RESUMO
Oral squamous cell carcinoma (OSCC) is the most common manifestation of oral cancer. It has been proposed that periodontal pathogens contribute to OSCC progression, mainly by their virulence factors. However, the main periodontal pathogen and its mechanism to modulate OSCC cells remains not fully understood. In this study we investigate the main host-pathogen pathways in OSCC by computational proteomics and the mechanism behind cancer progression by the oral microbiome. The main host-pathogen pathways were analyzed in the secretome of biopsies from patients with OSCC and healthy controls by mass spectrometry. Then, functional assays were performed to evaluate the host-pathogen pathways highlighted in oral cancer. Host proteins associated with LPS response, cell migration/adhesion, and metabolism of amino acids were significantly upregulated in the human cancer proteome, whereas the complement cascade was downregulated in malignant samples. Then, the microbiome analysis revealed large number and variety of peptides from Fusobacterium nucleatum (F. nucleatum) in OSCC samples, from which several enzymes from the L-glutamate degradation pathway were found, indicating that L-glutamate from cancer cells is used as an energy source, and catabolized into butyrate by the bacteria. In fact, we observed that F. nucleatum modulates the cystine/glutamate antiporter in an OSCC cell line by increasing SLC7A11 expression, promoting L-glutamate efflux and favoring bacterial infection. Finally, our results showed that F. nucleatum and its metabolic derivates promote tumor spheroids growth, spheroids-derived cell detachment, epithelial-mesenchymal transition and Galectin-9 upregulation. Altogether, F. nucleatum promotes pro-tumoral mechanism in oral cancer.
Assuntos
Carcinoma de Células Escamosas , Progressão da Doença , Fusobacterium nucleatum , Neoplasias Bucais , Proteômica , Humanos , Fusobacterium nucleatum/metabolismo , Neoplasias Bucais/microbiologia , Neoplasias Bucais/metabolismo , Carcinoma de Células Escamosas/microbiologia , Carcinoma de Células Escamosas/metabolismo , Interações Hospedeiro-Patógeno , Redes e Vias Metabólicas , Estudos de Casos e Controles , Espectrometria de MassasRESUMO
BACKGROUND: Hypovitaminosis D raised a significant public health concern due to its potential association with various diseases, including Oral Squamous Cell Carcinoma (OSCC). The objective of this study was to compare serum 25(OH)D3 levels between individuals with and without OSCC, and by subgroups based on their smoking habits. MATERIAL AND METHODS: A case-control study was conducted utilizing progressive multicenter recruitment, involving 46 patients with Oral Squamous Cell Carcinoma (OSCC) and 65 controls. Serum levels of 25(OH)D3 were evaluated via electrochemiluminescence. Patients were categorized according to their vitamin D levels into sufficiency, mild deficiency, moderate deficiency, and severe deficiency. Comparative analyses of serum 25(OH)D3 levels were performed between OSCC patients and controls, as well as among subgroups based on their smoking habits. Group comparisons were made with the Mann-Whitney test, and subgroup analyses used the Kruskal-Wallis test. Significance was set at p < 0.05 Results: 91% of participants, including both OSCC patients and controls, exhibited some degree of 25(OH)D3 deficiency. Among them, 71.7% of OSCC patients and 50.7% of controls had serum levels characterized by moderate to severe deficiencies. Patients with OSCC showed lower levels of 25(OH)D3, with medians of 20.2 ng/ml (IQR 9.48), compared to controls, with medians of 24.8 ng/ml (IQR 9.13) (p=0.002). Furthermore, when comparing the medians among the four study groups (smoking and non-smoking controls and smoking and non-smoking patients with OSCC), a significant difference was observed between non-smoking control patients with 25.04 ng/ml (IQR = 9.71) and smoking OSCC patients with 19.65 ng/ml (IQR = 12.14) (p < 0.05). CONCLUSIONS: Individuals with oral squamous cell carcinoma (OSCC) exhibited lower serum levels of vitamin D (25(OH)D3) compared to controls, suggesting a potential link between vitamin deficiency and the development of this type of cancer. Vitamin D supplementation could serve as a preventive and therapeutic strategy.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Deficiência de Vitamina D , Humanos , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/sangue , Neoplasias Bucais/sangue , Neoplasias Bucais/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Fatores de Risco , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/complicações , Idoso , Fumar/efeitos adversos , AdultoRESUMO
