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PURPOSE: The current data on the relationship between local inflammatory infiltration and prognosis in oral squamous cell carcinoma (OSCC) are limited and controversial, especially in different HPV status. In this study, we analyzed the relationship between peri-tumoral inflammatory infiltrate (PTI) and HPV status and prognosis of patients with OSCC after surgery. METHODS: A retrospective cohort of 99 primary OSCC patients who underwent surgery was constructed. P16 immunohistochemistry was used to determine HPV status. PTI was determined by hematoxylin-eosin staining and quantified into four levels: none (Score 0), weak (Score 1), moderate (Score 2) and strong (Score 3). The associations of PTI with clinico-pathological characteristics, HPV status and survival were examined. RESULTS: Most OSCC patients had weak to moderate PTI. PTI was significantly associated with lymph node metastasis (P = 0.041), and patients with moderate PTI had significantly better OS (P = 0.009) than those with no PTI. In HPV negative OSCC, patients with moderate PTI also had significantly better OS (P = 0.019) than those with no PTI. However, PTI was not significantly associated with survival in HPV positive OSCC. CONCLUSIONS: In HPV negative OSCC, moderate PTI may suggest a better postoperative prognosis than no PTI.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia , Papillomaviridae , Infecções por Papillomavirus/complicações , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgiaRESUMO
Herein, we detail a multidisciplinary approach and sequential treatment for two infants with congenital granular cell epulis (CGCE). Ultrasonic examinations at 34 weeks of gestation revealed prominent oral masses in both fetuses. To devise a carefully considered treatment strategy, a comprehensive multidisciplinary consultation including oral and maxillofacial surgeons, pediatricians, obstetricians, and anesthesiologists was convened. Following cesarean sections, the lesions were successfully removed, measuring approximately 30 × 15 mm and 30 × 20 mm in size, respectively. Immunohistochemical analysis showed that vimentin was positive, S-100 protein was negative, and NSE protein and CD68 protein were negative. These findings underscore the importance of prenatal diagnosis of congenital granular cell epulis for the effective management of these rare benign conditions.
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Tumor de Células Granulares , Diagnóstico Pré-Natal , Humanos , Feminino , Gravidez , Tumor de Células Granulares/cirurgia , Tumor de Células Granulares/patologia , Tumor de Células Granulares/congênito , Diagnóstico Pré-Natal/métodos , Recém-Nascido , Neoplasias Gengivais/cirurgia , Neoplasias Gengivais/patologia , Neoplasias Gengivais/congênito , Adulto , Masculino , Ultrassonografia Pré-NatalRESUMO
AIM: Galectin-3 (Gal-3) is a member of the carbohydrate-binding protein family that contributes to neoplastic transformation, tumor survival, angiogenesis, and metastasis. The aim of this study is to investigate the role of Gal-3 in human tongue cancer progression. METHODS: Human tongue cancer cell lines (SCC-4 and CAL27) were transfected with a small-interfering RNA against Gal-3 (Gal-3-siRNA). The migration and invasion of the cells were examined using a scratch assay and BD BioCoat Matrigel Invasion Chamber, respectively. The mRNA and protein levels of ß-catenin, Akt/pAkt, GSK-3ß/pGSK-3ß, MMP-9 in the cells were measured using RT-PCR and Western blotting, respectively. RESULTS: Transient silencing of Gal-3 gene for 48 h significantly suppressed the migration and invasion of both SCC-4 and CAL27 cells. Silencing of Gal-3 gene significantly decreased the protein level of ß-catenin, leaving the mRNA level of ß-catenin unaffected. Furthermore, silencing Gal-3 gene significantly decreased the levels of phosphorylated Akt and GSK-3ß, and suppressed the mRNA and protein levels of MMP-9 in the cells. CONCLUSION: Our data suggest that Gal-3 mediates the migration and invasion of tongue cancer cells in vitro via regulating the Wnt/ß-catenin signaling pathway and Akt phosphorylation.
