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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
131

Suc Khoe La Quan Trong Hon Sac Dep! Health is Better than Beauty! Improving Breast and Cervical Cancer Screening Outcomes among Vietnamese Women

Nguyen, Anh 27 April 2011 (has links)
Vietnamese women experience cancer screening disparities and inconsistent adherence to screening guidelines. The goal of this study was to implement and evaluate a breast and cervical cancer screening intervention to promote cancer screening knowledge, attitudes, self-efficacy, intention, and behavior for Vietnamese women. Secondary objectives of the study included examining the relationships between cultural variables (e.g., acculturation, ethnic identity, religiosity, and collectivism) and cancer screening variables. The study enrolled 102 women from the greater Richmond metropolitan area. Participants were assigned to an intervention group or a print material control group. In the intervention session, participants were exposed to information on female cancers and were taught how and where to access Pap tests and clinical breast exams (CBE). Follow-up data were collected six months after the intervention to determine whether or not there were longer-term program effects. Intervention participants also took part in focus groups that examined their reactions, thoughts, feelings, and experiences in regards to the intervention. In addition, focus groups explored participants’ sources of motivation for cancer screening and whether they shared information obtained in the sessions with other individuals. The intervention was effective in promoting immediate and longer-term gains in breast and cervical cancer knowledge, attitudes towards screening, self-efficacy for screening, and actual screening behaviors. The study’s findings indicated that acculturation was linked to higher levels of self-efficacy and screening behavior and less positive attitudes towards screening. Personal and social extrinsic religiosity were associated with more positive attitudes towards screening. Social extrinsic religiosity was also associated with more self-efficacy for screening and screening behavior. Intrinsic religiosity was linked to lower levels of self-efficacy for screening. Focus group discussions revealed that the women shared cancer-related information with friends, female family members, and husbands. Focus group discussions also revealed that emphasis on caretaking roles may help increase women’s adherence to screening guidelines. This study provides evidence for the effectiveness of culturally-tailored strategies in developing cancer screening interventions for the Vietnamese population. This study also demonstrates how health information is transmitted across informal channels within faith-based communities.
132

Cancers du col de l’utérus et infection à VIH en Afrique de l’Ouest : Epidémiologie descriptive, déterminants et dépistage / Cervical cancer and HIV infection in West Africa : Epidemiology, determinants and screening

