Made available in DSpace on 2014-12-02T11:16:50Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-04-15Bitstream added on 2014-12-02T11:21:24Z : No. of bitstreams: 1 000796075.pdf: 1459054 bytes, checksum: 3ebaa1c352570cfcac9e744f29da4078 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O carcinoma epidermóide de pênis (CEP) é um tumor epitelial invasivo relativamente raro com alta morbidade, decorrente da própria doença ou de seu tratamento. Pacientes sem tratamento geralmente vão a óbito dentro de dois anos após o diagnóstico, devido o descontrole loco-regional ou a metástases distantes. Nos últimos anos, tem sido constatado que a infecção pelo vírus do papiloma humano (HPV), de alto risco, é um dos principais fatores de risco para o desenvolvimento do CEP. Sabe-se que duas proteínas virais, E6 e E7, estão associadas ao desenvolvimento tumoral em outros tipos de carcinomas causados por HPV. Porém, no CEP, os mecanismos moleculares envolvidos na replicação viral e suas interações com a célula hospedeira ainda não estão bem esclarecidos. A proteína viral E6 está associada à degradação de p53 enquanto a proteína E7 está associada à desestabilização da via de fosforilação da proteína Rb, na qual a ciclina D1 e a proteína p16 estão estreitamente relacionadas. O objetivo deste projeto foi correlacionar a presença de HPV de alto risco com os níveis de expressão das proteínas celulares p53, p16 e ciclina D1 em amostras de CEP. Foi realizado estudo comparativo com 61 amostras de pacientes infectados por HPV de alto risco e pacientes sem infecção. Observou-se que em tecidos com HPV de alto risco há diminuição da expressão de p53 e ciclina D1 e aumento de expressão de p16 em relação às amostras negativas (p<0,05). Não existem muitos estudos sobre este tumor. O presente trabalho pode contribuir para uma maior compreensão deste tumor e permitindo melhores tratamentos e prognósticos do paciente, além de contribuir para a definição de novas metodologias para a distinção entre lesões associadas ou não ao HPV de alto risco / Squamous cell carcinoma of the penis (SCCP) is a relatively rare invasive epithelial tumor with high morbidity due to the disease itself or its treatment. Untreated patients usually die within two years after diagnosis, due to the uncontrolled locoregional recurrence or distant metastases. In the last years, it has been observed that infection by the high risk human papilloma virus (HPV) is one of the main risk factors for SCCP development. It is known that the E6 and E7 viral proteins are associated with tumor development in other HPV associated carcinomas. However, about SCCP, the molecular mechanisms involved in viral replication and its interactions with the host cell are not well understood. The E6 viral protein is linked to the p53 cellular degradation whereas the E7 is linked with destabilization via phosphorylation of Rb protein, in which cyclin D1 and p16 are closely related. The goal of this project was to correlate the high-risk HPV presence with the expression levels of cellular proteins p53, p16 and cyclin D1 in SCCP samples. Comparative study was conducted with 61 samples from patients infected or not with high-risk HPV. It was observed that in high-risk HPV tissues there is down expression of p53 and cyclin D1 and overexpression of p16 when compared to negative samples (p <0.05). There are not many studies on this tumor. This study may contribute to a greater understanding of this tumor, allowing better treatments and prognoses for patients, and contribute to the development of new methodologies for the distinction between lesions associated or not with high-risk HPV

