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1
Jolly, Carol Elizabeth. "The effects of leptomycin B on HPV-infected cells /". St Andrews, 2008. http://hdl.handle.net/10023/900.
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Tidy, John Anthony. "Human papillomaviruses and cervical neoplasia". Thesis, Imperial College London, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267104.
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Matsha, Tandi Edith. "Human Papillomaviruses in oesophageal cancer". Doctoral thesis, University of Cape Town, 2003. http://hdl.handle.net/11427/3140.
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Fothergill, Thomas. "Receptor signalling and internalisation of papillomaviruses /". [St. Lucia, Qld.], 2006. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe19808.pdf.
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Brestovac, Brian. "Human papillomavirus and cervical cancer in Western Australia". University of Western Australia. School of Biomedical and Chemical Sciences, 2005. http://theses.library.uwa.edu.au/adt-WU2006.0037.
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Smith, Lisa G. "HPV knowledge of college females and their intention to receive the HPV vaccination". Virtual Press, 2008. http://liblink.bsu.edu/uhtbin/catkey/1399190.
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The purpose of this study was to determine the HPV knowledge of college women and their intentions to receive the HPV vaccination.An original data collection instrument was created. This instrument consisted of nine HPV knowledge questions, one intention to receive the vaccine stage question, and three demographic questions. Data were collected during Fall semester of 2007. The participants of this study were females (n=361) who were enrolled in an introductory personal health course. There was a statistically significant difference in intentions to receive the vaccine stage and HPV knowledge level. Those females who had higher mean knowledge scores were more likely to have made a decision about receiving the vaccine or they are still trying to decide. Those females who had lower mean knowledge scores were more likely to be unaware of the vaccine or have not thought about receiving the vaccine.Department of Physiology and Health Science
7
Wong, Weng-man Valerie. "Prevalence, genotypes and risk factors of human papillomavirus infection among women in Macao a cross-sectional study /". Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B42998013.
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Cheung, Yim-hing. "Rare types and polymorphic variants of HPV in Hong Kong". Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B25176559.
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Pakarian, Farzin Bouzorgmehr. "Perinatal transmission and persistence of human papillomaviruses". Thesis, University of Leicester, 1998. http://hdl.handle.net/2381/29553.
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This thesis investigates whether human papillomaviruses are transmitted from mothers to their infants. Cervical/vaginal swabs were taken from 69 pregnant women. Buccal and genital samples were taken from their infants (all delivered vaginally) at 24 h (n=70; one set of twins), six weeks (n-49) and six months (n=19). All samples were examined for HPV-6, -11, -16, -18, -31 and -33 us polymerase chain reaction (PCR). Thirty seven (54%) women had detectable detectable in sixteen (23%) infants at 24 h and seven (14%) at six weeks; a perinatal transmission rate of 23% (6/37) and persistence of 14% (7/37). All infants tested at six months were HPV negative. At 24h, HPV-6 was demonstrated in 9 mother-infant pairs, HPV-18 in 1 mother-infant pair, HPV-11 in 1 mother-infant pair, dual infection with HPV type 16 and 18 in 3 mother-infant pairs. Two infants with HPV-18 were delivered to mothers in HPV-16/18. At 6 weeks, 5 infants remained HOV-16 positive, one infant HPV-18 positive, whilst one infant who was HPV 16/18 positive was now HPV-16 positive. To examine whether HPVs were acquired in utero or intrapartum, genital swabs were collected from 33 women who had amniotic fluid collected either at caesarean section (n=29) or at amniocentesis (n=4). Analysis of these samples demonstrated genital HPV in 10 (10%) of the women and none of the amniotic fluid samples. To demonstrate persistence and source of infectivity at 2 years, the same group sequenced a 521 bp segment of the upstream regulatory (URR) of HPV-16 DNA isolated from 13 maternal samples, samples taken from their infants. In conclusion, HPVs can be transmitted perinatally. HPV DNA persisted up to 2 years of age. In addition women with a high genital HPV load were more likely to transmit the virus.
10
Shah, S. D. "Understanding the evolutionary history of the papillomaviruses". Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1366951/.
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This thesis focuses on the evolutionary history of the papillomaviruses (PVs) using phylogenetic approaches. Two aspects have been examined: the first is the level of phylogenetic compatibility among PV genes and the second is determining the ancestral diversification mechanisms of the PVs in order to explain the origin of the observed associations with host species. Bayesian phylogenetic analysis has been used to make evolutionary inferences. The existence of phylogenetic compatibility among genes was examined by estimating constrained and unconstrained phylogenies for pairs of PV genes. The Bayes' factor statistic derived from comparison of the constrained and unconstrained models indicated significant evidence against identical phylogenies between any of the 6 PV genes investigated and may indicate the existence of ancestral recombination events. The formation of new host-virus associations can occur via a process of 'codivergence', where, following host speciation, the ancestral virus association is effectively inherited by the descendant host species; 'prior divergence' of the virus, which results in multiple virus associations with the host; and 'host transfer', in which the virus lineage is transferred between contemporaneous host species. To distinguish between these mechanisms of virus diversification, an approach based on temporal comparisons of host and virus divergence times was devised. Difficulties associated with the direct estimation of PV divergence times led to the incorporation of a biased sampling approach into Bayesian phylogenetic estimation. This allowed for viral divergence events to be biased in favour of codivergence but allowed sampling of times that violate this assumption and therefore indicate either prior divergence or host transfer. Statistical evaluation of the proportion of violations at each viral divergence identified significant evidence of prior divergence events behind many of the observed PV-host associations and one ancestral host transfer event.
11
Gu, Zhengming. "Studies on molecular mechanisms of transformation by human papillomavirus : the role of E6 and E5 oncogenes". Thesis, McGill University, 1996. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=40133.