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Galectina 3/genética , Interferência de RNA , Neoplasias da Língua/patologia , Língua/patologia , beta Catenina/genética , Linhagem Celular Tumoral , Movimento Celular , Regulação para Baixo , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , Língua/metabolismo , Neoplasias da Língua/genética , Neoplasias da Língua/metabolismo , Transfecção , Via de Sinalização Wnt , beta Catenina/metabolismoRESUMO
PURPOSE: This report describes the effect of periosteal-derived cells transfected with adenovirus-mediated bone morphogenetic protein-2 (BMP-2) on the repair of mandibular defects in rabbits. MATERIALS AND METHODS: Periosteal-derived cells were transfected with a replication-defective adenoviral vector encoding BMP-2, and the expression of BMP-2 was examined in transfected cells using in situ hybridization and enzyme-linked immunosorbent assay. In addition, the proliferation ability and activity of alkaline phosphatase of transfected cells were examined using the 3-[4,5-dimethylthiazol-2-Yl]-2,5-diphenyltetrazolium bromide method and enzymology, respectively. In vitro critical-size defects (about 10 × 6 mm) were made bilaterally in each rabbit mandible, and individual sites were implanted with tissue-engineered bone modified with an adenovirus construct encoding the recombinant human BMP-2 gene (Ad-BMP-2), tissue-engineered bone without modification, single bioactive glass ceramic, or no implants (control). New bone formation was evaluated by histochemical stain. RESULTS: BMP-2 expression in the supernate of infected cells was detected from the first day after Ad-BMP-2 transfection and remained at a high level for at least 2 weeks. Alkaline phosphatase expression in transfected cells was significantly greater than in uninfected cells. The group of Ad-BMP-2-modified periosteal-derived cells formed more new bone than the other group at any time point. CONCLUSION: Gene-modified tissue-engineered bone grafts have greater osteogenic potential than single tissue-engineered bone and single bioactive glass ceramic graft. Ex vivo Ad-BMP-2 transfer to periosteal-derived cells can increase bone formation in critical-size bone defects. Further studies are needed to determine if modified engineered cells can be developed for safe and effective clinical applications.
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Adenoviridae/genética , Proteína Morfogenética Óssea 2/uso terapêutico , Vetores Genéticos/genética , Doenças Mandibulares/cirurgia , Periósteo/citologia , Engenharia Tecidual/métodos , Alicerces Teciduais , Transfecção , Fator de Crescimento Transformador beta/uso terapêutico , Fosfatase Alcalina/análise , Animais , Regeneração Óssea/genética , Substitutos Ósseos/química , Técnicas de Cultura de Células , Proliferação de Células , Transplante de Células , Cerâmica/química , Corantes , Ensaio de Imunoadsorção Enzimática , Regeneração Tecidual Guiada/métodos , Humanos , Hibridização In Situ , Osteogênese/fisiologia , Coelhos , Proteínas Recombinantes/uso terapêutico , Sais de Tetrazólio , Tiazóis , Transplante HomólogoRESUMO
Introduction: An effective tool is needed to predict the prognosis of head and neck squamous cell carcinoma (HNSCC). Human papillomavirus (HPV) positive HNSCC patients generally have a favorable survival and a promising responsiveness to radiotherapy, chemoradiotherapy and checkpoint blockades. However, HPV negative patients, the majority of HNSCC patients, have been largely overlooked. Cell death has been involved in the therapeutic resistance of cancers. To this end, we aimed to identify the association of autophagy, apoptosis and pyroptosis-related genes with the prognosis of HNSCC, and construct a prognostic signature to predict the prognosis for HNSCC, especially for HPV negative HNSCC. Methods: Autophagy and apoptosis-related genes were obtained from Gene Set Enrichment Analysis (GSEA) website, and pyroptosis-related genes were obtained from GSEA and Gene Ontology (GO) database. We established the cell death index (CDI) based on RNA sequencing (RNA-seq) data and clinicopathological information from The Cancer Genome Atlas (TCGA) dataset. The prognostic value of CDI was verified by Kaplan-Meier, receiver operating characteristic (ROC) and univariate and multivariate Cox regression analyses in TCGA dataset, and validated with the datasets from Gene Expression Omnibus (GEO) and Qilu Hospital of Shandong University. We further assessed the immune microenvironment of patients with high and low CDI scores. Moreover, the expression of the signature genes in HNSCC cell lines were