Objetivos: O objetivo do nosso estudo foi verificar se a umidificação dos comprimidos com formulação brasileira de misoprostol vaginal aumenta a dilatação cervical antes da aspiração manual por vácuo (AMIU), em comparação com o uso de misoprostol seco nos abortos espontâneos no primeiro trimestre. O objetivo secundário foi verificar se houve correlação entre o pH vaginal e o grau de dilatação cervical usando um comprimido de misoprostol umedecido ou seco. Métodos: Estudo unicêntrico, duplo cego e randomizado, com 46 pacientes com aborto espontâneo de primeiro trimestre foram alocados aleatoriamente para o tratamento com 400 μg de misoprostol seco ou umedecido (com 200 μl de água destilada). Resultados: A dilatação cervical mediana (intervalo) nos grupos úmido e seco foi de 8 mm (6-12 mm) e 7 mm (5-10 mm), respectivamente ( p = 0,06). O tempo médio entre a inserção de misoprostol e a realização do procedimento não diferiu entre os grupos seco (406 min, intervalo 180-550 min) e molhado (448 min, intervalo 180-526 min) ( p = 0,1). Não foi encontrada correlação entre o pH vaginal e a dilatação cervical usando dados continuos ( p = 0.57; r = 0.08; intervalo de confiança de 95% -0.02, 0.3) ou dados dicotômicos (pH ≤5 /> 5, dilatação cervical ≥8 mm ou <8 mm; p = 0,8). Conclusão: Não foi observada diferença na dilatação cervical entre o uso de misoprostol umedecido e não umedecido antes do AMIU. / Objectives: The aim of our study was to ascertain whether moistening the Brazilian formulation of vaginal misoprostol tablets increases cervical dilation before manual vacuum aspiration (MVA), compared with use of dry misoprostol, in first-trimester miscarriage. The secondary objective was to ascertain whether there was any correlation between vaginal pH and the degree of cervical dilation using a moistened or dry misoprostol tablet. Methods: In a single-centre, double-blind, randomised trial, 46 patients with first-trimester miscarriage were randomly allocated to treatment with dry or moistened (with 200 μl distilled water) 400μg of misoprostol. Results: The median (range) cervical dilation in the wet and dry groups was 8 mm (6–12 mm) and 7 mm (5–10 mm), respectively (p=0.06). The median time between misoprostol insertion and carrying out the procedure did not differ between the dry (406 min, range 180–550 min) and wet (448 min, range 180–526 min) groups (p=0.1). No correlation was found between vaginal pH and cervical dilation using continuous data (p=0.57; r=0.08; 95% confidence interval -0.02, 0.3) or dichotomous data (pH ≤5/>5; cervical dilation ≥8 mm or <8 mm; p=0.8). Conclusion: No difference was observed in cervical dilation between moistened and non-moistened misoprostol use prior to MVA.