BACKGROUND: Oral cancer screening requires analysis capable of detecting changes preceding the clinical manifestation. Oral cytopathology studies as an oral cancer screening have shown promising results. This study aims to evaluate the use of cytopathology in a quali-quantitative analysis using Papanicoloau staining. METHODS: Four experimental groups were evaluated: control (CG), exposed to carcinogens (EG), potentially malignant disorder with and without epithelial dysplasia (D-OPMDG and ND-OPMDG) and oral squamous cell carcinoma (OSCCG). Oral smears were collected using a Cytobrush® and conventional exfoliative cytology. RESULTS: Oral Papanicolaou smears from 143 individuals were analysed in 8100 images. Qualitatively, non-lesional groups exhibited minimal suspected cases (20% in CG and 5% in EG), in the OPMD groups the ability to identify altered cells was low (40% in D-OPMDG and 0% in ND-OPMDG). Conversely, a notable 100% accuracy was achieved in the OSCCG. Quantitatively, a higher percentage of anucleated and a lower percentage of intermediate cells were observed in the OPMDG; a higher proportion of parabasal/suspicious cells was observed in OSCCG. The optimal threshold for improved accuracy in detecting suspected malignancies occurs when the count of parabasal/suspicious cells exceeds 8/100 cells examined. Cytomorphometric analysis revealed a higher nucleus/cytoplasm ratio (N/C) in OSCCG, with a best cutoff point indicating enhanced accuracy in discerning suspected malignancies when exceeding 17% of cells exhibiting this elevated ratio. CONCLUSION: It is possible to suggest updates in cytomorphometric and quantitative analysis in the modified Bethesda system for the oral cavity including objective criteria in the risk classification, therefore improving oral cancer screening.
Assuntos
Citodiagnóstico , Detecção Precoce de Câncer , Neoplasias Bucais , Teste de Papanicolaou , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/diagnóstico , Teste de Papanicolaou/métodos , Feminino , Detecção Precoce de Câncer/métodos , Citodiagnóstico/métodos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico , Adulto , IdosoRESUMO
We hypothesized that cell energy metabolic profiles correlate with normal, dysplastic, and tumor cell/tissue statuses and may be indicators of aggressiveness in oral squamous cell carcinoma (OSCC) cells. The energy-related proteins that were differentially expressed in human OSCC fragments (n = 3) and their adjacent epithelial tissue (TAE) were verified using mass spectrometry (MS). Immunohistochemistry for 4-hydroxynonenal (4-HNE) was performed to evaluate the oxidative stress patterns in OSCC (n = 10), epithelial dysplasia (n = 9), and normal epithelial (n = 4) biopsies. The metabolic energy profile of OSCC aggressiveness was investigated in human OSCC cell lines with different levels of epithelial-mesenchymal transition proteins. The genes associated with the proteins found by MS in this study were analyzed using survival analysis (OS), whereas the genes associated with a poorer prognosis were analyzed using context-specific expression, Gene Ontology (GO) and Cancer Hallmarks for function enrichment analysis. The rationale for all experimental approach was to investigate whether the variation in energy metabolism profile accompanies the different phenotypes (from epithelial to mesenchymal) during the epithelial-mesenchymal transition. All OSCC fragments exhibited an increase in glycolysis-related proteins and a decrease in mitochondrial activity compared to the TAE region (p < 0.05), probably due to the downregulation of pyruvate dehydrogenase and antioxidant proteins. Additionally, the OSCC cell lines with a mesenchymal profile (SCC4, SCC9, and SCC25) had a lower mitochondrial mass and membrane potential and generated lower levels of reactive oxygen and nitrogen species than the TAE region. When we analyzed 4-HNE, the reactive species levels were increased in the epithelial regions of OSCC and potentially malignant lesions. A decrease in the levels of 4-HNE/reactive species was observed in the connective tissue underlying the dysplastic regions and the OSCC invasion zone. Based on this scenario, aggressive OSCC is associated with high glycolytic and oxidative metabolism and low mitochondrial and antioxidant activities, which vary according to the differentiation level of the tumor cells and the stage of carcinogenesis.