explored. Results: We found that CDI was an independent prognostic indicator for overall survival (hazard ratio 3.80, 95% confidential interval: 2.70-5.40, P < 0.001). Furthermore, HNSCC patients with high CDI scores obtained increased overall survival post radiation indicating benefits from radiotherapy of this subgroup. On the other hand, HPV negative HNSCC patients with low CDI exhibited increased checkpoint gene expressions, an inflamed tumor microenvironment and an enriched immune response-related functions, suggesting the potential benefits from checkpoint immunotherapies of this subgroup. Moreover, we validated the baseline and induced expressions of above 16 genes in two HPV negative HNSCC cell lines, CAL27 and SCC-15. Discussion: We established a prognostic signature and emphasized its implements in the therapeutic choices of HPV negative HNSCC patients, the majority and the poor outcome population of HNSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Prognóstico , Piroptose/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Infecções por Papillomavirus/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Apoptose/genética , Autofagia/genética , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: The need for an effective tool to predict prognosis of head and neck squamous cell carcinoma (HNSCC) patients is critical and unmet. Microbiota has recently been found involved in tumor progression and response to immunotherapy. However, the association of microbiota with the prognosis of HNSCC patients remains obscure. This study aims to investigate the association between tumor microbiota and outcomes of HNSCC patients. METHODS: A retrospective study including 129 primary tumors of HNSCC was conducted. Using 16S rRNA sequencing, the profile and the composition of tumor microbiota were measured and their associations with overall survival (OS) and disease free survival (DFS) were examined. RESULTS: We observed a reduced richness and enriched abundances of genera Schlegelella and Methyloversatilis in tumor microbiota of HNSCC patients with poor prognosis. However, a richer tumor microbiota with greater abundances of genera Bacillus, and Lactobacillus and Sphingomonas was characterized in the patients with favorable prognosis.The ratio of these differentially abundant taxa, microbial dysbiosis index (MDI), was significantly associated with OS (hazard ratio [HR], 4.67, 95% confidence interval [CI], 2.51 to 8.69,P < 0.001) and DFS (HR, 2.89; 95% CI, 1.74 to 4.80, P < 0.001) independently of age, tumor size, lymph node metastasis, differentiation and p16 status. The risk score of multivariate Cox regression exhibited an excellent performance for estimating three-year OS (AUC of 0.826). We also found a richer tumor microbiota was correlated with moderate peritumoral inflammatory infiltration. CONCLUSION: These results indicate that tumor microbiota associates with outcomes of HNSCC patients.
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Neoplasias de Cabeça e Pescoço , Microbiota , Disbiose , Humanos , RNA Ribossômico 16S/genética , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: The helix-loop-helix (HLH) protein Id-1 (inhibitor of DNA binding/differentiation) has been demonstrated to play an important role in tumor development. Our previous in vitro research has shown that Id-1 is a potential target in the treatment of human adenoid cystic carcinoma (ACCM). The purpose of this study was to analyze the influence of Id inhibition on ACCM in mice. MATERIALS AND METHODS: To suppress the expression of Id-1 gene, we used lentivirus-mediated RNA interference to silence the Id-1 gene post-transcriptionally in ACCM models that stably express GFP in mice. Tumor development was evaluated by size measurement. Effects of Id-1 siRNA on mRNA and protein expression of Id-1 were analyzed using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting respectively. Ki-67 expression was measured by immunohistochemistry. In vitro studies of Hoechst staining for cell apoptosis, Boyden-chamber assay for cell invasion, and MTT-tests for cell growth were performed as well. RESULTS: Id-1 knockdown resulted in inhibition of tumor growth in mice. Id-1 siRNA significantly decreased not only Id-1 in mRNA and protein level, but also Ki-67 expression. In addition, apoptosis was induced and cell proliferation activity and invasion were significantly reduced. CONCLUSIONS: Lentivirus-mediated gene knockdown by silencing Id-1 constitute a valid methodological approach, which may represent an attractive, potent and specific therapeutic tool for the treatment of ACCM.
