Vulvar cancer, although a rare neoplasia, implicates in serious problems due to the extensive surgery and consequent mutilation. It affects primarily elderly women, and has been more frequent in young patients associated with HPV infection. With the aim to identify pertaining factors evaluated in the genesis and progression of this tumor, an evaluation was carried out by immunohistochemistry (StrepABC), to identify the presence of estrogen and progesterone receptor in the epithelia and stroma of 45 vulvar lesions, of which 22 are invasive squamous cell carcinomas (ISCC), 12 are high-grade intraepithelial lesions (HSIL) and 11 are low-grade intraepithelial lesions (LSIL). Furthermore p53 protein expression and the cell proliferating index, through MIB1, were evaluated. The cases came from the Cancer Institute of Cearà (CIC), the Hamilton Monteiro Laboratory of Pathology (HML) and the Laboratory of Pathology of UFC. A descriptive analysis of the parameters and their correlations were carried out with a statistical significance level of at least 95% (p ≤ 0,05). Results and inferences: 1 - Age: The ISCC occurred between the ages of 34 and 76 years (average 58.59 and median 60.5), the HSIL ranges from 18 to 59 years (average 40,91 and median 42) and the LSIL-papilloma within the ages of 18-58 (average 32.63 and median 32), in the expected age groups and interval ranges, according to the natural history reports of such lesions, highlighting the growing of ISCC in patients ever younger. 2 - Hormonal receptor: The nuclear receptors of estrogen and progesterone were detected in the three groups analyzed, with a growing tendency of tumoral progression, however without significant statistical correlation in the epithelia level. Thus they cannot be considered a predictive and prognostic factor in the follow-up of these lesions. However in the stroma the presence of nuclear immunostain is significant (more with ER) in the HSIL and ISCC, which can be important to the tumor growth. The high and frequent immunostain was also observed in the cytoplasm of keratinocytes of in situ carcinomas and keratinizing invasive squamous cell carcinoma. These findings will be evaluated in the future. 3 - p53: The expression of p53 was detected in all groups, ISCC (68,18%), HSIL (66,66%) and LSIL (63,63%), having more frequent high scores in carcinomas (53,33%) than in LSIL (0,00%). The behavior of HSIL is similar to the behavior of ISCC. It is evident that there is an accumulation alteration of p53 with the tumoral progression. 4 - MIB1- There were significant differences between ISCC and LSIL (p=0,00), also among HSIL and LSIL (p=0,03). There was no significant difference between ISCC and HSIL. This expresses the tendency of high index cell proliferation with tumoral progression. In addition, the independence of the variables, MIB1 and p53, were verified. . / O cÃncer de vulva, embora entidade rara, envolve problemas sÃrios de tratamento devido à extensÃo cirÃrgica e conseqÃente mutilaÃÃo. à uma neoplasia que acomete preferencialmente mulheres em idade mais avanÃada, tendo havido uma crescente incidÃncia em pacientes de menor faixa etÃria com infecÃÃo pelo HPV. Com o objetivo de identificar fatores envolvidos na gÃnese e na progressÃo dessas neoplasias, foi avaliada, por imunoistoquÃmica (StrepABC), a presenÃa de receptores hormonais de estrÃgeno e de progesterona no epitÃlio e estroma de 45 lesÃes vulvares, sendo 22 carcinomas epidermÃides invasores (CEC), 12 lesÃes intra-epiteliais escamosas de alto grau (LIEAG) e 11 lesÃes intra-epiteliais escamosas de baixo grau (LIEBG); tambÃm, a expressÃo da proteÃna p53 e o Ãndice de proliferaÃÃo celular, mediante o MIB1, conforme a idade. Os casos foram oriundos do Instituto de PrevenÃÃo do CÃncer do Cearà (IPCC), do LaboratÃrio de Patologia Dr. Hamilton Monteiro (LHM) e do LaboratÃrio de Patologia da UFC. Procedeu-se à anÃlise descritiva dos parÃmetros e de suas correlaÃÃes, com nÃvel de significÃncia de pelo menos 95% (p≤0,05). Resultados e inferÃncias: 1- idade: os CEC incidiram dos 34 aos 76 anos de idade (mÃdia aos 58,59 anos e mediana aos 60,5 anos); as LIEAG ocorreram dos 18 aos 59 anos (mÃdia aos 40,91 anos e mediana aos 42 anos) e as LIEBG, dos 18 aos 58 anos (mÃdia aos 32,63 anos e mediana aos 32 anos), dentro das faixas e intervalos etÃrios esperados conforme relatos da histÃria natural de tais lesÃes, destacando-se a ocorrÃncia crescente de CEC em pacientes de faixa etÃria cada vez menor; 2- receptores hormonais: os receptores nucleares de estrÃgeno e de progesterona estÃo presentes nos trÃs grupos analisados, com tendÃncia crescente com a progressÃo tumoral; todavia, sem correlaÃÃo estatisticamente significativa ao nÃvel do epitÃlio, nÃo podendo ser considerados como marcadores preditivos / prognÃsticos no seguimento dessas lesÃes. Entretanto, no estroma, à significativa a presenÃa maior de nÃcleos marcados (mais com RE) nas LIEAG e nos CEC, o que pode ter importÃncia no crescimento tumoral. Viu-se, ainda, marcaÃÃo citoplasmÃtica forte e freqÃente para progesterona em lesÃes escamosas in situ e invasoras ceratinizantes, devendo esses achados serem mais bem avaliados em pesquisas subseqÃentes; 3- p53: houve expressÃo de p53 em todos os grupos, CEC (68,18%), LIEAG (66,66%) e LIEBG (63,63%), sendo significativa a preponderÃncia de escores altos nos carcinomas (53,33%) em relaÃÃo Ãs LIEBG (0,00%). O comportamento das LIEAG em relaÃÃo à p53 à similar ao comportamento dos CEC; fica patente que hà alteraÃÃo acumulada da p53 com a progressÃo tumoral; 4- MIB1: houve diferenÃa significativa dos nÃcleos marcados para MIB1 entre os CEC e as LIEBG (p=0,00), assim como entre as LIEAG e as LIEBG (p=0,03). NÃo houve diferenÃa significativa entre os CEC e as LIEAG. Isso expressa uma tendÃncia ao maior Ãndice de proliferaÃÃo celular com a progressÃo tumoral. Verificou-se ainda a independÃncia das variÃveis p53 e MIB1.

Orientadores: Paulo Cesar Giraldo, Egberto Ribeiro Turato / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-03T16:27:35Z (GMT). No. of bitstreams: 1 Cordeiro_SilviaNogueira_M.pdf: 264608 bytes, checksum: f70bfd788536b476721cf668d79bad30 (MD5) Previous issue date: 2003 / Resumo: As vulvovaginites constituem-se seguramente uma das principais queixas ginecológicas que levam as mulheres aos consultórios médicos. O motivo pelo qual existem freqüentes recorrências ainda não estão claramente estabelecidos. Objetivos: Este trabalho teve a finalidade de identificar fatores socioeconômicos, sexuais e psicológicos que poderiam estar associados à recorrência de vulvovaginites. Sujeitos e Métodos: Foram estudadas 51 mulheres com diagnóstico confirmado de vulvovaginite recorrente e outras 61 mulheres-controles. O estudo foi realizado no Departamento de Tocoginecologia da Universidade Estadual de Campinas. Após consentimento informado, todas foram submetidas a uma entrevista estruturada sobre sua condição socioeconômica e seu comportamento sexual. Utilizou-se também questionário com perguntas fechadas e semi-abertas, para investigação dos aspectos psicológicos, que possibilitou o aprofundamento das questões relacionadas às vivências afetivas. A análise dos resultados para testar a associação entre os grupos e as variáveis independentes relacionados a fatores socioeconômicos e sexuais, foi realizada através da estimativa por odds ratio, com intervalo de confiança de 95%. A associação entre aspectos psicológicos e os grupos estudados foi abordada segundo o teste de análise de correspondência múltipla. Resultados: As análises apontaram que as condições econômicas não estiveram associadas com a ocorrência de vulvovaginite recorrente. As mulheres