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Ameloblastoma (AM), periapical cyst (PC), and chronic suppurative osteomyelitis (CSO) are prevalent maxillofacial diseases with similar imaging characteristics but different treatments, thus making preoperative differential diagnosis crucial. Existing deep learning methods for diagnosis often require manual delineation in tagging the regions of interest (ROIs), which triggers some challenges in practical application. We propose a new model of Wavelet Extraction and Fusion Module with Vision Transformer (WaveletFusion-ViT) for automatic diagnosis using CBCT panoramic images. In this study, 539 samples containing healthy (n = 154), AM (n = 181), PC (n = 102), and CSO (n = 102) were acquired by CBCT for classification, with an additional 2000 healthy samples for pre-training the domain-adaptive network (DAN). The WaveletFusion-ViT model was initialized with pre-trained weights obtained from the DAN and further trained using semi-supervised learning (SSL) methods. After five-fold cross-validation, the model achieved average sensitivity, specificity, accuracy, and AUC scores of 79.60%, 94.48%, 91.47%, and 0.942, respectively. Remarkably, our method achieved 91.47% accuracy using less than 20% labeled samples, surpassing the fully supervised approach's accuracy of 89.05%. Despite these promising results, this study's limitations include a low number of CSO cases and a relatively lower accuracy for this condition, which should be addressed in future research. This research is regarded as an innovative approach as it deviates from the fully supervised learning paradigm typically employed in previous studies. The WaveletFusion-ViT model effectively combines SSL methods to effectively diagnose three types of CBCT panoramic images using only a small portion of labeled data.
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Diabetic patients are at high risk of developing lacrimal gland dysfunction, and the antimalarial drug artesunate (ART) was recently used to induce experimental-induced diabetes mellitus. This study's objective is to investigate the lacrimal gland alteration and the effect of ART on experimentally induced diabetes rat models and its related mechanisms. Forty rats were divided into five groups (8 rats/group): healthy control group (HC), diabetic group (DM), 50 mg/kg ART intervention diabetic group [DM + ART (50 mg/kg)], 100 mg/kg ART intervention diabetic group [DM + ART (100 mg/kg)] and 6 U/kg Insulin intervention diabetic group (DM + INS). The morphology of the eyeball and lacrimal gland tissues was determined using hematoxylin and eosin staining. In addition, external lacrimal glands were harvested for electronic microscopic examination, NFκB1, and TNF-α protein expression evaluation by immunohistochemistry and mRNA expression analysis by RT-PCR. Histopathological and ultrastructural changes suggest ART intervention has an improved structural effect. Protein expression of NFκB1 in the DM + ART (100 mg/kg) group was decreased. TNF-α significantly decreased in the DM + ART (50 mg/kg) and insulin groups. We concluded that ART improves structural changes in a lacrimal gland in diabetic rats. The present study provides further evidence of the therapeutic effect of ART on the lacrimal gland of diabetic rats by decreasing the expression of NFκB1 and TNF-α.
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Artesunato , Diabetes Mellitus Experimental , Aparelho Lacrimal , Animais , Artesunato/farmacologia , Artesunato/uso terapêutico , Aparelho Lacrimal/efeitos dos fármacos , Aparelho Lacrimal/metabolismo , Aparelho Lacrimal/patologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Ratos , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Artemisininas/farmacologia , Artemisininas/uso terapêuticoRESUMO
To explore the effect of periodontal disease on the progression of diabetic kidney disease (DKD), to observe the effects of artesunate (ART) intervention on periodontal and kidney tissues in type 1 diabetic rats with periodontitis, and to explore the possibility of ART for the treatment of DKD. Rat models of diabetes mellitus, periodontitis, and diabetes mellitus with periodontitis were established through streptozotocin (STZ) intraperitoneal injection, maxillary first molar ligation, and P. gingivalis ligation applied sequentially. Ten weeks after modeling, ART gavage treatment was given for 4 weeks. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot were used to investigate the inflammatory factors, fibrogenisis, autophagy-related factors, and proteins in periodontal and kidney tissues, and 16S rDNA sequencing was used to detect the changes in dental plaque fluid and kidney tissue flora. Compared to the control group, the protein expression levels of transforming growth factor ß1 (TGF-ß1) and COL-IV in the periodontal disease (PD) group were increased. The protein expression of TGF-ß1, Smad3, and COL-IV increased in the DM group and the DM + PD group, and the expression of TGF-ß1, Smad3, and COL-IV was upregulated in the DM + PD group. These results suggest that periodontal disease enhances renal fibrosis and that this process is related to the TGF-ß1/Smad/COL-IV signaling pathway. Among the top five dominant bacteria in the kidney of the DM + PD group, the abundance of Proteobacteria increased most significantly, followed by Actinobacteria and Firmicutes with mild increases. The relative abundance of Proteobacteria, Actinobacteria, and Firmicutes in the kidney tissues of DM and PD groups also showed an increasing trend compared with the CON group. Proteobacteria and Firmicutes in the kidney of the PD group and DM + PD group showed an increasing trend, which may mediate the increase of oxidative stress in the kidney and promote the occurrence and development of DN. Periodontal disease may lead to an imbalance of renal flora, aggravate renal damage in T1DM, cause glomerular inflammation and renal tubulointerstitial fibrosis, and reduce the level of autophagy. ART delays the process of renal fibrosis by inhibiting the TGF-ß-Smad signaling pathway.
