Current Insights on Neoplasms and Adequate Dental Care for Patients with Oral Cancer / Actualización sobre Neoplasmas y su Correcta Atención Odontológica en Pacientes con Cancer Oral

The present study aimed to review the literature on the main complications of antineoplastic therapies and the degree of knowledge of dental surgeons about these complications. A bibliographic search was conducted in the main health databases PUBMED (www.pubmed.gov) and Scholar Google (www.scholar.google.com.br), in which studies published from 1987 to 2023 were collected. Laboratory studies, case reports, systematic and literature reviews, which were developed in living individuals, about the main neoplastic genes and their relationship with the cells of individuals affected by neoplasms in the head and neck region, and studies on the care with this group of patients, were included. Therefore, articles that did not deal with neoplasm and the main complications of antineoplastic therapies were excluded. Neoplasm is a clonal disorder, caused by mutations, resulting from changes in the genetic structure of cells. Each healthy cell has instructions on how to grow and divi de. In the presence of any error in these instructions (mutation), it can result in a diseased cell that, when proliferating, may cause a tumor. Countless knowledge has been accumulated over the years on the main characteristics of neoplasms, whether they are cancer cell biology, carcinogenesis mechanism, neoplasms of the maxillofacial system and sequels of antineoplastic treatments. In this context, methods have been developed that offer a better quality of life for patients diagnosed with this pathology, as well as preventive vaccine models that may, in the not too distant future, contribute to this goal to be successfully achieved.

El presente estudio tuvo como objetivo revisar la literatura sobre las principales complicaciones de las terapias antineoplásicas y el grado de conocimiento de los odontólogos sobre este abordaje. Se realizó una búsqueda bibliográfica en las principales bases de datos de salud PUBMED (www.pubmed.gov) y Scholar Google (www.scholar.google.com.br), en la que se recopilaron estudios publicados entre 1987 y 2023. Fueron incluidos estudios de laboratorio, relatos de casos, revisiones de la literatura y revisiones sistemáticas, desarrolladas en individuos vivos, que incluyeran los principales genes neoplásicos y su relación con las células de individuos afectados por neoplasias en la cabeza y el cuello. También, se tuvieron en cuenta estudios relacionados con la atención a este grupo de pacientes. La neoplasia es un trastorno clonal, causado por mutaciones, como resultado de cambios en la estructura genética de las células. Cada célula sana tiene instrucciones sobre cómo crecer y dividirse. En presencia de cualquier error en estas instrucciones (mutación), puede provocar una célula alterada que, al proliferar, puede causar un tumor. Se han acumulado innumerables conocimientos a lo largo de los años sobre las principales características de las neoplasias, ya sea sobre biología de células cancerosas, el mecanismo de la carcinogénesis, la neoplasias del sistema maxilofacial y las diferentes secuelas de tratamientos antineoplásicos. En este contexto, se han desarrollado métodos que ofrecen una mejor calidad de vida para los pacientes diagnosticados con esta patología, así como modelos de vacunas preventivas que, en un futuro no muy lejano, pueden contribuir a alcanzar este objetivo con éxito.

Carcinogenesis Colorrectal. Nuevas perspectivas e implicancias clínicas para su detección / Colorectal Carcinogenesis. New perspectives and clinical implications for its detection

El cáncer colorrectal (CCR) es una de las principales causas de morbilidad y mortalidad a nivel mundial. Clásicamente se considera a los adenomas como las lesiones precursoras del CCR y se estipula un tiempo de 10 a 15 años para completar la secuencia adenoma-carcinoma. El CCR evoluciona a través de la acumulación progresiva de alteraciones genéticas y epigenéticas, las que conducen a la transformación de la mucosa colónica normal en cáncer invasivo. La identificación de diferentes vías moleculares de carcinogénesis colorrectal ha demostrado la naturaleza heterogénea del cáncer colónico. De reciente descripción, las lesiones aserradas muestran cambios moleculares y patológicos distintos a los adenomas tradicionales, estimándose que presentan un tiempo más acelerado de evolución hacia la malignidad. El objetivo de esta revisión es actualizar conocimientos sobre la génesis tumoral y sus bases biomoleculares a fin de posibilitar su aplicación a etapas clínicas concretas como la prevención y el tratamiento

Colorectal cancer (CRC) is one of the main causes of morbidity and mortality worldwide. Adenomas are classically regarded as precursor lesions of CRC and between 10 and 15 years is thought to elapse to complete the adenoma-carcinoma sequence. CRC evolves through the progressive accumulation of genetic and epigenetic alterations that lead to invasive cancer through the transformation of normal colonic mucosa. The identification of different molecular pathways of colorectal carcinogenesis has demonstrated the heterogeneous nature of colon cancer. Recent description of serrated lesions shows molecular and pathological changes other than traditional adenomas with an estimated faster time of progression to malignancy. The aim of this review is to update the knowledge about tumorigenesis and its biomolecular basis for clinical application in early stages providing firm ground for prevention and treatment

