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Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 04/2010; 45(4):237-8.
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Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 03/2009; 67(2):431-5. · 1.58 Impact Factor
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ABSTRACT: It has been speculated that chemokines and neurotransmitters might be involved in the organ-specific development of metastases because cancer metastasis is similar to the regulation of migratory activity in leukocytes. Here, we aimed to examine the expression of beta(2)-adrenergic receptor (beta(2)-AR) in oral squamous cell carcinoma (OSCC), and to investigate its correlation with tumor development and metastasis.
Expression of beta(2)-AR was examined in 65 cases of OSCC specimens, 10 cases of normal oral mucosa, and two cell lines using immunohistochemistry, Western blot and RT-PCR. The differences in beta(2)-AR expression between various groups were evaluated using SPSS 13.0 Statistical Software. Cell proliferation assays were assayed by beta-adrenergic receptors agonists (norepinephrine) and antagonists (propranolol). Norepinephrine-mediated cell migration was assayed in Matrigel-coated chemotaxis chamber.
beta(2)-AR was highly expressed on OSCC compared to normal controls. In OSCC, positive beta(2)-AR expression was significantly correlated with cervical lymph node metastasis (P = 0.001), age (P = 0.003), tumor size (P = 0.001) and clinical stage (P = 0.001), but not with gender. RT-PCR and Western blot also confirmed positive beta(2)-AR expression in OSCC and TCa8113 cell line, and negative beta(2)-AR expression in normal oral mucosa and ACC cell line. beta-adrenoreceptor agonist (norepinephrine) was a potent mitogen for TCa8113 and ACC cell lines, and completely inhibited by the selective antagonist of beta-adrenergic receptors (propranolol). Norepinephrine induced migratory activity of OSCC cells in a dose-dependent manner.
Increased expression of beta(2)-AR may play an important role in the formation and metastasis of OSCC.
Journal of Oral Pathology and Medicine 01/2009; 38(4):371-6. · 1.63 Impact Factor
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ABSTRACT: To investigate the expression of chemokine receptor CCR7 in oral squamous cell carcinoma (OSCC) and its possible role in directional neck lymph node metastasis.
The expression of chemokine receptor CCR7 was examined in 85 cases of OSCC, normal oral mucosa, and Tca8113 and adenoid cystic carcinoma (ACC-M) cell lines using immunohistochemistry, RT-PCR and Western blotting. The relationship between the expression and clinicopathological factors of OSCC was analyzed. After treatment with or without CCR7 antibody, in vitro adhesion assay was performed to compare the adhesion of Tca8113 and ACC-M cells to lymph nodes.
CCR7 was expressed in 66% (56/85) of OSCC cases, and there was a significant difference in CCR7 expression between metastasis group (31/39, 79%) and non-metastasis group (25/46, 54%). RT-PCR and Western blotting also confirmed the presence of positive CCR7 expression in OSCC. Tca8113 cells expressing CCR7 showed stronger ability to adhere to lymph nodes as compared to CCR7-negative ACC-M cells and could be actively inhibited by CCR7 antibody.
CCR7 may play an important role in the development and lymph node metastasis of oral squamous cell carcinoma.
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 11/2008; 43(10):592-6.
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ABSTRACT: Tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. The present study was designed to examine the expression of chemokine receptor CCR7 in oral squamous cell carcinoma (OSCC), and to investigate the possible role of CCR7/CCL21 interaction in neck lymph node metastasis of OSCC. By using immunohistochemistry, RT-PCR and Western Blot, expression of CCR7 was examined in 85 cases of oral squamous cell carcinoma, and Tca8113 and ACC cell lines. CCL21-mediated cell migration was assayed in Matrigel-coated chemotaxis chamber. In vitro adhesion assay was shown for banding of tumor cell lines to submandibular lymph nodes with or without anti-CCR7 antibody treatment. Immunohistochemical staining showed 65.9% (56/85) of positive CCR7 expression in OSCC tissues. CCR7 expression was significantly higher in patients with lymph node metastasis compared with those without lymph node metastasis (P=0.015) and was also associated with tumor size (P=0.014), and clinical stage (P=0.009). RT-PCR and Western Blot also confirmed positive CCR7 expression in oral squamous cell carcinoma and Tca8113 cell line, and negative CCR7 expression in normal oral mucosa and ACC cell line. CCL21 stimulation increased the ability of CCR7-positive Tca8113 cells passing through the Matrigel membrane. CCR7-positive Tca8113 cells also showed stronger adhesion to lymph nodes, which could be partly blocked by anti-CCR7 antibody incubation. These results indicated that the chemotactic CCR7/CCL21 interaction may be a possible mechanism for induction of directional lymph node metastasis by oral squamous cell carcinoma.
