Hiroyuki Yamada

Tsurumi University, Yokohama, Kanagawa, Japan

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Publications (48)53.25 Total impact

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    ABSTRACT: Poly(ADP-ribosyl)ation is known to be involved in a variety of cellular processes, such as DNA repair, cell death, telomere regulation, genomic stability and cell differentiation by poly(ADP-ribose) polymerase (PARP). While PARP inhibitors are presently under clinical investigation for cancer therapy, little is known about their side effects. However, PARP involvement in mesenchymal stem cell (MSC) differentiation potentiates MSC-related side effects arising from PARP inhibition. In this study, effects of PARP inhibitors on MSCs were examined. MSCs demonstrated suppressed osteogenic differentiation after 1 µM PJ34 treatment without cytotoxicity, while differentiation of MSCs into chondrocytes or adipocytes was unaffected. PJ34 suppressed mRNA induction of osteogenic markers, such as Runx2, Osterix, Bone Morphogenetic Protein-2, Osteocalcin, bone sialoprotein, and Osteopontin, and protein levels of Bone Morphogenetic Protein-2, Osterix and Osteocalcin. PJ34 treatment also inhibited transcription factor regulators such as Smad1, Smad4, Smad5 and Smad8. Extracellular mineralized matrix formation was also diminished. These results strongly suggest that PARP inhibitors are capable of suppressing osteogenic differentiation and poly(ADP-ribosyl)ation may play a physiological role in this process through regulation of BMP-2 signaling. Therefore, PARP inhibition may potentially attenuate osteogenic metabolism, implicating cautious use of PARP inhibitors for cancer treatments and monitoring of patient bone metabolism levels.
    International Journal of Molecular Sciences 10/2015; 16(10):24820-24838. DOI:10.3390/ijms161024820 · 2.86 Impact Factor
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    Nippon Koku Geka Gakkai zasshi 01/2015; 61(3):164-167. DOI:10.5794/jjoms.61.164

  • 01/2015; 28(3):221-225. DOI:10.15214/jsodom.28.221

  • Nippon Koku Geka Gakkai zasshi 01/2015; 61(1):36-40. DOI:10.5794/jjoms.61.36
  • Go Tsumuraya · Hiroyuki Yamada · Hajime Shimizu · Yoshiki Hamada ·
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    ABSTRACT: This is the first report to our knowledge of an intramuscular lipoma that arose in the masseter muscle. Excision biopsy under general anaesthesia showed that the mass could easily be separated from the surrounding soft tissues on the lateral side, but was firmly adherent to the muscle on the medial side, so complete excision required resection of part of the masseter. Histopathological examination showed that it was an intramuscular lipoma. Two years and 6 months postoperatively there was no evidence of recurrence.
    British Journal of Oral and Maxillofacial Surgery 04/2014; 52(4). DOI:10.1016/j.bjoms.2014.01.013 · 1.08 Impact Factor
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    ABSTRACT: Myofibroma is a benign tumor composed of myoid spindle cells. The prevalence of myofibroma in the oral cavity is very low, with the mandible being the most common site. This report describes an adult case of myofibroma that arose on the mandible and includes magnetic resonance imaging (MRI) and positron emission tomography (PET) findings. On the MRI T1-weighted images, the tumor appeared with signal iso-intensity and was highly and heterogeneously enhanced with contrast material. On the T2-weighted images, it appeared with increased signal intensity. 18 F-fluorodeoxyglucose (FDG)-PET imaging showed abnormal strong accumulation of FDG in the left mandibular region. The tumor was removed by marginal resection of the left mandible under general anesthesia. Histopathological findings revealed that the tumor stroma contained abundant thin-walled vessels. The postoperative course was uneventful, and we found no evidence of recurrence at the postoperative 34-month follow-up.