brancas, OR 3,03 e IC de 95% (1,25 a 7,33) e as que usavam condom, OR 2,44 e IC de 95% (0,47 a 12,63) apresentaram-se mais associadas às vulvovaginites recorrentes. Inversamente, o uso de medroxiprogesterona de depósito, OR 0,05 e IC de 95% (0,01 a 0,50) e amenorréia, OR 7,99 e IC (1,73 a 36,87), estiveram mais associados ao grupo-controle. Os hábitos de higiene, vestuário e comportamento sexual não tiveram associados às vulvovaginites recorrentes. Os aspectos psicológicos analisados mostraram que as características maternas estiveram mais associadas às mulheres com vulvovaginite recorrente e que os pais destas mulheres não tinham um bom relacionamento entre si. Os aspectos relacionados ao desenvolvimento psicossexual não mostraram clara associação com o grupo de estudo. Conclusão: O conjunto das características socioeconômicas não parece interferir com a recorrência de vulvovaginite. O comportamento sexual das mulheres do grupo de estudo não parece ter influenciado nas recorrências. As vulvovaginites recorrentes parecem ser uma expressão psicossomática, possivelmente associada a conflitos relacionados ao desajuste conjugal das figuras parentais e a dificuldades no relacionamento com a figura materna / Abstract: Episodes of Vulvovaginitis are quite definitely one of the most common gynecological complaints that lead women to consult a gynecologist. The reasons for frequent recurrences have not been clearly established. Objectives: identify the social-economical, sexual and psychological factors that can be associated to the recurrence of vulvovaginitis. Subjects and Methods: fifty-one women presenting a diagnosis of recurrent vulvovaginitis and 61 controls were studied. The study was carried out at the department of Gynecology the State University of Campinas (UNICAMP, SP. Brazil). After informed consent all the patients were submitted to a structured interview regarding their social-economical level and sexual behavior. The questionnaire used closed and semi-open questions so as to investigate the psychological aspects, which allowed an in-depth aspect in the questions related to their emotional life. The analysis of the results to test the association between the groups and the independent variables related to social-economical and sexual factors was carried out by odds ratio (confidence interval of 95%). The association between the psychological aspects and the study groups was carried out based on the multiple correspondence analysis test. Results: the analyses point out that the social-economic conditions were not associated to the occurrence of RVV. White women, O.R. 3.03 and confidence interval of 95% (1.25 to 7.33) and those that use condoms, O.R. 2.44 and confidence interval of 95% (0.47 to 12.63) presented more associations to recurrent vulvovaginitis. Contrary, to this, the use of medroxiprogesterona depo and amenorreia was more associated to the control group. Hygiene, clothing and sexual behavior did not seem to influence the risk of recurrent vulvovaginitis. The psychological aspects analyzed showed that maternal characteristics were more associated to women presenting recurrent vulvovaginitis and to the fact that their parents did not have a good relationship. The psycological aspects related to sexuality did not show a clear association with the study group. Conclusion: the set of social-economic characteristics does not seem to interfere with the recurrence of vulvovaginitis. The sexual behavior of the women from the study group does not seem to have influenced the recurrences. Recurrent vulvovaginitis seem to have been a psycho-somatic expression, possibly associated to conflicts related to marital strife between the patients'parents, and the patients'difficulties in relating to the maternal figure / Mestrado / Ciencias Biomedicas / Mestre em Tocoginecologia