Diversas alterações de expressão proteica decorrentes do desenvolvimento canceroso cervical e dependentes do papilomavírus humano (HPV) vêm sendo apontadas na literatura, dentre elas destacam-se proteínas diretamente influenciadas pela ação de oncoproteínas do HPV, como: transglutaminase 2 (TG2) e p53 e proteínas com expressão modificada relacionada a alterações de controle de ciclo celular, como: p16INK4a, ki-67 e bcl-2. Neste estudo, objetivou-se analisar níveis expressionais de TG2, p16INK4a, p53, Ki-67 e bcl-2 em amostras de lesões escamosas intraepiteliais de baixo (LEIBG) e alto grau (LEIAG), precursoras do carcinoma escamoso de colo uterino e relacionar esta expressão a diferentes tipos virais do HPV. Foram utilizadas amostras histológicas obtidas por biópsia dirigida do colo uterino de pacientes, previamente confirmadas quanto à presença do HPV-DNA por reação em cadeia da polimerase (PCR) e tipagem viral. A quantificação da expressão ocorreu por meio da técnica de imunohistoquímica. Observou-se em LEIBG a elevada expressão de TG2 (p<0.05) e diminuída expressão de p16INK4a (p<0.05) enquanto que em LEIAG, esta proporção inverteu-se (Pearson value = -0.269). A expressão de p53 demonstrou-se variável em relação aos graus de lesão. As expressões de Ki-67 e bcl-2 variaram conforme os níveis teciduais das biópsias coletadas. A proteína p16INK4a apresentou sua expressão associada a HPV considerados de alto risco oncogênico (p<0.001), TG2 teve sua expressão associada ao HPV tipo 11 (p<0.05). Não foram evidenciadas associações significantes entre a expressão de p53, Ki-67 e bcl-2 e os tipos virais. Conclui-se que a expressão dos marcadores estudados foi influenciada pelo processo canceroso no colo uterino e pela infecção do HPV. / Submitted by Ana Guimarães Pereira (agpereir@ucs.br) on 2016-12-01T15:25:28Z No. of bitstreams: 1 Tese Karen Olivia Bazzo.pdf: 1961310 bytes, checksum: 63b5807c5c5cf317075c1e19cf0f168c (MD5) / Made available in DSpace on 2016-12-01T15:25:28Z (GMT). No. of bitstreams: 1 Tese Karen Olivia Bazzo.pdf: 1961310 bytes, checksum: 63b5807c5c5cf317075c1e19cf0f168c (MD5) Previous issue date: 2016-12-01 / Universidade de Caxias do Sul, UCS. / Changes in protein expression resulting from cervical cancer development and dependent on human papillomavirus (HPV) have been indicated in the literature, among them there are proteins directly influenced by HPV oncoproteins, such as transglutaminase 2 (TG2), p53; and proteins with modified expression related to cell cycle control changes, such as p16 INK4a a, ki-67 and bcl-2. This study aimed to analyze expressionais levels of TG2, p16INK4a, p53, ki-67 and bcl-2 in High-grade (HSIL) and low-grade (LSIL) squamous intraepithelial lesion and relate this expression to different viral types of HPV. Tissue samples obtained by biopsy were used directed cervical patients, previously genotyped HPV-DNA. Expression quantification were performed by immunohistochemical technique. It was observed in LSIL the overexpression of TG2 (p<0.05) and decreased expression of p16INK4a (p<0.05) although in HSIL, the proportion was reversed (Pearson value = -0.269). P53 expression was variable in relation to the degree of injury. The expression of ki-67 and bcl-2 levels varied depending beyond the basal layer. p16INK4a presented its expression associated with high-risk types of HPV (p<0.001) and TG2 expression was associated with HPV 11 (p<0.05). No significant associations were found between the viral types and the ki-67, p53 and bcl-2 expression. In conclusion, the expression of the marker is affected by cancerous process and by HPV infection, and expression analysis of these markers may reveal new biomarkers associated with cervical cancer process.

Os papilomavírus constituem uma extensa família de vírus associados a lesões epiteliotrópicas, assim como acometem o tecido mucoso onde podem causar tumores benignos que podem evoluir para a malignização. A papilomatose bovina é uma doença economicamente relevante, já que há a desvalorização dos animais a serem comercializados devido à aparência e depreciação do couro. Em humanos, a identificação dos tipos de papilomavírus (HPV) envolvidos bem como o relato de co-infecções são bem estabelecidos. Já foram descritos na literatura mais de 200 tipos de HPVs, o que ainda é pouco explorado na área da Medicina Veterinária, em que somente 21 tipos de papilomavírus bovino (BPV) foram caracterizados até o momento. A presente dissertação visou investigar a diversidade de BPV presentes em um papiloma de um bovino oriundo do Estado de Rondônia. A partir do DNA extraído da lesão, foi realizada a rooling circle amplification (RCA) seguida do sequenciamento de última geração (Ilumina MiSeq). O emprego dessas metodologias culminou na identificação do BPV13, que atualmente é bem caracterizado, e de três prováveis novos tipos de BPVs que haviam sido descritos em um único estudo recente. Estes resultados confirmam a presença de co-infecção em lesões de papilomatose bovina e demonstram que estas técnicas possibilitaram a detecção de espécies que não são identificadas pelos métodos convencionais. Este conhecimento sobre a diversidade de BPV servirá de base para o melhor entendimento da biologia do vírus e para a geração de vacinas profiláticas ou terapêuticas eficazes. / Papillomaviruses are an extensive family of viruses associated with epitheliotropic lesions, as well as affecting mucosal tissue where they can cause benign tumors that may progress to malignancy. Bovine papillomatosis is an economically relevant disease, since there is a devaluation of the animals to be marketed due to the appearance and depreciation of the leather. In humans, the identification of the types of papillomavirus (HPV) involved as well as the reporting of co-infections is well established. More than 200 types of HPV have been described in the literature, which is still little explored in the area of Veterinary Medicine, in which only 21 types of bovine papillomavirus (BPV) have been characterized. This study aimed to investigate the diversity of BPV present in a papilloma of a bovine animal from the State of Rondônia. From the DNA extracted from the lesion, the rooling circle amplification (RCA) was performed followed by the last generation sequencing (Ilumina MiSeq). The use of these methodologies culminated in the identification of BPV13, which is currently well characterized, and of three putative new BPVs types that had been described in a single recent study. These results confirm the presence of co-infection in bovine papillomatosis lesions and demonstrate that these techniques enabled the detection of species that are not identified by conventional methods. This knowledge on BPV diversity will serve as a basis for a better understanding of the biology of the virus and for the generation of effective prophylactic or therapeutic vaccines.