Assuntos
Carcinoma de Células Escamosas , Metabolismo Energético , Transição Epitelial-Mesenquimal , Neoplasias Bucais , Efeito Warburg em Oncologia , Humanos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Estresse Oxidativo , Masculino , Feminino , Glicólise , Pessoa de Meia-Idade , Prognóstico , Regulação Neoplásica da Expressão Gênica , Mitocôndrias/metabolismo , Aldeídos/metabolismo , IdosoRESUMO
BACKGROUND: Oral leiomyomatous hamartoma (OLH) corresponds to an abnormal, benign and disorganized overgrowth of mature smooth muscle tissue, which can develop in any site where this tissue is found in healthy conditions. The present systematic review aimed to analyze the clinicopathological characteristics of OLH. MATERIALS AND METHODS: The protocol of this study was constructed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and was registered in the Open Science Framework (OSF): OSF.IO/BMPUX. Five electronic databases were used to identify studies for this systematic review: PubMed, Web of Science, Dentistry & Oral Science Source, Scopus and ScienceDirect, from January 15th, 1945 to January 10th, 2024. The Joanna Briggs Institute (JBI) tool was used to assess the risk of bias and the quality of the included reports and case series. RESULTS: A comprehensive search yielded 5,562 articles, of which 55 met the inclusion criteria. The total number of subjects studied in the included investigations was sixty-six. The subjects' ages varied from newborns to 61 years, with a mean age ± standard deviation of 71.23 ± 123.01 months. 50.7% were males and 49.3% were females. Most lesions presented normochromic color (24.24%), pedunculated base (31.81%), firm consistency (22.72%), with an average size of 1.20 cm, present on the dorsum of the tongue (31.81%) or anterior part of the alveolar border of the maxilla (30.30%). Treatment was carried out by surgical excision (78.46%) and half of the studies report that there were no recurrences. CONCLUSIONS: The cases described in the medical-dental literature provide valuable information to date on the clinicopathologic and immunohistochemical profile of OLH. Although it is a rare lesion, it should be considered as part of the differential diagnosis in newborns, infants, children and young adults with lingual and/or maxillary masses present in the midline.
Assuntos
Hamartoma , Humanos , Hamartoma/patologia , Hamartoma/cirurgia , Hamartoma/diagnóstico , Prognóstico , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Doenças da Boca/patologia , Doenças da Boca/cirurgia , Leiomioma/patologia , Leiomioma/cirurgiaRESUMO
Emerging evidence suggests that aberrant expression levels of Sigma1 (SIGMAR1, also known as sigma-1 receptor) have been implicated in the progression of various diseases, including cancer. However, its significance in oral cancer (OC) has not been thoroughly explored. To advance in this field, the present study aimed to investigate the impact of SIGMAR1 knockdown in oral cancer cells. To do so, we included in this study our cohort of human OC samples and OC cell lines, which were utilized for experimental verification through several in vitro assays. Our findings revealed that SIGMAR1 overexpression was associated with poor survival rates and positively correlated with PD-L1 overexpression in human oral cancer samples. Furthermore, SIGMAR1 inhibition led to a decrease in PD-L1 expression and sensitized oral cancer cells to cisplatin treatment by enhancing apoptosis. These results suggest that SIGMAR1 knockdown may present a promising strategy worthy of further exploration in the management of oral cancer.
Assuntos
Antígeno B7-H1 , Cisplatino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Neoplasias Bucais , Receptores sigma , Receptor Sigma-1 , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Cisplatino/farmacologia , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Receptores sigma/genética , Receptores sigma/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética , Masculino , Feminino , Antineoplásicos/farmacologia , Pessoa de Meia-Idade , Resistencia a Medicamentos Antineoplásicos/genéticaRESUMO
Head and neck squamous cell carcinoma (SCC) predisposing factors include smoking and alcohol consumption. However, other agents have been investigated, including viruses. We aimed to investigate the presence of DNA of four different types of human polyomavirus (HPyV) in the oral cavity and oropharyngeal SCC samples from an oncology center in Brazil and evaluate the association between HPyV detection and clinical and sociodemographic characteristics. Sixty fresh frozen samples from three different anatomical sites (tongue, floor of the mouth, and oropharynx, 20 samples for each region) were retrospectively selected. Data from medical records such as age, sex, alcohol consumption, smoking, tumor staging and death in less than 5 years of diagnosis were collected. DNA was extracted for the identification of MCPyV, BKPyV, JCPyV, and TSPyV using PCR followed by Sanger sequencing of positive samples. The identity of the generated DNA sequences was confirmed by alignment reference sequences. The investigation of the presence of HPyV DNA showed positivity of 5% for MCPyV (n = 3), 0% for both BKPyV or TSPyV, and 60% for JCPyV (n = 36). No association was found between the positivity of any HPyV in samples with any clinical or sociodemographic characteristics of the patients, nor with a certain anatomical site, except for the association between death in less than 5 years after diagnosis and positivity for JCPyV (p = 0.009). Positivity for HPyV in oral cavity and oropharyngeal SCC was low for MCPyV, high for JCPyV and null for BKPyV and TSPyV. Further studies should be carried out to better understand the high prevalence of JCPyV found in oral cavity and oropharyngeal SCC.