Jaquet, Antoine 18 December 2012 (has links)
Le cancer du col de l’utérus est la première cause de cancer chez la femme en Afrique de l’Ouest, une région du monde où le virus de l’immunodéficience humaine (VIH) sévit de manière endémique. Ce travail s’inscrit dans le cadre de l’étude du lien entre ces deux pathologies ainsi que des spécificités du dépistage du cancer du col dans le contexte de l’infection à VIH.Notre travail de recherche a été conduit en plusieurs étapes. Une enquête hospitalière a tout d’abord comparée la fréquence du VIH chez des femmes atteintes de cancer du col et chez des femmes atteintes d’autres cancers. Nous avons ensuite mis en place un programme de dépistage des cancers du col par inspection visuelle au sein de trois cliniques VIH à Abidjan offrant cette intervention pendant une période de plusieurs mois. Un échantillon de ces femmes dépistées a enfin été prélevé pour la recherche de papillomavirus humains (PVH). Sur les 152 cas de cancer du col inclus dans la première enquête, 25% étaient VIH-positifs contre 4,7% chez les 257 patientes du groupe de comparaison, donnant un Rapport de Côte (RC) ajusté de 7,6 (3,6 – 16,2) pour l’association entre ces deux morbidités sévères. Un total de 4 046 femmes a été dépisté par inspection visuelle. La fréquence d’un test positif était de 9,0% (8,0 – 10,0) chez les 2 998 femmes VIH-positives et 3,9% (2,7 – 5,1) chez les 1 048 femmes VIH-négatives. La prévalence de l’infection à PVH oncogène était de 33,0% chez les 191 femmes VIH-négatives et de 52,8% chez les 254 femmes VIH-positives ayant pu être testé par PCR. Un taux de CD4<200 cellules/mm3 était associé à la présence d’un PVH oncogène (RC= 2,8 [1,1 – 8,3] Ref. CD4 ≥500). L’infection à VIH est fortement associée au risque de cancer du col ainsi qu’à la présence de ses précurseurs que sont les PVH. La mise en place de programmes de dépistage associé à une bonne reconstitution immunitaire semble être des mesures essentielles pour réduire le fardeau de ce cancer chez les femmes VIH-positives en Afrique de l’Ouest à l’ère de l’accès élargi aux antirétroviraux. / Cervical cancer is the leading cause of cancer among women in West Africa, where infection with the Human Immunodeficiency Virus (HIV) is endemic. This work study the link between these two pathologies as well as the specificities linked to cervical cancer screening in the context of HIV infection. Our research project was conducted in several stages. A first hospital-based study compared the prevalence of HIV in women with cervical cancer and in women with other cancers. We then implement a cervical cancer screening program with visual inspection methods in three HIV clinics in Abidjan during several months. A sample of women screened was finally selected and collected for human papillomavirus (HPV) identification. Of the 152 cases of cervical cancer included during the first study, 25% were HIV-positive compared to 4.7% among the 257 patients of the comparison group, giving an adjusted odd ratio (OR) of 7.6 (3.6 - 16.2). A total of 4,046 women were screened by visual inspection. The frequency of a positive test was 9.0% (8.0 - 10.0) in the 2,998 HIV-positive women and 3.9% (2.7 - 5.1) in the 1,048 HIV-negative women. The prevalence of oncogenic HPV was 33.0% in the 191 HIV-negative women and 52.8% in the 254 HIV-positive women that underwent PCR testing. A CD4 count <200 cells/mm3 was associated with the presence of oncogenic HPV (OR = 2.8 [1.1 - 8.3] Ref. CD4≥500). HIV infection is strongly associated with cervical cancer and the presence of its precursors, oncogenic HPV. The implementation of adapted screening programs combined with good immune reconstitution seems to be key measures to reduce the burden of cervical cancer in HIV-positive women in West Africa in the era of expanded access to antiretroviral drugs.
133

Etude des marqueurs de progression tumorale dans les cancers HPV-induits / Study of tumor progression biomarkers in HPV-induced cancers

