博士（歯学）, 北海道大学, Mar. 1997

口腔顎顔面外科学

Oral and Maxillofacial Surgery

Life Science, Surgical dentistry

Bachelor's degree program, School of Dental Medicine

Doctoral (PhD) degree program, Graduate school of Dental Medicine

Protein fractions associated with Prevotella intermedia suppress the growth of HSC-3 oral squamous cell carcinoma cells
Miyuki Kashiwabara; Machiko Kasai; Shintaro Nakano; Katsuki Takebe; Shiho Suzuki; Mariko Naito; Mikio Shoji; Ji-Won Lee; Tsukasa Akasaka; Yasuhiro Yoshida; Akira Hasebe; Yoichi Ohiro
Journal of Oral Biosciences, 68, 5, 100803, 100803, Elsevier BV, Oct. 2026, [Peer-reviewed]
English, Scientific journal, 49195926

Morphological changes in the nasal base formation after secondary alveolar bone grafting for patients with alveolar clefts
Shoko Kirikoshi; Yuki Arimura; Tadashi Yamanishi; Mika Yokoyama; Takahiro Nishio; Tetsuya Seikai; Yoichi Ohiro; Juntaro Nishio
Journal of Cranio-Maxillofacial Surgery, 54, 6, 104496, 104496, Elsevier BV, Jun. 2026
Scientific journal

Antiviral effect of cetylpyridinium chloride on SARS-CoV-2 in patients with COVID-19: An Observational Study.
Ryo Takeda; Hirofumi Sawa; Michihito Sasaki; Yasuko Orba; Nako Maishi; Takuya Tsumita; Yoichi Ohiro; Akira Hasebe; Hidehiko Sano; Yoshimasa Kitagawa; Kyoko Hida; Yasuhiro Hida
Journal of oral biosciences, 68, 2, 100772, 100772, Apr. 2026, [International Magazine]
English, Scientific journal, OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral agent responsible for the COVID-19 pandemic and primarily invades the body through the oral cavity. Cetylpyridinium chloride (CPC), a widely used component of oral care products, has demonstrated antiviral effects against SARS-CoV-2; however, the clinical evidence remains limited. This study investigated the virucidal effects of oral CPC in patients with COVID-19 and its impact on reverse transcription polymerase chain reaction (RT-PCR) positivity. METHODS: Thirty-four patients with COVID-19 were initially recruited after obtaining positive PCR test result. This study was conducted during a nationwide Delta-variant-driven epidemic characterized by high viral loads and enhanced transmissibility. Saliva was collected at seven predefined time points to assess the effects of CPC-containing tablets and mouthwash. Viral RNA levels and infectious viral titers were quantified using qRT-PCR and plaque assays. Sixteen patients with detectable SARS-CoV-2 RNA in baseline saliva samples who completed all scheduled samplings constituted the final analytical cohort. RESULTS: During the Delta-variant-predominant period, CPC-containing tablets reduced both SARS-CoV-2 RNA levels and viral infectivity in saliva. In contrast, CPC-containing mouthwashes did not significantly reduce viral RNA levels compared to baseline samples. The RT-PCR positivity rates after CPC use varied according to the applied cycle threshold (Ct) cutoff values. CONCLUSIONS: CPC-containing tablets transiently decrease the SARS-CoV-2 salivary viral load and infectivity and may help reduce the risk of transmission in public settings. When CPC formulations are used prior to saliva-based PCR testing, the Ct cut-off values may require adjustment. CLINICAL SIGNIFICANCE: Despite challenges in conducting saliva-based clinical research in COVID-19 patients, this study provides clinical evidence supporting the antiviral efficacy of CPC formulations on salivary SARS-CoV-2 during the Delta-variant pandemic.

Exploratory transcriptomics and in vivo analyses of suramin in tongue squamous cell carcinoma
Wataru Kakuguchi; Masahiro Morimoto; Kenta Takahashi; Nako Maishi; Kyoko Hida; Takao Nomura; Satoko Otsuguro; Katsumi Maenaka; Yoichi Ohiro
Biomedical Reports, 24, 3, 1, 10, Spandidos Publications, 23 Jan. 2026
Scientific journal

Evaluation of the performance of an artificial intelligence model in recognizing the habitual mixed language in Taiwan for generating periodontal charting text reports
Yi-June Lo; Yung-Chun Chang; Chien-Hung Chen; Hsuan-Po Wang; Hao-Chen Wang; Yoichi Ohiro; Chih-Yuan Fang
Journal of Dental Sciences, 21, 1, 494, 500, Elsevier BV, Jan. 2026, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal

Zygomatic fracture characteristics and their association with brain injury: Evidences from a 10-year retrospective study in northern Taiwan
Wei-Che Tsai; Chen-Yin Yong; Sam Li-Sheng Chen; Yoichi Ohiro; Chih-Yuan Fang
Journal of Dental Sciences, 21, 1, 250, 257, Elsevier BV, Jan. 2026, [Peer-reviewed], ［Internationally co-authored］
English, Scientific journal

T4a classification for oral cancer using mandibular canal invasion instead of bone marrow invasion in the TNM staging system
Masaya Okura; Nobuhiro Yamakawa; Mitsunobu Otsuru; Takumi Hasegawa; Yusuke Yokota; Shin Rin; Hironori Sakai; Shin-ichi Yamada; Eiji Hirai; Yuichi Ashikaga; Kozo Yamamoto; Michihiro Ueda; Tadaaki Kirita; Masahiro Umeda; Masaya Akashi; Hiroshi Kurita; Yoichi Ohiro; Tomofumi Naruse; Souichi Yanamoto
Oral Oncology, 171, 107771, 107771, Elsevier BV, Dec. 2025
Scientific journal

Localization of high endothelial venules is important for the prognosis of patients with oral squamous cell carcinoma
Takashi Niiyama; Aya Matsuda; Nako Maishi; Yasuhiro Hida; Alam Mohammad Towfik; Saki Shinohara; Amane Mizuno; Ren Zixiao; Lihong Lin; Wataru Kakuguchi; Kenichiro Sakata; Yoichi Ohiro; Yoshimasa Kitagawa; Hiroaki Suzuki; Michihiro Ueda; Kyoko Hida
Journal of Oral Biosciences, 67, 4, 100695, 100695, Elsevier BV, Dec. 2025
Scientific journal

Analysis of the distribution of HEV by immunohistochemistry using a mouse oral squamous cell carcinoma model.
Zixiao Ren; Aya Matsuda; Nako Maishi; Yasuhiro Hida; Takashi Niiyama; Li Yu; Weihan Sun; Yoichi Ohiro; Kyoko Hida
Journal of oral biosciences, 67, 3, 100684, 100684, Sep. 2025, [International Magazine]
English, Scientific journal, OBJECTIVE: The density of tumor-associated high endothelial venule (TA-HEV) correlates with a favorable prognosis in various tumors, including oral squamous cell carcinoma (OSCC). Despite the association of TA-HEVs with a better prognosis, their changes during tumor progression remain unclear. Therefore, this study aimed to examine these alterations in a mouse OSCC model. METHODS: Mice were treated with water containing 4NQO to establish a mouse OSCC model. Immunohistochemical analyses were performed using CD31 and MECA 79 antibodies to evaluate TA-HEV alterations during tumor progression. RESULTS: Tongue samples were histologically classified into untreated, normal, dysplasia, and carcinoma groups. During the dysplastic stage, the number of blood vessels increased, and pericyte coverage was reduced as the carcinoma developed. Moreover, HEVs were more abundant in the dysplasia and carcinoma groups, with an increased number of HEVs infiltrated with CD8+ T cells as the lesion progressed. The location and morphology of the HEVs changed during the transition from normal tissue to carcinoma, with the distribution of the TA-HEVs associated with the tumor growth patterns. Specifically, TA-HEVs were frequently found within the tumor in endophytic carcinomas, and at the tumor margins in exophytic carcinomas. Margin TA-HEVs correlated with a higher number of T cells than HEVs within the tumors. CONCLUSION: OSCC-associated HEVs increase in density with tumor progression, and margin TA-HEVs suggests a better anti-tumor prognosis compared with intra-TA-HEVs.

SARS-CoV-2 infection promotes lung thrombosis by inducing integrinβ3 expression in vascular endothelial cells
Wataru Ito; Yuya Sakurai; Nako Maishi; Ryo Takeda; Takahito Teshirogi; Li Yu; Yasuhiro Hida; Michihito Sasaki; Yasuko Orba; Takuya Tsumita; Haruhisa Watanabe; Tadahiro Iimura; Terufumi Kubo; Shinsuke Toba; Akihiko Sato; Aya Matsuda; Daisuke Kyuno; Makoto Osanai; Yoichi Ohiro; Toshihiko Torigoe; Hirofumi Sawa; Kyoko Hida
Scientific Reports, 15, 1, Springer Science and Business Media LLC, 01 Jul. 2025
Scientific journal

Sclerosing rhabdomyosarcoma of the infratemporal fossa in an adult: A favorable long-term outcome
Chikako Yura; Wataru Kakuguchi; Naohiro Ogawa; Daigo Matsuyama; Shin Ariga; Koichi Yasuda; Taku Maeda; Aya Yanagawa-Matsuda; Yuichi Ashikaga; Yoichi Ohiro
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, Elsevier BV, Jul. 2025, [Peer-reviewed], [Last author]
Scientific journal

Histopathological analysis of tumor microenvironmental changes after near-infrared photoimmunotherapy
Takehiro Chida; Aya Matsuda; Nako Maishi; Kohei Nakajima; Mineyoshi Sato; Zi Jia; Yoichi Ohiro; Mikako Ogawa; Yasuhiro Hida; Kyoko Hida
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 37, 4, 807, 817, Elsevier BV, Jul. 2025, [Peer-reviewed]
English, Scientific journal, 33946510

Histochemical assessment of the anabolic effects of abaloparatide on the femoral metaphyses of ovariectomized mice
Xuanyu Liu; Tomoka Hasegawa; Mako Sakakibara; Tomomaya Yamamoto; Mai Haraguchi-Kitakamae; Hotaka Ishizu; Yan Shi; Jiaxin Cui; Weisong Li; Wang Haoyu; Hiromi Hongo; Tomohiro Shimizu; Yoichi Ohiro; Norio Amizuka
Journal of Oral Biosciences, 67, 2, 100663, 100663, Elsevier BV, Jun. 2025, [Peer-reviewed]
English, Scientific journal

Validity and Utility of a Risk Prediction Model for Wound Infection After Lower Third Molar Surgery
Akira Yamagami; Katsuya Narumi; Yoshitaka Saito; Ayako Furugen; Shungo Imai; Keisuke Okamoto; Yoshimasa Kitagawa; Yoichi Ohiro; Ryo Takagi; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
Oral Diseases, Wiley, 10 Jan. 2025, [Peer-reviewed]
Scientific journal, ABSTRACT

Objectives

To externally validate a clinical prediction model for surgical site infection (SSI) after lower third molar (L3M) surgery and evaluate its clinical usefulness.

Methods

We conducted a retrospective cohort study of patients who underwent L3M surgery at Hokkaido University Hospital. The study was designed to evaluate the historical and methodological transportability. Clinical usefulness was evaluated using decision curve analysis on the data of the non‐antibiotic‐treated patients.

Results

We obtained 2543 validation cohorts from April 2020 to March 2023, and 640 non‐antibiotic cohorts from July 2010 to September 2023. The incidences of SSI after L3M surgery were 5.3% (135/2543) and 7.7% (49/640) in the validation and non‐antibiotic cohorts, respectively. The discrimination ability of the prediction model was acceptable for the external validation cohort (c‐statistic: 0.67; 95% CI: 0.62–0.71) and adequate for the non‐antibiotic cohort (c‐statistic: 0.72; 95% CI: 0.63–0.79). In both cohorts, the model showed excellent calibration between the observed and predicted probabilities. Decision curve analysis showed increased net benefit across a range of meaningful risk thresholds.

Conclusion

A simple risk prediction model for SSI after L3M surgery demonstrated clinical transportability and usefulness. This model may help surgeons/clinicians determine the appropriateness of prophylactic antibiotics administration for patients in L3M surgery.

Peripheral Osteoma of the Subcondylar Region in the Mandible Treated Using the High Perimandibular Approach: A Case Report
Tamaki Sekiguchi-Yamada; Kazuhiro Matsushita; Rieko Yoshitatsu; Aya Yanagawa Matsuda; Tomoka Hasegawa; Yoichi Ohiro
Case Reports in Dentistry, 2025, 1, N/A, N/A, Wiley, Jan. 2025, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, Osteomas are benign tumors composed of mature, compact, or cancellous bone that commonly arise in the sinuses and exhibit slow and asymptomatic growth. Surgical resection may be performed using intraoral or extraoral approaches when functional or morphological deficits are present. A 63‐year‐old female presented with an osteoma in the subcondylar region, which had doubled in size 9 years after the initial diagnosis. Considering the potential risk of functional impairment, the osteoma was excised using the high perimandibular approach. Two years postsurgery, the patient remained asymptomatic, with no functional or morphological deficits or recurrence of the disease.

This case report describes the successful use of the high perimandibular approach for managing an osteoma in the subcondylar region and highlights its clinical versatility.

Reply to Accurate Risk Prediction Model for Surgical Site Infection After Lower Third Molar Surgery.
Akira Yamagami; Katsuya Narumi; Yoshitaka Saito; Ayako Furugen; Shungo Imai; Yoshimasa Kitagawa; Yoichi Ohiro; Ryo Takagi; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
Oral diseases, 03 Nov. 2024, [Peer-reviewed], [International Magazine]
English

MIAT promotes myofibroblastic activities and transformation in oral submucous fibrosis through sponging the miR-342-3p/SOX6 axis.
Ming-Yi Lu; Chih-Yuan Fang; Pei-Ling Hsieh; Shih-Chi Chao; Yi-Wen Liao; Yoichi Ohiro; Chen-Chia Yu; Dennis Chun-Yu Ho
Aging, 16, 19, 12909, 12927, 07 Oct. 2024, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, Oral submucous fibrosis (OSF) is an oral potentially malignant disorder that is closely related to the habit of areca nut chewing. Long non-coding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) has been identified as an essential regulator in the fibrosis progression. However, the role of MIAT in the development of OSF remains unknown. The transcriptomic profile showed that MIAT is significantly overexpressed in the OSF cohort, with a positive correlation to fibrotic markers. The silencing of MIAT expression in primary buccal mucosal fibroblasts (BMFs) markedly inhibited arecoline-induced myofibroblast transformation. Mechanistically, MIAT functioned as a miR-342-3p sponge and suppressed the inhibitory effect of miR-342-3p on SOX6 mRNA, thereby reinstating SOX6 expression. Subsequent RNA expression rescue experiments confirmed that MIAT enhanced resistance to apoptosis and facilitated myofibroblastic properties such as cell mobility and collagen gel contraction by regulating the miR-342-3p/SOX6 axis. Taken together, these results suggest that the abnormal upregulation of MIAT is important in contributing persistent activation of myofibroblasts in fibrotic tissue, which may result from prolonged exposure to the constituents of areca nut. Furthermore, our findings demonstrated that therapeutic avenues that target the MIAT/miR-342-3p/SOX6 axis may be a promising approach for OSF treatments.

Dental implants could be considered as a reliable treatment in florid cemento-osseous dysplasia patients after total excision
Wei-Che Tsai; Yang-Che Wu; Yoichi Ohiro; Chih-Yuan Fang
Journal of Dental Sciences, 19, 4, 2452, 2454, Elsevier BV, Oct. 2024, [Peer-reviewed]
English, Scientific journal

Extensive oral bisphosphonate related osteonecrosis of the maxilla: utilization of bone scintigraphy for detection of the combination of HBO therapy and surgery:case report and hypothesis.
Moritani Y.; Donen M.; Fujimori M.; Tei K.; Ohiro Y.
Hokkaido J. Dent. Sci., 45, 76, 82, 15 Sep. 2024, [Peer-reviewed], [Last author]
English, Scientific journal

Effects of liquid-diet feeding on growth of rat periodontal ligament and cementum
中道祥之; 高橋 茂; 山本恒之; 大廣 洋一
北海道歯学雑誌, 45, 40, 49, 15 Sep. 2024, [Peer-reviewed], [Last author]
Japanese, Scientific journal

COVID-19mRNAワクチン接種後に発症した三叉神経第III枝帯状疱疹の1例
箭原 元基; 格口 渉; 桐越 晶子; 中野 晋太郎; 鄭 漢忠; 大廣 洋一
北海道歯学雑誌, 45, 56, 62, 北海道歯学会, Sep. 2024, [Peer-reviewed]
Japanese

Targeting MetaLnc9/miR-143/FSCN1 axis inhibits oxidative stress and myofibroblast transdifferentiation in oral submucous fibrosis.
Ming-Yi Lu; Pei-Ling Hsieh; Shih-Chi Chao; Chih-Yuan Fang; Yoichi Ohiro; Yi-Wen Liao; Cheng-Chia Yu; Min-Te Chang
Journal of dental sciences, 19, 3, 1416, 1425, Jul. 2024, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, BACKGROUND/PURPOSE: Persistent activation of myofibroblasts is attributed to various dysregulated biological events conferring multiple types of fibrosis diseases, including oral submucous fibrosis (OSF). Although the significance of non-coding RNAs (ncRNAs) in the occurrence of fibrosis has been appreciated, the detailed mechanisms still have not been fully elucidated. The aim of this study was to identify key dysregulated ncRNAs and elucidate their pro-fibrotic mechanisms in promoting myofibroblast activation and the pathological development of OSF. MATERIALS AND METHODS: Expression of non-coding RNAs and mRNAs in OSF cohort was determined using RNA sequencing and qRT-PCR. The molecular axis of pro-fibrotic ncRNAs were exploited via luciferase reporter activity assay and RNA expression rescue experiments. Functional assays, including collagen gel contraction, wound healing ability, cell migration, and reactive oxygen species (ROS) production, were conducted to assess the changes in the myofibroblastic phenotypes of primary human buccal mucosal fibroblasts. RESULTS: Herein, we found that long non-coding RNA MetaLnc9 was upregulated in OSF specimens and positively associated with several fibrosis markers. Silencing of MetaLnc9 diminished the features of activated myofibroblasts and the production of ROS. We not only showed that MetaLnc9 functioned as a competitive endogenous RNA of microRNA (miR)-143, but also demonstrated that the pro-fibrosis effect of MetaLnc9 on myofibroblast activities was mediated by suppression of miR-143. Moreover, our data showed that fascin actin-bundling protein 1 (FSCN1) was a direct target of miR-143 and positively related to MetaLnc9. CONCLUSION: Upregulation of MetaLnc9 may enhance the activation of myofibroblasts by sponging miR-143 and titrating its inhibitory property on FSCN1.

Nonspecific inflammatory pseudotumor of the maxillary and temporal fossa: a study of seven cases
Wataru Kakuguchi; Yuichi Ashikaga; Yasuhito Moritani; Shintaro Nakano; Naohiro Ogawa; Rieko Yoshitatsu; Aya Yanagawa-Matsuda; Nako Maishi; Akihiko Kudo; Nanase Okazaki; Yuji Nakamaru; Ichiro Yabe; Yoshihiro Matsuno; Yoichi Ohiro
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, Elsevier BV, Jun. 2024, [Peer-reviewed]
Scientific journal

Epithelial-mesenchymal transition in oral cancer cells induced by prolonged and persistent Fusobacterium nucleatum stimulation
Shintaro Nakano; Machiko Kasai; Keisuke Nakamura; Tsukasa Akasaka; Yasuhiro Yoshida; Shiho Suzuki; Yoichi Ohiro; Akira Hasebe
Journal of Oral Biosciences, Elsevier BV, May 2024, [Peer-reviewed]
Scientific journal

Oral cancer practice for elderly patients
青木隆幸; 上田倫弘; 山城正司; 柳本惣市; 寺尾保信; 三浦雅彦; 本間義崇; 中山秀樹; 八木原一博; 大廣洋一; 伏見千宙; 林信; 長島文夫; 太田嘉英
日本口腔腫瘍学会誌, 36, 3, 2024

Speech Outcome in Patients with Complete Unilateral Cleft Lip and Palate Following Two-stage Palatoplasty―Evaluation after hard palate closure―
SOGABE Izumi; MIKOYA Tadashi; TAKAZAWA Rina; TANAKA Soichi; SEIKAI Tetsuya; ITO Yumi; KATO Junya; KIRIKOSHI Shoko; KANEKO Tomoo; MICHIDA Tomohiro; IMAI Satoko; MATSUZAWA Yusuke; OHIRO Yoichi
Journal of Japanese Cleft Palate Association, 49, 1, 23, 35, Japanese Cleft Palate Association, 2024, [Peer-reviewed]
Japanese, Purpose: In two-stage palatal repair, the soft palate and the posterior half of the hard palate are closed at 1 year 6 months in the first operation. In the second, closure of the residual anterior half of the hard palate and alveolar bone grafting are performed simultaneously at 6-7 years of age. We evaluated the impact of this procedure on speech function.
 Methods: The subjects were 36 consecutively treated patients with complete unilateral cleft lip and palate. Patients underwent the first and second operation at a mean age of 1 year 8 months and 6 years 8 months, respectively. After the first operation, 18 patients did not wear a palatal plate as an obturator (non-plate group) as the unclosed cleft reduced remarkably in the anterior half of the hard palate. A total of 18 patients wore a palatal plate (plate group) as the unclosed cleft was opened widely and there was nasal emission, affecting adequate articulation. Velopharyngeal closure function (VPC) and articulation were evaluated at a mean age of 5 years 1 month and 7 years 5 months before (age 5) and after the second operation (post-2nd), respectively, and we considered the non-plate and plate groups.
 Results: In all cases, the acquisition rate of excellent and good VPC was 88.9％ at age 5 and 94.4％ at post-2nd. The acquisition rate of acceptable and intelligible speech (adequate articulation) increased from 44.4％ at age 5 to 61.1％ at post-2nd. The acquisition rate of excellent and good VPC in the plate group was significantly lower at 77.8％ compared to 100％ in the non-plate group at age 5. VPC was good with no significant difference at 94.4％ in both groups at post-2nd. No significant difference was observed in the acquisition rate of adequate articulation in the non-plate (55.6％) and plate group (33.3％) at age 5. The acquisition rate increased to 83.3％ in the non-plate group but remained significantly low at 38.9％ and showed no improvement in the plate group at post-2nd.
 Conclusions: Half of all cases that were able to avoid the use of a palatal plate obtained good VPC at age 5 and adequate speech outcome in almost all cases at post-2nd. Articulation disorder in the other half that needed to use the palatal plate did not improve even at post-2nd. To facilitate speech development without delay, an unclosed cleft should be reduced to the appropriate size without adversely affecting VPC acquisition before 5 years of age at the latest.

