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ABSTRACT: Matrix metalloproteinases (MMPs) regulated by ets transcription factors facilitate carcinoma cell invasion. An ets family member, ESE-1, is expressed specifically in epithelial tissues, but its association with MMPs is obscure. In this study, we investigated whether ESE-1 regulates invasion of oral squamous cell carcinoma (SCC) via transcriptional activity of MMP-9.
HSC-3 and KB were used as human oral SCC lines. The expression of ESE-1 and MMP-9 was detected by in situ hybridization and immunohistochemistry. Invasion assay, gelatin zymography and Northern blotting were used to detect the invasion activity, the gelatinolytic activity and the expression of MMP-9 in the ESE-1 transfectants. Luciferase assays and mutation analysis were used for the transcriptional analysis of MMP-9 promoter region by ESE-1.
ESE-1 was expressed in the intermediate layer but not in the invasive area, in which MMP-9 was expressed, in the oral SCC tissues. ESE-1 suppressed invasion activity and 92 kDa gelatinolytic activity in HSC-3 as a result of transfection. ESE-1 regulates MMP-9 expression in a negative manner and the ets binding site on the MMP-9 promoter contributed to suppression by ESE-1.
These findings indicate that ESE-1 negatively regulates the invasion of oral SCC via transcriptional suppression of MMP-9.
Oral Diseases 04/2008; 14(2):144-9. · 2.49 Impact Factor
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ABSTRACT: Current oncolytic viruses exert only limited antitumor activity on their own. There is a need to increase their oncolytic capability. We evaluated the effect of a differentiating reagent, hexamethylene bisacetamide (HMBA), on the antitumor activity of a gamma(1)34.5-deficient herpes simplex virus type 1 (HSV-1) R849 for human oral squamous cell carcinoma (SCC) cells. Hexamethylene bisacetamide increased the viral yield, especially at a low input multiplicity of infection (MOI), and the transcription of immediate early genes of HSV-1. Hexamethylene bisacetamide treatment promoted the cytopathic effect of R849 and increased the proportion of dead cells. Hexamethylene bisacetamide produced more apoptotic cells in R849-infected cells as compared with parental HSV-1(F)-infected cells. The growth of oral SCC xenografts in nude mice was markedly suppressed by treatment with R849 in combination with HMBA, and the survival of the co-treated animals was significantly prolonged as compared with that of animals treated with R849 only. Herpes simplex virus type 1 mRNA was expressed in tumors and trigeminal neurons, but not in brain, lung, liver, and kidney. These results indicate that HMBA enhances the antitumor activity of R849 through the expression of immediate early genes without increasing its toxicity. Hexamethylene bisacetamide can be used as an enhancing agent for oncolytic therapy with HSV-1 mutants.
Cancer Gene Therapy 09/2006; 13(8):780-91. · 2.80 Impact Factor
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ABSTRACT: Mandibular reconstruction is required after segmental resection of the mandible. Several techniques have been proposed but have several drawbacks. A modified system (based on Leibinger's titanium-positioning system) that can reposition the residual mandible easily and accurately without interfering with the reconstructive procedure was developed. This system has been used successfully in more than 10 patients, with no complications.
International Journal of Oral and Maxillofacial Surgery 04/2006; 35(3):270-3. · 1.51 Impact Factor
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ABSTRACT: PKC inhibitor safingol suppressed the growth of human oral squamous cell carcinoma (SCC) cells significantly at concentrations that inhibit PKC isoforms. Safingol inhibited the translocation of PKC following treatment with 12-o-tetradecanoylphorbol 13-acetate (TPA) in PKC alpha-EGFP-transfected cells, but not in PKC beta-EGFP- transfected cells, indicating selective inhibition for PKC alpha in oral SCC cells. Flow cytometric analysis and DNA analysis by agarose gel electrophoresis revealed an increase in the proportion of sub-G(1) cells and DNA fragmentation in safingol-treated cells. Mitochondrial membrane potential was decreased, and cytochrome c was released from mitochondria. However, the safingol-induced cell death was not accompanied by activation of caspase 3 and cleavage of poly (ADP-ribose) polymerase (PARP). The broad-spectrum caspase inhibitor BD-fmk failed to prevent safingol-induced cell death. Another apoptogenic factor endonuclease G, but not apoptosis-inducing factor (AIF), was also released from mitochondria and translocated to the nucleus. These results suggest that PKC alpha inhibitor safingol induces an endonuclease G- mediated apoptosis in a caspase-independent manner.
