RESUMO
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.
Assuntos
Humanos , Assistência Odontológica , Genes Neoplásicos/genética , Neoplasias de Cabeça e Pescoço/genéticaRESUMO
Gastric cancer is one of the most common cancers, and an increasing number of studies have found that microRNAs (miRNAs) play essential roles in gastric cancer progression; however, the roles of specific miRNAs involved in the immune response to this disease remain unclear. We compared the miRNA expression in tissues from primary gastric cancer patients and healthy controls to find miRNAs dysregulated in gastric cancer and used bioinformatics tools to determine potential roles of these miRNAs in the immune system. We evaluated 25 primary gastric cancer tissues and five healthy gastric tissues. Quantitative real-time polymerase chain reaction was performed for a set of miRNAs, followed by the prediction of their target genes and functional enrichment analysis of these targets. Analysis of a microarray dataset showed that the miRNA miR-196a-5p was significantly upregulated, while miR-374a-5p and miR-375 were downregulated in gastric cancer patients. In addition, miR-374-5p was significantly downregulated in patients with metastasis compared with its expression levels in non-metastatic patients (p = 0.03). Bioinformatics analysis suggested that the pathways regulated by these differentially expressed miRNAs were related to the immune response, cell adhesion, and cell migration. Most importantly, this study provides a new insight into the potential use of multiple miRNAs to find distinct pathways of immune regulation in gastric cancer.
Assuntos
MicroRNAs/genética , Transdução de Sinais/imunologia , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes Neoplásicos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Estômago/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Evasão Tumoral/genéticaRESUMO
OBJECTIVE: To investigate associations between genetic mutations and qualitative as well as quantitative features on MRI in rectal adenocarcinoma at primary staging. METHODS: In this retrospective study, patients with rectal adenocarcinoma, genome sequencing, and pretreatment rectal MRI were included. Statistical analysis was performed to evaluate associations between qualitative features obtained from subjective evaluation of rectal MRI and gene mutations as well as between quantitative textural features and gene mutations. For the qualitative evaluation, Fisher's Exact test was used to analyze categorical associations and Wilcoxon Rank Sum test was used for continuous clinical variables. For the quantitative evaluation, we performed manual segmentation of T2-weighted images for radiomics-based quantitative image analysis. Thirty-four texture features consisting of first order intensity histogram-based features (n = 4), second order Haralick textures (n = 5), and Gabor-edge based Haralick textures were computed at two different orientations. Consensus clustering was performed with 34 computed texture features using the K-means algorithm with Euclidean distance between the texture features. The clusters resulting from the algorithm were then used to enumerate the prevalence of gene mutations in those clusters. RESULTS: In 65 patients, 45 genes were mutated in more than 3/65 patients (5%) and were included in the statistical analysis. Regarding qualitative imaging features, on univariate analysis, tumor location was significantly associated with APC (p = 0.032) and RASA1 mutation (p = 0.032); CRM status was significantly associated with ATM mutation (p = 0.021); and lymph node metastasis was significantly associated with BRCA2 (p = 0.046) mutation. However, these associations were not significant after adjusting for multiple comparisons. Regarding quantitative imaging features, Cluster C1 had tumors with higher mean Gabor edge intensity compared with cluster C2 (θ = 0°, p = 0.018; θ = 45°, p = 0.047; θ = 90°, p = 0.037; cluster C3 (θ = 0°, p = 0.18; θ = 45°, p = 0.1; θ = 90°, p = 0.052), and cluster C4 (θ = 0°, p = 0.016; θ = 45°, p = 0.033; θ = 90°, p = 0.014) suggesting that the cluster C1 had tumors with more distinct edges or heterogeneous appearance compared with other clusters. CONCLUSIONS: Although this preliminary study showed promising associations between quantitative features and genetic mutations, it did not show any correlation between qualitative features and genetic mutations. Further studies with larger sample size are warranted to validate our preliminary data.
