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1.
World J Surg Oncol ; 19(1): 279, 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34535149

RESUMO

BACKGROUND: The administration of postoperative radiotherapy remains controversial in pN1 oral cavity cancer patients without extranodal extension. The aim is to determine whether postoperative radiotherapy reduces the neck recurrence rate and improves the survival outcomes of pN1 patients. METHODS: This study consecutively enrolled 1056 patients with newly diagnosed oral squamous cell carcinoma who underwent tumor wide excision and neck dissection from September 2002 to November 2019. One hundred two pN1 patients without extranodal extension were eligible for analysis. Then, a subgroup analysis of 40 patients was performed after patients with other adverse risk factors (positive margins, close margins, lymphovascular invasion, perineural invasion, tumor depth ≥ 10 mm, and poor histological differentiation) were excluded. RESULTS: Of the 102 eligible pN1 patients, 26 patients received surgery alone, and 76 received postoperative radiotherapy. No significant differences were observed in the neck recurrence rate (7.7% vs. 15.8%, p = 0.30). Similarly, in patients without other adverse risk factors, no significant differences were observed in the neck recurrence rate (5% vs. 20%, p = 0.15) between surgery alone group and postoperative radiotherapy group. Moreover, no significant difference was found in the neck recurrence-free survival rate, overall survival, and disease-specific survival (77.1% vs. 52.5%, p = 0.42, 83.5% vs. 64.5%, p = 0.81, and 88.2% vs. 67.9%, p = 0.34, respectively). CONCLUSION: Postoperative radiotherapy did not significantly decrease the probability of neck recurrence and survival outcomes in pN1 patients without extranodal extension. Radical surgery alone may be considered sufficient treatment for pN1 patients without other adverse risk factors.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Extensão Extranodal , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
2.
Int J Mol Sci ; 22(16)2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34445087

RESUMO

The miR-31 host gene (MIR31HG) encodes a long non-coding RNA (LncRNA) that harbors miR-31 in its intron 2; miR-31 promotes malignant neoplastic progression. Overexpression of MIR31HG and of miR-31 occurs during oral squamous cell carcinoma (OSCC). However, the downstream effectors modulated by MIR31HG during OSCC pathogenesis remain unclear. The present study identifies up-regulation of MIR31HG expression during the potentially premalignant disorder stage of oral carcinogenesis. The potential of MIR31HG to enhance oncogenicity and to activate Wnt and FAK was identified when there was exogenous MIR31HG expression in OSCC cells. Furthermore, OSCC cell subclones with MIR31HG deleted were established using a Crispr/Cas9 strategy. RNA sequencing data obtained from cells expressing MIR31HG, cells with MIR31HG deleted and cells with miR-31 deleted identified 17 candidate genes that seem to be modulated by MIR31HG in OSCC cells. A TCGA database algorithm pinpointed MMP1, BMP2 and Limb-Bud and Heart development (LBH) as effector genes controlled by MIR31HG during OSCC. Exogenous LBH expression decreases tumor cell invasiveness, while knockdown of LBH reverses the oncogenic suppression present in MIR31HG deletion subclones. The study provides novel insights demonstrating the contribution of the MIR31HG-LBH cascade to oral carcinogenesis.


Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Bucais/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/genética , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma de Células Escamosas/patologia , Progressão da Doença , Humanos , Neoplasias Bucais/patologia , Regulação para Cima
3.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361027

RESUMO

The experimental animal model is still essential in the development of new anticancer drugs. We characterized mouse tumors derived from two-dimensional (2D) monolayer cells or three-dimensional (3D) spheroids to establish an in vivo model with highly standardized conditions. Primary cancer-associated fibroblasts (CAFs) were cultured from head and neck squamous cell carcinoma (HNSCC) tumor tissues and co-injected with monolayer cancer cells or spheroids into the oral mucosa of mice. Mice tumor blood vessels were stained, followed by tissue clearing and 3D Lightsheet fluorescent imaging. We compared the effect of exosomes secreted from 2D or 3D culture conditions on the angiogenesis-related genes in HNSCC cells. Our results showed that both the cells and spheroids co-injected with primary CAFs formed tumors. Interestingly, vasculature was abundantly distributed inside the spheroid-derived but not the monolayer-derived mice tumors. In addition, cisplatin injection more significantly decreased spheroid-derived but not monolayer-derived tumor size in mice. Additionally, exosomes isolated from co-culture media of FaDu spheroid and CAF upregulated angiogenesis-related genes in HNSCC cells as compared to exosomes from FaDu cell and CAF co-culture media under in vitro conditions. The mouse tumor xenograft model derived from 3D spheroids of HNSCC cells with primary CAFs is expected to produce reliable chemotherapy drug screening results given the robust angiogenesis and lack of necrosis inside tumor tissues.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Bucais/patologia , Neovascularização Patológica/patologia , Esferoides Celulares/patologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma de Células Escamosas/metabolismo , Exossomos/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Bucais/metabolismo , Neovascularização Patológica/metabolismo , Cultura Primária de Células/métodos , Esferoides Celulares/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto/normas
4.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34445346