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BACKGROUND: Type 2 diabetes mellitus (T2DM) causes severe bone loss after tooth extraction as a hyperglycemic environment causes aberrant bone homeostasis. Artesunate (ART) is known to possess anti-inflammation and osteogenic properties. However, its osteogenesis property in alveolar bone remains unclear. This study aimed to explore the osteogenic and immunoregulatory effects of artesunate-loaded thermosensitive chitosan hydrogel (ART-loaded TCH) on maxilla tooth extraction in T2DM rats. METHODS: T2DM rats were induced by a high-fat diet and streptozotocin. Different concentrations of ART-loaded TCH were applied in tooth extraction sockets. Bone loss and the expression of osteogenic regulatory factors (OPG, ALP, RANK) were evaluated. The immunoregulatory effects of ART-loaded TCH were observed through detecting the infiltration of T lymphocytes and their cytokines. The underlying mechanisms were explored. RESULTS: Results showed that the 150 mg/ml ART-loaded TCH group significantly ameliorated maxilla bone height and bone mineral density when compared with the T2DM group (p < 0.05). It also improved the expression of OPG, ALP, and RANK. Although the alteration of CD4+ T, CD8+ T, and CD4+:CD8+ T ratio has no significant difference among groups, the release of Th1 and Th2 in the 150 mg/ml ART-loaded TCH group has been significantly regulated than in the T2DM group (p < 0.05). Besides, ART-loaded TCH treatment inhibited the expression of p38 MAPK and ERK1 in T2DM maxilla. CONCLUSIONS: Therefore, the results indicated that 150 mg/ml ART-loaded TCH could be an effective method to prevent bone loss in T2DM tooth extraction rats by modulating the immunoregulation of Th1 and Th2 and the MAPK signaling pathway.
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Quitosana , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ratos , Animais , Osteogênese , Hidrogéis/farmacologia , Quitosana/uso terapêutico , Quitosana/farmacologia , Artesunato/uso terapêutico , Artesunato/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Maxila , Linfócitos T/metabolismo , Extração Dentária/métodosRESUMO
Context: A comprehensive meta-analysis was carried out to investigate the impact of orthodontics on masticatory muscles.Methods: A thorough search of various databases, including CNKI, Wan Fang, VIP, CBM, MEDLINE, PubMed, Cochrane Library, EMBASE, Web of Science, and Google Scholar, was performed to identify relevant studies on patients undergoing orthodontics or functional corrections. Six case-control studies were finally included in this analysis, which specifically examined the effect of orthodontic treatment on masticatory muscle function.Results: The results revealed that the mean masticatory muscle voltage in patients treated with orthodontics was found to be higher after treatment compared to before treatment [odds ratio (OR)=1.57, 95% confidence interval (CI) (0.57, 2.57), p = 0.002], which could potentially have an impact on masticatory muscle function, particularly in individuals with Class II Division 1 malocclusion.Conclusion: These findings contribute to our understanding of the effects of orthodontic interventions on masticatory muscles, further highlighting the importance of orthodontics in optimising masticatory function.