APOPTOSIS 02/2006; 11(1):47-56. · 4.79 Impact Factor
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ABSTRACT: TS-1 is a novel oral 5-fluorouracil containing tegaful (prodrug of 5-FU) and two biochemical modulators. These modulators feature effect-enhancing and adverse reaction-reducing activity. We investigated the histological response and toxicities of combination chemotherapy with TS- 1 and low-dose cisplatin and evaluated its usefulness as preoperative chemotherapy Forty-four newly diagnosed patients with stage Il-IV oral squamous cell carcinoma were enrolled in this study from February 2002 to April 2004. Patients were administered TS-1 80 mg/m2/day (days 1-14) and cisplatin 5 mg/m2/day (days 1-5 and 8-12) followed by radical surgery within 2 weeks. The histopathological effect of chemotherapy, which was a surrogate endpoint of this trial, was evaluated with surgical or biopsy specimens. The rate of histological antitumor effect was as follows: complete response (CR) 36.4%, partial response (PR) 25.0%, minor response (MR) 18.1% and no change (NC) 20.5%. The rate of histological response (CR + PR) was 61.4%. The CR rate of effective cases was 59.3%. The main toxicities occurred in bone marrow and the digestive tract. The incidence of severe toxicity such as grade 3 or 4 was 4.5% in anemia, 9% in leukocytopenia, 11.4% in neutropenia, 4.5% in thrombocytopenia and 2.3% in anorexia, diarrhea and urticaria. Most patients showed no toxicity or mild toxicities. TS- 1 with low-dose cisplatin has highly effective antitumor activity and mild toxicities. In particular, the CR rate was very high. It is suggested that this regimen is suitable for neoadjuvant chemotherapy. We expect that this chemotherapy will contribute to avoidance of surgery for small tumors (stages I and II) and will enable function-preserving surgery for advanced tumors.
International journal of clinical pharmacology research 02/2005; 25(3):115-22.
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ABSTRACT: Preoperative chemotherapy should be effective against cancers and have few side effects that would prevent surgery. We investigated the histological effects and side effects of low- and high-dose CDDP chemotherapy against oral squamous cell carcinoma (SCC), and discuss the therapeutic benefits of each regimen. Thirty-six patients were divided into two groups as follows, in a non-randomized manner: A) low-dose CDDP (17 patients): CDDP 5 mg/m2/day + UFT 400 mg/day (day 1-5) (1 or 2 courses), B) high-dose CDDP (19 patients): CDDP 70-100 mg/m2/day (day 1) + peplomycin 5 mg/day (day 2-6) (1 or 2 courses). Curative surgery was conducted 1 week after protocol A or 2-3 weeks after protocol B. The histological antitumor effects were evaluated with Ohboshi & Shimosato's classification using surgical materials of primary tumors. In this classification, grade IIB, III and IV were as effective. Maximum histological effect was seen with grade IIB for regimen A and grade IV for regimen B. Four of 17 patients (23.5%) responded to regimen A and 13 of 19 patients (68.4%) to regimen B. Side effects, such as nausea, vomiting and myelosuppression, appeared with regimen B, but were seen little with regimen A. The 2-year survival rate was 93.3% with regimen A and 78.9% with regimen B. With regimen A, the 2-year survival rate of effective cases was 100% and that of ineffective cases was 91.7%. With regimen B, the rate was 92.3% and 50.0%, respectively. Effective cases showed good prognosis in both groups. The low-dose CDDP regimen was not so effective against primary tumors histologically, but the prognosis was good. The low-dose CDDP regimen appears to be useful for preoperative chemotherapy of oral SCC.
Gan to kagaku ryoho. Cancer & chemotherapy 04/2001; 28(3):337-43.
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ABSTRACT: We describe a case of a solitary fibrous tumor of the buccal mucosa and report the results of immunohistochemical studies of the lesion. Solitary fibrous tumors are extremely rare in the intraoral region. These tumors are generally difficult to diagnose because of their broad range of morphologic characteristics. We regard the expression of CD34 within the appropriate clinical and morphologic setting, in the absence of reactivity for other specific markers of differentiation, as evidence supporting the diagnosis of solitary fibrous tumor.
Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontics 11/1999; 88(4):461-5. · 1.46 Impact Factor
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ABSTRACT: Central acinic cell carcinoma is extremely rare; only six cases have been reported in the literature. An unusual case of central acinic cell carcinoma of the mandible in an 84-year-old Japanese woman is presented. This is thought to be the seventh case of central acinic cell carcinoma described in the English literature.
International Journal of Oral and Maxillofacial Surgery 01/1999; 27(6):448-50. · 1.51 Impact Factor
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Journal of Oral and Maxillofacial Surgery 09/1993; 51(8):932-4. · 1.64 Impact Factor
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