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田所 慶誠大学院医学系研究科 医科学専攻助教
研究活動情報
■ 受賞- 2026年05月 The 23rd Annual Meeting of the Japanese Society of Oral Care Joint Congress, Recommended presentation
- 2026年05月 第23回日本口腔ケア学会総会・学術大会, 推薦演題
- 2024年11月 ANZBMS 2024 Travel Award
- 2024年07月 第42回日本骨代謝学会学術集会, 優秀演題賞
- 2023年11月 第68回公益社団法人日本口腔外科学会総会・学術大会, 優秀ポスター発表賞
- 2023年06月 楠歯会学術奨励賞
- 2023年02月 第41回日本口腔腫瘍学会総会・学術大会, 優秀ポスター賞
- INTRODUCTION: Surgery has increasingly been reported as an effective treatment for medication-related osteonecrosis of the jaw (MRONJ), but concrete intervention criteria are lacking. On computed tomography (CT) images, the boundary between the healthy site and necrotic lesion, which we defined as "MRONJ demarcation line", is sometimes visible. This study aimed to identify the factors associated with this boundary to improve surgical planning. MATERIALS AND METHODS: 95 patients with MRONJ who underwent their first CT at our institution between May 2010 and June 2022 were included. The Mann-Whitney U test, Fisher's exact test, and multivariate logistic regression analysis were performed. The cumulative incidence rates were calculated using the Kaplan-Meier method. Statistical significance was set at p < 0.05. RESULTS: MRONJ demarcation line was observed in 63 patients and absent in 32. Significant associations were identified between MRONJ demarcation line formation and denosumab (p = 0.013), antiresorptive agent (ARA) discontinuation (p = 0.024), and periosteal reaction ( p = 0.034). The cumulative incidence rates of MRONJ demarcation line formation at 12, 24, and 36 months after discontinuation of high-dose ARA were 58.0%, 89.2%, and 96.4% for denosumab, and 29.9%, 68.8%, and 88.3% for bisphosphonates, respectively. In the low-dose group, the rates at 12, 24, and 36 months after discontinuation of denosumab were 41.7%, 51.4%, and 63.5%, respectively, while those for bisphosphonates were 22.2%, 35.8%, and 51.1%. CONCLUSION: Denosumab administration, ARA discontinuation, and periosteal reaction are significantly associated with the MRONJ demarcation line, which may help in establishing criteria for surgical intervention.2026年01月, Journal of bone and mineral metabolism, 英語, 国内誌研究論文（学術雑誌）
- BACKGROUND: Osteoradionecrosis (ORN) is a severe adverse effect of radiation therapy for head and neck cancers. Despite advances in radiation techniques and surgical management, reliable predictors of ORN prognosis remain lacking. PURPOSE: The purpose of this study was to measure the association between systemic inflammatory biomarkers and ORN prognosis. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study included patients with ORN treated between January 2010 and March 2022 at the Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine. Patients with unavailable blood test data were excluded. PREDICTOR VARIABLE: The predictor variables were pretreatment systemic inflammatory biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (LMR). The cutoff values for NLR, platelet-to-lymphocyte ratio, and LMR were determined using receiver operating characteristic curve analysis. Each marker was calculated at the time of diagnosis of ORN. MAIN OUTCOME VARIABLE: The outcome variable was prognosis. Subjects had a good prognosis if the ORN stage improved. The prognosis was poor if the ORN stage was stable or worse over time. COVARIATES: Sex, age, stage, onset region, primary tumor site, radiation dose, smoking history, medical history, steroid therapy, clinical symptoms, treatment methods, and computed tomography image findings were covariates. ANALYSES: Statistical analysis was performed using Mann-Whitney U nonparametric test, Fisher's exact test, χ2 test, and Cox regression analysis. Statistical significance was set at P < .05. RESULTS: The sample consisted of 75 subjects, of whom 16 (21.3%) had a poor prognosis. The median follow-up period was 88 (53 to 122) months. Bivariate analysis revealed that high NLR (P < .01) and low LMR (P = .02) were significantly associated with poor prognosis. In multivariate Cox regression analysis, poor prognosis was significantly associated with advanced age (hazard ratio [HR], 5.33; 95% CI, 1.61 to 17.65; P < .01), ORN stage 3, 4 (HR, 0.18; 95% CI, 0.06 to 0.56; P < .01), high NLR (HR, 14.78; 95% CI, 3.50 to 62.35; P < .01), and periosteal reaction (HR, 19.15; 95% CI, 4.65 to 78.87; P < .01). CONCLUSIONS AND RELEVANCE: We identified high NLR as a risk factor for poor prognosis in ORN. High NLR is considered to reflect worse local tissue and systemic health.2026年01月, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a common malignancy with a poor prognosis, partly due to interactions within the tumor microenvironment. Cancer-associated fibroblasts (CAFs), key stromal components, promote tumor progression by enhancing cancer cell