Orientador: Liliana Aparecida Lucci de Angelo Andrade / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-07-19T13:41:15Z (GMT). No. of bitstreams: 1 Engelman_DianaEliciSader_M.pdf: 6002097 bytes, checksum: 33ceda50142d22ad0fcec1bfc9d0c09c (MD5) Previous issue date: 1994 / Resumo: Recentemente tem sido observado um aumento da freqüência de diagnósticos de neoplasia intraepitelial vulvar grau III, principalmente em mulheres jovens. Estudos sobre o câncer genital apontam evidências de que a infecção pelo vírus do papiloma humano é um fator de risco importante para a transformação neoplásica epitelial. No período de 1983 a 1992 foram levantados 30 casos de l1eoplasia intraepitelial vulvar grau III e seis de carcinoma escamoso estádio Ia. A pesquisa do antígeno comum do capsídeo viral foi realizada através da imulloperoxidase. O estudo do tipo do vírus nas lesões foi realizada pela técnica de hibridização "in situ", com utilização de sondas biotiniladas dos HPV 6/11, 16/18 e 31/35/51. A idade média das pacientes com neoplàsia intraepitelial vulvar foi de 47,5 anos e das com carcinoma estádio Ia, 61,1 anos. Histologicamente foram observadas .atipias coilocitóticas em 83,3% dos casos. O exame da imunoperoxidase foi positivo em 36,1% dos casos, com idade,' média de 39,1 anos. A detecção do vírus pela hibridização "in situ" ocorreu em 41,7% dos casos, com idade média de 38,3 anos. Todos os casos positivos apresentaram o tipo 16/18, porém em quatro casos houve associação de diferentes tipos virais na mesma lesão. A positividade dos métodos não estava associada à presença ou ausência de atipias coilocitóticas. Quando se considerou a positividade para um ou outro método, a detecção do vírus ocorreu em 63,9% dos casos. A alto índice de detecção relaciona o papilomavírus humano com estas lesões, em especial o tipo 16/18, principalmente em grupos etários mais jovens. A ampla faixa etária de distribuição dos casos de neoplasia intraepitelial vulvar grau lU, sugere que o seu tempo de evolução é longo, demonstrando a importância do exame da vulva no exame ginecológico de rotina para melhor detecção e tratamento precoce das lesões / Abstract: Recently, an increase has been observed in the frequency of diagnosis of vulvar intraepithelial neoplasia grade III, special1y in young women. Studies in gynecologic cancer suggest that hwnan papillomavirus infections play an important role in the epithelial neoplastic transfOlmation. Between 1983 and 1992, 30 cases of vulvar intraepithelial neoplasia grade III and six cases of vulvar carcinoma stage Ia were analysed. The research for the common antigen of the viral capsid was done by the immunoperoxidase technique. The virus types were identified by the "in situ" hybridization technique, with biotinylated probes for HPV 6/11, 16/18 and 31/35/51. The mean age ofthe patients with vulvat. int:raepithelial neoplasia was 47,5 years an the ones with vulvar carcinoma stage Ia, 61, I years. Histologically, koilocytotic atypia was observed in 83,3% of the cases. The .immunoperoxidase teclmique was positive in 36,1% of the cases, with the mean age of 39, 1 years. The detection of the virus by "in situ" hybridization occurred in 41,7% of the cases, with mean age of 38,3 years. AlI the positive cases had the virus type 16/18, but in four of them there was association with other virus types in the same lesion. The positivity of these techniques was not related to the presence or absence of koiIocytotic atypia. When the positivity for one or the other method was considered, virus detection occulTed in 63,9% of the cases. This high rate of detection shows a relationship of the human papillomavirus with these vulvar Iesions, specially with type 16/18 and in younger age groups. The wide age range distribution of the vulvar intraepithelial neopIasia grade lU patients, suggests that its evolution is long, showing the importance of the vulvar region in routine gynecologic examination, to allow early detection and treatment of these lesions / Mestrado / Anatomia Patologica / Mestre em Ciências Médicas

