Urayasu, Japan
Urayasu, Japan

Meikai University is a private university in Urayasu, Chiba, Japan. It was founded in 1970, and obtained its present name in 1988.The university's School of Dentistry is located in Sakado, Saitama. Wikipedia.

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Inoue H.,Meikai University
Journal of oral science | Year: 2011

To examine the pathogenesis of intravascular papillary endothelial hyperplasia (IPEH), a relatively uncommon benign, non-neoplastic vascular lesion, clinicopathological and immunohistochemical studies were performed. Paraffin-embedded tissue specimens of 78 vascular lesions were examined histologically, and 9 cases of IPEH were investigated immunohistochemically using antibodies against CD34, vimentin, factor VIII antigen, α-smooth muscle actin (α-SMA), podoplanin, CD105, and ki-67 antigen. A thrombus or ulcer was found near the sites of all IPEH specimens. Histologic examination revealed papillary proliferated endothelial cells located toward the lumen of enlarged blood vessels. Immunohistochemistry showed that CD34, α-SMA, and factor VIII antigen were positive in lining endothelial cells. Vimentin was positive in the mesenchymal components. Immunohistochemical staining for podoplanin and CD105 was partially positive. Labeling index was 4.7 to 9.2 in ki-67-positive cases. IPEH is believed to result from reactive proliferation of blood endothelial cells that is caused by an abnormal process of organization in thrombosed blood vessels. The pathogenesis of IPEH might be related to inflammation or mechanical stimulus such as irritation.

Despite the rapid development of nanotechnology, the biological significance of TiO2 nanoparticles (NPs), possibly released from dental materials, is not well-understood. We investigated the effect of TiO2 NPs on the sensitivity of human oral squamous cell carcinoma (OSCC) cell line (HSC-2) to five popular chemotherapeutic agents. Viable cell number was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The aggregation and cellular uptake of TiO2 NPs were assessed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), respectively. Adsorption of TiO2 NPs to anticancer drugs was assessed by the antitumor activity recovered from the TiO2 NP-free supernatant. When mixed with culture medium, TiO2 NPs instantly aggregated, and some particles were incorporated into the cells, exclusively in the vacuoles. TiO2 NPs showed no cytotoxicity nor hormetic growth stimulation at lower concentrations. Doxorubicin, melphalan, 5-fluorouracil and gefitinib were cytotoxic, whereas docetaxel was cytostatic with or without TiO2 NPs. TiO2 NPs, at wide concentration ranges (0.2-3.2 mM), did not significantly affect the adsorption of NPs to any of these anticancer drugs, nor affected their cytotoxic or cytostatic activity. This experimental study demonstrated for the first time that TiO2 NP do not affect the antitumor potential of chemotherapeutic agents against the HSC-2 OSCC cell line.

Human podoplanin is a type-1 transmembrane sialomucin-like glycoprotein that is involved in cell migration, tumor cell invasion and metastasis. Our recent study of oral squamous cell carcinoma (OSCC) demonstrated that the degree of immunohistochemical expression of podoplanin was correlated with the severity of epithelial dysplasia and significantly associated with a poor pathologic grade of differentiation. Furthermore, it has been reported that Src directly associates with the epidermal growth factor receptor (EGFR) in OSCC cells upon stimulation with EGF and phosphorylates Crk-associated substrate (Cas), podoplanin acting downstream of Src and Cas to promote cell migration. However, the molecular function of podoplanin remains unclear. In this study we performed real-time RT-PCR, Western blotting and scratch assay using OSCC cell lines in order to clarify the molecular biological function of podoplanin expression associated with various growth factors including EGF and with the Src-Cas signaling pathway. Podoplanin was found to have a marked influence on cancer cell migration and the expression of matrix metalloprotease-9 (MMP-9) in the oral cavity upon stimulation with EGF. Podoplanin promotes oral cancer cell migration, and the EGF-Src-Cas pathway is one of the possible mechanisms responsible for progression of cancer in the oral cavity.

