Liliane Soares Yurgel

The role of epigenetic transcription repression and DNA methyltransferases in cancer

Epigenetic alterations such as DNA methylation have been implicated in the development and progression of various cancers. DNA methylation consists of the reversible addition of a methyl group to the carbon 5 position of cytosine in CpG dinucleotides and is considered essential for normal embryonic development. However, global genomic hypomethylation and aberrant hypermethylation of regulatory regions of tumor suppressor genes have been associated with chromosomal instability and transcription repression, respectively, providing neoplastic cells with a selective advantage. DNA methyltransferases are the enzymes responsible for the addition of methyl groups to CpG dinucleotides, which, together with histone modifiers, initiate the events necessary for transcription repression to occur. It has been demonstrated that increased expression of DNA methyltransferases may contribute to tumor progression through methylation‐mediated gene inactivation in various human cancers. Given their importance, this article reviews the main epigenetic mechanisms for regulating transcription and its implications in cancer development. Cancer 2011.

Perfil clínico-epidemiológico dos pacientes portadores de paracoccidioidomicose no Serviço de Estomatologia do Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul

The aim of the article was to describe clinical and epidemiological features of 61 oral paracoccidioidomycosis cases from the Stomatology Department of Sao Lucas Hospital, analyzed from July 1976 to June 2004. The State of Rio Grande do Sul is an endemic region due to ecoepidemiologic conditions, that are favorable for the development of the yeast. Men are the most affected gender, with 58 (95%) affected compared to 3 (5%) women. Ii is most prevalent (70.5%) between 40 and 59 years of age. Agricultural labor was the most common occupation with 27/61 (44.3%) patients. Tobacco smoking was prevalent in 52 (85.3%) of the sample, and alcoholism was a frequent finding. All the patients showed stomatologic manifestations, with ulcers and mulberry-like stomatitis the most prevalent, these oral lesions were also observed in many anatomical sites. Alterations were present in 32 (65.3%) of the pulmonary radiographs.

Evaluation of the nucleolar organizer region associated proteins in exfoliative cytology of normal buccal mucosa. Effect of smoking

An evaluation of cellular alterations in the smokers oral mucosal cells was performed. The Exfoliative Cytology technique was applied and the cytological smears stained with silver for the enumeration of Argyrophilic nucleolar organizer regions (AgNORs). Cytological smears were collected from two anatomic sites: floor of the mouth and tongue border, in both groups, smokers and non smokers, with a purpose of correlating the smoking habit to possible cellular alterations. The enumeration of the AgNORs showed that the average number of AgNORs is higher in smokers. There is a significant difference (P=0.0001) between smears from the floor of the mouth and from tongue border in the smoking group. In this study, no correlation between number of cigarettes, age and gender was found, but the results suggest that there might be a correlation between the smoking habit and an increased rate of cellular proliferation in the oral mucosal cells.

Oral erythroplakia and speckled leukoplakia: retrospective analysis of 13 cases

UNLABELLED Erythroplakia and speckled leukoplakia are oral precancerous lesions that have a high potential for malignant transformation. AIM A retrospective analysis was conducted to investigate the clinicopathologic features of 13 cases of oral erythroplakia and speckled leukoplakia in patients who were seen at a center specialized in stomatology and Histopathological diagnosis of oral diseases. MATERIALS AND METHODS All cases diagnosed with erythroplakia and speckled leukoplakia between 1978 and 2006 were retrieved from the service archives. RESULTS The lesions exhibited a predilection for males with a female-to-male ratio of 1:3.3. Mean age was 57 years old and soft palate was the site affected in 77% of the cases. Pain symptoms were reported by 61.5% of the patients and association with risk factors such as smoking and excessive alcohol intake was seen in 100% and in 46% of the cases, respectively. The lesions showed epithelial dysplasia, where more than 50% were diagnosed as in situ or invasive carcinoma. CONCLUSIONS Despite low prevalence, oral homogeneous erythroplakia and speckled leukoplakia show Histopathological alterations vary from epithelial dysplasia to invasive carcinoma. These lesions must be included among those oral lesions with the highest potential for malignant tranformation.

