Made available in DSpace on 2016-04-04T18:27:47Z (GMT). No. of bitstreams: 1 Taisa Borges Grun.pdf: 713408 bytes, checksum: 77588a2820092fa9e412dae8803c2312 (MD5) Previous issue date: 2009-02-16 / Head and Neck cancer are responsible for about 5% of the new cases of cancer. Surveys indicate that prolonged stress can contribute to its development and can damage patient s treatment and quality of life. Appropriate social relationships promote better health conditions and moderate stress. The purpose of this essay was to verify the existence of stress and deficit of social skills in patients suffering from larynx cancer in one of Curitiba s cancer hospital. Twenty and one patients took part on the study. The instruments used were identification form, Inventory of Symptoms of Stress for Adults of Lipp and questionnaire of social skills. The results revealed 12 participants with stress. Results gotten from social skills questionnaire has showed high average. It was not verified statistics associations between stress and social skills values. The data did not support the initial hypothesis, since it was expected a higher number of participants with stress and deficit of social skills. Regarding the stress of the sample, a discussion is the probable intervening variables that might have helped to avoid the disease became an aversive situation for those patients until the time of the interview. As for social skills, a discussion is the adequacy of the instrument used for this sample. It is suggested replication of this research with larger samples and using another tool for evaluation of social skills. It was concluded that the data is valuable for a starting point for future researches with similar samples. / C?nceres de cabe?a e pesco?o s?o respons?veis por cerca de 5% dos novos casos de c?ncer. Pesquisas apontam que o stress prolongado pode contribuir para seu desenvolvimento e prejudicar o tratamento e a qualidade de vida do paciente. Rela??es sociais adequadas promovem melhores condi??es de sa?de e moderam o stress. O objetivo do presente trabalho foi verificar a exist?ncia de stress e d?ficit em habilidades sociais em pacientes com c?ncer de laringe de um hospital de c?ncer em Curitiba. Participaram do estudo vinte e um pacientes. Os instrumentos utilizados foram ficha de identifica??o, Invent?rio de Sintomas de Stress para Adultos de Lipp e question?rio de habilidades sociais. Os resultados revelaram 12 participantes com stress. Resultados obtidos com o question?rio de habilidades sociais n?o mostraram altas m?dias. N?o foram verificadas associa??es estat?sticas entre os valores referentes ao stress e ?s habilidades sociais. Os dados n?o apoiaram as hip?teses iniciais, uma vez que se esperava um maior n?mero de participantes apresentando stress e d?ficit em habilidades sociais. Com rela??o ao stress da amostra, discutiram-se prov?veis vari?veis intervenientes, que talvez tenham contribu?do para evitar que a doen?a se tornasse uma situa??o aversiva para esses pacientes at? o momento da entrevista. Quanto ?s habilidades sociais, discutiu-se a adequa??o do instrumento utilizado para essa amostra. Sugere-se a replica??o da presente pesquisa em amostras maiores e utilizando outro instrumento de avalia??o das habilidades sociais. Conclui-se que os dados obtidos s?o de valia como ponto de partida para futuras pesquisas com amostras semelhantes.