Fujita Y.,Kyushu Dental College | Watanabe K.,Meikai University | Maki K.,Kyushu Dental College
Journal of Musculoskeletal Neuronal Interactions | Year: 2012

Objectives: This study evaluated the influence of diet-induced obesity on bone tissue quantity and quality in the proximal tibiae of growing mice and also examined the relationships between the serum total cholesterol, leptin, and adiponectin levels and trabecular and cortical bone mineral parameters. Methods: Six-week-old male C57BL/6J mice were divided into two groups; one received a control diet, and the other received a high-fat-diet. After treatment for 4, 8, or 12 weeks, the bone quantity and quality were analyzed using peripheral quantitative computed tomography (pQCT), micro-computed tomography and histomor-phometry. Results: In the early stages, trabecular bone density decreased with an increase in the number of adipocytes and the deterioration of trabeculae. In contrast, although cortical bone formation was slower in obese mice compared with control mice, bone formation on the periosteal surface increased with age. Serum leptin levels were correlated with trabecular, but not cortical bone density, whereas neither the adiponectin nor total cholesterol level was correlated with bone mass in mice with diet-induced obesity. Conclusions: We conclude that bone loss at these two sites is differentially regulated in mice. Furthermore, we demonstrate that serum leptin may be a useful indicator of risk for osteoporosis associated with diet-induced obesity.

Gonzalez-Alva P.,Meikai University
Journal of oral science | Year: 2011

Podoplanin, a sialomucin-like transmembrane glycoprotein, is currently used as a specific marker for lymphatic vessels. However, podoplanin expression has also been linked to tooth development. To investigate the expression of podoplanin in odontomas, 86 tissue samples were classified and then analyzed using immunohistochemical methods. Formalin-fixed, paraffin-embedded specimens were collected and classified, followed by immunohistochemical examination. The majority of the odontomas (66.3%) were the compound type, and the remainder (33.7%) were the complex type. The patients ranged in age from 2 to 89 years (mean, 23.9 years), and 45 (52.3%) of them were male and 41 (47.7%) were female. The most common location for complex odontomas was the molar region of the mandibular bone, and that for compound odontomas was the maxillary incisor region. Immunohistochemistry revealed that developing and mature odontoblasts, Tomes' fibers, and pulp cells near podoplanin-positive odontoblasts were positive for podoplanin. In addition, podoplanin positivity was evident in secretory ameloblasts, but not in mature ameloblasts. The pattern of podoplanin expression in odontomas corresponds to development of the tooth germ, and appears to be influenced by the stage of differentiation of the lesion, suggesting that the protein may participate in the process of differentiation.

Podoplanin, a transmembrane sialomucin-like glycoprotein, is a specific marker of lymphatic vessels, and its expression is also considered to be associated with tumor invasion and tooth development. In this study, we examined the expression of podoplanin in calcifying cystic odontogenic tumor (CCOT) in comparison with that in other so-called hard α-keratin-expressing tumors such as craniopharyngioma (CP) and pilomatrixoma (PM). Immunohistochemical staining for podoplanin was carried out using surgical specimens of 15 CCOTs of the jaw, 19 CPs of the pituitary gland, and 15 PMs of the skin. Positivity for hard α-keratin was evident in ghost, shadow and transitional cells in all of these tumors (100%). The podoplanin expression in CCOTs was evident in the periphery of ameloblastoma-like epithelium (86.6%) and the epithelial cells adjacent to ghost cells (60%). On the other hand, in adamantinomatous-type CPs, podoplanin expression was observed in epithelial components corresponding to the stratum intermedium (100%), but not in the periphery of ameloblastoma-like epithelium (0%). In squamous-type CPs podoplanin was expressed in basal cells (100%), but all of the PMs were podoplanin-negative (0%). In the periphery of the ameloblastoma-like epithelium or basophilic cell layer, podoplanin was expressed more strongly in CCOTs than in CPs or PMs. These findings suggest that the expression of podoplanin in CCOTs may reflect rapid turnover of cytoskeletal filaments and local invasiveness.

Activation-induced cytidine deaminase (AID) induces cytosine deamination to generate somatic hypermutation and class switch recombnation in immunoglobulin genes. AID expression is upregulated by inflammatory cytokines such as interferon-γ and tumor necrosis factor (TNF)-α, which in turn induce p53 mutations in inflammatory or cancer cells. In this study, the effects of growth factors, cytokines or sodium butyrate on AID mRNA expression were examined in human OSCC-derived cells using real-time RT-PCR. Expression of AID mRNA was detected in OSCC cells and the expression was increased by EGF, TNF-a, or sodium butyrate. These results suggest that aberrant AID expression may play an important role in the dysplasia-carcinoma sequence in the oral cavity.