Assuntos
Carcinoma de Células Escamosas , DNA Viral , Neoplasias Bucais , Neoplasias Orofaríngeas , Infecções por Polyomavirus , Polyomavirus , Humanos , Brasil/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Polyomavirus/isolamento & purificação , Polyomavirus/genética , Polyomavirus/classificação , Idoso , Prevalência , Estudos Retrospectivos , Infecções por Polyomavirus/epidemiologia , Infecções por Polyomavirus/virologia , Neoplasias Bucais/virologia , Neoplasias Bucais/epidemiologia , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/epidemiologia , Adulto , DNA Viral/genética , Carcinoma de Células Escamosas/virologia , Carcinoma de Células Escamosas/epidemiologia , Idoso de 80 Anos ou mais , Orofaringe/virologia , Boca/virologia , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologiaRESUMO
The present investigation aimed to assess the safety of photobiomodulation (PBM) on the oral carcinogenesis process induced by 4NQO, focusing on cell proliferation and apoptosis. Sixty-six Wistar rats received systemic 4NQO for 12 (n = 33) and 20 weeks (n = 33), divided into Control group, PBM 0.3 J, and PBM 1 J. Applications for PBM occurred three times a week. At weeks 12 and 20, the animals were euthanized. The immunoreactivity for anti-ROS1 and anti-p53 antibodies was also assessed. Statistical analysis was assessed by multiple t-tests, Kruskal-Wallis, and Spearman's correlation. At 12 weeks, PBM 1 J group had nodular lesions, distinct from control and PBM 0.3 J groups (p = 0.005). At 20 weeks, nodular lesions were common in control and PBM 0.3 J groups. Histopathological characteristics did not significantly differ between groups at 12 (p = 0.30) and 20 weeks (p = 0.58). Epithelial dysplasia (n = 21) was common at 12 weeks. After 20 weeks, most of the cases revealed squamous cell carcinoma (n = 24). No differences were observed in the immunostaining of p53 and ROS1 among the control and experimental groups and there was no correlation of these proteins with clinicopathological data. During the carcinogenesis process, the PBM did not modify the development of oral lesions and the expression of proliferative and apoptosis proteins.
Assuntos
4-Nitroquinolina-1-Óxido , Apoptose , Carcinogênese , Proliferação de Células , Neoplasias Bucais , Ratos Wistar , Animais , Apoptose/efeitos da radiação , Proliferação de Células/efeitos da radiação , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Ratos , Carcinogênese/efeitos da radiação , Carcinogênese/patologia , Masculino , Terapia com Luz de Baixa Intensidade/métodos , Proteína Supressora de Tumor p53/metabolismo , Modelos Animais de Doenças , Invasividade NeoplásicaRESUMO
PURPOSE: The objective of this study is to present the largest personal series of oral teratomas already published in English literature and discuss the diagnosis, neonatal management, and surgical treatment of this disorder. METHOD: The study included patients treated by the senior author (RSF) between 2004 and 2023. Data were collected regarding prenatal evaluation, perinatal approach, surgical management, evolution, and treatment of secondary deformities. In addition, we performed a literature review on the topic. RESULTS: Twelve patients with oral teratoma were included in this study. Seven cases did not have been submitted to any previous treatment, and five cases had already undergone some treatment in another institution. Four cases were diagnosed as epignathus (33.3%), two as true teratomas (16.6%), four as teratoid teratomas (33.3%), one as dermoid teratoma (8.3%) and one as fetus in fetus (8.3%). All patients, except for one, had the tumor surgically removed with good evolution. There was one case of recurrence, successfully operated. The most frequently associated comorbidity was 0-14 fissure, present in 66% of the cases. CONCLUSION: The experience of our twelve cases indicates that prenatal diagnosis, associated with good multidisciplinary planning of the delivery care, and complete resection of the masses reveal high success rates in the treatment of this pathology. CLINICAL TRIAL NUMBER: This study was performed in line with the principles of the declaration of Helsinki. Approval was granted by the Ethics Committee of Federal University of Paraná - 47102421.2.0000.5225.