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Músculos da Mastigação , Humanos , Músculos da Mastigação/fisiologia , Estudos de Casos e ControlesRESUMO
INTRODUCTION: Metabolic reprogramming is one of the important mechanisms of cell differentiation, and different cells have different preferences for energy sources. During the differentiation of naive CD4 + T cells into Th17 and Treg cells, these cells show specific energy metabolism characteristics. Th17 cells depend on enhanced glycolysis, fatty acid synthesis, and glutaminolysis. In contrast, Treg cells are dependent on oxidative phosphorylation, fatty acid oxidation, and amino acid depletion. As a potent antimalarial drug, artesunate has been shown to modulate the Th17/Treg imbalance and regulate cell metabolism. METHODOLOGY: Relevant literatures on ART, cellular metabolism, glycolysis, lipid metabolism, amino acid metabolism, CD4 + T cells, Th17 cells, and Treg cells published from January 1, 2010 to now were searched in PubMed database. CONCLUSION: In this review, we will highlight recent advances in which artesunate can restore the Th17/Treg imbalance in disease states by altering T-cell metabolism to influence differentiation and lineage selection. Data from the current study show that few studies have focused on the effect of ART on cellular metabolism. ART can affect the metabolic characteristics of T cells (glycolysis, lipid metabolism, and amino acid metabolism) and interfere with their differentiation lineage, thereby regulating the balance of Th17/Treg and alleviating the symptoms of the disease.
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Linfócitos T Reguladores , Células Th17 , Células Th17/metabolismo , Artesunato/farmacologia , Artesunato/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Diferenciação Celular , Ácidos Graxos/metabolismoRESUMO
Periodontitis is an inflammatory disease of the gums. Periodontitis in diabetic patients can aggravate insulin resistance; however, its molecular and biological mechanism remains unclear. This study aimed to explore the effects of diabetic periodontitis on liver function and determine the mechanism by which artesunate improves liver function. Rats with streptozotocin-induced diabetes were divided into five groups: normal control (NC), diabetic periodontitis (DM + PD), artesunate intervention (ART), insulin intervention (INS), and combined medication intervention (ART + INS) groups. Drug interventions were then administered to the rats in each group as follows: 50 mg/kg artesunate to the ART group, 6 U/kg insulin to the INS group, and 50 mg/kg artesunate + 6 U/kg insulin to the ART + INS group. Blood samples, liver tissues, and the maxillary alveolar bone were collected postsacrifice. ART was found to significantly ameliorate hyperglycemia, blood lipid concentrations, and liver function. The levels of inflammatory factors reduced; the effect was more pronounced in the ART + INS group. Artesunate presumably inhibits the TLR4/NF-κB signaling pathway and expression of downstream inflammatory factors, thereby exerting a protective effect on diabetes-related liver function. This offers a fresh approach to treat diabetes mellitus.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Periodontite , Animais , Artesunato/efeitos adversos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Insulina , Fígado , NF-kappa B/metabolismo , Periodontite/complicações , Periodontite/tratamento farmacológico , Periodontite/metabolismo , RatosRESUMO
BACKGROUND: Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. Moreover, the unique biological characteristics and complex structures of ACC contribute to its poor survival rates. Recently, proteasome inhibitors have been shown to elicit satisfactory therapeutic effects in the treatment of certain solid tumors, but few studies have been implemented to investigate the effects of proteasome inhibitor therapy for ACC. METHODS: In this present study, cell counting kit-8 assay and flow cytometry assay were performed to examine the effects of proteasome inhibitor (MG132) on cell viability and apoptosis. We applied western blot and immunofluorescence staining to explore the expression of the Nrf2/Keap1 signaling pathway and P62, additionally Nrf2 inhibitor (ML385) was utilized to evaluate the role of Nrf2/Keap1 signaling pathway in MG132-induced cell apoptosis. RESULTS: Our data indicated that MG132 significantly suppressed the growth of ACC-83 cells(MG132 10µM P = 0.0046; 40µM P = 0.0033; 70µM P = 0.0007 versus control) and induced apoptosis (MG132 10µM P = 0.0458; 40µM P = 0.0018; 70µM P = 0.0087 versus control). The application of MG132 induced the up-regulation of Nrf2/Keap1 signaling pathway. Furthermore, inhibition of Nrf2 attenuated the therapeutic effects of MG132 for ACC (both ML385 + MG132 10µM P = 0.0013; 40µM P = 0.0057; 70µM P = 0.0003 versus MG132). P < 0.05 was considered statistically significant. CONCLUSIONS: Our results revealed that proteasome inhibitors MG132 could inhibit the cell viability and induce the apoptosis of ACC through Nrf2/Keap1 signaling pathway.