In addition, we investigated the cytotoxic effect of a widely used chemotherapeutic agent 5Fu on laryngeal squamous cell cancer cell lines and evaluated the role of p53 in 5Fu treatment. We found that the apoptosis and G1/S cell arrest mediated by 5Fu in laryngeal cancers is p53-independent but p21 WAF1/CIP1-dependent. We further demonstrated the effect of 5Fu on HPV16-associated laryngeal cancer cells. Using cytotoxicity assay and Annexin V staining, we proved that 5Fu induces apoptosis in all of the transfected cells in a dose- and time-dependent manner, suggesting that the process was not prevented by HPV16 E6 or E7. 5Fu induced the accumulation of active pRb and cyclin dependent kinase inhibitor p21WAF1/CIP1 together with an increase in Bak and Bax expression and a decrease in Bcl-2 levels in all the transfected cells. In addition, G1/S phase cell cycle arrest was associated with the antiproliferation activity of 5Fu in all cell lines. Through RT-PCR, 5Fu also presented some effects on the E6 and E7 oncoproteins of HPV16 in transfected UMSCC 12 cells. / Our results suggest that HPV16 E6 and E7 oncoproteins do not prevent 5Fu medicated apoptosis and G1/S cell arrest in laryngeal cancers. The anti-cancer effect of 5Fu is probably decided by the level of p21 WAF1/CIP1 while the sensitivity of laryngeal cancer cells responded to 5Fu treatment is associated with the increase of Bak or/and the decrease in Bcl-2, not with the HPV16 viral proteins and p53 status. 5Fu also presented some effects on the E6 and E7 oncoproteins of HPV16 in laryngeal cancer. However, the anti-viral effect of 5Fu still needs further investigation. / Our study indicated that (1) the evasion of apoptosis mediated by HPV16 E6 and E7 plays a critical role in laryngeal carcinogenesis; (2) HPV16 E6 or E7 plays an important role in regulating the expression of Bak, Bax and Bcl-2; (3) The degradation of Bak by HPV16 E6 is not caused by interacting with the promoter of Bak; (4) The induction of Bcl-2 is mediated through HPV16 E7; (5) HPV16 transfection does not interfere with the apoptosis and cell cycle arrest mediated by 5Fu in human laryngeal squamous cancer cells. / There is a growing body of evidence that human papillomavirus type 16 (HPV16) is involved in the development of human laryngeal cancer, especially in Chinese population. The two oncoproteins, HPV16 E6 and E7 that target host cell tumor suppressor proteins p53 and Rb respectively, may generate antiapoptotic effects and induce cell immortalization. However, the effect of both oncoproteins on apoptosis in laryngeal cancers is not completely clear. In this study, we demonstrated the possible mechanism of high risk HPV16 in laryngeal carcinogenesis and evaluated the effect of 5Fu on HPV16-positive laryngeal cancer cells. / We employed two human laryngeal cancer cell lines---UMSCC12 (with truncated p53) and UMSCC11A (with mutant but functional p53) in this study. These two cell lines were stably transfected with HPV16 E6, E7 or empty vector, pcDNA3.1, which provided a good foundation for further study on the carcinogenic mechanism of HPV16 E6 or E7 in human laryngeal cancers. Through Annexin V staining and protein stability assay, we found that the transfection of HPV16 E6 and E7 induced fewer spontaneous apoptosis in both UMSCC11A and UMSCC12 cells accompanied with enhanced protein stability of Bcl-2 and increased protein degradation of Bak. Similar results were obtained when E6- and E7-transfected cells exposed to apoptosis stimuli---TNF-alpha/CHX. These results indicate that stable transfection of E6 and E7 in human laryngeal cancer cells on one hand shortened the half-life of Bak protein, and on the other hand, enhanced the steady-state levels of Bcl-2 protein. In order to gain insight into the role of Bak and Bcl-2 in regulating apoptosis in HPV-associated laryngeal cancer cells, we performed transient transfection of Bcl-2 into E6- and E7-transfected cells. It is found that HPV16 E7 statistically enhanced the expression of Bcl-2 in laryngeal cancer, indicating that the induction of Bcl-2 require the transfection of HPV16 E7. Furthermore, Luciferase assay was performed to investigate whether the viral proteins E6 and E7 altered the stability of Bak through interaction with the promoter of Bak. Negative results were obtained, suggesting that E6 or E7 do not alter the transcription activity of Bak, indicating the degradation of Bak by E6 or E7 may be mediated through other mechanisms. / Liu Han-ching. / "August 2006." / Advisers: C. A. van Hasselt; George G. Chen. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1569. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 245-274). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2017-03-17T11:55:11Z No. of bitstreams: 1 Andréa Baldi de Freitas.pdf: 2935316 bytes, checksum: 8e78d079f9f3d9d0a47dccfce2ee3790 (MD5) / Made available in DSpace on 2017-03-17T11:55:11Z (GMT). No. of bitstreams: 1 Andréa Baldi de Freitas.pdf: 2935316 bytes, checksum: 8e78d079f9f3d9d0a47dccfce2ee3790 (MD5) Previous issue date: 2017-03-10 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Introduction: several methods of imaging have been used to investigate the swallowing process. Ultrasound images (USG) have stood out among the different techniques to assess the swallowing function, since it does not expose subjects to radiation, is low-cost, and enables the offering of food in usual situations. To our knowledge, to the present time there are no studies that establish a relation between swallowing and vocal quality using ultrasound images. Objective: to investigate swallowing from the physiological perspective (ultrasound) and relate findings to the perceptive findings of vocal quality adjustments, seeking to describe larynx, pharynx, and muscular tension behaviors in different tasks. Method: swallowing and speech ultrasound samples were collected from 28 healthy adults, with ages ranging from 18 to 66 years of age, both male and female. To analyze ultrasound data related to swallowing, we used a modified proposal for measures related to duration and excursion of the hyoid bone (elevation, anteriorization and return). For the perceptive analysis, utterances regarding the speech corpus were analyzed by a juror trained in elements of vocal dynamics and in the Vocal Profile Analysis Scheme - VPAS-PB script of vocal quality. Swallowing and speech data were investigated statistically based on multivariate analysis. Results: the data found for duration and excursion of the hyoid bone and vocal quality measures can be positively related to findings. Likewise, vocal quality findings regarding adjustments in larynx height, speech (of vocal fold vibration modes) and muscular tension adjustments of the vocal tract showed positive correlations with swallowing ultrasound measures. Conclusion: ultrasound imaging enabled assessing swallowing of individuals with no particular complaints and relate findings to vocal quality adjustments. It is necessary to expand the existing database to have access to a system to clinically classify hyoid bone excursion measures, relating them to vocal quality adjustments of subjects with swallowing alterations / Introdução: com o propósito de estudar a deglutição, vários métodos de investigação por imagem têm sido utilizados. Dentre as técnicas de avaliação da função da deglutição, a ultrassonografia (USG) ganha destaque, por não expor o sujeito à radiação, ter baixo custo e propiciar a oferta de alimento na situação habitual. Até o momento, não foram encontrados estudos que esboçam relação entre a deglutição e a qualidade vocal, utilizando a técnica de ultrassonografia. Objetivo: investigar a deglutição do ponto de vista fisiológico (ultrassonografia) relacionando aos achados perceptivos de ajustes de qualidade vocal, buscando descrever o comportamento laríngeo, faríngeo e de tensão muscular em diferentes tarefas. Métodos: foram coletadas amostras ultrassonográficas de deglutição e de fala de 28 sujeitos adultos saudáveis, na faixa etária de 18 a 66 anos, ambos os gêneros. Para a análise dos dados de ultrassonografia relacionados à deglutição, utilizamos proposta modificada para medidas de duração e de excursão do osso hioide (elevação, anteriorização e retorno). Para a análise perceptiva, as sentenças referentes ao corpus de fala foram analisadas por um juiz com formação no uso do roteiro Vocal Profile Analysis Scheme - VPAS-PB da qualidade vocal e elementos de dinâmica vocal. Os dados de deglutição e de fala foram tratados estatisticamente, por meio da análise de natureza multivariada. Resultados: para as medidas de duração e de excursão do osso hioide e qualidade vocal, encontramos dados que relacionam positivamente os achados. Da mesma forma, os achados de qualidade vocal referentes aos ajustes de altura de laringe, fonatórios (de modos de vibração de pregas vocais) e de tensão muscular do trato vocal também mostraram correlação positiva com as medidas ultrassonográficas da deglutição. Conclusão: pela ultrassonografia foi possível avaliar a deglutição de indivíduos sem queixas e relacionar com os ajustes de qualidade vocal. Há a necessidade de ampliar o banco de dados para possibilitar a criação de um sistema de classificação clínica da medida de excursão do osso hioide relacionando com os ajustes de qualidade vocal dos sujeitos com alteração de deglutição

Thesis. 1976. Ph.D.--Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. / Microfiche copy available in Archives and Engineering. / Vita. / Bibliography: leaves 138-140. / Ph.D.

Thesis (Sc.D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1980. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Vita. / Bibliography: leaves 264-270. / by Ursula Gisela Goldstein. / Sc.D.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1981. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND ENGINEERING. / Bibliography: leaves 185-192. / by Marcia Ann Bush. / Ph.D.