    World Journal of Surgical Oncology 03/2014; 12(1):69. DOI:10.1186/1477-7819-12-69 · 1.41 Impact Factor
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    ABSTRACT: In this paper, we report the clinical course of a 11-year-old boy with an ameloblastic fibrodentinoma developing in the right side of the mandible. Clinically, there were no specific findings, except for an unerupted right mandibular first molar. Panoramic radiography and dental computed tomography revealed a well-defined radiolucent lesion with small calcified particles in the right side of the mandible. Moreover, an impacted tooth, which appeared to be the unerupted first molar, existed below the radiolucent lesion. A biopsy was performed, and the lesion was histopathologically diagnosed as ameloblastic fibrodentinoma. The tumor was removed with preservation of the impacted tooth under general anesthesia. As of 3 years after surgery, there have been no signs of recurrence, and the impacted tooth has erupted spontaneously in the dentition and functions as the first molar.
    Nippon Koku Geka Gakkai zasshi 01/2014; 60(4):204-208. DOI:10.5794/jjoms.60.204
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    ABSTRACT: Abstract The objective of this study is to evaluate usefulness of mandibular reconstructions using a custom-made titanium mesh (Ti-mesh) tray and particulate cancellous bone and marrow (PCBM). A consecutive nine patients who underwent mandibular reconstruction were enrolled in this study. They were five men and four women (mean age: 53.9 years). Virtual reality simulation was performed using computer software based on the pre-operative computed tomography data. A 3-dimensional (3-D) skull model was constructed using a 3-D printer. A tray was custom-made from a Ti-mesh sheet bent to adapt to the model. After PCBM harvesting from bilateral posterior ilia, the tray was fixed to the host bone. New bone formation and configuration of the reconstructed mandible were assessed radiologically. Complications were recorded in each patient during the follow-up period. Patients, satisfaction with post-operative facial contour was evaluated using a visual analogue scale (VAS score, range = 0-100). In six of nine patients, excellent new bone formation was recognised and expected results were radiologically achieved. Complications occurred in four patients. These complications included Ti-mesh fracture, Ti-mesh exposure in the oral cavity, and delayed infection. Mean VAS score on patient satisfaction was 77.6. Although the data are preliminary, the results suggest that this method is clinically useful.
    10/2013; 48(3). DOI:10.3109/2000656X.2013.848809
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    ABSTRACT: Objective: This study aimed to establish a mouse model in which dental pulp cells (DPCs) could be used as a cell source for the treatment of salivary gland hypofunction. Design: DPCs were isolated from green fluorescent protein (GFP)-expressing mice and were differentiated into dental pulp endothelial cells (DPECs). DPEC behaviour was studied in vitro and in vivo to investigate their capacity to participate in neovascularisation. For in vivo assessment, a combination of DPECs and Matrigel was subcutaneously injected into nude mice. Two weeks after injection, Matrigel plugs were analysed for CD31 and GFP. Furthermore, both submandibular glands of the irradiated mice were injected with DPECs. Eight weeks after irradiation, the effect of DPECs on saliva secretion was evaluated by measuring amounts of saliva secretion. Results: DPECs showed typical endothelial morphology, including a cobblestone appearance. RT-PCR analysis of DPECs showed positive expression of CD31, foetal liver kinase-1, vascular-endothelial-cadherin, vascular endothelial growth factor-A and von Willebrand factor. DPECs reorganised into tube-like structures on Matrigel after 24h in vitro. Positive merged staining for both CD31 and GFP was observed in the tube-like structures, representative of the injected DPECs. The average saliva flow rate in mice treated with DPECs was significantly higher than that observed in mice treated with PBS (P=0.0452). Conclusions: Our results show that radiation-induced salivary hypofunction is partially reverted following transplantation of DPECs. We established a mouse model in which DPCs could be used as a cell source for the treatment of salivary gland hypofunction.
    Archives of Oral Biology 04/2013; DOI:10.1016/j.archoralbio.2013.02.015 · 1.74 Impact Factor
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    ABSTRACT: In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.International Journal of Oral Science (2013) 5, doi:10.1038/ijos.2013.10; published online 15 March 2013.