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-06-15T14:12:19Z No. of bitstreams: 1 Renata Aparecida Belotto.pdf: 1572353 bytes, checksum: fbf4acd7b5d75990f32c4e21593fe951 (MD5) / Made available in DSpace on 2018-06-15T14:12:19Z (GMT). No. of bitstreams: 1 Renata Aparecida Belotto.pdf: 1572353 bytes, checksum: fbf4acd7b5d75990f32c4e21593fe951 (MD5) Previous issue date: 2015-12-14 / Vulvar Lichen Sclerosus (VLS) is a chronic lymphocyte mediated dermatosis with unclear etiopathogenesis and difficult clinical control besides the risk of malignant transformation to squamous cell carcinoma of the vulva. The treatment is based on topical steroids that can cause undesirable side effects, however photonic therapies have been described in autoimmune diseases of the skin which encouraged this study. There were evaluated twenty eight women with histological diagnosis of VLS distributed into three groups: Photodynamic Therapy (PDT), Low Intensity Laser Therapy (LILT) and Topical Steroids and the objective was to compare the clinical effects before and after treatment by measuring pruritus, skin thickness, lesion area and temperature. No significant difference was observed in the intensity of pruritus between the groups. The Steroid therapy group showed significant variation in the longitudinal thickness of the skin in relation to LILT group (p = 0.000) with a reduction of -8.48%, while in LILT increased 24.8% as well as the PDT group with 20.9 %. However the variation of the transverse thickness was not different between the groups. The change in the lesion area showed no difference between groups. The LILT group showed significant temperature increase (3.03%) compared to PDT (-2.29%) and steroid (-1.45%) (p = 0.002) groups. Recurrences were registered in the corticosteroid group in two months, PDT in one and LILT in four months post treatment. The results showed that photonic therapies may be considered as treatment for VLS. / O Líquen Escleroso Vulvar (LEV) é uma dermatose crônica linfócito mediada com etiopatogenia não definida, de difícil controle clínico além de apresentar risco de malignização para o carcinoma escamoso de vulva. O tratamento da doença baseia-se no uso de corticosteroides tópicos que podem causar efeitos colaterais indesejáveis, no entanto terapias fotônicas vêm sendo descritas em processos inflamatórios autoimunes em pele o que estimulou esse estudo. Foram avaliadas vinte e oito mulheres com diagnóstico histológico de LEV que foram distribuídas em três grupos: Terapia Fotodinâmica (TFD), Terapia Laser de baixa intensidade (TLBI) e Corticosteroide tópico com o objetivo de comparação dos efeitos clínicos pré e pós-tratamento através da medição do prurido, espessura da pele, área da lesão e temperatura. Foi observado que a variação da intensidade do prurido entre os grupos não demonstrou diferença estatística significante. O grupo Corticoterapia apresentou variação significante na espessura longitudinal da pele em relação ao grupo TLBI (p = 0,000) com redução de -8,48%, enquanto no TLBI houve aumento de 24,8% e no grupo TFD de 20,9%. No entanto, a variação da espessura transversal não foi diferente entre os grupos. A variação da área da lesão não apresentou diferença entre os grupos. O grupo TLBI apresentou aumento significante da temperatura (3,03%) em relação aos grupos TFD (-2,29%) e Corticoterapia (-1,45%) (p= 0,002). Recorrências foram registradas nos grupos Corticoterapia, em dois meses, TFD, em um mês e TLBI, em quatro meses. Os resultados favorecem considerar as terapias fotônicas como possibilidades terapêuticas para o LEV.