Assuntos
Neoplasias Bucais , Teratoma , Humanos , Teratoma/cirurgia , Teratoma/congênito , Feminino , Neoplasias Bucais/cirurgia , Neoplasias Bucais/congênito , Neoplasias Bucais/patologia , Masculino , Recém-Nascido , Gravidez , LactenteRESUMO
O câncer de boca é o sexto câncer mais comum em todo o mundo e representa um problema global crescente. Apesar disso, 70% desses cânceres são diagnosticados em estágios avançados, reforçando a importância de estratégias para prevenção e detecção precoce do câncer. Este trabalho tem como objetivo investigar a aplicabilidade de estratégias para detecção precoce do câncer de boca. Como existem diversas revisões sistemáticas já publicadas sobre o tema, a proposta é realizar uma revisão guarda-chuva das revisões sistemáticas. As buscas realizadas nas bases de dados resultaram em 2145 artigos, e outras fontes de informações acrescentaram mais 114 artigos. Após a detecção de artigos duplicados eletrônica e manualmente, em conjunto com a primeira fase da revisão, 83 artigos foram selecionados para a segunda fase da revisão. Por fim, 46 revisões sistemáticas foram incluídas neste estudo, tendo 9 artigos sido considerados confiáveis para sumarização da evidência atual. Artigos cuja estratégia foi de exame clínico convencional realizado por profissionais treinados e estudos em que houve um maior acesso dos indivíduos à saúde bucal, apresentaram um resultado mais preciso, confiável e custo-efetivo na avaliação dos grupos de indivíduos de alto risco. Em geral, os métodos auxiliares que apresentaram resultados promissores foram aqueles à base de autofluorescência e citopatologia. As estratégias de rastreamento não devem ser descartadas, uma vez que ainda há uma carência de estudos de alta qualidade nesse tema.
Assuntos
Neoplasias Bucais , Programas de Rastreamento , Morbidade , Mortalidade , Diagnóstico Precoce , DiagnósticoRESUMO
BACKGROUND: The role of microbiome, particularly Fusobacterium nucleatum (Fn), in periodontal disease and oral squamous cell carcinoma (OSCC) has been recently explored. This study aimed to evaluate the Fn presence and its levels in oral rinse samples from Brazilian OSCC patients and healthy individuals and its association with sociodemographic, clinical, and oral health features. METHODS: In this case-control study, 80 participants were included, 31 OSCC patients and 49 individuals without a cancer history. Clinical data were collected, and an oral exam was done on a subset of the cohort. Fn levels were evaluated by droplet digital PCR (ddPCR) in oral rinse samples and were categorized as Fn-high or Fn-low based on the median number of copies per reaction. RESULTS: OSCC patients showed higher levels of Fn (68%, p = 0.03) than controls, and all OSCC cases were diagnosed with periodontal disease (100%, p = 1.0). In the univariate analysis, Fn-high level was more frequently present in OSCC cases compared to controls (p = 0.01). It was also observed that Fn-high level OSCC cases were significantly associated with self-reported non-white ethnicity (71.4%, p = 0.01) and had more infiltrative lesions (57.1%, p = 0.02) than Fn-low OSCC cases. Fn-high levels in oral rinse samples, were significantly more prevalent among OSCC than in controls. CONCLUSIONS: In OSCC patients, Fn-high levels were associated with non-white ethnicity and lesions with infiltrative clinical aspects. Among OSCC cases, all had periodontal disease.
