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Background/purpose: Mercury within dental amalgam has been criticized for the potential toxicity and environmental hazard. Phasing down the use of dental amalgam is the transition for amalgam free dentistry. However, little is known about dental amalgam filling (AMF) in Taiwan. In this study, time trends of AMF were measured by using National Health Insurance Research Database (NHIRD). Materials and methods: A retrospective study was conducted to analyze the AMF data in registered database compiled by Taiwanese NHIRD from 1997 to 2013. The AMF data were further analyzed according to sex, age, and geographic location, respectively. Time trends of dental visits for AMF and medical expenses for AMF were also evaluated. Results: The average annual AMF ratio was 8.965% of nationwide population in Taiwan. The prevalence of AMF was significantly decreased both in male and female from 1997 to 2013 (P for trend <0.0001). The decreased pattern of AMF was found by the age stratification (P for trend <0.0001). The significant fall of AMF was also displayed in six districts (P for trend <0.0001). The number of dental visits were ranged from 821,749 in 1997 to 1,313,734 in 2013. However, time trends of dental visits for AMF were significantly decreased (P for trend <0.0001). The medical expenses for AMF were simultaneous significantly decreased from 1997 to 2013 (P for trend <0.0001). Conclusion: Form the results of this nationwide population-based database, a significant decrease of AMF in Taiwan was observed during past 17 years.
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Background/purpose: Bibliometric analysis is a method for quantifying the article distribution, impact, and performance. The purpose of this study was to identify the most top-cited articles published in Journal of Dental Sciences (JDS) and further analyze their main characteristics. Materials and methods: Web of Science, Journal Citation Reports database was searched to retrieve the most-cited articles in JDS published from 2007 to July 31, 2022. Among the included top-cited articles, the following parameters were recorded and analyzed: article title, article type, year, country, number of citations, and average citations pre year. Microsoft Excel was applied for the descriptive bibliometric analysis. Results: 41 top-cited articles were filtered from total 1165 JDS articles in Web of Science database. The results showed that 41 top-cited articles were cited between 20 and 186 times from Journal Citation Reports. Most of the article types are original article (28/41, 68.29%) following by review article (7/41, 17.07%). The majority of articles were originated from Taiwan (23/41, 56.10%). The top 4 most cited articles were relative to the research topic on COVID-19, lateral canal, guided-tissue regeneration barriers, and platelet-rich fibrin, respectively. However, articles analyzed by the average citations per year since publication were focused on COVID-19 followed by artificial intelligence. Conclusion: This bibliometric analysis illustrates the progress and trend of researches in JDS. The results may also offer a reference for recognizing the hot issues with the most citations in JDS.
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Bisphenol A-glycidyl methacrylate (BisGMA) is a methacrylate monomer that is mainly used in three-dimensional structures to reconstruct dental and bony defects. BisGMA has toxic and proinflammatory effects on macrophages. Rutin is a natural flavonol glycoside that is present in various plants and has useful biological effects, such as anti-inflammatory, anticancer, and antioxidative effects. The aim of this study was to investigate the anti-inflammation of rutin in macrophages after exposure to BisGMA. Pretreatment of the RAW264.7 macrophage with rutin at 0, 10, 30, and 100 µM for 30 min before being incubated with BisGMA at 0 or 3 µM. Proinflammatory cytokines and prostaglandin (PG) E2 were detected by enzyme-linked immunosorbent assay (ELISA). Nitric oxide (NO) was detected by the Griess assay. Expression and phosphorylation of proteins were measured by Western blot assay. Pretreatment with rutin inhibited the BisGMA-induced generation of proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and PGE2, in macrophages. Rutin also suppressed the BisGMA-induced secretion of NO and expression of inducible nitric oxide synthase (iNOS) in a concentration-dependent manner. Furthermore, rutin suppressed the mitogen-activated protein kinase (MAPK) phosphorylation in a concentration-dependent manner. Finally, rutin suppressed the BisGMA-induced phosphorylation of nuclear factor (NF)-κB p65 and degradation of inhibitor of κB (IκB). These results indicate that the concentration of rutin has an inhibitory effect on proinflammatory mediator generation, MAPK phosphorylation, NF-κB p65 phosphorylation, and IκB degradation. In conclusion, rutin is a potential anti-inflammatory agent for BisGMA-stimulated macrophages through NF-κB p65 phosphorylation and IκB degradation resulting from MAPK phosphorylation.