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The ability of the HPV-18 E6 gene to impair p53-mediated transcriptional activity induced by DNA damaging agents was investigated. It is demonstrated that E6 can abolish DNA damage induced p53-mediated transcription and that a region from amino acid residue 113 to 117 of HPV-18 E6 protein was necessary for E6 to direct the degradation of p53. The biological importance of the E6/p53 interaction was then directly examined in HPV-16 containing cervical carcinoma derived cells by introducing the monomeric p53 mutant which is resistant to E6 mediated degradation. The two major observations made from this study were: (i) loss of p53 activity plays an important role in maintaining the malignant phenotype of these cells with respect to cell proliferation; (ii) the monomeric p53 mutant without its C-terminal regulatory region was biologically functional with respect to impairing cell proliferation in HPV-16 containing cervical carcinoma derived cells. Finally, it was revealed that the cellular MAP kinase signal transduction pathway was more active in cells expressing the HPV-16 E5 gene than in control cells or cells expressing E6 and E7. These observations help to define the mechanisms by which HPV oncogenes contribute to the development and maintenance of the neoplastic phenotype.
12
Jolly, Carol E. "The effects of leptomycin B on HPV-infected cells". Thesis, University of St Andrews, 2008. http://hdl.handle.net/10023/900.
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Cervical cancer is a major cause of death in women and is strongly associated with infection by human papillomavirus (HPV). Integration of HPV is thought to form a key step in the formation of cancer, and is thought to involve the upregulation of HPV E6 and E7 due to the loss of E2 transcriptional control. Leptomycin B (LMB), a nuclear export inhibitor, has previously been shown to induce apoptosis in HPV-containing cancer cell lines and HPV 16 E7 or E6/E7 transduced primary keratinocytes, but not in normal cells. This thesis shows that LMB can induce apoptosis and a reduction in the colony survival of derivatives of the W12 cell line that contain HPV 16 in either episomal or integrated form. The HPV genome status, including variations in viral integration type, appears to influence the cumulative and temporal pattern of LMB-induced apoptosis. The effects of LMB were also apparent in cells grown in organotypic raft culture, with differences in behaviour again apparent between cells containing episomal and integrated HPV. As previously noted, treatment with LMB was associated with increased expression of the cell regulators p53 and p21; however, the induction of apoptosis was not dependent upon transcriptionally active p53. It is therefore likely that induction and mediation of LMB-induced apoptosis occurs via alternative, currently unidentified, pathways. These findings suggest that LMB can induce apoptosis in keratinocytes containing HPV 16 in either episomal or integrated form, with genome status and potentially lesion grade likely to influence the response of HPV-associated anogenital lesions to LMB treatment.
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Strauss, Susanne. "Studies on the molecular epidemiology of human papillomaviruses". Thesis, Open University, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437780.
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Verstraten, Ruth. "Innate immune evasion strategies of persistent human papillomavirus 16". Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708295.
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Barker, Emily Mary. "Virus-host interactions in the innate immune response to high-risk human papillomavirus". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610618.
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Giannoudis, Athina. "Human papillomaviruses in squamous intraepithelial lesions of the cervix". Thesis, University of Liverpool, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.250230.
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Kaye, Jeremy Neil. "Vertical transmission and persistence of cancer-associated human papillomaviruses". Thesis, King's College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.392521.
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Lanham, Stuart Andrew. "Molecular biology of papillomaviruses in pre-malignant cervical infection". Thesis, University of Southampton, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.323803.
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Tomlins, Christine Helen. "Induction of anti-apoptotic factors by cutaneous Human Papillomaviruses". Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:121b0494-9cca-4fee-a800-b54fc36fe43e.
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Human Papillomaviruses (HPVs) are small DNA viruses which specifically infect keratinocytes at different body sites. An association between cutaneous Squamous Cell Carcinoma (SCC) formation, UV irradiation and infection with a high-risk subset of cutaneous HPVs has been postulated although the underlying molecular mechanisms by which HPV may play a role in SCC development are not yet fully elucidated. Expression of the viral E6 oncoprotein has been shown to interfere with DNA damage responses and inhibit UV induced apoptosis, suggesting HPV can contribute to early stages in tumourigenesis. Here, expression of E6 from HPV types 5, 8, 10, 18 and 77 was shown to reduce UV- or Fas-induced apoptosis, and the changes in a range of intracellular apoptotic regulators were investigated. Additionally, the subject of cutaneous SCCs, in contrast to HPV-associated anogenital cancers, not harboring HPV DNA in every tumor cell was explored. Results herein show that expression of E6 from skin cancer-associated HPV types 5 and 8 induced the secretion of factors that were able to inhibit UV-induced apoptosis in non-HPV expressing cell lines and primary human keratinocytes. The anti-apoptotic effect of HPV E6 expression was found to be mediated in part by upregulation of Osteoprotegerin (OPG) and Interleukin 6 (IL6). Purified OPG and IL6, when added to cells together, but not individually, reduced apoptosis following UV irradiation. Evidence is shown that OPG and IL6 inhibit the extrinsic and intrinsic apoptotic pathways respectively. Furthermore immunohistochemistry of HPV-typed SCC sections shows that IL6 protein is up-regulated in HPV positive tumors compared to HPV-negative cancers. To further test the effects of HPV5E6 expression, in combination with UV irradiation, on primary human keratinocytes microarray studies were performed. These findings support the hypothesis that a small number of HPV infected cells influence UV induced apoptosis in the skin and contribute to tumourigenesis.
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Lyman, Rachel C. "Cell cycle control and its modulation in HPV infected cells /". St Andrews, 2009. http://hdl.handle.net/10023/863.