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Carcinoma Adenoide Cístico , Fator 2 Relacionado a NF-E2 , Carcinoma Adenoide Cístico/tratamento farmacológico , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Leupeptinas , Fator 2 Relacionado a NF-E2/metabolismo , Inibidores de Proteassoma/farmacologia , Transdução de SinaisRESUMO
BACKGROUND: The present study aimed to evaluate the effect of artesunate (ART) on the reduction of cardiovascular complications in a type 1 diabetes model and to investigate the associated mechanism based on the receptor for advanced glycation end-product (RAGE)/NF-κB signaling pathway. METHODS: A total of 40 male Sprague-Dawley rats were randomly divided into five groups: The healthy, diabetic, 50 mg/kg ART (ig) treatment diabetic, 100 mg/kg ART (ig) treatment diabetic, and 6 U/kg insulin (iH) treatment diabetic groups. The treatment lasted 4 weeks after the diabetic model was established via intraperitoneal injection of streptozotocin. Blood samples were collected, and cardiovascular tissues were harvested and processed to measure various parameters after the animals were sacrificed. The myocardium and aortic arch tissues were evaluated using hematoxylin-eosin and Masson staining. Expression levels of RAGE, NF-κB, matrix metalloproteinase MMP9, MMP1 and CD68 in the myocardium and aortic arch tissues were detected using immunohistochemistry, and mRNA expression was determined using reverse transcription-quantitative PCR. RESULTS: The results of the present study demonstrated that ART treatment may restrain diabetes-induced cardiovascular complications by maintaining heart and body weight while reducing blood glucose, as well as regulating blood lipid indicators to normal level (P < 0.05). The expression levels of NF-κB, CD68, MMP1, MMP9 and RAGE were decreased in the ART-treated diabetic rats (P < 0.05). CONCLUSIONS: ART treatment may have a protective role against diabetes-associated cardiovascular complications in diabetic rats by inhibiting the expression of proteins in the RAGE/NF-κB signaling pathway and downstream inflammatory factors. High concentrations of ART had a hypoglycemic effect, while a low concentration of ART prevented cardiovascular complications.
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Artesunato/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Hipoglicemiantes/uso terapêutico , Animais , Aorta Torácica/patologia , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/patologia , Cardiomiopatias Diabéticas/patologia , Lipídeos/sangue , Masculino , Miocárdio/patologia , NF-kappa B/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
Although immunotherapy has recently demonstrated a substantial promise in treating advanced thyroid carcinoma (THCA), it is not appropriate for all THCA patients. As a result, this study aims to identify biomarkers for predicting immunotherapy efficacy and prognosis in THCA patients based on a constructed prognostic model. The transcriptomic and corresponding clinical data of THCA patients were obtained from the Cancer Genome Atlas (TCGA) database. We identified differentially expressed genes (DEGs) between THCA and normal samples and performed an intersection analysis of DEGs with immune-related genes (IRGs) downloaded from the ImmPort database. Functional enrichment analysis was performed on the chosen immune-related DEGs. Subsequently, Cox and LASSO regression analyses were conducted to obtain three hub immune-related DEGs, including PPBP, SEMA6B, and GCGR. Following that, a prognostic risk model was established and validated based on PPBP, SEMA6B, and GCGR genes to predict immunotherapy efficacy and THCA prognosis. Finally, we investigated the association between the constructed risk model and tumor mutational burden (TMB), abundance of tumor-infiltrating immune cells (TICs) as well as immunotherapeutic targets (PDL-1, PD-1, and CTLA4) in THCA. THCA patients in the high-risk score (RS) group showed higher TMB levels and worse prognosis than the low RS group. Patients in the high-RS group had higher proportions of monocytes, M2 macrophages, and activated dendritic cells, whereas those in the low-RS group exhibited higher numbers of M1 macrophages and dendritic resting cells. Our data implied that the constructed THCA prognostic model was sound and we concluded that the THCA patients having high TMB and low PD-L1 expression levels might respond poorly to immunotherapy. Taken together, we constructed a novel prognostic model for THCA patients to predict their prognosis and immunotherapy efficacy, providing a viable option for the future management of THCA patients in the clinic.