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Proteínas Quinases Ativadas por Mitógeno , NF-kappa B , NF-kappa B/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Bis-Fenol A-Glicidil Metacrilato/metabolismo , Bis-Fenol A-Glicidil Metacrilato/farmacologia , Rutina/farmacologia , Macrófagos , Citocinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismoRESUMO
Rutin, also called quercetin-3-rhamnosyl glucoside, is a natural flavonol glycoside present in many plants. Rutin is used to treat various diseases, such as inflammation, diabetes, and cancer. For polymeric biomaterials, triethylene glycol dimethacrylate (TEGDMA) is the most commonly used monomer and serves as a restorative resin, a dentin bonding agent and sealant, and a bone cement component. Overall, TEGDMA induces various toxic effects in macrophages, including cytotoxicity, apoptosis, and genotoxicity. The aim of this study was to investigate the protective mechanism of rutin in alleviating TEGDMA-induced toxicity in RAW264.7 macrophages. After treatment with rutin, we assessed the cell viability and apoptosis of TEGDMA-induced RAW264.7 macrophages using an methylthiazol tetrazolium (MTT) assay and Annexin V-FITC/propidium iodide assay, respectively. Subsequently, we assessed the level of genotoxicity using comet and micronucleus assays, assessed the cysteinyla aspartate specific proteinases (caspases) and antioxidant enzyme (AOE) activity using commercial kits, and evaluated the generation of reactive oxygen species (ROS) using a dichlorodihydrofluorescein diacetate (DCFH-DA) assay. We evaluated the expression of heme oxygenase (HO)-1, the expression of nuclear factor erythroid 2 related factor (Nrf-2), and phosphorylation of AMP activated protein kinase (AMPK) using the Western blot assay. The results indicated that rutin substantially reduced the level of cytotoxicity, apoptosis, and genotoxicity of TEGDMA-induced RAW264.7 macrophages. Rutin also blocked the activity of caspase-3, caspase-8, and caspase-9 in TEGDMA-stimulated RAW264.7 macrophages. In addition, it decreased TEGDMA-induced ROS generation and AOE deactivation in macrophages. Finally, we found that TEGDMA-inhibited slightly the HO-1 expression, Nrf-2 expression, and AMPK phosphorylation would be revered by rutin. In addition, the HO-1 expression, Nrf-2 expression, and AMPK phosphorylation was enhanced by rutin. These findings indicate that rutin suppresses TEGDMA-induced caspase-mediated toxic effects through ROS generation and antioxidative system deactivation through the Nrf-2/AMPK pathway. Therefore, rutin has the potential to serve as a novel antitoxicity agent for TEGDMA in RAW264.7 macrophages.
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Proteínas Quinases Ativadas por AMP , Rutina , Proteínas Quinases Ativadas por AMP/metabolismo , Antioxidantes/farmacologia , Apoptose , Ácido Aspártico , Materiais Biocompatíveis/farmacologia , Cimentos Ósseos/farmacologia , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Caspases/metabolismo , Adesivos Dentinários , Glucosídeos/farmacologia , Glicosídeos/farmacologia , Macrófagos/metabolismo , Polietilenoglicóis , Ácidos Polimetacrílicos , Propídio , Quercetina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Rutina/farmacologiaRESUMO
Composites, resins, and sealants that are commonly used in orthopedics and dentistry are based on 2,2-bis[p-(2'-hydroxy-3'-methacryloxypropoxy)phenylene]propane (BisGMA), which induces proinflammatory responses in macrophages. The present study aimed to explore the anti-inflammatory responses of wogonin, which is a natural dihydroxyl flavonoid compound, in BisGMA-treated macrophages. According to the findings, wogonin exhibits anti-inflammatory, antiallergic, anticancer, and antioxidative properties. The generation of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) were noted to be inhibited by wogonin in BisGMA-treated macrophages. Furthermore, the production of proinflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 was reduced. In addition, BisGMA-induced nuclear factor (NF)-κB p65 phosphorylation and inhibitor of κB (IκB) degradation were inhibited. Finally, the BisGMA-induced phosphorylation of mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) was inhibited. All these effects were induced by wogonin in the macrophages in a concentration-dependent manner. Similar inhibitory effects of wogonin were observed on the production of NO and proinflammatory cytokines, expression of iNOS, phosphorylation of NF-κB p65 and MAPK, and degradation of IκB. These results indicated that rutin is a potential anti-inflammatory agent for BisGMA-treated macrophages that undergo NFκB p65 phosphorylation and IκB degradation through upstream MAPK phosphorylation. Therefore, wogonin inhibits BisGMA-induced proinflammatory responses in macrophages through the regulation of the NFκB pathway and its upstream factor, MAPK.