Assuntos
Adenocarcinoma/patologia , Mutação/genética , Medicina de Precisão , Neoplasias Retais/patologia , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Genes Neoplásicos/genética , Genômica/métodos , Humanos , Metástase Linfática , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Neoplasias Retais/genética , Estudos RetrospectivosRESUMO
BACKGROUND: The origin of melanoma has always been a debated subject, as well as the role of adjacent melanocytic naevi. Epidemiological and histopathological studies point to melanomas arising either de novo or from a naevus. OBJECTIVES: To evaluate the presence of mutations in genes from well-known melanomagenesis pathways in a large series of naevus-associated melanomas. MATERIALS AND METHODS: Sixty-one melanomas found in association with a pre-existing naevus were microdissected, after careful selection of cell subpopulations, and submitted to Sanger sequencing of the BRAF, NRAS, c-KIT, PPP6C, STK19 and RAC1 genes. Each gene was evaluated twice in all samples by sequencing or by sequencing and another confirmation method, allele-specific fluorescent polymerase chain reaction (PCR) and capillary electrophoresis detection or by SNaPshot analysis. Only mutations confirmed via two different molecular methods or twice by sequencing were considered positive. RESULTS: The majority of cases presented concordance of mutational status between melanoma and the associated naevus for all six genes (40 of 60; 66.7%). Nine cases presented concomitant BRAF and NRAS mutations, including one case in which both the melanoma and the adjacent naevus harboured V600E and Q61K double mutations. In two cases, both melanoma and associated naevus located on acral sites were BRAF mutated, including an acral lentiginous melanoma. CONCLUSIONS: To our knowledge this is the largest naevus-associated melanoma series evaluated molecularly. The majority of melanomas and adjacent naevi in our sample share the same mutational profile, corroborating the theory that the adjacent naevus and melanoma are clonally related and that the melanoma originated within a naevus.
Assuntos
Genes Neoplásicos/genética , Melanoma/genética , Mutação/genética , Neoplasias Cutâneas/genética , GTP Fosfo-Hidrolases/genética , Humanos , Proteínas de Membrana/genética , Dados de Sequência Molecular , Nevo Pigmentado/genética , Proteínas Nucleares/genética , Fosfoproteínas Fosfatases/genética , Reação em Cadeia da Polimerase , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas rac1 de Ligação ao GTP/genéticaRESUMO
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
Assuntos
Humanos , Adulto , Colonoscopia , Epigênese Genética/genética , Genes Neoplásicos/genética , Lesões Pré-Cancerosas/patologia , Neoplasias Colorretais/patologia , Prevenção de Doenças , Diagnóstico/prevenção & controle , Fenótipo , Hereditariedade/genética , Instabilidade Cromossômica/genética , Instabilidade de Microssatélites , Literatura de Revisão como Assunto , Mucosa/anormalidades , Metilação de DNARESUMO
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.áDe 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(AU)
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 (AU)
Assuntos
Humanos , Adulto , Neoplasias Colorretais/patologia , Lesões Pré-Cancerosas/patologia , Epigênese Genética/genética , Colonoscopia , Prevenção de Doenças , Genes Neoplásicos/genética , Literatura de Revisão como Assunto , Fenótipo , Diagnóstico/prevenção & controle , Mucosa/anormalidades , Metilação de DNA , Instabilidade de Microssatélites , Instabilidade Cromossômica/genética , Hereditariedade/genéticaRESUMO
A new method, which allows for the identification and prioritization of predicted cancer genes for future analysis, is presented. This method generates a gene-specific score called the "S-Score" by incorporating data from different types of analysis including mutation screening, methylation status, copy-number variation and expression profiling. The method was applied to the data from The Cancer Genome Atlas and allowed the identification of known and potentially new oncogenes and tumor suppressors associated with different clinical features including shortest term of survival in ovarian cancer patients and hormonal subtypes in breast cancer patients. Furthermore, for the first time a genome-wide search for genes that behave as oncogenes and tumor suppressors in different tumor types was performed. We envisage that the S-score can be used as a standard method for the identification and prioritization of cancer genes for follow-up studies.
