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ABSTRACT: Despite the importance of dentin matrix protein 1 (DMP1) in the formation of mineralized tissue, including dentinogenesis and osteogenesis, its precise role in cementogenesis remains to be clarified fully. The purpose of our study was to demonstrate the ultrastructural immunolocalization of DMP1 in monkey molar tooth cementum. Japanese Macaca fuscata monkeys were fixed by perfusion. The upper molar teeth and accompanying periodontium then were dissected and demineralized with EDTA. Cryosections were obtained, incubated in anti-DMP1 polyclonal antibody, and processed by immunoperoxidase and immunogold labeling. Intense immunoperoxidase staining for DMP1 was observed in acellular extrinsic fiber cementum, particularly in Sharpey's fibers. Cementocyte lacunae with canaliculi showed DMP1 staining in the apical region of the tooth root. Electron immunomicroscopy revealed the close proximity of DMP1 to collagen fibrils in Sharpey's fibers at the mineralization front. Intense immunogold labeling was localized on the walls of the cementocyte lacunae in cellular cementum. These results should contribute to better understanding of the role of DMP1, not only in Sharpey's fiber biomineralization, but also in the maintenance of the cementocyte lacunar space in cementum.
Biotechnic & Histochemistry 03/2012; 87(5):360-5. · 0.67 Impact Factor
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ABSTRACT: This clinical report describes the successful management of a patient who underwent extensive resection of a maxillary cancer, by introduction of a maxillary obturator prosthesis using zygoma implants. The patient was a 57-year-old man with cancer of the upper anterior gingiva. The maxillary bone in the affected region had been extensively excised by radical surgery. Owing to loss of teeth retaining the denture, the existing prosthesis was unstable, and the patient experienced severe speech and mastication disorders. Four zygoma implants (two on each side), and two conventional dental implants (one each at both maxillary tuberosities) were used as denture retainers. The obturator prosthesis was stabilized by the implants, and the patient's oral function improved. High-level compatibility between the implant and surrounding tissue was obtained by mucosal regeneration around the implant. The results suggest that the combination of zygoma and conventional dental implants improves postoperative oral function by facilitating retention of the obturator prostheses.
International Journal of Oral and Maxillofacial Surgery 01/2011; 40(1):113-7. · 1.51 Impact Factor
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ABSTRACT: Radiotherapy is commonly used to treat oral squamous cell carcinoma (OSCC), but its therapeutic effects are unpredictable. To determine which genes correlate with radiation resistance in oral cancer, the authors evaluated radiation sensitivity using a standard colony formation assay with a gene microarray system for seven OSCC cell lines. They found significant associations between dozens of gene-expression levels and radiation resistance of OSCC cell lines. Following analysis of the different radiosensitive cancer cell lines, the friend leukaemia insertion (Fli)-1 gene was selected as a prediction marker gene for OSCC radiotherapy resistance. Fli-1 expression was associated with radiation resistance in OSCC patients. These data help to predict the effects radiation therapy has on OSCC, in turn contributing to the development of alternative radiation therapies.
International Journal of Oral and Maxillofacial Surgery 11/2010; 39(11):1115-9. · 1.51 Impact Factor
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ABSTRACT: The purpose of this study was to measure the bone volume necessary for secondary bone grafting in the alveolar cleft using surgical simulation software based on three-dimensional computed tomography (CT) scan data, to compare this measurement with the actual volume of the bone graft, and to evaluate consistency. The subjects were 13 patients with cleft lip and palate who underwent CT using a cone-beam CT unit (CB-CT) 1 month before surgery, followed by bone grafting with particulate cancellous bone and marrow (PCBM) to close the cleft. The bone volume necessary for grafting was measured based on the CB-CT scan data. Correlation analysis, a test of the population mean between two samples, and Wilcoxon's signed rank test were conducted between these measurements and the actual bone volume (PCBM volume) used for grafting. SPSS was used for statistical analysis, and the level of significance was set below the 5% level. The results showed a significant correlation, with no significant differences between the two in all tests. These results suggest that measuring and preoperatively calculating the bone volume necessary for bone grafting with surgical simulation software using CB-CT scan data is beneficial.
