-differentiated squamous cell carcinoma in the animals that presented, from the beginning of the exposition to the carcinogen, the presence of periodontal inflammation (p<0,05). It may be concluded that the presence of periodontal inflammation seems to be a potential modulator of the carcinogenic process.

Estudos publicados recentemente têm sugerido uma possível associação entre câncer e doença periodontal. A avaliação do impacto da doença periodontal sobre a patogênese de câncer de língua não foi estudada até o presente momento. Para tanto, o objetivo deste trabalho foi analisar o efeito da presença de doença periodontal induzida por ligadura e o desenvolvimento experimental de câncer de língua pelo carcinógeno 4-nitroquinolina 1-óxido (4NQO) em ratos Wistar. Foram utilizados 72 ratos machos Wistar com 60 dias de idade distribuídos em três grupos experimentais: Grupo 4NQO, no qual os animais foram expostos ao uma solução de 50 ppm do carcinógeno por 140 dias; Grupo Ligadura+4NQO, no qual foi induzida a doença periodontal por meio de ligadura no segundo molar superior direito por 14 dias e, após, exposição ao 4NQO por mais 140 dias; Grupo 4NQO+Ligadura, no qual os animais foram expostos ao 4NQO por 140 dias, após os quais doença periodontal foi induzida por ligadura durante 14 dias. O peso dos animais foi monitorado ao longo do estudo. Os animais foram mortos ao final do experimento e as peças maxilares e línguas foram analisadas em relação a perda óssea alveolar e lesões histopatológicas. Cinquenta e seis animais completaram o estudo. Não houve diferenças estatisticamente significativas na perda óssea alveolar no lado que não recebeu colocação de ligaduras; no lado com ligaduras houve uma maior perda óssea nos grupos a elas expostos. Observou-se uma menor ocorrência de carcinoma bem diferenciado nos animais que apresentavam, desde o início da exposição ao carcinógeno, a presença de inflamação periodontal (p<0,05). Conclui-se que a presença de inflamação periodontal parece ter potencial de modular o processo de carcinogênese. / Recent studies have suggested a possible association between cancer and periodontal disease. The evaluation of the impact of periodontal disease on the pathogenesis of tongue cancer has not been studied up to the present moment. Therefore, the objective of this study was to analyze the effect of the presence of ligature induced periodontal disease on the experimental development of tongue cancer by the carcinogen 4-Nitroquinoline 1-Oxide (4NQO) in Wistar rats. Seventy-two 60-day-old male Wistar rats were distributed in three experimental groups: Group 4NQO, in which animals were exposed to a 50 ppm solution of the carcinogen for 140 days; Group Ligature+4NQO, in which the periodontal disease was induced by ligature in the second upper molar for 14 days and, after, the exposition to 4NQO for more 140 days; Group 4NQO+Ligature, in which the animals were exposed to 4NQO for 140 days, and, after, periodontal disease was induced for 14 days. Weight of the animals was monitored during the whole study. Animals were sacrificed at the end of the experiment and the maxillary specimens and the tongues were analyzed in relation to alveolar bone loss and histopathological alterations. Fifty-six animals completed the study. No statistically significant difference was observed in the sides without ligatures; a higher degree of bone loss was observed in the side that received ligature. There was a lower occurrence of well-differentiated squamous cell carcinoma in the animals that presented, from the beginning of the exposition to the carcinogen, the presence of periodontal inflammation (p<0,05). It may be concluded that the presence of periodontal inflammation seems to be a potential modulator of the carcinogenic process.