Made available in DSpace on 2015-04-14T13:30:39Z (GMT). No. of bitstreams: 1 389375.pdf: 1505128 bytes, checksum: 29ca32c28db465421da5e36f67d4e748 (MD5) Previous issue date: 2007-01-19 / Este estudo avaliou a velocidade de crescimento da mand?bula considerando a rela??o do crescimento com a matura??o esquel?tica das v?rtebras cervicais, em indiv?duos brasileiros, portadores de maloclus?o de Classe I, II e III esquel?tica, durante o per?odo puberal. Foram analisadas telerradiografias de perfil, obtidas em dois momentos, com intervalo de 6 a 18 meses, de 133 indiv?duos, sendo 54 do g?nero masculino e 79 do feminino, com idades entre 7 e 18 anos de idade. A amostra foi dividida em cinco grupos, de acordo com os est?gios de matura??o das v?rtebras. As telerradiografias de perfil foram tra?adas e os pontos cefalom?tricos digitalizados no Software DentoFacial Planner Plus (DFL Plus, 2.0). O ?ngulo ANB foi determinado para caracteriza??o da amostra. Foram avaliadas as dist?ncias entre Co-Go, Go-Gn e Co-Gn entre as duas cefalometrias, obtendo-se uma taxa de crescimento anual. No tratamento estat?stico utilizou-se an?lise de vari?ncia e teste de Tukey para comparar a velocidade de crescimento mandibular entre os est?gios de matura??o das v?rtebras cervicais e entre as classes, e teste t-student para comparar a velocidade de crescimento entre os g?neros. Os resultados indicaram que a velocidade m?dia de crescimento da mand?bula foi maior no est?gio 2 de matura??o das v?rtebras cervicais. Os indiv?duos do g?nero masculino apresentaram pico de velocidade de crescimento nos est?gios 2 e 3, enquanto nos indiv?duos do g?nero feminino, a velocidade de crescimento da mand?bula foi maior nos est?gios 1, 2 e 3. Embora os indiv?duos com padr?o esquel?tico de Classe III exibissem as maiores dimens?es iniciais da mand?bula, verificou-se similaridade para as velocidades de crescimento da mand?bula entre os portadores de Classes I, II e III

Orientador: Luis Gustavo Gosuen Gonçalves Dias / Resumo: Identificar alterações nos músculos paravertebrais cervicais e do ligamento nucal que possam estar relacionadas à espondilomielopatia cervical (EMC) em cães das raças Doberman Pinscher (DP) e Dogue Alemão (DA). Determinar as áreas de secção transversa (AST) de músculos paravertebrais cervicais e identificar possível assimetria entre os antímeros. Classificar o grau de alteração morfológica destas musculaturas e correlacionar os achados com o quadro neurológico dos pacientes. Material e métodos – Estudo retrospectivo em que foram analisadas imagens transversais de ressonância magnética de 60 cães das raças Doberman Pinscher (DP) e Dogue Alemão (DA), sendo 29 clinicamente normais (CN) e 31 acometidos pela EMC. Foram mensuradas as AST dos músculos, a espessura do ligamento nucal e determinado o índice de assimetria dos músculos entre os antímeros. O grau de alteração morfológica, por meio da presença de hipersinal nos músculos extensores paravertebrais foi determinado e correlacionado aos sinais clínicos neurológicos. Resultados – Cães DP-EMC apresentaram menor AST dos mm. longo do pescoço ao nível de C5 (p < 0,034) e dos mm. cleidomastoideo ao nível de C3 (p < 0,017), C4 (p < 0,012) e C5 (p < 0,014), quando comparados aos DP-CN. Para os cães DA foram encontradas diferenças significativas entre as AST dos mm. cleidomastóideo ao nível de C5 (p < 0,022) e entre as espessuras do ligamento nucal, sendo que os cães DA-EMC apresentam menores AST e espessuras do ligamento. Para as duas... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The aim of this study was to identify changes in the cervical paravertebral muscles and nuchal ligament related to cervical spondylomyelopathy (CSM) disease in the Doberman Pinscher (DP) and Grate Dane (GD) breed dogs. Measure the cross-sectional area (CSA) of the selected paraspinal muscles and to assess their asymmetry. Also, to grade the morphological changes of the extensor muscles and correlate to the patient’s neurological status. Materials and methods – Retrospective resonance image study of 60 dogs: 29 clinically normal and 31 CSM-affected. The CSA of the muscles and the thickness of the nuchal ligament were measured, and the asymmetry index between the right and left sides of the selected extensor muscles was determined. The grades of morphological changes in the extensor muscles were obtained and associated to the patients’ neurological status. Results – Mean CSA of longus colli muscles at C5 (p < 0,034) and of cleidomastoideus muscles at the level of C3 (p < 0,017), C4 (p < 0,012) and C5 (p < 0,014) were significantly smaller in CSM-affected DP compared with those in the clinically normal DP. Significant differences were present between clinically normal and CSM-affected GD for the mean CSA of cleidomastoideus muscles at the C5 level (p < 0,022) and for the thickness of the nuchal ligament, with those measurements smaller in the CSM-affected dogs. All CSM-affected dogs were found to have high grades of morphological changes in the extensor muscles compared to the c... (Complete abstract click electronic access below) / Doutor