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Carcinoma Adenoide Cístico/patologia , Proliferação de Células , Inativação Gênica/fisiologia , Proteína 1 Inibidora de Diferenciação/antagonistas & inibidores , Proteína 1 Inibidora de Diferenciação/genética , Interferência de RNA/fisiologia , Animais , Apoptose/fisiologia , Carcinoma Adenoide Cístico/fisiopatologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Regulação Neoplásica da Expressão Gênica/fisiologia , Proteínas de Fluorescência Verde/genética , Humanos , Proteína 1 Inibidora de Diferenciação/fisiologia , Lentivirus/genética , Masculino , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
AIMS: Lymphatic vessel density (LVD) for the evaluation of tumor metastasis and prognosis remains controversial. The aim of this study was to elucidate the association between tumor cells and lymphatic vessels, and evaluate LVD in oral squamous cell carcinoma (OSCC). MAIN METHODS: 128 OSCC cases were used to determine the expression of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and vascular endothelial growth factor C (VEGF-C). Mann-Whitney or Kruskal-Wallis tests were employed to analyze the association between clinicopathological data and intratumoral LVD (ILVD), peritumoral LVD (PLVD), and VEGF-C; comparisons between ILVD and PLVD were made with t-test. Correlations between LVD and VEGF-C were analyzed by Spearman's correlation coefficient. Disease-specific survival curves were obtained with Kaplan-Meier method and compared using the log-rank test. Cox multiple regression was used to clarify the independent effect of clinicopathological data on clinical outcome. KEY FINDINGS: Tumor tissues were positively stained with LYVE-1 and VEGF-C. Both tumor metastasis and recurrence were associated with ILVD. A significant association between ILVD and VEGF-C expression was observed (P < 0.05). A significant association between high ILVD and poor disease-specific survival was observed (P < 0.05). SIGNIFICANCE: This study showed that ILVD was significantly associated with increased lymphatic metastasis, tumor recurrence, and reduced disease-specific survival in patients with OSCC. ILVD could be an indicator to predict the prognosis of OSCC.
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Vasos Linfáticos/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , China/epidemiologia , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Linfangiogênese , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/patologia , Neovascularização Patológica/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Fator C de Crescimento do Endotélio Vascular/análise , Fator C de Crescimento do Endotélio Vascular/metabolismo , Proteínas de Transporte Vesicular/análise , Proteínas de Transporte Vesicular/metabolismoRESUMO
Patients with human papillomavirus (HPV) negative oral squamous cell carcinoma (OSCC) generally have poor clinical outcomes and worse responses to radiotherapy. It is urgent to explore the underlining mechanisms of the distinct prognoses between HPV negative and HPV positive OSCC and to develop effective therapy strategy to increase the survival rate of HPV negative OSCC patients. We conducted a retrospective cohort of 99 resected OSCC patients to evaluate the prognosis of HPV negative and HPV positive OSCC patients receiving radiation or not. We further addressed the association of CD68+ macrophage infiltration with HPV status and the effects on survival of OSCC patients. We also used the TCGA-OSCC cohort for further verification. Based on the cohort study, we applied a synthetic dsRNA polymer, polyriboinosinic-polyribocytidylic acid (poly(I:C)), on CAL-27 (HPV negative OSCC cells). We co-cultured its condition medium with THP-1 derived macrophage and examined the cytokines and macrophage migration. We found that high CD68+ macrophage infiltration associated with poor overall survival in HPV negative OSCC patients receiving radiation. In vitro, poly(I:C) could induce apoptosis and enhance the radiosensitivity, but increase macrophage recruitment. Targeting HMGB1 could inhibit IL-6 induction and macrophage recruitment. Our findings indicated that CD68+ macrophage might play an important role in the outcomes of HPV negative OSCC patients receiving radiation. Our findings also suggested that radiation combined poly(I:C) might be a potential therapy strategy to increase the radiation response and prognosis of HPV negative OSCC. Notably, HMGB1 should be targeted to inhibit macrophage recruitment and enhance overall therapy effects.