Brochot-Dorigny, Alexandra 25 March 2013 (has links)
Les infections à papillomavirus humains à haut-risque (HPV-HR) sont responsables de 100% des cancers cervico-utérins et de 50% des carcinomes de l'oropharynx. Les infections du col utérin sont généralement transitoires et bénignes. Cependant, en cas d'infection persistante, elles peuvent s'accompagner d'une progression vers des lésions (pré)cancéreuses du col utérin. Les facteurs viraux qui favorisent la persistance ou la clairance virale sont encore mal connus. Dans une première partie, nous avons étudié la méthylation des régions 3'L1 et LCR dans des frottis cervico-utérins HPV16+ / cytologie normale, prélevés chez 37 femmes qui présenteront soit une infection transitoire soit une infection persistante avec progression vers une lésion précancéreuse. Nous avons montré que certains îlots CpG présentaient des taux de méthylation différents en fonction de l'évolution ultérieure de l'infection HPV et pourraient être utilisés comme marqueurs prédictifs.Les cancers de l'oropharynx associés à une infection à HPV-HR présentent un pronostic plus favorable que ceux associés à une intoxication alcoolo-tabagique. Les mécanismes responsables de ce meilleur pronostic sont encore mal compris. Dans une seconde partie, nous avons caractérisé le statut HPV dans 202 cas de cancers de l'oropharynx. Au sein des 32 cancers présentant une infection HPV16 active (avec expression des ARNm E6/E7), nous avons étudié la méthylation des régions 3'L1 et LCR et l'intégration du génome viral. Nous avons montré que les niveaux de méthylation de certains sites CpG, notamment des sites de liaison à la protéine virale E2 (E2BS3 et E2BS4) sont fortement méthylés dans les formes épisomales et mixtes mais sont non méthylés dans les formes intégrées pures.Enfin dans une troisième partie, nous avons étudié des marqueurs de transition épithélio-mésenchymateuse (TEM) dans des modèles cellulaires et des cancers oropharyngés, en fonction du statut HPV. Une moindre TEM, connue pour être impliquée de façon importante dans les phénomènes d'invasion tumorale, pourrait expliquer le meilleur pronostic associé aux cancers HPV-induits. Nous avons montré que la vimentine, marqueur le plus représentatif de l'acquisition de capacités migratoires et invasives, est plus exprimée dans les cellules tumorales HPV positives que dans les cellules HPV négatives. Le pronostic différentiel observé entre les 2 étiologies des cancers oropharyngés ne serait donc pas corrélé à la TEM.Mots-clés : Cancer, HPV, col utérin, oropharynx, biomarqueurs, méthylation, intégration, TEM. / High-risk human papillomavirus (HR-HPV) infections are responsible for 100% of cervical cancers and 50% of oropharyngeal cancers. Cervical infections are usually transient and benign. Persistent infections may however progress and lead to cervical (pre)cancerous lesions. Viral factors contributing to persistence or clearance are poorly understood. In a fist part, we studied methylation of 3'L1 and LCR regions in HPV16+ / normal cytology cervical smears, taken in 37 women who will present either a transient infection, or a persistent infection with progression to a precancerous lesion. We demonstrated that some CpG sites harbored differential methylation rates in relation with later outcome of HPV infection and may be used as predictive biomarkers.HR-HPV related oropharyngeal cancers present a better prognostic that their alcohol-and-tobacco-induced counterparts. Mechanisms responsible for this better prognostic are mainly unknown. In a second part, we characterized the HPV status in 202 oropharyngeal cancers. In the 32 cases presenting with HPV16 active infections (expressing E6/E7 mRNA), we studied 3'L1 and LCR methylation and integration of viral genome. We showed that methylation rates of some CpG sites, especially in E2 binding sites (E2BS3 & 4), were strongly methylated in episomal and mixed forms but were unmethylated in purely integrated forms.In a third part, we studied epithelial-to-mesenchymal-transition (EMT) markers in cellular models and oropharyngeal cancers, according to HPV status. A lesser EMT, known as an important phenomenon implicated in tumor invasion, could explain the better prognostic associated with HPV-induced cancers. We showed that vimentin, the more representative marker for migration and invasion ability acquisition is more expressed in HPV+ tumor cells than in HPV-negative cells. So the differential prognosis observed between the 2 oropharyngeal cancer etiologies may not be linked to EMT.Key-words: Cancer, HPV, cervical cancer, oropharynx, biomarkers, methylation, integration, EMT.
134

Disposição cinética dos enantiômeros da ifosfamida em pacientes portadoras de câncer de colo do útero / Kinetic disposition of the ifosfamide enantiomers in patients with cervical cancer

Rocha, Otávio Pelegrino 03 April 2013 (has links)
A ifosfamida é um pró-fármaco que apresenta um átomo de fósforo quiral, disponível na clínica como mistura racêmica dos enantiômeros(+)-(R)-ifosfamida e (-)-(S)-ifosfamida para a utilização na quimioterapia. O objetivo do presente estudo foi o de avaliar a disposição cinética dos enantiômeros da ifosfamida em plasma de pacientes portadoras de câncer de colo do útero. As pacientes investigadas (n=6) receberam 2,5 g/m2 de ifosfamida racêmica administrada como infusão de 12 horas, sendo coletadas amostras de sangue imediatamente antes da administração e em 6, 10, 11, 12, 13, 14, 16, 18, 20 e 22 horas após a administração do fármaco. Os enantiômeros da ifosfamida foram quantificados por LC-MS/MS, sendo separados na coluna OD-R em aproximadamente 14 min empregando como fase móvel mistura de acetonitrila e água (20:80) adicionada de 0,2% de ácido fórmico. O método é linear no intervalo de 1-100 ?g de cada enantiômero/mL de plasma a partir de extrações de alíquotas de 25 ?L de plasma, compatíveis com a aplicação em farmacocinética de infusão de curta duração da ifosfamida em pacientes com câncer de colo do útero.A disposição cinética da ifosfamidaéenantiosseletiva, com observação de maiores valores de AUC (437,31 vs349,18 h.?g/mL) e menores valores de clearance(4,17 vs5,22 L/h) para o enantiômero(+)-(R)-ifosfamida. / The prodrugifosfamide has a chiral phosphorus atom, and is available clinically as a racemic mixture of the enantiomers (+)-(R)-ifosfamide and (-)-(S)-ifosfamide for use in chemotherapy. The aim of this study was to evaluate the kinetic disposition of the enantiomers of ifosfamide in plasma of patients with cancer of the cervix. The investigated patients (n = 6) received 2.5 g/m2 of racemic ifosfamide administered as infusion of 12 hours and blood samples were collected immediately before administration and at 6, 10, 11, 12, 13, 14, 16, 18, 20 and 22 hours after drug administration. The enantiomers of ifosfamide were quantified by LC-MS/MS and were separated in an OD-R column in about 14 min using as mobile phase a mixture of acetonitrile and water (20:80) plus 0.2% of formic acid. The method is linear within the range of 1-100 mg of each enantiomer/mL of plasma from extractions of 25 mL aliquots of plasma, suitable for the application in pharmacokinetics of short duration infusion of ifosfamide in patients with cervical cancer. The kineticdisposition of ifosfamide is enantioselective, with observation of higher values of AUC (437.31 vs 349.18 h.?g/mL) and lower values of clearance (4.17 vs 5.22 L/h) for the enantiomer (+)-(R)-ifosfamide.
135