Le cancer du col de l'utérus est le seul cancer pour lequel nous disposons de 2 outils complémentaires de prévention : la vaccination anti HPV (Human Papillomavirus) et le dépistage par frottis cervico-utérin. Malgré ces outils, ce cancer est responsable de 1000 décès chaque année en France, la plupart survenant chez des femmes avec un suivi non conforme aux recommandations concernant le dépistage. Notre premier article, utilisant les données du registre des cancers gynécologiques de Côte-d'Or, s'est intéressé aux facteurs associés à la mortalité par cancer du col de l'utérus. Il confirme une association significative entre non compliance au dépistage et décès. On retrouve par ailleurs des marqueurs de vulnérabilité socio-économique marqués dans notre population.Notre deuxième article avait pour objectif de déterminer la couverture vaccinale anti-HPV dans notre département ainsi que les facteurs associés à la vaccination. Une étude transversale a été menée entre octobre 2010 et mai 2011 auprès de 948 jeunes filles de 14 ans et plus scolarisées en Côte-d’Or. Pour rappel, les recommandations nationales avant 2012 ciblaient les jeunes filles de 14 ans et celles de 15 à 23 ans pour la vaccination de rattrapage. Les taux d’initiation de la vaccination étaient de 42,1% chez les filles de 14 ans et de 57,3% chez les plus âgées, insuffisants pour obtenir une efficacité optimale de la vaccination. Les freins parentaux rapportés par les jeunes filles étaient complexes. Les jeunes filles avaient une connaissance confuse et parcellaire des infections sexuellement transmissibles en général et des infections à HPV en particulier.Notre troisième article porte sur le dépistage des cancers cervical et colorectal au sein d'une population de femmes résidant en Côte-d'Or et sensibilisées à la question de la prévention des cancers, car compliantes au dépistage du cancer du sein. En France, le dépistage du cancer du col de l'utérus relève d'une initiative individuelle à l'inverse des dépistages du cancer du sein et colorectal qui fonctionnent sur un mode organisé. Au total, 1 856 femmes âgées de 50 à 65 ans ont répondu à un questionnaire envoyé par voie postale. L'objectif était de déterminer le taux de participation aux dépistages du cancer du col de l'utérus et du cancer colorectal ainsi que les facteurs associés. Les taux retrouvés étaient respectivement de 78,3% et 56,6% et cachaient des disparités notamment socio-économiques et de recours au système de soin.A l’issue de ce travail, des questions restent à explorer eu égard à ces deux modes de prévention complémentaires. Le suivi des cohortes de jeunes filles vaccinées permettra à long terme d’évaluer l’impact de la vaccination sur l’incidence des cancers du col de l’utérus, l’épidémiologie des HPV et la protection conférée vis à vis des autres cancers HPV positifs. Il conviendra également de définir les modalités du dépistage de ces jeunes filles en incluant peut être les tests HPV dans leur suivi. / Two complementary prevention tools exist for cervical cancer : HPV vaccination (Human Papillomavirus) and screening using Pap smear. Despite these effective tools, this cancer is responsible for 1,000 deaths each year in France, mostly in women who are not in accordance with the national recommendations regarding screening. Our first article, using data from the registry of gynecological cancers of Côte-d'Or, aimed to identify factors associated with mortality from cervical cancer. A significant association between non adequate follow up by screening and death was found. Association with socio-economic vulnerability and cancers was also noticed.The purpose of our second article was 1) to assess HPV vaccine coverage in a representative population of girls, aged 14 and above, attending school in Côte-d'Or and 2) to identify correlates of vaccines initiation and completion. A cross-sectional