LIN-12/Notch is a conserved transmembrane receptor that is required during animal development for proper cell-fate decisions and specification. In Caenorhabditis elegans, activation of LIN-12 occurs through binding to ligand expressed by an adjacent cell. This binding event triggers two cleavage steps and results in the release of the LIN-12 intracellular domain [LIN-12(intra)], which translocates to the nucleus to form a ternary complex with two other proteins: LAG-1/Su(H)/Cbf1 and SEL-8/Mastermind/Mastermind-like. This ternary complex will then transcriptionally activate target genes via LAG-1 Binding Sites (LBSs). LAG-1 is the sole DNA-binding component within the complex, and in the absence of LIN-12(intra), can act as a transcriptional repressor. LIN-12 signal transduction can be studied in the C. elegans Vulval Precursor Cells (VPCs), which exhibit precise spatiotemporal patterning regulated by LIN-12 activity. Here, I show that LAG-1 is positively autoregulated by LIN-12 activity in cells where LIN-12 activity is high. Autoregulation is mediated by an enhancer element that contains a cluster of 18 LBSs that are located within a conserved high occupancy target region, which is a span of DNA that is pulled down promiscuously in ChIP-Seq experiments. Mutation of the LBSs abrogates preferential expression mediated by the enhancer in cells with high LIN-12 signal transduction. When the HOT region is deleted from the endogenous lag-1 locus, expression in the VPCs is strongly reduced and no overt Lag phenotype occurs. Instead, cold-sensitive vulval and egg-laying defects, reminiscent of phenotypes seen in lin-12 hypomorphs, are found. Autoregulation of lag-1, therefore, appears to contribute to the robustness of LIN-12 cell fate specification in response to stochastic environmental and genetic perturbations. Under adverse environmental conditions, C. elegans enter a state of diapause in which they form dauer larvae, which are long-lived and stress-resistant. The VPCs of dauer larvae remain developmentally arrested indefinitely until favorable conditions are reintroduced. Experimentally, this arrest can be relieved by depletion of the Forkhead transcription factor DAF-16. I show that expression of the components of the LIN-12/SEL-8/LAG-1 ternary complex are downregulated during the L2d-dauer molt (prior to dauer entry) and that this downregulation is not relieved by DAF-16 depletion. Instead, DAF-16 depletion leads to resumption of LIN-12 signaling and expression of ternary complex only in completely formed dauer larvae. These observations suggest that DAF-16 is required for the maintenance but not the initiation of blocking LIN-12 signaling. The components of the ternary complex are required to effect LIN-12 signaling. This work contributes to better understanding how these components are regulated and how their expression can affect LIN-12 -mediated cell fate decisions.

<p>Induction of vulval fates in the C. elegans hermaphrodite is mediated by a conserved RTK/Ras/MAP kinase signalling pathway, in which the core components can be placed into a linear genetic and biochemical pathway. However, the events that occur downstream of this pathway are not yet well understood. This thesis describes studies on three genes, lin-1, lin-25 and sur-2 that function genetically downstream of the RTK/Ras/MAP kinase pathway in vulva induction. lin-1 encodes an ETS protein that appears to be a direct target of the RTK/Ras/MAP kinase pathway during the induction of vulval fates. To understand more in detail how Ras signalling in C. elegans affects cell fate specification we have analysed the effects of lin-1 mutations on various Ras-mediated cell fate specification events. Our results show that lin-1, besides its function in vulval induction, functions in most other Ras-mediated cell fate specification events in C. elegans, and that lin-1 appears to have a negative function in a majority of these events. Two other genes, lin-25 and sur-2, also function genetically downstream of the RTK/Ras/MAP kinase pathway during induction of vulval fates. Previously, two different models have been proposed for the function of these genes (I) that they function together with a gene in the homeotic cluster to specify the identity of the vulval precursor cells or (II) that they constitute components of the RTK/Ras/MAP kinase signalling pathway. To