Introdução: O prognóstico dos carcinomas epidermóides de laringe é limitado e a taxa de sobrevida em cinco anos é menor que 70%. A relação de características clínicas e epidemiológicas tem sido investigada na sobrevida de pacientes com tumores de laringe, mas pouco se conhece sobre o efeito dos polimorfismos genéticos no prognóstico da doença. Objetivo: Estudar o papel dos polimorfismos genéticos de genes relacionados aos processos de invasão e metástase (MMP1 e MMP3), de inflamação (Interleucina 2, Interleucina 6, LTA) e reparo de DNA(XRCC1) no prognóstico do carcinoma epidermóide de laringe. Material e métodos: Coorte com 170 pacientes com carcinoma epidermóide de laringe,confirmados por exame anátomo-patológico. Os casos tiveram origem em estudo caso-controle conduzido em cinco hospitais de São Paulo, um hospital em Porto Alegre e outro em Goiânia. As informações sobre o status vital dos pacientes foram levantadas dos prontuários médicos e dos bancos de óbitos municipais e estaduais. A extração do DNA das amostras de sangue dos pacientes foi realizada pelo Instituto de Medicina Tropical da USP e a genotipagem dos polimorfismos genéticos pela Fundação Hemocentro de Ribeirão Preto da Faculdade de Medicina da USP. Resultados: Os polimorfismos genéticos estudados (MMP1 1607, MMP1 -519,MMP3 -1171, IL2 -384, IL2 114, IL6 -174, LTA 252 e XRCC1) não apresentaram efeitos com significância estatística na sobrevida global ou específica pela doença quando analisados isoladamente. Para a sobrevida global, o consumo excessivo de álcool, em g/L/dia, reduziu a sobrevida dos pacientes (80-119 g/L/dia: hazard ratio(HR)=4,0 intervalos com 95% de confiança (IC95%)=1,10-14,53; _120 g/L/dia: HR=5,6 IC95%=1,71-18,24). No modelo de Cox múltiplo, quando ajustados pelo polimorfismo genético MMP3 -1171, a sobrevida piorou para esses pacientes (80-119 g/L/dia: HR=4,9 IC95%=1,07-22,91; _120 g/L/dia: HR=6,3 IC95%=1,49-26,84). Para a sobrevida específica pela doença, o estadiamento clínico IV reduziu a sobrevida dos pacientes (HR=3,5 IC95%=1,67-7,28). No modelo de Cox múltiplo,com ajuste pelos polimorfismos genéticos IL6 -174 e MMP1 1607, a sobrevidaespecífica pela doença piorou para esses pacientes (HR=4,7 IC95%=1,38-16,25).Conclusões: Na coorte examinada, somente três dos oito polimorfismos genéticos estudados relacionaram-se com a sobrevida global e específica pela doença, porém apenas alterando o efeito dos valores dos HR brutos dos fatores consumo de álcool e estadiamento clínico, respectivamente na sobrevida global e sobrevida específica pela doença. Isoladamente, nenhum polimorfismo genético estudado interferiu na sobrevida dos pacientes com câncer de laringe. / Introduction: The prognosis of laryngeal squamous cell carcinoma is limited and survival rate is lower than 70%. The relationships between clinical and epidemiological characteristics have been fully investigated on the survival of patients with laryngeal tumors, but the effect of genetics polymorphisms on squamous cell carcinoma of larynx is not well-known. Objective: To study the role of genetic polymorphisms of genes related to the processes of invasion and metastasis (MMP1 and MMP3), inflammation (Interleukin 2, Interleukin 6, and LTA) and repair of DNA (XRCC1) in the prognosis of laryngeal squamous cell carcinoma. Material and methods: Cohort with 170 laryngeal squamous cell carcinoma patients with histological confirmation. The cases have their origin in a case-control study carried out in hospitals of Sao Paulo, Porto Alegre and Goiania. The information about vital status of patients had been raised from medical records. The extraction of DNA was carried out by Institute of Tropical Medicine of USP and genotyping was carried out by the Center of Cellular Therapy of the Hemocentro of Ribeirao Preto of Medical School of USP. Results: The studied genetic polymorphisms (MMP1 1607, MMP1 -519, MMP3 -1171, IL2 -384, IL2 114, IL6 -174, LTA 252 and XRCC1), separately analyzed, did not have any statistical significant effect on the overall and cause-specific survival. High levels of alcohol consumption (g/L/day) reduced the overall survival (80-119 g/L/day: hazard ratio(HR)=4.0 intervals with 95% of