study was carried out between October 2010 and May 2011 in 948 girls. Vaccine initiation rates were 42.1% among 14-year-old girls and 57.3% among the oldest, insufficient to achieve optimal vaccination efficacy. Parental concerns about the acceptability of HPV vaccination were found and barriers to vaccination initiation and completion were complex. Girls had poor and confuse knowledge about sexually transmitted diseases in general and HPV in particular. Our third article deals with cervical and colorectal cancers screening in a population of women living in Côte-d'Or and up to date for breast cancer screening. In France, cervical cancer screening is an individual initiative, unlike screenings for breast and colorectal cancers, which are organized at a national level. Overall, 1856 women aged 50 to 65 returned a self-reported questionnaire delivered by post. The objective was to determine participation rates and factors associated with participation in both colorectal and cervical cancer screenings. Respectively 78.3% and 56.6% women were up to date for the two screenings with disparities regarding socioeconomic status and health care facilities access.Additional questions have to be explored on these two complementary modes of prevention. Follow up of cohorts of vaccinated girls will allow assessing the impact of vaccination on the incidence of cervical cancers, HPV epidemiology and the protection afforded against other HPV positive cancers. It is also important to define how vaccinated girls should be screened. HPV tests in this context are promising.

by Yam Hin Fai. / "June 1998." / Thesis (Ph.D.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (p. 118-151). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstract in Chinese.

Entre mulheres com HIV/AIDS há um maior número de casos de infecções persistentes pelo HPV contribuindo para um risco aumentado do desenvolvimento de lesões intraepiteliais escamosas cervicais. Ademais, a expressão anormal de moléculas HLA-E pode modular o sistema imunológico através da ligação com o receptor inibitório (CD94/NKG2A) ou estimulatório (CD94/NKG2C) de células NK e linfóticos T CD8+, diminuindo imunovigilância favorecendo a evasão de céulas infectadas por vírus. Diante da escassez de estudos avaliando a molécula HLA-E na interação com o HPV, mais especificamente na infecção pelo HIV-1, este estudo teve como objetivo avaliar a expressão de HLA-E em lesões intraepiteliais cervicais em mulheres portadoras do HPV, apresentando ou não a infecção pelo HIV-1. Trata-se de um estudo transversal, ao qual foram submetidos ao processo imunohistoquímico tecido do colo do útero parafinado de 67 mulheres infectadas pelo HIV-1 e 62 mulheres não infectadas, todas com lesão intraepitelial cervical com HPV, o qual foi tipificado. A expressão da molécula HLA-E foi analisada quantitativamente como sem expressão, de 1% a 30%, de 31% a 70% e de 71% a 100%. Os resultados mostraram que a infecção por herpes vírus foi maior entre as participantes HIV+ (P=0,005). Na análise imunohistoquímica, ficou evidente que as lesões intraepiteliais cervicais de mulheres infectadas pelo HIV-1 apresentaram redução na expressão da molécula HLA-E de 31% a 100% em comparação com mulheres sem a infecção pelo HIV- 1 (P=0,001), sugerindo que essa redução possa ser um mecanismo de escape viral, que acarreta a redução da apresentação de peptídeos virais para os linfócitos T CD8+. A expressão do HLA-E não foi associada aos graus de lesões intraepiteliais cervicais. Outros estudos são necessários para melhor compreensão do padrão e da função da expressão das moléculas HLA-E em lesões intraepiteliais cervicais de mulheres infectadas pelo HIV- 1 / Among women with HIV / AIDS there is a greater number of cases of persistent HPV infections contributing to an increased risk of developing squamous intraepithelial lesions of the cervix. In addition, abnormal expression of HLA-E molecules can modulate the immune system by binding to the inhibitory (CD94 / NKG2A) or stimulatory (CD94 / NKG2C) receptor NK cells and CD8+ T lymphocytes, decreasing immunovigilance and favoring the evasion of infected cells infected with virus. Due to the lack of studies evaluating the HLA-E molecule in the interaction with HPV, more specifically in HIV-1 infection, this project aimed to evaluate the expression of HLA-E in cervical intraepithelial lesions of infected women or not by HIV- 1, with the infection by HPV. It is a cross-sectional study, which was