Associação entre manifestações estomatológicas e características socioeconômicas e culturais de crianças brasileiras e norte-americanas infectadas pelo HIV

OBJETIVO: Investigar as caracteristicas socioeconomicas e culturais de criancas infectadas pelo HIV e de suas familias, relacionando-as com a presenca de manifestacoes estomatologicas da AIDS, e identificar as manifestacoes estomatologicas mais frequentes na amostra estudada. METODO: A amostra foi composta por 184 criancas de ambos os sexos, com idade entre 0 e 13 anos, atendidas no Hospital de Clinicas de Porto Alegre e Hospital Sao Lucas da Pontificia Universidade Catolica, em Porto Alegre, Brasil, e no hospital universitario da Universidade do Estado de Nova Iorque em Stony Brook, Estado de Nova Iorque, Estados Unidos. Os dados foram analisados pelos testes do qui-quadrado, t de Student e analise de variância. RESULTADOS: Dos 184 pacientes, 63,59% eram do Hospital de Clinicas de Porto Alegre; 22,28% do hospital de Stony Brook; e 14,13% do Hospital Sao Lucas. Na amostra brasileira, 42,66% das criancas residiam com os pais naturais (principalmente com a mae), enquanto que nos Estados Unidos 56,10% das criancas moravam com pais adotivos. Em relacao a renda, 39,86% das familias no Brasil ganhavam entre 180 e 450 dolares mensais; 33,57% nao tinham renda ou nao forneceram seus dados. Nos Estados Unidos, a pergunta sobre renda nao foi autorizada, mas todas as familias foram classificadas pelos assistentes sociais do hospital como tendo renda abaixo de 1 000 dolares. O HIV foi adquirido por transmissao vertical em 97,20% dos casos no Brasil e 97,56% nos Estados Unidos. A frequencia das manifestacoes estomatologicas foi maior nas criancas brasileiras (72,73%) do que nas norte-americanas (53,66%) (P = 0,01). CONCLUSOES: As condicoes socioeconomicas e culturais, estrutura e renda familiar, acesso a informacao sobre AIDS e a adesao aos esquemas terapeuticos influenciaram a frequencia das manifestacoes estomatologicas nas duas amostras.

Evaluation of salivary endothelin-1 levels in oral squamous cell carcinoma and oral leukoplakia

Oral squamous cell carcinoma (OSCC) is the most frequent malignant neoplasia of the oral cavity, which largely compromises the patients life quality. Therefore, the identification of biomarkers for this kind of cancer is essential to provide a better diagnosis and prognosis for patients. Endothelin-1 is a peptide produced mainly by endothelial cells, and might be found in several body fluids, such as saliva, milk, urine, cerebrospinal fluid and plasma. It has been demonstrated that expression of this peptide is increased in a great number of neoplasias, including oral carcinoma. The identification of salivary biomarkers would be a useful tool for scanning and monitoring patients with risk of developing OSCC, as well to early detect recurrence, or the formation of a new primary tumor. In the present study, we have analyzed the levels of endothelin-1 in saliva obtained from patients with OSCC or oral leukoplakia, in comparison to healthy control patients. This study also evaluated the salivary ET-1 levels in patients with complete remission of OSCC. The results revealed no statistical difference in salivary endothelin-1 levels, neither in OSCC nor in oral leukoplakia, even when conditions such as elderly, sex and hypertension were taken into consideration. Although, ET-1 might display an important role in OSCC, its levels in saliva do not seem to be a good marker of neoplasias grade or malignant transformation.

Squamous cell carcinoma of the tongue after bone marrow transplantation in a patient with Fanconi anemia

Fanconi anemia (FA) is an autosomal recessive disorder that might cause a variety of congenital and developmental abnormalities. The most important features of FA are progressive bone marrow failure and development of malignancies, particularly acute myeloid leukemia and solid tumors. This paper reports the case of a 12-year-old patient with FA assisted at the Stomatology and Bucomaxillofacial Cancer Prevention Service of São Lucas Hospital, Brazil, who had been submitted to bone marrow transplantation (BMT) at the age of 5 and exhibited oral lesions characteristic of chronic graft versus host disease (GVHD). The patient was treated and followed-up for the oral lesions. Eleven years after the BMT, he developed squamous cell carcinoma of the tongue with an aggressive behavior, which was considered an untreatable condition. The patient died few months later from asphyxia at the age of 16. The reasons for development of these malignant conditions are unknown. However, chromosomal instability typically observed in FA cases, BMT factors and GVHD have been considered. Systematic follow-up of these patients allows early and less invasive therapeutic approaches.

