Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Yoshihide Mori Last modified date:2020.01.10

Professor / Maxillofacial Diagnostic and Surgical Sciences  / Department of Dental Science / Faculty of Dental Science

1. Naoyuki Fukuda, Masayuki Kanazawa, Kanji Tsuru, Akira Tsuchiya, Sunarso, Riki Toita, Yoshihide Mori, Yasuharu Nakashima, Kunio Ishikawa, Synergistic effect of surface phosphorylation and micro-roughness on enhanced osseointegration ability of poly(ether ether ketone) in the rabbit tibia, Scientific reports, 10.1038/s41598-018-35313-7, 8, 1, 2018.12, This study was aimed to investigate the osseointegration ability of poly(ether ether ketone) (PEEK) implants with modified surface roughness and/or surface chemistry. The roughened surface was prepared by a sandblast method, and the phosphate groups on the substrates were modified by a two-step chemical reaction. The in vitro osteogenic activity of rat mesenchymal stem cells (MSCs) on the developed substrates was assessed by measuring cell proliferation, alkaline phosphatase activity, osteocalcin expression, and bone-like nodule formation. Surface roughening alone did not improve MSC responses. However, phosphorylation of smooth substrates increased cell responses, which were further elevated in combination with surface roughening. Moreover, in a rabbit tibia implantation model, this combined surface modification significantly enhanced the bone-to-implant contact ratio and corresponding bone-to-implant bonding strength at 4 and 8 weeks post-implantation, whereas modification of surface roughness or surface chemistry alone did not. This study demonstrates that combination of surface roughness and chemical modification on PEEK significantly promotes cell responses and osseointegration ability in a synergistic manner both in vitro and in vivo. Therefore, this is a simple and promising technique for improving the poor osseointegration ability of PEEK-based orthopedic/dental implants..
2. Naoyuki Fukuda, Akira Tsuchiya, Sunarso, Riki Toita, Kanji Tsuru, Yoshihide Mori, Kunio Ishikawa, Surface plasma treatment and phosphorylation enhance the biological performance of poly(ether ether ketone), Colloids and Surfaces B: Biointerfaces, 10.1016/j.colsurfb.2018.09.032, 173, 36-42, 2019.01, Poly(ether ether ketone) (PEEK) has emerged as an alternative endosseous material to metal implants mainly because of its lack of allergic sensitivity and radiolucency, while maintaining similar mechanical properties with bone. However, a disadvantage of PEEK is its weak osseointegration ability compared with metal implants. To overcome this, we prepared a phosphate group-modified PEEK by plasma treatment and subsequent phosphorylation reaction. Plasma treatment and phosphate modification of PEEK changed its hydrophobic surface to a hydrophilic surface while maintaining the original surface topography and roughness. Phosphate modification increased the bioactivity of rat bone marrow stromal cells (BMSCs), including proliferation, alkaline phosphatase activity, and bone-like nodule formation; however, this effect was negligible in plasma-treated PEEK. In addition, phosphate modification attenuated the phenotypic polarization of lipopolysaccharide-primed RAW264.7 macrophages to an inflammatory phenotype, based on the finding that macrophages on phosphate-modified PEEK produced decreased levels of the inflammatory cytokine and increased levels of the anti-inflammatory cytokine. Finally, in an animal study, phosphate-modified PEEK exhibited a doubled pullout force from the femur bone cavity compared with bare PEEK. Thus, we conclude that phosphate modification can significantly improves the implant-bone bonding strength of PEEK by enhancing BMSCs activity and reducing excessive inflammation..
3. Tomohiro Yamada, Goro Sugiyama, Ken Higashimoto, Azusa Nakashima, Hiroyuki Nakano, Tomoki Sumida, Hidenobu Soejima, Yoshihide Mori, Beckwith-Wiedemann syndrome with asymmetric mosaic of paternal disomy causing hemihyperplasia, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 10.1016/j.oooo.2018.07.053, 127, 3, e84-e88, 2019.03, Beckwith-Wiedemann syndrome (BWS) is a congenital disorder with 3 main features—overgrowth in infancy, macroglossia, and abdominal wall defects. Here, we report on a 5-month old girl with hemihyperplasia and macroglossia caused by paternal uniparental disomy (pUPD) asymmetric mosaic on chromosome 11p15.5. She could not retract her tongue into her mouth and the midline of the tongue was shifted to the left. Glossectomy was performed at age 1 year. A specimen of the tongue showed normal skeletal muscle, but the muscle fibers were closely spaced, and there were fewer stroma components in the tissue from the right side of the tongue than that from the left side. With respect to pUPD of chromosome 11p15.5, microsatellite marker analysis of the tongue tissue specimen revealed a higher mosaic rate in the tissue from the right side of the tongue (average 48.3%) than that from the left side (average 16.9%). Methylation analysis of Kv differentially methylated region (DMR) 1 (KvDMR1) and H19DMR revealed hypomethylation of KvDMR1 and hypermethylation of H19DMR in the tissue on the right side of the tongue (hyperplastic side). In this case, the difference in mosaic rate of pUPD in the 11p15.5 region was hypothesized to influence the expression level of insulin-like growth factor 2. This result may be helpful to clinicians, especially surgeons, when planning plastic surgery for hemihyperplasia..
4. Hiroyuki Nakano, Kazuya Inoue, Tomoki Sumida, Tomohiro Yamada, Yoshihide Mori, Osteosynthesis using the uncalcined and unsintered hydroxyapatite/Poly-L-Lactic acid system, Annals of Maxillofacial Surgery, 10.4103/ams.ams_192_17, 8, 1, 116-117, 2018.01, The poly-L-lactic acid mini-plate system accomplished rapid development. However, the system still has a variety of problems. One such problem is the breakage of screws. In this technical report, we develop the temporary fixing screws made from stainless with hexagon steel that exhibit a hexagonal head and thread part that also features a tapping function..
5. Yu Kamata, Tomoki Sumida, Ryuichi Murase, Hiroyuki Nakano, Tomohiro Yamada, Yoshihide Mori, Blockade of androgen-induced malignant phenotypes by flutamide administration in human salivary duct carcinoma cells, Anticancer Research, 10.21873/anticanres.11196, 36, 11, 6071-6075, 2016.11, Background/Aim: Androgens are known to play a critical role in prostate cancer progression, but their effect on malignant phenotypes in salivary gland cancer is unclear. The androgen-androgen receptor (AR) axis may be involved in malignant phenotypes of salivary duct carcinoma (SDC) cells and therefore may be a new target for SDC treatment. To test this hypothesis, we investigated the effect of the androgen 5α-dihydrotestosterone (DHT) on proliferation, migration, and invasiveness of SDC cells. Materials and Methods: We used a wound-healing assay to measure cell migration and a Boyden chamber invasion assay to investigate SDC cell invasive capacity. Results: DHT treatment increased cell proliferation, migration, and invasion. However, treatment with flutamide, an AR inhibitor, blocked the effects of DHT. Conclusion: These results suggest that the androgen-AR axis is involved in SDC malignancy and may be an effective therapeutic target for treatment of human SDC..
6. Akihiko Matsumoto, Masanori Sasaki, Rainer Schmelzeisen, Yukiko Oyama, Yoshihide Mori, Pit Jacob Voss, Primary wound closure after tooth extraction for prevention of medication-related osteonecrosis of the jaw in patients under denosumab, Clinical Oral Investigations, 10.1007/s00784-016-1762-y, 21, 1, 127-134, 2017.01, Objectives: Some recent reports have indicated that local infection causes osteonecrosis of the jaw and described that tooth extraction may not be a direct cause of developing medication-related osteonecrosis of the jaw (MRONJ) in patients receiving antiresorptive medications. Tooth extraction and elimination of the source of infection are expected to reduce the risk of developing MRONJ. However, there is no data regarding prevention for developing osteonecrosis of the jaw in patients receiving denosumab. Therefore, the aim of this study was to investigate the outcome of tooth extractions with proper wound closure in patients receiving denosumab. Patients and methods: Forty teeth in 19 patients treated with denosumab therapy were extracted under preoperative intravenous antibiotics. Patients who had already developed MRONJ in the extraction sites or who had a history of radiation therapy were excluded. During surgery, bone edges were smoothed and all wounds were closed using the double-layered technique. Results: Thirty-seven extraction sites (92.5 %) in 17 out of 19 patients (89.5 %) were healed. However, three extraction sites in two patients had complications; one patient had exposed bone and developed MRONJ (stage 1) and the other developed a mucosa fistula. Additional surgical procedures were performed and all wounds were completely healed. Conclusions: Tooth extractions in patients receiving denosumab can be performed in an appropriate manner and result in good outcomes. Clinical relevance: This study indicated that tooth extraction with proper wound closure to avoid secondary infection may be effective for the prevention of MRONJ even in high-risk patients..