submitted to immunohistochemical processing the paraffin-embedded cervix tissue of 67 HIV-1 women infected with HIV-1 and 62 uninfected women, all of them with cervical intraepithelial lesion with HPV, which was typified. The expression of HLA-E was quantitatively analyzed as non- expressed, 1% to 30%, 31% to 70% and 71% to 100%. The results showed that the herpes virus infection was higher among HIV + participants (P = 0.005). In immunohistochemical analysis, it became evident that cervical intraepithelial lesions in HIV-1 infected women showed a reduction the expression of HLA-E molecule from 31% to 100% compared to women without HIV-1 infection (P = 0.001) Suggesting that this reduction may be a viral escape mechanism, which leads to a reduction in the presentation of viral peptides to CD8+ T lymphocytes. The expression of HLA-E was not associated with cervical intraepithelial lesions. More studies are need to better understand the pattern and function of HLA-E molecule expression in cervical intraepithelial lesions of infected women by HIV-1

Cervical cancer is the third leading cause of cancer death in women worldwide. Although cervical cancer is commonly infected with human papillomavirus (HPV), HPV infection alone is insufficient to induce malignant changes. Many characteristic genetic and epigenetic alterations have been identified in invasive cervical carcinomas but relatively little is known about the specific genetic and molecular alterations that allow pre-invasive epithelial cells to acquire the ability to progress to invasive squamous cell carcinomas. Recently, a family of small non-coding RNAs termed microRNAs (miRNAs) with specific inhibitory functions on target gene expression has been suggested to play an important role in the pathogenesis of human cancers including lung and breast cancer but remain undefined in cervical cancer. / Genome wide chromosomal copy number changes in cervical cancer by Agilent high-density array Comparative Genomic Hybridization demonstrated that only a very limited number of genomic imbalances have an impact on the miRNA profile in cervical cancer cells, although a high proportion of genomic loci containing miRNA genes exhibited DNA copy number alterations in other cancers. The impact of the genomic aberration on their mRNA expression was then confirmed by Aligent Whole Human Genome gene expression array. This suggests that the regulation of miRNA and mRNA expression may be different in cervical cancer. / In conclusion, our global miRNA profiling identified the common differentially expressed and genomic aberration independent miRNAs in cervical cancer. We further revealed the inhibition of hsa-miR-182 reduced tumor cell growth in vitro and in vivo through apoptosis and cell cycle mechanism. This provides new evidence that hsa-miR-182 may contribute to the pathogenesis of cervical cancer. / Keywords. MicroRNA, Cervical Cancer, Tumor Growth / To identify microRNA(s) associated with the tumorigenesis of cervical cancer, we firstly used the TaqMan MicroRNA Assays to survey and quantify a panel of 157 known human miRNAs in cervical cancer cell fines and micro-dissected normal cervical epithelium cells. We identified 2 microRNAs that were differentially up-regulated (fold change > 2, p &lt; 0.05) and 9 differentially down-regulated (fold change > 2, p &lt; 0.05) in cervical cancer cell lines comparing with normal cervical epithelium. Further investigation in tumor samples confirmed these two up-regulated miRNAs (hsa-miR-182 and -183 ) and 3 down-regulated miRNA (hsa-miR-145, 150, 195) from 4 investigated downregulated miRNAs (hsa-miR-145, 150, 195 and 328). / To investigate the biological function of those aberrantly expressed microRNAs, we chose one of the most aberrantly up-regulated microRNA ( hsa-miR-182, fold change > 10) for further investigation. Inhibition of hsa-miR-182 by antisense oligonucleotides inhibited HeLa cervical cancer cell growth in vitro and reduced tumor cell volume in vivo. Gene expression array analysis of HeLa cells with hsa-miR-182 knockdown and over-expression showed specific hsa-miR-182 targeting pathway in apoptosis and cell cycle. It indicated the roles of hsa-miR-182 in cervical cancer growth through apoptosis and cell cycle functions. / Tang, Tao. / Adviser: Richard K W Choy. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3446. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 155-169). / 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.