help clarify the role of lin-25 and sur-2, we have caried out studies of the effects of lin-25 and sur-2 mutations on other cells in the worm in which the RTK/Ras/MAP kinase pathway functions. The results exclude the possibility that lin-25 and sur-2 solely function in vulva induction and suggest that the two genes are intimately involved in Ras-mediated signalling. In addition we show that the major focus for lin-25 during vulval induction is in the vulva precursor cells themselves. Furthermore, results presented here suggest that LIN-25 and SUR-2 function together in the same process in the cell. We show here by both genetic and immunological experiments that LIN-25 is associated with Mediator in C. elegans, a multiprotein complex required for transcriptional regulation. Taken together, these results suggest that lin-25 and sur-2 function in regulating transcription of genes in response to Ras signalling.</p>

Induction of vulval fates in the C. elegans hermaphrodite is mediated by a conserved RTK/Ras/MAP kinase signalling pathway, in which the core components can be placed into a linear genetic and biochemical pathway. However, the events that occur downstream of this pathway are not yet well understood. This thesis describes studies on three genes, lin-1, lin-25 and sur-2 that function genetically downstream of the RTK/Ras/MAP kinase pathway in vulva induction. lin-1 encodes an ETS protein that appears to be a direct target of the RTK/Ras/MAP kinase pathway during the induction of vulval fates. To understand more in detail how Ras signalling in C. elegans affects cell fate specification we have analysed the effects of lin-1 mutations on various Ras-mediated cell fate specification events. Our results show that lin-1, besides its function in vulval induction, functions in most other Ras-mediated cell fate specification events in C. elegans, and that lin-1 appears to have a negative function in a majority of these events. Two other genes, lin-25 and sur-2, also function genetically downstream of the RTK/Ras/MAP kinase pathway during induction of vulval fates. Previously, two different models have been proposed for the function of these genes (I) that they function together with a gene in the homeotic cluster to specify the identity of the vulval precursor cells or (II) that they constitute components of the RTK/Ras/MAP kinase signalling pathway. To help clarify the role of lin-25 and sur-2, we have caried out studies of the effects of lin-25 and sur-2 mutations on other cells in the worm in which the RTK/Ras/MAP kinase pathway functions. The results exclude the possibility that lin-25 and sur-2 solely function in vulva induction and suggest that the two genes are intimately involved in Ras-mediated signalling. In addition we show that the major focus for lin-25 during vulval induction is in the vulva precursor cells themselves. Furthermore, results presented here suggest that LIN-25 and SUR-2 function together in the same process in the cell. We show here by both genetic and immunological experiments that LIN-25 is associated with Mediator in C. elegans, a multiprotein complex required for transcriptional regulation. Taken together, these results suggest that lin-25 and sur-2 function in regulating transcription of genes in response to Ras signalling.

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Made available in DSpace on 2016-08-10T10:38:52Z (GMT). No. of bitstreams: 1 Tatiane Ribeiro da Fonseca.pdf: 3044117 bytes, checksum: d604b5b291d33d0e053ad75336e7a264 (MD5) Previous issue date: 2014-06-26 / This study evaluated the sociodemographic and clinicopathological aspects of patients with cancer of the vulva and the vagina diagnosed in Araújo Jorge Hospital, Goiânia - GO as well as the prevalence of HPV and HPV16 and 18 genotypes in these tumors. The sample consisted of paraffin embedded samples from 57 patients with primary invasive vulvar cancer and 20 patients with primary invasive cancer of the vagina. The HPV detection was made by polymerase chain reaction (PCR) with SPF (short PCR fragment) 1-2 primers and the HPV 16 and 18 genotyping was performed with primers designed to detect these two genotypes. The results were analyzed by Fisher s exact test. The prevalence of HPV in vulvar cancer samples was 89%. The HPV16 genotype was detected in 42% of positive cases and HPV18 in 24%. The HPV