Thesis (M.Sc.). / Written for the Dept. of Epidemiology, Biostatistics and Occupational Health. Title from title page of PDF (viewed 2008/12/05). Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 73-87).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2009.

Diss. (sammanfattning)--Stockholm : Karolinska institutet, 2009.

Thesis (Ph. D.)--University of New South Wales, 2007. / Title from caption (viewed on May 7, 2008).

Chan Kay Sheung Paul. / "December 2002." / Thesis (M.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 225-254). / 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 Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web.

O Papilomavírus humano (HPV) é um vírus, sexualmente transmissível, com potencialidade carcinogênica para a cérvice uterina, o que torna a infecção de mulheres pelo HPV um problema de saúde pública. Conhecer as necessidades de cuidado de mulheres infectadas pelo HPV inclui também saber suas experiências vividas durante o processo de infecção. A prevenção de doenças e a promoção de saúde ainda estão determinadas por concepções tradicionais da prática médica. É necessário pensar em um cuidado que vá além das necessidades físicas, emocionais e sociais que considere o sujeito com base em seu modo de ser no mundo e que valorize suas experiências, juntamente com suas crenças e valores. O objetivo deste estudo foi compreender a vivência das mulheres infectadas pelo HPV e conhecer quais são suas necessidades de cuidado. Tratou-se de um estudo qualitativo, com referencial da Fenomenologia existencial de Martim Heidegger. Os sujeitos foram 14 mulheres que tinham recebido o diagnóstico de HPV. As questões norteadoras foram: Como é para você estar com HPV? Conte-me sua experiência desde que soube do diagnóstico até hoje. Como está sendo a assistência que você tem recebido? Como resultado, emergiram quatro unidades temáticas: ser-aí mulher com HPV; ser-com nas relações; buscando o cuidado como solicitude e o caminho de transcendência da mulher com HPV. O referencial utilizado possibilitou melhor apreensão dos significados de estar com HPV, assim como o compartilhamento da vivência dessas mulheres em seu cotidiano. Constatou-se a necessidade de implementar ações de promoção e prevenção à saúde, que devem ser executadas por profissionais capacitados e com um perfil adequado para atenção à mulher. As mulheres devem ser encorajadas a demonstrarem suas próprias necessidades de cuidado, e as questões culturais e de gênero devem ser consideradas. É preciso que os profissionais da área da saúde avancem no cuidado com as mulheres infectadas pelo HPV, superando o trabalho restrito à racionalidade das ciências biomédicas. A informação sobre o HPV deve ser compartilhada pelas mulheres, respeitando-se suas necessidades e seu nível de compreensão. É necessário um cuidado mais efetivo e afetivo, no qual as mulheres infectadas pelo HPV exerçam um papel ativo no processo do cuidado e as interações sejam verdadeiras. / The human Papillomavirus (HPV) is a virus, sexually transmittable, with potentiality carcinogenic for the uterine cervix, making women\'s infection by the HPV a problem for the public health. To know the necessities of care of women infected by the HPV includes also knowing their experiences during the process of infection. Diseases prevention and health promotion are still determined by traditional conceptions of medical practice. It is necessary to think about a care that goes besides the physical, emotional and social necessities, that considers the individual based on of her way of being in the world and considers her experiences, beliefs and values. The objective of this study was to understand the life experience of the women infected by the HPV and to know their necessities of care. This research have had a qualitative focus, with reference to the Existential Phenomenology by Martim Heidegger. Were subjected to this research 14 women HPV positive. The research was based on these questions: What does being HPV positive mean for you? Tell me the experience that you have had since you have known you were infected until today. How is the aid that you have been receiving? As result, four thematic topics surfaced: to be there a woman with HPV; to be a woman with HPV in relationships; looking for care as solicitude and the way of transcendence of the woman with HPV. The used referential made possible a better apprehension of the meanings of being with HPV, as well as the share of the existence of these women in their daily life. The necessity of implementing health promotion and prevention actions was noted, and these actions must be executed by enabled professionals with a profile adapted for attention to the woman. The women must be encouraged to demonstrating their necessities of care themselves and questions of culture and of gender must be considered. It is necessary that professionals of the health area keep advancing in the care of women infected by the HPV, surpassing the work limited to the rationality of biomedical sciences. The information on the HPV must be shared by the women, respecting their necessities and their level of understanding. It is necessary a more effective and affectionate care, in which the women infected by the HPV play an active part in the process of the care and the interactions are true.

