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Genital human papillomaviruses studies of their occurrence, type spectrum and expression /Forslund, Ola. January 1997 (has links)
Thesis (Ph. D.)--Lund University, 1997. / Added t.p. with thesis statement inserted.
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Plasma carotenoids and retinol and dietary intake : association with in situ and invasive cervical carcinomas in Bangkok, Thailand /Kaunda, Jean R. January 1900 (has links)
Thesis (Ph. D.)--Oregon State University, 2007. / Printout. Includes bibliographical references. Also available on the World Wide Web.
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Studies on molecular mechanisms of transformation by human papillomavirus : the role of E6 and E5 oncogenesGu, Zhengming January 1996 (has links)
No description available.
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Studies on molecular mechanisms of transformation by human papillomavirus : the role of E6 and E5 oncogenesGu, Zhengming January 1996 (has links)
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.
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Expression of the chimeric SAF gene from Human Papillomavirus in the methylotrophic yeasts Pichia pastoris and Hansenula polymorphaBurke, Arista 03 1900 (has links)
Thesis (MSc (Microbiology))--Stellenbosch University, 2011. / ENGLISH ABSTRACT: The link between infection with Human Papillomavirus (HPV) and the development of cervical
cancer has been established by several epidemiology studies. Cervical cancer is the second most
common cancer among women and it occurs at a rate of 22.8 cases per 100 000 women in South
Africa. Approximately 86% of newly reported cases of cervical cancer occur in developing
countries where limited access to medical facilities hampers efforts to prevent and screen for
HPV infection. Two commercial virus-like particle (VLP) vaccines consisting of HPV major
structural protein L1, which protect against the most common high-risk HPV-types, are currently
available. The high cost and type specificity of these commercially available vaccines have
necessitated the development of a low cost, broad-spectrum HPV vaccine. Inclusion of the minor
structural protein L2 has been shown to induce broadly cross-neutralizing antibodies and
therefore a chimera was constructed that contains an epitope of L2 inserted within the L1
sequence. This construct, renamed SAF, was shown to be highly immunogenic and thus has the
potential to be used as a prophylactic cervical cancer vaccine. Methylotrophic yeasts are known
to be excellent producers of recombinant proteins due to their strongly inducible promoters that
allow culturing of these yeasts to very high cell densities. Pichia pastoris and Hansenula
polymorpha have been employed in several studies for heterologous protein production and
levels of protein higher than 1 g/L have been reported. These yeasts also have GRAS status and
can therefore be used to manufacture products for use in humans.
In this study, the potential of H. polymorpha and P. pastoris to produce SAF intracellularly was
evaluated. The effect of increased gene dosage and peroxisomal targeting on SAF production
was examined as possible strategies to increase the yield of SAF. Peroxisomal targeting was
achieved by fusing the SAF gene at the C-terminal end with the Peroxisomal Targeting
Sequence 1 (PTS1) which consists of a short tri-peptide: –SKL. The functionality of PTS1 was
confirmed using green fluorescent protein (GFP), fluorescence microscopy and peroxisome
isolation. Peroxisomal targeting was shown to have a negative effect on SAF production levels
in both H. polymorpha and P. pastoris. An increase in gene dosage had no discernable effect on
SAF yield in H. polymorpha which is in contrast to previous research. The highest production
levels were achieved by P. pastoris KM71 (24.86 mg/L) which compares well to levels of L1 achieved by other research groups. The most significant insight emerging from this work was
that all the strains that produced SAF at detectable levels were equally efficient at the production
of SAF. Increased biomass was therefore the biggest contributor to high SAF levels (mg/L) in
the P. pastoris strains as significantly higher cell densities were achieved during culturing of
these strains. With the necessary optimisation, the methylotrophic yeasts have the potential to be
used as hosts for the production of a broad-spectrum HPV vaccine. / AFRIKAANSE OPSOMMING: Die skakel tussen infeksie met Mens Papilloomvirus (HPV) en die ontwikkeling van servikale
kanker is deur verskeie epidemiologiese studies bevestig. Servikale kanker is die tweede mees
algemene kanker onder vroue en dit kom voor teen ‘n tempo van 22.8 gevalle per 100 000 vroue
in Suid Afrika. Ongeveer 86% van alle nuwe gevalle kom voor in ontwikkelende lande waar
beperkte toegang tot mediese fasiliteite pogings om HPV infeksie te voorkom en te behandel,
belemmer. Twee pseudovirale-partikel (VLP) entstowwe teen HPV is tans op die mark
beskikbaar en hierdie entstowwe verleen immuniteit teen die mees algemene hoë-risiko HPV
tipes. Die hoë koste en nou spektrum van hierdie entstowwe het dit nodig gemaak om ‘n
goedkoop, wye-spektrum HPV entstof te ontwikkel. Navorsing het bewys dat die insluiting van
die strukturele L2 proteïen in die VLP entstof, lei tot die indusering van neutraliserende
teenliggame, wat wye spektrum antigenisiteit tot gevolg het. ‘n Chimeriese proteïen wat ‘n
epitoop van L2 binne die L1 volgorde bevat is gekonstrueer, en hierdie proteïen is benoem SAF.