Assuntos
Carcinoma de Células Escamosas , Fusobacterium nucleatum , Neoplasias Bucais , Doenças Periodontais , Reação em Cadeia da Polimerase , Humanos , Fusobacterium nucleatum/isolamento & purificação , Masculino , Feminino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Neoplasias Bucais/microbiologia , Doenças Periodontais/microbiologia , Carcinoma de Células Escamosas/microbiologia , Idoso , Brasil , Adulto , Infecções por Fusobacterium/microbiologiaRESUMO
Objective: This study aimed to review the current body of literature on underexplored areas of photobiomodulation (PBM) for preventing and/or treating oral adverse events. Background: Recent studies suggest that PBM may offer potential benefits in managing cancer-related toxicities other than oral mucositis. Nevertheless, further research to establish conclusive evidence is still missing. Methods: A panel of specialists conducted a narrative review to evaluate the evidence on PBM therapy for oral mucositis, xerostomia, dysgeusia, dysphagia, and trismus/fibrosis. Each topic was reviewed by two specialists who discussed treatment rationale, summarized current evidence, evaluated risk/benefit ratio, and identified future research directions. Results: The current evidence suggests promising outcomes in nonroutine uses of PBM for xerostomia, dysgeusia, odynophagia, oral mucositis (extraoral PBM and the pediatric population), and trismus/fibrosis. However, the primary studies are often small and may have biases that require further evaluation, particularly regarding treatment safety. Conclusion: Despite the overall positive impression of PBM therapy for oral adverse events of cancer treatment, robust evidence from large multicentered studies is necessary to support its widespread clinical use.
Assuntos
Terapia com Luz de Baixa Intensidade , Humanos , Trismo/radioterapia , Trismo/etiologia , Neoplasias Bucais/radioterapia , Xerostomia/etiologia , Xerostomia/radioterapia , Estomatite/radioterapia , Estomatite/etiologia , Transtornos de Deglutição/radioterapia , Transtornos de Deglutição/etiologia , Disgeusia/etiologiaRESUMO
The oral cavity is a frequent site for head and neck cancers, which rank as the sixth most common cancer globally, with a 5-year survival rate slightly over 50%. Current treatments are limited, and resistance to therapy remains a significant clinical obstacle. IsCT1, a membrane-active peptide derived from the venom of the scorpion Opisthacanthus madagascariensis, has shown antitumor effects in various cancer cell lines, including breast cancer and chronic myeloid leukemia. However, its hemolytic action limits its potential therapeutic use. This study aims to assess the antitumor and antiproliferative activities of synthetic peptides derived from IsCT1 (IsCT-P, AC-AFPK-IsCT1, AFPK-IsCT1, AC-KKK-IsCT1, and KKK-IsCT1) in the context of oral squamous cell carcinoma. We evaluated the cytotoxic effects of these peptides on tongue squamous cell carcinoma cells and normal cells, as well as their impact on cell cycle phases, the expression of proliferation markers, modulators of cell death pathways, and mitochondrial potential. Our results indicate that the IsCT1 derivatives IsCT-P and AC-AFPK-IsCT1 possess cytotoxic properties towards squamous cell carcinoma cells, reducing mitochondrial membrane potential and the proliferative index. The treatment of cancer cells with AC-AFPK-IsCT1 led to a positive modulation of pro-apoptotic markers p53 and caspases 3 and 8, a decrease in PCNA and Cyclin D1 expression, and cell cycle arrest in the S phase. Notably, contrary to the parental IsCT1 peptide, AC-AFPK-IsCT1 did not exhibit hemolytic activity or cytotoxicity towards normal cells. Therefore, AC-AFPK-IsCT1 might be a viable therapeutic option for head and neck cancer treatment.
Assuntos
Antineoplásicos , Carcinoma de Células Escamosas , Proliferação de Células , Neoplasias Bucais , Venenos de Escorpião , Humanos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Venenos de Escorpião/farmacologia , Venenos de Escorpião/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Animais , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/síntese química , Apoptose/efeitos dos fármacos , Escorpiões/química , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacosRESUMO
OBJECTIVE: This study aims to explore the effects of miR-223-3p and miR-155-5p on epithelial-mesenchymal transition (EMT) and migration in oral squamous cell carcinoma (OSCC). METHODOLOGY: EMT markers (E-cadherin, N-cadherin, P120 catenin (P120ctn), and vimentin) expression was determined by qRT-PCR and western blot analysis in SCC-9 cells which overexpress miR-155-5p and/or not express miR-223-3p. Scratch assays and Transwell migration assays were conducted to evaluate cell migration ability. RESULTS: When miR-223-3p was inhibited in OSCC cells, P120ctn and E-cadherin mRNA levels were dramatically downregulated (P<0.05), while N-cadherin levels were significantly upregulated, and the migration ability of OSCC cells increased. The overexpression of miR-155-5p in OSCC cells upregulated miR-223-3p significantly (34-fold) compared to the control group. It also led to significant downregulation of the mRNA of P120ctn and E-cadherin and significant upregulation of the mRNA of N-cadherin and Vimentin (P<0.05). Meanwhile, the migratory ability of OSCC cells significantly increased. When miR-155-5p was overexpressed while miR-223-3p was inhibited, the highest expression of E-cadherin and P120ctn mRNA and the lowest expression of N-cadherin(P<0.05) was observed. Simultaneously, tumor cell migration was significantly facilitated. CONCLUSION: miR-223-3p inhibits the migration of OSCC cells, while miR-155-5p can elevate the miR-223-3p mRNA expression. The simultaneous miR-155-5p overexpression and miR-223-3p inhibition can activate pEMT, increasing OSCC migration in vitro. This provides a novel approach and potential target for the effective treatment of OSCC.
