RESUMO
Tongue squamous cell carcinoma (TSCC) is one of the most common cancers in the oral cavity. Notch signaling is frequently dysregulated in cancer. However, the role of Notch2 in TSCC is not well understood. The aim of this study was to investigate the effect of abnormal expression of Notch2 in TSCC. The expression of Notch2 was tested in 47 pairs of tissues from tongue cancer and normal samples by using immunohistochemical staining. Tongue cancer cells were transfected with siRNA or plasmid. The proliferation of the cells was tested by the CCK8 assay and colony formation assay. Subcutaneous tumor model was established to observe tumor growth. Transwell assay was used to detect the changes of cell migration and invasion ability. A humanized anti-Notch2 antibody was used to TSCC cells. We found that Notch2 was upregulated in tongue carcinoma tissues. Knocking down the expression of Notch2 by siRNA in the TSCC cell lines decreased proliferation ability both in vitro and in vivo. In addition, migration and invasion abilities were inhibited by knockdown of Notch2 in the TSCC cells. However, overexpression of Notch2 increased tongue cancer cell proliferation, invasion and migration. The humanized anti-Notch2 antibody inhibited TSCC cell growth. The results indicated that Notch2 is an oncogene in tongue squamous cell carcinoma and may become the target of a new approach for treating TSCC.
Assuntos
Carcinogênese/genética , Carcinoma de Células Escamosas/genética , Receptor Notch2/genética , Neoplasias da Língua/genética , Animais , Carcinoma de Células Escamosas/patologia , Movimento Celular/genética , Proliferação de Células/genética , Células Cultivadas , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias da Língua/patologia , Regulação para Cima/genéticaRESUMO
BACKGROUND: Matrix metalloproteinase 7 (MMP7), as the smallest member of the matrix metalloproteinase family, has been verified to be implicated in cancer progression, especially metastasis. However, its expression pattern and function in tongue cancer is not clear. METHODS: The expression of MMP7 in human tongue squamous cell carcinoma (TSCC) specimens compared with their respective paired nontumour tissues by real-time PCR and immunohistochemical staining. The effect of MMP7 on the proliferation, apoptosis, migration, invasion of tongue cancer cells was tested in appropriate ways after MMP7 siRNA knockdown or overexpression. The effect of MMP7 on lymph node metastasis in vivo was analyzed using a high-metastasis orthotopic nude mouse tongue transplanted tumour model. RESULTS: We found markedly elevated expression of MMP7 in human TSCC specimens compared with their respective paired nontumour tissues, and this high expression was correlated with the patients' lymph node metastasis. Furthermore, the results of molecular functional assays confirmed that MMP7 promotes cell proliferation, migration and invasion of TSCC cells. Knockdown of MMP7 inhibited lymph nodes metastasis in vivo. CONCLUSIONS: MMP7 plays an oncogenic role in carcinogenesis and metastasis of tongue cancer, and may serve as a potential therapeutic target for tongue cancer.
Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Metaloproteinase 7 da Matriz/genética , Neoplasias da Língua/genética , Adulto , Idoso , Animais , Apoptose , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular/genética , Modelos Animais de Doenças , Feminino , Humanos , Imuno-Histoquímica , Masculino , Metaloproteinase 7 da Matriz/metabolismo , Camundongos , Pessoa de Meia-Idade , Neoplasias da Língua/metabolismo , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Many studies have explored whether the Notch signaling pathway has a tumor-suppressive or an oncogenic role in various tumors; however, the role of the Notch signaling pathway in salivary adenoid cystic carcinoma (SACC) is still unknown. In this study, we attempt to define the role of Notch2 signaling in cell growth, invasion, and migration in SACC. We compared Notch2 expression in clinical SACC samples with that of normal samples by using immunohistochemical staining. Then, we down-regulated Notch2 expression to observe the effect of Notch2 on proliferation, invasion, migration, and the expression of known target genes of Notch signal pathway. According to our results, Notch2 expression was higher in SACC tissues compared with normal tissues. Knockdown of Notch2 inhibited cell proliferation, invasion, and migration in vitro and down-regulated the expression of HEY2 and CCND1. The results of this study suggest that Notch2 has an essential role in the cell growth, invasion, and migration of SACC. Notch2 may therefore be a potential target gene for the treatment of SACC by interfering with cell growth and metastasis.