RESUMO

Corosolic acid (CA; 2α-hydroxyursolic acid) is a natural pentacyclic triterpenoid with antioxidant, antitumour and antimetastatic activities against various tumour cells during tumourigenesis. However, CA's antitumour effect and functional roles on human oral squamous cell carcinoma (OSCC) cells are utterly unknown. In this study, our results demonstrated that CA significantly exerted an inhibitory effect on matrix metalloproteinase (MMP)1 expression, cell migration and invasion without influencing cell growth or the cell cycle of human OSCC cells. The critical role of MMP1 was confirmed using the GEPIA database and showed that patients have a high expression of MMP1 and have a shorter overall survival rate, confirmed on the Kaplan-Meier curve assay. In the synergistic inhibitory analysis, CA and siMMP1 co-treatment showed a synergically inhibitory influence on MMP1 expression and invasion of human OSCC cells. The ERK1/2 pathway plays an essential role in mediating tumour progression. We found that CA significantly inhibits the phosphorylation of ERK1/2 dose-dependently. The ERK1/2 pathway played an essential role in the CA-mediated downregulation of MMP1 expression and in invasive motility in human OSCC cells. These findings first demonstrated the inhibitory effects of CA on OSCC cells' progression through inhibition of the ERK1/2-MMP1 axis. Therefore, CA might represent a novel strategy for treating OSCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Triterpenos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 1 da Matriz/metabolismo , Neoplasias Bucais/metabolismo , Metástase Neoplásica , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Células Tumorais Cultivadas
5.
J Evid Based Dent Pract ; 21(2): 101573, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34391558

RESUMO

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Oh LJ, Phan K, Kim SW, Low TH, Gupta R, Clark JR. Elective neck dissection vs observation for early-stage oral squamous cell carcinoma: Systematic review and meta-analysis. Oral Oncol. 2020;105:104,661. doi:10.1016/j.oraloncology.2020.104661. SOURCE OF FUNDING: Funding information not available. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Esvaziamento Cervical , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço
6.
Int J Mol Sci ; 22(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361070

RESUMO

In cancer therapy, radioresistance or chemoresistance cells are major problems. We established clinically relevant radioresistant (CRR) cells that can survive over 30 days after 2 Gy/day X-ray exposures. These cells also show resistance to anticancer agents and hydrogen peroxide (H2O2). We have previously demonstrated that all the CRR cells examined had up-regulated miR-7-5p and after miR-7-5p knockdown, they lost radioresistance. However, the mechanism of losing radioresistance remains to be elucidated. Therefore, we investigated the role of miR-7-5p in radioresistance by knockdown of miR-7-5p using CRR cells. As a result, knockdown of miR-7-5p increased reactive oxygen species (ROS), mitochondrial membrane potential, and intracellular Fe2+ amount. Furthermore, miR-7-5p knockdown results in the down-regulation of the iron storage gene expression such as ferritin, up-regulation of the ferroptosis marker ALOX12 gene expression, and increases of Liperfluo amount. H2O2 treatment after ALOX12 overexpression led to the enhancement of intracellular H2O2 amount and lipid peroxidation. By contrast, miR-7-5p knockdown seemed not to be involved in COX-2 and glycolysis signaling but affected the morphology of CRR cells. These results indicate that miR-7-5p control radioresistance via ROS generation that leads to ferroptosis.


Assuntos
Ferroptose , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Bucais/patologia , Tolerância a Radiação , Espécies Reativas de Oxigênio/metabolismo , Araquidonato 12-Lipoxigenase/metabolismo , Células HeLa , Humanos , Peróxido de Hidrogênio/metabolismo , Potencial da Membrana Mitocondrial , Neoplasias Bucais/genética , Neoplasias Bucais/radioterapia , Transdução de Sinais , Células Tumorais Cultivadas
7.
Br J Oral Maxillofac Surg ; 59(7): 814-819, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34325947