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Tsang, Chi-kit Percy. "HPV genotyping and integration in cervical cancer and precursor lesions /". View the Table of Contents & Abstract, 2005. http://sunzi.lib.hku.hk/hkuto/record/B3149416X.
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Sze, S. M. Candy. "Evaluation and comparison of molecular diagnostic methods for detection of human papillomavirus (HPV) in relation to cervical neoplasia /". View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B37552752.
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Stewart, Deborah. "P53 regulatory mechanisms by human papillomavirus (HPV) E6 and alternative splicing". Thesis, McGill University, 2004. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=85651.
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In normal cells, the p53 tumour suppressor induces cell cycle arrest or apoptosis in response to a variety of stresses, including DNA damage and ectopic oncogene expression. However, cellular pathways controlled by p53 are compromised in virtually all cancers. Defining the mechanisms regulating p53 activity in normal and tumour cells has therefore been a major priority in cell biology and cancer research.In this study, we characterized two important regulatory mechanims of p53 activity: (i) Human papillomavirus (HPV) E6 interaction and (ii) alternative splicing. Recognized as the major etiological agents for cervical cancer, the oncogenic potential of HPVs correlates with their ability to target p53 for degradation. This study demonstrates that both p53 and HPV-18 E6 are exported from the nucleus when co-expressed, via a process that involves the C-terminal nuclear export signal (NES) of p53. However, neither nuclear export nor the p53 C-terminal NES is required for HPV-18 E6-mediated ubiquitination or degradation of p53.
This study also demonstrates that both low- and high-risk HPV E6 proteins are degraded by the ubiquitin-proteasome pathway, and thus provides an explanation for the low levels of E6 detected in cervical cancer cells.
Also reported in this study is a novel mechanism of p53 regulation arising through alternative splicing. This novel mRNA encodes a N-terminal deleted isoform of p53, termed p47. As demonstrated within, p47 does not supress cell viability but impairs both p53-mediated transcriptional activity and growth suppression. Interestingly, p47 increases both p53 monoubiquitination and nuclear export. We propose that p47 induces nuclear export of p53 by a mechanism involving monoubiquitination, as supported by recent findings from Li and colleagues (2003). The p47 protein also protects p53 from both Mdm2- and HPV-18 E6-mediated degradation. A number of cancers display abnormal localization of wildtype p53, and it will be important to examine the role of p47 in these tumours.
Taken together, the regulation of p53 activity by both HPV E6 and the alternative splice variant p47 involves alterations in p53 ubiquitination status, protein stability, and cell localization. Insight gained into these negative regulatory mechanisms may aid in the design of therapeutic strategies for reactivating wild-type p53 in HPV-associated and non-associated cancers.
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Lam, Wai-hung y 林偉雄. "The current situation of human papillomavirus (HPV) associated oropharyngeal cancer : a multi-institutional cohort study in Hong Kong". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206586.
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Despite the advance in modern oncology, there was limited improvement over the survival outcome of head and neck cancers. Until the discovery of the etiological association between Human Papillomavirus (HPV) and oropharyngeal cancer, an accelerated evolution in the field of head and neck oncology began. This viral-related tumor has ignited tremendous effort in American and European countries to explore the optimal treatment approaches. In contrast, the paucity of comprehensive and robust studies commonly exists in many Chinese and Asian countries. Little is known about the current situation of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) in Hong Kong.
This retrospective local multi-institutional study attempted to explore the HPV-associated OPSCC in Hong Kong from various aspects, including demographics, risk factors, clinical and histological features, molecular profile, as well as clinical outcomes. Finally, attempts were made to determine any predictive factors to stratify high-risk patients in this distinct disease entity and explore the most appropriate detection algorithm of the biologically active HPV infection in our locality.
With the support from the Hong Kong Cancer Registry and nine public hospitals, 141 (43.3%) of 326 newly diagnosed OPSCC in the whole population of Hong Kong between 2005 and 2009 were recruited. Inclusion criteria were histologically proven OPSCC with tumor specimens available for prospective laboratory tests. Those with non-SCC, non-oropharyngeal in origin and incomplete clinical records were excluded. Prospective HPV PCR and genotyping, and immunohistochemical staining with p16, p53, cyclin D1 and HER-2 were performed. Univariate and multivariate analyses were performed to assess the correlations between various parameters and HPV-associated OPSCC.
Epidemiologically, based on the combined positivity in HPV PCR and p16, the prevalence of HPV-associated OPSCC was 22%. Thirty (96.8%) of thirty one were HPV-16, the remaining one was HPV-18. In the univariate analysis, this cancer directly correlated with female gender (p=0.014), younger age (p=0.012), non-smoker (p=0.02), non-drinker (p=0.06) and early primary tumor (p=0.001). Histologically, basaloid differentiation (p<0.001), non-keratinization (p=0.007) and high tumor infiltrating lymphocyte (TIL) level (p<0.001) showed significant correlations. A distinct molecular profile was identified, with p16 positivity noted in all cases (p<0.001), few of p53 (p<0.001) and cyclin D1 positivity (p<0.001) and absence of HER2 over-expression.
Significantly superior prognosis was demonstrated in HPV-associated OPSCC. The 5-year overall and disease specific survivals were 67.0% and 88.6% compared with 27.8% (p<0.001) and 41.3% (p<0.001) in the non-viral counterpart respectively. Other good prognostic factors identified for OS and DSS included early primary disease (T1/T2) (p=0.02; p=0.001), absence of distant metastasis (both p<0.001), high TIL level (both p<0.001), p16-positivity (p=0.002; p=0.003), non-smoker (p=0.021; p=0.014). In the multivariate analysis, the HPV-associated tumor (HR: 0.28; 95% CI: 0.08 – 0.93; p=0.038), early primary tumor (HR: 0.52; 95% CI 0.30 – 0.89; p=0.017) and absence of distant metastasis (HR=0.15 95% CI: 0.07 – 0.3; p<0.001) were associated with lower risk of death from any causes after controlling other confounding factors.