Oral Oncology 09/2008; 45(6):480-5. · 2.86 Impact Factor
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ABSTRACT: Dystroglycan (DG), a non-integrin adhesion molecule, is formed by two subunits, alpha- and beta-DG, which bind to extracellular matrix molecules and cytoskeleton. DG expression is frequently reduced in human cancers and has been related to tumor grade and aggressiveness. The exact proteolytic processing of beta-DG remains largely unknown. In this study, we investigated the correlation of beta-DG degradation with invasiveness in oral squamous cell carcinoma (OSCC) and its possible processing by matrix metalloproteinases (MMP). Immunohistochemical staining was used to assess beta-DG expression in 60 cases of OSCC. The effects of the MMP inhibitor 1,10-phenanthroline on tumour cell invasion and beta-DG degradation were investigated using in vitro invasion assays and immunoblot analysis. Co-immunoprecipitation and N-terminal sequencing were performed to determine the possible cleavage site of beta-DG by MMP. The alpha- and beta-DG expression was reduced or lost in OSCC. In four cell lines studied (SCC-4, SCC-9, SCC-15 and SCC-25), Western blot revealed a 30kDa fragment of beta-dystroglycan (beta-DG30) in addition to beta-DG itself. beta-DG degradation was almost abolished using 1,10-phenanthroline and there was a significant decrease in tumor cell invasion. The N-terminal sequence of beta-DG30 was detected as Ile-Asn-Thr-Asn, or Ile-Val-Thr-Gln. We conclude that beta-DG degradation may play a role both in OSCC invasion and metastasis. MMP activity seems to be one mechanism for beta-DG processing into beta-DG30.
Oral Oncology 06/2008; 44(12):1139-46. · 2.86 Impact Factor
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ABSTRACT: Eph-ephrin binding has been linked to tumor biology and VEGF has been reported to participate in the tumor angiogenesis regulated by Eph-ephrin. The present study was designed to evaluate the expression of EphA2 and VEGF in relation to angiogenesis and clinical outcome in squamous cell carcinoma of oral tongue. Immunohistochemical staining was used to determine the protein expression levels of EphA2 and VEGF in 59 surgically resected tongue carcinomas and 10 tumor-free mucosas. In all cases, microvessel density (MVD) was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters. Both EphA2 and VEGF staining activities in squamous cell carcinoma of oral tongue were more significant than those in normal mucosa (P<0.01). MVD had significant correlations with EphA2 and VEGF expression (P<0.01). The EphA2, VEGF, and MVD were significantly correlated with tumor size, clinical stage, lymph invasion, recurrence, and distant metastasis (P<0.05). Multivariate analysis showed EphA2, VEGF expression, MVD, and clinical stage had an independent prognostic effect on overall survival. We conclude that the overexpression of EphA2 and VEGF are related to malignancy in squamous cell carcinoma of oral tongue. Clinical outcomes raised the possibility that the overexpression of those proteins might contribute to tumor angiogenesis and have prognostic value in tongue cancer.
Oral Oncology 05/2008; 44(12):1110-7. · 2.86 Impact Factor
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ABSTRACT: To investigate both serum vascular endothelial growth factor (VEGF) concentrations and VEGF expression in patients with oral squamous cell carcinoma (OSCC), and to clarify whether upregulation of VEGF in OSCC patients is associated with increased microvessel density and various clinicopathologic features of patients with OSCC.
The study population included 31 patients with OSCC and 10 normal individuals. Concentration of serum VEGF was determined by using an ELISA kit. Immunohistochemistry was used to evaluate VEGF expression and microvessel density in OSCC.
Our results showed that both serum VEGF levels and VEGF positivity were closely associated with both regional lymph node status and clinical stage of patients with OSCC. Increased microvessel density in oral cancer tissues was significantly higher in VEGF-positive tumors than VEGF-negative tumors.
Our present study indicated that upregulation of VEGF in oral cancer was correlated with both tumor angiogenesis and disease severity.
Journal of Oral and Maxillofacial Surgery 02/2007; 65(1):17-21. · 1.64 Impact Factor
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ABSTRACT: To study the characteristics of mandible and condyle in Dmp1 gene knockout mice, and to investigate the role of Dmp1 in the osteogenesis and mineralization of bone and cartilage.
Dmp1-/-mice were executed at birth, 2 weeks, 2 months, 3 months and 5 months, and the mandible was taken out for physical, radiography, transmission electron microscopic, and histological examination. The difference between Dmp1 knockout mouse (ko) and wild type mouse (wt) in bone development, bone densitometry and histology were compared.
There were obvious changes in the mandible and condyle of Dmp1-/-mouse, such as incomplete ossification, low density, decreased volume and condyle cartilage degeneration.
Dmp1 is the key factor in the formation of growth plates and secondary ossification center, and plays an important role in the process of bone and cartilage formation and bone nodule remodeling. Dmp1 may be the candidate gene that controls the development of mandible and cartilage.
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 08/2005; 40(4):335-7.