International Journal of Oral and Maxillofacial Surgery 09/2010; 39(9):904-8. · 1.51 Impact Factor
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ABSTRACT: Cancer of the salivary gland is one of the common cancers in the head and the neck regions. This type of cancer develops in the minor and the major salivary glands, and it sometimes metastasizes to other organs, particularly the lung. Morphologic mimicry and similarity in the expression of steroid hormone receptors between salivary gland tumors (SGTs) and breast tumors are well-known phenomena and are occasionally debated in the field of surgical pathology. Progesterone (Pg), one of the female sex steroid hormone, is intimately involved in the development of the mammary gland. Further, it is believed that Pg plays a role in breast cancer progression. However, little is known regarding its role in SGTs. In this study, we used ACCM, a human adenoid cystic carcinoma cell line established from the salivary gland, in order to clarify the role of the Pg receptor (PR) on cell proliferation. No effect of Pg on cell proliferation was observed in the PR-deficient aggressive ACCM cells. However, after introducing PR into the ACCM cells, Pg markedly inhibited the proliferative activity of the cells. This inhibitory effect on cell proliferation was accompanied by p21 upregulation, and Id1 and c-myc downregulation. Moreover, Pg-treated PR transfectants showed significant morphological change; they appeared more flattened and spread out when compared with the ethanol-treated control cells. Our results provided significant insights into the mechanism of suppression of the proliferative property of the cells via the function of PR, and suggested that PR reintroduction therapy might be a viable method of inhibiting human SGT progression.
Endocrine Related Cancer 01/2008; 14(4):1107-16. · 4.36 Impact Factor
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ABSTRACT: Development of new molecular target therapeutic agents is expected to improve clinical outcome, ideally with efficacy in both single and combined treatment modalities. Because of the potential for affecting multiple signaling pathways, inhibition of the molecular chaperone heat shock protein 90 (Hsp90) may provide a strategy for enhancing tumor cell radiation sensitivity. Therefore, we have investigated the effects of Hsp90 inhibitor 17-Allylamino-17-demethoxygeldanamycin (17-AAG) on radiation sensitivity of human tumor cells in vitro. We evaluated the effects of 17-AAG using oral squamous cell carcinoma (OSCC) cell lines (HSC2, HSC3 and HSC4), including two types of SAS cells with a wild-type (SAS/neo), or a mutated p53 status (SAS/Trp248). Apoptosis and clonogenic survival were examined after exposure of the cells to radiation. For mechanistic insight, we analyzed cell cycle, several signaling factors and molecular markers including Akt, Raf-1, p38 MAPK, Cdc25B, Cdc25C, Cdk2 and p21. Treatment of OSCC cell lines with 17-AAG resulted in cytotoxicity and, when combined with radiation, enhanced the radiation response. However, the responses depended on p53 status. 17-AAG enhanced the radiation sensitivity significantly and induced apoptosis in the SAS/neo cell which has a wild-type p53. But the radiation sensitizing effect of 17-AAG was limited in the SAS/Trp248 cell which has a mutated p53. We also measured the total levels of several prosurvival and cell cycle signaling proteins. Akt, Raf-1 and Cdc25C expression were down-regulated in 17-AAG-treated cells. These data indicate that 17-AAG inhibits the proliferation and enhances the radiation sensitivity of human OSCC cells in various levels. However, enhancement of radiation sensitivity by the Hsp90 inhibitor depended on p53 status. Therefore, Hsp90 therapy combined with radiation might synergize with conventional therapies in patients with wild-type p53.
International Journal of Oncology 12/2006; 29(5):1111-7. · 2.40 Impact Factor
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ABSTRACT: P16 promoter methylation occurs frequently in oral squamous cell carcinoma (OSCC). For the early detection of tumour-related aberrant DNA, we examined p16 methylation using the methylation-specific polymerase chain reaction (MSP) in tumour and serum samples of 17 OSCC patients. Aberrant p16 methylation was detected in 11 (64.7%) cases of primary OSCC. Of these 11 patients, 6 (54.5%) showed the same alteration in their serum. No methylation was found in control groups. Interestingly, DNA was detected in the serum of 3 out of 4 patients with recurrence. These results suggest that the MSP may be a sensitive and useful method for detecting recurrent OSCC.
International Journal of Oral and Maxillofacial Surgery 05/2006; 35(4):362-5. · 1.51 Impact Factor
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ABSTRACT: We report a case of diffuse sclerosing osteomyelitis of the mandible responded to alendronate, after a poor response to intravenous antibiotics, antibiotic irrigation-perfusion, and decortication. The patient was given an intravenous infusion of 10mg of alendronate. Pain resolved within 24 h. There were no severe adverse events. Increased uptake of 99mTc in the mandible almost completely disappeared 3 months after treatment.