    International Journal of Oral Science 03/2013; 5(1). DOI:10.1038/ijos.2013.10 · 2.53 Impact Factor
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    ABSTRACT: This case report presents an unusual case of a simple mandibular bone cyst with remarkable tooth resorption. A 52-year-old woman was referred to our clinic for examination of a radiolucent lesion located in the right third mandibular molar region. The lesion could not be identified on panoramic radiograph at 6 years ago. Imaging examinations demonstrated a relatively well demarcated radiolucent lesion in the right mandible with marked resorption of the third molar. Based on the tentative diagnosis of an intraosseous benign tumor, biopsy was performed. The lesion was a simple bone cavity containing sanguineous fluid with no evidences of a cystwall lining or tumoral tissue. Intraoperative diagnosis was a simple bone cyst, and the lesion including the remained third molar was carefully removed. Histopathologically, thin fibrous connective tissue without epithelial cover was observed on the surface of the bony wall. The histopathologic findings were consistent with those of a simple bone cyst. However, myxofibromatous connective tissue and woven bone were observed only on the surface of the resorbed dental hard tissue. This case may be associated with the fibro-osseous lesion to some degree. One year later, complete healing was observed.
    01/2013; 25(1):93–96. DOI:10.1016/j.ajoms.2012.01.015
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    ABSTRACT: This paper introduces the mandibular reconstruction using a custom-made titanium mesh (Ti-mesh) tray and autogenous particulate cancellous bone and marrow (PCBM), with a representative case report. The Ti-mesh tray is accurately adapted to the mandibular defect and its configuration is suitable for reproducing the final dental occlusion in each patient by utilizing computer-aided design/computer-aided manufacture (CAD/CAM) and dental laboratory technology. Eleven patients with mandibular defects (9 segmental defects and 2 marginal defects) underwent the present mandibular reconstruction. All reconstructive surgeries were successful and postoperative facial contour was acceptable for most patients. Although fracture of the Ti-mesh tray was recognized within 3 months after surgery in 2 patients with mandibular defect including the mentum area, we carried out successful additional reconstructive surgeries using a reinforced Ti-mesh tray and PCBM in these 2 patients. Although the present mandibular reconstruction requires several improvements, it seems to be clinically more predictive than the conventional mandibular reconstruction.
    Japanese Journal of Head and Neck Cancer 01/2013; 39(4):422-429. DOI:10.5981/jjhnc.39.422
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    ABSTRACT: Clenbuterol, a β(2) -adrenergic agonist, increases the hypertrophy of skeletal muscle. Insulin-like growth factor (IGF) is reported to work as a potent positive regulator in the clenbuterol-induced hypertrophy of skeletal muscles. However, the precise regulatory mechanism for the hypertrophy of skeletal muscle induced by clenbuterol is unknown. Myostatin, a member of the TGFβ super family, is a negative regulator of muscle growth. The aim of the present study is to elucidate the function of myostatin and IGF in the hypertrophy of rat masseter muscle induced by clenbuterol. To investigate the function of myostatin and IGF in regulatory mechanism for the clenbuterol-induced hypertrophy of skeletal muscles, we analysed the expression of myostatin and phosphorylation levels of myostatin and IGF signaling components in the masseter muscle of rat to which clenbuterol was orally administered for 21 days. Hypertrophy of the rat masseter muscle was induced between 3 and 14 days of oral administration of clenbuterol and was terminated at 21 days. The expression of myostatin and the phosphorylation of smad2/3 were elevated at 21 days. The phosphorylation of IGF receptor 1 (IGFR1) and akt1 was elevated at 3 and 7 days. These results suggest that myostatin functions as a negative regulator in the later stages in the hypertrophy of rat masseter muscle induced by clenbuterol, whereas IGF works as a positive regulator in the earlier stages. Copyright © 2012 John Wiley & Sons, Ltd.
    Cell Biochemistry and Function 12/2012; 30(8). DOI:10.1002/cbf.2848 · 2.01 Impact Factor
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    ABSTRACT: Stem cell-based therapy has been proposed as a promising strategy for regenerating tissues lost through incurable diseases. Side population (SP) cells have been identified as putative stem cells in various organs. To examine therapeutic potential of SP cells in hypofunction of exocrine glands, SP cells isolated from mouse exocrine glands, namely, lacrimal and salivary glands, were transplanted into mice with irradiation-induced hypofunction of the respective glands. The secretions from both glands in the recipient mice were restored within 2 months of transplantation, although the transplanted cells were only sparsely distributed and produced no outgrowths. Consistent with this, most SP cells were shown to be CD31-positive endothelial-like cells. In addition, we clarified that endothelial cell-derived clusterin, a secretory protein, was an essential factor for SP cell-mediated recovery of the hypofunctioning glands because SP cells isolated from salivary glands of clusterin-deficient mice had no therapeutic potential, whereas lentiviral transduction of clusterin restored the hypofunction. In vitro and in vivo studies showed that clusterin had an ability to directly inhibit oxidative stress and oxidative stress-induced cell damage. Thus, endothelial cell-derived clusterin possibly inhibit oxidative stress-induced hypofunction of these glands.