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Lipopolissacarídeos , NF-kappa B , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Macrófagos , Anti-Inflamatórios/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fosforilação , Citocinas/metabolismo , Ciclo-Oxigenase 2/metabolismoRESUMO
BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF) a well-recognized oral premalignant disorder. Several studies have demonstrated that periostin, a matricellular protein, is involved in the development and pathogenesis of fibrosis diseases. Nevertheless, the contribution of periostin in OSF remains to be uncovered. The purpose of the study was to illustrate the functional role of periostin involved in OSF pathogenesis. METHODS: RNA-sequencing was employed to screen for differentially expressed genes in normal and OSF tissues. Validation of the upregulation of periostin in OSF specimens and fibrotic buccal mucosal fibroblasts (fBMFs) was conducted by qRT-PCR. The correlation of the gene expression of periostin and various fibrosis markers was analyzed. In addition, the functional role of periostin in myofibroblast features was tested using collagen gel contraction and transwell migration assays. RESULTS: We observed overexpression of periostin in OSF specimens using RNA-sequencing and confirmed its upregulation in OSF tissues and patient-derived fBMFs. Besides, there was a positive relationship between the expression of periostin and several fibrosis-associated markers, including ACTA2 (α-smooth muscle actin; α-SMA), COL1A1 (type 1 collagen α1 chain), TGFB1 (TGF-ß1), and FN1 (fibronectin). Furthermore, we examined the effect of silencing periostin on the maintenance of myofibroblast characteristics and showed that knockdown of periostin suppressed the expression of α-SMA. Also, inhibition of periostin markedly downregulated the myofibroblast activities (collagen gel contraction and migration capacities). CONCLUSION: Our results indicate the aberrant expression of periostin in OSF tissues and myofibroblasts. Moreover, the expression of periostin is positively associated with fibrosis markers, and repression of periostin may be a promising direction to alleviate the progression of OSF.
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Miofibroblastos , Fibrose Oral Submucosa , Transdiferenciação Celular , Fibroblastos , Fibrose , Humanos , Mucosa Bucal/patologia , Fibrose Oral Submucosa/genética , Fibrose Oral Submucosa/patologiaRESUMO
Migraine is considered to be a neurovascular disease that manifests as a throbbing headache, possibly caused by the activation of the trigeminovascular system. Several studies have supported the role of inflammation in the pathogenesis of migraine. Chronic periodontitis (CP) is an infectious inflammatory disease triggered by bacterial products evoking an immune response which could result in the destruction of the periodontium. However, little is known about the longitudinal association between CP and migraine. In this study, we designed a nationwide population-based cohort study to investigate the risk of migraine and CP exposure in Taiwan. In total, 68,282 patients with CP were identified from the National Health Insurance Research Database (NHIRD), and 68,282 comparisons were randomly captured and matched by age, sex, monthly income, urbanization and comorbidities. The association between CP exposure and migraine risk was evaluated by Cox proportional hazards regression models. In this study, 785 migraine patients were identified in the CP cohort, and 641 migraine cases were found in the non-CP cohort. The incidence rate of migraine was significantly higher in the CP cohort than the non-CP cohort (adjusted HR: 1.21, 95% CI: 1.09-1.34, p < 0.001) during the 13-year follow-up period. Females had a 2.69-fold higher risk for migraine than males (95% CI: 2.38-3.04, p < 0.001). In summary, CP is associated with an increased risk of subsequent migraine in Taiwan.