Manifestações estomatológicas, contagem de linfócitos T-CD4+ e carga viral de crianças brasileiras e norte-americanas infectadas pelo HIV

Oral manifestations related to HIV infection were evaluated in 184 children of both genders, aging 0-13 years. The oral exams were carried out at the Ambulatory of Pediatric AIDS, São Lucas Hospital and at the Clinics Hospital, both in Porto Alegre, RS, Brazil, and at the University Hospital and School of Dentistry, State University of New York, Stony Brook, NY, USA, from January 1999 to May 2000. A high prevalence of oral manifestations was observed both in Brazilian (72.73%) and American (53.66%) children. The most frequent manifestations were cervical lymphadenopathy, swelling of the parotids, erythematous candidiasis, petechia, gingivitis, xerostomia and angular cheilitis. Children with oral manifestations had almost normal counts of CD4+ T lymphocytes and high viral load.Oral manifestations related to HIV infection were evaluated in 184 children of both genders, aging 0-13 years. The oral exams were carried out at the Ambulatory of Pediatric AIDS, Sao Lucas Hospital and at the Clinics Hospital, both in Porto Alegre, RS, Brazil, and at the University Hospital and School of Dentistry, State University of New York, Stony Brook, NY, USA, from January 1999 to May 2000. A high prevalence of oral manifestations was observed both in Brazilian (72.73%) and American (53.66%) children. The most frequent manifestations were cervical lymphadenopathy, swelling of the parotids, erythematous candidiasis, petechia, gingivitis, xerostomia and angular cheilitis. Children with oral manifestations had almost normal counts of CD4+ T lymphocytes and high viral load.

Comparative Analyses Between the Smoking Habit Frequency and the Nucleolar Organizer Region Associated Proteins in Exfoliative Cytology of Smokers' Normal Buccal Mucosa

An evaluation of the cellular alterations in the smokers oral mucosal cells was performed. Exfoliative Citology technique were applied and the cytologic smears stained with silver for quantitative analyses of Argyrophilic nucleolar organizer regions. (AgNORs). Cytologic smears were collected from two anatomic sites, mouth floor and tongue border with the purpose of relating the frequency of smoking with the quantitative analyses of the AgNORs. This study showed that the average number of AgNORs/nucleus is related with the number of cigarettes per day in the mouth floor of smokers. These results suggest a possible relation between the number of cigarettes per day and an increase rate of cellular proliferation in the oral mucosal cells.

Eritroplasia e leucoeritroplasia oral: análise retrospectiva de 13 casos

Eritroplasia e leucoeritroplasia sao lesoes orais cancerizaveis com elevado potencial de transformacao maligna. OBJETIVOS: Neste estudo retrospectivo foram analisadas as caracteristicas clinico-patologicas de 13 casos de eritroplasias e leucoeritroplasias orais de pacientes atendidos em um Servico especializado em Estomatologia e diagnostico histopatologico. MATERIAL E METODO: Foram revisados os registros de biopsia de pacientes atendidos entre os anos de 1978 e 2006. Foram registradas e caracteristicas clinicas e histopatologicas das lesoes, bem como sexo, idade dos pacientes e associacao com fatores de risco. RESULTADOS: As lesoes exibiram predilecao por pacientes do sexo masculino na proporcao de 1:3.3. A media etaria dos individuos foi de 57 anos e o palato mole foi o sitio envolvido em 77% dos casos. Sintomatologia dolorosa foi relatada por 61,5% dos pacientes e associacao com tabagismo e etilismo foi observada em 100% e em 46% dos casos, respectivamente. As lesoes analisadas exibiam displasia epitelial e mais de 50% foram diagnosticadas como carcinoma in situ ou carcinoma invasivo. CONCLUSOES: Apesar de apresentarem baixa prevalencia, as eritroplasias homogeneas e as leucoplasias salpicadas exibem alteracoes epiteliais que vao de displasia epitelial a carcinoma invasivo, o que justifica sua inclusao entre as lesoes bucais com maior potencial de malignizacao.