Preoperative chemoradiotherapy for locally advanced oral squamous cell carcinoma: A multicenter retrospective study
Nobuhiro Yamakawa; Hiroyuki Harada; Hideki Nakayama; Yoichi Ohiro; Hiroki Bukawa; Tadaaki Kirita
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, Elsevier BV, Jan. 2024, [Peer-reviewed]
Scientific journal

A case of Applying a Bone Anchored Device for Oligodontia
長 太一; 三上 格; 板橋基雅; 吉村麻里奈; 齋藤紘子; 上林 毅; 吉谷正純; 吉谷; 夏純; 吉村治範; 長 清美; 平松孝夫; 大廣洋一
Journal of Japanese Society of Oral Inmplantology, 36, 4, 262, 267, Dec. 2023, [Peer-reviewed], [Last author]
Japanese, Scientific journal

Oronasal fistula: A rare complication of mesiodens
Tetsuya Seikai; Soichi Tanaka; Naohiro Ogawa; Hirotake Murakami; Yoichi Ohiro
Advances in Oral and Maxillofacial Surgery, 12, 100453, 100453, Elsevier BV, Dec. 2023, [Peer-reviewed]
Scientific journal

Comparison of the 8th edition of TNM staging of oral cancer with the 7th edition and its prognostic significance using clinical depth of invasion and extranodal extension
Yusuke Yokota; Takumi Hasegawa; Nobuhiro Yamakawa; Shin Rin; Mitsunobu Otsuru; Shin-ichi Yamada; Eiji Hirai; Yuichi Ashikaga; Kozo Yamamoto; Michihiro Ueda; Tadaaki Kirita; Masahiro Umeda; Masaya Akashi; Hiroshi Kurita; Yoichi Ohiro; Souichi Yanamoto; Masaya Okura
Oral Oncology, 145, 106519, 106519, Elsevier BV, Oct. 2023, [Peer-reviewed]
Scientific journal

Development of a risk prediction model for surgical site infection after lower third molar surgery.
Akira Yamagami; Katsuya Narumi; Yoshitaka Saito; Ayako Furugen; Shungo Imai; Yoshimasa Kitagawa; Yoichi Ohiro; Ryo Takagi; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
Oral diseases, 27 Sep. 2023, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: There is little evidence regarding risk prediction for surgical site infection (SSI) after lower third molar (L3M) surgery. METHODS: We conducted a nested case-control study to develop a multivariable logistic model for predicting the risk of SSI after L3M surgery. Data were obtained from Hokkaido University Hospital from April 2013 to March 2020. Multiple imputation was applied for the missing values. We conducted decision tree (DT) analysis to evaluate the combinations of factors affecting SSI risk. RESULTS: We identified 648 patients. The final model retained the available distal space (Pell & Gregory II [p = 0.05], Pell & Gregory III [p < 0.01]), depth (Pell & Gregory B [p < 0.01], Pell & Gregory C [p < 0.01]), surgeon's experience (3-10 years [p = 0.25], <3 years [p < 0.01]), and simultaneous extraction of both L3M [p < 0.01]; the concordance-statistic was 0.72. The DT analysis demonstrated that patients with Pell and Gregory B or C and simultaneous extraction of both L3M had the highest risk of SSI. CONCLUSIONS: We developed a model for predicting SSI after L3M surgery with adequate predictive metrics in a single center. This model will make the SSI risk prediction more accessible.

Pre-operative virtual planning followed by fabrication of patient-specific guiding instruments for mandibular deformity after fibula free flap reconstruction
Ashikaga, Yuichi; Shinohara, Saki; Nakano, Shintaro; Ogawa, Naohiro; Matsuyama, Daigo; Murakami, Hirotake; Kuribayashi, Kazuyo; Ohiro, Yoichi
Hokkaido journal of dental science, 44, 69, 72, 15 Sep. 2023, [Peer-reviewed]
English, Scientific journal, Corrective osteotomy for secondary mandibular reconstruction is complex, and it is extremely difficult to achieve desirable three-dimensional positioning. The authors present a case for repositioning the mandibular segments of mandibular deformity after fibula free flap reconstruction using computer-assisted surgical simulation and patient-specific guiding instruments. A 69-year-old man developed severe mandibular deviation after segmental mandibulectomy and reconstruction with fibula free flap for basal cell carcinoma of the mental region. A virtual osteotomy was performed between the mandible and fibula on a 3D virtual model using simulation software. The proximal mandibular segments were placed in the ideal position using a 3D virtual model. The original contour of the mandible before the primary resection was used as a reference for repositioning. Patient-specific guiding instruments were fabricated for the pre-osteotomy and intraoperative positioning of the osteotomized mandible, enabling bone fragments to be repositioned and fixed using the pre-operative plan. Post-operative CT showed that the mandibular segments were precisely repositioned. In this case, virtual planning and patient-specific guiding instruments were useful in corrective surgery for mandibular deformity after fibula free flap reconstruction.

下顎エナメル上皮腫に反復処置法を適応し,腫瘍による歯根吸収を伴う歯を無治療で温存した1例
足利 雄一; 篠原 早紀; 関口 珠希; 格口 渉; 大廣 洋一
北海道歯学雑誌, 44, 73, 80, 北海道歯学会, Sep. 2023, [Peer-reviewed]
Japanese

下顎エナメル上皮腫に反復処置法を適応し,腫瘍による歯根吸収を伴う歯を無治療で温存した1例
足利 雄一; 篠原 早紀; 関口 珠希; 格口 渉; 大廣 洋一
北海道歯学雑誌, 44, 73, 80, 北海道歯学会, Sep. 2023, [Peer-reviewed], [Last author]
Japanese

Investigating the relationship between the remodeling of TMJ bony structures and condylar rest position following orthognathic surgery in class II and class III skeletal malocclusions
Nguyen Thi Trang; Yuichi Ashikaga; Kazuhiro Matsushita; Yoichi Ohiro
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 35, 4, 308, 316, Elsevier BV, Jul. 2023, [Peer-reviewed], [Last author]
Scientific journal

A 10-year retrospective study on mandibular fractures in Northern Taiwan
Chih-Yuan Fang; Han-Yu Tsai; Chen-Yin Yong; Yoichi Ohiro; Yu-Chao Chang; Nai-Chia Teng
Journal of Dental Sciences, 18, 3, 1330, 1337, Elsevier BV, Jul. 2023, [Peer-reviewed], ［Internationally co-authored］
Scientific journal

II級・III級骨格性不正咬合に対する顎矯正手術後の下顎頭および下顎窩リモデリングの3次元的解析
足利 雄一; Trang Nguyen Thi; 松下 和裕; 大廣 洋一
日本骨形態計測学会雑誌, 33, 1, 149, 149, 日本骨形態計測学会, May 2023
Japanese

Human antigen R knockdown attenuates the invasive activity of oral cancer cells through inactivation of matrix metalloproteinase-1 gene expression
Wataru Kakuguchi; Tetsuya Kitamura; Tomomi Takahashi; Aya Yanagawa-Matsuda; Chih-Yuan Fang; Yoichi Ohiro; Fumihiro Higashino
Journal of Dental Sciences, Elsevier BV, May 2023, [Peer-reviewed], ［Internationally co-authored］
Scientific journal

Downregulation of histone deacetylase 8 (HDAC8) alleviated the progression of oral submucous fibrosis
Hui-Wen Yang; Yi-Hwa Sun; Chih-Yuan Fang; Yoichi Ohiro; Heng-Yi Liao; Yi-Wen Liao; Yu-Hsun Kao; Cheng-Chia Yu
Journal of Dental Sciences, 18, 2, 652, 658, Elsevier BV, Apr. 2023, [Peer-reviewed], ［Internationally co-authored］
Scientific journal

Significant association of Yamamoto-Kohama classification and pathological depth of invasion with cervical lymph node metastasis in early-stage tongue squamous cell carcinoma (Stage I/II)
Wataru Kakuguchi; Yuichi Ashikaga; Aya Yanagawa-Matsuda; Kazuyo Kuribayashi; Saki Shinohara; Naohiro Ogawa; Nako Maishi; Kyoko Hida; Chih-Yuan Fang; Yoichi Ohiro
Journal of Dental Sciences, 18, 4, 1663, 1668, Elsevier BV, Feb. 2023, [Peer-reviewed], [Last author], ［Internationally co-authored］
Scientific journal

Multicentre retrospective study of nivolumab for recurrent/metastatic oral squamous cell carcinoma
Nobuhiro Yamakawa; Masahiro Umeda; Yumi Yoshii; Kenji Mitsudo; Makoto Noguchi; Jingo Kusukawa; Akira Katakura; Hideki Nakayama; Masashi Sasaki; Tadahide Noguchi; Michihiro Ueda; Hiroki Bukawa; Kazuhiro Yagihara; Akihisa Horie; Akihiro Miyazaki; Daichi Chikazu; Kei Tomihara; Katsuaki Mishima; Mitsunobu Otsuru; Seiji Asoda; Shigeyoshi Fujiwara; Yoshio Ohyama; Hiroshi Kurita; Hitoshi Kawamata; Masayuki Fukuda; Yukari Shintani; Takanori Kobayashi; Takahiro Kanno; Ichiro Oh‐iwa; Kenji Kawano; Yoshio Yamashita; Wataru Kobayashi; Yoichi Ohiro; Katsuhiro Uzawa; Yoshihide Ota; Tadaaki Kirita
Oral Diseases, Wiley, 15 Dec. 2022, [Peer-reviewed]
English, Scientific journal

The Impact of Pretreatment Low Body Mass Index on Cause-Specific Mortality in Patients with Squamous Cell Carcinoma of the Oral Cavity.
Kyoko Kurioka; Shin Rin; Mitsunobu Otsuru; Tomohumi Naruse; Takumi Hasegawa; Nobuhiro Yamakawa; Shin-Ichi Yamada; Eiji Hirai; Kozo Yamamoto; Michihiro Ueda; Tadaaki Kirita; Masaya Akashi; Hiroshi Kurita; Yoichi Ohiro; Masaya Okura
Nutrition and cancer, 1, 12, 12 Oct. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, The association between the pretreatment body mass index (BMI) and oral squamous cell carcinoma (SCC) outcomes is controversial. We aimed to examine the association between BMI and cause-specific mortality due to cancer of the oral cavity and patterns of failure that correlate with increased mortality. We enrolled 2,023 East Asian patients in this multicenter cohort study. We used the cumulative incidence competing risks method and the Fine-Gray model to analyze factors associated with cause-specific mortality, local recurrence, regional metastasis, and distant metastasis as first events. The median follow-up period was 62 mo. The 5-year cause-specific mortality for patients with underweight was 25.7%, which was significantly higher than that for patients with normal weight (12.7%, P < 0.0001). The multivariate model revealed that underweight was an independent risk factor for cause-specific mortality and regional metastasis (P < 0.05). Moreover, patients with underweight displayed a 51% and 55% increased risk of cause-specific mortality and regional metastasis, respectively, compared with their normal weight counterparts. Local recurrence was not associated with the BMI categories; however, the incidence of distant metastasis inversely decreased with BMI value. In summary, being underweight at diagnosis should be considered a high-risk mortality factor for oral SCC.

Histochemical assessment of accelerated bone remodeling and reduced mineralization in Il-6 deficient mice.
Yasuhito Moritani; Tomoka Hasegawa; Tomomaya Yamamoto; Hiromi Hongo; Yimin; Miki Abe; Hirona Yoshino; Ko Nakanishi; Haruhi Maruoka; Hotaka Ishizu; Tomohiro Shimizu; Masahiko Takahata; Norimasa Iwasaki; Minqi Li; Kanchu Tei; Yoichi Ohiro; Norio Amizuka
Journal of oral biosciences, 64, 4, 410, 421, 11 Oct. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, OBJECTIVES: Interleukin-6 (IL-6) contributes to the regulation of functions in various tissues and organs. Even though IL-6 has been reported to modulate bone metabolism in previous studies, this finding is controversial. This study aims to evaluate the possible involvement of IL-6 in bone metabolism by examining the histological activity of osteoblasts and osteoclasts in the femora of Il-6 deficient (Il-6-/-) mice. METHODS: Eight-week-old male Il-6-/- mice and their wild-type littermates were fixed with a paraformaldehyde solution, and their femora were extracted for micro-CT analysis, immunohistochemistry, and real-time PCR analysis. RESULTS: Il-6-/- femora showed an increased bone volume/tissue volume (TV) but a reduced bone mineral density compared with the wild-type. Furthermore, the tissue-nonspecific alkaline phosphatase positive area/TV ratio, the expression of Runx2, Osterix, and Rankl, and the number of tartrate-resistant acid phosphatase-positive osteoclasts were all increased in the Il-6-/- mice. A considerable number of unmineralized areas within the bone matrix and abundant sclerostin-reactive osteocytes were observed in Il-6-/- femoral metaphyses but not in the wild-type. Interestingly, the gene expression of Cd206 was elevated in Il-6-/- femora, and many F4/80-positive macrophages/monocytes and CD206-immunoreactive macrophages in the primary trabeculae had migrated closer to the growth plate, where intense RANKL immunoreactivity was detected. These results suggest that, in an IL-6-deficient state, CD206-positive macrophages may differentiate into osteoclasts when in contact with RANKL-reactive osteoblastic cells. CONCLUSION: In a state of IL-6 deficiency, the population and cell activities of osteoblast, osteoclasts, and macrophages seemed to be facilitated, except for the reduced mineralization in bone.

Primary Teeth-Derived Demineralized Dentin Matrix Autograft for Unilateral Maxillary Alveolar Cleft during Mixed Dentition
Yusuke Matsuzawa; Naoto Okubo; Soichi Tanaka; Haruhiko Kashiwazaki; Yoshimasa Kitagawa; Yoichi Ohiro; Tadashi Mikoya; Toshiyuki Akazawa; Masaru Murata
Journal of Functional Biomaterials, 13, 3, 153, 153, MDPI AG, 15 Sep. 2022, [Peer-reviewed]
English, Scientific journal, This clinical report describes the immediate autograft of primary (milk) teeth-derived demineralized dentin matrix (DDM) granules for a 6-year-old boy with unilateral alveolar cleft. First, four primary teeth were extracted, crushed in an electric mill for 1 min, and the crushed granules were demineralized in 2% HNO3 solution for 20 min. Simultaneously, the nasal mucoperiosteum was pushed upwards above the apices of the permanent central incisor adjacent to the cleft. The nasal and palatal openings were closed by suturing the mucoperiosteum on both sides of the cleft with absorbable threads. The wet DDM granules were grafted into the managed cleft triangle space, and a labial flap was repositioned. The radiographic images at 6 months showed the continuous hard tissues in the cleft area and DDM granules onto lateral incisor (22) and impacted canine (23). The 3D-CT views at 2 years showed impacted tooth (22) blocked by primary canine and the replacement of DDM granules by bone near teeth (22,23). At 4 years, tooth crown (22) was situated just under the mucous membrane, and teeth (22,23) erupted spontaneously until 6 years without a maxillary expansion and a tow guidance of canine. The DDM granules contributed to bone formation without the inhibition of spontaneous tooth eruption. We concluded that autogenous primary teeth DDM graft should become a minimally invasive procedure without bone harvesting and morbidities for unilateral alveolar cleft.

Application of "Dredging Method" for the patients with odontogenic keratocyst.
Ohiro Y; Kakuguchi W; Moritani Y; Kitamura T; Maishi N; Hida K
Hokkaido J Dent Sci., 43, 63, 69, 北海道歯学会, 15 Sep. 2022, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

Protocol for a multicentre, prospective observational study of elective neck dissection for clinically node-negative oral tongue squamous cell carcinoma (END-TC study)
Souichi Yanamoto; Yasuyuki Michi; Mitsunobu Otsuru; Toru Inomata; Hideki Nakayama; Takeshi Nomura; Takumi Hasegawa; Yoshiko Yamamura; Shin-ichi Yamada; Jingo Kusukawa; Nobuhiro Yamakawa; On Hasegawa; Michihiro Ueda; Yoshimasa Kitagawa; Akimitsu Hiraki; Toshihiro Hasegawa; Yoichi Ohiro; Wataru Kobayashi; Seiji Asoda; Takanori Kobayashi; Mitsuyoshi Iino; Masayuki Fukuda; Naomi Ishibashi-Kanno; Koji Kawaguchi; Reona Aijima; Kazuma Noguchi; Masaya Okura; Akira Tanaka; Tsuyoshi Sugiura; Yukari Shintani; Kazuhiro Yagihara; Masashi Yamashiro; Yoshihide Ota; Akihiro Miyazaki; Akinori Takeshita; Hitoshi Kawamata; Iwabuchi Hiroshi; Kenichiro Uchida; Masahiro Umeda; Hiroshi Kurita; Tadaaki Kirita
BMJ Open, 12, 9, e059615, e059615, BMJ, 13 Sep. 2022, [Peer-reviewed]
Scientific journal, Introduction

In early-stage oral tongue squamous cell carcinoma (OTSCC), elective neck dissection (END) is recommended when occult lymph node metastasis is suspected; however, there is no unanimous consensus on the risks and benefits of END in such cases. The management of clinically node-negative (cN0) OTSCC remains controversial. This study, therefore, aimed to evaluate the efficacy of END and its impact on the quality of life (QoL) of patients with cN0 OTSCC.

Methods and analysis

This is a prospective, multicentre, nonrandomised observational study. The choice of whether to perform END at the same time as resection of the primary tumour is based on institutional policy and patient preference. The primary endpoint of this study is 3-year overall survival. The secondary endpoints are 3-year disease-specific survival, 3-year relapse-free survival and the impact on patient QoL. Propensity score-matching analysis will be performed to reduce selection bias.

Ethics and dissemination

This study was approved by the Clinical Research Review Board of the Nagasaki University. The protocol of this study was registered at the University Hospital Medical Information Network Clinical Trials Registry. The datasets generated during the current study will be available from the corresponding author on reasonable request. The results will be disseminated internationally, through scientific and professional conferences and in peer-reviewed medical journals.

Trial registration number

UMIN000027875.

Gargling with povidone iodine has a short-term inhibitory effect on SARS-CoV-2 in patients with COVID-19
T. Seikai; A. Takada; A. Hasebe; M. Kajihara; K. Okuya; T. Sekiguchi (Yamada); W. Kakuguchi; S. Konno; Y. Ohiro
Journal of Hospital Infection, 123, 179, 181, Elsevier BV, May 2022, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Multiple Routes of Antibody-Dependent Enhancement of SARS-CoV-2 Infection.
Kosuke Okuya; Takanari Hattori; Takeshi Saito; Yoshihiro Takadate; Michihito Sasaki; Wakako Furuyama; Andrea Marzi; Yoichi Ohiro; Satoshi Konno; Takeshi Hattori; Ayato Takada
Microbiology spectrum, 10, 2, e0155321, 27 Apr. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, Antibody-dependent enhancement (ADE) of infection is generally known for many viruses. A potential risk of ADE in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has also been discussed since the beginning of the coronavirus disease 2019 (COVID-19) pandemic; however, clinical evidence of the presence of antibodies with ADE potential is limited. Here, we show that ADE antibodies are produced by SARS-CoV-2 infection and the ADE process can be mediated by at least two different host factors, Fcγ receptor (FcγR) and complement component C1q. Of 89 serum samples collected from acute or convalescent COVID-19 patients, 62.9% were found to be positive for SARS-CoV-2-specific IgG. FcγR- and/or C1q-mediated ADE were detected in 50% of the IgG-positive sera, whereas most of them showed neutralizing activity in the absence of FcγR and C1q. Importantly, ADE antibodies were found in 41.4% of the acute COVID-19 patients. Neutralizing activity was also detected in most of the IgG-positive sera, but it was counteracted by ADE in subneutralizing conditions in the presence of FcγR or C1q. Although the clinical importance of ADE needs to be further investigated with larger numbers of COVID-19 patient samples, our data suggest that SARS-CoV-2 utilizes multiple mechanisms of ADE. C1q-mediated ADE may particularly have a clinical impact since C1q is present at high concentrations in plasma and its receptors are ubiquitously expressed on the surfaces of many types of cells, including respiratory epithelial cells, which SARS-CoV-2 primarily infects. IMPORTANCE Potential risks of antibody-dependent enhancement (ADE) in the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been discussed and the proposed mechanism mostly depends on the Fc gamma receptor (FcγR). However, since FcγRs are exclusively expressed on immune cells, which are not primary targets of SARS-CoV-2, the clinical importance of ADE of SARS-CoV-2 infection remains controversial. Our study demonstrates that SARS-CoV-2 infection induces antibodies that increase SARS-CoV-2 infection through another ADE mechanism in which complement component C1q mediates the enhancement. Although neutralizing activity was also detected in the serum samples, it was counteracted by ADE in the presence of FcγR or C1q. Considering the ubiquity of C1q and its cellular receptors, C1q-mediated ADE may more likely occur in respiratory epithelial cells, which SARS-CoV-2 primarily infects. Our data highlight the importance of careful monitoring of the antibody properties in COVID-19 convalescent and vaccinated individuals.