7. Naoyuki Fukuda, Kanji Tsuru, Yoshihide Mori, Kunio Ishikawa, Effect of citric acid on setting reaction and tissue response to β-TCP granular cement, Biomedical Materials (Bristol), 10.1088/1748-605X/aa5aea, 12, 1, 2017.02, We recently reported that when an acidic calcium phosphate solution is mixed with β-tricalcium phosphate (β-TCP) granules, the resulting dicalcium phosphate dihydrate (DCPD) crystals form bridges between the β-TCP granules, creating a set interconnected porous structure in approximately 1 min. Although this self-setting β-TCP granular cement (β-TCPGC) is useful for clinical applications, the short setting time is a key drawback for handling. In this study, the setting time of β-TCPGC was adjusted with the addition of citric acid, which is a known inhibiter of DCPD crystal growth. As the concentration of citric acid in the acidic calcium phosphate solution increased, the amount of DCPD formation in the set β-TCPGC decreased, and the crystal morphology of DCPD became elongated. β-TCPGC prepared with various citric acid concentrations were used as grafting material in rat calvarial bone defects to evaluate bone regeneration in vivo. Four weeks after implantation, no inflammatory reaction and approximately 20% new bone formation were observed, regardless of the presence or absence of citric acid in the liquid phase of β-TCPGC. We concluded, therefore, that citric acid might be a useful retarder of β-TCPGC setting times..
8. Azusa Nakashima, Hiroyuki Nakano, Tomohiro Yamada, Kazuya Inoue, Goro Sugiyama, Kumamaru Wataru, Yasumichi Nakajima, Tomoki Sumida, Takeshi Yokoyama, Katsuaki Mishiama, Yoshihide Mori, The relationship between lateral displacement of the mandible and scoliosis, Oral and Maxillofacial Surgery, 10.1007/s10006-016-0607-9, 21, 1, 59-63, 2017.03, Objectives: Idiopathic scoliosis is an orthopaedic disease of childhood, with onset and progress occurring until adolescence. Here, the relationship between lateral displacement of the mandible and scoliosis was analysed quantitatively. Methods: Seventy-nine non-syndromic Japanese patients (18 men, 61 women), who were diagnosed with jaw deformities and underwent surgical orthognathic treatment at Kyushu University Hospital from January 2011 to August 2014, were enrolled. Their mean age at the time of radiography was 25.3 ± 8.7 years. Postero-anterior cephalometric radiographs and chest radiographs were examined. In postero-anterior cephalometric radiographs, a horizontal baseline (X-axis) was drawn as a straight line that intersects both the zygomatic bases, and a vertical line (Y-axis) was marked perpendicular to the X-axis, with an intersection at the anterior nasal spine (ANS). Point A was defined as the intersection of the X- and Y-axes, and line A was defined as the line connecting point A to the menton. The angle made by the X-axis and line A (i.e., lateral displacement of the mandible) was measured. We designated an absolute value even if the mandibular menton was located on the right or left side. In chest radiographs, Cobb’s method was used to measure scoliosis curves; the direction of the curve was designated similarly. Results: Nine (11.4%) individuals had a Cobb angle >10°. There was a positive correlation between the Cobb angle and the degree of mandibular deviation (p < 0.05). Conclusion: Lateral displacement of the mandible and scoliosis are related..
9. Ayako Kozuma, Masanori Sasaki, Katsuhiro Seki, Takeshi Toyoshima, Hiroyuki Nakano, Yoshihide Mori, Preoperative chronic sinusitis as significant cause of postoperative infection and implant loss after sinus augmentation from a lateral approach, Oral and Maxillofacial Surgery, 10.1007/s10006-017-0611-8, 21, 2, 193-200, 2017.06, Objectives: Among intra/postoperative complications of sinus augmentation from a lateral approach, postoperative infection and implant loss are particularly important because they have irreversible consequences. The purpose of this study was to determine the causes of postoperative infection and implant loss after a lateral approach and to determine the appropriate prophylaxis and therapy. Materials and methods: In total, 109 patients (121 sinuses, 252 implants) were included in this study. The correlation between postoperative infection and implant loss and clinical variables was assessed using logistic regression analyses. Results: Postoperative infection and implant loss occurred in 8/121 sinuses (6.6%). Infection had the strongest correlation to preoperative chronic sinusitis (p = 0.007), followed by timing of implant insertion. Implant loss had the strongest correlation to preoperative chronic sinusitis (p = 0.007), followed by sex, diabetes, postoperative use of dentures, and intraoperative perforation of the sinus membrane. Conclusions: Preoperative chronic sinusitis could be a significant cause of postoperative infection and implant loss when using sinus augmentation from a lateral approach. For appropriate prophylaxis and therapy, it is necessary to diagnose the presence of chronic sinusitis that should be treated with proper methods prior to sinus augmentation..
10. Kana Ishibashi, kotaro ishii, Goro Sugiyama, Yu Kamata, Azusa Suzuki, Kumamaru Wataru, Yukiko Ohyama, Hiroyuki Nakano, Tamotsu Kiyoshima, Tomoki Sumida, Tomohiro Yamada, Yoshihide Mori, Regulation of β-catenin phosphorylation by PR55β in adenoid cystic carcinoma, Cancer Genomics and Proteomics, 10.21873/cgp.20064, 15, 1, 53-60, 2018.01, Background/Aim: Adenoid cystic carcinoma (AdCC) is a rare cancer of the salivary gland with high risk of recurrence and metastasis. Wnt signalling is critical for determining tumor grade in AdCC, as it regulates invasion and migration. β-catenin dephosphorylation plays an important role in the Wnt pathway, but its underlying molecular mechanism remains unclear. Materials and Methods: Because the regulatory subunits of protein phosphatase 2A (PP2A) drive Wnt signalling via target molecules, including β-catenin, we used qRT-PCR and immunoblot analysis to investigate the expression of these subunits in an AdCC cell line (ACCS) and a more aggressive subline (ACCS-M). Results: PR55β was highly expressed in ACCS-M, suggesting its functional importance. In addition, PR55β expression was associated with tumor grade, with ACCS-M exhibiting higher PR55β levels. More importantly, knockdown of PR55β in ACCS-M cells significantly reduced invasiveness and metastatic ability. Furthermore, dephosphorylation and total levels of β-catenin were dependent on PR55β in ACCS-M. Finally, we confirmed a correlation between PR55β staining intensity and histopathological type in human AdCC tissues. Conclusion: Our study provides new insight into the interaction between PR55β and β-catenin and suggests that PR55β may be a target for the clinical treatment of AdCC..
11. Kana Ishibashi, kotaro ishii, Goro Sugiyama, Tomoki Sumida, Tsuyoshi Sugiura, Yu Kamata, Katsuhiro Seki, Takahiro Fujinaga, Kumamaru Wataru, Yosuke Kobayashi, Naomi Hiyake, Hiroyuki Nakano, Tomohiro Yamada, Yoshihide Mori, Deregulation of nicotinamide N-methyltransferase and gap junction protein alpha-1 causes metastasis in adenoid cystic carcinoma, Anticancer Research, 10.21873/anticanres.12207, 38, 1, 187-197, 2018.01, Background/Aim: Adenoid cystic carcinoma (AdCC) is a malignant tumor that occurs in the salivary glands and frequently metastasizes. The aim of this study was to identify factors mediating AdCC metastasis. Materials and Methods: We established three AdCC cell lines by orthotropic transplantation and in vivo selection: parental, highly metastatic (ACCS-M-GFP), and lymph node metastatic (ACCS-LN-GFP) cells. Results: We examined the three cell lines. DNA microarray indicated significantly altered processes in ACCS-LN-GFP cells: particularly, the expression of nicotinamide N-methyltransferase (NNMT) was enhanced the most. NNMT is associated with tumorigenesis and is a potential tumor biomarker. Concomitantly, we found-significant down-regulation of gap junction protein alpha-1. We suggest that ACCS-LN-GFP cells acquire cancer stem cell features involving the up-regulation of NNMT and the loss of gap junction protein alpha-1, leading to epithelial-mesenchymal transition and consequent AdCC metastasis. Conclusion: NNMT is a potential biomarker of AdCC..