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Periodontite Crônica , Transtornos de Enxaqueca , Periodontite Crônica/complicações , Periodontite Crônica/epidemiologia , Estudos de Coortes , Comorbidade , Feminino , Humanos , Incidência , Masculino , Transtornos de Enxaqueca/complicações , Transtornos de Enxaqueca/epidemiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
BACKGROUND/PURPOSE: Oct4, a key transcription factor, could reprogram human somatic fibroblasts into embryonic stem cell-like pluripotent cells. The exact mechanism of cyclosporine A (CsA)-induced gingival overgrowth is still unclear. The aim of this study was to investigate the effects of CsA on the expression of Oct4 in cultured human gingival fibroblasts (HGFs) in vitro. MATERIALS AND METHODS: The effects of CsA on HGFs were used to elucidate whether Oct4 expression could be induced by CsA by using quantitative real-time reverse transcription-polymerase chain reaction and western blot. Cell growth in CsA-treated HGFs with Oct4 lentiviral-mediated shRNAi knockdown was evaluated by tetrazolium bromide reduction assay. RESULTS: CsA was found to upregulate Oct4 transcript in a dose-dependent manner (pâ¯<â¯0.05). CsA also dose-dependently increased Oct4 protein expression (pâ¯<â¯0.05). The lentivirus expressing sh-Oct4 successfully prevented the CsA-induced Oct4 mRNA and protein in HGFs (pâ¯<â¯0.05). However, knockdown of Oct4 was insufficient to inhibit CsA-stimulated cell growth in HGFs. Furthermore, double knockdown with pluripotency-associated transcription factor Nanog showed that the down-regulation of Oct4/Nanog by lentiviral infection significantly inhibited CsA-stimulated cell growth (pâ¯<â¯0.05). CONCLUSION: Taken together, CsA was first found to upregulate Oct4 mRNA and protein expression in HGFs. The silencing Oct4 could not suppress cell growth unless Nanog was repressed simultaneously.
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Pneumonia is a common respiratory infectious disease that involves the inflammation of the pulmonary parenchyma. Periodontal disease is widespread and correlated with pneumonia. However, the relationship between periodontal treatment and clinical infectious outcomes in patients with pneumonia has remained undetermined. The aim of this study was to investigate the association between periodontal treatment and the risk of pneumonia events in the Taiwanese population. A nationwide population-based cohort study was conducted using data from the Taiwanese National Health Insurance Research Database (NHIRD). A total of 49,400 chronic periodontitis patients who received periodontal treatment from 2001 to 2012 were selected. In addition, 49,400 healthy individuals without periodontal diseases were picked randomly from the general population after propensity score matching according to age, gender, monthly income, urbanization, and comorbidities. The Cox proportional hazard regression analysis was adopted to assess the hazard ratio (HR) of pneumonia between the periodontal treatment cohort and the comparison cohort. The average ages of the periodontal treatment and comparison groups were 44.25 ± 14.82 years and 44.15 ± 14.5 years, respectively. The follow up durations were 7.66 and 7.41 years for the periodontal treatment and comparison groups, respectively. We found 2504 and 1922 patients with newly diagnosed pneumonia in the comparison cohort and the periodontal treatment cohort, respectively. The Kaplan-Meier plot revealed that the cumulative incidence of pneumonia was significantly lower over the 12 year follow-up period in the periodontal treatment group (using the log-rank test, p < 0.001). In conclusion, this nationwide population-based study indicated that the patients with periodontal treatment exhibited a significantly lower risk of pneumonia than the general population.
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Periodontite Crônica/terapia , Assistência Odontológica , Pneumonia/prevenção & controle , Adulto , Idoso , Periodontite Crônica/epidemiologia , Estudos de Coortes , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Pneumonia/epidemiologia , Pontuação de Propensão , Modelos de Riscos Proporcionais , Fatores de Risco , Taiwan/epidemiologia , Adulto JovemRESUMO
Tumor-initiating cells (TICs) are defined as a specialized subset of cells with tumor-initiating capacity that can initiate tumor growth, tumor relapse and metastasis. In the present study, osteosarcoma TICs (OS-TICs) were isolated and enriched from the osteosarcoma U2OS and MG-63 cell lines using sphere formation assays and serum-depleted media. These enriched OS-TICs showed the expression of several typical cancer stemness markers, including octamer-binding transcription factor 4, Nanog homeobox, cluster of differentiation (CD)117, Nestin and CD133, and the expression of ATP binding cassette subfamily G member 2, multidrug resistance protein 1 (MDR1) and dihydrofolate reductase (DHFR). Notably, in vitro and in vivo tumorigenic properties were enhanced in these OS-TICs. Additionally, methotrexate and doxorubicin are the most widely used anticancer agents against osteosarcoma, and the observed enhanced chemoresistance of OS-TICs to these two agents could be associated with the upregulation of DHFR and MDR1. These findings suggest that the upregulation of DHFR and MDR1 is associated with the development of chemoresistance of OS-TICs.