Assuntos
Carcinoma Adenoide Cístico/patologia , Proliferação de Células , Invasividade Neoplásica , Metástase Neoplásica , Receptor Notch2/metabolismo , Neoplasias das Glândulas Salivares/patologia , Transdução de Sinais , Carcinoma Adenoide Cístico/metabolismo , Linhagem Celular Tumoral , Técnicas de Silenciamento de Genes , Humanos , Receptor Notch2/genética , Neoplasias das Glândulas Salivares/metabolismoRESUMO
Jaw cysts commonly affect the oral and maxillofacial region, involving adjacent tooth roots. The management of these teeth, particularly regarding root canal therapy and apicoectomy, lacks consensus. This study introduces a novel treatment concept and refined surgical approach to preserve pulp viability in teeth involved in jaw cysts. The objective was to investigate the effectiveness and potential benefits of this approach over a 36-month follow-up period. A conservative management approach prioritized vitality preservation, reserving root canal treatment and apicectomy for cases with post-operative discomfort. A comprehensive follow-up of 108 involved teeth from 36 jaw cyst cases treated with the modified method was conducted. Clinical observation, X-ray imaging, cone-beam computed tomography (CBCT), and pulp vitality testing assessed changes in cyst size, tooth color, pulp vitality, root structure, and surrounding alveolar bone. After 36 months, our modified surgical approach successfully preserved tooth vitality in 84 involved teeth. Adverse symptoms in 19 teeth, such as redness, swelling, fistula, and pain, resolved with postoperative root canal therapy. Follow-up was lost for five teeth in two cases. No cyst recurrences were observed, and in 34 cases, the bone cavity gradually disappeared, restoring normal bone density during long-term follow-up. Our modified surgical method effectively preserves tooth vitality in jaw cysts. This innovative approach has the potential to improve the management of teeth involved in jaw cysts.
Assuntos
Cistos , Cistos Maxilomandibulares , Dente , Humanos , Seguimentos , Dente/diagnóstico por imagem , Tratamento do Canal Radicular/métodos , Tomografia Computadorizada de Feixe Cônico/métodosRESUMO
OBJECTIVES: Evidence on serum arsenic and oral cancer risk was limited. We aimed to evaluate the association between serum arsenic and the risk of oral cancer in a southeast China population. METHODS: Serum arsenic was determined for 325 oral cancer patients and 648 controls using inductively coupled plasma-mass spectrometry (ICP-MS). Logistic regression and restricted cubic spline were analysed the association between serum arsenic level and oral cancer risk, and crude and adjusted odds ratios (aOR) with 95% confidence interval (95% CI) were calculated. Factors adjusted for included age, gender, BMI, smoking, drinking, education, residence, marital status and dietary factors. Stratification analysis was further performed according to drinking, smoking and dietary characteristics. RESULTS: Serum arsenic level was lower in the case group (P50 = 19.2µg/L, IQR = 11.6 ~ 26.4µg/L) than in the control group (P50 = 30.2 µg/L, IQR = 25.0 ~ 36.4 µg/L). An inverse but nonlinear association was observed between arsenic level and oral cancer risk by restricted cubic spline. These with moderate serum arsenic levels had a lower risk of oral cancer than those with low levels (OR = 0.11; 95%CI: 0.07-0.18), after adjusting for demographic and dietary intake factors. We also kept serum arsenic as a continuous variable in a regression model, where a similar inverse association between arsenic and oral cancer was observed, with OR = 0.86 (95%CI: 0.84-0.88). Stratification analysis revealed no significant multiplicative interactions between serum arsenic and smoking, drinking or dietary intake. CONCLUSION: Serum arsenic is inversely related to oral cancer risk. Relative to those with low levels of arsenic, people with moderate serum arsenic levels had a lower risk of oral cancer. If confirmed, serum arsenic level may be a useful predictive marker for oral cancer risk.