Most importantly, high TIL level in HPV-associated OPSCC patients was associated with 89% (HR: 0.11; 95% CI: 0.02 – 0.61; p=0.012) lower risk of death from any causes than those with low TIL level, but not present in non-HPV counterpart. In addition, either HPV PCR complemented with typical high-risk genotyping results or p16 IHC positivity complemented with HPC PCR positivity using specific designed primers were two reasonably sensitive and specific detection algorithms based on the local genotypic distribution of this disease.
In summary, this is the first most comprehensive and robust local study indicating the importance of HPV-associated OPSCC in Hong Kong. It successfully illustrated various distinctive characteristics of this viral-related cancer. Additionally, it has suggested a potential predictor to identify the minority with more aggressive diseases and the most effective laboratory detection algorithms in this locality. It definitely facilitates the next step in exploring this disease via larger and prospective trials in coming future.published_or_final_version
Surgery
Master
Master of Medical Sciences
25
Al-ayadhy, Bushra Y. "The effect of CD21 on proliferation and differentiation on human cervical epithelium". Thesis, University of Aberdeen, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388944.
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CD21 is a transmembrane receptor molecule, previously known as the CR2, C3d or EBV receptor, which was originally identified and characterized on the B-cell lymphoid series. It has also been described in various squamous cells but these reports are diverse and sometimes conflicting. This thesis is a study of putative CD21 on the squamous cells of the human cervix uteri. The introduction provides background information on the cervix and on CD21 and indicates lines of investigation followed later. Experimental studies commence with an immunohistochemical study in which a panel of anti-CD21 monoclonal antibodies was applied to fresh frozen sections of the cervix. Only one antibody, HB5 reacted positively and this was consistent. HB5 located to the cell membrane of normal squamous ectocervical cells in a band-like manner, above the basal layers and beneath the superficial layers. Significantly HB5 did not react with CIN or koilocytes. That only HB5 reacted was subsequently confirmed by flow cytometry. That it reacted only with cell membrane was confirmed by confocal laser microscopy. Further, the lower limit of the HB5 positive band was confirmed by a dual labeling study employing HB5 and MIB-1 which recognizes cycling cells. Cells labeled with these antibodies appear mutually exclusive. Cycling cells in vivo are not HB5 positive. Western blotting studies on extracts of normal cervical epithelium indicated that HB5 reacted with a molecule larger than that found on lymphoid cells. However, they do share the same epitope. Having demonstrated an HB5 epitope on epithelial cells which were not cycling but were not yet fully differentiated, a series of in vitro experiments were conducted to see if the epitope was functional in a receptor sense, or was an epiphenomenon. Monolayer cultures, with appropriate controls, were exposed to HB5. Small effects were demonstrated in thymidine incorporation, protein synthesis and cell numbers, in early culture stages. The concluding general discussion gives some thought to the possible role of maturation in the control of neoplasia.
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Condjella, Rachel. "Unique properties of the canine papillomavirus type II E5 protein". Connect to Electronic Thesis (ProQuest) Connect to Electronic Thesis (CONTENTdm), 2009. http://worldcat.org/oclc/457185147/viewonline.
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Graham, Andrew Keith. "Human papillomaviruses and cervical neoplasia : detection, prevalence and prognostic significance". Thesis, University of Hertfordshire, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387195.
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Arends, Mark J. "Regulation of tumour growth and apoptosis by oncogenes and papillomaviruses". Thesis, University of Edinburgh, 1992. http://hdl.handle.net/1842/19771.
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The role of HPV genomes in human cervical neoplasia was re-examined using a new, sensitive PCR-based assay. This demonstrated increasing HPV prevalence with increasing grade of histological abnormality in cervical neoplasia. In contrast, HPV was not observed in histologically normal epithelium from a control group of women defined without reference to attendance at gynaecological or sexually transmitted disease clinics. HPV 16 was associated more with squamous cell carcinomas, and HPV 18 with cancers showing glandular differentiation - the histological type with a poorer prognosis. HPV 18 had a higher cancer/CIN prevalence ratio than HPV 16 indicative of a more rapid transition from CIN to carcinoma. Thus, HPV 18 appeared to be a more aggressive type than HPV 16. A rodent fibroblast model was developed to investigate the effects of HPVs and the myc and ras oncogenes on tumour cell apoptosis and growth rate. These genes were introduced into immortalised fibroblasts, which were studied both in vitro and in vivo. Regardless of the introduced genes, fibroblast proliferation in vitro differed little between the resulting cells lines. In contrast, the rates of cell death (which was uniformly effected by apoptosis) differed widely. Each tumour cell line had a characteristic rate of apoptosis, which determined large differences between the lines in their rates of population expansion in vitro. The tumours produced by subcutaneous injection of these cells into immune suppressed mice also showed large differences in size, which demonstrated a consistent relationship to the relative frequencies of mitosis and apoptosis. Thus, apoptosis appeared to be a major determinant of tumour growth in vitro and in vivo. The ratio of apoptosis to mitosis appeared to be characterised by the genes inserted into these cells. The c-myc oncogene and high risk HPV genomes stimulated tumour cell apoptosis. HPV 18 was associated with lower levels of tumour cell apoptosis than HPV 16. In contrast, the activated ras oncogene suppressed apoptosis, either alone or in combination with the other genes, contributing to the faster growth of ras transfected fibroblasts.
29
張艷馨 y Yim-hing Cheung. "Rare types and polymorphic variants of HPV in Hong Kong". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31970448.
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Yan, Chun-kit y 甄俊傑. "Prevalence and pattern of human papillomavirus infection in females, with cytology correlation: the Hong Kongexperience". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48421492.