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BACKGROUND/PURPOSE: Gingival overgrowth is a common side effect of medication with the immunosuppressant cyclosporine A (CsA). This study proposed to verify whether Nanog, an embryonic stem cell marker, contributes to gingival overgrowth stimulated with CsA in human gingival fibroblasts (HGFs). MATERIALS AND METHODS: The effect of CsA on HGFs was used to elucidate whether Nanog expression could be induced by CsA using quantitative real-time reverse transcription-polymerase chain reaction and Western blotting. Cell growth in CsA-treated HGFs with Nanog lentivirus-mediated short hairpin RNA interference knockdown was evaluated by tetrazolium bromide reduction assay. RESULTS: CsA upregulated Nanog transcript in HGFs in a dose-dependent manner (P < 0.05). CsA was also shown to increase Nanog protein expression in HGFs in a dose-dependent manner (P < 0.05). In addition, downregulation of Nanog by lentiviral infection significantly inhibited CsA-stimulated cell growth in HGFs (P < 0.05). CONCLUSION: CsA upregulated Nanog expression and cell growth in HGFs, while silencing Nanog effectively reversed these phenomena. Nanog may act as a major switch in the pathogenesis of CsA-induced gingival overgrowth.
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BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF), a chronic progressive scarring disease, has been considered as a precancerous condition of oral mucosa. In this study, we investigated the functional role of Twist, an epithelial-mesenchymal transition (EMT) transcriptional factor, in myofibroblastic differentiation activity of OSF. METHODS: Arecoline, a major areca nut alkaloid, was used to explore whether expression of Twist could be changed dose-dependently in human primary buccal mucosal fibroblasts (BMFs). Collagen gel contraction and migration capability in arecoline-stimulated BMFs and primary oral submucous fibrosis-derived fibroblasts (OSFs) with Twist knockdown was presented. RESULTS: We observed that the treatment of arecoline dose-dependently increased Twist expression transcript and protein levels in BMFs. The myofibroblast activity including collagen gel contraction and migration capability also induced by arecoline, while knockdown of Twist reversed these phenomena. Importantly, inhibition of Twist led to the suppression collagen contraction and wound healing capability of primary cultivated OSFs. Clinically, Twist transcript and protein expression was higher in areca quid chewing-associated OSF tissues than in normal oral mucosa tissues. CONCLUSION: This evidence suggests that upregulation of Twist might be involved in the pathogenesis of areca quid-associated OSF through dysregulation of myofibroblast activity.
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Arecolina/efeitos adversos , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Proteínas Nucleares/metabolismo , Fibrose Oral Submucosa/genética , Proteína 1 Relacionada a Twist/metabolismo , Areca/química , Células Cultivadas , Humanos , Mucosa Bucal/patologia , Proteínas Nucleares/genética , Lesões Pré-Cancerosas , Taiwan , Proteína 1 Relacionada a Twist/genéticaRESUMO
BACKGROUND/PURPOSE: Matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs (TIMPs) have been shown to play an important role in the pathogenesis of tissue destruction in periodontitis. The associations between single nucleotide polymorphisms (SNPs) in the promoter regions of MMP-2, MMP-9, and TIMP-2 genes and the risk of aggressive periodontitis (AgP) and chronic periodontitis (CP) were investigated in a Taiwanese population. MATERIALS AND METHODS: MMP-2 C-1306T, C-735T, T-790G, and MMP-9 C-1562T and TIMP-2 G-418C SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 69 patients and 129 patients with AgP and CP, respectively, and 117 periodontal healthy individuals who served as healthy controls (HC). Chi-square test and logistic regression analysis were used to investigate the possible association of genotypes with periodontitis. RESULTS: No significant differences in the distributions of the C-1306T and C-735T variants between periodontitis and HC were detected. Patients with genotype of MMP-2 -790 TT or T allele of MMP-2-790T/G as compared to genotypes of GT + GG genotypes or G allele, were less susceptible to CP [odds ratio (OR) = 0.50, 95% confidence interval (CI) = 0.25-1.00 and OR = 0.52, 95% CI = 0.28-0.96, respectively]. The frequencies of TIMP-2 G-418C gene polymorphisms in nonsmokers were statistically significantly different among AgP, CP, and HC groups (P = 0.024). The nonalcohol drinking participants with C allele of MMP-9 C-1562T as compared to T allele, were less susceptible to AgP (adjusted OR = 0.4; 95% CI, 0.18-0.90). CONCLUSION: It is suggested that MMP-2 T-790G, MMP-9 C-1562T, and TIMP-2 G-418C gene polymorphisms might be associated with periodontitis in the Taiwanese Han population.