Estudos têm demonstrado que o microambiente tumoral é rico em ATP e adenosina, sugerindo o envolvimento da sinalização purinérgica no desenvolvimento e/ou manutenção do câncer. Ainda, o receptor purinérgico P2X7, conhecido pelo seu papel na indução de apoptose, encontra-se reduzido em alguns tecidos tumorais em comparação aos tecidos saudáveis, indicando que a sua redução possa ser um mecanismo de resistência celular à apoptose. Dessa forma, compreender o papel da sinalização purinérgica no contexto do câncer se torna indispensável e permite que novas abordagens terapêuticas sejam implementadas. Nesse trabalho, avaliamos a função dos nucleotídeos e nucleosídeos da adenina, bem como do receptor P2X7 na indução da morte celular em células de câncer cervical. Também verificamos o efeito do heat shock na potencialização da atividade do receptor P2X7 frente à curta exposição ao ATP em células de câncer de cólon. De acordo com os nossos resultados, o efeito citotóxico do ATP extracelular nas linhagens de câncer cervical é mediado principalmente pela ação do seu metabólito adenosina, que ao entrar no interior das células, promove o aumento dos níveis intracelulares de AMP, ativação de AMPK, aumento da p53 e indução de autofagia. O papel do receptor P2X7 nesse contexto parece ser apenas coadjuvante, visto que o seu bloqueio ou silenciamento impediu em apenas 20% a morte celular. Além disso, utilizando células de câncer de cólon, nós demonstramos que o heat shock aumenta a funcionalidade do receptor P2X7, independente da interação com heat shock proteins ou canais do tipo conexina/panexina, potencializando o efeito citotóxico do ATP. Esse efeito parece estar relacionado à mudanças na composição e arquitetura da membrana celular, visto que o uso do agente fluidizador de membrana benzil álcool foi capaz de mimetizar o efeito do heat shock na potencialização do receptor P2X7 a 37ºC. Este estudo fornece evidências adicionais sobre o papel da sinalização purinérgica no contexto da biologia celular tumoral e abre novas perspectivas para o uso dos nucleotídeos de adenina associados a hipertermia como agentes adjuvantes na terapia do câncer. / The tumor microenvironment is rich in ATP and adenosine, suggesting an involvement for purinergic signaling in cancer development and surveillance. The P2X7 receptor, among the P2 purinergic receptors, is broadly recognized as the “death receptor”, because it promotes cell apoptosis when exposed to high levels of extracellular ATP. Researches have been shown that P2X7 protein levels are decreased at the tumor site in comparison to adjacent healthy tissue, suggesting a mechanism of tumor escape to cell death. Thus, understanding purinergic signaling in a cancer context becomes urgent and opens a new field for therapeutic strategies. Here, we evaluated adenine nucleotides and nucleosides cytotoxicity, as well as P2X7 role in cell death induction using cervical cancer cell lines. Indeed, we investigated heat shock effect on P2X7 functionality through exposing colon cancer cell shortly to ATP at 40ºC. According to our data, adenosine uptake formed from ATP metabolism is the main responsible for the extracellular ATP cytotoxicity in cervical cancer cells. While inside of the cell, adenosine is converted to AMP, leading to AMPK activation, p53 increase and autophagy induction. ATP induced cell death per se through P2X7 in this context seems to be less important, since P2X7 blockage or knocking down reduced only 20% of cell death. In colon cancer cells, we found that heat shock stress was able to increase P2X7 pore formation independently of heat shock protein interaction or native pore-forming transporters association (e.g pannexin-or connexin-type channels), thus leading to an increase ATP cytotoxicity. The mechanism enrolled in this process seems to be related to changes in the lipid composition and architecture of membrane, as the membrane fluidizer benzyl alcohol could reproduce heat stress effect in potentiating P2X7 activation at 37ºC. In conclusion, our work provides further evidence for a purinergic signaling role in the cancer biology context and opens new perspectives for the utility of purine-based drugs associated to hypertermia as adjunctive agents in cancer therapy.