12. Naoyuki Fukuda, Kanji Tsuru, Yoshihide Mori, Kunio Ishikawa, Fabrication of self-setting β-tricalcium phosphate granular cement, Journal of Biomedical Materials Research - Part B Applied Biomaterials, 10.1002/jbm.b.33891, 106, 2, 800-807, 2018.02, Bone defect reconstruction would be greatly improved if β-tricalcium phosphate (β-TCP) granules had the ability to self-set without sacrificing their osteoconductivity potential. This study aimed to identify a method to permit β-TCP self-setting whilst maintaining good osteoconductivity. When mixed with acidic calcium phosphate solution, β-TCP granules were found to readily set, forming a fully interconnected porous structure. On mixing, dicalcium phosphate dihydrate crystals formed on the surface of β-TCP granules, bridging the granules and resulting in the setting reaction. The setting time of the β-TCP granular cement (β-TCP GC) was approximately 1 min and its mechanical strength, in terms of diametral tensile strength, was approximately 0.8 MPa. The β-TCP GC and β-TCP granules both showed the same level of osteoconductivity within rat calvaria bone defects. At 2 and 4 weeks post-implantation, new bone formation was comparable between the two β-TCP based bone substitutes. We conclude that β-TCP GC has excellent potential for use as a cement in bone defect reconstruction..
13. Mhd Hassan Albogha, Yoshihide Mori, Ichiro Takahashi, Three-dimensional titanium miniplates for fixation of subcondylar mandibular fractures
Comparison of five designs using patient-specific finite element analysis, Journal of Cranio-Maxillo-Facial Surgery, 10.1016/j.jcms.2017.12.020, 46, 3, 398-412, 2018.03, Purpose: The purpose of the current study is to compare the performance of five designs of three-dimensional titanium miniplates (lambda, strut, delta, rhombic and trapezoid) for fixation of subcondylar mandibular fracture. Materials and methods: Three-dimensional models were constructed for the five miniplates with their screws and integrated into a virtually fractured mandible that was derived from a computed tomographic image of living human. Patient-specific finite element models were analyzed to compare the performances of the miniplates. Miniplates were compared for titanium hardware volume, condylar head displacement, bone strains and miniplates’ stresses. Results: Least condylar head displacement, and thereby best fixation primary stability, was found in the trapezoid miniplate. On the other hand, the greatest displacements were found in lambda and strut miniplates. Bone strains, as an indicator of secondary stability, predicted high strains in bone around the screws affixing the delta miniplate. Therefore, high risk of failure due to screws loosening is expected when using the delta miniplate. Stresses in miniplates were excessive in the strut and lambda miniplates, which implies a high risk of miniplate fracture. Conclusions: The current findings predicted significant differences in performance among the different designs of three-dimensional miniplates. The trapezoid miniplate seems to have the best performance, as it provided the greatest rigidity with relatively low bone strains..
14. Azusa Nakashima, Tomohiro Yamada, Hiroyuki Nakano, Goro Sugiyama, Tomotaka Sugi, Y. U. Kamata, Tomoki Sumida, Yoshihide Mori, Jaw asymmetry may cause bad posture of the head and the spine—A preliminary study, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 10.1016/j.ajoms.2018.01.001, 30, 3, 242-246, 2018.05, Objective: Dental occlusion may relate to general conditions including posture, however, there is little evidence of jaw deformities and general posture. The objective of this study is to assess the relationship between skeletal jaw asymmetry and head/body posture. Methods: Forty-five mandibular asymmetry patients were included in this study. Lateral mandibular deviation, head inclination, and vertebrae deviation were studied before and after orthognathic surgery. Results: There was a correlation between mandibular deviation and head inclination, however, there were no correlation between vertebrae deviation and head inclination. On average, head inclination and vertebrae deviation were not changed after orthognathic surgery. But, for cases with a large deviation, they improved after surgery. Conclusions: Lateral mandibular deviation influences head and spine posture, in most cases reversibly..
15. Tomoki Sumida, Akiko Ishikawa, Yu Kamata, Hiroyuki Nakano, Tomohiro Yamada, Yoshihide Mori, Estrogen nhances malignant phenotypes in human salivary adenoid cystic carcinoma cells, Anticancer Research, 36, 6, 2793-2798, 2016.06, Background/Aim: Adenoid cystic carcinoma (SGC) is a common type of salivary gland cancer (SGC). Surgery is the first treatment choice because chemoradiotherapy is usually not effective. Therefore, new treatment modalities are urgently needed. In this study, it was investigated whether the estrogen axis could be a treatment target or not. Materials and Methods: Adenoid cystic carcinoma (ACC) ACCM cells, were used. The specific cell line lacks estrogen receptor (ER). ER was introduced in ACCM cells, and the effect of 17estradiol (E2) was investigated on cell proliferation, cell-cycle distribution, and cell motility. Results: E2 induced cell proliferation, and the S-phase fraction increased in a dose-dependent manner. Cell motility was also up-regulated compared to control cells. Conclusion: The estrogen/ER system up-regulated malignant phenotypes in ER-positive ACC, and hormone therapy may have a potential as effective treatment for this malignancy..
16. Tomoki Sumida, Akiko Ishikawa, Yoshihide Mori, Stimulation of the estrogen axis induces epithelial-mesenchymal transition in human salivary cancer cells, Cancer Genomics and Proteomics, 13, 4, 305-310, 2016.07, Background: Salivary gland cancer is a common type of head and neck cancer characterized by occasional deep invasion and lung metastasis. The precise role of sex steroid hormones in salivary gland cancer is unclear. To address this issue, we investigated whether the estrogen axis modulates salivary adenocarcinoma (SAC) and whether hormone therapy can be an effective treatment. Materials and Methods: The estrogen receptor (ER) was overexpressed in HSG human SAC cells that lack endogenous ER and the cells were treated with and without 17β-estradiol (E2). Results: E2 enhanced malignant phenotypes. Moreover, E2 treatment reduced E-cadherin expression, while increasing that of N-cadherin, vimentin, and inhibitor of differentiation 1 proteins that are associated with the epithelial-mesenchymal transition. Cell invasion was enhanced through activation of matrix metalloproteinase-9. Conclusion: These results indicate that hormone therapy used in breast cancer may also be effective for ER-positive SAC..
17. Tomoki Sumida, Akiko Ishikawa, Hiroyuki Nakano, Tomohiro Yamada, Yoshihide Mori, Pierre Yves Desprez, Targeting ID2 expression triggers a more differentiated phenotype and reduces aggressiveness in human salivary gland cancer cells, Genes to Cells, 10.1111/gtc.12389, 21, 8, 915-920, 2016.08, Inhibitors of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. We previously determined that ID1 was highly expressed in aggressive salivary gland cancer (SGC) cells in culture. Here, we show that ID2 is also expressed in aggressive SGC cells. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. Moreover, ID2 knockdown almost completely suppresses invasion and the expression of matrix metalloproteinase 9. In conclusion, ID2 expression maintains an aggressive phenotype in SGC cells, and ID2 repression triggers a reduction in cell aggressiveness. ID2 therefore represents a potential therapeutic target during SGC progression. ID proteins are negative regulators of basic helix-loop-helix transcription factors and generally stimulate cell proliferation and inhibit differentiation. ID2 knockdown triggers important changes in cell behavior, that is, it significantly reduces the expression of N-cadherin, vimentin and Snail, induces E-cadherin expression and leads to a more differentiated phenotype exemplified by changes in cell shape. ID2 therefore represents a potential therapeutic target during SGC progression..
18. Tomoki Sumida, Yu Kamata, Yosuke Kobayashi, Akiko Ishikawa, Yoshihide Mori, ID1 controls aggressiveness of salivary gland cancer cells via crosstalk of IGF and AKT pathways, Anticancer Research, 36, 8, 3865-3870, 2016.08, Background: Inhibitor of differentiation or DNA binding 1 (ID1) is overexpressed in human salivary gland cancer (SGC). The insulin growth factor (IGF) system is an attractive target in cancer control because it is associated with various cancer progressions. Materials and Methods: The human SGC cell line HSY with abundant ID1 was used. ID1 knockdown and its effect on the IGF system were investigated. Cell proliferation and invasion, as well as associated protein expression, were analyzed. Phospho-AKT was also evaluated. Results: ID1 knockdown reduced cell proliferation and invasion, while the expression of proteins associated with malignant phenotypes was altered. IGF-II expression was suppressed, suggesting that this system is one of the mechanisms underlying effects of ID1 in SGC cells. c-Myc was up-regulated, whereas p21 and p27 were downregulated. Moreover, phospho-AKT was reduced in ID1-knockeddown cells. Conclusion: ID1 down-regulation induced parallel changes in the IGF and AKT pathways. The crosstalk of these pathways may enhance malignant phenotypes in SGCs..