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Objectives
To analyze the prevalence and pattern of HPV infection in women of different age groups in Hong Kong, with respect to liquid-based cytologic diagnosis.
Materials and Methods
A total of 2,055 liquid-based gynecologic cytology cases using either SurePath or ThinPrep during the period from July 1, 2007 to July 31, 2012 were retrieved from the archival files of CH Pathology Limited for retrospective analysis. Cytologic diagnosis was first given. Polymerase chain reaction (PCR)-based human papillomavirus (HPV) genotyping was subsequently performed in cases either as requested simultaneously by gynecologists or if the cytologic diagnosis was “atypical squamous cells of undetermined significance (ASC-US)” or above. IBM SPSS statistics 20 was used for data analysis and assessment of possible statistical significance.
Results
The overall prevalence of HPV infection in the studied population was 67.7%, with 37.2% cases with “negative” cytologic findings being HPV positive. Cases with “lowgrade squamous intraepithelial lesion (LSIL)”, “atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H)” and “high-grade squamous intraepithelial lesion (HSIL)” were highly associated with HPV infection (97.8%, 91.5% and 98.4%, respectively). Amongst the “ASC-H” and “HSIL” cases, most of them were shown to harbor high-risk HPV DNA (87.2% and 93.4%, respectively).
The overall prevalence of HPV infection was higher in women younger than 25 years and in women older than 54 years, with the peak at post-menopausal age group. The patterns for infection by single HPV genotype or high-risk HPV genotype(s) alone were similar to the overall pattern, with the first peak at women younger than 25 years, followed by a drop at aged 25 to 34 and rebound again when age afterward. As for infection by multiple HPV genotypes or low-risk HPV genotype(s) alone, the patterns were less consistent.
Amongst all the HPV-positive cases, the commonest high-risk HPV genotypes were type 52 and type 16. HPV type 62 and type 81 represented the commonest low-risk HPV genotypes detected in the population studied. Infection by other HPV genotypes showed various patterns in different age groups.
Conclusions
The overall prevalence of HPV infection in Hong Kong females correlates with age of the patients and corresponding cytologic diagnosis. Women younger than 25 years and older than 54 years are more likely to harbor HPV. The patterns of HPV infection in local patients can be useful in future preventive measures such as vaccination.published_or_final_version
Medical Sciences
Master
Master of Medical Sciences
31
Perrons, Christopher John. "Papovaviruses in humans". Thesis, University College London (University of London), 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368850.
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Parish, Joanna L. "The induction of apoptosis by the human papillomavirus type 16 E2 protein". Thesis, University of Bristol, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391157.
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He, Dan. "Clinical and pathological significance of HPV infection and p53 mutation in human esophageal cancer /". Hong Kong : University of Hong Kong, 1997. http://sunzi.lib.hku.hk/hkuto/record.jsp?B1961620X.
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Giacomini, Rosane. "Expressão imunohistoquímica de biomarcadores e sua relação com o Papiloma vírus humano em carcinomas de cabeça e pescoço". reponame:Repositório Institucional da UCS, 2017. https://repositorio.ucs.br/handle/11338/3665.
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O câncer de cabeça e pescoço é considerado a sexta neoplasia mais prevalente no mundo, com mais de seiscentos mil novos casos diagnosticados a cada ano, e a quinta mais prevalente no Brasil, com mais de mil e quinhentas pessoas acometidas anualmente, tornando-se responsável, mundialmente, por quatro por cento da mortalidade por câncer. O tipo mais comum é o carcinoma epidermoide (CECP), sendo sua patogênese historicamente associada ao uso de tabaco e álcool, porém, nas últimas décadas, a infecção pelo HPV tem sido associada à doença. Definir o prognóstico e o risco de desenvolvimento, assim como o sucesso do tratamento em resposta a uma determinada medicação e/ou procedimento, constituem a principal razão para a identificação de biomarcadores, já que sua expressão pode refletir diversos processos em andamento nas células tumorais. Vários estudos correlacionaram a expressão de survivina, nos tumores sólidos, com um curso clinicamente desfavorável da doença, resistência a fármacos, pior prognóstico e menor sobrevida do paciente. p16 pode fornecer evidências do potencial maligno de uma lesão, e sua superexpressão pode ser considerada um marcador de prognóstico favorável. A expressão elevada de PD-L1 pode ser um importante facilitador para o crescimento tumoral e metástases. O objetivo deste trabalho foi identificar, por imunohistoquímica, os níveis de expressão de p16, survivina e PD-L1 em amostras de lesões malignas de cabeça e pescoço na presença e na ausência de infecção viral por HPV e relacioná-los com os achados clínicos dos pacientes. Foram utilizadas trinta e três amostras teciduais, obtidas por biópsia de lesões de cabeça e pescoço, com finalidade diagnóstica, provenientes do Serviço de Oncologia Do Hospital Geral de Caxias do Sul e do banco de dados do Laboratório Diagnose. As amostras foram selecionadas retrospectivamente, tendo como critério de seleção a presença de carcinoma epidermoide de cabeça e pescoço. A determinação da presença do HPV e tipagem viral foi realizada pelo método da reação em cadeia da polimerase e a expressão proteica por imunohistoquímica. Os resultados foram avaliados considerando a proporção de células positivas comparadas ao número total de células no campo. A superexpressão de