Assuntos
Arsênio , Neoplasias Bucais , Arsênio/efeitos adversos , Arsênio/análise , Estudos de Casos e Controles , China/epidemiologia , Humanos , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/etiologia , Razão de ChancesRESUMO
PURPOSE: It was aimed to apply computer virtual design and digital surgical templates to simulate postoperative position of tooth and guide the accuracy of socket preparation during tooth autotransplantation. METHODS: The study enrolled 10 patients who underwent tooth autotransplant surgery. Cone-bean CT (CBCT) data were imported into Proplan CMF 3.0 software. The donor tooth was transferred to the recipient site according to the occlusion and space situation. A digital template was designed to guide socket preparation. Computer-aided rapid prototyping (RP) technique was used to print the surgical template and tooth model. RESULTS: With computer virtual design and digital template, it was possible to accurately guide socket preparation in recipient site. The six-month follow-up results showed the periodontal space in the radiographs was continuous and intact. There was no mobility in all cases and the probing depth of the tooth was <4 mm. The related data showed a favorable survival and success rates of the donor teeth. CONCLUSIONS: Computer virtual design can successfully simulate postoperative position in tooth autotransplantation while simplifying the surgical procedure, and enhance the accuracy of socket preparation.
Assuntos
Cirurgia Assistida por Computador , Dente , Desenho Assistido por Computador , Tomografia Computadorizada de Feixe Cônico , Humanos , Impressão Tridimensional , Alvéolo Dental , Transplante AutólogoRESUMO
Our previous study demonstrated a close relationship between the NOTCH signaling pathway and salivary adenoid cystic carcinoma (SACC). Its receptor gene, NOTCH1, and its downstream gene, HES1, contribute to the proliferation, invasion and metastasis of SACC. Accumulating evidence supports HEY1 as another effector of the signaling pathway. The purpose of this study was to explore the effects of the NOTCH1-HEY1 pathway on the proliferation, invasion and metastasis of SACC cells. Our results verified that HEY1 is a specific molecular target of the NOTCH signaling pathway in SACC cells and that its expression in carcinoma is much higher than that in paracarcinoma tissues. The expression of NOTCH1 and HEY1 are positively correlated in the salivary adenoid cystic carcinoma tissues. NOTCH1 is significantly related to the activation of HEY1 in SACC, and that HEY1 reciprocally regulates NOTCH1 expression in SACC. HEY1 promotes cell proliferation and spheroid formation and inhibits cell apoptosis in vitro. In addition, HEY1 enhances the tumorigenicity of SACC in vivo. Furthermore, HEY1 increases cell invasion and metastasis by driving the expression of epithelial-mesenchymal transition (EMT)-related genes and MMPs. The results of this study indicate that the NOTCH1-HEY1 pathway is specifically upregulated in SACC and promotes cell proliferation, self-renewal, invasion, metastasis and the expression of EMT-related genes and MMPs. Our findings suggest that a NOTCH1-HEY1 pathway inhibitor might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Proteínas de Ciclo Celular/metabolismo , Receptor Notch1/metabolismo , Glândulas Salivares/patologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinoma Adenoide Cístico/genética , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Receptor Notch1/genética , Glândulas Salivares/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Tiazolidinas/farmacologiaRESUMO
OBJECTIVES: Evidence about ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and oral cancer risk were limited. We aimed to evaluate the association of erythrocyte ω-3 PUFAs with the risk of oral cancer in a population from China. METHODS: Erythrocyte ω-3 PUFAs of 236 oral cancer patients and 300 controls were determined by gas chromatography. Restricted cubic spline and logistic regression were used to analyze the association between erythrocyte ω-3 PUFAs and oral cancer risk. The crude and adjusted OR with 95% CI was calculated. Stratification analysis was performed to explore the potential interaction between ω-3 PUFAs and other traditional risk factors such as smoking and drinking. RESULTS: Eicosapentaenoic acids (EPA), docosahexaenoic acids (DHA) and ω-3 index were negatively but non-linearly related to risk of oral cancer as observed by restricted cubic spline. The adjusted OR of EPA, DHA, and ω-3 index were 0.52 (95% CI: 0.35-0.76), 0.19 (95% CI: 0.08-0.44), 0.20 (95% CI: 0.09-0.44), respectively. Stratification analysis showed that the adverse correlation between EPA and oral cancer was only significant in the non-smoking group, while the adverse correlation of É-linolenic acid (ALA), EPA, and DHA were only significant in the non-drinking group. General multiplicative interactions were observed between ω-3 PUFAs and smoking or drinking. CONCLUSIONS: Adverse but non-linear associations were observed between erythrocyte EPA, DHA, ω-3 index, and oral cancer risk. Additionally, there were multiplicative interactions between ω-3 PUFAs and other behavior factors such as smoking and drinking. The protective effect of ω-3 PUFAs maybe more significant in the non-smoking or non-drinking population.