Evaluation of the strategies to reduce third‐generation oral cephalosporins in dentistry at a Japanese academic hospital: An interrupted time series analysis
Akira Yamagami; Katsuya Narumi; Yoshitaka Saito; Ayako Furugen; Shungo Imai; Yoshimasa Kitagawa; Yoichi Ohiro; Ryo Takagi; Yoh Takekuma; Mitsuru Sugawara; Masaki Kobayashi
Journal of Clinical Pharmacy and Therapeutics, 47, 7, 1010, 1019, Wiley, 07 Mar. 2022, [Peer-reviewed], [International Magazine]
English, Scientific journal, WHAT IS KNOWN AND OBJECTIVE: Third-generation oral cephalosporins, especially cefcapene-pivoxil (CFPN-PI), have been used frequently in the Japanese dental field. In December 2014 and April 2016, the newly published clinical guidelines recommended the use of amoxicillin (AMPC). Thus, it is important to evaluate the impact of these guidelines on the prescription profiles of prophylactic antibiotics, clinical outcomes and cost-effectiveness of antibiotics. METHODS: We conducted a retrospective study to analyse an interrupted time series analysis from April 2013 to March 2020 at the Department of Dentistry of Hokkaido University Hospital. A segmented regression model was used to estimate the changes in the incidence of infectious complications following tooth extraction. Prescribed antibiotic data were evaluated via days of therapy (DOT). Antibiotic costs were calculated in terms of the Japanese yen (JPY). RESULTS AND DISCUSSION: We identified 17,825 eligible patients. The incidence rates of infectious complications (SSI + dry socket) and SSI after tooth extraction were 3.2% and 2.2%, respectively, during the entire period. The extraction of impacted third molars corresponded to 5.0% and 3.4%, respectively. However, their incidence rates were not significantly different during this period. The use of prophylactic antibiotics and antibiotic cost showed consistent trends following the implementation of guidelines. The mean DOT of CFPN-PI decreased (ranging from 4893.6 DOTs/1000 patients [March 2013 to November 2014] to 3856.4 DOTs/1000 patients [December 2014 to March 2016]; p < 0.001, and from 3856.4 DOTs/1000 patients [December 2014 to March 2016] to 2293.9 DOTs/1000 patients [April 2016 to March 2020]; p < 0.001). In contrast, the mean DOT of AMPC was found to be increased (ranging from 1379.7 DOTs/1000 patients [March 2013 to November 2014] to 3236.3 DOTs/1000 patients [December 2014 to March 2016]; p < 0.001, and from 3236.3 DOTs/1000 patients [December 2014 to March 2016] to 4597.8 DOTs/1000 patients [April 2016 to March 2020]; p < 0.001). The mean monthly cost was decreased (ranging from 905.3 JPY [March 2013 to November 2014] to 788.7 JPY [December 2014 to March 2016]; p = 0.003, and from 788.7 JPY [December 2014 to March 2016] to 614.0 JPY [April 2016 to March 2020]; p < 0.001). WHAT IS NEW AND CONCLUSION: After December 2014, prophylactic antibiotics were switched from CFPN-PI to AMPC, and the incidence rate of infectious complications was not significantly different over time. However, changing antibiotics is useful from a cost-effectiveness perspective.

Trigeminocardiac reflex-related sudden bradycardia and hypotension can be induced by drain removal after superficial parotidectomy
Yi-Hua Sun; Kuan-Chou Lin; Yoichi Ohiro; Chih-Yuan Fang
Journal of Dental Sciences, 16, 4, 1320, 1321, Elsevier BV, Oct. 2021, [Peer-reviewed], ［Internationally co-authored］
English, Scientific journal

Peri‐operative management of multiple tooth extractions in a patient with congenital hypofibrinogenemia receiving anticoagulant therapy
Wataru Kakuguchi; Yoshiyuki Nakamichi; Kazue Kasahara; Masaaki Horikawa; Yoichi Ohiro
Oral Science International, 1, 5, Wiley, 15 Sep. 2021, [Peer-reviewed], [Last author]
English, Scientific journal

Effect of varying storage conditions on diagnostic test outcomes of SARS-CoV-2
Satoshi Oguri; Shinichi Fujisawa; Keisuke Kamada; Sho Nakakubo; Yu Yamashita; Junichi Nakamura; Hiroshi Horii; Kazuki Sato; Mutsumi Nishida; Takanori Teshima; Yoichi Ohiro; Ayato Takada; Satoshi Konno
Journal of Infection, 83, 1, 119, 145, Elsevier BV, Jul. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal

Correlation between endothelial CXCR7 expression and clinicopathological factors in oral squamous cell carcinoma
Misa Yanagiya; Randa I. H. Dawood; Nako Maishi; Yasuhiro Hida; Chisaho Torii; Dorcas A. Annan; Hiroshi Kikuchi; Aya Yanagawa Matsuda; Tetsuya Kitamura; Yoichi Ohiro; Masanobu Shindoh; Shinya Tanaka; Yoshimasa Kitagawa; Kyoko Hida
Pathology International, 71, 6, 383, 391, Wiley, Jun. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Oral squamous cell carcinoma (OSCC) impairs functionality and sensuousness resulting in poor quality of life. Biomarkers can predict disease trajectory and lead to effective treatments. Transcriptomics have identified genes that are upregulated in tumor endothelial cells (TECs) compared with normal endothelial cells (NECs). Among them, chemokine receptor 7 (CXCR7) is highly expressed in TECs of several cancers and involved in angiogenesis of TECs. However, levels of CXCR7 in OSCC blood vessels have not been fully investigated. In this study, we analyzed the correlation between CXCR7 expression in TECs and clinicopathological factors in OSCC. Immunohistochemistry for CXCR7 and CD34 was performed on 59 OSCC tissue specimens resected between 1996 and 2008 at Hokkaido University Hospital. CXCR7 expression in blood vessels was evaluated by the ratio of CXCR7+/CD34+ blood vessels. CXCR7 expression was 42% and 19% in tumor and non-tumor parts, respectively, suggesting that CXCR7 expression is higher in TECs than in NECs. CXCR7 expression in TECs correlated with advanced T-stage and cancer stage. Overall survival and disease-free survival rates were higher in low-expressing CXCR7 patients than in high-expressing. These results suggest that CXCR7 expression in blood vessels may be a useful diagnostic and prognostic marker for OSCC patients.

A case of a large ameloblastic carcinoma of the mandible with cervical lymph node metastasis
Tamaki SEKIGUCHI (YAMADA; Yoichi OHIRO; Yuichi ASHIKAGA; Kazuyo SATO; KURIBAYASHI; Tetsuya KITAMURA; Kanchu TEI
Japanese Journal of Oral and Maxillofacial Surgery, 67, 5, 275, 280, Japanese Society of Oral and Maxillofacial Surgeons, 20 May 2021, [Peer-reviewed]
Japanese, Scientific journal

Overexpressed tumor protein p53 and the impaired function in aggressively growing calcifying odontogenic cyst: a case report.
Ohiro Y; Kakuguchi W; Kuribayashi K; Kitamura T; Tei K
Hokkaido J Dent Sci, 41, 2, 143, 146, Mar. 2021, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

A case of sarcoma suspected to be radiation-induced occurring for a short time after postoperative radiation therapy for carcinoma of the maxillary gingiva
Tamaki Sekiguchi (Yamada); Kanchu Tei; Yoichi Ohiro; Kazuyo Kuribayashi; Akihiro Kudo; Yuichi Ashikaga
Journal of Japanese Society of Oral Oncology, 32, 4, 229, 236, Japan Society for Oral Tumors, Dec. 2020, [Peer-reviewed]
Japanese, Scientific journal

COVID-19 Pandemic and Future of Dentistry
Yoichi Ohiro
Hokkaido J Dent Sci, 41, 1, 19, 24, Sep. 2020
Japanese, Scientific journal

miR-10b regulated by Twist maintains myofibroblasts activities in oral submucous fibrosis
Chih-Yuan Fang; Cheng-Chia Yu; Yi-Wen Liao; Pei-Ling Hsieh; Yoichi Ohiro; Pei-Ming Chu; Yu-Cheng Huang; Chuan-Hang Yu; Lo-Lin Tsai
Journal of the Formosan Medical Association, 119, 7, 1167, 1173, Elsevier BV, Jul. 2020, [Peer-reviewed], ［Internationally co-authored］
English, Scientific journal

A case of ameloblastic fibroma treated conservatively by impacted tooth preservation
CHO Taichi; OHIRO Yoichi; KITAMURA Tetsuya; HORIMUKAI Hiromasa; SATO Yuji; MINOWA Kazuyuki
Japanese Journal of Oral and Maxillofacial Surgery, 66, 3, 147, 151, Mar. 2020, [Peer-reviewed]

Application of the dredging method in a case of recurrent ameloblastoma that had spread over a large region of the mandible
Wataru Kakuguchi; Yoichi Ohiro; Seitaro Nakazawa; Ryo Naito; Yasuhito Moritani; Yoshiyuki Nakamichi; Hiromasa Horimukai; Tetsuya Kitamura; Kanchu Tei
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 32, 1, 44, 48, Elsevier BV, Jan. 2020, [Peer-reviewed]
English, Scientific journal

Robin Sequence患者における舌前方固定術前・後の栄養摂食経路および体重増加に関する検討
青海 哲也; 大廣 洋一; 古郷 幹彦; 鄭 漢忠
北海道歯学雑誌, 40, 1, 13, 19, 北海道歯学会, Sep. 2019, [Peer-reviewed]
Japanese

下顎埋伏智歯抜歯術におけるセフカペンピボキシルとアモキシシリンの手術部位感染予防効果の比較
山神 彰; 山田 武宏; 北川 善政; 大廣 洋一; 佐藤 淳; 石黒 信久; 今井 俊吾; 小林 正紀; 井関 健
医療薬学, 45, 5, 254, 261, (一社)日本医療薬学会, May 2019, [Peer-reviewed]
Japanese, 下顎埋伏智歯抜歯術においてセフカペンピボキシル(CFPN-PI)またはアモキシシリン(AMPC)の予防投与を受けた患者の手術部位感染(SSI)発生率を比較した。解析対象となったのはCFPN-PI群129例(男性50例、女性79例、中央値24.0歳)、AMPC群164例(男性75例、女性89例、中央値25.0歳)であった。SSI発生率はCFPN-PI群において11.6%(15/129)、AMPC群において2.4%(4/164)であり、CFPN-PI群のSSI発生率は有意に高かった。次いで、SSI発生に影響する要因分析を行った。単変量解析において抗菌薬(CFPN-PIの使用)、性別(女性)、術後入院、手術難易度、反対側下顎埋伏智歯抜歯の有無、Pell-Gregory分類がP≦0.2となり、これらを多変量解析における解析対象因子として抽出した。解析対象因子のvariance inflation factorはいずれも4未満であり多重共線性はみられなかった。多変量解析の結果、抗菌薬(CFPN-PIの使用)および術後入院がそれぞれオッズ比5.61、4.66を示し、SSIに影響する独立因子として抽出された。

Modified “Dredging Method” for complicated solid/multicystic ameloblastoma in the mandible: Report of a case treated by fractionated enucleation
Yoichi Ohiro; Tamaki Yamada; Wataru Kakuguchi; Ichizo Kobayashi; Tetsuya Kitamura; Kanchu Tei
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 31, 2, 121, 125, Mar. 2019, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

A Multicenter Retrospective Study of Elective Neck Dissection for T1-2N0M0 Tongue Squamous Cell Carcinoma: Analysis Using Propensity Score-Matching
Mitsunobu Otsuru; Yoshihide Ota; Souichi Yanamoto; Masaya Okura; Masahiro Umeda; Tadaaki Kirita; Hiroshi Kurita; Michihiro Ueda; Takahide Komori; Nobuhiro Yamakawa; Takahiro Kamata; Takumi Hasegawa; Takahiko Shibahara; Yoichi Ohiro; Yoshihiro Yamashita; Kazuma Noguchi; Tadahide Noguchi; Kazunari Karakida; Hiroyuki Naito; Tomonao Aikawa; Tetsuro Yamashita; Daijiro Kabata; Ayumi Shintani
Annals of Surgical Oncology, 26, 2, 555, 563, Feb. 2019, [Peer-reviewed]
English, Scientific journal

Study on tooth preservation in patients with ameloblastomas arising in the mandible and treated by the dredging method
YAMADA Tamaki; OHIRO Yoichi; ASHIKAGA Youichi; KURIBAYASHI Kazuyo; MATSUZAWA Yusuke; NAGAMINE Kyosuke; TANAKA Soichi; KITAMURA Tetsuya; TEI Kanchu
日本口腔外科学会雑誌, 64, 6, 347, 354, Jun. 2018, [Peer-reviewed]
Japanese, Scientific journal

Long-Term Changes in Bone Height After Mandibular Reconstruction Using a Free Fibula Graft in an Elderly Population
Kosuke Ishikawa; Yuhei Yamamoto; Hiroshi Furukawa; Yoichi Ohiro; Akira Satoh; Toshihiko Hayashi
JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, 75, 12, 2682, 2688, Dec. 2017, [Peer-reviewed]
English, Scientific journal

Application of vacuum-assisted closure therapy and hyperbaric oxygen therapy for an exposed titanium plate after mandible reconstruction: a case report
Toshihiko Hayashi; Yuichi Ashikaga; Y. Ohiro; Kanchu Tei; S. Tanaka; Taku Maeda; R. Yoshitatsu; Kazuyo Kuribayashi
International Journal of Oral and Maxillofacial Surgery, 46, 336, Elsevier BV, 01 Mar. 2017

Vasohibin-1 as a Novel Prognostic Factor for Head and Neck Squamous Cell Carcinoma
Chisaho Torii; Yasuhiro Hida; Masanobu Shindoh; Kosuke Akiyama; Noritaka Ohga; Nako Maishi; Yoichi Ohiro; Mitsunobu Ono; Yasunori Totsuka; Yoshimasa Kitagawa; Kanchu Tei; Yasufumi Sato; Kyoko Hida
ANTICANCER RESEARCH, 37, 3, 1219, 1225, Mar. 2017, [Peer-reviewed]
English, Scientific journal

ALDH1 and podoplanin expression patterns predict the risk of malignant transformation in oral leukoplakia
Umma Habiba; Kyoko Hida; Tetsuya Kitamura; Aya Yanagawa Matsuda; Fumihiro Higashino; Yoichi M. Ito; Yoichi Ohiro; Yasunori Totsuka; Masanobu Shindoh
ONCOLOGY LETTERS, 13, 1, 321, 328, Jan. 2017, [Peer-reviewed]
English, Scientific journal

Therapeutic strategies for etiologies in the oral and maxillofacial regions.
Tei K; Ohiro Y; Matsushita K; Matsuzawa Y; Satoh K; Yamada T
Hokkaido Journal of Dental Science, 38, 151, 156, 北海道歯学会, 2017
English, Research institution, In this paper we describe our strategies for treatment of oral cancer, jaw deformity, and odontogenic tumors. Details of the strategy for cleft palate is introduced in a separate report, by Professor Mikoya. Newly applied strategies for patients with post-surgical swallowing dysfunction and dentoalveolar surgery are also introduced. Oral cancer, jaw deformity, cleft, and odontogenic tumors are the main etiologies in the oral and maxillofacial region. Early stages of oral cancer (StageI and StageII) are mainly treated with surgery or radiotherapy alone, and the 5-year survival rate is 80 to 90%. With advanced oral cancer (StageIII and StageIV) a combination of chemotherapy and radiotherapy with or without surgery is the norm, but the 5-year survival rate is below 50% overall. Therefore, there is a need for an effective combination of therapies for advanced oral squamous cell carcinomas. The treatment goal for jaw deformities is to achieve a functional and desirable occlusion. To achieve desirable occlusion, treatment by the team approach is introduced, it includes oral and maxillofacial surgeons, orthodontists, and prosthodontists. A unique method, termed the "Dredging Method" is used in the treatment strategies of odontogenic tumors. The method was introduced to remove all of the tumor and restore the form and function of the jaw through bone generation. The Dredging Method involves four steps: Deflation, Enucleation, Dredging, and Follow up. Tooth autotransplantation in our department stands out in comparison with other facilities in the field of dentoalveolar surgery. The annual number of cases exceeds 150, and up to December of 2015 the total number of cases reached 1,100. The 5-year survival rate for cases with transplanted third molars to the molar region is 86%. Post-surgical swallowing dysfunction is strongly dependent on the extent of the surgery and type of reconstruction. Here, post-surgical swallowing dysfunction can be accurately predicted prior to the surgery, and to develop plans for individual rehabilitation programs to overcome post-surgical swallowing dysfunction is crucial.

Clinical study of multiple primary oral cancer
足利雄一; 栗林和代; 大廣洋一; 小野貢伸; 鄭 漢忠
北海道歯学会雑誌, 37, 1, 20, 24, 北海道歯学会, Sep. 2016, [Peer-reviewed]
Japanese, Scientific journal, 1984年１月から2011年12月までの27年間に当科で治療を行った口腔扁平上皮癌一次症例373例のうち，口腔内多発癌と診断した22例を対象に臨床的検討を行った．発生時期は同時性3例，異時性10例，同・異時性が９例であった．部位別では頰粘膜，下顎歯肉，舌，上顎歯肉に多く発生していた．第１癌から第２癌までの発生間隔は平均80.6か月，第２癌から第３癌までの発生間隔は平均82.5か月であった．治療法は主に手術を主体とした治療が行われていた．局所再発は50.7％，頸部リンパ節転移は59.1％にみられた．病因特異的累積生存率は５年で81.8％ であったが，10年では50.3％であった．口腔内多発癌は発生間隔が長いだけでなく，局所再発，リンパ節転移が多いため長期にわたる経過観察が必要であり，早期発見だけではなく，より良い口腔内環境を維持しできるだけ発症を抑制させる様な予防策も念頭において治療を行っていく必要がある．In this study 22 patients with multiple primary oral cancers (out of 373 oral squamous cell carcinoma) were observed. These patients were treated at Oral Surgery of Hokkaido University Hospital from 1984 to 2011. 3 synchronous, 10 metachronous and 9 synchro-metachronous carcinomas were observed. The buccal mucosa, lower gingiva, tongue, upper gingiva were seen frequently. The mean interval between the first and the second carcinomas was 80.6 months, while that between the second and third carcinomas was 82.5 months. Surgical treatment was performed for most cases. Local recurrence rate was 50.7% and cervical lymph node metastasis rate was 59.1%. The 5-year and the 10-year disease-specific cumulative survival rate were 81.8% and 50.3%, respectively. The long developmental period, high local recurrence and regional metastasis indicate the necessity of a long term followup and maintenance of good oral environment to inhibit tumor pathogenesis.

Management of the N0 Neck in Early Stage Oral Squamous Cell Carcinoma．
Ono M; Kuribayashi K; Ashikaga Y; Ohiro Y; Tei K
北海道歯学雑誌, 36, 2, 128, 133, 北海道歯学会, Mar. 2016, [Peer-reviewed]
English, Research institution, Management of clinically node negative neck patients with oral squamous cell carcinoma (OSCC) remains controversial. Elective neck dissection (END) is used on an assumption of difficulty in diagnosing subclinical nodal metastases in the neck. This is also the case when early dissection allows better prognosis if nodal metastases actually exist. However, the disadvantage of prophylactic END is that truly N0 neck patients undergo unnecessary neck dissection and have to bear shoulder complaints and dysfunction. Our strategy has been a" wait and see" policy for the management of the neck among patients with T1-2 oral cancer without clinical nodal metastases unless the neck was being opened for reconstruction requirements. The purpose of this study is to assess the outcome of patients who underwent trans-oral tumor excision and" wait-and-see" policy for the N0 neck. A total of 94 previously untreated patients with T1-2N0 classification were investigated. Elective neck dissection (END) was carried out on 10 patients (10.6%) at the time of treatment of the primary resection with reconstruction (END group), and 84 patients were observed without neck dissection (Observation group). The 5-year disease specific survival rates were 90.0% for the END group and 95.9% for the observation group. The 5-year over all survival rates were 90.0% in the END group and 88.8% in the observation group. In the observation group of 84 patients, 16 patients (19.0%) had delayed metastasis in the neck subsequently. 15 patients underwent salvage neck dissection. The salvage rate was 86.6% (13/15 patients). The treatment strategy "wait and see" policy for T1-2N0 OSCC resulted in a good outcome at our institution. Unnecessary neck dissection can be avoided for the truly N0 patients.

A case of malignant lymphoma arising in the bone marrow of the mandible
山田 珠希; 栗林 和代; 大廣 洋一; 篠原 早紀; 松田 光平; 鈴木 豊典; 北村 哲也; 進藤 正信; 鄭 漢忠
北海道歯学雑誌, 36, 2, 134, 141, 北海道歯学会, Mar. 2016, [Peer-reviewed]
Japanese, 顎顔面領域に発症する悪性リンパ腫の顎骨における発生は極めてまれである．今回われわれは下顎骨骨髄から発生した悪性リンパ腫の１例を経験したので報告する． 患者は59歳，男性．2014年９月に右耳下腺咬筋部の腫脹を自覚し，その後腫脹の増大傾向を認めたため，10月に病院歯科口腔外科を受診した．同院では臨床所見ならびに画像所見から歯に起因する炎症性疾患と診断され，抗菌薬による消炎処置後，原因歯の抜歯術が施された．腫脹は一時改善傾向を示したが，その後再燃したため，腫瘍性病変が疑われ2015年１月に紹介受診した．初診時の口腔外所見では顔貌左右非対称で右耳下腺咬筋部に弾性硬の著明な腫脹を認め，右オトガイ部皮膚と下唇に知覚鈍麻を認めた．口腔内所見では右頬粘膜下に腫瘤性病変を認めたが，表面を被覆する粘膜は正常であった．画像検査では右下顎骨体，下顎枝，下顎頭の骨髄内からその周囲に比較的境界明瞭な腫瘤性病変を認め，また，皮質骨全体に点状の骨欠損を認めた．PET-CT検査では腫瘤と一致した部位にSUV max 22.5の集積亢進を認めた．臨床検査所見では特記すべき所見は認められなかった．下顎骨骨髄由来の腫瘍の臨床診断のもと，右頬粘膜部から腫瘤性病変の生検を行い，びまん性大細胞性B細胞リンパ腫と診断された．血液内科に対診し，R-COHP療法ならびに放射線治療により寛解が得られ，現在血液内科にて経過観察中である．Malignant lymphoma arising in the mandible is extremely rare. In this study we report on a case of malignant lymphoma arising in the bone marrow of the mandible. The patient was a 59-year-old man. In September 2014, he noticed a swelling in the right parotid masseteric region. The swelling was getting bigger, and thereafter he visited an oral surgeon's hospital in October, 2014. In the hospital, antibiotics were administered and he had the diagnosis of an odontogenic inflammation from clinical and imaging findings. The swelling was improved temporarily, but the symptom recurred soon. Other diseases, including lesions, were suspected. He was then referred to our hospital. At the first visit, an extra-oral examination showed facial asymmetry caused by the swelling and hypoesthesia of the right mental region and lower lip. An intraoral examination showed a mass under the right normal buccal mucosa. Contrast enhanced CT and an MRI showed irregular and punctate bone resorption in the cortical bone of the right mandible and uniformly enhanced soft tissue. PET-CT revealed an abnormal uptake in the right mandible region (SUV max : 22.5). In blood tests there were no apparent abnormalities. Biopsy of the tissue showed diffuse large B-cell lymphoma. He received chemotherapy with R-CHOP and irradiation at the department of hematology. He has remained in remission six months after treatment.