p16 nos CECPs pode ser um indicativo da participação da infecção por HPV durante o processo de carcinogênese, sendo que a relação entre a superexpressão de p16 e presença de infecção por HPV não foi observada em alguns dos casos avaliados, podendo indicar: falha na realização da PCR, não detectando a presença do HPV; a não participação do HPV no processo de carcinogênese; o sinergismo entre as vias carcinogênicas HPV+ e HPV- (tabagismo/etilismo). Além disso, a superexpressão de p16 em conjunto com a expressão de survivina e/ou PD-L1 indicam um comportamento intermediário entre os cânceres HPV+ e HPV- (via carcinogênica tabagismo/etilismo). p16, survivina e PD-L1 são indicativos da via carcinogênica HPV+ e podem predizer se houve sinergismo entre as vias carcinogênicas, bem como indicar o comportamento dos tumores, entretanto não devem ser utilizados isoladamente, incluindo a PCR para HPV. Os biomarcadores avaliados neste trabalho podem ser úteis no manejo clínico dos pacientes, além de auxiliar no desenvolvimento de novas modalidades terapêuticas, sendo necessária a obtenção de um maior número de casos e de informações sobre a expressão desses biomarcadores.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES
Head and neck cancer is considered the sixth most prevalent neoplasm in the world, with more than six hundred thousand new cases diagnosed each year and the fifth most prevalent in Brazil, with more than one thousand five hundred people affected annually, being responsible, worldwide, by four percent of cancer mortality. The most common type is squamous cell carcinoma (CECP), its pathogenesis has been historically associated with tobacco and alcohol use, but in the last decades HPV infection has been associated with the disease. Defining the prognosis and risk of development, as well as the success of the treatment in response to a particular medication and/ or procedure, are the main reason for the identification of biomarkers, and their expression may reflect several processes in progress in tumor cells. Several studies have correlated the expression of survivin in solid tumors with a clinically unfavorable course of the disease, drug resistance, worse prognosis and shorter patient survival. p16 may provide evidence of the malignant potential of an injury, and its overexpression may be considered a favorable prognostic marker. Elevated PD-L1 expression may be an important facilitator for tumor growth and metastasis. The objective of this work was to identify, by immunohistochemistry, the levels of expression of p16, survivin and PD-L1 in samples of head and neck malignant lesions in the presence and absence of HPV viral infection and to relate them to the clinical findings of patients. Thirty-three tissue samples were used, obtained by biopsy of head and neck lesions, for diagnostic purposes, coming from the Oncology Service of the General Hospital of Caxias do Sul and from the Diagnose Laboratory database. Samples were retrospectively selected, having as selection criterion the presence of squamous cell carcinoma of the head and neck. The determination of the presence of HPV and viral typing was performed by the polymerase chain reaction method and the protein expression by immunohistochemistry. The results were evaluated considering the proportion of positive cells compared to the total number of cells in the field. The overexpression of p16 in CECPs may be indicative of the participation of HPV infection during the carcinogenesis process, being that the relationship between p16 overexpression and the presence of HPV infection was not observed in some of the evaluated cases, which may indicate: failure in the PCR achievement, not detecting the presence of HPV; the non-participation of HPV in the process of carcinogenesis; the synergism between the carcinogenic pathways HPV+ and HPV- (smoking/alcoholism). In addition, the overexpression of p16 in conjunction with the expression of survivin and/or PD-L1 indicates an intermediate behavior, between cancers HPV+ and HPV- (pathway carcinogenic smoking/alcoholism). p16, survivin and PD-L1 are indicative of the carcinogenic pathway HPV+, and may predict if there was synergism between carcinogenic pathways as well as indicate the behavior of tumors, however should not be used in isolation, including PCR for HPV. The biomarkers evaluated in this study may be useful in the clinical management of patients, besides helping in the development of new therapeutic modalities, being necessary to obtain a greater number of cases and information on the expression of these biomarkers.
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Kan, Chin-Yi. "Human Papillomavirus in human breast cancer and cellular immortalisation". Sydney : University of New South Wales. Biotechnology and Biomolecular Sciences, 2007. http://www.library.unsw.edu.au/~thesis/adt-NUN/public/adt-NUN20071004.080541/.
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Green, Jonathan. "The role of semen in the transmission of genital human papillomaviruses". Thesis, University of Surrey, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334308.
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Kell, Barbara. "Studies on the E5 and E7 proteins of genital human papillomaviruses". Thesis, King's College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266401.
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Forslund, Ola. "Genital human papillomaviruses studies of their occurrence, type spectrum and expression /". Malmö : Dept. of Medical Microbiology, Section of Virology, Lund University, University Hospital, 1997. http://catalog.hathitrust.org/api/volumes/oclc/44966987.html.
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Cesur, Ozlem. "Using RNA aptamers to manipulate the functions of human papillomaviruses (HPV)". Thesis, University of Leeds, 2015. http://etheses.whiterose.ac.uk/9312/.