Diversas alterações de expressão proteica decorrentes do desenvolvimento canceroso cervical e dependentes do papilomavírus humano (HPV) vêm sendo apontadas na literatura, dentre elas destacam-se proteínas diretamente influenciadas pela ação de oncoproteínas do HPV, como: transglutaminase 2 (TG2) e p53 e proteínas com expressão modificada relacionada a alterações de controle de ciclo celular, como: p16INK4a, ki-67 e bcl-2. Neste estudo, objetivou-se analisar níveis expressionais de TG2, p16INK4a, p53, Ki-67 e bcl-2 em amostras de lesões escamosas intraepiteliais de baixo (LEIBG) e alto grau (LEIAG), precursoras do carcinoma escamoso de colo uterino e relacionar esta expressão a diferentes tipos virais do HPV. Foram utilizadas amostras histológicas obtidas por biópsia dirigida do colo uterino de pacientes, previamente confirmadas quanto à presença do HPV-DNA por reação em cadeia da polimerase (PCR) e tipagem viral. A quantificação da expressão ocorreu por meio da técnica de imunohistoquímica. Observou-se em LEIBG a elevada expressão de TG2 (p<0.05) e diminuída expressão de p16INK4a (p<0.05) enquanto que em LEIAG, esta proporção inverteu-se (Pearson value = -0.269). A expressão de p53 demonstrou-se variável em relação aos graus de lesão. As expressões de Ki-67 e bcl-2 variaram conforme os níveis teciduais das biópsias coletadas. A proteína p16INK4a apresentou sua expressão associada a HPV considerados de alto risco oncogênico (p<0.001), TG2 teve sua expressão associada ao HPV tipo 11 (p<0.05). Não foram evidenciadas associações significantes entre a expressão de p53, Ki-67 e bcl-2 e os tipos virais. Conclui-se que a expressão dos marcadores estudados foi influenciada pelo processo canceroso no colo uterino e pela infecção do HPV. / Universidade de Caxias do Sul, UCS. / Changes in protein expression resulting from cervical cancer development and dependent on human papillomavirus (HPV) have been indicated in the literature, among them there are proteins directly influenced by HPV oncoproteins, such as transglutaminase 2 (TG2), p53; and proteins with modified expression related to cell cycle control changes, such as p16 INK4a a, ki-67 and bcl-2. This study aimed to analyze expressionais levels of TG2, p16INK4a, p53, ki-67 and bcl-2 in High-grade (HSIL) and low-grade (LSIL) squamous intraepithelial lesion and relate this expression to different viral types of HPV. Tissue samples obtained by biopsy were used directed cervical patients, previously genotyped HPV-DNA. Expression quantification were performed by immunohistochemical technique. It was observed in LSIL the overexpression of TG2 (p<0.05) and decreased expression of p16INK4a (p<0.05) although in HSIL, the proportion was reversed (Pearson value = -0.269). P53 expression was variable in relation to the degree of injury. The expression of ki-67 and bcl-2 levels varied depending beyond the basal layer. p16INK4a presented its expression associated with high-risk types of HPV (p<0.001) and TG2 expression was associated with HPV 11 (p<0.05). No significant associations were found between the viral types and the ki-67, p53 and bcl-2 expression. In conclusion, the expression of the marker is affected by cancerous process and by HPV infection, and expression analysis of these markers may reveal new biomarkers associated with cervical cancer process.