Transparent, resin-based, three-dimensional model to help visualise intraosseous tumours.
Kakuguchi W; Ohiro Y; Matsushita K
Br J Oral Maxillofac Surg, 55, 4, 431, 432, 2016, [Peer-reviewed]
English

The improvement on swallowing function by wearing denture in the patients received mandibular reconstruction
Toshihiko Hayashi; Y. Yamzaki; Yuichi Ashikaga; Kazuyo Kuribayashi; H. Hamada; Mitsunobu Ono; Kanchu Tei; Y. Ohiro
International Journal of Oral and Maxillofacial Surgery, 44, e272, Elsevier BV, 01 Oct. 2015

Cytoplasmic expression of HuR may be a valuable diagnostic tool for determining the potential for malignant transformation of oral verrucous borderline lesions
Umma Habiba; Tetsuya Kitamura; Aya Yanagawa-Matsuda; Kyoko Hida; Fumihiro Higashino; Yoichi Ohiro; Yasunori Totsuka; Masanobu Shindoh
ONCOLOGY REPORTS, 31, 4, 1547, 1554, Apr. 2014, [Peer-reviewed]
English, Scientific journal

Expression of parathyroid hormone-related protein confers malignant potential to mucoepidermoid carcinoma
Kyosuke Nagamine; Tetsuya Kitamura; Aya Yanagawa-Matsuda; Yoichi Ohiro; Kanchu Tei; Kyoko Hida; Fumihiro Higashino; Yasunori Totsuka; Masanobu Shindoh
Oncology Reports, 29, 6, 2114, 2118, Jun. 2013, [Peer-reviewed]
English, Scientific journal

最新の歯学；口腔癌治療における術前化学療法併用放射線治療の現状．
大廣洋一; 栗林和代; 足利雄一; 小野貢伸; 鄭 漢忠; 北村哲也; 進藤正信
北海道歯学会雑誌, 33, 2, 192, 195, May 2013
Japanese, Scientific journal

Dose swallowing recover in the long term in patients with surgically treated tongue.
Tei K; Sakakibara N; Yamazaki Y; Ohiro Y; Ono M; Totsuka Y
Journal of Oral and Maxillofacial Surgery, 70, 11, 2680, 2686, Elsevier, Nov. 2012, [Peer-reviewed]
English, Scientific journal, Purpose: The present study aims to measure the post-surgical swallowing function in patients five years after operative treatment of tongue carcinoma. Patients and Methods: Using a retrospective cohort study design, the investigators enrolled post-surgical patients treated for tongue carcinomas in Hokkaido University Hospital. The primary outcome variable was the Oropharyngeal Swallow Efficiency (OPSE) determined by videofluoroscopic evaluation and the OPSE at present was compared with that at discharge. Other variables included present nutritional status (Body Mass Index: BMI, Serum Albumin), dietary intake, self-rating of the present swallowing function, and occurrence of pneumonia. Statistical analysis used the paired t-test and Spearman's rank correlation. Results: The swallowing function was assessed in 20 patients (11 males and 9 females) subjected to surgical treatment of tongue carcinomas; the median age was 70 years (range 56-90 years) at the present evaluation. The mean values of the liquid OPSE and paste OPSE at present were 26.6±21.2 and 21.9±22.5, respectively. The mean values for BMI and serum albumin at present were 22.2±3.4 and 4.5±0.3g/dl respectively. All patients had a full oral intake of foods, with a mean self-rated value of 6.4±2.5, an acceptable value as evaluated by the patients. Pneumonia requiring hospitalization had not occurred in these patients. Conclusions: Long-term follow-up of patients following operative treatment of tongue carcinomas demonstrate acceptable levels of oral function and nutritional status despite objective measures of poor swallowing efficiency assessed using a videofluoroscopy.

A large ameloblastic carcinoma of the mandible with multiple pulmonary metastases : Report of a case
SATO(KURIBAYASHI) Kazuyo; ONO Mitsunobu; ASHIKAGA Yuichi; OHIRO Youichi; SHINDOH Masanobu; TOTSUKA Yasunori
Journal of Oral Surgery Society of Japan, 58, 3, 137, 141, Japanese Society of Oral and Maxillofacial Surgeons, 2012, [Peer-reviewed]
Japanese, Scientific journal, We describe a large ameloblastic carcinoma of the mandible with multiple pulmonary metastases. The patient was a 62-year-old woman. In March 1994, she underwent enucleation of a tumor in the anterior part of the mandible at another hospital. The histopathological diagnosis was a typical ameloblastoma. She was lost to followup soon after the operation. In March 2008, she was referred to Hokkaido University Hospital. She had a large hemorrhagic tumor, which projected outside of the mouth. Chest radiography revealed many nodular opacities in both lung fields. In May 2008, we performed a segmental mandibulectomy to improve her quality of life. The histological diagnosis was an ameloblastic carcinoma-secondary type, intraosseous. There has been no sign of tumor recurrence for 2 years postoperatively.

Evaluation of PLGA-collagen hybrid mesh in the healing process of bony cavities in rabbit mandibles.
野呂洋輔; 大廣洋一; 鄭 漢忠; 吉村善隆; 出山義昭; 飯塚 正; 鈴木邦明; 戸塚靖則
Hokkaido Journal of Dental Science, 31, 2, 62, 69, 2010, [Peer-reviewed]
Japanese

Inhibitory effects of epigallocatechin-3 gallate, a polyphenol in green tea, on tumor-associated endothelial cells and endothelial progenitor cells
Noritaka Ohga; Kyoko Hida; Yasuhiro Hida; Chikara Muraki; Kunihiko Tsuchiya; Kohei Matsuda; Yoichi Ohiro; Yasunori Totsuka; Masanobu Shindoh
CANCER SCIENCE, 100, 10, 1963, 1970, Oct. 2009, [Peer-reviewed]
English, Scientific journal

Pim-1 activation of cell motility induces the malignant phenotype of tongue carcinoma
Souichi Tanaka; Tetsuya Kitamura; Fumihiro Higashino; Kyoko Hida; Yoichi Ohiro; Mitsunobu Ono; Masanobu Kobayashi; Yasunori Totsuka; Masanobu Shindoh
MOLECULAR MEDICINE REPORTS, 2, 2, 313, 318, Mar. 2009, [Peer-reviewed]
English, Scientific journal

Serum p53 antibodies as a prognostic indicator in oral squamous cell carcinoma
Yutaka Yamazaki; Itsuo Chiba; Makoto Ishikawa; Chiharu Satoh; Ken-ichi Notani; Yoichi Ohiro; Yasunori Totsuka; Shigeaki Mizuno; Yoshimasa Kitagawa
ODONTOLOGY, 96, 1, 32, 37, Jul. 2008, [Peer-reviewed]
English, Scientific journal

Expression of E1AF, an ets-oncogene transcription factor, highly correlates with malignant phenotype of malignant melanoma through up-regulation of the membrane-type-1 matrix metalloproteinase gene
Hironobu Hata; Tetsuya Kitamura; Fumihiro Higashino; Kyoko Hida; Koichi Yoshida; Yoichi Ohiro; Yasunori Totsuka; Yoshimasa Kitagawa; Masanobu Shindoh
ONCOLOGY REPORTS, 19, 5, 1093, 1098, May 2008, [Peer-reviewed]
English, Scientific journal

悪性腫瘍との鑑別に苦慮した下顎骨骨髄炎の一例
格口 渉; 馬渕 亜希子; 大廣 洋一; 箕輪 和行; 鄭 漢忠; 進藤 正信; 戸塚 靖則
日本口腔外科学会雑誌, 54, 1, 26, 26, (公社)日本口腔外科学会, Jan. 2008
Japanese

低酸素下におけるVEGFとAngiopoietin-like4の相互制御機構(Cross-regulation of VEGF and Angiopoietin-like4 under hypoxia)
鎌田 卓; 夏井坂 光輝; 中川 宏治; 大廣 洋一; 進藤 正信; 東野 史裕; 小出 秀之; 小林 正伸; 戸塚 靖則
日本癌学会総会記事, 66回, 311, 311, (一社)日本癌学会, Aug. 2007
English

Recovery from postsurgical swallowing dysfunction in patients with oral cancer
Kanchu Tei; Kuniaki Maekawa; Hideaki Kitada; Yoichi Ohiro; Yutaka Yamazaki; Yasunori Totsuka
JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, 65, 6, 1077, 1083, Jun. 2007, [Peer-reviewed]
English, Scientific journal

Cross-regulation of VEGF;Angiopoietin-like;under hypoxia
KAMADA Suguru; NATSUIZAKA Mitsuteru; NAKAGAWA Koji; OHIRO Yoichi; SHINDO Masanobu; HIGASHINO Fumihiro; KOIDE Hideyuki; KOBAYASHI Masanobu; TOTSUKA Yasunori
Hokkaido Journal of Dental Science, 27, 2, 96, 103, 2006, [Peer-reviewed]
Japanese, Scientific journal

ElAF expression is closely correlated with malignant phenotype of tongue squamous cell carcinoma through activation of MT1-MMP gene promoters
Y Izumiyama; Y Ohiro; F Higashino; K Yoshida; K Taguchi; S Todo; T Kohgo; Y Totsuka; M Shindoh
ONCOLOGY REPORTS, 13, 4, 715, 720, Apr. 2005, [Peer-reviewed]
English, Scientific journal

Remarkable regression of lower alveolus and gingival carcinoma by chemotherapy with TS-1 : Report of two cases
TAKANO Masashi; ONO Mitsunobu; OHIRO Yoichi; TEI Kanchu; TOTSUKA Yasunori; SHINDOH Masanobu
Journal of Oral Surgery Society of Japan, 50, 10, 608, 611, Japanese Society of Oral and Maxillofacial Surgeons, 2004, [Peer-reviewed]
Japanese, We describe two cases of lower gingival carcinoma deeply invading the mandible that remarkably regressed in response to TS-1 chemotherapy. Patient 1, a 73-year-old woman, presented with hypoesthesia of the right lower lip. Clinical examination revealed an ulcerated lesion with induration in the right lower side of the gingiva. Orthopantomography showed a tumor deeply invading the mandible. Biopsy revealed a well-differentiated squamous cell carcinoma. Electrocardiography showed ischemic heart disease, requiring immediate treatment. She underwent percutaneous transluminal coronary angioplasty (PTCA) before mandiblectomy. Twelve days before the operation, she was given TS-1, because the bone defect worsened despite treatment with UFT during cardiovascular therapy. Patient 2, a 61-year-old woman, presented with an ulcerative lesion in the right lower side of the gingiva. Orthopantomography showed an extensive bone defect in the right side of the mandible. After histopathological diagnosis confirmed squamous cell carcinoma, chemotherapy with TS-1 was started 8 days before the operation. Histopathological findings showed that the tumors in both patients regressed remarkably in response to TS-1.

ONO-4007, a synthetic lipid A analog, induces Th1-type immune response in tumor eradication and restores nitric oxide production by peritoneal macrophages
K Matsushita; Y Kuramitsu; Y Ohiro; Kobayashi, I; T Watanabe; M Kobayashi; M Hosokawa
INTERNATIONAL JOURNAL OF ONCOLOGY, 23, 2, 489, 493, Aug. 2003, [Peer-reviewed]
English, Scientific journal

口腔扁平上皮がんにおけるVEGF-Cの発現とリンパ節転移の関連．
小堀善則; 進藤正信; 大廣洋一; 向後隆男; 戸塚靖則
北海道歯学雑誌, 24, 2, 151, 160, 2003, [Peer-reviewed]
Japanese, Scientific journal

Malignant phenotype of tongue squamous cell carcinoma is closely correlated with expression of E1AF, MT1-MMP
IZUMIYAMA Yuri; SHINDOH Masanobu; OHIRO Yoichi; HIGASHINO Fumihiro; KOHGO Takao; TOTSUKA Yasunori
北海道歯学雑誌, 24, 2, 142, 150, 2003, [Peer-reviewed]
Japanese, Scientific journal

Arthrocentesis following arthroscopic examination in patients with closed lock of the temporomandibular joint
YURA Shinya; TOTSUKA Yasunori; OOI Kazuhiro; MABUCHI Akiko; HORIMUKAI Hiromasa; ASHIKAGA Yuichi; DEYAMA Ayako; YOSHIKAWA Tetsuya; OHIRO Yoichi; HIDA Kyoko
Journal of Oral Surgery Society of Japan, 49, 4, 246, 251, Japanese Society of Oral and Maxillofacial Surgeons, 2003, [Peer-reviewed]
Japanese, We describe procedures for arthrocentesis based on arthroscopic findings and report the therapeutic usefulness of these procedures in 46 patients with closed lock of the temporomandibular joint.
Arthroscopic examination was done under local anesthesia in the outpatient clinic. An 18-gauge needle and a trocar for a 0.8-mm rod-lens fiberscope were inserted into the anterior and posterior compartments of the upper joint space, respectively. The anterior compartment was then observed with special respect to the presence of adhesion. In joints without adhesion, irrigation was done under low hydraulic pressure. In joints with adhesion, irrigation was performed under sufficient hydraulic pressure (maximum pressure exerted, 40 KPa) to widen the upper joint space. Manipulation was performed after irrigation.
Eight weeks after these two procedures, the range of maximum mouth opening increased from 2 to 20 mm and averaged 10.3 mm in 18 patients without adhesion. In 28 patients with adhesion, the increase in maximum mouth opening ranged 3 to 25 mm and averaged 9.1 mm. There was no significant difference in the increase in maximum mouth opening between these two groups.

Inhibition of stress-inducible kinase pathways by tumorigenic mutant p53
Y Ohiro; A Usheva; S Kobayashi; SL Duffy; R Nantz; D Gius; N Horikoshi
MOLECULAR AND CELLULAR BIOLOGY, 23, 1, 322, 334, Jan. 2003, [Peer-reviewed], [Lead author], [International Magazine]
English, Scientific journal

Arthroscopic examination and arthroscopic findings of the upper joint space with an ultra-thin arthroscope
YURA Shinya; TOTSUKA Yasunori; MABUCHI Akiko; DEYAMA Ayako; YOSHIKAWA Tetsuya; OHIRO Yoichi
Journal of Oral Surgery Society of Japan, 49, 1, 43, 46, Japanese Society of Oral and Maxillofacial Surgeons, 2003, [Peer-reviewed]
Japanese, Scientific journal, Arthroscopic examination with an ultra-thin arthroscope is an easy, minimally invasive procedure for examination of the inside of joints. However, one disadvantage of arthroscopy is the risk of scope breakage in narrow joint spaces. We describe an improved procedure for arthroscopic examination of the upper joint space and describe the findings thus obtained.
Arthroscopic examination is done with the patient under local anesthesia in the outpatient clinic. To observe the synovium in the posterior compartment, an 18-gauge needle and a trocar for a 0.8mm rod-lens fiberscope are inserted into the anterior and posterior compartments of the upper joint space, respectively. The articular cartilage of the glenoid fossa and eminence is also observed. Finally, the presence or absence of adhesion in the anterior compartment is examined. In narrowed joint spaces with severe adhesions, injection of normal saline under sufficient pressure is performed to widen the upper joint space. The fiberscope is then advanced from the posterior compartment to the anterior compartment via the lateral paradiscal groove.
This procedure enables us to observe synovitis with capillary hyperemia or hyperplasia of the synovium, cartilage changes with fibrillation or exposure of subchondral bone, and the distribution and degree of adhesion.

Upregulation of Membrane-type1 Matrix Metalloproteinase correlate with the expression of E1AF in Malignant Melanoma
HATA Hironobu; SHINDOH Masanobu; OHIRO Yoichi; HIGASHINO Fumihiro; NOTANI Kenichi; KOHGO Takao; FUKUDA Hiroshi
北海道歯学雑誌, 23, 2, 191, 202, 北海道歯学会, 15 Dec. 2002, [Peer-reviewed]
Japanese, Scientific journal, 悪性黒色腫細胞4株と1例の悪性黒色腫患者からの新鮮材料により抽出したRNAを用いてノーザンブロッティング及び定量RT-PCRによりE1AFとMT1-MMPの発現に関する検索を行った.悪性黒色腫細胞は4株ともmRNAレベルにおいてE1AFとMT1-MMPの相関する発現が認められ,その発現量は浸潤活性の検索結果とも強い相関関係が認められた.臨床検体の検索においても同様の結果が得られ,これらの結果からE1AFがMT1-MMPの転写を亢進することにより悪性黒色腫の浸潤活性の増強に関与していことが示唆された

A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF)
Y Ohiro; Garkavtsev, I; S Kobayashi; KR Sreekumar; R Nantz; BT Higashikubo; SL Duffy; R Higashikubo; A Usheva; D Gius; N Kley; N Horikoshi
FEBS LETTERS, 524, 1-3, 163, 171, Jul. 2002, [Peer-reviewed], [Lead author]
English, Scientific journal

Intra-articular pressure of the temporomandibular joint increases along with occlusal force
YURA Shinya; TOTSUKA Yasunori; OOI Kazuhiro; MABUCHI Akiko; YOSHIKAWA Tetsuya; DEYAMA Ayako; OHIRO Yoichi; GOTODA Akihito; MATSUKI Takamitsu; OKADA Kazuki; YAMAGUCHI Taihiko; KOMATSU Takayuki; INOUE Nobuo
Gakukansetsu Kenkyukaishi, 14, 2, 200, 204, The Japanese Society for Temporomandibular Joint, 2002, [Peer-reviewed]
Japanese, Scientific journal, To clarify the correlation between occlusal force and intra-articular pressure of the temporomandibular joint, we simultaneously measured occlusal force and intra-articular pressure in the upper joint space.
Four patients (4 joints) with closed lock of the temporomandibular joint, and 4 volunteers (4 joints) without temporomandibular disorders, were selected for this study. A prescale 50 H type R, and a transducer for monitoring arterial blood pressure, were used to measure occlusal force and intra-articular pressure, respectively.
The correlation coefficient between occlusal force and intra-articular pressure ranged from 0.710 to 0.954, and the coefficient of determination ranged from 0.504 to 0.910. These results show that intra-articular pressure is in direct proportion to occlusal force. The regression coefficient of the subjects ranged widely (15.3∼270.9).
These results indicate that an increase of occlusal pressure is one factor for weighting of overload in the temporomandibular joint.

A case of metastasis to the lateral lingual lymph nodes in a patient with a preoperative diagnosis of carcinoma of the tongue
OHIRO Yoichi; TEI Kanchu; KASHIWAZAKI Haruhiko; TOTSUKA Yasunori; IIZUKA Tadashi; MINOWA Kazuyuki
Journal of Oral Surgery Society of Japan, 48, 7, 359, 362, Japanese Society of Oral and Maxillofacial Surgeons, 2002, [Peer-reviewed], [Lead author]
Japanese, Scientific journal, A case of squamous cell carcinoma of the tongue with metastasis to the lateral lingual lymphnodes is reported. Preoperative computed tomography and magnetic resonance imaging revealed a mass0.5cm in diameter with heterogenous enhanced signal intensity outside of the left genioglossus muscle.Radical neck dissection, partial left glossectomy, and reconstruction with a forearm flap were performedin a pull-through manner after external radiation and chemotherapy. Histopathologically, the mass had alymph-node structure with small cancer nests at the margin.

A trial of adjuvant chemotherapy based on chronomodulation in two patients with advanced oral cancer
KASHIWAZAKI Haruhiko; TEI Kanchu; OHIRO Yoichi; SATOH Akira; MORIYA Shingo; TOTSUKA Yasunori
Journal of Oral Surgery Society of Japan, 48, 10, 526, 529, Japanese Society of Oral and Maxillofacial Surgeons, 2002, [Peer-reviewed]
Japanese, Scientific journal, To decrease side effects, we used chronomodulation to administer the second course of adjuvant chemotherapy to two patients with advanced oral cancer who had severe side effects during the first course. During the first course, chemotherapy was administered according to a conventional schedule, and during the second course chemotherapy was based on the circadian rhythms of the human body (chronomodulation). The first patient, a 58-year-old woman with squamous cell carcinoma in the left side of the tongue, received two courses of adjuvant chemotherapy (CDDP 80mg/m², day 1+5-FU 800mg/m²/day, days 1-5) after operation. She had grade 4 stomatitis during the first course, but the side effect improved to grade 2 during the second course. The second patient, a 68-year-old man, received two courses of adjuvant chemotherapy (CDDP 80mg/m², ADR 50mg/m²/day, CPA 500mg/m²) for lung metastasis from an adenoid cystic carcinoma arising in the floor of the mouth. Grade 2 nausea and vomiting occurred during the first course, but the second course of chronomodulated chemotherapy caused no nausea or vomiting. This therapy, administered in accordance with the theory of chronomodulation, caused fewer side effects and is thus considered a promising treatment for oral cancer.

Measurement of inta-articular pressure of the temporomandibular joint during arthrocentesis under sufficient hydraulic pressure
YURA Shinya; TOTSUKA Yasunori; OOI Kazuhiro; MABUCHI Akiko; YOSHIKAWA Tetsuya; DEYAMA Ayako; OHIRO Yoichi; TAKASHI Noriyuki; SATO Chiharu; INOUE Nobuo
Journal of Oral Surgery Society of Japan, 48, 10, 515, 519, Japanese Society of Oral and Maxillofacial Surgeons, 2002, [Peer-reviewed]
Japanese, To investigate the effect of distension and removal of adhesion in the upper joint space after lavage under sufficient hydraulic pressure during arthrocentesis, we measured changes in intra-articular pressure in the joint space and performed arthroscopic examinations during the procedure.
Eight patients (8 joints) with closed lock of the temporomandibular joint who underwent arthrocentesis and arthroscopic examination were studied. Adhesion was observed in 5 joints on arthroscopic examination before irrigation; the remaining 3 joints had no adhesion. Changes in intra-articular pressure during irrigation under high pressure (40KPa) were measured in these 8 joints. In 5 joints with adhesion, arthroscopic examination was repeated to confirm whether the adhesion was removed after irrigation.
Immediately after application of pressure, the intra-articular pressure in the joints without adhesion was 9.1-14.7 KPa, and that in the joints with adhesion was 10.0-13.3 KPa. After applying pressure to the joints without adhesion, 30 seconds were required until a stable pressure was reached, whereas 2 to 5minutes were required in joints with adhesion. In all 5 joints with adhesion, removal of the adhesion was observed on arthroscopic examination after the intra-articular pressure decreased to a stable level.
These results indicate that lavage under sufficient hydraulic pressure, which is a 2-to 5-minute procedure, can widen a narrowed joint space and remove adhesion.