confidence (95%CI)=1.10-14.53; _120 g/L/day:HR=5.6 95%CI=1.71-18.24). Multiple Cox model revealed, when adjusted for MMP3 -1171 genetic polymorphism, lower survival for those patients (80-119g/L/day: HR=4.9 95%CI=1.07-22.91; _120 g/L/day: HR=6.3 95%CI=1.49-26.84). The clinical staging (CS) IV was a factor for low cause-specific survival (CS IV:HR=3.5 95%CI 1.67-7.28). In the multiple Cox model, adjusted for genetic polymorphism IL6 -174 and MMP1 1607, the survival of those patients droppe(HR=4.7 95%CI=1.38-16.25). Conclusions: In this cohort, only three of eight genetic polymorphisms studied were showed to be related with overall and causespecific survival, however only modifying the effect of unadjusted HR of alcohol consumption and tumor clinical staging in the overall and cause-specific survival respectively. None of the studied genetic polymorphisms, when analyzed separately,affected the survival of laryngeal cancer patients.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2014-09-03T19:05:12Z No. of bitstreams: 2 Análise epidemiológica dos cânceres de pulmão e da laringe em 30 anos.pdf: 985787 bytes, checksum: 31e7777e04381a2403335ed5d4f54552 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2014-09-03T19:05:12Z (GMT). No. of bitstreams: 2 Análise epidemiológica dos cânceres de pulmão e da laringe em 30 anos.pdf: 985787 bytes, checksum: 31e7777e04381a2403335ed5d4f54552 (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2014-06-26 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / Introduction: Studies have shown a relationship between smoking and various cancers, especially in the respiratory tract, causing major impact on public health. Lung cancer is the leading cause of cancer death in the world, accounting for 20 %, while Laryngeal cancer represents 3 %. Objective: To analyze trends in incidence and mortality from lung and larynx cancer in Goiania in 20 years and to assess trends in mortality for these cancers, over the past 30 years for the Brazilian regions. Methods: All incident cases of lung cancer and larynx were obtained from the database registered in Goiania RCBP/ACCG and deaths were extracted from the Mortality Information System (SIM/MS) for both, Goiania as for other Brazilian regions. Incidence rates and standardized mortality rates were calculated using the world standard population and calculating the trend used the Poisson regression model using Joinpoint Regression Program, Version 4.0.4. Graphs and tables were made using the Excel 2013 software. Results: Two points were analyzed: the first showed that the trend of incidence for lung and larynx cancers in both sexes and age groups in Goiania, were in contrast to trend mortality for lung cancer in women over 50 increased by 2.5% per year, during the study period in Goiania. The second article assessed the trends in national mortality for cancers of the lung and larynx showing that in Brazil, the mortality rates for lung cancer ranged from 14.30 to 15.52/100,000 in men and 3.99 to 7.37/100,000 in women from 1980 to 2009. Laryngeal cancer in this variation was from 3.76 to 3.59/100,000 for males and 0.47 to 0.38/100,000 in the female. The analysis of trends showed increased mortality for lung cancer in both male and female genders respectively (APC 1.7 %; 95% CI 1.6 to 1.8, p < 0.001, and APC 4.1%; 95% CI 3.9, the 4.2, p < 0.000). Mortality rates for laryngeal cancer in men the increase was 1.4 % (95% CI 1.2 to 1.5 p < 0.0001), the rate for women increased by 1.3 % (95 % 0.9 -1.6, p < 0.0001) during the study period, so there were similar for both neoplasms. Conclusion: Incidence trends were stable for lung and larynx cancer in both sexes and age groups, in contrast, for women aged over 50 years there has been increasing trends in mortality in Goiania. When Abstract xviii analyzing mortality at the national level, there was decline for lung cancer in south and southeast whereas for cancer of the larynx, there was a decrease only in southeastern Brazil. / Introdução: Estudos têm mostrado a relação entre fumo e diversos cânceres, especialmente do trato respiratório, causando grande impacto na saúde pública. O câncer de pulmão é a principal causa de morte