19. Tomoki Sumida, Yosuke Kobayashi, Akiko Ishikawa, Kozue Shinohara, Emi Matsumoto, Satoshi Kamakura, Yoshihide Mori, Bite force and masticatory performance using implant-supported overdentures after treatment of mandibular cancer, Anticancer Research, 36, 8, 4077-4080, 2016.08, Aim: To evaluate overdentures with regard to artificial restoration of oral function following mandibular cancer. Materials and Methods: We examined 32 patients who had undergone mandibular bone resection as treatment for malignancy and were using implant-supported overdentures. The patients were aged 55-87 years (mean=68.6) with a male to female ratio of 23:9. Marginal resection was performed in 29 patients and segmentectomy in 3. Results: Before and after using the attachment for overdenture, oral function differed significantly. After the setting of implant-retained overdentures, maximum bite force increased on average by 362% (average, from 16.2 N to 58.8 N; p<0.01). Xylitol gum examination showed a 363% increase in masticatory performance (average, 3.1 to 8.0 points; p<0.01). Conclusion: Implant-retained overdenture resulted in improved oral function, that was lost after treatment for mandibular cancer..
20. Kouhei Hayashi, Tatsuya Ikari, Goro Sugiyama, Tsuyoshi Sugiura, Yukiko Ohyama, Kumamaru Wataru, Kanemitsu Shirasuna, Yoshihide Mori, Involvement of the T-box transcription factor Brachyury in early-stage embryonic mouse salivary gland, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2016.06.140, 477, 4, 814-819, 2016.09, The mouse submandibular gland (SMG) is important organ for embryonic development, and branching morphogenesis is regulated by many molecules containing transcription factors. Real-time reverse transcriptase polymerase chain reaction revealed that the expression of Brachyury increased in the SMG and peaked between E12.5–E13.5, concomitant with the early stage of branching morphogenesis. The expression of Brachyury in SMG rudiments between E12.5–E13.5 was confirmed by western blotting. In addition, fibronectin and Btbd7 (regulated by fibronectin), which are both essential for cleft formation, were expressed strongly during the same period. The Sox2 and Wnt3a, which regulate cell growth, were also expressed strongly during E12.5–E13.5. On the other hand, cleft formation and branching morphogenesis was suppressed by knockdown of Brachyury gene, suggesting that Brachyury plays a central role in regulating cell growth and cleft formation in early-stage embryonic mouse salivary gland development..
21. Toshihiro Noma, Fumi Takahashi-Yanaga, masaki arioka, Yoshihide Mori, Toshiyuki Sasaguri, Inhibition of GSK-3 reduces prostaglandin E2 production by decreasing the expression levels of COX-2 and mPGES-1 in monocyte/macrophage lineage cells, Biochemical Pharmacology, 10.1016/j.bcp.2016.07.014, 116, 120-129, 2016.09, Inflammatory stimuli induce prostaglandin E2 (PGE2) synthesis by upregulating cycloxgenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1). Glycogen synthase kinase-3 (GSK-3) reportedly plays an important role in inflammatory reactions, whereas the role of this enzyme in inflammatory PGE2 production remains unclear. In the present study, therefore, we examined whether inhibition of GSK-3 can reduce inflammatory PGE2 production in vitro and in vivo. When macrophage-like cells differentiated from THP-1 were stimulated with lipopolysaccharide (LPS), PGE2 production and the expression levels of COX-2 and mPGES-1 were markedly elevated. GSK-3 inhibitors LiCl and SB216763 strongly suppressed their protein levels through inhibition of mRNA expressions. Subsequently, we examined the effect of GSK-3 inhibitors on nuclear factor κB (NF-κB) and early growth response-1 (Egr-1). The GSK-3 inhibitors had no significant effect on the NF-κB pathway, whereas they significantly decreased the expression level of Egr-1. Pharmacological and genetic inhibitions of GSK-3 also strongly suppressed PGE2 production in cultured peritoneal macrophages and in inflammatory air pouches made under the skin of living mice. These results suggested that GSK-3 plays a key role in PGE2 production by increasing COX-2 and mPGES-1 probably through Egr-1-mediated transcription and GSK-3 inhibitors may be potential as novel anti-inflammatory drugs..
22. Yasumichi Nakajima, Hiroyuki Nakano, Tomoki Sumida, Tomohiro Yamada, Kazuya Inoue, Goro Sugiyama, Katsuaki Mishima, Yoshihide Mori, High Le Fort I osteotomy for correction of mid-face deformity in Crouzon syndrome, Congenital Anomalies, 10.1111/cga.12168, 56, 5, 240-242, 2016.09, An 18-year-old woman with mild Crouzon syndrome was referred with malocclusion and mandibular protrusion. Examination revealed Class III canine and molar relationships, hypoplastic maxilla, 1-mm overbite, and −2-mm overjet. Analysis showed 69° sella-nasion-A, 73.6° sella-nasion-B, and −4.6° A point-nasion-B point angles. Polysomnography revealed respiratory disturbance and 6.3% oxygen desaturation indices of 5.4/h and 9.0/h. We performed double-jaw surgery using high Le Fort I osteotomy and bilateral sagittal split ramus osteotomy for midfacial deformity correction. Twelve months post-surgery, her measures were 70.8°, 72°, −1.2°, 3.0/h, and 6.1/h, respectively. Esthetics were satisfactory. High Le Fort I osteotomy is effective for midfacial deformity correction in patients with Crouzon syndrome..
23. Minami Shibuya, Tatsuya Ikari, Goro Sugiyama, Yukiko Ohyama, Kumamaru Wataru, Koki Nagano, Tsuyoshi Sugiura, Kanemitsu Shirasuna, Yoshihide Mori, Efficient regulation of branching morphogenesis via fibroblast growth factor receptor 2c in early-stage embryonic mouse salivary glands, Differentiation, 10.1016/j.diff.2016.05.005, 92, 4, 216-224, 2016.10, Salivary gland (SG) defects have a wide range of health implications, including xerostomia, bacterial infections, and oral health issues. Branching morphogenesis is critical for SG development. A clear understanding of the mechanisms underlying this process will accelerate SG regeneration studies. Fibroblast growth factor receptor 2 (FGFR2) interacts with multiple fibroblast growth factors (FGFs), which promote development. FGFR2 consists of two isoforms, FGFR2b and FGFR2c. FGFR2b is critical for SG development, but little is known about the expression and function of FGFR2c. We investigated the expression of all FGFR family members in fetal SGs between embryonic day 12.5 (E12.5) and E18.5. Based on RT-PCR, we observed an increase in the expression of not only Fgfr2b, but also Fgfr2c in early-stage embryonic mouse SGs, suggesting that FGFR2c is related to SG development. The branch number decreased in response to exogenous FGF2 stimulation, and this effect was suppressed by a mouse anti-FGFR2c neutralizing antibody (NA) and siRNA targeting FGFR2c, whereas FGFR2b signaling was not inhibited. Moreover, the expression of marker genes related to EMT was induced by FGF2, and this expression was suppressed by the NA. These results suggested that branching morphogenesis in SGs is regulated by FGFR2c, in addition to FGFR2b. Interestingly, FGFR2c signaling also led to increased fgf10 expression, and this increase was suppressed by the NA. FGFR2c signaling regulates branching morphogenesis through the activation of FGFR2b signaling via increased FGF10 autocrine. These results provide new insight into the mechanisms by which crosstalk between FGFR2b and FGFR2c results in efficient branching morphogenesis..