Cáncer de mama en gemelas: a propósito de un caso / Breast cancer in twins: a case report

El cáncer de mama es la neoplasia más frecuente en la mujer. Solo 20% de las pacientes que presentan cáncer mamario tienen un antecedente familiar de la enfermedad, lo cual aumenta el riesgo relativo global. Casi en el 5% a 10% de los cánceres mamarios tiene una base hereditaria, sin embargo, solo el 0,1% de los casos están asociados a mutaciones de los genes BCRA-1 y BCRA-2. Actualmente se investigan otros genes relacionados a la enfermedad. Se presenta el caso de dos hermanas gemelas con diagnóstico de cáncer de mama derecha y antecedente familiar de tía materna fallecida por cáncer de mama

Breast cancer is the most frequent woman´s neoplasm. Only 20% from the patients have familiar history of breast cancer, with an increase over the global relative risk. Almost 5% to 10% of the breast cancer patients have a hereditary base, never less, only the 0.1% of the cases has any kind of association with a mutation of the gene BCRA-1 and BCRA-2. Actually, are under research another types of genes associated with the illness. The case of two sister monocygotics twins, with right breast cancer and a familiar history with a maternal aunt dead by complications from her breast cancer, is presented

Pituitary tumors in patients with MEN1 syndrome

We briefly review the characteristics of pituitary tumors associated with multiple endocrine neoplasia type 1. Multiple endocrine neoplasia type 1 is an autosomal-dominant disorder most commonly characterized by tumors of the pituitary, parathyroid, endocrine-gastrointestinal tract, and pancreas. A MEDLINE search for all available publications regarding multiple endocrine neoplasia type 1 and pituitary adenomas was undertaken. The prevalence of pituitary tumors in multiple endocrine neoplasia type 1 may vary from 10% to 60% depending on the studied series, and such tumors may occur as the first clinical manifestation of multiple endocrine neoplasia type 1 in 25% of sporadic and 10% of familial cases. Patients were younger and the time between initial and subsequent multiple endocrine neoplasia type 1 endocrine lesions was significantly longer when pituitary disease was the initial manifestation of multiple endocrine neoplasia type 1. Tumors were larger and more invasive and clinical manifestations related to the size of the pituitary adenoma were significantly more frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Normalization of pituitary hypersecretion was much less frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Pituitary tumors in patients with multiple endocrine neoplasia type 1 syndrome tend to be larger, invasive and more symptomatic, and they tend to occur in younger patients when they are the initial presentation of multiple endocrine neoplasia type 1.

Signals in the promoter regions of several cancerous genes.

The eukaryotic core promoter regions are complex and fuzzy, usually lacking any conserved regions. However, they contain signals in the form of short stretches of nucleic acid sequences, for transcription start sites (TSS) that are recognized by the transcription factors (TFs). The core promoter region thus plays an important role in biological pathways (gene network and activation). It has been reported that these signals are composed of nucleotide hexamers in the promoter sequence (smaller sequences are likely to have too little information to be useful and longer sequences are too complex to be recognized by proteins) reasonably close to the TSS. The signals (nucleotide hexamers) have been identified by a similarity search on the eukaryotic promoter database (EPD, Homo sapiens). The signals have been classified, depending on their base composition. They have been have clustered using an algorithm, such that there are two and three nucleotide differences between the classes and a single nucleotide difference within a class. We have reclassified the hexamers taking the highest frequent hexamers present in the EPD (Homo sapiens) as the class representatives. Also we have tried to find whether the same composition is reflected on the miRNAs but found that they probably have other functions unrelated to promoter recognition. In this report melanoma carcinoma pathway has been chosen as the reference pathway and the promoters of the driver genes has been searched for the presence of the major classes. A few of these were found and are reported here. Several non-cancerous genes have also been studied as reference and comparison.

Estudo imunohistoquímico das expressões: hMLH1, hMSH2 e Cox-2 em pólipos do cólon / Study of immunohistochemical expressions of: hMLH1, hMSH2 and Cox-2 in colon polyps

Estudaram-se 167 pólipos, 6 biópsias de mucosa colônica normal e 23 biópsias de adenocarcinomas colorretais coletados por via endoscópica no período de 2000 a 2004 no Hospital Geral da Faculdade de Medicina de Caxias do Sul, quanto à presença de alterações de imunoexpressão do hMLH1, hMSH2 e Cox-2. Houve alteração na imunoexpressão do hMLH1 em por cento, hMSH2 em por cento e Cox-2 em por cento dos adenomas, respectivamente. Não houve associação entre as imunoexpressões e o sexo, idade, localização da lesão, histologia ou displasia. A imunoexpressão para o Cox-2 associou-se ao aumento do número de adenomas no mesmo paciente. As alterações de imunoexpressões de hMLH1 e Cox-2 em adenomas e adenocarcinomas de cólon, em pacientes sem história familial de câncer colorretal, são eventos relativamente freqüentes...