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HPV is the most common viral infection of reproductive tract, affecting both females and males. High-risk oncogenic types are the cause of cervical cancer by the expression of E6 and E7 viral oncoproteins. High-risk oncogenic types are also responsible for up to 90% of anal and 12 % of oropharyngeal cancers. The well-characterised interaction of HPV16 E7 is with the cell cycle control protein pRb, promoting pRb degradation and resulting in cell cycle misregulation. E7 can interact with many other cellular proteins. In this study, RNA aptamers identified against HPV16 E7 were used to study E7 interactions further. The aptamers were generated previously by an in vitro technique known as the systematic evolution of ligands by exponential enrichment (SELEX), in which molecules from a random pool are isolated for binding to the target with a high affinity and specificity. Aptamers are single-stranded oligonucleotides that can form complex structures and bind target molecules in a conformation-dependent manner. The E7 aptamers have been stabilised by the inclusion of modified pyrimidines. Aptamers have therapeutic potential; examples include the aptamer Macugen (also called Pegaptanib). Several HPV16 E7 aptamers were able to induce apoptosis in an HPV16-transformed cervical carcinoma cell line (SiHa) that actively express both E6 and E7. Of particular interest is the E7 aptamer A2. In order to ensure apoptosis is not due to the innate immune response, immune stimulatory effects of E7 aptamers were studied by quantitative PCR. Effects of aptamers on the steady state levels of E7 and cellular proteins were analysed by western blotting. Treatment of cells with A2 resulted in loss of the E7 oncoprotein and a rise in cellular pRb levels. We have evidence that some of the HPV16 E7 aptamers can also target HPV18 E7. Several inhibitor molecules of protein degradation were used to determine the pathway of E7 loss following aptamer transfection in HPV16-transformed cervical carcinoma cell line, CaSki. Results suggested that aptamer transfection did not appear to alter normal degradation pathway of E7, which was mainly 26S proteasome-mediated. Co-localisation of aptamers (model aptamers) with cellular markers was studied by immunofluorescence. Co-localisation of E7 with cellular markers in the presence or absence of HPV16 E7 aptamers suggested the accumulation of E7 in the endoplasmic reticulum (ER) in A2 transfected cells, suggesting an alternative pathway, leading to a model for E7 degradation. Aptamers can be advantageous in terms of developing novel potential therapeutics. In Chapter 5, model aptamers were shown to internalise into keratinocytes and cervical cancer cells without the need for lipofection. This novel ability of aptamers might enable topical use of aptamers. The mechanism of aptamer entry was also studied using endocytosis inhibitors for receptor-mediated uptake as well as macropinocytosis. The result suggested that reagent-free internalisation can be both energy-dependent (receptor-mediated) and passive (macropinocytosis) and that uptake can be sequence-dependent.
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Savini, Federica <1985>. "Host Jump in BPVs: is Species- Specificity Still Appropriate for Papillomaviruses?" Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7639/2/Tesi_dottorato_Savini_31.3.16.pdf.
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Into the family Papillomaviridae, four different genera Delta Epsilon Xi and Dyoxi include the fifteen Bovine Papillomaviruses (BPVs) that have been characterized so far in cattle, even though it has been estimated that type number may exceed 20. Current classification system assumes that the host species in which a PV was firstly detected, is the original host, and the identified types are therefore named after it. Papillomaviruses (PVs) are indeed generally considered to be highly specific for their hosts; however, within the Delta-PVs, BPV types 1, 2 and 13 are well recognized to infect multiple species. Our results deepen the knowledge on circulation of BPV types in Italy and further contribute to a better understanding on their intra-genus variability. Besides observing that BPVs can contribute to the spread of other epitheliotropic viruses, we confirmed the host-jumping ability of the Delta PVs.
The presence of co-infections between BPVs belonging to Delta and Xi genera in the healthy skin and mucosa of chamois and deer strongly suggest the reservoir role of wild ruminants belonging to the Bovidae and Cervidae families for domestic ruminant PVs.
Furthermore, we identified the Eqsarc1 variant in healthy subjects and in non-equid species, suggesting an “equine adaptation” of the virus variant.
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Savini, Federica <1985>. "Host Jump in BPVs: is Species- Specificity Still Appropriate for Papillomaviruses?" Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7639/.
Texto completoResumen
Into the family Papillomaviridae, four different genera Delta Epsilon Xi and Dyoxi include the fifteen Bovine Papillomaviruses (BPVs) that have been characterized so far in cattle, even though it has been estimated that type number may exceed 20. Current classification system assumes that the host species in which a PV was firstly detected, is the original host, and the identified types are therefore named after it. Papillomaviruses (PVs) are indeed generally considered to be highly specific for their hosts; however, within the Delta-PVs, BPV types 1, 2 and 13 are well recognized to infect multiple species. Our results deepen the knowledge on circulation of BPV types in Italy and further contribute to a better understanding on their intra-genus variability. Besides observing that BPVs can contribute to the spread of other epitheliotropic viruses, we confirmed the host-jumping ability of the Delta PVs.
The presence of co-infections between BPVs belonging to Delta and Xi genera in the healthy skin and mucosa of chamois and deer strongly suggest the reservoir role of wild ruminants belonging to the Bovidae and Cervidae families for domestic ruminant PVs.
Furthermore, we identified the Eqsarc1 variant in healthy subjects and in non-equid species, suggesting an “equine adaptation” of the virus variant.
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Herrington, Charles Simon. "In situ analysis of human papillomaviruses and chromosome aberrations in cervical neoplasia". Thesis, University of Oxford, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279806.
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Mackintosh, Lorna J. "The role of Human Papillomaviruses and their replication in nonmelanoma skin cancer". Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3388/.