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Polydipsia and xerostomia are the most common complications that seriously affect oral health in patients with diabetes. However, to date, there is no effective treatment for diabetic xerostomia. Recent studies have reported that artesunate (ART) and metformin (Met) improve salivary gland (SG) hypofunction in murine Sjögren's syndrome. Therefore, aim of this study was to investigate the effect and underlying mechanism of artesunate (ART) alone and in combination with metformin (Met) on hyposalivation in type 2 diabetes mellitus (T2DM) rats. T2DM rats were induced using a high-fat diet and streptozotocin. SPF male Sprague-Dawley rats were divided into the following five groups: normal control group, untreated diabetic group, ART-treated diabetic group (50 mg/kg), Met-treated diabetic group (150 mg/kg), and ART/Met co-treated diabetic group (50 mg/kg ART and 150 mg/kg Met). ART and Met were intragastrically administered daily for 4 weeks. The general conditions, diabetes parameters and serum lipids were evaluated after drug treatment. Furthermore, we observed changes in the central superior salivatory nucleus (SSN) and SG, and changes in the AQP5 expression, parasympathetic innervation (AChE and BDNF expression), and PI3K/AKT pathway- (p-AKT, and p-PI3K), apoptosis- (Bax, Bcl-2, and Caspase3), and autophagy- (LC3 and P62) related markers expression in T2DM rats after treatment. Our results showed that ART or Met alone and ART/Met combination attenuated a range of diabetic symptoms, including weight loss, urine volume increase, water consumption increase, hyperglycemia, insulin resistance, glucose intolerance and dyslipidemia. More importantly, we found that these three treatments, especially ART/Met combination, mitigated hyposalivation in the T2DM rats via improving the central SSN and SGs damage in hyperglycemia. Our data also indicated that ART/Met attenuated SG damage though regulating the PI3K/Akt pathway to inhibit apoptosis and autophagy of SGs in the T2DM rats. Moreover, ART/Met preserved parasympathetic innervation (AChE and BDNF expression) in SGs to alleviate diabetes-induced hyposalivation likely through rescuing central SSN damage. Taken together, these findings might provide a novel rationale and treatment strategy for future treatment of diabetes-induced xerostomia in the clinic.
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Artesunate (ART) is the derivative of artemisinin isolated from the traditional Chinese medicine qinghao. Although several studies reported the efficiency of artesunate in the treatment of malaria, inhibiting fibroblasts and collagen synthesis, the association between artesunate and scar formation is unclear. The research was designed to study the significance of artesunate (ART) on the expression of transforming growth factor (TGF-ß1) and small mother against decapentaplegic (SMAD3) in rabbit's ear hypertrophic scar model. Twenty-four New Zealand white rabbits were randomly divided into six groups: control group, matrix group, low-concentration artesunate group (0.48%), medium-concentration artesunate group (0.96%), high-concentration artesunate group (1.92%) and silicone gel group. Punched defects were established on each rabbit's ear which resulted in a hypertrophic scar. On the 28th day, topical artesunate creams were applied twice a day except on the control group. On the 56th day, scar samples were collected for histopathology and immunoassay. Hematoxylin and eosin staining, Van Gieson staining, immunohistochemistry and Western blot analysis were done. Amongst the six groups, findings showed that the medium-concentration artesunate group (0.92%) efficiently decreased hypertrophic scar formation and significantly reduced fibroblasts and collagen synthesis. The results had also shown a decrease in the expression of transforming growth factor (TGF-ß1) and declined small signal mother against decapentaplegic (Smad3). The overall study shows efficacy and mechanism of artesunate. It concluded that the medium concentration of artesunate (0.92%) could be an effective therapeutic agent for hypertrophic scars.
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Artesunato/administração & dosagem , Cicatriz Hipertrófica/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Administração Cutânea , Animais , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Orelha , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Coelhos , Pele/citologia , Pele/efeitos dos fármacos , Pele/patologia , Creme para a Pele/administração & dosagem , Cicatrização/efeitos dos fármacosRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0186860.].