Assuntos
Western Blotting , Caderinas , Carcinoma de Células Escamosas , Cateninas , Movimento Celular , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Neoplasias Bucais , Vimentina , MicroRNAs/genética , Humanos , Caderinas/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Cateninas/genética , delta Catenina , Regulação para Baixo , Regulação para Cima , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Tempo , Ensaios de Migração CelularRESUMO
Oral mucosal melanomas (OMMs) are aggressive neoplasms commonly found in dogs but rare in humans. Utilizing whole exome sequencing (WES), which focuses on protein-coding regions to reveal mutation profiles, we conducted a comparative analysis of canine OMM and human melanomas. This study involved DNA extraction, exome enrichment, and sequencing from three canine OMM cell lines (CMGD-2, CMGD-5, TLM-1), five canine OMM frozen samples, a human OMM cell line (MEMO), and a human commercial skin melanoma cell line (SK-MEL-28). The sequencing and subsequent analysis of FASTQ files yielded final variant files, leading to the identification of mutations. Our findings revealed a total of 500 mutated genes in canine OMM, including significant ones such as EP300, FAT4, JAK3, LRP1B, NCOR1, and NOTCH1. Notably, 82 shared mutations were identified between human melanomas and canine OMM genomes. These mutations were categorized based on the gene functions. The identification of these mutations provides critical insights that can pave the way for the development of novel therapeutic strategies for both canine and human OMM, offering hope for more effective treatments in the future.
Assuntos
Sequenciamento do Exoma , Melanoma , Mucosa Bucal , Neoplasias Bucais , Mutação , Cães , Melanoma/genética , Melanoma/veterinária , Melanoma/patologia , Humanos , Animais , Neoplasias Bucais/genética , Neoplasias Bucais/veterinária , Neoplasias Bucais/patologia , Mucosa Bucal/patologia , Mucosa Bucal/metabolismo , Linhagem Celular Tumoral , Doenças do Cão/genéticaRESUMO
OBJECTIVES: To determine the prevalence and association of HPV and Herpesviruses in saliva and tissue samples of patients with orofacial tumors. METHODS: Biopsies of tumors were done, and saliva samples were collected from patients with orofacial tumors for the determination of viruses using nested multiplex PCR. Independent variables were sex, age, comorbidities, tumor stage, and length of stay. Outcome variables were the presence or absence of herpesviruses and HPV. Descriptive summaries and inferential statistics were done. RESULTS: A hundred patients were included in the study. Prevalence of herpesviruses and HPV were 17.6 % and 57.0 % in tumors, and 48.3 % and 60.0 % in the saliva of patients respectively. Herpesviruses detected included EBV (21.3 %), HHV-7 (11.2 %), CMV (6.7 %), HSV-1 (5.1 %), HSV-2 (1.1 %), VZV (1.1 %), and Kaposi sarcoma virus (0.6 %). The most prevalent HPV genotypes were HPV-42 (29 %), HPV-43 (22.7 %), HPV-52 (22.2 %), HPV-39 (18.8 %), and HPV-18 (9.1 %). The odds of EBV being detected in malignant orofacial tumors were 2 times that of benign orofacial tumors. HPV DNA in the saliva of patients with orofacial tumors was 69.7 %, compared to 18.2 % of the control sample (p < 0.001). The median length of stay for all participants was 6.5 days, those associated with viruses stayed longer. CONCLUSION: There was a high prevalence of Herpesviruses and HPV in saliva and tumor samples of patients with orofacial tumors, signalling some potential for more work to be done in this area.