The aim of this study was the immunohistochemical expressions hMLH1, hMSH2 and Cox-2 in ressected colon polyps through endoscopy to check alterations in lesions that can be labeled as premature in the carcinogenesis of colorectal cancer. Moreover, the aim was to examine a possible association among the variables: age, sex, localization, size, histology and dysplasia grade. Prospectively, 167 colon polyps were ressected through endoscopies between the years 2000 and 2004 at the Digestive Endoscopy Department of Hospital Geral da Faculdade de Medicina in Caxias do Sul. Six normal colonical mucosa biopsies and 23 biopsies of colorectal adenocarcinomas from different segments were collected. All the material was studied through histopathology and immunohistochemistry. In the tubular adenomas there was loss of expression of the hMLH1 in 37.1 per cent and in 14.5 per cent there was loss of expression of the hMSH2. The Cox-2 was shown to be altered in 7 per cent of the tubular adenomas. There was no loss of expression of the genes hMLH1 e hMSH2 in the villous adenomas; however, the Cox-2 was shown to be altered in 100 per cent of the villous adenomas. In the tubular-villous adenomas there was loss of expression of the hMLH1 in 17.6 per cent and loss of 28.6 per cent of expression of the hMSH2...

Impacto do encaminhamento para ambulatório de câncer hereditário na qualidade de vida de pacientes portadoras de câncer de mama / Impacto of hereditary breast cancer evaluation the quality of life of patients diagnosed with breast cancer

Neste trabalho, medimos o impacto da avaliação do risco de mutações dos genes BRCA1/2 na qualidade de vida (QV) de pacientes (pts) com câncer de mama, avaliada pelos questionários EORTC QLQ-C30 e QLQ-BR23. Convidamos 282 pts a participar, respondendo aos questionários antes e depois da avaliação do risco pelos métodos de Frank, Evans e BRCAPRO. Consideramos risco elevado pelo menos 10 por cento. 272 foram incluídas e 198 completaram o estudo. Nas 180 avaliáveis, não detectamos alterações significativas da QV. Classificamos 45 como risco elevado por Frank, 35 pelo BRCAPRO e 21 por Evans, 12 pelos 3 métodos. Concluímos que pts com câncer de mama desejam ser informadas quanto ao seu risco de câncer hereditário e que a avaliação não causa stress adicional. Instrumentos locais de mensuração de risco são também desejáveis...

Here we evaluated the impact of breast cancer hereditary cancer risk evaluation on the quality of life (QOL) in a population of breast cancer patients (pts), as measured by the EORTC questionnaires QLQ-C30 and QLQ-BR23. Of the 282 invited pts, 272 agree to participate and answered QLQ before and after the risk determination by Frank, Evans and BRCAPRO methods. High risk was defined as at least 10 per cent. Overall 198 pts completed the study. In the 180 evaluable pts., we did not detected significant differences in QOL. There were 45 pts classified as high risk by Frank, 35 by the BRCAPRO and 21 by Evans, agreement being reached in 12. We conclude that pts wish to know about their hereditary breast cancer risk, and this do not cause necessarily more stress. Apart from that, there is a need for local methods of risk calculation...

Definição in sílico do transcriptoma de diferentes tipos de tumor / In silico definition of the transcriptome of different types of tumor

Nesta tese são apresentados dois estudos in silico de conjuntos de dados de expressão. Ambos os estudos originaram-se de conjuntos de dados de expressão feitas de "Open Reading Frame ESTs" ou ORESTES. Estes ORESTES foram gerados no projeto genoma humano de câncer da FAPESP/LICR. A ênfase da primeira parte da tese está no estudo de expressão diferencial de genes em tumor de mama, enquanto a segunda parte da tese está no estudo da expressão de novos genes em câncer colorretal. A combinação do uso de ORESTES e a informação disponível dos bancos de dados de UniGene e SAGE caracterizaram o transcriptoma de células normais e tumorais de mama. Neste estudo, identificamos 154 genes como candidatos de genes que são super-expressos em células tumorais de mama... Neste trabalho demonstramos que a metodologia ORESTES pode contribuir para a descoberta de novos genes. Em câncer colorretal observa-se um tipo específico de instabilidade genômica, caracterizado por alterações no tamanho das unidades simples de seqüência repetitiva ou microsatélites. Muitos dos transcritos de baixa abundância podem ser essenciais para determinar fenótipos celulares normais e patológicos e podem ser responsáveis pelas diferenças fundamentais poucos compreendidas entre os diferentes fenótipos de câncer colorretal... As análises aqui apresentadas poderão contribuir para o entendimento das diferenças fundamentais em características clínicas, patológicas e moleculares dos cânceres coloretais com estabilidade (MSS) e instabilidade (MSI) de microsatélites. Com a abordagem computacional apresentada, observamos que a metodologia ORESTES pode ser complementar a outras tecnologias de larga escala de expressão gênica (SAGE, bibliotecas normalizadas de ESTs) na identificação de genes novos com importantes papéis em tumorigênese...