Selective transendothelial migration of hematopoietic progenitor cells: A role in homing of progenitor cells
K Imai; M Kobayashi; JX Wang; Y Ohiro; J Hamada; Y Cho; M Imamura; M Musashi; T Kondo; M Hosokawa; M Asaka
BLOOD, 93, 1, 149, 156, Jan. 1999, [Peer-reviewed]
English, Scientific journal

Combination therapy of active hexose correlated compound plus UFT significantly reduces the metastasis of rat mammary adenocarcinoma
K Matsushita; Y Kuramitsu; Y Ohiro; M Obara; M Kobayashi; YQ Li; M Hosokawa
ANTI-CANCER DRUGS, 9, 4, 343, 350, Apr. 1998, [Peer-reviewed]
English, Scientific journal

The mechanism of locally enhanced production of tumor necrosis factor-alpha in tumor tissues by the administration of a new synthetic lipid A analog, ONO-4007, in hepatoma-bearing rats
Y Kuramitsu; Y Ohiro; K Matsushita; M Obara; M Kobayashi; M Hosokawa
ANTI-CANCER DRUGS, 8, 9, 886, 893, Oct. 1997, [Peer-reviewed]
English, Scientific journal

Therapeutic effects of a new synthetic lipid A analog, ONO-4007, on rat hepatoma KDH-8 depend on tumor necrosis factor-sensitivity of the tumor cells
Y Kuramitsu; K Matsushita; Y Ohiro; M Obara; M Kobayashi; M Hosokawa
ANTI-CANCER DRUGS, 8, 9, 898, 901, Oct. 1997, [Peer-reviewed]
English, Scientific journal

A new synthetic lipid A analog, ONO-4007, stimulates the production of tumor necrosis factor-alpha in tumor tissues, resulting in the rejection of transplanted rat hepatoma cells
Y Kuramitsu; M Nishibe; Y Ohiro; K Matsushita; L Yuan; M Obara; M Kobayashi; M Hosokawa
ANTI-CANCER DRUGS, 8, 5, 500, 508, Jun. 1997, [Peer-reviewed]
English, Scientific journal

サイトカイン遺伝子導入によるPGE2産生腫瘍細胞のワクチン効果の増強.
大廣洋一
北海道医学雑誌, 72, 3, 273, 284, 1997, [Peer-reviewed], [Lead author]
Japanese, Others

LAK MIF produced in tumor tissues after chemotherapy
Y. Kuramitsu; M. Obara; Y. Ohiro; L. Yuan; K. Matsushita; M. Kobayashi; M. Hosokawa
Biotherapy, 11, 3, 352, 354, 1997
Japanese, International conference proceedings

非復位性関節円板前方転位症例の開口量ならびにMR像に関する年齢群別検討
馬渕 亜希子; 由良 晋也; 出山 文子; 由川 哲也; 大廣 洋一; 高師 則行; 佐藤 千晴; 井上 農夫男; 戸塚 靖則, 日本口腔外科学会雑誌, 47, 13, 1084, 1085, Dec. 2001
(公社)日本口腔外科学会, Japanese

プロスタグランジンE2による腫瘍免疫の抑制.
大廣洋一; 細川眞澄男, 臨床免疫, 29, 1, 1115, 1120, Sep. 1997, [Lead author]
Japanese, Introduction commerce magazine

Enhancement of vaccine effect of PGE2 productive tumor cells by cytokine gene transfer.
大廣洋一; 蔵満保宏; 小林正伸; 松下和裕; 岡田太; 中井一元; 細川真澄男, Biotherapy (Tokyo), 11, 3, 319, Mar. 1997, [Lead author]
Japanese, Introduction commerce magazine

癌化学療法により腫瘍局所に産生されるLAK遊走阻止因子.
藏滿保宏; 小原 効; 大廣洋一; 袁 嵐; 松下和裕; 小林正伸; 細川眞澄男, BIOTHERAPY, 11, 3, 352, 354, 1997
Japanese, Summary national conference

Ameloblastoma
Benny S. Latif; Iwan Tofani; Cholid Badri; Prodono; Corputty Johan E.M; Abdul Latifi; Lilies Dwi Sulistayani; Teguh Iman Santoso; Evy Eida Vitria; Rachmitha Anne; Dwi Ariawan; Vera Julia; Muhammad Adhitya; Diah Handjari; Ening Krisnuhoni; Ali Nina Liche Seniati; Anwar Soefi Ibrahim; Sastra Kusama Wijaya; Sutarmo Setiadji; Agri Suwandi; Parintosa A; Krista Bangun; Wenny Yulvie; Syurri Innadinna Syahraini; M. Dhani; Busrocho Bayu Kartiko; Santi Anggraini; Tia Sutiawati; Moch Kadri; Siska Wiwanto; Haulah Rachmah; Shierly Citra Khalisha Hannah; Yossi Nurul; Hananto A; Bramadita Satya; Minarma; Ira Suciati; Rusdiana; Norifumi Nkamura; Takao Fuchigamni; Toshiro Kibe; Kiyohide Ishihata; Takeshi Mitsuyasu; Yoshinori Higuchi; Hirofumi Koyama; Michiko Kishida; Yoshiaki Nishizawa; Mikio Iijima; Masahiro Ueda; Tohru Kiyono; Yoshimasa Maniwa; Shosei Kishida; Yoichi Ohiro; Takaya Yoshimura; Hajime Suzuki; Takayuki Ishida; Kazuhide Matsunaga; Etsuro Nozoe, Chapter 21, ”Dredging Method” - an Alternative Conservative Treatment for Ameloblastoma in the Jaw
University of Indonesia, Jan. 2019, [Contributor]

The Bicon Short Implant: a thirty-year perspective
大廣洋一; 小方頼昌; 齋藤成彦; 中村昇司; 南里篤太郎; 平山宗如, 第12章 サイナスリフトテクニック，第13章 リッジスプリッティングと分層粘膜弁，第14章 萎縮上顎歯槽突起，第15章 萎縮下顎歯槽突起
Vincent J. Morgan, クインテッセンス出版, Nov. 2018, 9784781206547, xv, 325p, Japanese, [Joint translation]

"Dredging Method" - An Alternative Conservative Treatment of Ameloblastoma-
Yoichi Ohiro
38th Annual Congress of Taiwanese Association of Oral and Maxillofacial Surgeons, 14 Mar. 2026, Taiwanese Association of Oral and Maxillofacial Surgeons., English, Nominated symposium
13 Mar. 2026 - 15 Mar. 2026, Kaohsiung, Taiwan, Province of China, [Invited]

SARPE施行後の上顎中切歯の変化について
松下 和裕; 山本 隆昭; 佐藤 嘉晃; 高道 理; 武藤 麻未; 中西 康; 格口 渉; 義達 理恵子; 関口 珠希; 道念 正樹; 大賀 則孝; 坂田 健一郎; 大廣 洋一
日本顎変形症学会雑誌, May 2025, (NPO)日本顎変形症学会, Japanese
May 2025 - May 2025

"Dredging Method" - An Alternative Conservative Treatment of Ameloblastoma-
Yoichi Ohiro
15th Annual conference of Nepalese Association Of OMFS and jointmeeting with Japanese society of OMFS, 08 Feb. 2025, Nepalese Association of Oral and Maxillifacial Surgeons, English, Invited oral presentation
08 Feb. 2025 - 08 Feb. 2025, Kathmandu, Nepal, [Invited], [International presentation]

QUAD shot により腫瘍が縮小し，QOL を維持で きた後期高齢者の舌癌の1 例
小川尚博; 格口渉; 由良周子; 栗林和代; 松下和裕; 足利雄一; 大廣洋一
第69 回(公社) 日本口腔外科学会総会・学術大会, 24 Nov. 2024, (公社) 日本口腔外科学会, Japanese, Oral presentation
22 Nov. 2024 - 24 Nov. 2024, 横浜, Japan, [Domestic Conference]

診断に苦慮した下顎骨骨肉腫の1 例
松山大悟; 格口渉; 箭原元基; 由良周子; 栗林和代; 松田彩; 足利雄一; 大廣洋一
第69 回(公社) 日本口腔外科学会総会・学術大会, 24 Nov. 2024, (公社) 日本口腔外科学会, Japanese, Oral presentation
22 Nov. 2024 - 24 Nov. 2024, 横浜, Japan, [Domestic Conference]

骨格性臼歯部開咬症に対し上下顎臼歯部歯槽骨 切り術を施行した1 例
義達理恵子; 松下和裕; 関口(山田) 珠希; 足利雄一; 大廣洋一
第69 回(公社) 日本口腔外科学会総会・学術大会, 23 Nov. 2024, (公社) 日本口腔外科学会, Japanese, Oral presentation
22 Nov. 2024 - 24 Nov. 2024, 横浜, Japan, [Domestic Conference]

二段階口蓋形成手術を施行した片側唇顎口蓋裂 症例の言語成績-硬口蓋閉鎖後の評価-
曽我部いづみ; 三古谷忠; 青海哲也; 伊藤裕美; 桐越晶子; 大廣洋一
第69 回(公社) 日本口腔外科学会総会・学術大会, 22 Nov. 2024, (公社) 日本口腔外科学会, Japanese, Oral presentation
22 Nov. 2024 - 24 Nov. 2024, 横浜, Japan, [Domestic Conference]

片側性唇顎口蓋裂患者における口蓋形成術前の 口蓋形態と言語成績の検討
桐越晶子; 青海哲也; 三古谷忠; 曽我部いづみ; 伊藤裕美; 大廣洋一
第69 回(公社) 日本口腔外科学会総会・学術大会, 22 Nov. 2024, (公社) 日本口腔外科学会
22 Nov. 2024 - 24 Nov. 2024, 横浜, Japan, [Domestic Conference]

反復処置法を適応した下顎エナメル上皮腫の再 発に関する臨床的検討
関口(山田) 珠希; 格口渉; 足利雄一; 大廣洋一
第69 回(公社) 日本口腔外科学会総会・学術大会, 22 Nov. 2024, English, Oral presentation
22 Nov. 2024 - 24 Nov. 2024

顎関節症・咀嚼筋痛障害の治療で改善した 特発性First bite syndromeの1例
箭原 元基; 格口 渉; 大廣 洋一
第78回日本口腔科学会学術集会, 19 Jul. 2024, Japanese, Oral presentation
19 Jul. 2024 - 21 Jul. 2024

COVID-19mRNAワクチン接種後に 発症した三叉神経第Ⅲ枝帯状疱疹の1例
箭原 元基; 格口 渉; 桐越 晶子; 中野 晋太郎; 鄭 漢忠; 大廣 洋一
第50回日本口腔外科学会北日本支部学術集会, 06 Jul. 2024, Japanese, Oral presentation
06 Jul. 2024 - 07 Jul. 2024

下顎前突症と下顎後退症における下顎頭応力分布の差異について CT-OAM法を用いた解析
松下 和裕; 松井 雄一郎; 遠藤 香織; 岩崎 倫政; 大廣 洋一
日本顎変形症学会雑誌, May 2024, (NPO)日本顎変形症学会, Japanese
May 2024 - May 2024

咀嚼筋腱・腱膜過形成症に伴う下顎骨の変形に対しガイドサージェリーを用いて治療した1例
高橋賢多; 格口渉; 武田叡司; 箭原元基; 鄭漢忠; 松田彩; 間石奈湖; 松下和裕; 松下和裕; 足利雄一; 大廣洋一
日本口腔科学会雑誌(Web), 2024
2024 - 2024

Concept of treatment of oral lesions extending into the maxillary sinus
Ohiro Y; Kakuguchi W; Sekiguchi-Yamada T; Ashikaga Y
The 68th Congress of the Japanese Society of Oral and Maxillofacial Surgeons, 10 Nov. 2023, Japanese, Nominated symposium
10 Nov. 2023 - 12 Nov. 2023

頭頸部アルミノックス治療におけるニードルカテーテル穿刺のためのガイドプレートの製作について
足利 雄一; 鈴木 崇祥; 若林 侑輝; 格口 渉; 関口 珠希; 栗林 和代; 本間 明宏; 大廣 洋一
頭頸部癌, May 2023, (一社)日本頭頸部癌学会, Japanese
May 2023 - May 2023

オトガイ形成術を行った患者における側貌軟組織の変化について
松下 和裕; 山本 隆昭; 佐藤 嘉晃; 高道 理; 武藤 麻未; 中西 康; 義達 理恵子; 関口 珠希; 町田 友梨; 足利 雄一; 道念 正樹; 小堀 善則; 大井 一浩; 原田 沙織; 格口 渉; 大賀 則孝; 坂田 健一郎; 山口 博雄; 大廣 洋一
日本顎変形症学会雑誌, May 2023, (NPO)日本顎変形症学会, Japanese
May 2023 - May 2023

下顎埋伏智歯抜歯手術における手術部位感染予測モデルの開発:リサンプリング手法を用いた予後予測モデル
山神彰; 鳴海克也; 鳴海克也; 齋藤佳敬; 古堅彩子; 今井俊吾; 北川善政; 大廣洋一; 高木諒; 武隈洋; 菅原満; 菅原満; 小林正紀; 小林正紀
日本医療薬学会年会講演要旨集(Web), 2023
2023 - 2023

Treatment of secondary deformity following free fibula flap mandibule reconstruction using a computer simulation system
中野晋太郎; 足利雄一; 格口渉; 関口珠希; 栗林和代; 大廣洋一
日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 2023
2023 - 2023

Clinical outcomes of the lower gingival squamous cell carcinoma treated based on the bone destruction pattern
Yoichi Ohiro
26th Congress of the European Association for Cranio-Maxillo-Facial Surgery, 28 Sep. 2022, English, Invited oral presentation
27 Sep. 2022 - 30 Sep. 2022, Madrid, Spain, [Invited], [International presentation]

The Role of Cancer Board with Multidisciplinary Specialists in the Treatment of Head and Neck Cancer in Hokkaido University Hospital
Yoichi Ohiro
8th World Congress of the International Academy of Oral Oncology, 23 Jun. 2022, English, Invited oral presentation
23 Jun. 2022 - 26 Jun. 2022, Chicago, United States, [Invited], [International presentation]

舌扁平上皮癌T1-2N0(UICC第8版)におけるリンパ節後発転移の有無に関する臨床病理学的検討
格口 渉; 足利 雄一; 松田 彩; 栗林 和代; 間石 奈湖; 樋田 京子; 大廣 洋一
頭頸部癌, May 2022, (一社)日本頭頸部癌学会, Japanese
May 2022 - May 2022

上下顎骨形成術を行った開咬患者における側貌軟組織の変化について
松下 和裕; 山本 隆昭; 佐藤 嘉晃; 高道 理; 武藤 麻未; 中西 康; 宮上 雄希; 義達 理恵子; 町田 友梨; 足利 雄一; 道念 正樹; 小堀 善則; 大井 一浩; 原田 沙織; Nguyen Thi Trang; 格口 渉; 坂田 健一郎; 山口 博雄; 大廣 洋一
日本顎変形症学会雑誌, May 2022, (NPO)日本顎変形症学会, Japanese
May 2022 - May 2022

II級およびIII級の骨格不正咬合に対する顎形成術後の関節窩および下顎頭のリモデリングの定量(Glenoid fossa and condyle remodeling following orthognathic surgery on class II and class III malocclusions)
Trang Nguyen; 足利 唯一; 松下 和裕; 大廣 洋一
日本顎変形症学会雑誌, May 2022, (NPO)日本顎変形症学会, English
May 2022 - May 2022

エナメル上皮腫に対する反復処置法の応用につ いて.
大廣 洋一; 関口(山田)珠希; 格口 渉
第40回日本口腔腫瘍学会総会・学術大会, 14 Feb. 2022, Japanese, Nominated symposium
14 Feb. 2022 - 13 Mar. 2022

先天性多数歯欠損に対してインプラント治療を行った1例
長 太一; 齋藤 紘子; 格口 渉; 松沢 祐介; 石橋 知代子; 小川 優; 和田 義行; 大廣 洋一
日本口腔インプラント学会誌, Dec. 2021, (公社)日本口腔インプラント学会, Japanese
Dec. 2021 - Dec. 2021

Application of “Dredging method”, an Alternative Conservative Treatment for Ameloblastoma in the Jaw
Ohiro Y
11th International Conference on Dental Science and Education- Hanoi Medical University School of Dentistry, 25 Nov. 2021, English, Keynote oral presentation
24 Nov. 2021 - 26 Nov. 2021, [Invited]

口腔扁平上皮癌における高内皮細静脈と臨床的因子との関連
新山 宗; 間石 奈湖; 松田 彩; 鄭 漢忠; 大廣 洋一; 上田 倫弘; 樋田 京子
日本口腔科学会雑誌, Jul. 2021, (NPO)日本口腔科学会, Japanese
Jul. 2021 - Jul. 2021

下顎埋伏智歯抜歯術におけるセフカペンピボキシルとアモキシシリンの手術部位感染予防効果の比較
山神 彰; 小林 正紀; 山田 武宏; 北川 善政; 大廣 洋一; 佐藤 淳; 石黒 信久; 今井 俊吾; 武隈 洋; 菅原 満; 井関 健
日本薬学会年会要旨集, Mar. 2020, (公社)日本薬学会, Japanese
Mar. 2020 - Mar. 2020

"Dredging Method" - An Alternative Conservative Approach for Treatment of Odontogenic Keratocyst –.
Ohiro Y; Yamada T; Kakuguchi W; Tei K
13rd Asian congress on Oral & Maxillofacial Surgery., 11 Nov. 2018, English, Oral presentation

Application of Dredging Method for Ameloblastoma and Odontogenic Keratocyst
OHIRO Yoichi
The 63rd Congress of the Japanese Society of Oral and Maxillofacial Surgeions, 03 Nov. 2018, Japanese, Nominated symposium
[Invited], [Domestic Conference]

"Dredging Method" - An Alternative Conservative Approach for Treatment of Odontogenic Keratocyst -.
Ohiro Y; Yamada T; Kakuguchi W; Tei K
5th National & 2nd International Bangladesh Conference on Oral & Maxillofacial Surgery., 20 Jan. 2018, English, Nominated symposium
[Invited], [International presentation]

反復処置法によるエナメル上皮腫の治療-再発腫瘍への対応-.
大廣 洋一
第６２回日本口腔外科学会総会・学術大会．, 21 Oct. 2017, Japanese, Public discourse
[Domestic Conference]

当院救急科に搬送され医科と連携して対応した広範囲顔面多発骨骨折の治療経験
松田光平; 松沢祐介; 山田珠希; 格口渉; 栗林和代; 大廣洋一; 鄭漢忠
口腔顎顔面外傷, 15 Oct. 2017, 日本口腔顎顔面外傷学会, Japanese
15 Oct. 2017 - 15 Oct. 2017

当科における過去17年間の腺様嚢胞癌症例の臨床的検討
山田珠希; 足利雄一; 小野貢伸; 栗林和代; 大廣洋一; 鄭漢忠
Japanese Journal of Head ＆Neck Surgery, 10 May 2017, 日本頭頸部癌学会, Japanese
10 May 2017 - 10 May 2017

当科における舌扁平上皮癌Stage I,II症例の腫瘍の深度と治療成績についての検討
栗林和代; 山田珠希; 足利雄一; 大廣洋一; 北村哲也; 鄭漢忠
Japanese Journal of Head ＆Neck Surgery, 10 May 2017, 日本頭頸部癌学会, Japanese
10 May 2017 - 10 May 2017

反復処置法によるエナメル上皮腫の治療.
大廣 洋一
第６１回日本口腔外科学会総会・学術大会．, 25 Nov. 2016, Japanese, Public discourse
[Domestic Conference]

T1-2N0M0舌扁平上皮癌の検討
大鶴 光信; 太田 嘉英; 柳本 惣市; 大倉 正也; 梅田 正博; 桐田 忠明; 栗田 浩; 上田 倫弘; 長谷川 巧実; 柴原 孝彦; 野口 忠秀; 野口 一馬; 山下 善弘; 大廣 洋一; 内藤 博之
日本癌治療学会学術集会抄録集, Oct. 2016, (一社)日本癌治療学会, Japanese
Oct. 2016 - Oct. 2016

T1-2N0M0舌癌に予防郭清を行うことの是非に関する多施設共同研究(JOOG RA1403)
大鶴 光信; 太田 嘉英; 梅田 正博; 柳本 惣市; 栗田 浩; 鎌田 孝広; 桐田 忠昭; 山川 延宏; 上田 倫弘; 山下 徹郎; 大倉 正也; 相川 友直; 大廣 洋一; 栗林 和代; 山下 善弘; 長井 健太郎; 野口 一馬; 岸本 裕充; 長谷川 巧実; 古森 孝英; 傳田 祐也; 内藤 博之; 柴原 孝彦; 野口 忠秀; 唐木田 一成
頭頸部癌, May 2016, (一社)日本頭頸部癌学会, Japanese
May 2016 - May 2016

Dredging Method－A Conservative Approach for the Treatment of Keratocystic Odontogenic Tumor.
Ohiro Y; Kakuguchi W; Yamada T; Tei K
The 57th Congress of the Korean Association of Oral and Maxillofacial Surgeons, 23 Apr. 2016, English, Oral presentation

角化嚢胞性歯原性腫瘍における歯牙の温存について．
大廣洋一; 格口渉; 鄭 漢忠; 角化嚢胞性歯原性腫瘍における歯牙の温存について
第34回日本口腔腫瘍学会総会・学術大会, 21 Jan. 2016, Japanese, Poster presentation