por câncer representando 20% no mundo, enquanto que o câncer da laringe representa 3% destas mortes. Objetivo: Analisar as tendências da incidência e mortalidade por câncer de pulmão e laringe, em Goiânia, em 20 anos, bem como avaliar a tendência da mortalidade para esses cânceres nos últimos 30 anos para as regiões brasileiras. Métodos: Os casos incidentes de câncer de pulmão e laringe foram obtidos no banco de dados registrados no Registro de Câncer de base Populacional (RCBP-Goiânia) da Associação de Combate ao Câncer em Goiás (ACCG) e os óbitos foram extraídos do Sistema de Informações de Mortalidade (SIM) do Ministério da Saúde (MS), tanto para Goiânia quanto para as demais regiões brasileiras. Foram calculadas taxas de incidência e mortalidade padronizadas utilizando a população padrão mundial, e para o cálculo da tendência utilizou-se o modelo de regressão de Poisson, utilizando o software Joinpoint Regression Program, Version 4.0.4. Gráficos e tabelas foram confeccionadas utilizando o software excel 2013. Resultados: Foram analisados dois pontos: o primeiro verificou a tendência de incidência para o câncer de pulmão, e da laringe em ambos os sexos e grupos etários em Goiânia, cujo resultado demonstrou estabilidade no período estudado. A tendência da mortalidade para o câncer de pulmão, em mulheres acima de 50, aumentou em 2,5% ao ano, em Goiânia. As tendências da mortalidade no Brasil, para os cânceres de pulmão e da laringe, mostraram que as taxas de mortalidade variaram de 14,30 a 15,52/100000, em homens e 3,99 a 7,37/100000, em mulheres, para o câncer de pulmão, entre 1980 a 2009. Para o câncer da laringe essa variação foi 3,76 a 3,59/100000 no sexo masculino e 0,47 a 0,38/100000 no feminino. A análise de tendências evidenciou aumento da mortalidade para o câncer de pulmão em ambos os sexos, masculino e feminino, respectivamente (Média Percentual Anual (MPA) 1,7% IC95% 1,6 a 1,8; p<0,001; e MPA 4,1% IC95% 3,9 a 4,2; p<0,000). As taxas de mortalidade Resumo xvi para câncer da laringe para os homens aumentou 1,4% ao ano (IC95% 1,2- 1,5 p<0,0001), para as mulheres, esse aumento foi 1,3% (IC95% 0,9 -1,6; p<0,0001), portanto foram semelhantes para ambos os sexos. Conclusão: As tendências de incidência se mantiveram estáveis para o câncer de laringe e do pulmão, em ambos os sexos e grupos de idade, em contrapartida, para mulheres com idade acima de 50 anos houve tendências de aumento da mortalidade em Goiânia. Ao analisar-se a mortalidade a nível nacional, observou-se declínio para o câncer de pulmão no sul e sudeste enquanto que para o câncer da laringe, houve declínio apenas na região sudeste do Brasil.

Introdução: A ciclina D1 constitui um importante regulador do ciclo celular e pode funcionar como co-regulador de transcrição. A superexpressão da ciclina D1 tem sido associada ao desenvolvimento e progressão do câncer. A degradação irregular da ciclina D1 pode ser responsável pelos seus níveis elevados em algumas neoplasias malignas. A ciclina D1, além disso, modula indiretamente a estrutura da cromatina e transcrição de genes envolvidos na proliferação e diferenciação. Mutações, amplificação e superexpressão da ciclina D1, que alteram a progressão do ciclo celular, são observadas frequentemente em várias apresentações de neoplasias malignas, incluindo o carcinoma epidermóide de laringe, e as elucidações inferidas destas observações podem trazer melhor entendimento à oncogênese. Objetivo: O objetivo deste estudo foi comparar a expressão imunoistoquímica de ciclina D1 e a ocorrência de metástase linfática em estádios III e IV de carcinoma epidermóide de laringe. Métodos: Estudo retrospectivo, coorte longitudinal, por avaliação imunoistoquímica e quantificação digital da imunoexpressão nuclear e citoplasmática de ciclina D1 em espécimes de tumor preservados em parafina oriundos de pacientes consecutivos submetidos à cirurgia oncológica radical, entre 1999 e 2004. A sobrevida global dos pacientes foi avaliada, bem como a idade, sexo, tabagismo, estado de comprometimento linfático, grau de diferenciação e estadiamento (pTNM). A análise estatística teve como significância valores de p< 0.05. A curva de sobrevida foi elaborada