Assuntos
Eritrócitos/metabolismo , Ácidos Graxos Ômega-3/sangue , Neoplasias Bucais/epidemiologia , Idoso , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Ácidos Graxos Ômega-3/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/sangue , Fatores de Risco , Fumar/epidemiologiaRESUMO
PURPOSE: The Notch signaling pathway plays an oncogenic role in tongue squamous cell carcinoma. The aim of this study was to inhibit the proliferation and self-renewal of tongue cancer cells by applying Notch signaling pathway inhibitor FLI-06 (Selleck, USA) and to lay a foundation for the clinically targeted treatment of tongue cancer for the future. METHODS: The mRNA expression level of Notch1 and the overall survival rate of patients with tongue cancer were examined by analyzing the TCGA database. Tongue cancer cells were treated with FLI-06. Cell proliferation, apoptosis, and stem cell self-renewal ability were tested in appropriate ways. A xenograft mouse model was established to observe tumor growth. RESULTS: From the TCGA data, we demonstrated that patients with high expression of Notch1 had a poor prognosis. We observed that the Notch signaling pathway inhibitor FLI-06 can restrain the activation of the Notch signaling pathway, decrease cell proliferation and induce cell apoptosis in vitro. The xenograft experiment indicated that intraperitoneal injection of FLI-06 inhibited tumor growth and increased cell apoptosis. FLI-06 suppressed both the mRNA and protein expression of Notch receptor and Notch targeted genes. We also observed that FLI-06 suppressed the proliferation of tongue cancer stem cells. CONCLUSION: FLI-06 can block the proliferation and self-renewal of tongue cancer cells. It is inferred that this compound, which inhibits the Notch signaling pathway, may serve as a potential targeted drug for the treatment of tongue cancer in the clinic.
RESUMO
Many studies have shown that FZD2 is significantly associated with tumor development and tumor metastasis. The purpose of the present study was to gain insight into the role of FZD2 in the cell proliferation and invasion of tongue squamous cell carcinoma. According to TCGA-HNSC dataset, among the 10 Frizzled receptors, FZD2 exhibited the highest degree of differential expression between cancer tissues and normal tissues, and the overall survival of patients with higher FZD2 levels was shown to be significantly shorter compared with those with lower FZD2 levels. The upregulation of FZD2 in clinical tongue cancer tissues was validated by real-time PCR. Knockdown of FZD2 inhibited the proliferation, migration and invasion of CAL-27 and TCA-8113 cells, whereas overexpression of FZD2 led to the opposite results. Further analysis revealed that FZD2 is positively correlated with WNT3A, WNT5B, WNT7A and WNT2 and is negatively correlated with WNT4. These results indicated that FZD2 may act as an oncogene in tongue squamous cell carcinoma. Therefore, FZD2 may be a target for the diagnosis, prognosis and gene therapy of tongue cancer.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Receptores Frizzled/fisiologia , Neoplasias da Língua/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Movimento Celular , Proliferação de Células , Feminino , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Neoplasias da Língua/genética , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Proteínas Wnt/metabolismoRESUMO
PURPOSE: Using Proplan virtual software to construct a virtual teaching platform for orthognathic surgery, and to explore an effective teaching model for orthognathic surgery. METHODS: One-hundred grade four students of stomatology in Fujian Medical University were divided into two groups. Traditional orthognathic surgery teaching method and Proplan virtual software teaching method were employed to teach the two groups of students, respectively. Orthognathic-surgery-related paper test was used to evaluate how the two groups of students understand orthognathic surgery; then the students were switched to the other teaching method, respectively. A follow-up questionnaire survey was conducted to further evaluate students' acceptance of the two teaching methods. Finally, a comprehensive statistical analysis was performed for students understanding of orthognathic surgery using SPSS 11.0 software package. RESULTS: According to the test scores, students in the experimental group scored higher than the control group, the difference was significant (P<0.01). The acceptance of different teaching methods displayed remarkable difference between the two groups. Token together, our finding showed that virtual model surgery teaching was an easier teaching method for students to understand and accept. CONCLUSIONS: Proplan virtual software teaching improves the teaching efficiency of orthognathic surgery and deserves further promotion.