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Nonmelanoma skin cancer (NMSC) is the commonest cancer worldwide and is a significant and increasing burden on health care resources. NMSC aetiology is fundamentally linked to sun exposure although infection with oncogenic viruses including Human Papillomaviruses (HPV) is thought to be a cofactor. Fair skinned populations residing in geographical areas with high sun exposure have an increased incidence of NMSC and an excess of NMSC is also observed in certain patient groups including immunosuppressed organ transplant recipients. This thesis describes the epidemiology of NMSC in the immunosuppressed renal transplant population in the West of Scotland. Clinical samples from this population were investigated for the presence of HPV utilising a PCR reverse hybridisation technique. This assay specifically examined for HPV of the genus Beta that have been previously linked to NMSC. The effect of presence of HPV in these samples was evaluated through an investigation of the expression of cellular biomarkers. A biomarker expression pattern specific to HPV infected lesions would add further support to the link between HPV and NMSC. Samples were probed for Ki67, p16, p53, MCM2 and MCM5 antigens in addition to novel antigen, Topoisomerase II Beta Binding Protein 1 (TopBP1). TopBP1 is a host cellular protein that is involved in the DNA damage response and is an interacting partner for HPV thus making it a likely candidate for involvement in cutaneous carcinogenesis. A biomarker expression pattern specific to HPV infected NMSC was not identified although aberrant expression of TopBP1 was identified in a subset of skin cancers. To investigate this novel observation, a molecular investigation of the interaction between TopBP1 and the viral replication factor E2 was carried out, firstly in HPV-16 before extending the work to the cutaneous virus HPV-8. A mutant of HPV-16E2 that failed to bind TopBP1 was generated. Failure to bind TopBP1 resulted in a phenotype exhibiting compromised viral replication. The equivalent mutation generated in HPV-8E2 resulted in an even more compromised replicative phenotype. In addition to this work, gene targets of TopBP1 were also identified by a microarray analysis. This was carried out using MCF7 cells untreated or damaged by ultraviolet radiation (UVR) with endogenous TopBP1 depleted by SiRNA treatment. These studies showed that TopBP1 is involved in a number of cellular processes and is likely to be involved in controlling DNA damage targets following UVR induced DNA damage. The work described in this thesis provides further evidence supporting the role of HPV in the aetiology of nonmelanoma skin cancer. Generation of an E2 mutant that fails to bind TopBP1 and exhibits a compromised replication phenotype provides further evidence to support the hypothesis that the E2-TopBP1 interaction is essential for viral replication and therefore the viral life cycle. This work may facilitate the development of anti-viral therapies for HPV-associated disease by targeting HPV DNA replication through disruption of the E2/TopBP1 interaction.
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Agaba, Charles Ateenyi. "Human papillomaviruses and their association with squamous cell carcinoma of the conjunctiva". Stockholm : Kampala : Karolinska Institutet ; Makerere University, 2009. http://diss.kib.ki.se/2009/978-91-7409-599-9/.
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Kwan, Tak-ching Tracy y 關德貞. "Human papillomavirus testing in cervical cancer screening: potential harms and implications for intervention". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B4658836X.
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Leung, Tsin-wah y 梁展華. "The role of human papillomavirus (HPV)-related molecular markers in cervical neoplasia, with emphasis on p-21 activated kinase type 1 (PAK 1)". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/195983.
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Since high-risk Human Papillomavirus (HPV) plays a critical role in cervical carcinogenesis, it is essential to improve our understandings on the role of HPV-related molecular markers in cervical neoplasia. The aim of this study was to investigate the expression and prognostic significance of selected HPV-related markers, including HPV16/18 E2 binding sites (E2BS) methylation, Pak 1, c-FLIP, Notch 1 and Brd4 expressions, as well as the potential functions of Pak 1 in cervical neoplasia.
First, the differential expressions of these markers among clinical samples of normal cervical epithelium, low-grade and high-grade cervical intraepithelial neoplasia (CINs) and cervical cancer were studied. Methylation status of E2BS 1, 2 and 4 was determined by pyrosequencing. Expressions of the target proteins were assessed by immunohistochemistry. Both HPV16/18 E2BS 1&2 and E2BS4 methylation progressively increased from normal cervix through CINs to cancer. More importantly, HPV16 E2BS1&2 (for transcriptional repression of E6/E7 oncoproteins) became more heavily methylated than E2BS4 (for transcriptional activation of E6/E7) in cervical cancer, favouring the differential binding of E2 protein to E2BS4.
Pak 1, c-FLIP, Notch 1 and Brd4 were all overexpressed in cervical cancer. Their expressions increased progressively from normal cervix to low-grade +/- high-grade CINs. Pak 1 and c-FLIP expression was positively correlated with HPV18 E6 and HPV16 E7 expression respectively. Notch 1 expression was inversely correlated with HPV16 E7 and HPV18 E6 expressions. Brd4 expression was positively correlated with HPV16 E2 and inversely correlated with HPV16 E7 expressions.
The prognostic significance of the molecular markers was investigated by correlation with clinical parameters. Heavier methylation at E2BS1&2 relative to E2BS4 was associated with better overall and disease-free survival in cervical cancer patients. HPV16 E2BS1&2 hypermethylation, weak cytoplasmic Brd4 expression, strong c-FLIP or Notch 1 expression were associated with higher risk of recurrent abnormal smears after treatment of CINs.
The role of Pak 1 in cervical cancer was further explored by comparing its functions between cervical cancer cell lines with and without transient knock-down of Pak 1 by siRNAs. It was demonstrated that the significant functions of Pak 1 in cervical cancer were on promoting cell proliferation and inhibiting apoptosis. Transient HPV16 E6 inhibition showed no effect on total / phosphorylated Pak 1 expressions.
Lastly, the function of Pak 1 on the regulation of cervical cancer cell radiosensitivity was also investigated. Pak 1 inhibition increased cell sensitivity in response to irradiation by enhancing apoptosis and inhibiting cell proliferation.
Conclusively, differential methylation status at HPV16/18 E2BS, as well as Pak 1, c-FLIP, Notch 1 and Brd4 proteins contribute to cervical carcinogenesis, and are potential prognostic markers in cervical cancer and CIN patients. Pak 1 inhibitor may be a potential adjunctive agent to improve radiotherapy.published_or_final_version
Obstetrics and Gynaecology
Doctoral
Doctor of Philosophy
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Ashby, Andrew Daniel Mark. "An investigation into the effects of the E5 family of transforming proteins on the vacuolar proton-translocating ATPase". Thesis, University of Glasgow, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341724.
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Scobie, Linda. "The role of p53 in cell transformation by BPV-4". Thesis, University of Glasgow, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.360279.
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Mota, Fernando Luis da Cruz Fernandes. "The immune microenvironment in HPV-related cervical neoplasia". Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287582.
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Daniels, Paula Rosamund. "Characterisation of HPV type 16 E6 interactions with p53 and E6-associated protein in vitro and ex vivo". Thesis, University of York, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387558.
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