Many human papilloma virus (HPV) types are sexually transmitted and HPV DNA types 16, 18, 31, and 45 account for more than 75% if all cervical dysplasia. Candidate vaccines are successfully completing US Federal Drug Agency (FDA) phase III testing and several drug companies are in licensing arbitration. Once this vaccine become available it is unlikely that 100% vaccination coverage will be probable; hence, the need for vaccination strategies that will have the greatest reduction on the endemic prevalence of HPV. This thesis introduces two discrete-time models for evaluating the effect of demographic-biased vaccination strategies: one model incorporates temporal demographics (i.e., age) in population compartments; the other non-temporal demographics (i.e., race, ethnicity). Also presented is an intuitive Web-based interface that was developed to allow the user to evaluate the effects on prevalence of a demographic-biased intervention by tailoring the model parameters to specific demographics and geographical region.

Tonsillar cancer (TC) presents an important part of head and neck cancers and its incidence is rising in the Czech Republic. Cigarette smoking and alcohol abuse are risk factors responsible for approximately two thirds of all head and neck cancers. Furthermore, a role of human papillomavirus (HPV) as an independent risk factor has been demonstrated recently. The aims of the present study were to find demographical differences between the group of HPV-positive and negative patients, to determine the prevalence of HPV in TC of Czech patients and also to find out whether the virus in HPV DNA positive tumors is transcriptionally active. Another aim was to test different markers of HPV infection for a precise selection of patients with HPV associated disease and to determine the prognostic role of these markers. A set of 109 patients with primary TC was examined for HPV DNA presence in tumor tissue and for the presence of HPV specific antibodies in serum. Data regarding risk factors were obtained by questionnaires. Forty-five samples were available for E6 and E2 mRNA analysis and for immunohistochemical analysis of p16 and p53 expression. The overall prevalence of HPV DNA in TC was 65%. In 93% of HPV16 DNA positive samples the virus was transcriptionally active. The E2 expression status has shown that in...

Tonsillar cancer (TC) presents an important part of head and neck cancers and its incidence is rising in the Czech Republic. Cigarette smoking and alcohol abuse are risk factors responsible for approximately two thirds of all head and neck cancers. Furthermore, a role of human papillomavirus (HPV) as an independent risk factor has been demonstrated recently. The aims of the present study were to find demographical differences between the group of HPV-positive and negative patients, to determine the prevalence of HPV in TC of Czech patients and also to find out whether the virus in HPV DNA positive tumors is transcriptionally active. Another aim was to test different markers of HPV infection for a precise selection of patients with HPV associated disease and to determine the prognostic role of these markers. A set of 109 patients with primary TC was examined for HPV DNA presence in tumor tissue and for the presence of HPV specific antibodies in serum. Data regarding risk factors were obtained by questionnaires. Forty-five samples were available for E6 and E2 mRNA analysis and for immunohistochemical analysis of p16 and p53 expression. The overall prevalence of HPV DNA in TC was 65%. In 93% of HPV16 DNA positive samples the virus was transcriptionally active. The E2 expression status has shown that in...

Thesis (MPH.) -- University of Limpopo, 2020 / Background of the study: Cervical cancer is a disease that is described as the state of overgrowth of tissue resulting from the disorganisation of cell division that is preceded by several earlier cervical changes, especially at the squamocolumnar junction of the cervix. Factors such as HPV, which is a sexually transmitted infection (STI), low socioeconomic status (SES), intercourse at a very early age, numerous childbirths, poverty and limited access to health care, are some of the contributing risk factors for cervical cancer. Most women in developing countries only seek professional help once the malignancy is already at an advanced stage. Purpose of the study: The aim of the study was to investigate the determinants of cervical cancer in patients seen in the gynaecology clinic at Mankweng hospital. And the objectives were: to profile the sociodemographic characteristics; to profile the contributory risk factors; and, to determine the association of risk factors for cervical cancer with the socio-demographic characteristics of the patients seen in the gynaecology clinic at Mankweng hospital. Research methodology: A quantitative, cross-section descriptive study, which has been validated and used in several studies globally, was conducted at Mankweng hospital, which is a tertiary referral academic hospital in the Limpopo Province, following all cervical cancer patients consulting at gynaecology outpatient clinic during the study period. Data were collected using a structured questionnaire and entered into computer software and analysed. Research findings: Thirty-seven percent of the women who participated in this study were single, 27% were married, 27% widowed and only 9% were divorced. Nearly half (46%) of the participants had secondary education and only 8% had tertiary education. The majority (91%) of the women were unemployed and only 9% were employed. The majority (40%) of the women were at stage II cervical cancer. Nearly two-thirds (62%) had had multiple partners. At the time of the study, 94% of the participants did not have multiple partners. Nearly two-thirds (64%) of the participants had heard about Pap smears before their current diagnosis and 62% of the participants had had a Pap smear before the current results. Few participants smoked cigarette (2%) or used contraceptive (3%). The young age group, single, divorced, with secondary and v tertiary education were more likely to be HIV positive. And the elderly, divorced, widowed and less educated were more likely to have high parity. Recommendations and conclusions: Information about the risk factors for developing cervical cancer, specifically the transmission of HPV, needs to be disseminated to young people. Rather than initiating cervical screening by age group, which may result in young women being refused screening irrespective of their risk, cervical screening guidelines should stipulate the initiation of cervical screening and HPV vaccine from the age of 15 onwards. Present study suggests that young women may be more prone to HPV and HIV due to the fact that young women who are single or divorced, with tertiary education were more likely to have multiple partners, which places them in a risk-based cervical screening target group. A final recommendation and conclusion is that a long-term, in-depth study on cervical cancer in young women in relation to the presence of the risk-factors should be carried out. Attempts should be made to reach women who rarely visit health care services.