Assuntos
Medicina Bucal , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Software , Medicina Bucal/educação , Estudantes , EnsinoRESUMO
OBJECTIVES: Notch1 regulates tumor biology in a complex, context-dependent manner. The roles of Notch1 in tongue cancer are still controversial. The aim of this study is to investigate the roles of Notch1 in tongue cancer. MATERIALS AND METHODS: The expression of Notch1 was tested between tongue cancer and normal samples by using immunohistochemistry. Tongue cancer cells were transfected with siRNA or plasmid, respectively. Cell proliferation, apoptosis, migration and invasion ability were tested in appropriate ways. The subcutaneous tumor model was established to observe the tumor growth. RESULTS: Notch1 was upregulated in tongue carcinoma tissues and the expression of Notch1 was related with tumor stage and differentiation. Overexpression of Notch1 could increase tongue cancer cells proliferation, invasion and migration. But inhibited the expression of Notch1 could decrease cells proliferation, invasion and migration and promote cell apoptosis in vitro and in vivo. CONCLUSION: Our results prove that the oncogenic role of Notch1 in tongue cancer and provide the direction of targeted therapy of tongue cancer.
Assuntos
Carcinoma de Células Escamosas/patologia , Receptor Notch1/fisiologia , Neoplasias da Língua/patologia , Animais , Apoptose , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/secundário , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Receptor Notch1/genética , Receptor Notch1/metabolismo , Neoplasias da Língua/genética , Neoplasias da Língua/metabolismoRESUMO
PURPOSE: To evaluate the clinical effect of improved alveolar cleft repair with bone grafting. METHODS: Forty one cases with alveolar cleft treated by modified operation between 2008-2016 were included. The modified techniques were as follow: incision design, preparation of bone graft bed, bone removal and bone grafting, etc. The therapeutic effect was analyzed. RESULTS: The successful rate was 92.8%. After 6-12 months of follow-up, bone graft survived well with no obvious complications. CONCLUSIONS: Iliac bone is a good source for bone graft. Improvement of tight tension-free suture in bone bed is the key to surgical success.
Assuntos
Enxerto de Osso Alveolar , Transplante Ósseo , Fenda Labial , Fissura Palatina , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Humanos , Ílio , Estudos RetrospectivosRESUMO
The cadherin-4 gene (CDH4) of the cadherin family encodes non-epithelial R-cadherin (R-cad); however, the function of this gene in different types of cancer remains controversial. In this study, we found higher expression of CDH4 mRNA in a salivary adenoid cystic carcinoma (SACC) cell line with low metastatic potential (SACC-83) than in a cell line with high metastatic potential (SACC-LM). By analyzing 67 samples of SACC tissues and 40 samples of paraneoplastic normal tissues, we found R-cad highly expressed in 100% of normal paraneoplastic tissue but only expressed in 64% of SACC tumor tissues (P<0.001). Knockdown of CDH4 expression in vitro promoted the growth, mobility and invasion of SACC cells, and in vivo experiments showed that decreased CDH4 expression enhanced SACC tumorigenicity. Furthermore, CDH4 suppression resulted in down-regulation of E-cadherin (E-cad), which is encoded by CDH1 gene and is a well-known tumor suppressor gene by inhibition of cell proliferation and migration. These results indicate that CDH4 may play a negative role in the growth and metastasis of SACC via co-expression with E-cadherin.