International Journal of Oral and Maxillofacial Surgery 08/2005; 34(5):576-8. · 1.51 Impact Factor
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ABSTRACT: Angiogenesis, the growth of capillary vessels, plays an important role in the metabolic functions of malignant tissues. Tumor growth and malignant transformation are considered to be dominated by uncontrolled angiogenesis. To understand the mechanism of increased vascularity associated with malignant tissues, we immunohistochemically evaluated microvessel density (MVD) and the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet-derived endothelial growth factor (PDGF) in oral cancers. Microvessel density did not differ significantly between normal oral mucosa and epithelial dysplasia, but was significantly increased in tumor tissues. Expression of angiogenic factors was not found in normal oral mucosa, but increased in association with increasing vascularity in OSCC tissue. In tumor tissue, angiogenic factor expression correlated with MVD. MVD in OSCC was related to T stage, tumor differentiation, and stage of invasion. VEGF expression also correlated with tumor differentiation and the stage of invasion. These findings suggest that VEGF might play an important role in tumor angiogenesis of OSCC.
International Journal of Oral and Maxillofacial Surgery 08/2005; 34(5):559-65. · 1.51 Impact Factor
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ABSTRACT: Malignant mesothelioma is a rare tumor arising from the pleura or peritoneum. Distant hematogenous metastasis is seen in more than half of cases, preferentially to the brain, lung, bone and soft tissues [Br. J. Dis. Chest 70 (1976) 246]. There has been only one previous report of this tumor metastasizing to the jaw bone [Pathologica 92 (2000) 273].
International Journal of Oral and Maxillofacial Surgery 01/2005; 33(8):798-800. · 1.51 Impact Factor
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ABSTRACT: Sentinel node navigation surgery (SNNS) has received considerable attention for its role in deciding whether to perform neck dissection in patients with early oral cancer. However, diagnostic accuracy and its intraoperative availability of results remain important concerns. First, we shortened the examination time required for genetic diagnosis. Second, we assessed the quality of the extracted mRNA. Third, 10 patients with early N0 oral cancer underwent SNNS, using our new technique for genetic diagnosis to determine whether neck dissection was required. The examination time of our one-step reverse-transcriptase polymerase chain reaction method using a minicolumn and LightCycler was successfully shortened to 2 h, permitting intraoperative genetic diagnosis. The extracted mRNA was of high quality. Six sentinel nodes in four patients were diagnosed to be metastatic on genetic diagnosis; these patients underwent neck dissection. The other six patients avoided unnecessary surgery. We conclude that intraoperative genetic diagnosis of micrometastasis holds promise of being a sensitive method that can be used to support SNNS.
International Journal of Oral and Maxillofacial Surgery 11/2004; 33(7):670-5. · 1.51 Impact Factor
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ABSTRACT: The p14(ARF), p15(INK4B) and p16(INK4A) genes were localized to 9p21, where genetic alterations have been reported frequently in various human tumors. We performed a molecular analysis of the mechanism of inactivation in cell lines and 32 oral squamous cell carcinoma (OSCC), using deletion screening, PCR-SSCP, methylation-specific-PCR and cycle sequencing. We detected homozygous deletion of p14(ARF)-1Ebeta in 9 (26.5%), of p15(INK4B) in one (3.1%), and of p16(INK4A) in 22 (56.3%) tumor samples. Three mutations were detected in the p16(INK4A) genes. We detected aberrant methylation of the p14(ARF) genes in 14 (43.8%), of the p15(INK4B) gene in 9 (28.1%), and of the p16(INK4A) gene in 16 (50.0%) tumor samples. Altogether, 87.5% of the samples harbored at least one of the alterations in the p14(ARF), p15(INK4B), and p16(INK4A) genes, indicating that the frequent inactivation of these genes may be an important mechanism during OSCC development.
Oral Oncology 10/2001; 37(6):498-504. · 2.86 Impact Factor
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S Shintani,
M Mihara,
N Terakado,
Y Nakahara,
T Matsumura,
Y Kohno,
H Ohyama,
J McBride,
R Kent,
R Todd,
T Tsuji,
D T Wong
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ABSTRACT: p12DOC-1 is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities. Expression of p12DOC-1 is reduced and/or lost in tumor tissues. The purpose of this study is to correlate in vivo the expression of p12DOC-1 in oral cancer tissues by immunohistochemistry with clinical and pathological parameters.