RESUMO

Dermal metastasis (DM) is, by definition, the involvement of the skin by cancer cells that originate from cancer elsewhere in the body. The skin is considered a rare site of distant failure in head and neck cancer and DM is the bearer of a poor outcome. Literature about it is limited so this study was undertaken to analyse the factors associated with its incidence and outcomes. A prospectively maintained database on operated cases of oral cancer at a tertiary cancer centre was analysed, and patients who developed dermal metastases during follow up were evaluated. Factors that contributed to early DM and predicted survival after its development were studied. A total of 68 patients (2.8%) had DM as the first presentation of recurrence after a median disease-free period of five months. Early DM was significantly associated with skin involvement by the primary tumour at the time of presentation (p=0.06), extracapsular extension of nodes (p=0.004), and with those who required adjuvant chemotherapy in view of aggressive histology (p=0.021). Median (range) survival after the detection of DM was 97 (5-328) days (3.25 months). Surgical excision of isolated cases was associated with significantly increased survival after detection (p=0.05). Whenever it is feasible without too much morbidity, solitary DM should be excised.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Quimioterapia Adjuvante , Estudos de Coortes , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos
8.
Mol Med Rep ; 24(4)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34328195

RESUMO

Oral squamous cell carcinoma (OSCC) is a cancer associated with high mortality (accounting for 3.1/100,000 deaths per year in Brazil in 2013) and a high frequency of amplification in the expression of the epidermal growth factor receptor (EGFR). Treatment with the EGFR inhibitor cetuximab leads to drug resistance in patients with OSCC due to unknown mechanisms. Galectin­3 (Gal­3) is a ß­galactoside binding lectin that regulates multiple signaling pathways in cells. The present study aimed to investigate the effect of Gal­3 in cetuximab­resistant (cet­R) OSCC. The OSCC HSC3 cell line was selected to establish a mouse xenograft model, which was treated with cetuximab to induce resistance. Subsequently, a Gal­3 inhibitor was used to treat cet­R tumors, and the tumor volume was monitored. The expression of Gal­3, phosphorylated (p)­ERK1/2 and p­Akt was assessed using immunohistochemistry. The combined effect of cetuximab and the Gal­3 inhibitor on HSC3 tumor xenografts was also investigated. HSC3 cells were cultured in vitro to investigate the regulatory effects of Gal­3 on ERK1/2 and Akt via western blotting. In addition, the effects of the Gal­3 inhibitor on the proliferation, colony formation, invasion and apoptosis of HSC3 cells were investigated by performing Cell Counting Kit­8, colony formation, Transwell and apoptosis assays, respectively. In cet­R OSCC tumors, increased expression of Gal­3, p­ERK1/2 and p­Akt was observed. Further research demonstrated that Gal­3 regulated the expression of both ERK1/2 and Akt in HSC3 cells by promoting phosphorylation. Moreover, the Gal­3 inhibitor decreased the proliferation and invasion, but increased the apoptosis of cet­R HSC3 cells. In addition, the Gal­3 inhibitor suppressed the growth of cet­R tumors. Collectively, the results indicated that the Gal­3 inhibitor and cetuximab displayed a synergistic inhibitory effect on OSCC tumors. In summary, the present study demonstrated that Gal­3 may serve an important role in cet­R OSCC. The combination of cetuximab and the Gal­3 inhibitor may display a synergistic antitumor effect, thereby inhibiting the development of cetuximab resistance in OSCC.


Assuntos
Proteínas Sanguíneas/antagonistas & inibidores , Carcinoma de Células Escamosas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Galectinas/antagonistas & inibidores , Neoplasias Bucais/tratamento farmacológico , Animais , Antineoplásicos Imunológicos/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Sanguíneas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cetuximab/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Galectinas/genética , Técnicas de Silenciamento de Genes , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Cochrane Database Syst Rev ; 7: CD010276, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34282854