Mutation-function analysis in vivo of the nuclear localization signals of L2 minor capsid proteins of high risk HPV16 and low risk HPV11

Bockstall, Katy Elizabeth January 2008 (has links)
Thesis advisor: Junona Moroianu / During the papillomavirus replication cycle, the L2 minor capsid protein enters the nucleus in the initial phase after uncoating of the incoming virions and in the productive phase when L2 together with L1 major capsid protein mediate the encapsidation of the newly replicated viral genome. L2 proteins of both high risk HPV16 L2 and low risk HPV11 L2 have two nuclear localization signals (NLSs): one at the N-terminus (nNLS) and one at the C terminus (cNLS). The purpose of these experiments is to determine the minimal mutations necessary to inhibit the function of the NLSs. In this study, subcellular localization of enhanced green fluorescent protein (EGFP) fusions with full length L2 and L2 mutants lacking either the cNLS (EGFP-L2ΔC), nNLS (EGFP-L2ΔN), or both NLSs (EGFP-L2ΔNΔC) was analyzed in HeLa cell transfection assays. Full length HPV16 L2 and HPV11 L2 proteins localize to the nucleus. For both HPV16 and 11 L2, each NLS could independently mediate nuclear import in vivo. EGFP fusions were also made with mutated nNLS (EGFP-L2ΔCSbN) or mutated cNLS (EGFP-L2ΔNSbC). Transfected HeLa cells were examined by fluorescence microscopy and quantitative studies were done. In both HPV16 and 11 L2 proteins, mutation of basic residues in either NLS inhibited its nuclear import ability. / Thesis (BS) — Boston College, 2008. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Biology. / Discipline: College Honors Program.
136

Characterization of the Nuclear Export Signal of Human Papillomavirus 16 L2 Minor Capsid Protein

Halista, Courtney Ellen January 2011 (has links)
Thesis advisor: Junona Moroianu / The L2 minor capsid protein of human papillomavirus is one of two structural proteins that comprise the icosahedral shell. Two potential, leucine-rich nuclear export signals (NESs) had been identified in the HPV16 L2 sequence, one in the n-terminus (51MGVFFGGLGI60) and one in the c-terminus (462LPYFFDSVSL471). DNA primers for mutant L2 proteins were designed to specifically target these two potential NES regions. Two primers had mutations in the n-terminal located NES (nNES), while the other two primers had mutations in the c-terminal NES (cNES). L2 nuclear retention mutants, RR297AA (“MS4”) and RTR313AAA (“MS5”), served as the templates for these NES mutations. Using mutagenesis, the desired secondary mutations were introduced into the mutant L2 genes in order to create four, distinct mutants: RR297AA + P463_ (“MS4 T1”), RR297AA + V469_ (“MS4 T2), RTR313AAA + P463_ (“MS5 T1”), and RTR313AAA + V469_ (“MS5 T2”). In contrast to the pancellular localization of the MS4 and MS5 L2 mutants, the “MS4 T1,” “MS4 T2,” “MS5 T1”, and “MS5 T2” mutants were all localized nuclearly. These results suggest that deletion of the cNES inhibits nuclear export of the HPV16 L2 minor capsid protein. / Thesis (BS) — Boston College, 2011. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: College Honors Program. / Discipline: Biology Honors Program. / Discipline: Biology.
137