Twenty-five cases of normal oral mucosa and 127 cases of oral squamous cell carcinomas were evaluated. Patients' charts were reviewed for clinical, pathological, and 10-year survival data. Because p12DOC-1 is a growth suppressor and associates with CDK2, parallel immunostaining was done for proliferating cell nuclear antigen and CDK2 to evaluate cell proliferation and potential correlation with CDK2.
Our results showed that strong p12DOC-1 staining was uniformly seen in normal oral mucosa. p12DOC-1 staining was reduced or absent in 81 cases (63.8%) of oral squamous cell carcinomas. Decreased p12DOC-1 staining (<25% of cells stained) correlated with tumor mode of invasion (P = 0.001) and higher proliferating cell nuclear antigen (P = 0.0028) and CDK2 (P = 0.0020) expression. Survival analysis showed significant correlation of low p12DOC-1 expression with the risk of cervical lymph node metastasis (P = 0.001) and patients' 10-year survival status (P = 0.0214).
These results allow us to conclude that reduction of p12DOC-1 protein expression is a frequent event in oral cancers. Intratumor immunohistochemical evaluation of p12DOC-1 expression can be an adjunctive prognostic indicator for patients with oral cancer.
Clinical Cancer Research 09/2001; 7(9):2776-82. · 7.74 Impact Factor
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ABSTRACT: Overexpression of cyclin D1, a G1 cell cycle regulator, is often found in many different tumor types, including oral squamous cell carcinomas (SCC). Recent laboratory experiments have demonstrated that cyclin D1 levels can influence radiosensitivity in various cell lines. This study evaluated the relationship between cyclin D1 expression levels and radiosensitivity in nine oral SCC cell lines (HSC2, HSC3, HSC4, SCC15, SCC25, SCC66, SCC111, Ca9-22, and NAN2) and 41 clinical patients with oral SCC who underwent preoperative radiation therapy. Radiosensitivity of the nine oral SCC cell lines differed greatly in their response to radiation, assessed by a standard colony formation assay. Likewise, the expression of cyclin D1 varied, and the magnitude of the cyclin D1 expression correlated with increased tumor radiosensitivity. The similar significant association between the response to preoperative radiation therapy and cyclin D1 overexpression was observed in the oral SCC patients who were treated with preoperative radiation therapy. These results suggest that cyclin D1 expression levels correlate to radiosensitivity and could be used to predict the effectiveness of radiation therapy on oral SCC.
International Journal of Cancer 07/2001; 96(3):159-65. · 5.44 Impact Factor
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ABSTRACT: Many studies focused on the tumour thickness in oral squamous cell carcinomas, suggesting a relationship with the occurrence of cervical metastasis. Accurate preoperative assessment of the tumour thickness of oral cancer would provide useful information for targeting those patients who need elective treatment of the neck. Some useful diagnostic aids to evaluate oral cancer are computed tomography (CT), magnetic resonance imaging (MRI), and intraoral ultrasonography. The purpose of the present study is to compare intraoral ultrasonography with CT and MRI in delineating the disease extent and in measuring the tumour thickness of oral carcinoma. Thirty-nine patients with oral cancer were preoperatively evaluated with intraoral ultrasonography, and CT, and in 26 of them MRI was carried out. High-quality ultrasonographic images were obtained and the tumour thickness was measured within 1 mm. However, in most tumours less than 5.0 mm in thickness, CT and MRI could not detect a sufficient density difference from the normal tissue to accurately delineate the extent of the tumour. There was a significant correlation between measurements by intraoral ultrasonography and the histological sections. The present study shows that ultrasonography is superior to CT and MRI in assessment of the primary lesion of oral carcinoma.