反復処置法による角化嚢胞性歯原性腫瘍の治療.
大廣 洋一
第６０回日本口腔外科学会総会・学術大会．, 16 Oct. 2015, Japanese, Public discourse
[Domestic Conference]

角化嚢胞性歯原性腫瘍における歯牙の温存について
格口渉; 大廣洋一; 山田珠希; 鄭漢忠
日本口腔科学会雑誌, 10 Jul. 2015, (NPO)日本口腔科学会, Japanese
10 Jul. 2015 - 10 Jul. 2015

エナメル上皮腫に対する反復処置法について
大廣 洋一
第69回日本口腔科学会学術集会, 13 May 2015, Japanese, Nominated symposium
[Domestic Conference]

Locoregional control in advanced resectable oral squamous cell carcinoma by concurrent preoperative chemoradiotherapy with Docetaxel and Cisplatin．
OHIRO Yoichi
Commemoration Ceremony of Sapporo Dental College & Hospital Scientific Seminar, 31 Oct. 2014, English, Invited oral presentation
[Invited], [International presentation]

反復処置法による角化嚢胞性歯原性腫瘍の治療
大廣 洋一
第59回日本口腔外科学会総会, 17 Oct. 2014, Japanese, Public discourse
[Domestic Conference]

Locoregional control in advanced resectable oral squamous cell carcinoma by concurrent preoperative chemoradiotherapy with Docetaxel and Cisplatin.
Ohiro Y; Kuribayashi K; Ashikaga Y; Ono M; Totsuka Y; Tei K
22nd European Association for Cranio-Maxillo Facial Surgery, Sep. 2014, English, Poster presentation

口腔扁平上皮癌における新規予後因子としてのVasohibin‐1
鳥居ちさほ; 鳥居ちさほ; 大賀則孝; 大賀則孝; 秋山廣輔; 間石奈湖; 北條敬之; 大廣洋一; 小野貢伸; 戸塚靖則; 北川善正; 鄭漢忠; 樋田泰浩; 進藤正信; 松野吉宏; 佐藤靖史; 樋田京子
日本病理学会会誌, 26 Mar. 2014, Japanese
26 Mar. 2014 - 26 Mar. 2014

Dredging Method－A Conservative Approach for the Treatment of Keratocystic Odontogenic Tumor.
Ohiro Y; Totsuka Y; Tei K
2014 Annual congress of ROC Association of Oral and Maxillofacial Surgeons, 08 Mar. 2014, English, Poster presentation

局所進行口腔癌における術前DOC・CDDP併用放射線療法の有用性.
大廣洋一; 栗林和代; 足利雄一; 小野貢伸; 進藤正信; 鄭 漢忠
第32回日本口腔腫瘍学会総会・学術大会, 23 Jan. 2014, Japanese, Oral presentation

口腔扁平上皮癌における新規予後因子Vasohibin-1の発現解析(Vasohibin-1 as a novel prognostic factor in oral squamous cell carcinoma)
鳥居 ちさほ; 大賀 則孝; 秋山 廣輔; 間石 奈湖; 北條 敬之; 大廣 洋一; 小野 貢伸; 戸塚 靖則; 鄭 漢忠; 樋田 泰浩; 進藤 正信; 佐藤 靖史; 樋田 京子
日本癌学会総会記事, Oct. 2013, 日本癌学会, English
Oct. 2013 - Oct. 2013

当科における口腔扁平上皮癌stage III,IVAの治療成績について
足利雄一; 栗林和代; 大廣洋一; 小野貢伸; 鄭漢忠
頭頸部癌, 2013, Japanese
2013 - 2013

Histopathological response of concurrent preoperative chemoradiotherapy with Docetaxel and Cisplatin for Oral Squamous Cell Carcinoma.
Ohiro Y; Kuribayashi K; Ashikaga Y; Ono M; Totsuka Y; Tei K
21st European Association for Cranio-Maxillo-Facial Surgery, Sep. 2012, English, Poster presentation

The effect of concurrent chemoradiotherapy of the metastatic lymph node in advanced lower gingival carcinoma.
Ohiro Y; Kuribayashi K; Ashikaga Y; Ono M; Tei K; Totsuka Y
2012 Annual congress of ROC Association of Oral and Maxillofacial Surgeons, Mar. 2012, English, Poster presentation

Dredging Method - A Conservative approach for the keratocystic odontogenic tumor.
OHIRO Yoichi
4th General Assembly of Guangxi Stomatological Association (GSA) & the 14th Annual Academic Meeting, 14 Dec. 2011, English, Invited oral presentation
[Invited], [International presentation]

Dredging Method - A Conservative approach for the keratocystic odontogenic tumor.
OHIRO Yoichi
Egyptian Dental Association The 15th International Dental Congress, 28 Oct. 2011, English, Invited oral presentation
[Invited], [International presentation]

当施設におけるびまん性硬化性下顎骨骨髄炎の臨床的検討 臨床病態について
小野寺 麻記子; 山崎 裕; 秦 浩信; 足利 雄一; 大廣 洋一; 松沢 祐介; 小野 貢伸; 戸塚 靖則; 箕輪 和行; 滝波 修一; 進藤 正信; 野谷 健一; 北川 善政
日本口腔外科学会雑誌, Sep. 2011, (公社)日本口腔外科学会, Japanese
Sep. 2011 - Sep. 2011

当施設におけるびまん性硬化性下顎骨骨髄炎の臨床的検討 治療効果について
足利 雄一; 山崎 裕; 秦 浩信; 小野寺 麻記子; 野谷 健一; 北川 善政; 松沢 祐介; 大廣 洋一; 小野 貢伸; 箕輪 和行; 滝波 修一; 進藤 正信; 戸塚 靖則
日本口腔外科学会雑誌, Sep. 2011, (公社)日本口腔外科学会, Japanese
Sep. 2011 - Sep. 2011

角化嚢胞性歯原性腫瘍に対する反復処置法の応用と要点．
大廣 洋一
第29回日本口腔腫瘍学会総会, 27 Jan. 2011, Japanese, Nominated symposium
[Domestic Conference]

Treatment of Oral Cancer.
OHIRO Yoichi
2nd Scientific Seminar, Sapporo Dental College Alumni Association, 22 Nov. 2010, English, Invited oral presentation
[Invited], [International presentation]

The pattern of residual tumors after concurrent chemoradiotherapy in advanced lower gingival carcinoma.
Ohiro Y; Kaneko M; Tei K; Totsuka Y
9th the Asian Congress on Oral and Maxillofacial Surgery, Nov. 2010, English, Poster presentation

下顎骨放射線性骨髄炎に対し下顎骨区域切除を行い自家腸骨移植により下顎骨再建を行った2例
足利 雄一; 萬 顕; 佐藤 和代; 大廣 洋一; 小野 貢伸; 鄭 漢忠; 戸塚 靖則
日本口腔科学会雑誌, Sep. 2009, (NPO)日本口腔科学会, Japanese
Sep. 2009 - Sep. 2009

緑茶ポリフェノールEGCGは腫瘍血管内皮に対する抑制効果を有する(Inhibitory Effects of Epigallocatechin-3 Gallate, a Polyphenol in Green Tea, on Tumor-Associated Endothelial Cells)
大賀 則孝; 樋田 泰浩; 土屋 邦彦; 村木 力; 秋山 広輔; 近藤 美弥子; 間石 奈湖; 黒須 拓郎; 大廣 洋一; 戸塚 靖則; 進藤 正信; 樋田 京子
日本癌学会総会記事, Aug. 2009, 日本癌学会, English
Aug. 2009 - Aug. 2009

下顎歯肉扁平上皮癌手術症例の治療成績の検討
栗林和代; 小野貢伸; 足利雄一; 大廣洋一; 鄭漢忠; 佐藤明; 野谷健一; 北川善政; 戸塚靖則
Japanese Journal of Head ＆Neck Surgery, 20 May 2009, Japanese
20 May 2009 - 20 May 2009

緑茶カテキンEGCGは腫瘍血管内皮細胞とならびに血管内皮前駆細胞に直接的な抑制効果を有する
大賀則孝; 樋田京子; 樋田泰浩; 村木力; 土屋邦彦; 大廣洋一; 戸塚靖則; 進藤正信
日本病理学会会誌, 20 Mar. 2009, Japanese
20 Mar. 2009 - 20 Mar. 2009

初回治療後20年以上経過して再発した上顎癌の3例
足利雄一; 栗林和代; 大廣洋一; 小野貢伸; 鄭漢忠; 大森桂一; 中村太保; 進藤正信; 戸塚靖則
頭頸部癌, 2009, Japanese
2009 - 2009

Residual tumors after concurrent preoperative chemoradiotherapy with Docetaxel and Cisplatin in squamous cell carcinoma of the lower alveolus.
Ohiro Y; Ono M; Shindoh M; Tei K; Totsuka Y
8th Asian Congress on Oral and Maxillofacial Surgery, Nov. 2008, English, Oral presentation

下顎歯肉癌における術前化学療法併用放射線療法後の腫瘍残存様式
大廣洋一; 進藤正信; 小泉雄; 小野貢伸; 足利雄一; 鄭漢忠; 山崎裕; 佐藤明; 野谷健一; 北川善政; 戸塚靖則
日本口腔科学会雑誌, 10 Sep. 2008, Japanese
10 Sep. 2008 - 10 Sep. 2008

腫瘍血管内皮細胞ならびに血管内皮前駆細胞は正常血管内皮細胞に比べ、緑茶ポリフェノールに感受性を有する(Tumor endothelial cells and EPC are more sensitive to EGCG compared to normal endothelial cells)
大賀 則孝; 樋田 京子; 村木 力; 樋田 泰浩; 土屋 邦彦; 大廣 洋一; 戸塚 靖則; 進藤 正信
日本癌学会総会記事, Sep. 2008, 日本癌学会, English
Sep. 2008 - Sep. 2008

口底癌手術例の治療成績
小野貢伸; 佐藤明; 足利雄一; 大廣洋一; 鄭漢忠; 野谷健一; 北川善政; 戸塚靖則
Japanese Journal of Head ＆Neck Surgery, 15 May 2008, Japanese
15 May 2008 - 15 May 2008

口腔癌術後患者における不飽和脂肪酸の免疫能に与える影響
松沢正宏; 大廣洋一; 鄭漢忠; 戸塚靖則; 山崎裕; 野谷健一; 北川善政
日本口腔科学会雑誌, 10 Jan. 2008, Japanese
10 Jan. 2008 - 10 Jan. 2008

悪性腫瘍との鑑別に苦慮した下顎骨骨髄炎の一例
格口 渉; 馬渕 亜希子; 大廣 洋一; 箕輪 和行; 鄭 漢忠; 進藤 正信; 戸塚 靖則
日本口腔外科学会雑誌, Jan. 2008, (公社)日本口腔外科学会, Japanese
Jan. 2008 - Jan. 2008

緑茶ポリフェノールによる腫瘍血管内皮細胞と血管内皮前駆細胞への抑制効果
大賀則孝; 樋田京子; 樋田泰浩; 村木力; 土屋邦彦; 松田光平; 大廣洋一; 戸塚靖則; 進藤正信
生化学, 2008, Japanese
2008 - 2008

摂食・嚥下 口腔癌術後患者における不飽和脂肪酸の免疫能に与える影響
松沢 正宏; 大廣 洋一; 鄭 漢忠; 戸塚 靖則; 山崎 裕; 野谷 健一; 北川 善政
日本口腔科学会雑誌, Jan. 2008, (NPO)日本口腔科学会, Japanese
Jan. 2008 - Jan. 2008

Pamidronate in the treatment of diffuse sclerosing osteomyelitis of the mandible.
Ohiro Y; Mabuchi A; Takashi N; Tei K; Totsuka Y
89th AAOMS Annual Meeting, Scientific Sessions and Exhibition in conjunction with Japanese Society of Oral and Maxillofacial Surgeons and the Korean Association of Oral and Maxillofacial Surgeons, Oct. 2007, English, Oral presentation

舌・口底癌における術前化学療法併用放射線療法後の腫瘍残存様式
小野貢伸; 進藤正信; 大廣洋一; 足利雄一; 鄭漢忠; 山崎裕; 野谷健一; 北川善政; 戸塚靖則
Japanese Journal of Head ＆Neck Surgery, 15 May 2007, Japanese
15 May 2007 - 15 May 2007

口腔癌患者における血清マーカーとしてのVEGFファミリーの有用性
山崎裕; 佐藤明; 佐藤千晴; 野谷健一; 大廣洋一; 小野貢伸; 鄭漢忠; 戸塚靖則; 北川善政
日本口腔科学会雑誌, 10 Jan. 2007, Japanese
10 Jan. 2007 - 10 Jan. 2007

2005年WHO新分類に基づいた歯原性腫瘍の臨床的・病理学的検討
山田珠希; 笠原和恵; 大廣洋一; 野呂洋輔; 山本栄治; 小林一三; 戸塚靖則; 佐藤明; 北川善政; 飯塚正; 進藤正信
日本口腔科学会雑誌, 10 Jan. 2007, Japanese
10 Jan. 2007 - 10 Jan. 2007

骨性異形成症の臨床病理学的研究
笠原 和恵; 山田 珠希; 山本 栄治; 大廣 洋一; 戸塚 靖則; 北川 善政; 飯塚 正; 進藤 正信
日本口腔外科学会雑誌, Sep. 2006, (公社)日本口腔外科学会, Japanese
Sep. 2006 - Sep. 2006

術前MRI検査による下顎歯肉扁平上皮癌の腫瘍浸潤深度の評価
足利 雄一; 鄭 漢忠; 野呂 洋輔; 高野 昌士; 大廣 洋一; 小野 貢伸; 戸塚 靖則; 山崎 裕; 野谷 健一; 北川 善政; 箕輪 和行
日本口腔外科学会雑誌, Sep. 2006, (公社)日本口腔外科学会, Japanese
Sep. 2006 - Sep. 2006

Histopathological Response of concurrent pre-operative Chemoradiotherapy with Docetaxel and Cisplatin in Oral Squamous Cell Carcinoma
Ohiro Y; Totsuka Y
18th Congress of the European Association for the Cranio-Maxillofacial Surgery, Sep. 2006, English, Oral presentation

下顎歯肉癌における顎骨浸潤様式の検討
高野昌士; 小野貢伸; 足利雄一; 大廣洋一; 鄭漢忠; 山崎裕; 野谷健一; 北川善政; 戸塚靖則
Japanese Journal of Head ＆Neck Surgery, 15 May 2006, Japanese
15 May 2006 - 15 May 2006

Histopathological response of concurrent pre-operative chemoradiotherapy with Docetaxel and Cisplatin in oral squamous cell carcinoma
Ohiro Y; Totsuka Y
12nd International Congress Egyptian Dental Association, 01 Dec. 2005, English, Invited oral presentation
[Invited]

Evaluation of concurrent preoperative chemoradiotherapy with Docetaxel and Cisplatin for oral cancer
KOBORI YOSHINORI; OHIRO YOICHI; TEI KANCHU; ONO MITSUNOBU; TOTSUKA YASUNORI; YAMAZAKI YUTAKA; NOTANI KEN'ICHI; KITAGAWA YOSHIMASA; SHINDO MASANOBU; KOGO TAKAO
日本口腔腫瘍学会誌, 15 Sep. 2005, Japanese
15 Sep. 2005 - 15 Sep. 2005

PETの解析 1 FDG‐PETによる頭頚部へん平上皮癌頚部リンパ節転移の診断に関する研究―リンパ節個々の病理組織学的所見との比較―
斉藤正晃; 山崎裕; 佐藤千晴; 佐藤明; 野谷健一; 北川善政; 大廣洋一; 鄭漢忠; 戸塚靖則
日本口腔科学会雑誌, 10 Sep. 2005, Japanese
10 Sep. 2005 - 10 Sep. 2005

頭頸部領域のFDG-PET診断 扁平上皮癌以外の症例について
阿部 貴洋; 山崎 裕; 齊藤 正晃; 佐藤 千晴; 野谷 健一; 大廣 洋一; 鄭 漢忠; 戸塚 靖則; 北川 善政
日本口腔外科学会雑誌, Sep. 2005, (公社)日本口腔外科学会, Japanese
Sep. 2005 - Sep. 2005

頭頸部悪性腫瘍患者の術後の顔貌の変形と心理状態に関する検討
村木 力; 鄭 漢忠; 小野 貢伸; 大廣 洋一; 足利 雄一; 高野 昌士; 戸塚 靖則; 山崎 裕; 北川 善政
日本口腔外科学会雑誌, Sep. 2005, (公社)日本口腔外科学会, Japanese
Sep. 2005 - Sep. 2005

FDG-PETによる頭頸部扁平上皮癌頸部リンパ節転移の診断に関する研究 リンパ節個々の病理組織学的所見との比較
齊藤 正晃; 山崎 裕; 佐藤 千晴; 佐藤 明; 野谷 健一; 北川 善政; 大廣 洋一; 鄭 漢忠; 戸塚 靖則
日本口腔科学会雑誌, Sep. 2005, (NPO)日本口腔科学会, Japanese
Sep. 2005 - Sep. 2005

口腔癌に対する術前Docetaxel・CDDP同時併用放射線療法の有用性の検討
大廣洋一; 小堀善則; 小野貢伸; 鄭漢忠; 山崎裕; 野谷健一; 北川善政; 進藤正信; 向後隆男
Japanese Journal of Head ＆Neck Surgery, 15 May 2005, Japanese
15 May 2005 - 15 May 2005

Stage III,IV舌癌手術例の検討
佐藤明; 野谷健一; 北川善政; 足利雄一; 小野貢伸; 大大廣洋一; 高野昌士; 小堀善則; 鄭漢忠
Japanese Journal of Head ＆Neck Surgery, 15 May 2005, Japanese
15 May 2005 - 15 May 2005

Clinico-pathological analysis of recurrent ameloblastoma treated by the “dredging method”.
Kobayashi I; Kasahara K; Ohiro Y; Henmi H; Yamamoto E; Inoue N; Totsuka Y; Iizuka T; Shindoh M; Kohgo T
Int J Oral Maxillofac Surg, 2005
2005 - 2005

口腔癌における腫瘍マーカーとしての血清p53抗体測定の意義
山崎 裕; 千葉 逸朗; 榊原 典幸; 佐藤 千晴; 野谷 健一; 大廣 洋一; 小野 貢伸; 鄭 漢忠; 戸塚 靖則; 水野 重孝
頭頸部腫瘍, May 2004, 日本頭頸部癌学会, Japanese
May 2004 - May 2004

口腔扁平上皮がんの術前治療への感受性の検討
浅香 雄一郎; 小堀 善則; 泉山 ゆり; 秦 浩信; 東野 史裕; 大廣 洋一; 山下 徹郎; 向後 隆男; 戸塚 靖則; 進藤 正信
日本癌学会総会記事, Aug. 2003, 日本癌学会, Japanese
Aug. 2003 - Aug. 2003

口腔扁平上皮がんにおけるTIMP-2発現の意義
小堀 善則; 泉山 ゆり; 大廣 洋一; 秦 浩信; 東野 史裕; 向後 隆男; 戸塚 靖則; 進藤 正信
日本病理学会会誌, Apr. 2003, (一社)日本病理学会, Japanese
Apr. 2003 - Apr. 2003

悪性黒色腫におけるetsがん遺伝群転写因子E1AF及びMT1-MMPの発現
秦 浩信; 大廣 洋一; 東野 史裕; 山下 利春; 吉田 幸一; 田口 和典; 高田 尚幸; 藤堂 省; 向後 隆男; 戸塚 靖則; 進藤 正信
日本癌学会総会記事, Oct. 2002, 日本癌学会, Japanese
Oct. 2002 - Oct. 2002

E1AF,MT1-MMP,TIMP-2の発現と舌扁平上皮がんの悪性形質との関連
泉山 ゆり; 大廣 洋一; 秦 浩信; 東野 史裕; 田口 和典; 高田 尚幸; 藤堂 省; 向後 隆男; 戸塚 靖則; 進藤 正信
日本癌学会総会記事, Oct. 2002, 日本癌学会, Japanese
Oct. 2002 - Oct. 2002

Mutant p53 alters the localization of Daxx in the cells.
Ohiro Y; Kitamura T; Hata H; Kobori Y; Izumiyama Y; Totsuka Y; Shindoh M
93rd Annual Meeting of American Association for Cancer Research, 06 Apr. 2002, English, Poster presentation

E1AF,MT1-MMPの発現と舌扁平上皮がんの悪性形質の関連
泉山 ゆり; 大廣 洋一; 秦 浩信; 東野 史裕; 田口 和典; 高田 尚幸; 藤堂 省; 向後 隆男; 戸塚 靖則; 進藤 正信
日本病理学会会誌, Mar. 2002, (一社)日本病理学会, Japanese
Mar. 2002 - Mar. 2002

悪性黒色腫におけるetsがん遺伝群転写因子E1AFの発現及び浸潤能への関与
秦 浩信; 大廣 洋一; 東野 史裕; 山下 利春; 西川 鑑; 吉田 幸一; 田口 和典; 高田 尚幸; 藤堂 省; 戸塚 靖則
日本病理学会会誌, Mar. 2002, (一社)日本病理学会, Japanese
Mar. 2002 - Mar. 2002

非復位性関節円板前方転位症例の開口量ならびにMR像に関する年齢群別検討
馬渕 亜希子; 由良 晋也; 出山 文子; 由川 哲也; 大廣 洋一; 高師 則行; 佐藤 千晴; 井上 農夫男; 戸塚 靖則
日本口腔外科学会雑誌, Dec. 2001, (公社)日本口腔外科学会, Japanese
Dec. 2001 - Dec. 2001

加圧関節洗浄療法における関節内圧の測定及び関節腔拡張効果に関する検討
由良 晋也; 大廣 洋一; 馬渕 亜希子; 由川 哲也; 出山 文子; 高師 則行; 戸塚 靖則; 佐藤 千晴; 井上 農夫男
日本口腔外科学会雑誌, Dec. 2001, (公社)日本口腔外科学会, Japanese
Dec. 2001 - Dec. 2001

悪性黒色腫におけるetsがん遺伝子群転写因子E1AFの発現
秦 浩信; 大廣 洋一; 東野 史裕; 安田 元昭; 戸塚 靖則; 山下 利春; 吉田 幸一; 田口 和典; 高田 尚幸; 藤堂 省
日本癌学会総会記事, Sep. 2001, 日本癌学会, Japanese
Sep. 2001 - Sep. 2001