Fung, Man See Joyce. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 111-120). / Abstracts in English and Chinese. / Table of Contents / Acknowledgements --- p.I / Abstract --- p.II / 論文摘要 --- p.VII / Table of Contents --- p.X / List of Figures --- p.XIV / List of Tables --- p.XVI / Abbreviations --- p.XVII / Chapter Chapter 1 - --- Introduction --- p.l / Chapter 1.1 --- Biology of HPV --- p.2 / Chapter 1.1.1 --- History --- p.2 / Chapter 1.1.2 --- Classification --- p.2 / Chapter 1.1.3 --- Genome structure --- p.3 / Chapter 1.2 --- HPV and cervical cancer --- p.8 / Chapter 1.2.1 --- Classification of cervical lesions --- p.8 / Chapter 1.2.2 --- Natural history of development of cervical cancer --- p.9 / Chapter 1.2.3 --- Risk factors --- p.11 / Chapter 1.3 --- Prevention of cervical cancer --- p.12 / Chapter 1.3.1 --- Vaccination --- p.12 / Chapter 1.3.2 --- Screening --- p.12 / Chapter 1.3.2.1 --- Pap test --- p.12 / Chapter 1.3.2.2 --- HPV DNA test --- p.13 / Chapter 1.3.2.3 --- Methylation pattern as a novel marker --- p.13 / Chapter 1.4 --- Biology of Methylation --- p.14 / Chapter 1.4.1 --- Definition --- p.14 / Chapter 1.4.2 --- Silencing effect --- p.18 / Chapter 1.4.3 --- Roles in normal development --- p.20 / Chapter 1.5 --- Methylation and human diseases --- p.20 / Chapter 1.5.1 --- Genetic diseases --- p.20 / Chapter 1.5.2 --- Cancers --- p.21 / Chapter 1.5.3 --- Methylation and oncogenic viruses --- p.23 / Chapter 1.5.4 --- Potential of methylation pattern as a novel biomarker of cancer --- p.24 / Chapter 1.5.5 --- Epigenetic therapy --- p.25 / Chapter 1.6 --- Methylation and HPV --- p.25 / Chapter 1.6.1 --- History --- p.25 / Chapter 1.6.2 --- Potential roles in transcription regulation of HPV --- p.26 / Chapter 1.6.3 --- Viral gene methylation --- p.27 / Chapter Chapter 2 - --- "Hypotheses, Objectives and Study Design" --- p.28 / Chapter 2.1 --- Hypotheses --- p.29 / Chapter 2.2 --- Objectives --- p.30 / Chapter 2.3 --- Study Design --- p.30 / Chapter Chapter 3 - --- Materials and Methods --- p.34 / Chapter 3.1 --- Work flow --- p.35 / Chapter 3.2 --- Study subjects --- p.37 / Chapter 3.2.1 --- Invasive cervical cancer group --- p.37 / Chapter 3.2.2 --- Low-grade group --- p.37 / Chapter 3.2.3 --- Cell lines --- p.38 / Chapter 3.3 --- DNA extraction --- p.38 / Chapter 3.4 --- HPV genotyping --- p.39 / Chapter 3.5 --- PCR of HPV16 LCR --- p.39 / Chapter 3.6 --- Sequencing of HPV 16 LCR --- p.42 / Chapter 3.6.1 --- Purification of PCR products --- p.42 / Chapter 3.6.2 --- Cycle sequencing reaction --- p.42 / Chapter 3.6.3 --- Purification of cycle sequencing products --- p.43 / Chapter 3.6.4 --- Sequencer and data analysis --- p.43 / Chapter 3.7 --- Bisulfite modification --- p.43 / Chapter 