International Journal of Oral and Maxillofacial Surgery 05/2001; 30(2):139-43. · 1.51 Impact Factor
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ABSTRACT: Cyclins and cyclin-dependent kinases (CDKs) play key roles in cell cycle regulation, a process of which dysregulation can lead to uncontrolled cell growth and hence to cancer. We have already reported the alteration of CDK4 and cyclin D1 expression in oral cancer. In this study, we examined by immunohistochemistry the expression of CDK2, and cyclins A and E in 20 normal oral mucosa, 42 dysplastic epithelia, and 103 oral squamous cell carcinomas (SCCs). The expressions of CDK2, and cyclins A and E were not detected in the normal epithelium and significantly altered from epithelial dysplasia to SCC. While there were no significant correlations between the expression of cyclins A, E and the patients' survival, CDK2 expression was significantly correlated with lymph node involvement (P = 0.025), tumor differentiation (P = 0.032), mode of tumor invasion (P = 0.017), and shorter survival period (P = 0.0173). These results suggest that the elevated expression of CDK2 is a critical factor in oral cancer progression and can be used as a negative predictive marker of the patients' prognosis.
Japanese journal of cancer research: Gann 04/2001; 92(3):352-60.
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ABSTRACT: p16(INK4A) inactivation was analyzed in ten squamous cell carcinoma (SCC) cell lines and 32 primary SCCs, using the polymerase chain reaction (PCR), PCR-single-strand conformation polymorphism, methylation-specific PCR, and cycle sequencing. In the study of cell lines, we detected three deletions in exon 1alpha and exon 2, and detected two methylations. Among tumor samples, we detected the homozygous deletions (HDs) of 43.8% in exon 1alpha 34.4% in exon 2, and methylation was found in 50.0%. The lack of p16(INK4A) with immunohistochemistry was detected in 71.9% and matched the alteration of p16(INK4A) gene. These results suggest that p16(INK4A) inactivation is predominantly caused by HD and methylation, and immunohistochemical evaluation of p16(INK4A) is a useful method.
Cancer Letters 03/2001; 163(2):221-8. · 4.24 Impact Factor
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ABSTRACT: Immunohistochemical analysis of Rb, p16(INK4A) and cyclin D1 expression was performed on 78 oral squamous cell carcinoma (SCC), 46 leukoplakia, and 20 normal mucosa. Rb and p16(INK4A) expression were observed in all normal mucosa and most of leukoplakia. Lack of Rb and p16(INK4A) was observed in 56.4 and 67.9% of SCC, respectively. The overexpression of cyclin D1 was not observed in normal mucosa and was observed in 35.9% of SCC. A strong reciprocal relationship between Rb and p16(INK4A) expression was observed in oral SCC, and all these SCC cases have at least one of the alterations in the Rb pathway.
Cancer Letters 12/2000; 160(1):3-8. · 4.24 Impact Factor
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ABSTRACT: Epidermal growth factor receptor (EGFR) frequently overexpresses in cancers, including oral squamous cell carcinomas (OSCC). We previously identified a truncated EGFR (tEGFR) in human oral keratinocytes. In this study, we evaluated the prognostic value of tEGFR in 45 cases of OSCC. tEGFR expression inversely correlated with EGFR expression (r=-0.83, P<0.01), decreased with T-stage progression and lymph-node metastasis (P<0.05). The EGFR/tEGFR ratio correlated with the lymph-node metastasis (P<0.05) and survival outcome (hazard ratio =3.601; P<0.05). These results suggest that tEGFR may play an important roles in oral carcinogenesis and that the EGFR/tEGFR ratio may be a prognostic factor for OSCC.
Cancer Letters 12/2000; 161(1):9-15. · 4.24 Impact Factor
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ABSTRACT: This study examined the relationship between tumor angiogenesis and the radiation-induced response, evaluated based on pathological changes, in oral squamous cell carcinoma patients treated with preoperative radiation therapy. Forty-one cases of squamous cell carcinoma treated with preoperative radiation therapy were investigated. Tumor angiogenesis was assessed by scoring the intratumor microvessel density (IMVD). Expression of vascular endothelial growth factor (VEGF) was also evaluated before and after preoperative radiotherapy. There was no correlation between IMVD in the specimens before therapy and the pathological response to radiation therapy. However, radiation therapy decreased IMVD in the specimens after therapy. A significant association was observed between VEGF expression and resistance to radiation therapy: only 4 of the 21 patients whose tumors exhibited a high level (2 + or 3 + ) of VEGF staining experienced a major (3 + or 4 + ) pathological response to radiation therapy. Furthermore, an increasing level of VEGF expression after radiation therapy was observed in non-effective (0 to 2 + ) response cases. These results suggest that VEGF expression and the induction of this protein are related to radiosensitivity and could be used to predict the effects of preoperative radiation therapy on oral squamous cell carcinoma.
Japanese journal of cancer research: Gann 11/2000; 91(10):1051-7.