RESUMO

BACKGROUND: Squamous cell carcinoma is the most common form of malignancy of the oral cavity, and is often proceeded by oral potentially malignant disorders (OPMD). Early detection of oral cavity squamous cell carcinoma (oral cancer) can improve survival rates. The current diagnostic standard of surgical biopsy with histology is painful for patients and involves a delay in order to process the tissue and render a histological diagnosis; other diagnostic tests are available that are less invasive and some are able to provide immediate results. This is an update of a Cochrane Review first published in 2015. OBJECTIVES: Primary objective: to estimate the diagnostic accuracy of index tests for the detection of oral cancer and OPMD, in people presenting with clinically evident suspicious and innocuous lesions. SECONDARY OBJECTIVE: to estimate the relative accuracy of the different index tests. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: MEDLINE Ovid (1946 to 20 October 2020), and Embase Ovid (1980 to 20 October 2020). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were also searched for ongoing trials to 20 October 2020. No restrictions were placed on the language or date of publication when searching the electronic databases. We conducted citation searches, and screened reference lists of included studies for additional references. SELECTION CRITERIA: We selected studies that reported the diagnostic test accuracy of the following index tests when used as an adjunct to conventional oral examination in detecting OPMD or oral cavity squamous cell carcinoma: vital staining (a dye to stain oral mucosa tissues), oral cytology, light-based detection and oral spectroscopy, blood or saliva analysis (which test for the presence of biomarkers in blood or saliva). DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for relevance. Eligibility, data extraction and quality assessment were carried out by at least two authors, independently and in duplicate. Studies were assessed for methodological quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis was used to combine the results of studies for each index test using the bivariate approach to estimate the expected values of sensitivity and specificity. MAIN RESULTS: This update included 63 studies (79 datasets) published between 1980 and 2020 evaluating 7942 lesions for the quantitative meta-analysis. These studies evaluated the diagnostic accuracy of conventional oral examination with: vital staining (22 datasets), oral cytology (24 datasets), light-based detection or oral spectroscopy (24 datasets). Nine datasets assessed two combined index tests. There were no eligible diagnostic accuracy studies evaluating blood or salivary sample analysis. Two studies were classed as being at low risk of bias across all domains, and 33 studies were at low concern for applicability across the three domains, where patient selection, the index test, and the reference standard used were generalisable across the population attending secondary care. The summary estimates obtained from the meta-analysis were: - vital staining: sensitivity 0.86 (95% confidence interval (CI) 0.79 to 0.90) specificity 0.68 (95% CI 0.58 to 0.77), 20 studies, sensitivity low-certainty evidence, specificity very low-certainty evidence; - oral cytology: sensitivity 0.90 (95% CI 0.82 to 0.94) specificity 0.94 (95% CI 0.88 to 0.97), 20 studies, sensitivity moderate-certainty evidence, specificity moderate-certainty evidence; - light-based: sensitivity 0.87 (95% CI 0.78 to 0.93) specificity 0.50 (95% CI 0.32 to 0.68), 23 studies, sensitivity low-certainty evidence, specificity very low-certainty evidence; and - combined tests: sensitivity 0.78 (95% CI 0.45 to 0.94) specificity 0.71 (95% CI 0.53 to 0.84), 9 studies, sensitivity very low-certainty evidence, specificity very low-certainty evidence. AUTHORS' CONCLUSIONS: At present none of the adjunctive tests can be recommended as a replacement for the currently used standard of a surgical biopsy and histological assessment. Given the relatively high values of the summary estimates of sensitivity and specificity for oral cytology, this would appear to offer the most potential. Combined adjunctive tests involving cytology warrant further investigation. Potentially eligible studies of blood and salivary biomarkers were excluded from the review as they were of a case-control design and therefore ineligible. In the absence of substantial improvement in the tests evaluated in this updated review, further research into biomarkers may be warranted.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Neoplasias Bucais/diagnóstico , Viés , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/patologia , Corantes , Detecção Precoce de Câncer , Humanos , Luz , Neoplasias Labiais/diagnóstico , Neoplasias Labiais/patologia , Boca/patologia , Neoplasias Bucais/patologia , Saliva/química , Sensibilidade e Especificidade
10.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299129

RESUMO

Oral cancer (OC) has been attracted research attention in recent years as result of its high morbidity and mortality. Costunolide (CTD) possesses potential anticancer and bioactive abilities that have been confirmed in several types of cancers. However, its effects on oral cancer remain unclear. This study investigated the potential anticancer ability and underlying mechanisms of CTD in OC in vivo and in vitro. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of CTD on OC cells; assessments for migration and invasion of OC cells were conducted by transwell; Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. The results revealed that CTD suppressed the proliferation, migration and invasion of oral cancer cells effectively and induced cell cycle arrest and apoptosis; regarding the mechanism, CTD bound to AKT directly by binding assay and repressed AKT activities through kinase assay, which thereby downregulating the downstream of AKT. Furthermore, CTD remarkably promotes the generation of reactive oxygen species by flow cytometry assay, leading to cell apoptosis. Notably, CTD strongly suppresses cell-derived xenograft OC tumor growth in an in vivo mouse model. In conclusion, our results suggested that costunolide might prevent progression of OC and promise to be a novel AKT inhibitor.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/farmacologia , Animais , Ciclo Celular , Movimento Celular , Proliferação de Células , Humanos , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Nus , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Br J Oral Maxillofac Surg ; 59(7): 771-775, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34127322