Assuntos
Herpesviridae , Papillomaviridae , Saliva , Humanos , Feminino , Saliva/virologia , Masculino , Pessoa de Meia-Idade , Herpesviridae/isolamento & purificação , Herpesviridae/genética , Adulto , Papillomaviridae/isolamento & purificação , Papillomaviridae/genética , Idoso , Biópsia , Adulto Jovem , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por Herpesviridae/virologia , Infecções por Herpesviridae/epidemiologia , Prevalência , DNA Viral/análise , Neoplasias Bucais/virologia , Neoplasias Bucais/patologia , Adolescente , Brasil/epidemiologia , Idoso de 80 Anos ou mais , Reação em Cadeia da Polimerase Multiplex , Papillomavirus HumanoRESUMO
OBJECTIVE: This review aims to provide a comprehensive analysis of the effectiveness of saliva as a non-invasive diagnostic marker for oral cancer. Despite progress in oral cancer diagnosis and prognosis, the 5-year survival rate remains low due to the resistance to treatment and delayed diagnosis, which can be attributed to various factors including tobacco and alcohol consumption, genetic damage, and human papillomavirus (HPV). The potential use of saliva as an easily accessible non-invasive screening and diagnostic method arises from its direct contact with the lesion site. METHODOLOGY: Data for this study were gathered via a comprehensive literature evaluation using search engines such as the PubMed, Web of Science, Google Scholar, and SciFinder. RESULTS: Identifying salivary biomarkers shows potential to transform oral cancer diagnostics by offering a reliable alternative to the traditional invasive methods. Saliva is an abundant reservoir for both cell-bound and cell-free organic and inorganic constituents. Thus, saliva is an appropriate field for research in proteomics, genomics, metagenomics, and metabolomics. CONCLUSION: This review provides a comprehensive elucidation of salivary biomarkers and their function in non-invasive oral cancer diagnosis, demonstrating their potential to enhance patient outcomes and reduce the impact of this devastating disease.
Assuntos
Biomarcadores Tumorais , Neoplasias Bucais , Saliva , Humanos , Neoplasias Bucais/diagnóstico , Saliva/química , Saliva/virologia , Biomarcadores Tumorais/análise , Detecção Precoce de Câncer/métodosRESUMO
Oral squamous cell carcinoma (OSCC) is the sixth most common type of cancer globally. While smoking is a key risk factor, rising cases in non-smokers highlight the need to explore other factors like diet. This scoping review aims to deepen the evidence on the relationship between OSCC and diet, following PRISMA-ScR guidelines, and was registered on Open Science Framework. Searches were performed in four electronic databases: MEDLINE, Embase, Web of Science, and Lilacs, without date or language restrictions. Studies were evaluated, extracted, and compiled in a narrative table. Seventeen studies with 10,954 patients were analyzed. Most patients were male (74.63%), aged 18-89 (average 50.62). Studies were mainly from high (82%) and medium (17%) Human Development Index (HDI) countries. Dietary surveys included a Food Frequency Questionnaire (FFQ) (58.8%), interviews/questionnaires (17.6%), and an FFQ with a photographic atlas (5.9%). Certain foods in excess like fruits, vegetables, and tea were inversely associated with OSCC, while salty meats, dairy, coffee, sausages, and fried and spicy foods were positively associated. Due to the heterogeneity of the tools used to obtain food frequency data, the results should be interpreted cautiously. New standardized studies and randomized trials are essential to advance understanding and control confounding factors in this field.
Assuntos
Carcinoma de Células Escamosas , Dieta , Neoplasias Bucais , Humanos , Neoplasias Bucais/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Idoso , Adulto Jovem , Adulto , Feminino , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adolescente , Idoso de 80 Anos ou maisRESUMO
Lymphoma is the most common tumor of hematopoietic origin in horses. The course of the disease and clinical signs vary greatly, depending on tumor location and extent. The aim of this report is to describe the occurrence of T-cell-rich oral large B-cell lymphoma with marked local infiltration in a 25-year-old Crioula mare. The mare showed an increase in volume on the right side of its face, dyspnea, anorexia, and progressive weight loss. The clinical assessment showed that the lesion was located in the rostral and caudal sinuses and was markedly invasive to adjacent structures. The autopsy revealed a yellow mass with a soft to firm consistency, infiltrating multiple bones in the skull, and extensively invading the hard palate and masseter muscle. Histologically the mass comprised an undifferentiated malignant neoplasm characterized by a densely cellular neoplasm composed of large CD20 + neoplastic B-lymphocytes admixed with sheets of small, CD3 + reactive T-lymphocytes supported by delicate fibrovascular stroma leading to the diagnosis of oral T-cell-rich large B-cell lymphoma.