Augmentation of vaccine effects of PGE2-producing tumor cells by transfection with cytokine genes.
Ohiro Y; Kuramitsu Y; Kobayashi M; Hosokawa M; Totsuka Y
13rd International Conference on Oral and Maxillofacial Surgery, 26 Sep. 1997, English, Oral presentation

大学院共通授業科目（教育プログラム）：外科系臨床医学研究の新展開 臨床解剖概論, 2024年, 修士課程, 大学院共通科目

発表・論文執筆法演習Ⅰ, 2024年, 博士後期課程, 歯学院

発表・論文執筆法演習Ⅱ, 2024年, 博士後期課程, 歯学院

発表・論文執筆法演習Ⅲ, 2024年, 博士後期課程, 歯学院

口腔顎顔面外科学, 2024年, 博士後期課程, 歯学院

口腔病態学実習Ⅴ, 2024年, 博士後期課程, 歯学院

口腔病態学実習Ⅰ, 2024年, 博士後期課程, 歯学院

口腔顎顔面外科学研究Ⅱ, 2024年, 博士後期課程, 歯学院

口腔病態学実習Ⅱ, 2024年, 博士後期課程, 歯学院

口腔再建外科学, 2024年, 博士後期課程, 歯学院

口腔再建外科学研究Ⅱ, 2024年, 博士後期課程, 歯学院

口腔再建外科学研究Ⅰ, 2024年, 博士後期課程, 歯学院

口腔病態学実習Ⅲ, 2024年, 博士後期課程, 歯学院

口腔病態学実習Ⅳ, 2024年, 博士後期課程, 歯学院

口腔顎顔面外科学研究Ⅰ, 2024年, 博士後期課程, 歯学院

歯科学概論Ⅱ, 2024年, 学士課程, 歯学部

外科学, 2024年, 学士課程, 歯学部

口腔顎顔面外科学臨床実習Ⅱ, 2024年, 学士課程, 歯学部

口腔顎顔面外科学臨床実習Ⅰ, 2024年, 学士課程, 歯学部

口腔顎顔面外科学, 2024年, 学士課程, 歯学部

フロンティア発展科目, 2024年, 学士課程, 歯学部

Apr. 2022 - Present
Japanese Society for Jaw Deformities

Dec. 2018 - Present
日本口腔インプラント学会

May 2012 - Present
Japanese Society of Oral Oncology

May 2005 - Present
JAPAN SOCIETY OF CLINICAL ONCOLOGY

Apr. 2003 - Present
JAPAN SOCIETY FOR HEAD AND NECK CANCER

1997 - Present
Asian Association of Oral and Maxillofacial Surgeons

Sep. 1992 - Present
JAPANESE SOCIETY OF ORAL AND MAXILLOFACIAL SURGEONS

Sep. 1992 - Present
JAPANESE STOMATOLOGICAL SOCIETY

転移におけるがん－腫瘍血管cluster形成機序解明と新規診断・治療法の開発
科学研究費助成事業
01 Apr. 2024 - 31 Mar. 2027
菊地 奈湖; 樋田 京子; 菊地 央; 樋田 泰浩; 大廣 洋一
日本学術振興会, 基盤研究(B), 北海道大学, 24K02637

ベイズモデリングによるデータ同化と位相的データ解析を用いた顎骨切削手術技能評価
科学研究費助成事業
01 Apr. 2024 - 31 Mar. 2027
中野 寛; 大井 一浩; 大廣 洋一; 格口 渉
日本学術振興会, 基盤研究(B), 東京工業大学, 24K00832

高内皮細静脈の多様性の解明による免疫チェックポイント阻害剤耐性の克服
科学研究費助成事業
Apr. 2024 - Mar. 2027
松田 彩; 菊地 奈湖; 大廣 洋一; 樋田 京子; 新山 宗
日本学術振興会, 基盤研究(C), 北海道大学, 24K13061

口腔がんの悪性形質獲得に関わる口腔常在菌の解析
日本学術振興会 科学研究費助成事業
Apr. 2023 - Mar. 2026
大廣 洋一、長谷部 晃、樋田 京子
基盤研究(C), 北海道大学大学院歯学研究院, Principal investigator, 23K09367

がんと腫瘍血管の相互作用による新たな転移促進機構の解明とその制御
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Apr. 2021 - Mar. 2024
菊地 奈湖; 樋田 京子; 樋田 泰浩; 篠原 信雄; 大廣 洋一; 松田 彩
転移は予後を左右する重要な因子であり，がん治療において転移の予測やその制御は重要である．申請者らはこれまで腫瘍血管を裏打ちする腫瘍血管内皮細胞の異常性について検討し，腫瘍血管内皮細胞由来液性因子によりがんの転移が促進することを報告した．したがって，腫瘍血管内皮細胞は単なる血行性転移の経路の入り口となるだけではなく，積極的にがんの悪性化にも影響を与えうることが示唆された．がんの転移は，原発巣での浸潤ならびに血管内侵入，血管内の移動，転移先臓器への漂着，転移先臓器での増殖・転移巣形成という複雑なカスケードを経て成立する．異常性を示す腫瘍血管内皮細胞は，転移の初期段階だけではなく，さまざまな過程において関与する可能性があるのではないかと考えた．最近，がん組織内で腫瘍血管内皮細胞ががん細胞と細胞塊を形成することが示唆されている．実際，手術摘出がん組織標本において，血管腔内に血管内皮細胞で囲まれる細胞塊が観察された．そこで本研究では，血液中で腫瘍血管内皮細胞ががん細胞と細胞塊を形成し，転移促進などがんの悪性化に関与すると仮説を立て，腫瘍血管内皮による新たながん悪性化促進機構を明らかにすることを目的とした．手術摘出組織標本を用いて，血管腔内における細胞塊をH-E染色ならびに血管内皮マーカーCD31の組織免疫染色で可視化し，評価した．腫瘍組織の血管腔内に血管内皮細胞で構成される細胞塊が存在することが示唆された．がん患者血液中に細胞塊が存在するかどうか，ショ糖密度勾配遠心法で単核球分画を濃縮し，赤血球を除いて検討したところ，UEA-1レクチンで染色される血管内皮細胞を含む細胞塊が検出された．さらに，Poly-HEMA coatingした非接着カルチャープレート上でがん細胞と血管内皮細胞を共培養して細胞塊を形成後，そのphenotypeについて検討した．
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Coinvestigator, 21K10107

Development of new anti-cancer strategy via activation of immunity by targeting tumor endothelial factors
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
Apr. 2021 - Mar. 2024
樋田 京子; 菊地 奈湖; 樋田 泰浩; 大廣 洋一; 松田 彩; 上田 倫弘
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, Coinvestigator, 21H04840

エナメル上皮腫の浸潤機構解明による新規治療法の開発
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Apr. 2019 - Mar. 2022
北村 哲也; 菊地 奈湖; 大廣 洋一; 樋田 京子; 東野 史裕; 松田 彩
本研究ではエナメル上皮腫の浸潤性増殖の解明を目的とし、主にbudding領域について詳細な検討を行ってきた。budding領域は、エナメル上皮腫の組織学的特徴の一つで、腫瘍から間質への出芽様構造のことであり、これが浸潤性増殖の原因と考えられている。これまで我々は、budding領域にHuRタンパク質と⊿Np63タンパク質が高発現していることを免疫組織学的に明らかにしてきた。そこで、HuRと⊿Np63との分子生物学的関連について着目した。HuRはmRNA結合タンパクであることから、HuRタンパクと⊿Np63 mRNAとの結合をRIP assay法によって検討した。細胞はエナメル上皮腫の培養細胞株であるAM-1細胞を用いた。その結果、HuRタンパクは⊿Np63 mRNAに結合することが明らかとなった。また、HuRタンパクとmRNAの結合を特異的に阻害するCMLD2を用いたところ、HuRタンパクと⊿Np63 mRNAとの結合は阻害された。
次に、HuRタンパクと⊿Np63 mRNAの結合の意義について検討した。AM-1細胞にCMLD-2を用いて、⊿Np63 mRNAの発現をreal time PCR法を用いて、⊿N63タンパク質の発現についてWestern blotting法を用いて検討した。⊿Np63 mRNAの半減期はCMLDを作用させると短くなり、⊿N63タンパク質は経時的に発現が減少した。このことから、HuRタンパクは⊿Np63 mRNAに結合して、mRNAを安定化させ、その結果タンパク質の発現を上昇させていることが明らかとなった。
これらの結果から、budding領域での生物学的機序が明らかとなった。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Coinvestigator, 19K10326

Association between oral bacteria and oral cancer metastasis
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Apr. 2019 - Mar. 2022
大廣 洋一; 北村 哲也; 樋田 京子; 長谷部 晃
細菌特異的な16s rDNAの発現をPCRで確認する際，バックグラウンドの低下と，精度を向上させるために下記を行った．
1) 腫瘍組織選択的なDNA 抽出条件の検討：手術標本の残余組織を用いて，①未染のパラフィン固定された組織，②ヘマトキシリン・エオジン（HE）染色された切片よりNucleoSpin DNA FFPE XSにてDNAを抽出した．HE染色により，腫瘍組織より選択的にDNAを回収できることを想定したが，HE染色によりDNA収量が30％程度以下になることを確認した．HEで染色では腫瘍部・非腫瘍部を判別するには簡便だが，DNAの抽出には不利であることがわかった．
2）ポジティブコントロールの調整：手術残余組織と細菌学教室より供与いただいたストレプトコッカス・ミュータンス（S. mutans）とを混合し，DNA抽出，PCRを行った．また，同様に大腸菌（E. Coli）を材料として上記手順を行ったところ組織とS. mutansの混合物ならびにE. Coliから回収したサンプルでは16sｒDNAの発現が確認された．
3）転移リンパ節標本からのDNA抽出条件の検討：リンパ節標本（15ｘ15mm大）ならびに原発腫瘍の深部（細菌に汚染されていない部分）のみからなる薄切（4.25 μm）切片10枚よりDNAを抽出し，さらにポジティブコントロールとして大腸菌（E.Coli）由来のDNAを用いて，PCRを行ったところ30サイクルではポジティブコントロールのみで発現したが，実験群では発現は確認できなかった．PCRの条件に問題はないが，標的臓器で確認するためには，キットの選定，プライマーの設定，サイクル数などの検討が必要と考えられた．
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, 19K10350

Elucidation of the mechanism for cancer metastasis induced by oral cancer exosome and development of novel therapy for metastatic cancer
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Apr. 2018 - Mar. 2021
Hida Kyoko
Cancer actively undergoes angiogenesis due to its progression and metastasis, and exosomes secreted by cancer cells are attracting attention because they change the traits of surrounding stromal cells. In this study, we will identify the exosome miRNA of cancer that causes phenotypic changes in the blood vessels of the primary lesion and distant organs and is involved in metastasis, clarify its molecular mechanism, and lead to the construction of a cancer metastasis inhibition strategy.
In an in vivo tumor model, we showed that cancer miRNA X is transported by exosomes and taken up by tumor vascular endothelial cells. We found that miRNA X attenuates the barrier function of the vascular endothelium and promotes metastasis, and clarified a new metastasis mechanism.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Coinvestigator, 18H02996

Development of new treatment strategy targeting for vascular niche of oral cancer stem cell
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Apr. 2013 - Mar. 2016
OHIRO Yoichi; AKIYAMA Kousuke; TEI Kanchu
Cancer stem cells (CSC) or matured cancer cells were fractionated from cancer cell lines. Tumor endothelial cells (TEC) were separated from transplanted tumors in vivo model. CSC were co-cultured with TEC or treated with TEC conditioned media (TEC-TM). These experiments revealed that activation of survival signal such as Akt or NF-kB, alteration of expression levels of CSC markers and inhibitory effect against apopotosis were induced in CSC. Furthermore, co-cultivation of CSC with TEC separated from highly metastatic tumor induce the formation of large sphenoid or inhibitory effect for anoikis by TEC.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, 25463106

Development of novel therapy targeting cancer stem cells by ROS regulation
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
Apr. 2012 - Mar. 2015
TOTSUKA yasunori; OHGA Noritaka; TEI Kanchu; OHIRO Yoichi
Reactive Oxygen Species (ROS) are known as the origin of oxidative stress. ROS are produced in response to hypoxia and nutrient deprivation. It is reported that tumor microenvironment is often exposed to hypoxic condition and nutrient deprivation because of the insufficient blood flow. ROS are accumulated in various cells in tumor microenvironment, and they promote cancer malignancy. In this study, we analyzed the effect on cancer stem cells and tumor blood endothelial cell that is reported to play a role as stem cell niche. ROS accumulation caused in alteration of gene expression profile both in cancer cells and tumor endothelial cells. One secreted protein from tumor endothelial cells was upregulated by ROS and attracted cancer cells. We analyzed the effect of ROS inhibition on cancer stem and tumor angiogenesis.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Coinvestigator, 24390448

Original approach to obtain intrinsic resistance genes to cisplatin
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2010 - 2012
OHIRO Yoichi; TOTSUKA Yasunori; KITAMURA Tetsuya; SHINDOH Masanobu
This study investigated the relationship between cisplatin resistance and osteopontin which is candidate gene responsible for drug resistance. Oral squamous cell carcinoma cells transfected with osteopontin were increased in resistance to cisplatin treatment and in activity of AKT. Knockdown of osteopontin chemosensitized cancer cells to cisplatin. The resistance mechanism of osteopontin was depend on AKT activation. These results suggest that osteopontin expression in oral cancer could be a useful predictable marker for the response to cisplatin.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, 22592237

Exploitation of gene-targeting therapy based on the cellular and biological features of oral-carcinoma stem cell and tumor microenvironment.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
2008 - 2011
TOTSUKA Yasunori; SHINDOH Masanobu; HIGASHINO Fumihiro; HIDA Kyoko; KITAMURA Tetsuya; OHBA Yusuke; MATSUMOTO Kenichi; OHIRO Yoichi
We have shown that the tumor endothelial cells which exist in cancer stroma have a different gene background from normal endothelial cells. It has been becoming clear that epithelial-mesenchymal transition (EMT) plays an important role in tumor invasion and metastasis. It is expected that the investigation on the interaction of the oral squamous cell carcinoma cell in epithelium nature and a mesenchymal cell will contribute to the establishment of effective therapeutic method because stromal cells have the ability to supply nutrition and oxygen to a tumor. HuR protein usually exists in the nucleus, and HuR is participating to stabilize AU-rich element (ARE) mRNA. We showed that ARE mRNA is stabilized through HuR by a viral carcinogenesis system that concerns cell transformation. Oral environment has a unique features including distinct organs such as salivary glands. We identified that RANKL, an osteoclast inducer, expression was higher in oral environment. Furthermore, when oral cancer cells were implanted in oral region of nude mice, cancer cells proliferated intentionally, and EMT was observed. Tumor microenvironment is deeply correlated with cancer cell proliferation and invasion/metastasis. We have isolated endothelial cells in tumor stroma, and investigated the biological feature of tumor endothelial cells. As a result, tumor angiogenesis was suppressed by inhibiting Cox-2 known also for the factor inducing inflammation, and the resistance for chemothrapy was acquired by MDR1 upregulatin caused by VEGF signaling
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (A), Hokkaido University, Coinvestigator, 20249079

Detection of cervical lymphnode micrometastasis in oral cancer
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2007 - 2009
ONO Mitsunobu; SHINDOH Masanobu; HIGASHINO Fumihiro; HIDA Kyoko; KITAMURA Tetsuya; OHIRO Yoichi; TOTSUKA Yasunori
腫瘍の転移は悪性腫瘍の治療においてその予後に影響する最も重要な因子であり、口腔悪性腫瘍の大部分を占める扁平上皮がんの治療にあたっても、転移の有無が予後と深く関わっている。口腔扁平上皮がんの転移の大部分は所属リンパ節である頸部リンパ節へのリンパ行性転移で、その治療にあたっては原発巣とともに転移したリンパ節の制御が必須であり、とくに現在画像診断的に検出が困難である径5mm以下の微小リンパ節転移の有無を術前に知ることが可能であればその意義は大きい。今回の検索は、口腔がんにおける転移形質に関与する遺伝子/遺伝子産物の同定を行うことを第一の目標としている。
ヒト口腔正常粘膜上皮、白板症、口腔がん組織より試料を採取し、直ちに液体窒素で凍結保存を行い、以後の実験に用いた。試料の一部よりRNAを抽出しDNAマイクロアレイにより網羅的解析を行ったところ、数十の発現亢進する遺伝子および発現が低下した遺伝子が認められた。
これらの中で口腔がんで発現が亢進しているPim-1に注目して検索を行った。口腔扁平上皮がん細胞株6種全てにPim-1のタンパク発現が認められた。北海道大学病院で口腔扁平上皮がんと診断された早期がん症例39例についてPim-1の発現を検索したところ17例(44%)にPim-1発現が認められた。Pim-1発現症例は有意に所属リンパ節転移、遠隔臓器転移が多く、Pim-1発現と転移の関連性が示唆された。転移形質とPim-1の関連を探るため、siRNAを用いて検討を行った。その結果、Pim-1に対するsiRNA導入細胞では細胞運動能の低下がみられ、この際にRac1の活性が低下することが明らかになった。
以上の結果は、Pim-1はRac1の活性化により口腔がん細胞の運動能を高め、転移形質に深く関与しており、Pim-1をターゲットにした画像診断の有用性を示唆するものだった。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Coinvestigator, 19592333

Roles of p53 family proteins on the risk-factor of recurrence in oral squamous cell carcinomas.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2007 - 2008
ISHIKAWA Makoto; SHINDOH Masanobu; KOBAYASHI Masanobu; HIGASHINO Fumihiro; OHIRO Yoichi
腫瘍の転移と再発は予後を左右する大きな要因であり、その防止対策が急務である。がん抑制遺伝子であるp53は多くの腫瘍でその変異がみられ、がん抑制遺伝子としての機能を喪失するだけでなく、より悪性度の高い腫瘍としての形質を獲得することが示され始めている。p53変異の導くリスクファクターとしての意義を明らかにし、腫瘍の再発の防止の一助とすることを目的に検索を行った。
11例の口腔扁平上皮がん患者について病理学的検索を行った。免疫染色でp53異常タンパクの蓄積が9例に認められ、変異型p53をゲノムにもつ可能性が示唆された。これらの症例からDNAおよびRNAを抽出し、遺伝子変異について検索したところ、全例でp53の変異が確認された。
抗がん剤は癌細胞にアポトーシスを引き起こし細胞死誘導を生じさせる。野生型p53はこの機構に重要な役割を演じているが、口腔がんの多くは変異型p53をゲノムにもち抗がん剤の効果を高める必要性がある。ゲノムに変異型p53をもち抗がん剤シスプラチンに抵抗性をもつ口腔がん細胞株HSC3を対象としてシスプラチンの細胞死誘導に及ぼすポリリン酸の影響について検索した。ポリリン酸は10数個から数百個の正リン酸が直鎖状に結合したポリマーで,ほとんど全ての生物に存在することが知られているが生物学的機能については不明な点が多い。その結果、ポリリン酸がシスプラチン処理により細胞に生じた細胞死誘導をさらに活性化し、低濃度のシスプラチンでも細胞死を誘導できることが明らかになり、この際にはp53被依存的にBaxの転写活性化にともなうCaspase9, PARPの活性化が生じていた。このような所見は、ポリリン酸がp53以外の転写因子の安定化にはたらきストレス経路によるアポトーシス誘導経路を刺激したものと思われた。
さらに患者血清中のp53タンパクの発現についてELISA法を用いて検討を行った。その結果、血清中にp53タンパクの発現がみられた症例では二次的なリンパ節転移の頻度が高く、予後との相関が得られた。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Coinvestigator, 19592279

顎骨骨折・顎骨欠損への再生医療の試み-ポリリン酸による顎骨誘導-
Grants-in-Aid for Scientific Research Grant-in-Aid for Exploratory Research
2006 - 2007
松沢 祐介; 進藤 正信; 小林 正伸; 東野 史裕; 北村 哲也; 大廣 洋一; 戸塚 靖則
再生医療は、各種の疾病により失われた臓器・組織・細胞を遺伝子工学・組織工学・細胞工学を利用して再生を図る治療で、高齢者の増加に伴う歯周組織の再生医療への要求はますます強まってくるものと考えられる。ポリリン酸は、原核生物ではエネルギー供与体、リン酸リザーバー、遺伝子発現制御因子、DNA導入時のチャンネルとして働く等の機能が明らかになっている。これに対して、真核細胞・生物では、細胞内や血漿中に存在し、神経細胞ではとくに長鎖のポリリン酸が存在することが明らかであるが、その生物学的機能は不明であった。
今回、ポリリン酸を培地に添加した際、ヒト歯肉線維芽細胞の増殖活性が亢進することを見いだした。線維芽細胞培養液中にポリリン酸を加えることでFGF-2半減期は著しく延長し、FGF-2が安定化することをWestern blottingで確認した。RI標識したポリリン酸はFGF-2に結合し、ポリリン酸と結合したFGF-2とFGFレセプターは強固に結合することをBiacoreを用いた実験で確認した。さらに、骨形成にはたらくTGF-βファミリー遺伝子産物の一つであるBMP-2の発現ベクターを導入した線維芽細胞においてBMP-2の発現がポリリン酸処理により亢進することを見出した。さらに、ポリリン酸処理により、骨芽細胞株MC3T3-E1細胞で骨形成タンパクであるOsteocalcin、Osteonectinが誘導されることを明らかにした。ヒト歯髄細胞(HDPC)を用いてポリリン酸の効果を検討した。歯髄細胞はFGFを分泌し、ポリリン酸添加によりHDPCの増殖は亢進し、細胞内でのMAPKカスケードであるERKのリン酸化が亢進し、HDPCの骨芽細胞への分化が誘導され、石灰化が認められた。このような所見はポリリン酸がFGFシグナル伝達経路を活性化し、stem cellの骨芽細胞への誘導・石灰化を促進することを示唆するものであった。
Japan Society for the Promotion of Science, Grant-in-Aid for Exploratory Research, Hokkaido University, Coinvestigator, 18659585