RESUMO

Oral squamous cell carcinoma (OSCC) remains the most common cancer among males in Sri Lanka. Metastasis to neck is a crucial prognostic factor. A modified radical/radical neck dissection including levels I -V, was performed in patients with OSCC who had a clinically positive neck (cN+). Currently, evidence suggests that sparing level V in a cN+ may be justified due to less chance of metastasis in early stages of the disease. To the best of our knowledge, the incidence of metastasis to level V in patients with cN+s has not been previously investigated in a Sri Lankan context. We aimed to determine level V lymph node metastasis and related clinicopathological indicators in cN+s in patients with OSCC. A multicentre retrospective study investigated postoperative biopsy reports of 187 patients for five years. OSCC patients with cN+s who underwent neck dissections of levels I-V were included. Only 6.4% of patients had histopathologically positive level V lymph nodes. A total of 127 lymph nodes were harvested from level V of those who showed level V positivity and out of them 68 were positive with a third of cases showing extranodal extension (ENE). The buccal mucosa (n=4) and lateral aspect of the anterior two thirds of the tongue (n=4) were the common primary sites for level V metastasis. In patients who showed positivity in levels III and IV, a considerably higher probability of level V nodes being positive was seen, which was statistically significant (p = 0.0001). We have concluded that the routine performance of a modified radical/radical neck dissection for cN+s should be stopped, as the incidence of Level V positivity is significantly low. Assessing the cN+ for N stage, status of levels III and IV, pattern of invasion, differentiation, and the site may be used instead as predictors for level V positivity.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Incidência , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Esvaziamento Cervical , Estadiamento de Neoplasias , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço
12.
J Photochem Photobiol B ; 221: 112245, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34182186

RESUMO

There is currently no clear understanding on the pathways involved in the process of cell inhibition by photobiomodulation (PBM). The present study evaluated the influence of PBM on the expression of autophagy markers in vitro in an in situ model of oral carcinoma. Oral squamous cell carcinoma (Cal27) and stromal fibroblasts (FG) cultures were used. The independent variables were 'cell type' (FG and CAL27) 'culture condition' (monocultures or co-cultures) and PBM (placebo and 36 J/cm2). The cultures were irradiated from a red LED source for mRNA expression and protein expression analyses. The autophagy markers evaluated were Beclin-1, LC3B and p62 as well as adjuvant markers (BAX Bcl-2, VEGF, CD105, CD34, PRDX1, PRDX4 and GRP78). The Cal27 cells upregulated the autophagy markers upon exposure to PBM both at the mRNA and protein expression levels, providing evidence to explain malignant cell inhibition by PBM.


Assuntos
Autofagia/genética , Luz , Regulação para Cima/efeitos da radiação , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Técnicas de Cocultura , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo
13.
Acta Cytol ; 65(5): 403-410, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34120116

RESUMO

INTRODUCTION: Tobacco contains several genotoxic agents including N-nitrosamine which has the potential to cause significant nuclear damage. Nuclear blebbing is a form of protrusion on the nuclear membrane and could potentially be caused by tobacco-induced genotoxicity and is closely associated with malignancy. Thus, the present study aimed to assess if tobacco-associated oral potentially malignant disorders including oral submucous fibrosis (OSF) and oral leukoplakia have a higher nuclear blebbing frequency than patients with normal oral mucosa with no history of tobacco use. METHODS: The sample consisted of patients with OSF (n = 30) and oral leukoplakia (n = 10) and normal oral mucosa (n = 10). Exfoliated cells collected from the study groups were smeared on a clean microscopic slide and stained by May-Grunwald-Giemsa stain. A baseline frequency of nuclear blebbing was evaluated using a bright-field microscope with a ×100 objective. The number of nuclear blebbing per 1,000 epithelial cells was recorded and expressed in percentage. ANOVA, the Mann-Whitney U test, and Spearman's correlation were used to analyze the data. RESULTS: The mean rank of distribution of nuclear blebbing showed significant difference between all 3 groups, with the highest frequency noted in leukoplakia, followed by oral submucous and normal oral mucosa. Within OSF, the frequency of nuclear blebbing significantly increased from early stage to advanced stage. In OSF, a statistically significant positive linear correlation was noted between duration (in years), frequency (per day) of tobacco use, clinical grading, and nuclear blebbing. DISCUSSION/CONCLUSIONS: The frequency of nuclear blebbing was significantly higher in oral potentially malignant disorders than normal mucosa. Nuclear blebbing also exhibited a strong dose- and time-dependent correlation with tobacco usage and clinical staging in OSF. The nuclear blebbing frequency could be a noninvasive, economic tool to assess malignant risk in tobacco-induced oral potentially malignant disorders.