Assuntos
Biologia Computacional/métodos , Genes Neoplásicos/genética , Neoplasias/genética , Variações do Número de Cópias de DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genômica , Humanos , Metilação , Mutação/genética , Oncogenes/genéticaRESUMO
Bladder cancer is a highly heterogeneous neoplasm. We examined the gene expression profile in 3 bladder cancer stages (Ta, T1, T2) using expression microarray analysis of 40 bladder tumors. Differentially expressed genes were found by the t-test, with <0.005 as the significance threshold. KEGG pathway-enrichment analysis was used to study the signaling pathways of the genes. We found 36 genes that could be used as molecular markers for predicting the transition from Ta-T1 to T1-T2. Among these, 11 overlapped between Ta-T1 and T1-T2 stages. Six genes were down-regulated at the Ta-T1 stage, but were up-regulated at the T1-T2 stage (ANXA5, ATP6V1B2, CTGF, GEM, IL13RA1, and LCP1); 5 genes were up-regulated at the Ta-T1 stage, but down-regulated at the T1-T2 stage (ACPP, GNL1, RIPK1, RAPGEF3, and ZER1). Another 25 genes changed relative expression levels at the T1-T2 stage. These genes (including COL1A1, COL1A2, FN1, ITGA5, LGALS1, SPP1, VIM, POSTN, and COL18A1) may be involved in bladder cancer progression by affecting extracellular matrix-receptor interaction and focal adhesion. The cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and calcium-signaling pathway were associated with bladder cancer progression at both the Ta-T1 and T1-T2 stages.
Assuntos
Regulação Neoplásica da Expressão Gênica , Transdução de Sinais/genética , Transcriptoma , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Genes Neoplásicos/genética , Humanos , Estadiamento de Neoplasias , Mapas de Interação de Proteínas/genéticaRESUMO
Although human papillomavirus was identified as an aetiological factor in cervical cancer, the key human gene drivers of this disease remain unknown. Here we apply an unbiased approach integrating gene expression and chromosomal aberration data. In an independent group of patients, we reconstruct and validate a gene regulatory meta-network, and identify cell cycle and antiviral genes that constitute two major subnetworks upregulated in tumour samples. These genes are located within the same regions as chromosomal amplifications, most frequently on 3q. We propose a model in which selected chromosomal gains drive activation of antiviral genes contributing to episomal virus elimination, which synergizes with cell cycle dysregulation. These findings may help to explain the paradox of episomal human papillomavirus decline in women with invasive cancer who were previously unable to clear the virus.
Assuntos
Antivirais/metabolismo , Ciclo Celular/genética , Redes Reguladoras de Genes/genética , Genes Neoplásicos/genética , Papillomaviridae/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Aberrações Cromossômicas , Cromossomos Humanos/genética , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genoma Humano/genética , Instabilidade Genômica , Humanos , Proteínas de Membrana Lisossomal/metabolismo , Metanálise como Assunto , Proteínas de Neoplasias/metabolismo , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Reprodutibilidade dos Testes , Neoplasias do Colo do Útero/patologia , Integração Viral/genéticaRESUMO
BACKGROUND: Uterine Leiomyomas (ULs) are the most common benign tumours affecting women of reproductive age. ULs represent a major problem in public health, as they are the main indication for hysterectomy. Approximately 40-50% of ULs have non-random cytogenetic abnormalities, and half of ULs may have copy number alterations (CNAs). Gene expression microarrays studies have demonstrated that cell proliferation genes act in response to growth factors and steroids. However, only a few genes mapping to CNAs regions were found to be associated with ULs. METHODOLOGY: We applied an integrative analysis using genomic and transcriptomic data to identify the pathways and molecular markers associated with ULs. Fifty-one fresh frozen specimens were evaluated by array CGH (JISTIC) and gene expression microarrays (SAM). The CONEXIC algorithm was applied to integrate the data. PRINCIPAL FINDINGS: The integrated analysis identified the top 30 significant genes (P<0.01), which comprised genes associated with cancer, whereas the protein-protein interaction analysis indicated a strong association between FANCA and BRCA1. Functional in silico analysis revealed target molecules for drugs involved in cell proliferation, including FGFR1 and IGFBP5. Transcriptional and protein analyses showed that FGFR1 (P = 0.006 and P<0.01, respectively) and IGFBP5 (P = 0.0002 and P = 0.006, respectively) were up-regulated in the tumours when compared with the adjacent normal myometrium. CONCLUSIONS: The integrative genomic and transcriptomic approach indicated that FGFR1 and IGFBP5 amplification, as well as the consequent up-regulation of the protein products, plays an important role in the aetiology of ULs and thus provides data for potential drug therapies development to target genes associated with cellular proliferation in ULs.