SAF het hoë immunogenisiteit en kan dus potensieel as ‘n voorkomende servikale kanker entstof
gebruik word. Metielotrofiese giste is bekend vir hulle vermoë om hoë vlakke rekombinante
proteïene te produseer as gevolg van hulle induseerbare promotors wat groei tot baie hoë sel
digthede toelaat. Pichia pastoris en Hansenula polymorpha is in menigte studies gebruik om
heteroloë proteïene te produseer tot vlakke bo 1 g/L. Hierdie giste en die proteïen produkte wat
hulle vorm word algemeen aanvaar as veilig vir menslike gebruik.
In hierdie studie het ons die potensiaal van H. polymorpha en P. pastoris om SAF intrasellulêr te
produseer, geevalueer. Die effek op SAF produksie van verhoogde geen dosering asook die
teiken van SAF na die peroksisoom was ondersoek as moontlike strategieë om die opbrengs van
SAF te verhoog. Die teiken van SAF na die peroksisoom is behaal deur die Peroksisomale
Teiken Volgorde 1 (PTS1) aan die C-terminaal van SAF te heg. Die funksionaliteit van PTS1
was bevestig deur gebruik te maak van groen fluoroserende proteïen (GFP), fluoressensie
mikroskopie en isolering van peroksisome. Teiken van SAF na die peroksisoom het ‘n negatiewe
uitwerking gehad op SAF uitdrukking in beide H. polymorpha en P. pastoris. ‘n Verhoging in
geen dosering het geen onderskeibare effek gehad op SAF opbrengs in H. polymorpha nie wat in
teenstelling is met vorige navorsing. Die hoogste produksie vlakke is opgelewer deur P. pastoris KM71 (24.86 mg/L) wat goed vergelyk met vlakke van L1 wat deur ander navorsings groepe
behaal is. Die belangrikste gevolgtrekking wat gemaak kan word uit hierdie studie is dat al die
rasse wat SAF geproduseer het in meetbare hoeveelhede ewe effektief was. Verhoogde biomassa
was dus die grootste bydraende faktor tot hoë SAF vlakke (mg/L) in die P. pastoris rasse as
gevolg van die hoë sel digthede wat hierdie rasse kan bereik. Dit is duidelik dat metielotrofiese
giste, met die nodige optimisering, oor die potensiaal beskik om as gasheer sisteme te dien vir die
produksie van ‘n wye spektrum HPV entstof. / The NRF and the Department of Microbiology for financial support
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Apoptotic mechanism of anti-tumor treatment in human laryngeal squamous cell cancer infected with human papillomavirus type 16 (HPV16). / CUHK electronic theses & dissertations collectionJanuary 2006 (has links)
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.
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The role of human papillomavirus DNA methylation in cervical lesion progression.January 2011 (has links)
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
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Social network simulation and mining social media to advance epidemiologyCorley, Courtney D. Mikler, Armin, January 2009 (has links)
Thesis (Ph. D.)--University of North Texas, Aug., 2009. / Title from title page display. Includes bibliographical references.
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Human papillomavirus and cervical cancer in Western AustraliaBrestovac, Brian January 2005 (has links)
[Abstract not available]
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Papillomatosis and carcinomatosis in the Western barred bandicoot (Perameles bougainville) /Woolford, Lucy. January 2008 (has links)
Thesis (Ph.D.)--Murdoch University, 2008. / Thesis submitted to the Faculty of Health Sciences. Inlcudes bibliographical references (leaves 241-286)
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