utilizando o método de Kaplan-Meier. Resultados: Houve imunomarcação citoplasmática em 566 (1,2%) células, imunomarcação nuclear em 13788 (29,6%) células, a relação do IPc e IPn foi de 0,007 (0,7%), ausência de imunomarcação celular foi observada em 32210 (69,1%) células, perfazendo um total de 46554 (100%) células investigadas. Entre os 28 (59,5%) casos que não apresentaram metástase linfática, o IPn foi de 26,8 (9,7 - 46,9) e o IPc foi de 0,1 (0 0,3); naqueles 19 (40,4%) em que foi observada metástase linfática, o IPn foi de 26,7 (16,7 39,0) e o IPc foi de 0,3 (0 - 1,0). Conclusões: Não houve associação estatisticamente significante entre expressão nuclear e citoplasmática de ciclina D1, em carcinoma epidermóide primário de laringe, e ocorrência de metástase linfática cervical, graus de diferenciação histológica, bem como recidiva loco-regional e metástase hematogênica. O presente estudo não subsidia a superexpressão de ciclina D1 como fator limitante de sobrevida global / Background: Cyclin D1 is an important regulator of cell cycle progression and can function as a transcriptional co-regulator. The overexpression of cyclin D1 has been linked to the development and progression of cancer. Abnormal cyclin D1 degradation appears to be responsible for the increased levels of cyclin D1 in several cancers. Recent findings have identified novel mechanisms involved in the regulation of cyclin D1 stability. Cyclin D1 belongs to the family of cyclin proteins which function as the regulatory subunits of cyclin/cyclin dependent kinase (Cdk) holoenzymes that regulate entry into and progression through the cell cycle. Cyclin D1 expression is induced upon stimulation by growth factors (e.g. EGF, IGF-I/II), aminoacids, hormones, and oncogenes such as Ras, Src, ErbB2, and SV40 T antigen. Cdk4 and Cdk6 can partner with cyclin D1 in early to mid-G1 phase to phosphorylate and inactivate the cell cycle inhibitory function of the retinoblastoma protein (pRB) in cooperation with cyclin E/Cdk2. Cyclin D1 is also known to modulate local chromatin structure and transcription of genes involved in proliferation and differentiation through CDK-independent association with histone acetylases (e.g. CBP, P/CAF) and deacetylases. Mutations, amplification or overexpression of cyclin D1, which alters cell cycle progression, are observed frequently in a variety of tumors, including laryngeal squamous cell carcinoma, and may contribute to oncogenesis. Methods: This was a retrospective study by immunohistochemical determination of cyclin D1 in fixated and paraffin-embedded tumour especimens from 47 consecutive patients with squamous cell carcinoma in larynx treated by curative oncological surgery from 1999 to 2004. Survival of patients was related to age, gender, nodal status and stage at termination of treatment. Significant differences were considered for p<0.05. Results: Cytoplasmic immunostain was observed in 566 (1,2%) cell, nuclear immunostain in 13788 (29,6%) cell, relationship between PIc and PIn was 0,007 (0,7%), absent cell immunostain was observed in 32210 (69,1%), and total 46554 (100%). Among 28 (59,5%) cases with no lymph node metastasis, PIn was 26,8 (9,7 - 46,9) and PIc was 0,1 (0 0,3); those 19 (40,4%) with lymph node metastasis, had a PIn of 26,7 (16,7 39,0) and PIc of 0,3 (0 -1,0). Conclusions: According to these results, it has been concluded that cyclin D1 showed nuclear and cytoplasmic expression in larynx squamous cell carcinoma; however, tumor cyclin D1 expression was not significantly associated with lymph node metastasis when quantified by quantitative or semiquantitative methods. Besides, cyclin D1 expression showed no influence in overall survival

Laryngectomy, as a treatment for malignant laryngeal lesions, requires the patient to seek a substitute method of producing speech. Three types of alaryngeal speech were described: esophageal, Asai, and artificial larynx. One consideration in deciding which mode of speech is best for the patient is how closely each type of alaryngeal speech approximates normal. This investigation was an objective examination of esophageal, Asai, and artificial larynx speech as compared with normal in males and females.