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BACKGROUND: The evidence for association between Epstein-Barr virus (EBV) infection and risk of oral squamous cell carcinoma (OSCC) is inconsistent in the literature. Therefore, this meta-analysis was conducted to clarify this association. METHODS: A literature search was conducted in electronic databases for English- and Chinese-language publications until March 31, 2017 to include eligible case-control studies. The pooled odds ratio (OR) and 95% confidence interval (95% CI) were estimated to determine the association between EBV infection and OSCC risk using a fixed- or random-effects model based on heterogeneity. Publication bias was assessed using funnel plot analysis. RESULTS: A total of 13 case-control studies with 686 OSCC patients and 433 controls were included based on predetermined inclusion and exclusion criteria. The pooled OR with 95% CI between EBV infection and OSCC risk was 5.03 (1.80-14.01) with significant heterogeneity observed (I2 = 87%). The subgroup analysis indicates that the year of publication, study location, economic level, sample size, tissue type, detection method and marker, control type, and language might explain potential sources of heterogeneity. Publication bias was not observed, and sensitivity analysis showed stable results. CONCLUSIONS: The results of the current meta-analysis suggest that EBV infection is statistically associated with increased risk of OSCC. However, additional high-quality studies with larger sample sizes are needed to further confirm the relationship between EBV and OSCC.
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Carcinoma de Células Escamosas/virologia , Infecções por Vírus Epstein-Barr/complicações , Neoplasias Bucais/virologia , Estudos de Casos e Controles , HumanosRESUMO
OBJECTIVE: To study the in vivo interference effects of vascular endothelial growth factor (VEGF) short hairpin RNA (shRNA) on xenografts of drug-resistant tongue cancer cells. METHODS: Drug-resistant tongue caner cells Tca/Cisplatin (DDP) were injected subcutaneously into nude mice to establish xenograft models, which were randomly divided into non-transfected group, mock control group, control group transfected with scrambled sequence plasmid, interference group transfected with VEGF-shRNA expression plasmid. Liposome-mediated plasmid transfection was done in the latter three groups every three days. Xenografts were observed and tumor growth curve was measured. After the 10th transfection, tumors were anatomized and weigh. Microvessel density was detected by immunohistochemical staining. In situ hybridization assay was used to test VEGF mRNA, and immunohistochemistry to test VEGF, P-glycoprotein (P-gp), B cell lymphoma/leukemia-2 (bcl-2) and extracellular signal-regultaed kinase 2 (ERK-2) protein. RESULTS: Tumor growth in VEGF-shRNA interference group was significantly slow. Tumor weight was (0.4781 ± 0.0860) g, microvessel density (7.35 ± 1.31)/view, VEGF mRNA (0.0767 ± 0.0234), VEGF protein (0.1301 ± 0.0433), P-gp (0.1517 ± 0.0184), bcl-2 (0.1218 ± 0.0251) and ERK-2 protein (0.1178 ± 0.0291) in VEGF-shRNA interference group; all of them were less than those in the other three groups (P < 0.05). CONCLUSIONS: Inhibition targeting VEGF may become a potential therapy for drug-resistant tongue cancer.
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Carcinoma de Células Escamosas , Interferência de RNA , RNA Interferente Pequeno/genética , Neoplasias da Língua , Fator A de Crescimento do Endotélio Vascular/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microvasos/patologia , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , RNA Mensageiro/metabolismo , Distribuição Aleatória , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia , Transfecção , Carga Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To determine the effect of tyrosine kinase A (TrkA) and vascular endothelial growth factor receptor 2 (VEGFR2) in the invasion and metastasis of salivary adenoid cystic carcinoma (SACC). METHODS: The expression of TrkA and VEGFR2 were detected by immunohistochemical staining in 47 cases of SACC of salivary glands. Clinical data were reviewed by multivariate prognostic analysis. RESULTS: The positive rate of TrkA and VEGFR2 in SACC was 87.23% (41/47) and 85.11% (40/47) respectively. Express of TrkA and VEGFR2 in perineural invasion and recurrence group were higher than non-perineural invasion and non-recurrence group. Significant difference was found in microvessel density (MVD) and VEGFR2 expression within different groups (P < 0.05). MVD in perineural invasion group (25.14 +/- 2.83) was significantly higher than that in none perineural invasion group (18.81 +/- 1.33) (P < 0.05). MVD in recurrence or metastasis group (26.58 +/- 2.38) was significantly higher than that (19.06 +/- 1.39) in none recurrence nor metastasis group (P < 0.05). CONCLUSION: Positive correlation between expression of TrkA, VEGFR2 and nerve invasion and vessel metastasis of SACC indicate that TrkA and VEGFR2 play important roles in the invasion and metastasis of SACC. It is possible that TrkA and VEGFR2 could be an aid for evaluating the prognosis of SACC patients.