24. Yu Kamata, Tomoki Sumida, Yosuke Kobayashi, Akiko Ishikawa, Kumamaru Wataru, Yoshihide Mori, Introduction of ID2 enhances invasiveness in ID2-null oral squamous cell carcinoma cells via the SNAIL axis, Cancer Genomics and Proteomics, 10.21873/cgp.20012, 13, 6, 493-498, 2016.11, Aim: Inhibitor of DNA-binding (ID) proteins are negative regulators of basic helix-loop-helix transcription factors that generally stimulate cell proliferation and inhibit differentiation. However, the role of ID2 in cancer progression remains ambiguous. Here, we investigated the function of ID2 in ID2-null oral squamous cell carcinoma (OSCC) cells. Materials and Methods: We introduced an ID2 cDNA construct into ID2-null OSCC cells and compared them with empty-vector-transfected cells in terms of cell proliferation, invasion, and activity and expression of matrix metalloproteinase (MMP). Results: ID2 introduction resulted in enhanced malignant phenotypes. The ID2-expressing cells showed increased N-cadherin, vimentin, and E-cadherin expression and epithelial-mesenchymal transition. In addition, cell invasion drastically increased with increased expression and activity of MMP2. Immunoprecipitation revealed a direct interaction between ID2 and zinc finger transcription factor, snail family transcriptional repressor 1 (SNAIL1). Conclusion: ID2 expression triggered a malignant phenotype, especially of invasive properties, through the ID2- SNAIL axis. Thus, ID2 represents a potential therapeutic target for OSCC..
25. K. Inoue, H. Nakano, Tomoki Sumida, Tomohiro Yamada, N. Otawa, N. Fukuda, Y. Nakajima, Kumamaru Wataru, K. Mishima, M. Kouchi, Ichiro Takahashi, Yoshihide Mori, A novel measurement method for the morphology of the mandibular ramus using homologous modelling, Dentomaxillofacial Radiology, 10.1259/dmfr.20150062, 44, 8, 2015.01, Objectives: It is important to assess the mandibular morphology when orthognathic surgery, especially mandibular ramus osteotomy, is performed. Several studies on three-dimensional (3D) facial asymmetry have reported differences in linear and angle measurements between the deviated and contralateral sides in asymmetric mandibles. However, methods used in these studies cannot analyse the 3D morphology of the ramus. In this study, we aimed to evaluate the differences in mandibular ramus between the deviated and contralateral sides in asymmetric mandibles using traditional measurements as well as 3D shape analysis. Methods: 15 Japanese females with jaw deformities treated by orthodontic surgery were enrolled. 3D CT images were reconstructed, and 14 landmarks were identified on the model surface. Ten linear and four angle measurements were calculated using these landmarks. Homologous ramus models were constructed for each sample, and after converting all homologous models to the right side, 30 homologous models of the ramus were analysed using principal component analysis. Results: Firstly, eight principal components explained .80% of the total variance. Differences between the deviated and contralateral sides in measurements and scores of the eight principal components were tested. Significant difference at the 5% level between the deviated and contralateral sides was observed in five linear measurements, three angle measurements and the third principal component. The variance of the deviated side was significantly larger in the diameter between the mandibular notch and coronoid process, horizontal dilated angle of the mandibular ramus and vertical dilated angle of the mandibular ramus. The variance of the contralateral side was significantly larger in the height of mandibular ramus, height of posterior of mandibular ramus, condylar width, height of condylar head and mandibular angle. The squared multiple correlation coefficient adjusted for the degrees of freedom was 0.815. The third principal component showed the difference between the deviated and contralateral sides. Shape variation represented by the third principal component visually indicated that the contralateral side was larger and had inwardly directed coronoid process and the deviated side had a mandibular angle that was turned inwards to a greater extent. Conclusions: In conclusion, we successfully created a homologous model of the mandibular ramus and demonstrated the effectiveness of this model in the 3D comparison of the ramus morphology between the contralateral and deviated sides in asymmetric mandibles..
26. Naoya Yoshihama, Koujiro Yamaguchi, Satomi Chigita, Mariko Mine, Masakazu Abe, kotaro ishii, Yosuke Kobayashi, Naonari Akimoto, Yoshihide Mori, Tsuyoshi Sugiura, A novel function of CD82/KAI1 in sialyl Lewis antigen-mediated adhesion of cancer cells
Evidence for an anti-metastasis effect by down-regulation of sialyl Lewis antigens, PLoS One, 10.1371/journal.pone.0124743, 10, 4, 2015.04, We have recently elucidated a novel function for CD82 in E-cadherin-mediated homocellular adhesion; due to this function, it can inhibit cancer cell dissociation from the primary cancer nest and limit metastasis. However, the effect of CD82 on selectin ligand-mediated heterocellular adhesion has not yet been elucidated. In this study, we focused on the effects of the metastasis suppressor CD82/KAI1 on heterocellular adhesion of cancer cells to the endothelium of blood vessels in order to further elucidate the function of tetraspanins. The over-expression of CD82 in cancer cells led to the inhibition of experimentally induced lung metastases in mice and significantly inhibited the adhesion of these cells to human umbilical vein epithelial cells (HUVECs) in vitro. Pre-treatment of the cells with function-perturbing antibodies against sLea/x significantly inhibited the adhesion of CD82-negative cells to HUVECs. In addition, cells over-expressing CD82 exhibited reduced expression of sLea/x compared to CD82-negative wild-type cells. Significant down-regulation of ST3 β-galactoside α-2, 3-sialyltransferase 4 (ST3GAL4) was detected by cDNA micro-array, real-time PCR, and western blotting analyses. Knockdown of ST3GAL4 on CD82-negative wild-type cells inhibited expression of sLex and reduced cell adhesion to HUVECs. We concluded that CD82 decreases sLea/x expression via the down-regulation of ST3GAL4 expression and thereby reduces the adhesion of cancer cells to blood vessels, which results in inhibition of metastasis..
27. Koki Nagano, Hiroshi Takeuchi, Jing Gao, Yoshihide Mori, Takahito Otani, Daguang Wang, Masato Hirata, Tomosyn is a novel Akt substrate mediating insulin-dependent GLUT4 exocytosis, International Journal of Biochemistry and Cell Biology, 10.1016/j.biocel.2015.02.013, 62, 62-71, 2015.05, Insulin triggers glucose uptake into skeletal muscle and adipose tissues by gaining the available number of glucose transporter 4 (GLUT4) on the cell surface. GLUT4-loaded vesicles are targeted to plasma membrane from the intracellular reservoir through multiple trafficking and fusion processes that are mainly regulated by Akt. However, it is still largely unknown how GLUT4 expression in the cell surface is promoted by insulin. In the present study, we identified tomosyn at Ser-783 as a possible Akt-substrate motif and examined whether the phosphorylation at Ser-783 is involved in the regulation of GLUT4 expression. Both Akt1 and Akt2 phosphorylated the wild-type tomosyn, but not the mutant tomosyn in which Ser-783 was replaced with Ala. Phosphorylation of tomosyn at Ser-783 was also observed in the intact cells by insulin stimulation, which was blocked by PI3K inhibitor, LY294002. In vitro pull-down assay showed that phosphorylation of tomosyn at Ser-783 by Akt inhibited the interaction with syntaxin 4. Insulin stimulation increased GLUT4 in the cell surface of CHO-K1 cells to promote glucose uptake, however exogenous expression of the mutant tomosyn attenuated the increase by insulin. These results suggest that Ser-783 of tomosyn is a target of Akt and is implicated in the interaction with syntaxin 4..
28. Mariko Mine, Kojiro Yamaguchi, Tsuyoshi Sugiura, Satomi Chigita, Naoya Yoshihama, Rumi Yoshihama, Naomi Hiyake, Yosuke Kobayashi, Yoshihide Mori, miR-203 inhibits Frizzled-2 expression via CD82/KAI1 expression in human lung carcinoma cells, PLoS One, 10.1371/journal.pone.0131350, 10, 7, 2015.07, CD82/KAI1, a member of the tetraspanin superfamily, is a suppressor of metastasis and CD82 inhibits canonical Wnt signaling via downregulation of several Frizzled (FZD) isoforms, resulting in accumulation of β-catenin at the cell membrane. In this study, we investigated the mechanism through which CD82 inhibited FZD expression by examining the effects of microRNAs (miRNAs). The miRanda algorithm predicted 11 miRNAs from FZD sequences. Among these miRNAs, CD82 caused upregulation of miR-203 (by 2.095-fold) and downregulation of miR-338-3p (by 0.354-fold) as compared with control cells. Transfection with miR-203 and miR338-3p mimics or inhibitors revealed that miR-203 downregulated FZD2 mRNA (by 0.268-fold) and protein expression (by 0.701-fold). Moreover, transfection with the miR-203 mimic also inhibited cell migration. Therefore, these findings suggested that CD82 enhanced the expression of miR-203 and directly downregulate FZD2 expression, suppressing cancer metastasis by inhibition of the Wnt signaling pathway..