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AIMS: Infantile hemangioma (IH) is one of the most common tumors in infancy, which etiology and pathogenesis has not been fully elucidated, hypoxia and abnormal glucose metabolism is regarded as critical pathogenic factors. This study investigated the expression and function of glycolysis-associated molecules (GLUT1, HK2, PFKFB3, PKM2, and LDHA) under normoxic and hypoxic conditions to further understand the pathogenesis of IH. MAIN METHODS: Hemangioma-derived endothelial cells (HemECs) were isolated from proliferating phase infantile hemangiomas and identified by immunofluorescence. HemECs and human umbilical vein endothelial cells (HUVECs) were cultured under normoxic and hypoxic conditions. RNA and protein expression of glycolysis-associated molecules were analyzed by quantitative real-time RT-PCR, western blotting, and immunohistochemistry. Glucose consumption, ATP production and lactate production were measured. Glycolysis-associated molecules were inhibited by WZB117, 3BP, 3PO, SKN, and GSK 2837808A and the resulting effects on HemECs proliferation, migration, and tube formation were quantified. KEY FINDINGS: Glycolysis-associated molecules were highly expressed at both mRNA and protein levels in HemECs compared with HUVECs (P < 0.05). Glucose consumption and ATP production were higher in HemECs than in HUVECs, while lactate production in HemECs was lower than in HUVECs (P < 0.05). Inhibition of some glycolysis-associated molecules reduced the proliferation, migration, and tube formation capacity of HemECs (P < 0.05). SIGNIFICANCE: Our study revealed that glycolysis-associated molecules were highly expressed in IH. Glucose metabolismin HemECs differed from normal endothelial cells. Altering the expression of glycolysis-associated molecules may influence the phenotype of HemECs and provide new therapeutic approaches to the successful treatment of IH.
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Glicólise/fisiologia , Hemangioma/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , China , Feminino , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glicólise/genética , Hemangioma/fisiopatologia , Hexoquinase/genética , Hexoquinase/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Hipóxia , Lactente , Recém-Nascido , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Masculino , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/genéticaRESUMO
DNA-binding protein inhibitor ID-1 (ID-1) plays a vital role in the development of cancer. In the present study, ID-1 expression in oral squamous cell carcinoma (OSCC), and its association with prognosis were investigated in 128 patients with OSCC, treated at the Qilu Hospital of Shandong University and followed up for an additional 10 years. Immunohistochemical analysis was performed to detect ID-1 expression, and the association between ID-1 expression and recurrence, and estimated disease-specific survival (DSS) time were subsequently analyzed using the Mann-Whitney U test and the Kaplan-Meier method, respectively. In addition, the log-rank test was implemented to compare the survival curves and multivariate Cox proportional hazards analysis was performed to assess the prognostic value of ID-1. The results demonstrated that ID-1 was highly expressed in the majority of OSCC tissues investigated, and ID-1 expression was significantly higher in cases with recurrence of local tumors and lymph node metastasis. Furthermore, higher ID-1 expression levels were associated with a shorter DSS time. Taken together, the results of the present study suggest that ID-1 may serve as an independent prognostic factor to predict DSS time in patients with OSCC.
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OBJECTIVE: To investigate the expression and role of human Dachshund homolog 1 (DACH1) in the tongue squamous cell carcinoma (TSCC). STUDY DESIGN: To explore the expression, regulation, and mechanism of DACH1 in TSCC, nine samples of fresh tumor and adjacent tissues, 51 samples of paraffin-embedded TSCC and paired adjacent tissues, and TSCC cell line SCC-25 were examined. Immunohistochemistry, real-time polymerase chain reaction, Western blot, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, Transwell, adhesion assays, and flow cytometry were used. RESULTS: The DACH1 expression level was significantly lower in tumors than in the adjacent tissues, and such low expression was associated with poor differentiation of tumors, late clinical stage, and lymph node metastasis. Moreover, overexpression of DACH1 might promote apoptosis and inhibit the proliferation, migration, and adhesion of SCC-25 cells. CONCLUSIONS: DACH1 may be a potential molecular target for the therapy of recurrent and metastatic TSCC.