Investigation of Disparities in Cervical Cancer Prevention in the United States: HPV Vaccination and PAP Screening in 18-30 Year Old Women

Newransky, Chrisann January 2013 (has links)
Thesis advisor: James Lubben / In 2011, an estimated 12,710 women suffered from cervical cancer and 4,290 died from it in the U.S. HPV vaccination (HPV-V) and PAP screening (PAP-S) could reduce this burden. Using 2010 National Health Interview Survey data, current disparities in the use of PAP-S and HPV-V in U.S. women aged 18-30 years were investigated. An adapted Behavioral Model of Health Care Utilization guided the study. Main outcomes were PAP-S in prior year and ever-HPV-V, both initiation and completion. Adjusted predictor estimates were obtained through multivariate logistic regressions with appropriate statistical procedures and weights for complex survey design. A sub-analysis focused on unvaccinated women. The sample had 3,129 women aged 18-30 years, representing about 27 million women of similar age in the U.S. PAP-S, HPV-V initiation and completion rates were 53.5%, 17.9%, and 10.3%, respectively. Hispanics were 33% less likely than Non-Hispanic-Whites to initiate HPV-V. Non-Hispanic-Blacks were 55% more likely and 57% less likely than Non-Hispanic-Whites to receive PAP-S and complete HPV-V, respectively. Non-Hispanic Asians were 36% less likely than Non-Hispanic-Whites to receive PAP-S, but this result was borderline significant. Younger age and being unmarried were predictors of lower PAP-S but higher HPV-V. Ever gave birth was a predictor of higher PAP-S but lower HPV-V. Preventative behaviors (PAP-S and flu vaccination) were predictors of higher HPV-V. STI-history was a predictor of higher HPV-V and PAP-S. Not having health insurance for over one year or recent health provider visit were predictors of lower PAP-S and HPV-V. Living in the South was a predictor of lower HPV-V. Household income was not a predictor of any outcomes. Most common reported reason for no HPV-V was "no need." Study findings indicate interventions to mitigate disparities in cervical cancer prevention are needed. Tailored education interventions for both women and health care providers along with opportunities associated with the 2010 Affordable Care Act, such as broader access to health care, emphasis on health information technology, and initiatives with PAP screening and adult vaccination as potential quality indicators for performance/payment, can reduce these disparities. Future research should focus on the feasibility of alternative venues for receiving HPV-V and PAP-S. / Thesis (PhD) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Social Work. / Discipline: Social Work.
138

Ações de equipes da estratégia saúde da família na prevenção do câncer de colo de útero / Actions of family health strategy teams in prevention of uterine cervical cancer