Assuntos
Transformação Celular Neoplásica/patologia , Mucosa Bucal/patologia , Neoplasias Bucais/etiologia , Fibrose Oral Submucosa/etiologia , Uso de Tabaco/efeitos adversos , Adulto , Núcleo Celular/patologia , Humanos , Leucoplasia Oral/patologia , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Fibrose Oral Submucosa/patologia , Tabaco
14.
Int J Mol Sci ; 22(9)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-34063159

RESUMO

Oral cancer is one of the leading malignant tumors worldwide. Despite the advent of multidisciplinary approaches, the overall prognosis of patients with oral cancer is poor, mainly due to late diagnosis. There is an urgent need to develop valid biomarkers for early detection and effective therapies. Long non-coding RNAs (lncRNAs) are recognized as key elements of gene regulation, with pivotal roles in various physiological and pathological processes, including cancer. Over the past few years, an exponentially growing number of lncRNAs have been identified and linked to tumorigenesis and prognosis outcomes in oral cancer, illustrating their emerging roles in oral cancer progression and the associated signaling pathways. Herein, we aim to summarize the most recent advances made concerning oral cancer-associated lncRNA, and their expression, involvement, and potential clinical impact, reported to date, with a specific focus on the lncRNA-mediated molecular regulation in oncogenic signaling cascades and oral malignant progression, while exploring their potential, and challenges, for clinical applications as biomarkers or therapeutic targets for oral cancer.


Assuntos
Neoplasias Bucais/genética , RNA Longo não Codificante/genética , Pesquisa Médica Translacional , Animais , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinogênese/patologia , Progressão da Doença , Humanos , Neoplasias Bucais/patologia
15.
Int J Mol Sci ; 22(9)2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-34065077

RESUMO

Advanced-stage oral cancers with lymph node metastasis are associated with poor prognosis and a high mortality rate. Although recent advancement in cancer treatment has effectively improved the oral cancer prognosis, the majority of therapeutic interventions are highly expensive and are associated with severe sideeffects. In the present study, we studied the efficacy of a diarylheptanoid derivative, platyphyllenone, in modulating the metastatic potential of human oral cancer cells. Specifically, we treated the human oral cancer cells (FaDu, Ca9-22, and HSC3) with different concentrations of platyphyllenone and measured the cell proliferation, migration, and invasion. The study findings revealed that platyphyllenonesignificantly inhibited the motility, migration, and invasion of human oral cancer cells. Mechanistically, platyphyllenone reduced p38 phosphorylation, decreased ß-catenin and Slug, increased E-cadherin expression, and reduced cathepsin L expression, which collectively led to a reduction in cancer cell migration and invasion. Taken together, our study indicates that platyphyllenone exerts significant anti-metastatic effects on oral cancer cells by modulating cathepsin L expression, the MAPK signaling pathway, and the epithelial-mesenchymal transition process.


Assuntos
Catepsina L/genética , Diarileptanoides/farmacologia , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias Bucais/etiologia , Neoplasias Bucais/metabolismo , Catepsina L/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Diarileptanoides/química , Humanos , Neoplasias Bucais/patologia , Metástase Neoplásica
16.
Head Neck ; 43(9): 2688-2697, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34008248

RESUMO

BACKGROUND: In this feasibility study we aimed to evaluate the value of previously reported molecular tumor biomarkers associated with lymph node metastasis in oral squamous cell carcinoma (OSCC) to optimize neck strategy selection criteria. METHODS: The association between expression of cortactin, cyclin D1, FADD, RAB25, and S100A9 and sentinel lymph node status was evaluated in a series of 87 (cT1-2N0) patients with OSCC treated with primary resection and SLNB procedure. RESULTS: Tumor infiltration depth and tumor pattern of invasion were independent prognostic markers for SLN status, while none of the tumor makers showed a better prognostic value to replace SLNB as neck staging technique in the total cohort. However, in the subgroup of patients with pT1N0 OSCC, cortactin expression (OR 16.0, 95%CI 2.0-127.9) was associated with SLN classification. CONCLUSIONS: Expression of cortactin is a promising immunohistochemical tumor marker to identify patients at low risk that may not benefit from SLNB or END.