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Carcinoma de Células Escamosas/metabolismo , Proteínas do Olho/metabolismo , Neoplasias da Língua/metabolismo , Fatores de Transcrição/metabolismo , Apoptose , Western Blotting , Carcinoma de Células Escamosas/patologia , Adesão Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias da Língua/patologiaRESUMO
Our previous study demonstrated that overexpression of Id-1 (inhibitor of differentiation/DNA binding) was associated with lymphatic metastasis in human oral squamous cell carcinoma (OSCC). In this study, we further unveiled the association of Id-1 with vascular endothelial growth factor-C (VEGF-C) and peritumoral lymphatic vessel density (PLVD), and the effect of silencing Id-1 on inhibiting lymphangiogenesis in OSCC. We found that Id-1 was associated with VEGF-C (r=0.569, p<0.001) and PLVD (r=0.240, p<0.001) in OSCC. Lentivirus-mediated RNA interference targeting Id-1 in an OSCC cell line Tca8113 resulted in down-regulation of VEGF-C (p=0.003, 0.007). Moreover, when Id-1 was suppressed by injecting Id-1-siRNA-lentivirus into the transplanted tumors in nude mice, VEGF-C was down-regulated (p=0.018) and the PLVD decreased (p=0.001). Our results suggest that Id-1 was correlated with lymphangiogenesis in OSCC. Silencing Id-1 could inhibit lymphangiogenesis through down-regulation of VEGF-C and it might be a promising treatment modality for the lymphatic metastasis of OSCC.
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Carcinoma de Células Escamosas/genética , Inativação Gênica , Proteína 1 Inibidora de Diferenciação/genética , Linfangiogênese/genética , Neoplasias Bucais/genética , Fator C de Crescimento do Endotélio Vascular/metabolismo , Animais , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Inativação Gênica/fisiologia , Humanos , Proteína 1 Inibidora de Diferenciação/metabolismo , Metástase Linfática , Camundongos , Camundongos Nus , Neoplasias Bucais/metabolismo , Fator C de Crescimento do Endotélio Vascular/genéticaRESUMO
OBJECTIVE: To establish a novel nude mice model which can be visualized in real time and detected in a continuous and dynamic way for the development and metastasis of adenoid cystic carcinoma. METHODS: Human adenoid cystic carcinoma cells, ACCM cell line, were infected with retroviral vector of pLEGFP-N1 and then screened for a single colony of ACCM-GFP cells. Cell proliferation and morphological analysis were conducted for ACCM and ACCM-GFP cells. Nude mice lingual carcinoma model was set up with ACCM-GFP cells injection and real time observation with fluorescence imaging on ACCM-GFP tumors was performed subsequently. Histological assay was analyzed for ACCM and ACCM-GFP tumors as well. RESULTS: ACCM-GFP cells were able to express GFP stably in the long term. ACCM and ACCM-GFP cells showed no significant difference in cell proliferation and morphology, and no significant difference of histological characteristics in vivo could be found between ACCM and ACCM-GFP tumors. Tumor development could be monitored in real time with fluorescence imaging system in vivo. CONCLUSION: GFP-expressing ACCM tumor model can be applied to detect and observe its development in the long term in a noninvasive, real time and dynamic way. It is also a kind of ideal in vivo mouse model for adenoid cystic carcinoma research.
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Carcinoma Adenoide Cístico , Proteínas de Fluorescência Verde , Animais , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos NusRESUMO
We analyzed the expression of Id-1 in oral squamous cell carcinoma (OSCC) immunohistochemically, and investigated the association of Id-1 expression with tumor angiogenesis and clinical prognosis. Overexpression of Id-1 protein was found in 83 out of 128 cases (64.8%). The expression of Id-1 was significantly associated with tumor size (p=0.013), lymph node metastasis (p=0.001), tumor stage (p=0.031) and tumor recurrence (p=0.003). Moreover, Id-1 expression was significantly correlated with intratumoral microvessel density (MVD) (r=0.223, p=0.011). The results suggest that overexpression of Id-1 was correlated with tumor angiogenesis and poor clinical outcome.