Oliveira, Iácara Santos Barbosa 18 March 2011 (has links)
O câncer de colo de útero (CCU) constitui um sério problema de saúde pública nos países em desenvolvimento, devido às altas taxas de prevalência e mortalidade, principalmente entre as mulheres de nível socioeconômico baixo e em fase produtiva de suas vidas. Representa a quarta causa de morte, por câncer, no sexo feminino, em nosso país, onde cerca de 70% dos casos desse câncer são diagnosticados em fase avançada. Isto ocorre devido ao fato de uma grande parte das mulheres brasileiras não se submeterem regularmente ao exame preventivo de Papanicolaou, um método aceito pela população e comunidade científica, seguro, de fácil execução, não invasivo e de baixo custo. Em Passos-MG, a cobertura desse exame está abaixo do preconizado pelo Ministério da Saúde (MS). Nesse sentido, este estudo descritivo e exploratório, com abordagem quantitativa, teve como objetivo identificar e analisar as ações implementadas pelas 17 equipes da Estratégia Saúde da Família (ESF) do município, para a prevenção e detecção precoce do CCU. Foram entrevistados 73 trabalhadores, sendo 11 médicos, 12 enfermeiros, 16 técnicos de enfermagem e 34 agentes comunitários de Saúde (ACS), que se mostraram empenhados em favorecer a prevenção, promoção e diagnóstico precoce do CCU e entendem que o controle desse depende, essencialmente, de ações desenvolvidas por eles. Deixaram evidente a necessidade de complementação das ações e atividades que já são realizadas junto às mulheres, uma vez que essas ações acontecem, mas de forma pouco sistemática e sem uma rotina adequada. Deficiências da infra-estrutura oferecida e a inserção inadequada dos profissionais no serviço de saúde, alguns sem vínculo empregatício, assim como a fragilidade ou inexistência, ou ainda a má divulgação de práticas de educação em saúde fazem com que a assistência seja comprometida. Por outro lado, evidenciou-se o despertar dos profissionais para essa prática e para sua efetivação é preciso adequação das equipes de saúde da família, tendo como foco o aperfeiçoamento dos profissionais e incentivos, possibilitando o conhecimento teórico, prático e as atualizações necessárias, pois o êxito de ações para prevenção desse câncer depende da reorganização da assistência à saúde nos serviços, visando a qualidade e continuidade das ações integrais para as mulheres. Alianças e parcerias, com escolas, indústrias entre outros, assim como a existência de um protocolo de atendimento poderão direcionar as ações, apoiar decisões e nortear a organização do processo de trabalho. É importante o envolvimento de todos os profissionais que compõem a ESF como conhecedores da epidemiologia, dos fatores de risco, dos sinais e sintomas e dos instrumentos existentes para a prevenção do referido câncer. É preciso, ainda, que haja uma real preocupação com a gravidade dessa doença, por parte dos profissionais e de todos os responsáveis nos níveis federal, estadual e municipal, de forma a garantir o acesso aos serviços de saúde, uma assistência de qualidade proporcionada por profissionais qualificados, dentro de uma infra-estrutura adequada. / The uterine cervical cancer (CCU) form a serious problem for the health public in developing countries, because of the high prevail and mortality rates, specially between low economic social level of women and in the productive phase of their lives. It represents the 4º causes of death, by cancer, in the female sex in our country where 70% of these cancer cases are diagnosed in an advanced phase. This fact happens because a great part of the Brazilian women don´t do the prevent Papanicolaou exam regularly, a method that is accepted by the population and the cientific comunity, it is safe, easy to be done, not invading and cheap. In Passos-MG the cost of this exam is bellow the commend publicly by the Ministry of Health (MS).This descripted and exploratory study, with quantity approach had as objective to identify and analyse the used actions by the 17 teams of the Family Health Strategy (ESF) of the municipal district to prevention and early detection of the CCU. They interviewed 73 workers, composed by 11 doctors, 12 nurses, 16 nursing technical and 34 health communitarian agents (ACS) that made every effort in propiciating the prevention, promotion and early diagnosys of the CCU and they know that the control of this depends, specially of actions and activities that they had already done with these women, since these actions are done, but in a little systematic form and without an adequate routine. Deficiency in the infrastructure offered and the inappropriate insert of professionals in the service of health, some of them without employed link and the fragility or inexistency or the bad divulgation of practice in health education make the help compromised. Otherwise it made evident the awaking of professionals to this practice and for its effectivation it needs changing in the family health teams, having in view the improving of professionals and incentive, making it possible the teoric and pratical knowledge and the necessary update, because the success of actions to prevent this cancer depends on the reorganization of view the quality and continuity of whole actions for women. Alliances and associations to schools, industries and others and an existence of a register of service can conduct the actions, give support to decisions and give directions to the organization of the process of work. It´s important to get all the professionals that form the ESF as experienced of the epidemiology of the coefficient of risk, signals and symptoms and instruments that exist to prevent this cancer. It is needed that there is a worry with the danger of this disease by professionals and all the responsable people on the federal state and municipal levels to make sure the access of the health services, a quality aid given by qualified professional, in a proper infrastructure.
139

Papel do metabolismo de tumores associados ao papilomavírus humano na modulação do fenótipo de macrófagos humanos. / The role of HPV-associated tumor metabolism on human macrophage phenotype.