Assuntos
Carcinoma de Células Escamosas , Cortactina , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Linfonodos/patologia , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Estadiamento de Neoplasias , Seleção de Pacientes , Biópsia de Linfonodo Sentinela , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Conduta Expectante
17.
Biochem Biophys Res Commun ; 559: 183-190, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33945996

RESUMO

Oral squamous cell carcinoma (OSCC) is one of the causes of cancer-related death worldwide. The abnormal proliferation ability of OSCC has become one of the major reasons for its poor prognosis. FK-506 binding protein 11 (FKBP11) is abnormally expressed in malignant tumors and affects many biological processes. The purpose of this study is to investigate the effect of FKBP11 on cell proliferation in OSCC and explore the possible regulatory mechanism. The expression of FKBP11 was detected by western blotting (WB) and/or real-time PCR in OSCC and paracancerous normal tissues in tongue squamous cell carcinoma (TSCC) cell lines, revealing high expression in OSCC and CAL-27 cells. Furthermore, FKBP11 knockdown inhibited the proliferation of CAL-27 cells by CCK-8 and colony formation assays. G2/M arrest and induction of apoptosis were observed using flow cytometry, Hoechst 33258 and Calcein-AM/PI staining, accompanied by changes in some cell cycle- and apoptosis-related proteins, including CDK1, Cyclin B1, p21, p27, p53, Bax, Bcl-2 and Caspase-3. Additionally, the expression of these proteins can be reversed by the use of pifithrin-α (PFT-α), a p53 inhibitor. An in vivo xenograft model further confirmed that FKBP11 enhanced OSCC progression. In conclusion, FKBP11 could promote cell proliferation by regulating G2/M phase and apoptosis via the p53/p21/p27 and p53/Bcl-2/Bax pathways, respectively, which suggests that it may be a new candidate target for the treatment of OSCC.


Assuntos
Carcinogênese/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Transdução de Sinais , Proteínas de Ligação a Tacrolimo/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Apoptose/genética , Carcinogênese/genética , Carcinoma de Células Escamosas/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/genética , Proteínas de Ligação a Tacrolimo/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-34020919

RESUMO

OBJECTIVE: Recurrent disease occurs in a significant proportion of early-stage oral squamous cell carcinoma (OSCC) despite removal of the entire tumor with clear surgical margins. Our study sought to identify clinicopathologic factors that increase the risk of locoregional recurrence in T1N0 OSCC. STUDY DESIGN: We conducted an observational retrospective analysis of 65 cases of T1N0 OSCC over a period of 13 years. For each case, we examined the clinical presentation, histopathologic appearance, and treatment characteristics of interest to evaluate the association between these variables and locoregional recurrence. RESULTS: The 5-year and 10-year locoregional recurrence rates were 29.2% and 33.8%, respectively. Individuals with prior oral dysplasia had significantly higher odds for locoregional recurrence (P < .01) and reduced 5-year disease-free survival rates (P < .01). OSCC of the tongue and floor of the mouth had lower recurrence odds than carcinomas of the gingiva, buccal mucosa, and palate (P < .05). Histologic grade (P = .80), depth of invasion (P = .82), and elective neck dissection (P = .80) did not appear to influence locoregional recurrence for T1N0 tumors. CONCLUSIONS: Given the morbidity and mortality associated with OSCC, understanding of the clinicopathologic factors associated with recurrent disease may lead to improved treatment and follow-up protocols for a subset of early-stage patients.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Esvaziamento Cervical , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço
19.
Anticancer Res ; 41(5): 2297-2306, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33952455

RESUMO

BACKGROUND/AIM: Phosphodiesterase 5 (PDE5) holds clinical relevance in several pathological states, including lung, breast, and prostate cancer. In this study, we examined PDE5 expression in oral squamous cell carcinoma (OSCC)-derived cell lines and tissues, and the anti-tumour effect of PDE5 inhibitor, sildenafil citrate (SC). MATERIALS AND METHODS: Cell proliferation, cell invasion, and gap closure assays were performed in six OSCC-derived cell lines upon treatment with varying concentrations of SC. PDE5 expression was determined in primary OSCC tissues by western blotting and immunohistochemistry. RESULTS: Elevated PDE5 expression was observed in all cell lines. A concentration-dependent decrease in cell viability, invasion rate, and migration was observed after SC treatment. A significant correlation (p=0.05) was observed between elevated PDE5 expression and lymphatic infiltration in OSCC tissues. CONCLUSION: PDE5 plays an important role in carcinogenesis of OSCC, and the specific inhibition of PDE5 may be an effective chemotherapeutic strategy.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5/metabolismo , Neoplasias Bucais/enzimologia , Citrato de Sildenafila/farmacologia , Western Blotting , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Imuno-Histoquímica , Neoplasias Bucais/patologia , Inibidores da Fosfodiesterase 5/farmacologia
20.
Rev. Ciênc. Plur ; 7(2): 107-118, maio 2021. tab, graf
Artigo em Português | LILACS, BBO - Odontologia | ID: biblio-1282976