3.8 --- PCR of bisulfite modified LCR --- p.45 / Chapter 3.9 --- Cloning --- p.48 / Chapter 3.9.1 --- Ligation --- p.48 / Chapter 3.9.2 --- Transformation --- p.48 / Chapter 3.9.3 --- Colony PCR --- p.49 / Chapter 3.10 --- Sequencing of clones --- p.51 / Chapter 3.10.1 --- Purification of PCR products --- p.51 / Chapter 3.10.2 --- Cycle sequencing reaction --- p.51 / Chapter 3.10.3 --- Purification of cycle sequencing products --- p.52 / Chapter 3.10.4 --- Sequencer and data analysis --- p.52 / Chapter 3.11 --- Statistical methods --- p.52 / Chapter Chapter 4 - --- Results --- p.54 / Chapter 4.1 --- Sample selection --- p.55 / Chapter 4.2 --- HPV16 LCR PCR and sequencing --- p.57 / Chapter 4.3 --- Methylation patterns --- p.61 / Chapter 4.3.1 --- Cell lines --- p.61 / Chapter 4.3.2 --- Cancer group --- p.63 / Chapter 4.3.2.1 --- Overview --- p.63 / Chapter 4.3.2.2 --- Methylation pattern of the cancer samples --- p.66 / Chapter 4.3.2.3 --- Methylation pattern of the promoter region --- p.74 / Chapter 4.3.3 --- Low-grade group --- p.76 / Chapter 4.3.3.1 --- Overview --- p.76 / Chapter 4.3.3.2 --- Methylation pattern of the low-grade samples --- p.79 / Chapter 4.3.4 --- Comparison of the methylation patterns of the cancer samples and the low-grade samples --- p.84 / Chapter Chapter 5 - --- Discussion --- p.95 / Chapter 5.1 --- Sequence variations of HPV 16 LCR --- p.96 / Chapter 5.2 --- Methylation patterns of CaSki and SiHa cell lines --- p.98 / Chapter 5.3 --- Methylation pattern of the cancer samples --- p.99 / Chapter 5.4 --- Methylation pattern of the low-grade samples --- p.100 / Chapter 5.5 --- Comparison of methylation patterns of the cancer samples and the low-grade samples --- p.101 / Chapter 5.5.1 --- Promoter region in 3' LCR --- p.102 / Chapter 5.5.1.1 --- SP1 binding site --- p.102 / Chapter 5.5.1.2 --- E2BS3 and E2BS4 --- p.103 / Chapter 5.5.2 --- Silencer region --- p.104 / Chapter 5.5.3 --- Enhancer region in central LCR --- p.105 / Chapter 5.5.4 --- CpG sites within 5' LCR --- p.106 / Chapter 5.6 --- Role of methylation in HPV 16 --- p.107 / Chapter 5.7 --- Potential as novel biomarker --- p.108 / Chapter 5.8 --- Conclusions --- p.109 / References --- p.111 / Appendix A

by Yang Lei. / Publication date from spine. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 110-126). / Acknowledgement --- p.i / Abstract --- p.ii / Abbreviations --- p.v / Table of Contents --- p.vi / Chapter Chapter 1 --- Introduction --- p.1 / Chapter Chapter 2 --- Literature Review --- p.4 / Chapter Chapter 3 --- Materials and Methods --- p.41 / Chapter Chapter 4 --- Results --- p.58 / Chapter Chapter 5 --- Discussion --- p.86 / References --- p.110 / Appendix --- p.120 / Publications --- p.125 / Illustrations --- p.127