Stone, Simone Cardozo 07 October 2016 (has links)
O lactato, produto do metabolismo alterado das células tumorais, possui papel na modulação de fenótipo supressor em células imunes. Macrófagos são uma das principais células do microambiente tumoral, sendo pró-tumorais em câncer cervical. O objetivo desse trabalho foi avaliar o efeito do lactato no fenótipo de macrófagos associados a células tumorais derivadas de câncer cervical. Linhagens celulares positivas e negativa para HPV foram utilizadas para formação de esferoides tumorais, os quais receberam monócitos de doadores saudáveis para diferenciação em macrófagos. Macrófagos cultivados com linhagens tumorais positivas para HPV apresentaram fenótipo misto e pró-tumoral, enquanto os cultivados com a linhagem negativa, um fenótipo mais anti-tumoral. A inibição da enzima lactato desidrogenase, nas células tumorais, promoveu diferentes efeitos no fenótipo dos macrófagos, dependendo do tipo celular a que estavam associados. Essas alterações diminuíram o aspecto pró-tumoral desses macrófagos, que induziram maior proliferação de linfócitos T e morte de células tumorais. / The lactate, product of the altered metabolism of tumor cells, is associated with the induction of a suppressor phenotype in immune cells. Macrophages are one of the major cells of the tumor microenvironment, and are pro-tumor in cervical cancer. The aim of this study was to evaluate the effect of lactate in the phenotype of macrophages associated with tumor cells derived from cervical cancer. HPV positive and negative cell lines were used for formation of tumor spheroids, which received healthy donor monocytes to differentiate into macrophages. Macrophages cultivated with HPV positive tumor cell lines presented a mixed and pro-tumor phenotype, while macrophages cultivated with the HPV negative cell line, a more anti-tumor phenotype. Inhibition of lactate dehydrogenase in the tumor cells promoted different effects on macrophages phenotype, depending on the cell type that they were associated. These changes decreased the pro-tumor property of macrophages, which were able to induced T cell proliferation and tumor cell death.
140

Expressão de genes de vias de reparo de dano ao DNA em células infectadas por papilomavírus humano (HPV). / Expression of DNA damage repair pathways associated genes in cells infected with human papillomavirus (HPV).

Prati, Bruna 25 April 2014 (has links)
Os papilomavírus humanos são vírus de DNA que infectam epitélios em regiões anatômicas específicas. Alguns tipos de HPV, coletivamente denominados de alto risco oncogênico, têm associação etiológica com o câncer do colo do útero. Estes vírus expressam dois oncogenes, E6 e E7, que alteram o ciclo celular e o programa de diferenciação das células. Isto promove o acúmulo de defeitos mitóticos e instabilidade genômica, contribuindo à transformação maligna. Alterações nos sistemas de reparo de dano ao DNA associadas à presença de HPV têm sido descritas em diferentes modelos experimentais, no entanto, não tem sido analisadas de maneira sistemática. No presente estudo, avaliamos a expressão de 135 genes envolvidos nas vias de reparo de dano ao DNA em queratinócitos primários humanos e em linhagens derivadas de carcinomas do colo do útero positivas e negativas para HPV. Nossos resultados indicam a presença de alterações importantes na expressão de genes envolvidos nas vias de reparo de dano ao DNA em linhagens derivadas de tumores do colo do útero. / Human papillomaviruses are DNA viruses that infect epithelia in specific anatomical regions. Some HPV types, collectively known as high-risk types are etiologically associated with cervical cancer. These viruses express two oncogenes E6 and E7 that alter the cell cycle and cell differentiation. Besides, they promote genomic instability and the accumulation of mitotic defects contributing to malignant transformation. Alterations in the DNA damage repair systems associated with HPV presence have been described in various experimental model systems. However, they have not been systematically analyzed. In this study, we evaluated the expression of 135 genes involved in the DNA damage repair pathways in primary human keratinocytes and cervical cancer derived cell lines. Our results show the presence of important alterations in the expression of DNA damage repair genes in cervical cancer derived cell lines.

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