migration, angiogenesis, and extracellular matrix remodeling. Transforming growth factor-beta (TGF-β) is known to induce CAF differentiation from normal fibroblasts (NFs), but its functional contribution in OSCC remains to be fully elucidated. This study explored the role of TGF-β in inducing the transition of NFs into CAFs and its impact on progression of OSCC. MATERIALS AND METHODS: In vitro, NFs were treated with TGF-β, and CAF induction was assessed by evaluating the expression of the CAF marker α-smooth muscle actin (α-SMA) using quantitative real-time PCR and fluorescent immunostaining. OSCC cell migration was analyzed using a scratch assay. In vivo, TGF-β-treated or untreated NFs were co-injected with OSCC cells. The tumor size and VEGF, MMP2, and MMP9 expression were analyzed via quantitative real-time PCR and immunohistochemistry. RESULTS: In vitro, TGF-β-treated NFs exhibited significantly increased α-SMA expression and enhanced the OSCC migratory ability. In vivo, the TGF-β-treated group demonstrated a marked increase in tumor growth and up-regulated expression of VEGF, MMP2, and MMP9 compared to the untreated group. CONCLUSION: These findings suggest that TGF-β induces CAF differentiation and facilitates tumor progression by promoting angiogenesis and extracellular matrix degradation. This study highlights the potential of targeting TGF-β as a therapeutic strategy and underscores the need for novel approaches to counteract the tumor-promoting effects of CAFs.2025年09月, Anticancer research, 45(9) (9), 3687 - 3700, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: The pathological evaluation of cancellous bone at resection margins of mandibular osteoradionecrosis (ORN) has not been well elucidated. Here, we developed a unique classification system for evaluating the degree of bone marrow fibrosis, one of most common pathological features, in patients with mandibular ORN, based on which we investigated its relationship with treatment outcome. METHODS: This study included 15 patients who underwent mandibulectomy and free fibula osteocutaneous flap reconstruction. The extent of mandibulectomy was determined, with safety margins of approximately 10 mm from the apparent osteolytic areas on preoperative computed tomography image. Special staining was performed on thin sections from center of the osteolytic areas (medial area) and bilateral resection margins, and the degree of bone marrow fibrosis was evaluated and investigated its relationship with presence of bone union as a treatment outcome. RESULTS: The degree of bone marrow fibrosis of medial area was significantly higher than those of resection margins. Although most resection margins had collagen fibers which indicate severe fibrosis, all transferred fibula flaps achieved bone union. CONCLUSION: When mandibulectomy is performed with safety margins of approximately 10 mm from the apparent osteolytic areas, all transferred fibula flaps achieved bone union regardless of the degree of bone marrow fibrosis at resection margin. In other words, the association between severe bone marrow fibrosis at resection margins and treatment outcome was not seen. CLINICAL RELEVANCE: Setting safety margins of approximately 10 mm may achieve bone union, but further study is needed.2024年11月, Clinical oral investigations, 28(11) (11), 626 - 626, 英語, 国際誌研究論文（学術雑誌）
- OBJECTIVES: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect of antiresorptive and/or antiangiogenic agents. As the treatment application for MRONJ is controversial, we aimed to identify the risk factors for poor prognosis and to help determine appropriate management. METHODS: This study included 119 patients. Relevant clinical data were obtained for all the patients. In computed tomography images, osteosclerosis, osteolysis, cortical perforation (buccal or lingual), periosteal reaction, and sequestration were evaluated. RESULTS: Multivariate analyses showed statistically significant associations between poor prognosis in patients with MRONJ and conservative treatment alone (hazard ratio [HR] 1.89), osteolysis (HR 4.67), and the absence of sequestration (HR 5.33). CONCLUSIONS: Conservative treatment alone without clear objectives needs to be avoided, and osteolytic change could be the criteria for surgical intervention. As the boundary between the lesion and vital bone is indistinct, we recommend extensive surgery in cases with unpredictable sequestration.2024年02月, Head & neck, 46(2) (2), 282 - 290, 英語, 国際誌研究論文（学術雑誌）
- 2024年, 日本口腔外科学会雑誌, 70(6) (6)自傷行為により側頭筋および咬筋に発症した外傷性化骨性筋炎の1例