    Stem Cells 09/2012; 30(9):1925-37. DOI:10.1002/stem.1173 · 6.52 Impact Factor
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    ABSTRACT: Solitary fibrous tumor (SFT) is an uncommon spindle-cell mesenchymal tumor of probable fibroblastic derivation that most often occurs in the pleura, where it is typically benign. This report describes a case of a large SFT that arose in the buccal space, and includes computerized tomography, magnetic resonance imaging, and positron emission tomography (PET) findings. (18)F-Fluorodeoxyglucose (FDG) PET axial imaging showed weak abnormal accumulation of FDG in the left buccal region. The tumor was located behind the posterior wall of the maxilla, adjacent to the medial aspect of the coronoid process and was compressed between the coronoid and maxillary alveolar processes. We resected it with the use of a transoral approach in combination with coronoidectomy. Coronoidectomy was chosen because it facilitated safe removal of the tumor by improving its visibility and providing enough working space to resect it through a transoral approach.
    07/2012; 114(1):e9-e14. DOI:10.1016/j.tripleo.2011.07.044
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    ABSTRACT: The purpose of this study was to investigate the effect of stereotactic radiosurgery on local control and organ preservation in cases of primary head and neck cancer. In this retrospective study, 14 patients with a mean age of 73 years were treated between March 2006 and September 2007 with stereotactic radiosurgery for the management of primary head and neck cancer. The patients had biopsy confirmation of disease before treatment and all patients were confirmed with squamous cell carcinoma. The staging consisted of T2 (5 cases), T3 (3 cases), T4 (6 cases), N0 (13 cases), and N1 (1 case). Marginal doses were 3,500 to 4,200 cGy in 3 or 5 fractions. The outcome was assessed according to Response Evaluation Criteria in Solid Tumors criteria based on magnetic resonance imaging and positron emission tomography/computed tomography. Significant tumor reduction was noted at the third month of follow-up with 5 complete responses and 9 partial responses. At a mean follow-up of 36 months (range, 14-40 mo) the local control and overall survival rates were 71.4% (10/14) and 78.6% (11/14), respectively. These results show the feasibility of using stereotactic radiosurgery for primary head and neck cancer and its potential benefit in local control and organ preservation.
    Journal of oral and maxillofacial surgery: official journal of the American Association of Oral and Maxillofacial Surgeons 07/2011; 70(2):461-72. DOI:10.1016/j.joms.2011.02.063 · 1.43 Impact Factor
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    ABSTRACT: This study aimed to investigate the roles of the epidermal growth factor receptor (EGFR) family members and their ligands in oral lichen planus (OLP). The expressions of 4 EGFR-like receptors and 6 EGF-like ligands were measured in OLP tissues from 10 patients and compared with the levels in normal oral mucosa (NOM) from 10 healthy donors. Of the receptors, only EGFR mRNA and protein were more highly expressed in OLP compared with NOM tissues. Regarding the ligands, the mRNAs of amphiregulin (AREG), epiregulin (EREG), and heparin-binding EGF-like growth factor (HB-EGF) were more highly expressed in OLP compared with NOM tissues. These ligands were strongly expressed by infiltrating lamina propria lymphocytes as well as epithelial keratinocytes in OLP lesions, as shown by immunohistochemistry. The enhanced EGFR expression on the keratinocytes in OLP lesions and the up-regulation of EGF-like ligands in keratinocytes and infiltrating mononuclear cells could contribute to the carcinogenesis and pathogenesis of OLP.
    Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 10/2010; 110(6):748-54. DOI:10.1016/j.tripleo.2010.06.022 · 1.46 Impact Factor
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    ABSTRACT: For many years, gingival tumors of what appear to be peripherally located intraosseous ameloblastoma (IA) arising from the alveolar bone surface have often been confused with peripheral ameloblastoma (PA) causing resorption of the underlying bone. We analyzed a series of five cases of ameloblastoma that demonstrated a combined PA and IA architecture. The tumor commonly involved the anterior-premolar area, mostly in the maxilla and mainly in middle-aged men. The clinical presentation was an exophytic gingival mass inferior to which was a small bone defect. The predominant extraosseous component showed a papillary gross surface, reflecting the histologic proof of fusion between the submucosal tumor and the surface epithelium. In addition to the PA-like growth pattern, common to all was the presence of neoplastic destruction of the alveolar process, corresponding to an associated radiolucent lesion. This restrained component was acceptable as IA. In two cases, recurrence was observed deep in the alveolar bone with no involvement of the gingiva. These tumors appear to be IA that arose from the marginal alveolar bone and grew preferentially in the gingiva, forming a PA-like appearance. From diagnostic, therapeutic and prognostic points of view, this type of IA should not be confused with PA.
    Head and Neck Pathology 09/2010; 4(3):192-7. DOI:10.1007/s12105-010-0182-6
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    ABSTRACT: Objective: This study aimed to explore the risk factors of poor clinical outcome of visually guided irrigation (VGIR) in patients with chronic closed lock (CCL) of the temporomandibular joint (TMJ). Materials and methods: Sixty-one patients with unilateral CCL who underwent a VGIR were enrolled in this study. At the 3-month follow-up after VGIR, the 61 patients were divided into either the good outcome (g-) group (n=37) or poor outcome (p-) group (n=24), according to the clinical success criteria. Age, gender, duration of symptoms, preoperative painless range of mandibular motion (P-ROM), preoperative TMJ pain, muscle symptoms, MRI findings (the severity of bony change, disc deformity and joint effusion), and arthroscopic findings (the severity of osteoarthritic change, synovial lesion and fibrous adhesion) were selected as the candidates of prognostic factors for VGIR. Each factor was compared between the two groups. Moreover, multiple logistic regression analysis was performed. Result: The preoperative P-ROM of the p-group was significantly lower than that of the g-group. The severity of osteoarthritic change in the p-group was significantly greater than that of the g-group. Regarding the MRI findings, there were no significant differences between the two groups. The multivariate adjusted odds ratio showed that only a decreased preoperative P-ROM was significantly predictive for a poor clinical outcome of VGIR. Conclusion: A pronounced decrease of preoperative P-ROM would be a significant risk factor for a poor clinical outcome of TMJ irrigation in patients with CCL.
    Asian Journal of Oral and Maxillofacial Surgery 09/2010; 22(3):133-137. DOI:10.1016/j.ajoms.2010.04.001
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    ABSTRACT: This study aimed to elucidate the differences in antitumor immune responses between primary tumors and metastatic regional lymph nodes in head and neck squamous cell carcinoma (HNSCC). The clonality of tumor-infiltrating lymphocytes in tissue specimens from 17 HNSCC patients was examined regarding their T-cell receptor (TCR) repertoires and their complementary determining region 3 (CDR3) size spectratyping. Cytokine expression profiles and T-cell phenotypes also were measured by using real-time quantitative polymerase chain reaction. The host immune responses to HNSCC cells, reflected by the TCR repertoire, differed between primary tumors and metastatic lymph nodes. CD8+-T cells and T helper type 1 (TH1)/T cytotoxic 1 (TC1) cell cytokine production in metastatic and nonmetastatic lymph nodes were similar. The antitumor immune response to HNSCC cells changes during lymph node metastasis, and HNSCC cells can escape the cytotoxic immune responses mediated by CD8+-T cells and TH1/TC1 cells. These results suggest that lymph node metastasis might be associated with changes in the nature of the primary tumor antigens.
    Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology 09/2010; 110(3):341-50. DOI:10.1016/j.tripleo.2010.03.030 · 1.46 Impact Factor

Publication Stats

230 Citations
53.25 Total Impact Points


  • 2004-2014
    • Tsurumi University
      • • Department of Oral and Maxillofacial Surgery
      • • Department of Oral Medicine
      • • School of Dental Medicine
      • • Department of Pathology
      Yokohama, Kanagawa, Japan
  • 2006
    • Center For Oral & Maxillofacial Surgery
      Georgia, United States