29. Tomoki Sumida, Naruto Otawa, Yu Kamata, Tomohiro Yamada, Kenichiro Uchida, Hiroyuki Nakano, Hiroyuki Hamakawa, Tetsuya Yamamoto, Yoshiya Ueyama, Yoshihide Mori, A clinical investigation of oral sarcomas at multi-institutions over the past 30 years, Anticancer Research, 35, 8, 4551-4556, 2015.08, Background/Aim: Sarcoma of the oral cavity is rare accounting for around 1% of all malignant oral tumors. The purpose of this study was to find important prognostic factors for patients with oral sarcoma. Patients and Methods: The study included 1,643 patients examined from April 1980 to March 2010 at the Departments of oral and maxillofacial surgery at multi-institutions who had a histopathological diagnosis of malignant oral tumors. Results: Sarcoma accounted for 19 of 1,643 cases (1.16%) in malignant oral tumors. Histologically, osteosarcoma was most common in 6 of the 19 patients, followed by 3 cases each of leiomyo - sarcoma and malignant fibrous histiocytoma, 2 of rhabdomyosarcoma and 1 each of angiosarcoma, Ewing's sarcoma, malignant schwannoma, malignant rhabdoid tumor and undifferentiated sarcoma. Irrespective of the histological type, tumor diameter on initial examination was >50 mm in 8 patients, 7 of whom died. Tumor diameter was <50 mm in 11 patients, 6 of whom survived. Distant metastasis was present in 11 patients, 10 of whom died. The local control rate was 42.1% and 5-year survival rate was 36.8%. Conclusion: Treatment of patients with tumors over 50-mm long in diameter and distant metastasis is extremely difficult. The incidence of oral sarcoma is very low. However, tumor diameter and presence of distant metastasis are important prognostic factors for oral sarcoma according to this multiinstitutional study..
30. Naruto Otawa, Tomoki Sumida, Hisashi Kitagaki, Kiyoyuki Sasaki, Shunsuke Fujibayashi, Mitsuru Takemoto, Takashi Nakamura, Tomohiro Yamada, Yoshihide Mori, Tomiharu Matsushita, Custom-made titanium devices as membranes for bone augmentation in implant treatment
Modeling accuracy of titanium products constructed with selective laser melting, Journal of Cranio-Maxillo-Facial Surgery, 10.1016/j.jcms.2015.05.006, 43, 7, 1289-1295, 2015.09, Objective The purpose of this study was to verify the modeling accuracy of various products, and to produce custom-made devices for bone augmentation in individual patients requiring implantation. Materials and methods Two-(2D) and three-dimensional (3D) specimens and custom-made devices that were designed as membranes for guided bone regeneration (GBR) were produced using a computer-aided design (CAD) and rapid prototyping (RP) method. The CAD design was produced using a 3D printing machine and selective laser melting (SLM) with pure titanium (Ti) powder. The modeling accuracy was evaluated with regard to: the dimensional accuracy of the 2D and 3D specimens; the accuracy of pore structure of the 2D specimens; the accuracy of porosity of the 3D specimens; and the error between CAD design and the scanned real product by overlapped images. Results The accuracy of the 2D and 3D specimens indicated precise results in various parameters, which were tolerant in ISO 2768-1. The error of overlapped images between the CAD and scanned data indicated that accuracy was sufficient for GBR. In integrating area of all devices, the maximum and average error were 292 and 139 μm, respectively. Conclusions High modeling accuracy can be achieved in various products using the CAD/RP-SLM method. These results suggest the possibility of clinical applications..
31. Tomoki Sumida, Hiroyuki Nakano, Hiroyuki Hamakawa, Yoshihide Mori, Dental implants in oral rehabilitation of a maxillary cancer reconstruction
A case report, Journal of Oral Implantology, 10.1563/AAID-JOI-D-13-00136, 41, 6, 737-739, 2015.12.
32. Tomoki Sumida, Naruto Otawa, Yu Kamata, Satoshi Kamakura, Tomiharu Mtsushita, Hisashi Kitagaki, Shigeo Mori, Kiyoyuki Sasaki, Shunsuke Fujibayashi, Mitsuru Takemoto, Atsushi Yamaguchi, Taiji Sohmura, Takashi Nakamura, Yoshihide Mori, Custom-made titanium devices as membranes for bone augmentation in implant treatment
Clinical application and the comparison with conventional titanium mesh, Journal of Cranio-Maxillo-Facial Surgery, 10.1016/j.jcms.2015.10.020, 43, 10, 2183-2188, 2015.12, Objective Development of new custom-made devices to reconstruct alveolar bone for implantation, and comparison with conventional methods were the goals of this study. Materials and methods Using a computer-aided design technique, three-dimensional images were constructed. From these data, custom-made devices were produced by a selective laser melting method with pure titanium. Clinical trials also have been conducted with 26 participants who needed bone reconstruction before implantation; they were divided into 2 groups with 13 patients each. The first group uses custom-made devices; the other uses commercial titanium meshes that need to bend during operation. Some clinical aspects are evaluated after the trial. Results The custom-made devices can be produced closely by following the data precisely. Devices are fit for bone defect site. Moreover, the operation time of the custom-made group (75.4 ± 11.6 min) was significantly shorter than that of the conventional group (111.9 ± 17.8 min) (p < 0.01). Mucosal rupture occurs, without significant difference (p = 0.27), in a patient in the custom-made without severe infection (7.7%), and 3 in conventional (23.1%), respectively. The retaining screw is significantly fewer in the custom-made group than commercial mesh group (p < 0.01). Conclusion These results indicate that our novel protocol could be simple and safe for providing powerful support for guided bone regeneration..
33. Rumi Yoshihama, Koujiro Yamaguchi, Ikumi Imajyo, Mariko Mine, Naomi Hiyake, Naonari Akimoto, Yosuke Kobayashi, Satomi Chigita, Kumamaru Wataru, Tamotsu Kiyoshima, Yoshihide Mori, Tsuyoshi Sugiura, Expression levels of SOX2, KLF4 and brachyury transcription factors are associated with metastasis and poor prognosis in oral squamous cell carcinoma, Oncology Letters, 10.3892/ol.2015.4047, 11, 2, 1435-1446, 2016.02, The prognosis of oral squamous cell carcinoma (OSCC) patients is affected by tumor recurrence and metastasis, and cancer stem cells are hypothesized to be involved in these processes. Thus, the aim of the present study was to determine whether the expression levels of five stem cell-related transcription factors, sex determining region Y-box 2 (SOX2), octamer-binding transcription factor 4 (Oct4), avian myelocytomatosis viral oncogene homolog (c-Myc), Krüppel-like factor 4 (KLF4) and brachyury, are associated with metastasis and survival in OSCC. Immunohistochemistry was performed to analyze the expression of these proteins in biopsy specimens obtained from 108 OSCC patients. The results revealed that the expression of SOX2, Oct4, KLF4 and brachyury were significantly associated with lymph node metastasis (P=0.002, P=0.031, P=0.003 and P=0.007, respectively). In addition, the expression of KLF4 and brachyury were significantly associated with distant metastasis (P=0.014 and P=0.012, respectively). Furthermore, multivariate analysis revealed that SOX2 and KLF4 are predictive factors for lymph node metastasis [odds ratios (ORs), 4.526 and 4.851, respectively], and KLF4 is also a predictive factor for distant metastasis (OR, 9.607). In addition, OSCC patients with low co-expression of SOX2, KLF4 and brachyury exhibited a significantly lower disease-specific survival rate (78.6 vs. 100%, P=0.025, χ2=5.033) and disease-free survival rate (60.7 vs. 90.9%, P=0.015, χ2=5.897) when compared with OSCC patients with high co-expression of these factors. The results indicate that SOX2, KLF4 and brachyury serve important roles in tumor progression, and these transcription factors may thus represent clinically useful prognostic markers for OSCC..
34. Yosuke Kobayashi, Tomoki Sumida, Akiko Ishikawa, Yoshihide Mori, The contribution of dental implants to functional artificial restoration after treatment of oral cancer, Anticancer Research, 36, 6, 3053-3056, 2016.06, Background/Aim: The aim of this study was to evaluate dental implants with regard to artificial restoration of oral function and quality of life in patients with oral cancer. Patients and Methods: We examined 134 implants in 41 patients who had undergone jawbone resection as treatment for oral cancer. The patients were aged 44-89 (mean=61.5) years, and the male to female ratio was 27:14. Results: The 5-year implant success rate was 91.0%. Of the 12 unsuccessful implants, four were embedded on bone grafts with skin flaps, four were embedded on skin flaps using muscle, and four were embedded after peripheral resection. Of the 41 patients, 11 received radiation, but exposure to radiation was not associated with implant loss. The level of satisfaction on the visual analog scale before development of oral cancer was set at 100 mm. Satisfaction fell to 47.0 mm after primary treatment, but recovered to 82.6 mm after implant therapy. Conclusion: Patient satisfaction after implant therapy was high, and the implants resulted in improved quality of life. A high proportion of cases involving use of skin flaps resulted in implant loss. Constructing an immobile mucous membrane by replacement of a skin flap with a skin graft may facilitate selfmaintenance of implants..