- Cancer cachexia causes skeletal muscle atrophy, impacting the treatment and prognosis of patients with advanced cancer, but no treatment has yet been established to control cancer cachexia. We demonstrated that transcutaneous application of carbon dioxide (CO2) could improve local blood flow and reduce skeletal muscle atrophy in a fracture model. However, the effects of transcutaneous application of CO2 in cancer-bearing conditions are not yet known. In this study, we calculated fat-free body mass (FFM), defined as the skeletal muscle mass, and evaluated the expression of muscle atrophy markers and uncoupling protein markers as well as the cross-sectional area (CSA) to investigate whether transcutaneous application of CO2 to skeletal muscle could suppress skeletal muscle atrophy in cancer-bearing mice. Human oral squamous cell carcinoma was transplanted subcutaneously into the upper dorsal region of nude mice, and 1 week later, CO2 gas was applied to the legs twice a week for 4 weeks and FFM was calculated by bioimpedance spectroscopy. After the experiment concluded, the quadriceps were extracted, and muscle atrophy markers (muscle atrophy F-box protein (MAFbx), muscle RING-finger protein 1 (MuRF-1)) and uncoupling protein markers (uncoupling protein 2 (UCP2) and uncoupling protein 3 (UCP3)) were evaluated by real-time polymerase chain reaction and immunohistochemical staining, and CSA by hematoxylin and eosin staining. The CO2-treated group exhibited significant mRNA and protein expression inhibition of the four markers. Furthermore, immunohistochemical staining showed decreased MAFbx, MuRF-1, UCP2, and UCP3 in the CO2-treated group. In fact, the CSA in hematoxylin and eosin staining and the FFM revealed significant suppression of skeletal muscle atrophy in the CO2-treated group. We suggest that transcutaneous application of CO2 to skeletal muscle suppresses skeletal muscle atrophy in a mouse model of oral squamous cell carcinoma.2024年, PloS one, 19(4) (4), e0302194, 英語, 国際誌研究論文（学術雑誌）
- PURPOSE: In this study, we prospectively investigated the relationship between bone marrow edema (BME) and odontogenic cysts and explored the possibility of using dual-energy computed tomography (DECT) as an auxiliary tool for the diagnosis of odontogenic cysts. METHODS: This cross-sectional study included 73 patients who underwent the DECT scan and surgery for odontogenic cysts or odontogenic tumors. The virtual noncalcium (VNCa) computed tomography (CT) values and CT values were measured at several sites. The predictor variable was diagnosis, and the other variables included age, sex, and sites. The primary outcome was VNCa CT value. Variables were tested using the chi-square test or the Kruskal-Wallis test. The VNCa CT and CT values were tested using the Scheffe test for multiple comparisons. All variables were analyzed as independent variables affecting the VNCa CT values around the lesion in the multiple regression analysis. RESULT: There were 35 men and 38 women. The mean patient age was 50.0 ± 19.5 years (range: 8-86). The VNCa CT values (- 6.2 ± 34.3) around the lesion in patients with RCs were significantly higher than those in patients with dentigerous cysts (- 44.4 ± 28.6) and odontogenic keratocysts (- 67.3 ± 19.5). In multiple regression analysis, the VNCa CT values around the lesion showed a significant positive correlation with histological results (regression coefficient: - 0.605, P < 0.001). CONCLUSION: The presence of BME is associated with radicular cysts, and DECT can be used as an auxiliary tool for radicular cyst diagnosis.2023年12月, Oral and maxillofacial surgery, 27(4) (4), 675 - 684, 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Head and neck cancers that cause severe aesthetic and functional disorders normally metastasize to the cervical lymph nodes. Patients with cervical lymph node metastasis are undergoing neck dissection. Shoulder complaints are common after neck dissection, with patients reporting symptoms such as pain, weakness, shoulder droop, and disability. However, no safe and effective treatment is available for this condition at present. We will conduct a double-blinded, randomized controlled trial to evaluate the efficacy of carbon dioxide (CO2) paste in relieving pain in patients after neck dissection. OBJECTIVE: This will be the first clinical study to compare the efficacy of CO2 paste with placebo in relieving postoperative pain in patients who underwent neck dissection. METHODS: We will perform this trial at the Kobe University Hospital in Japan. Patients will be randomized 1:1 into the CO2 paste and control groups. Patients in the CO2 paste group will have the CO2 paste applied to the cervical surface skin for 10 minutes once per day for 14 consecutive days. The primary end point of the study is a change in the visual analog scale (VAS) scores of neck pain from baseline on day 1 (preapplication) to the end of drug application (day 15). Secondary end points include changes in the following parameters from baseline on day 1 to the end of drug application (day 15) or the study (day 29): neck