Introdução: Os Papilomavírus Humano (HPV) são vírus com capacidade de infectar a pele ou as mucosas. Existem mais de 100 tipos diferentes; destes, 13 são considerados oncogênicos. Avaliar a Qualidade de Vida (QV) em mulheres com HPV tem sido reportado como importante estratégia para implementar intervenções quanto ao impacto físico, psicossocial e econômico, além de fomentar a decisão de implantação de um programa de imunização efetivo. Considerando-se a inexistência de instrumentos brasileiros específicos para a avaliação da QV entre mulheres com HPV, a elaboração de um instrumento será de grande importância para avaliar esse construto. Objetivo: Desenvolver a Fase 1 da elaboração da escala para avaliação de qualidade de vida de mulheres com diagnóstico de Papilomavírus Humano (EQUALI-HPV). Metodologia: Trata-se de uma pesquisa metodológica. Esse tipo de estudo versa sobre a elaboração, a validação e a avaliação dos instrumentos e das técnicas de investigação, bem como refere-se aos estudos sobre métodos de obtenção, de organização e análise de dados. O processo de elaboração seguiu as etapas de elaboração dos itens, validação aparente e de conteúdo, validação semântica e pré-teste. Fizeram parte da amostra: 20 mulheres com HPV na fase de elaboração dos itens; cinco especialistas na etapa de validação semântica e 38 mulheres com HPV para o pré-teste. Os dados foram inseridos em planilha Excel, com dupla digitação e uso de procedimento de validação. Após, utilizou-se análise estatística descritiva para a caracterização dos sujeitos segundo variáveis sociodemográficas e clínicas por meio do software Statistical Package for the Social Sciences (SPSS), 20.0. Resultados: A partir da realização da revisão integrativa da literatura e de entrevistas com a população alvo, foram elaborados 98 itens os quais foram submetidos à validação aparente e de conteúdo em que 66 itens do instrumento sofreram mudanças na redação ou na alocação de domínio. Após, 11 mulheres procederam à validação semântica do instrumento e, por fim, foi aplicado o pré-teste em 38 mulheres com HPV. Conclusão: Foram finalizadas as etapas de elaboração dos itens, validação aparente e de conteúdo, validação semântica e pré- teste que constituem a Fase 1 deste estudo, a Fase 2 contemplará a realização de testes psicométricos para que a EQUALI-HPV esteja apta ao uso / Introduction: The Human Papillomavirus (HPV) are types of viruses with the capability of infect the skin and mucous. There are more than 100 different types; among those, 13 are considered oncogenic. Evaluating the Quality of Life (QoL) in women with HPV has been reported as an important strategy to implement interventions regarding the physical, psychosocial, and economic impact, and also, besides promoting the decision of implantation of an effective immunization program. Considering the non existence of Brazilian instruments that are specific to evaluate the QoL among women with HPV, and the elaboration of an instrument will be of great importance to evaluate this construct. Objective: To develop the phase 1 of the development of the scale to evaluate the quality of life of women with a diagnosis of Human Papillomavirus (EQUALI-HPV). Methodology: It is a methodological research. This type of study presents a discussion about the elaboration, validation, and evaluation of the instruments and the techniques of investigation, as well as how it refers to the studies about methods of obtainment, organization, and analysis of the data. The process of elaboration followed the elaboration steps of the items, the apparent validation and of the content, the semantic validation, and pre-test. Sample was constituted by: 20 women with HPV in the phase of elaboration of the items; five specialists in the semantic validation phase and 38 women with HPV for pre-test. The data were inserted in Excel spreadsheets, with double digitation and with use of a validation procedure. Then, it was used a descriptive statistical analysis for the characterization of the subjects according to sociodemographic and clinical variables by using the software Statistical Package for the Social Sciences (SPSS), 20.0. Results: From the development of an integrative review of the literature and interviews with the target public, 98 items were elaborated and submitted to the apparent and content validations, a total of 66 items of the instrument suffered changes or in the domain allocation. Then, 11 women preceded to the semantic validation of the instrument and, at last, the pre-test was applied to 38 women with HPV. Conclusion: The following steps were concluded: elaboration of the items, apparent validation and of the content, semantic validation, and pre-test that constituted the phase 1 of this study. The phase 2 includes the conducting of psychometric tests so that the EQUALI-HPV will be able to be used

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.