Assuntos
Caderinas/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Animais , Antígenos CD , Caderinas/genética , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/secundário , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Interferência de RNA , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Transdução de Sinais , Fatores de Tempo , Transfecção , Carga TumoralRESUMO
PURPOSE: To discuss the diagnosis and treatment of necrosis of jaws caused by leakage of arsenite trioxide, and to emphasize the consequences of its use. METHODS: Ten cases of arsenical necrosis of the jaws from Jan, 2009 to Jun, 2014 treated in our department were collected and analyzed, with emphasis on the key points of diagnosis and treatment. RESULTS: Diagnosis was based on medical history, clinical examinations, X-ray findings, and preoperative or intraoperative cone-beam CT (CBCT) scans. Nine patients were cured with primary operation, one patient was cured by secondary extended surgery. CONCLUSIONS: Because of the high toxicity, there is no justification for the use of arsenite trioxide in clinic.
Assuntos
Tomografia Computadorizada de Feixe Cônico , Idoso , Trióxido de Arsênio , Arsenicais , Arsenitos , Humanos , Doenças Maxilomandibulares , Osteonecrose , ÓxidosRESUMO
BACKGROUND: Numerous studies have reported both the tumor-suppressive and oncogenic roles of the Notch pathway, indicating that Notch activity regulates tumor biology in a complex, context-dependent manner. The aim of the present study was to identify the role of NOTCH1 in the cell growth and metastasis of SACC. METHODS: We analyzed the expression of NOTCH1 in clinical SACC samples using immunohistochemical staining. We silenced the expression of NOTCH1 and overexpressed activated NOTCH1 to elucidate the effects of NOTCH1 on proliferation, migration and invasion. NOTCH1 target genes were validated by real-time PCR. RESULTS: Our results showed that NOTCH1 was upregulated in SACC tissues when compared with normal tissues, and this upregulation was further enhanced in SACC tissues with metastasis and recurrence when compared with SACC tissues without metastasis. Overexpression of NOTCH1 in SACC cells promoted cell growth, migration and invasion, and knockdown of NOTCH1 inhibited cell proliferation in vitro and tumorigenicity in vivo by inducing cell apoptosis. CONCLUSIONS: The results of this study suggest that NOTCH1 plays a key role in the cell growth, anti-apoptosis, and metastasis of SACC. NOTCH1 inhibitors might therefore have potential therapeutic applications in treating SACC patients by inhibiting cancer cell growth and metastasis.
Assuntos
Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Receptor Notch1/biossíntese , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Animais , Apoptose/fisiologia , Carcinoma Adenoide Cístico/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Feminino , Expressão Gênica , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética , Receptor Notch1/genética , Receptor Notch1/metabolismo , Neoplasias das Glândulas Salivares/genética , Transdução de Sinais , Transfecção , Regulação para CimaRESUMO
OBJECTIVE: To fabricate a rapid prototyping (RP) 3-D image models for individual reconstruction of orbital bony loss. METHODS: The skull was placed on a helical CT scanner table and the Frankfort plane was perpendicular to the table. The CT data was obtained by a Aquilion (TOSHIBA, Japan) with 1 mm thickness section in spiral mode. By adjusting of CT threshold value and pixels in order to stack the segmental defects, we obtained an approximate 3-dimension visual model of the scanned skull using MedGraphics software. An orbital RP model based on the dataset of the 3-dimension visual model was fabricated by RP machine. Both 3-dimension visual model and RP model were measured against the skull with several anatomic landmarks to examine the accuracy of the models, and the errors were analysed. RESULTS: Integrity precision rapid RP models of the orbital region were reconstructed. The anterior orbital rim, middle orbital section and posterior orbital section were all fabricated. Optic foramen, superior orbital fissure, infraorbital foramen, inferior orbital fissure, lacrimal sac socket and naso-lacrimal duct were shown clearly. But some fine hole and slot, such as the anterior ethmoidal foramen, posterior ethmoidal foramen and zygomaticofrontal suture were not obviously seen. The mean difference between the 3-dimension visual model and the skull was 0.10 +/- 1.02mm. For the RP and dry skull, the mean difference was 0.22 +/- 1.04mm. There were no statistical differences between them. CONCLUSIONS: Integrity precision orbital RP models were fabricated which fulfilled the requirements of the individual reconstruction with bony orbital pathologic changes. The keys to fabricate the precision orbital RP models included a closer cooperation between the surgeon and engineer, thin CT slice in 1mm thick and an appropriated threshold value. Better results for the orbital deformities should be achieved for the contour of orbital region or eye function.