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Carcinoma Adenoide Cístico/metabolismo , Receptor trkA/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Carcinoma Adenoide Cístico/patologia , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia , Neoplasias das Glândulas Salivares/patologia , Receptor 2 de Fatores de Crescimento do Endotélio VascularRESUMO
<p><b>AIM</b>To detect the expression of nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) in salivary adenoid cystic carcinoma (SACC) tissues, as well as to determine the correlation between growth factor expression and prognosis in SACC.</p><p><b>METHODOLOGY</b>Medical records of 63 patients surgically treated for SACC between January 1988 and October 2005 were reviewed. Immunohistochemistry was performed to examine the expression of NGF and VEGF in tumor tissues. Kaplan-Meier analysis and Cox's proportional hazard regression model were applied to assess predictors of survival.</p><p><b>RESULTS</b>NGF and VEGF were overexpressed in SACC tissues, compared with those in normal salivary tissues (P < 0.05), and the staining intensity of these two factors was stronger in groups of solid subtype, advanced TNM stage, perineural invasion and recurrence. Patients with high-expression of NGF and VEGF, solid subtype, advanced stage, perineural invasion, recurrence and extended resection alone had worse survival rates (P < 0.05).</p><p><b>CONCLUSION</b>NGF and VEGF are expressed increasingly in the tissues of SACC cases with invasion and metastasis. NGF expression and VEGF expression are independent</p>
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Carcinoma Adenoide Cístico , Patologia , Cirurgia Geral , Nervos Cranianos , Patologia , Seguimentos , Imuno-Histoquímica , Terapia Neoadjuvante , Invasividade Neoplásica , Recidiva Local de Neoplasia , Patologia , Estadiamento de Neoplasias , Fator de Crescimento Neural , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias das Glândulas Salivares , Patologia , Cirurgia Geral , Glândulas Salivares , Patologia , Glândulas Salivares Menores , Patologia , Taxa de Sobrevida , Fator A de Crescimento do Endotélio VascularRESUMO
BACKGROUND: Our aim was to review our experience with liposarcoma of the head and neck region. METHODS: This is a retrospective case series at a comprehensive cancer center (1945-2005). RESULTS: Of 30 patients, 10 (33%) were initially misdiagnosed. Local recurrences were common (overall rate = 53%), and 4 patients (13%) developed distant metastases. Decreased crude disease-specific survival rates were significantly associated with recurrence (especially distant recurrence [0%]), age less than 38 years (40%), and pleomorphic subtype (45%); however, in Kaplan-Meier analyses, only larger tumor size, negative margins, round cell subtype, and pleomorphic subtype were associated with significantly decreased disease-specific survival (log-rank test p = .048, .041, .021, and .012, respectively). CONCLUSIONS: Based on this limited experience and existing literature, we continue to recommend surgery with negative margins as the treatment of choice and that adjuvant therapies should be considered in patients with high-grade histology, large tumors, positive margins, or certain subsites.
Assuntos
Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/cirurgia , Lipossarcoma/mortalidade , Lipossarcoma/cirurgia , Adulto , Institutos de Câncer , Terapia Combinada , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Estimativa de Kaplan-Meier , Lipossarcoma/tratamento farmacológico , Lipossarcoma/patologia , Lipossarcoma/radioterapia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos , Texas , Adulto JovemRESUMO
This review is the first section of tumor biology pertaining to head and neck squamous cell carcinoma (SCCHN). It is intended to introduce the basic concepts of cancer biology to enhance the translational research. The basic tumour biology relates to the aberrations in the normal cell cycle. cell growth and cell death. The genetic aspects of cancer focus upon the roles of oncogenes, tumor suppressor genes and stability genes. The epigenetic mechanisms of the cancer relates to DNA methylation and histone acetylation. This review, discusses the basics of these concepts.
RESUMO
The essential steps implicated in carcinogenesis are acquisition of autonomous proliferative signaling; inhibition of growth inhibitory signals; evasion of apoptosis; immortalization; angiogenesis; tissue invasion and metastasis. A considerable progress in understanding the process of carcinogenesis has further stimulated the high throughput translational methods and systems biology approach to revolutionize this field of cancer biology. The era of molecular targeted therapy has dawned and would soon replace the more 'toxic' classical 'broad-spectrum' cancer chemotherapy. This review summarises the steps of carcinogenesis and the concepts involved in translational methods, systems-biology and molecular targeted therapy.