Suda N.,Meikai University | Moriyama K.,Tokyo Medical and Dental University | Ganburgedc G.,Ulaanbaatar University
Infection and Immunity | Year: 2013

Marfan syndrome is an autosomal dominant disease characterized by aneurysm and dilatation of the aortic root, tall stature, and ectopia lentis. These manifestations reflect excessive signaling of transforming growth factor beta (TGF-Β). Moreover, cases are frequently associated with severe periodontitis, which is a chronic inflammation of the gingiva, periodontal ligament, and alveolar bone. Recently, angiotensin II receptor blockers (ARBs) were discovered to be an effective drug class that can prevent aortic aneurysm and dilation in Marfan syndrome by inhibiting TGF-Β signaling. To investigate the effect of ARB on the progression of periodontitis, the application of a potent ARB, telmisartan, was examined in a mouse model of Marfan syndrome (Mgδ). Six-week-old male heterozygous Mgδ and wild-type mice were challenged with Porphyromonas gingivalis, which causes chronic periodontitis, with and without telmisartan application. After infection, alveolar bone resorption was measured by micro-computed tomography (μCT), and inflammatory cytokine levels were examined. Infection of Porphyromonas gingivalis induced alveolar bone resorption in both Mgδ and wild-type mice. The amount of resorption was significantly larger in the former than the latter. Immunoarray and enzyme-linked immunosorbent assay (ELISA) analyses demonstrated that interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α) levels were significantly higher in infected Mgδ mice than infected wild-type mice. Telmisartan treatment significantly suppressed the alveolar bone resorption of infected Mgδ mice. Telmisartan also significantly decreased levels of TGF-Β, IL-17, and TNF-α in infected Mgδ mice to levels seen in infected wild-type mice. This study suggests that ARB can prevent the severe periodontitis frequently seen in Marfan syndrome. © 2013, American Society for Microbiology.

Kadoma Y.,Tokyo Medical and Dental University | Fujisawa S.,Meikai University
Molecules | Year: 2011

The radical-scavenging activity of dietary phytophenols has been investigated by many researches due to their antioxidant, anti-inflammatory and anticancer property but the radical-scavenging effect of 2-phytophenol and the phytophenol:co-antioxidants, vitamin C and thiol combination under nearly anaerobic conditions still remains unknown. The radical-scavenging activity for seventeen phytophenols and for six synthetic phenols (positive controls) was investigated using the induction period method in the polymerization of methyl methacrylates (MMA) initiated by thermal decomposition of benzoyl peroxide (BPO) by monitoring differential scanning calorimetery (DSC). The kinh for the phytophenols was likely with the range 0.5 × 10 3 M -1s -1-2.2 × 10 3 M -1s -1, whereas that for synthetic phenols, hydroquinone and galvinoxyl, was with the range 7 × 10 3 M -1s -1-8 × 10 3 M -1s -1. Also, the additive scavenging effect of the (-)-epigallocatechin (EGC):(-)-epicatechin (EC) and the (+)-catechin:epicatechin (EC) combination was observed at 1:1 molar ratio, whereas that of the EC:quercetin combination showed the cancel (prooxidative) effect. Furthermore, the EGC:ASDB (L-ascorbyl 2,6-dibutylate) or 2-ME (2-mercaptoethanol) combination showed the prooxidative effect. Such enhancement of prooxidation in the combination may increase their toxic effects due to their cooxidation. Also, the synergic, additive or cancel effects of the flavonoid:vitamins E combination on the induction period in the BPO (a PhCOO* radical) and 2,2'-azobisisobutyronitrile (AIBN, an R*radical) systems are discussed. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Garcia-Contreras R.,Meikai University
In vivo (Athens, Greece) | Year: 2014

Despite recent progress in the research of nanoparticles (NPs) spanning in many scientific fields, study of NPs in dentistry is limited. This triggered us to investigate the effect of TiO2 NPs on the drug-sensitivity of oral squamous cell carcinoma and inflammation of human gingival fibroblasts (HGFs). The number of viable HGF cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Prostaglandin E2 (PGE2) was quantified by enzyme-linked immunosorbent assay. Contamination with lipopolysaccharide (LPS) was assayed by the endotoxin assay kit. Intracellular uptake and distribution of TiO2 NPs were assessed by transmission electron microscopy. TiO2 NPs (0.05-3.2 mM) did not affect HGF cell viability, although TiO2 NPs clusters were dose-dependently incorporated into the vacuoles of cells. Interleukin-1β (IL-1β) (3 ng/ml) stimulated the secretion of PGE2 into the culture medium by HGF cells. TiO2 NPs also induced PGE2 production, in synergy with IL-1β. Since only a minor amount of LPS was detected in TiO2 NPs, the enhanced production of PGE2 was not simply due to LPS contamination. The present study demonstrates, for the first time to our knowledge, that TiO2 NPs at concentrations higher than 0.2 mM exert an pro-inflammatory action against HGF cells, regardless of the presence or absence of IL-1β.

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