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ABSTRACT: Angiogenesis is a crucial step in the successful growth, invasion, and metastasis of a tumor. It has been popularly accepted that vascular endothelial growth factor (VEGF) is the most potent angiogenic factor in tumor angiogenesis. As another possible star molecule responsible for tumor angiogenesis, the role of nitric oxide (NO) in tumor biology has gained much attention in recent years. The aim of this study was to investigate whether the expression of endothelial nitric oxide synthase (eNOS) and VEGF in oral squamous cell carcinoma (OSCC) is associated with angiogenesis. The present study also made a preliminary exploration of the possible cross-talking existing between eNOS and VEGF during tumor angiogenesis.
In this study, expression of eNOS and VEGF were studied immunohistochemically in tissue sections from 40 patients with OSCC and 20 normal controls. To exclude eNOS antibody cross-reactivity with inducible or neuronal nitric oxide (iNOS or nNOS), eNOS expression was confirmed by using an eNOS mRNA in situ hybridization kit. The intratumoral microvessels were highlighted by immunostaining with anti-factor VIII-related antigen monoclonal antibody and counted as well-established methods. Then, chi-square test or Student's t-test was performed to study the correlations between the expression of eNOS and VEGF, microvessel density (MVD), and various clinicopathologic factors.
Both eNOS and VEGF expression significantly increased in OSCC tissues, with a positive rate of 47.5% and 50%, respectively. The average MVD in OSCC tissues was 23.45 per high-power field (HPF), showing an obvious association with lymph node metastasis and clinical stages of patients with OSCC. Either eNOS or VEGF positivity was correlated with vessel involvement and OSCC progression. The mean MVD was significantly higher in eNOS- or VEGF-positive tumors than in eNOS- or VEGF-negative tumors. An obvious, correlation was also seen between eNOS and VEGF expression in OSCC tissues in this study.
Overexpression of eNOS and VEGF might make an important contribution to the tumor angiogenesis in OSCC. NO generation by eNOS might be implicated in the VEGF-associated angiogenic process. Further investigation of the possible cross-talking between eNOS and VEGF with respect to tumor angiogenesis is necessary.
Journal of Oral Pathology and Medicine 04/2005; 34(3):134-9. · 1.63 Impact Factor
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ABSTRACT: To investigate the method and results of disk reposition in the treatment of traumatogenic TMJ ankylosis.
In 19 cases of traumatogenic ankylosis of TMJ, the dislocated disks were repositioned during anthroplasty. In the operation, the dissection of dislocated disk was performed carefully around the TMJ. The disk was repositioned to its anatomic location over the top of condylar stump, then the lateral aspect of the disk was sutured to the soft tissue of zygomatic root.
At the last follow-up examination, interincisal opening distance ranged from 24 to 43 mm in all cases (mean 32.63 mm), which approached or reached the normal level. No recurrence and TMJ symptom were found during the period of follow-up.
The disk repositioning in treatment of traumatogenic TMJ ankylosis is a feasible and effective approach to reconstruct the structure and function and prevent recurrence.
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology 02/2004; 39(1):5-8.
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Journal of Oral and Maxillofacial Surgery 06/2003; 61(5):621-5. · 1.64 Impact Factor
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ABSTRACT: Nitric oxide (NO) is a newly found unstable free radical gas, serving as an important mediator, messenger, and signal transduction molecule and involved in a variety of pathophysiologic processes. Recently, NO has been reported to have cytotoxic effects on several tumor cells as an effector molecule of activated macrophage. The objective of this study was to investigate the effects of exogenous NO on oral squamous cell carcinoma cell line and to try to clarify the possible mechanisms by which it kills tumor cells.
TSCCa cell line, established from a patient with oral squamous cell carcinoma of the tongue, was exposed to various concentrations of exogenous NO that were released from an NO donor, sodium nitroprusside (SNP), for 48 hours. Nitrite/nitrate levels in the culture supernatant were determined with a commercial available NO kit. Both morphologic and ultrastructural changes were evaluated by reverse phase contrast microscopy or transmission electron microscopy. The DNA was harvested from SNP-treated or untreated TSCCa cells and assessed by agarose gel electrophoresis.
SNP released NO into medium in a dose-dependent manner. NO had a concentration-dependent cytotoxicity against TSCCa cells. NO induced tumor cell death through apoptosis, which was characterized by incompleteness of nuclear membrane, disappearance of nucleole and nuclear condensation, chromatin margination, or chromatin homogenization. Agarose gel electrophoresis showed a typical internucleosomal DNA cleavage pattern (DNA ladder), a reliable indicator of apoptosis.
Our results suggested that NO had a tumoricidal potential against oral cancer cells. NO might exert its cytotoxicity as an effector molecule of activated microphage through at least apoptosis.
Journal of Oral and Maxillofacial Surgery 09/2002; 60(8):905-10; discussion 910-1. · 1.64 Impact Factor