In this thesis, two in silico studies of expression datasets are presented. Both studies start with datasets of ORESTES or "Open Reading Frame Expressed Sequence Tags". These ORESTES were produced within the human cancer genome project of the FAPESP I LICR. The emphasis of the first part of the thesis is on the differential expression of genes in breast tumors. The second part of the thesis emphasizes the study o f novel genes in colorectal cancer. The combination o f the use of ORESTES and the publicly available information in the databases o f Uni Gene and SAGE lead to the characterization o f the transcriptome o f normal and tumour breast cells. In this study, we identified 154 genes as candidate up-regulated genes in breast tumour cells. Among these, 28 genes have been shown by others to be overexpressed in breast or other tumours. Using RT-PCR, we tested 11 candidate genes and found that 9 were indeed overexpressed in breast tumour cells. Furthermore, 99 genes were validated in silico by SAGE data. Of the 55 genes that were not confirmed by SAGE, 42 have their corresponding cluster composed solely by ESTs. These 42 clusters have no functional annotation and the function of these genes is unknown. The transcripts of the genes that are represented by these 42 clusters are likely to be expressed at low leveis in breast tissue. These results led to a more profound study of low abundance genes among which probably most of the novel genes can be found. As the majority of novel genes are expressed at low leveis, difficulties are encountered in identifying them with gene expression techniques like SAGE (Serial Analysis of Gene Expression) or EST (Expressed Sequence Tag) libraries. In this work we show the contribution of the ORESTES methodology in identifying novel genes. In colorectal cancer, a specific type of genetic instability characterized by length alterations within simple repeated sequences, termed microsatellite instability (MSI) is seen in the majority of hereditary nonpolyposis colorectal cancers (HNPCCs) and in a subset o f sporadic cancers. Many o f the low abundance transcripts could distinguish between different phases of tumorigenesis. The analyses presented in this work could contribute to the understanding of fundamental clinicai, pathological and molecular differences between colorectal cancers with stability in microsatellites and colorectal cancers with instability in microsatellites. With the described computational approach, we observed that the ORESTES methodology could be complementary to other large scale gene expression technologies (SAGE, normalized EST libraries) in the identification of novel genes with important roles in tumorigenesis (AU)

A genética do câncer colorretal: princípios para o cirurgiäo / Genetics of colorectal cancer: principles for the surgeon

O câncer colorretal ainda é uma das neoplasias de maior importância no mundo ocidental. O grande desenvolvimento da genética e biologia molecular nos últimos anos permitiu um melhor conhecimento dos mecanismos biomoleculares no câncer, e em especial, no câncer colorretal. Oncogenes (K-ras), genes supressores de tumor (p53, DCC e APC) e genes reparadores de DNA (hMSH2, MLH1, PMS1 e 2) estäo envolvidos na progressäo da seqüência adenoma-carcinoma no cólon e no reto. Algumas características anatômicas, histopatológicas, epidemiológicas e o comportamento biológico dos tumores parecem estar relacionados com alteraçöes genéticas específicas nestes genes. O conhecimento dos mecanismos genéticos que promovem a carcinogênese dos tumores colorretais abre novas perspectivas para o diagnóstico, tratamento, prognóstico e seguimento dos pacientes acometidos por esta neoplasia

Clinical, histologic and genetic characterization of non-Hodgkin's lymphomas in mexicans

En este artículo describimos la distribución anatómica, las características histológicas y moleculares de 32 casos de LNH. La estadificación clínica y clasificación histológica por grados se hizo de acuerdo a esquemas aceptados convencionalmente. Los arreglos detectados en genes que codifican para Ig o el RcT sirvieron para identificar la estirpe celular y el estadio de diferenciación de las células neoplásicas. El análisis de 26 muestras de suero reveló la existencia de anticuerpos contra epítopes de EBV; ocho de estos pacientes contenían secuencias virales integradas en el genoma del tumor. Nuestros estudios indican que el uso de diferentes métodos es fundamental para profundizar en el conocimiento de la historia natural de los LNH.