Development of gene delivery system using nanocoloid and its application for gene targeting therapy
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2006 - 2007
SHINDOH Masanobu; KOBAYASHI Masanobu; FUGETSU Bunshi; HIGASHINO Fumihiro; HIDA Kyoko; KITAMURA Tetsuya
Trials of gene therapies have been carried out for malignant tumors and congenital gene disorders,; however, there are problems such as the low efficiency and risk for applying human being, and ideal methods of gene therapy are not yet developed.. We designed nanocoloid that enclosed expression plasmid inside and, ligand peptide outside of small particle for development of a specific gene delivery system. When We searched expression of EGFR in oral squamous cell carcinoma cell lines (9.22, HSC2, HSC3, HSC4, Ca SAS) by Western blot, and all cell lines expressed EGFR We examined the binding affinity of EGFR and synthesized EGF peptide by BireCore X. As a result, it became clear that synthesized peptide bound to EGFR. Next, we examined the induction effect of nanocoloid to oral carcinoma cell lines. The efficiency of transfection was approximately 30%, and we aimed to improve the efficiency. We next examined the effects of adrenomedullin antagonist that has the ability to inhibit angiogenesis. The vector that has the sequence for inhibitory effects on aderenomedullin reduced the Growth of tumor xenografts in nude mice.
These results imply that specific gene delivery for tumor environment could be the therapeutic agents for solid cancers.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Coinvestigator, 18390531

Gene Targeting Therapy against tumor endothelial cells
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2006 - 2007
TOTSUKA Yasunori; SHINDOH Masanobu; HIDA Kyoko; HIGASHINO Fumihiro; KOBAYASHI Masanobu; OHIRO Yoichi
Tumor is a genetic disorder, and gene targeting therapy for cancer cells has been conducted. However, tumor gene abnormalities arre complicated, and it is quite difficult to improve efficiency of cancer treatment targeting single gene product.
On the other hand, since neovasculization in tumor stroma is essential for tumor survival and Growth, therapy for disturbing neovasculaizaion would be effective in cancer therapy.
It has been considered that the blood vessels in tumor stroma was composed of normal endothelial cells; however, Hida et al. have reported that tumor endothelial cells have genetically varied character compared to the normal endothelial cells by isolation of tumor endothelial cells from mouth xenograft models of human cancers.
We established human tumor endothelial cells by using magnetic beads method from the operation materials of oral carcinoma, renal carcinoma and lung carcinoma. These cells express CD34 and CD131, and confirmed as endothelial cells. RNA was extracted and DNA microarray has been carried out, and we have identified 70 genes that were upregulated in tumor endothelial cells. We confirmed the expression of these gene product by real-time RT-PCR, Western blotting and immunohistochemisty. Proliferation of tumor endothelial cells was decreased by introducing siRNA into the cells. In addition, we found that motility and proliferative activity of tumor endothelial cells were selectively decreased by Cox-2 inhibitor treatment.
These results imply the significance of targeting tumor endothelial cells for favorable cancer therapy.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Coinvestigator, 18390530

Evaluation of pre-operative Chemoradiotherapy in Oral Squamous Cell Carcinoma. -Integration of molecular biology and clinical state-
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2005 - 2006
OHIRO Yoichi; SHINDOH Masanobu; KOBAYASHI Masanobu
The predictive value of tumor suppressor protein of p53 and related genes for the effect of chemoradiation therapy on oral squamous cell carcinoma is still controversial. Recently, it is clear that tumor tissues are exposed to low-oxygen environmental (hypoxic state) so tumor cells alter their gene expression profile to survive in a severe condition. We estimate the proteins expression for p53 and p53R2 (p53-dependent kinase gene) in biopsy specimen to examine these proteins are valuable predictors for concurrent chemoradiotherapy. We also examined hypoxia-inducible factor (HIF) responsible proteins, vascular endothelial growth factor (VEGF) and Angiopoietin-like4 (ANGPTL4) in vitro to understand their relation under hypoxic state.
Thirty five cases were enrolled in this study. Fifteen patients were received radiation therapy only and 20 patients were given concurrent chemoradiotherapy before the operation. Biopsy specimens were examined by immunohistochemistry. The positive rate of p53 was 80% and p53R was 73.3 in all patients. Statistical anaylysis revealed that the combination with p53 positive/negative and p53R positive/negative couldn't predict the sensitivity to preoperative concurrent chemoradiotherapy.
In vitro study, VEGF and hypoxic condition stimulate the expression for ANGPTL4. Under hypoxic condition, over expression of ANGPTL4 down-regulates the expression of VEGF. These results suggest that under hypoxic condition, VEGF expression is negatively regulated by ANGPLT4.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, 17592062

Roles of Pim-1 oncogene in oral squamous cell carcinoma.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2005 - 2006
ISHIKAWA Makoto; SHINDOH Masanobu; KOBAYASHI Masanobu; HIGASHINO Fumihiro; OHIRO Yoichi
The cancer cell autonomy designates that it multiplies as one offeature, as for the result cancer organization is many a thing which has fallen to hypoxia state. Hypoxia Inducible Factor (HIF) was identified as the transcription factor which maintains the homeostasis of the cell in hypoxia state. There are reports that Pim-1 oncogene is closely associated with blood cell ondogenesis ; however, there is no report in the solid cancer. We identified Pim-1 oncogene in the downstream of HIF using DNA micro array. We examined roles of Pim-1 in oral squamous cell carcinogenesis.
Pim-1 was detected in all of the oral carcinoma cell lines ezamined by Western blot. Thirty-nine cases of T1 and T1 tongue squamous cell carcinoma who consulted the Hokkaido University Hospital were examined. Immunohistochemical detection of HIF-1 a, Pim-1 and MIB-1, a marker for proliferating cells was conducted. Pim-1 was detected in 17 of 39 cases. Pim-1 positive signals were seen in the nucleus of cancer cells, HIF-1α was positive in 12 of 39 cases and 9 of 12 cases were both Pim-1 and HIF-1 a positive. In contrast, Pim-1 was detected in 8 of 27 cases with HIF-1 a negative cases which had shown the significant correlation between Pim-1 and HIF-1 a expression..MIB-1, a proliferating cell marker was highly expressed in 14 of 39 cases. Concerning the Pim-1 revelation, MIB-1 was highly expressed in 10 of 17 Pim-1positivegroup, whereas only 4 cases were MIB-1 highly expressed among 22 cases of PIM-1 negative group..
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Coinvestigator, 17592059

An exploitation of gene targeting therapy against hypoxic condition of oral carcinoma.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2005 - 2006
ONO Mitsunobu; SHINDOH Masanobu; KOBAYASHI Masanobu; HIGASHINO Fumihiro; OHIRO Yoichi; TOTSUKA Yasunori
Cancer cells are exposed to hypoxic state because of their high proliferation rate: however, cancer cells are resistant to hypoxia-induced cell death. Hypoxia Inducible Factor (HIF) was identified as the transcription factor which maintains the homeostasis of the cell in hypoxic state. We examined the downstream genes of HIF by DNA micro array and we found that adenomemedullin, a blood vessel expansive peptide encoding gene product.
Twenty-two cases of tongue squamous cell carcinoma who consulted the Hokkaido University Hospital were examined by immunohistochmistry. Adrenomedullin was detected in 11 of 22 cases examined. They were investigated clinico-pathologically. mong the 12 cases of cervical lymph node metastasis cases, 8 cases were positive for aderenomedullin. In contrast, only 3 cases were positive for adrenomedullin in 10 cases without lymph node metastasis.
We reconstruct two mutant expression plasmids of adrenomedullin that are thought to function as antagonist, AMA214 is deletion and mutant plasmid with 27-115 amino acid deletion and 116 threonine into serine..AMA224 has deletion of 95-115 amino acid and the same mutation in 116 amino acid. AMA214 and AMA224 injection induced the regression of transplanted tumors in SCID mouse. CD31-positive tumor endothelial cells were disappeared in these animals.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Coinvestigator, 17592061

Vascular endothelial growth factor and its receptor to diagnose lymph node metastasis in patients with oral cancer
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2004 - 2005
YAMAZAKI Yutaka; OHIRO Youichi
Objective. To evaluate the clinical usefulness of vascular endothelial growth factor (VEGF) family in patients with oral squamous cell carcinoma (OSCC).
Methods. Preoperative serum values of VEGF family (VEGF-A,-C, and -D) and their receptor (sVEGF-R1,sVEGF-R2) were measured by enzyme-linked immunosorbent assay in 129 patients with fresh primary oral SCCs. The relationship among VEGF family, clinicopathological parameters, response to therapy and prognosis was investigated.
Results. Serum VEGF-A,-C, and -D levels were significantly higher in patients with OSCC than in the healthy control, but both sVEGF-R1 and sVFGF-R2 were not. On the basis of comparision to the 95% range of distribution of serum VEGF family titers in healthy control subjects, the positivity rates of VEGF-A,-C and -D were 41, 31, and 57%, respectively. The serum level of VEGF-A correlated significantly with sex, tumor size and Stage. VEGF-C concentration correlated significantly with distant metastasis, but not with lymph node metastasis. The VEGF-C positive group showed a significantly lower 5-year survival rate than the VEGF-C negative group (63.2% vs. 83.5%, p<0.05). The level of VEGF-D negative correlated with lymph node metastasis and mode of invasion. Moreover, we examined expression of VEGF-C,Flt-4,CD34,CD31 and D2-40 for 24 gingival cancers by immunohistochemistry. Both expressions of VEGF-C and Flt-4 did not correlated with lymph node metastasis. There was no relationship between immunohistochemical and serological methods.
Conclusion. The serum level of VEGF-C might have potential usefulness as biological marker of OSCC, but it is necessary to confirm relationship between immunohistochemical and serological methods by a larger scale study
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), HOKKAIDO UNIVERSITY, Coinvestigator, 16591977

Translation research for predicting the prognosis of oral malignant tumors.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2004 - 2005
TOTSUKA Yasunori; SHINDOH Masanobu; KOBAYASHI Masanobu; HIGASHINO Fumihiro; OHIRO Yoichi
E1AF is an ets-oncogene family transcription factor and it has been shown to upregulate multiple MMPs whereas MMP-2, a potent extracellular matrix degrading enzyme, is not upregulated. Chloramphenicol acetyltransferase (CAT) assay was utilized to investigate whether E1AF is able to upregulate MT1-MMP, which is known to activate MMP-2. Expression of the CAT reporter gene under the control of the MT1-MMP promoter was increased approximately 40-fold by co-transfection with the E1AF expression vector. Real-time RT-PCR study was carried out in 25 patients with tongue squamous cell carcinoma, and the mRNA expression level of E1AF,MT1-MMP was synergistically increased.
These results indicate that E1AF positively regulates transcription from MT1-MMP genes, which plays an important role in invasion and metastasis of squamous cell carcinoma of the tongue by converting pro-MMP-2 into active-MMP-2.
We investigated the relationship between Bcl-2 family gene expression and the effect of chemo- and radiotherapy. Bax was shown to reduce the expression in all carcinoma cases. High expression levels of Bcl-2 were observed in resistant cases for chemo- and radiotherapy. These results suggest that examination of Bcl-2 family gene expression levels would be the predictive factors of sensitivity for preoperative therapies.
Ets-1,Ets-2, and GnT-V mRNA expression were analyzed by the reverse transcription-polymerase chain reaction method in biopsy materials of 19 SCC cases and 4 premalignant lesions and compared with the expression levels of normal tongue tissues. Immunohistochemical detection of GnT-V and the relationship between clinico-pathological features were investigated. All premalignant lesions and SCC cases examined showed significantly escalated Ets-1 mRNA levels compered with normal tongue tissues by real-time PCR. Ets-2 and GnT-V mRNAs levels were also increased in SCC cases, but in contrast, their levels were not enhanced in premalignant lesions in comparison to normal tissues. The levels of GnT-V mRNA were correlated with Ets-1 and Ets-2 expression (rs=0.7;p<0.01). Ets-1 and GnT-V expression in SCC were positively associated with the tumor invasive pattern and cervical lymph node metastasis. On the contrary, Ets-2 expression has little relationship with these characteristics. These results suggest that Ets-1 plays a significant role in regulating GnT-V in human tongue squamous cell carcinoma and might be involved in the potential for malignancy via the action of GnT-V.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Coinvestigator, 16390576

Gene targeting therapy for oral carcinoma using adrenomedullin antagonisit.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2004 - 2005
SHINDOH Masanobu; KOBAYASHI Masanobu; HIGASHINO Fumihiro; OHIRO Yoichi; ONO Mitsunobu; TOTSUKA Yasunori
We have recently reported that intra-tumoral injection of adrenomedullin (AM) antagonist (AMA ; AM(22-52)) peptides significantly reduced the in vivo growth of a pancreatic cancer cell line in SCID mice. In this study, we examined the effects of intra-tumoral and intra-muscular transfers of naked DNA encoding. AMA on the in vivo growth of cancer cell lines. We demonstrated here that the intra-tumoral and intra-muscular transfers of naked DNA encoding AMA induced the regression of a pancreatic cancer cell line and a breast cancer cell line. We further demonstrated that CD31-positive cells completely disappeared from the tumor tissues treated with the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA. These results suggest that the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA might be a promising tool for treating cancers
E4orf6 plays an important role in the transcription of cellular and viral mRNAs. We show that E4orf6 interacts with pp32/LAMP and exports pp32/LAMP from the nucleus to the cytoplasm with its binding partner, HuR, which binds to an AU-rich element (ARE) present within many protooncogene and cytokine mRNAs. We found that ARE-mRNAs, such as c-fos,c-myc and Cox-2, were exported to and stabilized in the cytoplasm of E4orf6-expressing cells.The oncodomain of E4orf6 was necessary for both binding to pp32/LAMP and defect for ARE-mRNA. Moreover, inhibition of CRM1-dependent export pathway failed to block the export of ARE-mRNAs mediated by E4orf6. Thus, E4orf6 interacts with pp32/LAMP to modulate the fate of ARE-mRNAs by altering the CRM1-dependent export pathway.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Coinvestigator, 16390575

口腔悪性腫瘍術前診断におけるトランスレーショナル・リサーチ
Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
2003 - 2004
大廣 洋一
一般的に,悪性腫瘍の治療方針は,臨床診断ならびに生検材料による病理診断に基づいて決定される.口腔癌では,手術前に放射線ならびに化学療法を併用し手術の確実性を高める方法が選択されることが多い.しかし,現在の診断技術では手術前に行われる放射線ならびに化学療法に対する感受性の予測は困難であり,治療のタイミングを逸する可能性を示唆している.近年,遺伝子工学的手法の発達により,腫瘍組織の生物学的背景をとらえることが比較的容易に可能となっている.
本研究では,化学療法ならびに放射線療法に対する感受性を左右する因子を明らかにし,結果を患者に還元することを目的とする.
1.下顎歯肉癌の免疫染色におけるp53,p21の発現について.
15症例の下顎歯肉癌の生検材料を用いて検討した結果,p53陽性8例(放射線治療有効6例,無効2例)であった.陰性7例(有効5例,無効2例)で,両群間に有意差は認めなかった(p>0.99).一方,p21陽性10例(放射線治療有効9例,無効1例)で,陰性5例(有効2例,無効3例)で,両群間に有意差(p=0.011)を認めた.現在のところ,放射線感受性にはp53が陽性(変異)であることよりも,p21の発現が重要な予測因子であることがわかった.
2.術前化学療法併用放射線治療の改善と病理組織学的治療効果
現在,当科で施行している術前治療の治療効果について,生検材料と手術摘出標本を比較検討した.対象症例31例中,放射線治療単独群では,15例中有効例4例(27%),化学療法併用放射線治療群では16例中有効例11例(69%)と有意に化学療法併用群で高い治療効果を得ている.これらの生検材料を用いて,上記と同様の分子を標的に検討を加えている.
Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Hokkaido University, Principal investigator, 15791157

カーボンナノチューブによる細胞・組織へのデリバリーシステムの構築
Grants-in-Aid for Scientific Research Grant-in-Aid for Exploratory Research
2003 - 2004
戸塚 靖則; 進藤 正信; 古月 文志; 小林 正伸; 東野 史裕; 大廣 洋一
遺伝子導入用Toolとしてカーボンナノファイバーを用い、ターゲットとする細胞へ、特異的かつ効率的に遺伝子導入を行うことを目的に実験を行った。
カーボンナノファイバーを水溶化し細胞培養液中に加えたところ、細胞活性には変化を及ぼさず、細胞への生物学的活性はほとんどないものと考えられた。水溶化したカーボンナノファイバーにインターカレーターであるanthraquinoe-1-diazoniumを結合させ、その後インターカレーター結合でb-Gal発現プラスミドを結合させた。結合の有無をPCRにより検討したところ、カーボンナノファイバーにプラスミドが結合していることが確認された。このようなカーボンナノファイバー/beta-Gal発現プラスミド結合体を用いて、ヒト肺がん由来細胞株H1299への遺伝子導入を試みた。カーボンナノファイバーは酸処理〜破砕後フィルターにより分離した数種類のサイズのものを用いて実験を行った。その結果、カーボンナノファイバーの長径が200nmを超えるサイズのものでは遺伝子導入効果は認められなかったが、200nm以下のサイズを含むフラクションのものでは、青色のbeta-Gal遺伝子発現が認められた。
細胞表面にはそれぞれの組織・細胞に応じた特有のレセプター構造が存在し、このレセプターには特異的に結合するリガンドが同定されている。ヒト肺がん細胞株A431はEGFレセプターを高発現していることが知られている。EGFレセプターに結合するEGFのアミノ酸配列をもとに、ペプチドを合成し、このペプチドをカーボンナノファイバーに結合させた。ペプチドはN末端にビオチンを標識し、以後の検索に用いた。
このようなカーボンナノファイバー/beta-Gal発現プラスミド/EGFペプチド結合体を用いて、ヒト肺がん由来細胞株A431への遺伝子導入を試みた。その結果、EGFレセプターを発現するA431への特異的な遺伝子導入が認められ、今後、腫瘍特異的発現分子を標的にした遺伝子治療への展望が開かれた。
Japan Society for the Promotion of Science, Grant-in-Aid for Exploratory Research, Hokkaido University, Coinvestigator, 15659471

Identification of HIF-1a target genes and their biological roles in oral carcinoma.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
2002 - 2003
ONO Mitsunobu; HIGASHINO Fumihiro; KOBAYASHI Masanobu; SHINDOH Masanobu; TOTSUKA Yasunori; OHIRO Yoichi
Hypoxia-inducible factor 1(HIF-1) is an oxygen-regulated transcriptional activator that plays an essential role in the maintenance of oxygen homeostasis. We examined HIF-1a protein, vascularization and p53 protein in 39 biopsy specimens from tongue SCC patients HIF-1a was identified in 12 of 39 (31%) cases examined. A significant correlation was observed between HIF-1a expression and cancer cell metastasis into the cervical lymph nodes and distant organs. HIF-1a-positive tumors showed a high ratio of neovascularization with a large number and smaller diameter of blood vessels. Mutant-p53(mt-p53) expression was not significantly associated with HIF-1a expression, however, mt-p53/HIF-1a-positive cases highly correlated with metastasis, and showed significant by shorter cumulative overall survival. These results indicate that HIF-1a expression in combination with p53 status would be an indicator of neovasculanzation, which could be a new predictive and prognostic parameter for metastasis in tongue SCC.
DNA microarray analysis revealed that several candidated genes responsive for HIF-1, and pim-1 and adrenomedullin were included. pim-1 was shown to inhibit apoptosis cooperating with myc and induce tumorigenesis in blood cells. We examined pim-1 in tongue squamous cell carcinomas and pim-1 was detected in about 40% tumors Correlated expression of HIF-1a and pim-1, and the close relationship between proliferative potential and distant metastasis were identified. Adrenomedullin was identified in about 40% of oral carcinoma, and high metastatic potential with neovasculization was shown.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Coinvestigator, 14571878

Research on factors involved in prognosis of oral carcinoma.
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2002 - 2003
SHINDOH Masanobu; OHIRO Yoichi; HIGASHINO Fumihiro; KOBAYASHI Masanobu; TOTSUKA Yasunori; YASUDA Motoaki
EWS/ETS is a chimeric protein identified in most Ewing's sarcomas. We demonstrate that telomerase is a new target of EWS/ETS fusions TERT mRNA were up-regulated by EWS/Ets ; however, EWS/Ets function in an EBS-independent manner and EWS/ETS fusion proteins were shown to activate human telomerase activity as a transcriptional co-activator. The adenovirus E4orf6 is a viral oncoprotein and it has been shown to inhibit the apoptotic activities of p53 and p73. We demonstrate that the adenovirus E4ort6 protein directly inhibits apoptosis mediated by BNIP3 and Bik, which are BH3-only proteins of the Bcl-2 family and that the export signal of E4orf6 from the nucleus to the cytoplasm was shown to be important for the inhibition of apoptotic activity.
We investigated the activation mechanism of MMP-2 in oral squamous cell carcinomas. CAT assay revealed that MT1-MMP promoter was activated by E1AF and Real-time RT-PCR study in 25 patients with tongue squamous cell carcinoma showed synergistical increasing expression of E1AF and MT1-MMP. These results indicate that E1AF positively regulates transcription from MT1-MMP genes, which plays an important role in invasion and metastasis of squamous cell carcinoma of the tongue by converting pro-MMP-2. into active-MMP-2 We investigated expression levels of VEGF-C mRNA in 48 cases of 0SCC by real-time RT-PCR. High levels of VEGF-C expression were identified 20 of 48 cases examined Expression level of VEGF-C was significantly associated with cancer cell metastasis in cervical lymph node. These results suggest that high expression of VEGF-C would be a predictive parameter for cervical lymph node metastasis of 0SCC, especially in the early stage tumors.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), HOKKAIDO UNIVERSITY, Coinvestigator, 14370654

Jun. 2021 - Present
日本口腔科学会指導医

Mar. 2015 - Present
FIBCSOMS
Fellow of the International Board for the Certification of Specialists in Oral and Maxillofacial Surgery

Apr. 2010 - Present
Japanese Board Certification in Cancer Therapy
Japanese Board Certification in Cancer Therapy

Oct. 2007 - Present
Japanese Board Certified Specialist in Oral and Maxillofacial Surgery
Japanese Board Certification in Oral and Maxillofacial Surgery

Oct. 2003 - Present
Board Certified Specialist in Oral and Maxillofacial Surgery
Board Certified Specialist in Oral and Maxillofacial Surgery