35. Nakano Hiroyuki, Mishima Katsuaki, Nakano Asuka, Suga Hokuto, Miyawaki Yuichiro, Mano Yakamitsu, Yoshihide Mori, Yoshiya Ueyama, Relationships between airway morphology and sleep breathing indices in jaw defoemity patients, journal of Sleep Disorder & Therapy,, 4, 1, 1000187, 2015.01.
36. Takahito Otani, Akiko Mizokami, Yoshikazu Hayashi, Jing Gao, Yoshihide Mori, Seiji Nakamura, Hiroshi Takeuchi, Masato Hirata, Signaling pathway for adiponectin expression in adipocytes by osteocalcin, CELLULAR SIGNALLING, 10.1016/j.cellsig.2014.12.018, 27, 3, 532-544, 2015.03.
37. Yosuke Kobayashi, Tsuyoshi Sugiura, Ikumi Imajyo, Miyuki Shimoda, Ishii Kotaro, Naonari Akimoto, Naoya Yoshihama, Yoshihide Mori, Knockdown of the T- box transcription factor Brachyury increases sensitivity of adenoid cystic carcinoma cells to chemotherapy and radiation in vitro: Implications for a new therapeutic principle, INTERNATIONAL JOURNAL OF ONCOLOGY, 10.3892/ijo.2014.2292, 44, 4, 1107-1117, 2014.04.
38. Takahiro Fujinaga, Kumamaru Wataru, Tsuyoshi Sugiura, Yosuke Kobayashi, YUKIKO OHYAMA, TATSUYA IKARI, Mitsuho Onimaru, Naonari Akimoto, Rumi Jogo, Yoshihide Mori, Biological characterization and analysis of metastasis-related genes in cell lines derived from the primary lesion and lymph node metastasis of a squamous cell carcinoma arising in the mandibular gingiva, INTERNATIONAL JOURNAL OF ONCOLOGY, 10.3892/ijo.2014.2332, 44, 5, 1614-1624, 2014.05.
39. Masaki Arioka, Fumi Takahashi, MASANORI SASAKI, Yoshihara Tatsuya, Sachio Morimoto, Masato Hirata, Yoshihide Mori, Toshiyuki Sasaguri, Acceleration of bone regeneration by local application of lithium: Wnt signal-mediated osteoblastogenesis and Wnt signal-independent suppression of osteoclastogenesis (vol 90, pg 397, 2014), BIOCHEMICAL PHARMACOLOGY, 10.1016/j.bcp.2014.08.012, 91, 4, 552-553, 2014.10.
40. Tomoki Sumida, 中野 旬之, Hiroyuki hamakawa, Yoshihide Mori, Dental implants in oral rehabilitation of a maxillary cancer reconstruction: A case report, J Oral Implantol, 2014.05, A 67-year-old man presented reporting difficulty eating, and intraoral investigation revealed that he had undergone a hemimaxillectomy at another hospital 2 years previously. The resected area was covered with a thick abdominal myocutaneous flap (AMF). Dental implants were placed in the residual left alveolar ridge. After treatment, masticatory performance and maximum bite force both improved dramatically, from a score of 2 to 9, and from 0.03 kN to 1.58 kN, respectively. Dental implants can significantly improve the biting force and masticatory performance in oral cancer patients with jawbone resection, even in cases where half of the alveolar ridge has been resected..
41. Takamitsu Mano, Yoshihide Mori, Yoshiaki Kato, Hiroyuki Nakano, Yoshiya Ueyama, Closure of oro-antral fistula after partial maxillectomy using laterally based tongue flap: A case report, J Oral Maxillofac Surg Med Pathol, 10.1016/j.ajoms.2012.05.012, 25, 3, 244-246, 2013.07, [URL], Use of a tongue flap has been advocated for the treatment of various defects in the mouth, and application for the closure of extended oro-nasal fistulae is widespread because of its rich blood supply. We report herein closure of an oro-antral fistula after partial maxillectomy using a laterally based tongue flap.

A 63-year-old man was diagnosed as upper gingival carcinoma. Partial maxillectomy was performed under general anesthesia. After the operation, maxillary defect was sealed with partial denture. About 5 years postoperatively, the patient complained of an unpleasant feeling of the partial denture. Closure operation was performed under general anesthesia. A tongue flap was raised from the dorsum of the tongue including mucosa and underlying muscle, based laterally. The tongue flap was turned upward and the tip was sutured to the lateral edge of the maxillary defect, then the base was sutured to the middle of the maxillary defect. The flap was well vascularized and necrosis of the flap did not occur. Five months postoperatively, the oro-antral fistula was kept completely closed. Therefore, closure of the oro-antral fistula using a tongue flap is useful for medium-sized maxillectomy defects.
42. Masaki Arioka, Fumi Takahashi, MASANORI SASAKI, Tatsuya Yoshihara, Sachio Morimoto, Akihiko Takashima, Yoshihide Mori, Toshiyuki Sasaguri, Acceleration of bone development and regeneration through the Wnt/beta-catenin signaling pathway in mice heterozygously deficient for GSK-3, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2013.09.126, 440, 4, 677-682, 2013.11, Glycogen synthase kinase (GSK)-3 beta plays an important role in osteoblastogenesis by regulating the Wnt/beta-catenin signaling pathway. Therefore, we investigated whether GSK-3 beta deficiency affects bone development and regeneration using mice heterozygously deficient for GSK-3 beta (GSK-3 beta(+/-)). The amounts of beta-catenin, c-Myc, cyclin D1, and runt-related transcription factor-2 (Runx2) in the bone marrow cells of GSK-3 beta(+/-) mice were significantly increased compared with those of wild-type mice, indicating that Wnt/beta-catenin signals were enhanced in GSK-3 beta(+/-) mice. Microcomputed tomography of the distal femoral metaphyses demonstrated that the volumes of both the cortical and trabecular bones were increased in GSK-3 beta(+/-) mice compared with those in wild-type mice. Subsequently, to investigate the effect of GSK-3 beta deficiency on bone regeneration, we established a partial bone defect in the femur and observed new bone at 14 days after surgery. The volume and mineral density of the new bone were significantly higher in GSK-3 beta(+/-) mice than those in wild-type mice. These results suggest that bone formation and regeneration in vivo are accelerated by inhibition of GSK-3 beta, probably through activation of the Wnt/beta-catenin signaling pathway. (C) 2013 Elsevier Inc. All rights reserved..
43. Lee, Sung-Tak, Yoshihide Mori, Minami, Katsuhiro, An, Chang-Hyeon, Park, Jin-Woo, Kwon, Tae-Geon, Does skeletal surgery for asymmetric mandibular prognathism influence the soft tissue contour and thickness?, J Oral Maxillofac Surg, 10.1016/j.joms.2013.04.008, 71, 9, 1577-1587, 2013.09, Purpose: The purpose of the present study was to investigate whether asymmetric mandibular prognathism accompanies a fundamental difference in soft tissue thickness and whether asymmetric mandibular setback surgery would influence the contour and thickness of the soft tissue of the chin.

Materials and Methods: The present retrospective study included skeletal class III patients with significant mandibular chin deviation greater than 6 mm at the pogonion, who had undergone cone-beam computed tomography before and 6 months after surgery during a 2-year period. The predictor variables were timing (pre- and postoperatively) and side (asymmetric vs contralateral). The outcome measures were the hard and soft tissue contours and soft tissue thickness of the chin at the infradentale, B-point, and pogonion level evaluated with reformatted computed tomography images. The study variables were statistically compared using regression model and correlation analysis.

Results: The present study consisted of 20 patients (10 males and 10 females; average age 20.2 years; range, 18 to 25). Preoperatively, the chin deviation side showed a more prominent hard and soft tissue outline but had a thinner soft tissue thickness, which camouflaged the hard tissue asymmetry. After surgery, the hard and soft tissue outline was greatly improved, and the soft tissue thickness had become nearly symmetric. Most of the soft tissue thickness changes correlated negatively with the hard tissue changes.