Indiana University-Purdue University Indianapolis (IUPUI) / Human papillomaviruses (HPVs) are one of the most common causes of sexually transmitted disease in the world. HPVs are divided into high-risk (HR) or low-risk (LR) types based on their oncogenic potential. HPVs 16 and 18 are considered HR types and can cause cervical cancer. HPVs 6 and 11 are classified as LR and are associated with condyloma acuminata (genital warts). Viral proteins of both HR and LR HPVs must be able to facilitate a replication competent environment. The E7 proteins of LR and HR HPVs are responsible for maintenance of S-phase activity in infected cells. HR E7 proteins target all pRb family members (pRb, p107 and p130) for degradation. LR E7 does not target pRb or p107 for degradation, but does target p130 for degradation. Immunohistochemistry experiments on HPV 6 infected patient biopsies of condyloma acuminata showed that detection of p130 was decreased in the presence of the whole HPV 6 genome. Further, the effect of HR HPV 16 E7 and LR HPV 6 E7 on p130 intracellular localization and half-life was examined. Experiments were performed using human foreskin keratinocytes transduced with HPV 6 E7, HPV 16 E7 or parental vector. Nuclear/cytoplasmic fractionation and immunofluorescence showed that, in contrast to control and HPV 6 E7-expressing cells, a greater amount of p130 was present in the cytoplasm in the viii presence of HPV 16 E7. The half-life of p130, relative to control cells, was decreased in the cytoplasm in the presence of HPV 6 E7 or HPV 16 E7, but only decreased by HPV 6 E7 in the nucleus. Inhibition of proteasomal degradation extended the half-life of p130, regardless of intracellular localization. Experiments were also conducted to detect E7-binding partners. Cyclin C and cullin 5 were identified as proteins capable of binding to both HPV 6 E7 and HPV 16 E7. Preliminary experiments showed that decreasing protein levels of p600, a binding partner of both HPV 6 E7 and HPV 16 E7, by RNA interference might affect p130 stability. Elucidating the mechanisms of p130 degradation may identify potential targets for preventing degradation of p130 and allowing restoration of cell cycle control.

The utility of narrative as a persuasive mechanism has been increasingly investigated in recent years especially within the context of health behaviors. Although many studies have noted the effectiveness of narrative-based persuasive appeals, conceptual inconsistencies have made it difficult to determine what specific aspects of narrative messages lead to the most effective persuasive outcomes. In the present study, 145 female college students were randomly assigned to read one of four narrative health messages about a female freshman college students experiences with the human papillomavirus (HPV). Two elements of the narrative message structure were manipulated: the message frame (gain framed vs. loss framed), and the grammatical person of the text (first-person vs. third-person).The messages were presented via the medium of an online blog. After reading a narrative participants responded to a brief questionnaire designed to measure perceptions of threat regarding HPV contraction, perceptions of efficacy regarding HPV prevention, and intentions to get the Gardasil vaccine. Participants exposed to loss framed messages reported higher levels of perceived threat (susceptibility and severity) than participants exposed to gain framed messages although participants in the gain framed message conditions reported higher levels of perceived self-efficacy. Significant correlations were also found between levels of reported character identification and the two threat variables. No effects were found for grammatical person.