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The myeloid zinc finger 1 (MZF1) is a zinc finger transcription factor which regulates myeloid differentiation and oncogenesis. However, little information is available concerning the MZF1 expression in oral squamous cell carcinoma (OSCC) and its correlation with patients' prognosis. We detected the expression of MZF1 in 274 patients with OSCC using tissue microarrays (TMAs) and evaluated the associations between nuclear MZF1 expression and the clinical parameters of OSCC patients. We found that nuclear MZF1 expression was present in 190/274 (69.3 %) cases, and loss of nuclear expression of MZF1 was associated with more advanced clinical stages (p = 0.011) and larger tumor size (p = 0.002), but not associated with positive lymph node metastasis and distal metastasis. Importantly, tongue squamous cell carcinomas (SCC) patients with negative nuclear MZF1 expression had significantly worse overall survival rates (log-rank test, p = 0.028). In conclusion, our results revealed that the loss of nuclear expression of MZF1 in OSCC samples can predict the progression of OSCC and the survival of OSCC patients in Taiwan.
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Carcinoma de Células Escamosas/genética , Fatores de Transcrição Kruppel-Like/biossíntese , Neoplasias Bucais/genética , Análise Serial de Tecidos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Fatores de Transcrição Kruppel-Like/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Prognóstico , TaiwanRESUMO
OBJECTIVES: Metastasis is the most common cause of oral squamous cell carcinoma (OSCC)-related death. The physiological function of S100A4 in the pathogenesis of areca quid chewing-associated OSCC has not been uncovered. METHOD: OSCC tissues from areca quid chewers were analyzed by immunohistochemistry for S100A4 expression. The functions of S100A4 in invasiveness of arecoline-treated oral epithelial (OE) cells were determined by loss function approaches. RESULTS: Expression of S100A4 was positively correlated with clinical grading and lymph node metastasis of OSCC. Upregulated S100A4 is correlated with poor survival outcome of OSCC patients. Arecoline led to dose-dependent elevation of S100A4 expression in oral epithelial (OE) cells. Down-regulation of S100A4 significantly reversed arecoline-induced oncogenecity in OE cells. The additions of pharmacological agents LY294002, SP600125, and CAY10585 were found to inhibit arecoline-induced S100A4 expression in OE cells. CONCLUSION: Arecoline-induced S100A4 expression was down-regulated by LY294002, SP600125, or CAY10585 treatment. Targeting S100A4 might offer a new strategy for the treatment of OSCC patients with metastasis.
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Carcinoma de Células Escamosas/patologia , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Proteínas S100/metabolismo , Antracenos/farmacologia , Areca/efeitos adversos , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/mortalidade , Cromonas/farmacologia , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Metástase Linfática , Masculino , Mastigação , Morfolinas/farmacologia , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/mortalidade , Invasividade Neoplásica , Proteína A4 de Ligação a Cálcio da Família S100 , Proteínas S100/efeitos dos fármacos , Taxa de SobrevidaRESUMO
BACKGROUND: Lymph node (LN) metastasis is the most common cause of oral squamous cell carcinoma (OSCC)-related death. Searching the detailed molecular mechanisms involved LN metastasis in OSCC is still an open question. METHODS: Paired tissue samples from tumor (T) and adjacent non-cancerous matched tissues (NCMT) parts, as well as LN metastatic lesions in patient with OSCC tissues were subjected to quantitative real-time PCR analysis for the expression levels of Lin28B. Arecoline, a major areca nut alkaloid, was to explore whether expression of Lin28B could be changed dose dependent in oral epithelial cells. Control and Lin28B-knockdown arecoline-stimulated oral epithelial cells were subjected to migration/invasion/anchorage-independent growth assay. RESULTS: Compared with NCMT samples from the same OSCC patient, the expression of Lin28B was increased in all of the tumor samples. A similar upregulation of Lin28B was also observed in LN metastatic when compared with local tumors. Arecoline treatment dose dependently induced Lin28B expression in SG and FaDu cells. Lentiviral-mediated silencing Lin28B expression significantly attenuated arecoline-induced oncogenicity including proliferation, migration, invasiveness, and anchorage-independent growth in SG and FaDu cells. CONCLUSIONS: Lin28B may be a useful biomarker and novel molecular target for LN metastasis OSCC patients' treatment.