prevalence in vaginal cancer samples was 90%. Among these, 56% were infections by HPV16 and HPV18 by 18%. Over 70% of patients with vulvar and vaginal cancer and positive for HPV detection were over 50 years. Statistical analyzes of the data showed significance of smoking for cancer of the vulva (p = 0.0110). A relationship between lymph node metastasis and cancer of the vulva was also observed (p = 0.0304). A better prognosis for patients with vaginal cancer HPV positive was found (p = 0.0158). A relationship between the degree of tumor differentiation and the presence of HPV in patients with cancer of the vulva was suggested (p = 0.0541). Based on the results presented, it is estimated that the HPV vaccine could have prevented 58% of cases of vulvar cancer and 65% of cases of vaginal cancer of the sample investigated. / O presente estudo avaliou os aspectos sociodemográficos e clinicopatológicos de pacientes com câncer de vulva e vagina diagnosticadas no Hospital Araújo Jorge, Goiânia-GO, bem como a prevalência do HPV e dos genótipos do HPV16 e 18 nesses tumores. A casuística consistiu de amostras parafinizadas de 57 pacientes com câncer invasor primário de vulva e 20 pacientes com câncer invasor primário de vagina. A detecção do HPV foi feita por meio de reação em cadeia da polimerase (PCR) com oligonucleotídeos iniciadores SPF (do inglês short PCR fragment) 1-2 e a genotipagem do HPV16 e 18 foi realizada com oligonucleotídeos iniciadores projetados para a detecção desses dois genótipos. Os resultados foram analisados por Teste Exato de Fisher. A prevalência do HPV nas amostras de câncer de vulva foi de 89%. O genótipo HPV16 foi detectado em 42% dos casos positivos e o HPV18 em 24%. A prevalência do HPV nas amostras de câncer de vagina foi de 90%. Dentre estas, 56% eram infecções pelo HPV16 e 18% pelo HPV18. Mais de 70% das pacientes com câncer de vulva e de vagina positivas para a detecção do HPV tinham mais de 50 anos. As análises estatísticas dos dados demonstraram significância do tabagismo para o câncer de vulva (p=0,0110). Uma relação entre metástase linfonodal e câncer de vulva também foi observada (p=0,0304). Um melhor prognóstico para pacientes com câncer de vagina HPV positivas foi constatado (p= 0,0158). Uma relação entre o grau de diferenciação tumoral e a presença do HPV em pacientes com câncer de vulva foi sugerida (p= 0,0541). Com base nos resultados apresentados, estima-se que a vacina contra o HPV poderia ter prevenido 58% dos casos de câncer de vulva e 65% dos casos de câncer de vagina da casuística investigada.

Based on thirteen months of ethnographic fieldwork in a large research hospital in the U.S., this dissertation analyzes the experiences of eighty American women seeking relief for chronic genital pain. Through extended interviews with diagnosed women, and participant-observation in a vulvar speciality clinic, I investigate the barriers--linguistic, cultural and corporeal--faced by patients who must engender greater familiarity and comfort with their sexual and genital bodies in order to successfully recover from their symptoms. Written as a cultural analysis of the vulva, the dissertation examines the ambivalent relationships between female external genitalia, U.S. dominant culture, and an autonomous female sexuality. Attentive to the transgression, confusion and disorder evoked by the symptoms of vulvar pain, the dissertation redefines the clinical diagnostic phrase "other causes of genital discomfort" in sociolcultural terms. The concepts of "genital dis-ease" and "unwanted genital experience" are introduced and analyzed as corporeo-cultural phenomena that contribute to a profound sense of alienation between many diagnosed women and their genital bodies. In addition to an extended introduction and a description of both the clinical fieldsite and conditions under investigation, the dissertation uses four progressive chapters--Accumulation, Manifestation, Integration and Generation--to theorize the lived experience of vulvar pain. Through a critical dialogue with current clinical literature, through which vulvar pain is understood in increasingly physiological terms, the dissertation argues that an acknowledgment of collective and cultural genital "discomfort" must be included in the emerging diagnostic and treatment regimens for women with chronic and unexplained genital pain. / text