RESUMO

Introdução:Os tumores de cabeça e pescoço têm expressiva incidência e mortalidade, assim comoalta letalidade, e constituem um relevante problema de saúde pública, particularmente nos países em desenvolvimento. Dentre as neoplasias malignas diagnosticadas no mundo, aproximadamente 10% estão localizadas na boca, sendo esse o sexto tipo de câncer mais incidente. Objetivo:Avaliar o perfil epidemiológico de pacientes diagnosticados com câncer de boca e faringe da Liga Mossoroense de Estudos e Combate ao Câncer do município de Mossoró, Rio Grande do Norte,Brasil,entre janeiro 2013 e junho de 2018.Metodologia:Estudo transversal, fundamentado na análise retrospectiva e descritiva de prontuários médicos.Resultados:Dos221 prontuáriosanalisados, a cor branca (56,6%) e o gênero masculino (70,6%) foram os mais prevalentes, com média de idade entre 55 e65 anos. A maioria (61,9%) apresentava ensino fundamental incompleto, sendo residentes de área urbana (59,6%) com histórico de uso de tabaco (64,6%) e/ou bebidas alcoólicas (53,9%). Osítio mais prevalente de câncer em boca foi a base da língua (12,7%).Conclusões:Conhecer o perfil dos pacientes com câncer de boca e orofaringe é um importante passo para melhor traçar e direcionar ações de saúde pública visando tanto àprevenção quanto o diagnóstico precoce (AU).


Introduction:Head and neck tumors have a significant incidence and mortality, as well as high lethality, and are a relevant public health problem, particularly in developing countries. Among the malignant neoplasms diagnosed in the world, approximately 10% are located in the mouth, this being the sixth most frequent type of cancer. Objective:To evaluate the epidemiological profile of patients diagnosed with oral and pharyngeal cancer of the Mossoroense League of Studies and Cancer Fighting in the municipality of Mossoró, Rio Grande do Norte, Brazil,between January 2013 and June 2018.Methodology:Cross-sectional study, based on retrospective and descriptive analysis of medical records.Results:Of the 221 records analyzed, white (56.6%) and male (70.6%) were the most prevalent, with a mean age between 55 and 65 years. Most (61.9%) had incomplete primary education, being residents of an urban area (59.6%) with a history of tobacco use (64.6%) and / or alcoholic beverages (53.9%).The most prevalent site of cancer in the mouth was the base of the tongue (12.7%). Conclusions:Knowing the profile of patients with oral and oropharyngeal cancer is an important step to better outline and direct public health actions aimed at both prevention and early diagnosis (AU).


Introducción: Los tumores de cabeza y cuello tienen una expresiva incidencia y mortalidad, así como alta letalidad, y constituyen un relevante problema de salud pública, especialmente en los países en desarrollo. Entre las neoplasias malignas diagnosticadas en el mundo,aproximadamente el 10% están localizadas en la boca, siendo este el sexto tipo de cáncer más común.Objetivo: Evaluar el perfil epidemiológico de pacientes diagnosticados con cáncer de boca y faringe de la Liga Mossoroense de Estudos e Combate ao Câncer del municipio de Mossoró, Rio Grande do Norte, Brasil,entre enero de 2013 y junio de 2018.Metodologia: Estudio transversal, basado en el análisis retrospectivo y descriptivo de los registros médicos.Resultados: De los 221 registros analizados, blancos (56,6%) y varones (70,6%) han sido los más prevalentes, con una media de edad entre 55 y 65 años. La mayoría (61,9%) presentaba educación primaria incompleta, siendo residentes de área urbana (59,6%) con antecedentes de uso de tabaco (64,6%) y/o bebidas alcohólicas (53,9%). El sitio más prevalente de cáncer en boca fuelabase de la lengua (12,7%). Conclusiones: Conocer el perfil de los pacientes con cáncer de boca y orofaringe es un importante paso para mejor delinear y dirigir acciones de salud pública objetivando tanto la prevención como el diagnóstico precoz (AU).


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Perfil de Saúde , Brasil/epidemiologia , Neoplasias Bucais/patologia , Neoplasias Orofaríngeas/patologia , Diagnóstico Precoce , Registros Médicos , Estudos Transversais/métodos , Interpretação Estatística de Dados , Pesquisa Qualitativa
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