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Carcinoma de Células Escamosas , Proteína 1 Inibidora de Diferenciação/metabolismo , Neoplasias Bucais , Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular/metabolismo , Carcinoma de Células Escamosas/irrigação sanguínea , Carcinoma de Células Escamosas/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/irrigação sanguínea , Neoplasias Bucais/metabolismo , Neovascularização Patológica/patologia , Prognóstico , Fatores de Risco , Resultado do Tratamento , Carga TumoralRESUMO
The aim of this study was to examine the Kif2a expression and its role in tumor progression, invasion and metastasis in squamous cell carcinoma of the oral tongue (SCCOT). The study included 44 cases of primary tumor and the corresponding adjacent tissues, 20 cases of primary tumor with lymph node metastasis. Immunohistochemistry was used to observe the Kif2a expression and its correlation with clinicopathologic factors in oral tongue cancer. The immunohistochemistry showed that Kif2a expression was stronger in oral tongue cancer tissues than in paired adjacent tissues (P<0.01), and the higher expression of Kif2a was also significantly associated with lymph node metastasis (P<0.01), tumor clinical stage (P<0.01). In addition, in vitro results from transwell chamber assay showed that Tca8113 cells transfected with Kif2a-siRNA had a decreased migratory ability (P<0.01) compared to nonsense-siRNA-transfected cells. Therefore we speculate the overexpression of Kif2a might be involved in the progression, invasion and metastasis of SCCOT and Kif2a should be as a predictor for prognosis.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Cinesinas/metabolismo , Neoplasias da Língua/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Língua/patologiaRESUMO
To investigate the expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its effects on angiogenesis and lymphangiogenesis in oral carcinoma. Immunohistochemistry was used to study the expression of CEACAM1, LYVE1 and CD31, double-labelling immunofluorescence was used to detect the co-expression of CEACAM1 and LYVE1, and double-labelling immunohistochemistry was performed to observe the co-expression of LYVE1 and CD31 in vessels. Membranous CEACAM1 was expressed in well-differentiated squamous cell carcinoma and cytoplastic CEACAM1 in poorly and moderately differentiated carcinoma (P<0.05). More CEACAM1-positive vessels were observed in CEACAM1-positive tumors with cytoplasmic expression than with membranous expression (P<0.001). Co-expression of CEACAM1 and LYVE1, LYVE1 and CD31 in vessels was more common in CEACAM1-positive tumors with cytoplasmic expression than with membranous expression (P<0.001). CEACAM1 has different distribution in oral carcinoma. Membranous CEACAM1 inhibits angiogenesis and lymphangiogenesis, but cytoplasmic CEACAM1 promotes angiogenesis, and even promotes lymphangiogenesis by mediating the transformation of vascular endothelial cells (VECs) into lymphatic endothelial cells (LECs).
Assuntos
Antígenos CD/metabolismo , Antígenos CD/fisiologia , Carcinoma de Células Escamosas/metabolismo , Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/fisiologia , Linfangiogênese/fisiologia , Neoplasias Bucais/metabolismo , Proteínas de Neoplasias/fisiologia , Neovascularização Patológica/etiologia , Carcinoma de Células Escamosas/irrigação sanguínea , Células Endoteliais/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/irrigação sanguínea , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/patologia , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Proteínas de Transporte Vesicular/metabolismoRESUMO
OBJECTIVE: To culture and amplify the young rabbit's bone marrow stromal cells (BMSCs) in vitro, and to observe the effect of hypothermia on the cells' growing behavior and biological function. METHODS: BMSCs were acquired from the rabbit' tibia bone marrow and induced to mature osteoblasts in vitro. The cultured cells growing well in vitro were preserved in liquid nitrogen. The anabiotic cells having cryopreserved for 1 week were chosen as the experimental group, and the routine 7th generation as the control group. Their biological function in comparion by the examination of morphological changes, cells' proliferation ability, colone forming ratio, synthesis ability of ALP and protein, mineralized nodes forming ability were observed. RESULTS: As contrast to the control groups, the anabiotic cells also grew and proliferated well in vitro except a little more slowly than before. They had the similar general shape in all the time segments, but a little differences in cells' ultrastructure. The experimental groups also had the typical characters of mature osteoblasts, and high abilities of the synthesis of ALP and proteins. The statistic data showed that these two groups had no significant difference (P > 0.05). CONCLUSION: The cryopreserved osteoblasts had the same biological functions and the similar growing behaviors as before. These results suggest that it is practical to use the cryopreserved osteoblasts for further study on bone tissue engineering.