Conclusions: Asymmetric mandibular prognathism accompanied the 3-dimensional soft tissue contour and thickness asymmetry. Because the soft tissue responds favorably after skeletal surgery, the correction of 3-dimensional asymmetry of bone should be emphasized in patients with asymmetric mandibular prognathism. (C) 2013 American Association of Oral and Maxillofacial Surgeons.
44. Mie Imai, Hiroyuki Ishibashi, Yoshiki Nariai, Takahiro Kanno, Joji Sekine, Mitsuho Onimaru, Yoshihide Mori, Transfection of hypoxia-inducible factor-1 decoy oligodeoxynucleotides suppresses expression of vascular endothelial growth factor in oral squamous cell carcinoma cells, Journal of Oral Pathology and Medicine, 10.1111/j.1600-0714.2012.01161.x, 41, 9, 675-681, 2012.10, Vasculature development is thought to be an important aspect in the growth and metastasis of solid tumors. Among the many angiogenic factors produced by tumor cells, vascular endothelial growth factor (VEGF) is considered to play a key role in angiogenic processes. VEGF synthesis is modulated by hypoxia-inducible factor-1 (HIF-1) function within the hypoxic microenvironment of growing cancer tissue. To inhibit HIF-1 activation, oligodeoxynucleotides (ODNs) were synthesized and transferred with either the consensus sequence for HIF-1 binding or a mutated form of this sequence. If we could transfer a large number of ODNs into the cancer cell nucleus, activated HIF-1 might bind to the ODNs, resulting in inhibition of hypoxia-induced VEGF synthesis. We transferred these ODNs into cultured oral squamous cell carcinoma cells (SAS cells) using the hemagglutinating virus of Japan (HVJ)-liposome method. Hypoxia-mediated expression of VEGF by cancer cells was suppressed by transfection of HIF-1 decoy ODNs, but not by mutated HIF-1 decoy ODNs. HIF-1 decoy ODN transfection also inhibited VEGF protein synthesis. These results suggest that transfection with HIF-1 decoy ODNs is effective for regulating tumor growth by reducing VEGF..
45. Yasutaka Kubota, Chisa Kubo, Yoshihide Mori, Sialoadenoma papilliferum of the hard palate: A case report, J Oral Maxillofac Surg, 10.1016/j.joms.2011.08.012, 70, 7, 1609-1612, 2012.07.
46. Hiroyuki Nakano, Katsuaki Mishima, Yuko Ueda, Asuka Matsushita, Hokuto Suga, Yuichiro Miyawaki, Takamitsu Mano, Yoshihide Mori, Yoshiya Ueyama, A new method for determining the optimal CT threshold for extracting the upper airway, Dentomaxillofac Radiol, 10.1259/dmfr/26397438, 42, 3, 26397438, 2012.07, OBJECTIVES:

The purpose of this study was to evaluate the optimal upper threshold levels of a number of individuals and determine the most suitable upper threshold.


A phantom model and ten patients were used in this study. The phantom was made of acrylic resin and urethane resin and had nine pillar-shaped air spaces. The subjects were ten female patients with jaw deformities who were not affected by respiratory disease. The optimal threshold levels were determined using the "calculation of CT value disparities" (CCTD) technique, which we devised. In other words, the mean CT values along two lines (air space and soft tissue) were calculated and the optimal threshold level was determined as the level that produced the maximum difference between the CT values measured inside and outside of the air-space border.


The optimal upper threshold levels of the nine phantom holes calculated using the CCTD technique in the front-on standing position and side-on standing position were -434 HU and -456 HU, respectively. The optimal upper threshold level of the ten patients calculated using the CCTD technique was -472 HU. The true threshold level of each patient was defined as the optimal threshold level calculated using the CCTD technique. The mean threshold level was defined as -472 HU. The absolute differences between the volume measurements obtained with these two measures were considered. Therefore, the no error values were -460 HU and -470 HU.


We consider that the most suitable upper threshold level for extracting the airway is from -460 HU to -470 HU.
47. Hiroyuki Nakano, Katsuaki Mishima, Asuka Matsushita, Hokuto Suga, Yuichiro Miyawaki, Takamitsu Mano, Yoshihide Mori, Yoshiya Ueyama, Orthognatic surgery in an acromegalic patients with obstructive sleep apnea syndrome, Sleep Breath, 10.1007/s11325-012-0711-5, 17, 1, 29-32, 2012.05.
48. Yanai Yuta, Tsuyoshi Sugiura, Ikumi Imajo, Naoya Yoshihama, Naoyori Akimoto, Yosuke Kobayashi, Kohei Hayashi, Takahiro Fujinaga, Kamemitsu Shirasuna, Yasuharu TAKENOSHITA, Yoshihide Mori, Retrospective Study of Selective Submandibular Neck Dissection versus Radical Neck Dissection for N0 or N1 Necks in Level I Patients with Oral Squamous Cell Carcinoma, J Oncol, 10.1155/2012/634183, 2012, 634183, 2012.05, Objective. To evaluate the efficacy of selective submandibular neck dissection (SMND) in patients with oral squamous cell carcinoma (OSCC) with or without nodal metastasis. Patients. From a total of 384 patients with untreated OSCC who underwent radical excision, we identified 229 with clinically N0 necks and 68 with clinically N1 necks in level I. Main Outcome Measures. The Kaplan-Meier 5-year regional control and 5-year disease specific survival (DSS) were compared for SMND, radical neck dissection (RND), and modified radical neck dissection (MRND). Results. In clinically node-negative necks, the regional control rates were 85.2% with SMND and 83.3% with MRND (P = 0.89), and 5-year DSS rates were 86.5% and 87.0%, respectively, (P = 0.94). In clinically N1 necks, the regional control rates were 81.3% with SMND and 83.0% with RND (P = 0.72), and the DSS rates were 81.3% and 80.0%, respectively, (P = 0.94). Type of neck dissection was not significantly associated with regional control or DSS on either univariate or multivariate analysis using Cox's proportional hazard model. Conclusions. SMND can be effectively applied in elective and therapeutic management to patients with OSCC that are clinically assessed as N0 or N1 to level I of the neck..
49. Sugiyama,G., Takeuchi,H., Nagano,K., Gao,J., Ohyama,Y., Mori,Y., Hirata,M., Regulated interaction of protein phosphatase 1 and protein phosphatase 2A with phospholipase C-related, but catalytically inactive protein. , Biochemistry, 51, 16, 3394-3403, 2012.04.
50. Hiroyuki Nakano, Takamitsu Mano, Katsuaki Mishima, Daiju Horinaga, Yuichiro Miyawaki, Yoshihide Mori, Yoshiya Ueyama, A case of facial asymmetry due to condylar hyperplasia -A treatment strategy for active condylar hyperplasia-, Bull Yamaguchi Med Sch, 59, 3-4, 61-67, 2012.04.
51. Shudo,H., Sasaki,M., Yamashio,T., Tsunomachi,S., Takenoshita,Y., Kubota,Y., ImajoI., Ninomiya,T., Sugi,T., Tsuneyoshi,T., Mori,Y., Chikui,T., Yoshiura,K., Marsupialization for keratocystic odontogenic tumors: Longitudinal image analysis of the tumor size with 3D-visualized CT scans, Int J Oral Maxillofac Surg, 41, 290-296, 2012.02.
52. Kubota,Y., Yanai,Y., Kumamaru,W., Mori,Y., Multiple schwannomas in the oral floor: A case report, Br J Oral Maxillofac Surg, 49, 6, 33-35, 2011.06.
53. Lee,S.H., Lee,S.H., Mori,Y., Minami,K., Park,H.S., Kwon,T.G., Evaluation of pterigomaxillary anatomy using computed tomography: Are there any strucctual variations in cleft patients?, J Oral Maxillofac Surg, 69, 10, 2644-2649, 2011.10.
54. Mori,Y., Shimizu,H., Minami,M., Kwon,T.G., Mano,T., Development of a simulation system in mandibular orthognathic surgery based on integrated three-dimensional data, Oral Maxillofac Surg, 15, 3, 131-138, 2011.09.
55. Nakano,H., Mori,Y., Mano,T., Minami,K., Matsumoto,K., Ueyama,Y., Yura,Y., Diagnosis and treatment of an infant case with temporomandibular joint osteoarthritis caused by tumor., Oral Maxillofac Surg, 14, 119-121, 2010.09.