pain VAS score (days 1-29), grip strength (days 1-15 and 1-29), VAS scores for subjective symptoms (the feeling of strangulation, numbness, swelling, and warmth in the neck and shoulder region) for days 1-15 and 1-29, whether the VAS score improved more than 30% (days 1-15), the arm abduction test (days 1-15 and 1-29), shoulder range of motion (abduction and flexion) for days 1-15 and 1-29, occurrence of skin disorders, and occurrence of serious side effects. Periodic monitoring will be conducted for participants during the trial. This study was approved by the certified review board of Kobe University. RESULTS: The intervention commenced in May 2021 and will continue until March 2024. The collected data will provide information on the efficacy of the CO2 paste treatment. The primary end point will be compared using the Wilcoxon test, with the 1-sided significance level set at 5%. Each evaluation item will be summarized. Secondary efficacy end points will be analyzed to provide additional insights into the primary analysis. Findings based on the treatment effects are expected to be submitted for publication in 2025. CONCLUSIONS: This trial will provide exploratory evidence of the efficacy and safety of CO2 paste in relieving pain in patients after neck dissection. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier: jRCTs051210028; https://jrct.niph.go.jp/en-latest-detail/jRCTs051210028. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50500.2023年11月, JMIR research protocols, 12, e50500, 英語, 国際誌研究論文（学術雑誌）
- Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Cancer-associated fibroblasts (CAFs) are the main stromal cells in the tumor microenvironment (TME). As CAFs promote tumor progression and hypoxia in the TME, regulating the conversion of normal fibroblasts (NFs) into CAFs is essential for improving the prognosis of patients with OSCC. We have previously reported the antitumor effects of transcutaneous carbon dioxide (CO2) application in OSCC. However, the effects of reducing hypoxia in the TME remain unclear. In this study, we investigated whether CO2 administration improves the TME by evaluating CAFs marker expression. Human OSCC cells (HSC-3) and normal human dermal fibroblasts (NHDF) were coinjected subcutaneously into the dorsal region of mice. CO2 gas was applied twice a week for 3 weeks. The tumors were harvested six times after transcutaneous CO2 application. The expression of CAFs markers (α-SMA, FAP, PDPN, and TGF-β) were evaluated by using real-time polymerase chain reaction and immunohistochemical staining. The expression of α-SMA, FAP, PDPN, and TGF-β was significantly increased over time after co-injection. In the CO2-treated group, tumor growth was significantly suppressed after treatment initiation. In addition, the mRNA expression of these markers was significantly inhibited. Furthermore, immunohistochemical staining revealed a significant decrease in the protein expression of all CAFs markers in the CO2-treated group. We confirmed that transcutaneous CO2 application suppressed CAFs marker expression and tumor growth in OSCC xenograft mouse model.2023年, PloS one, 18(8) (8), e0290357, 英語, 国際誌研究論文（学術雑誌）
- A standard treatment for osteoradionecrosis (ORN) has not yet been established because of the diversity. Therefore, identifying the risk factors for a poor prognosis is essential. This study retrospectively investigated the factors associated with the prognosis of ORN in 68 patients. Relevant clinical data of all patients were obtained. Of the patients, 16 who underwent extensive surgery underwent histopathological analysis. The necrotic changes of the anterior and posterior margins in the cortical and cancellous bones were investigated. Multivariate analyses showed statistically significant associations between poor prognosis in patients with ORN and high radiation dose (hazard ratio [HR] 1.15), orocutaneous fistula (HR 2.93), and absence of sequestration (HR 2.49). Histopathological analysis showed a viable anterior margin of the middle portion of the cortical bone for all recovered cases; in contrast, most cases (75%) with a poor prognosis showed necrotic changes. The anterior margin of the cancellous bone was viable and resilient to high irradiation, regardless of the prognosis. These results suggest that patients with orocutaneous fistula should receive early surgical intervention, even if the affected area is limited or asymptomatic. In extensive surgery, a sufficient safety margin of necrotic bone, particularly in the anterior region, is required to improve the prognosis.2022年05月, International journal of environmental research and public health, 19(11) (11), 英語, 国際誌研究論文（学術雑誌）
- 2024年, 日本骨代謝学会学術集会プログラム抄録集(CD-ROM), 42nd薬剤関連顎骨壊死患者の予後不良となるリスク因子およびCT画像所見の同定
- 2024年, 炎症と免疫, 32(5) (5)組織線維化と線維症-その生理と病理
- 2024年, 生体の科学, 75(6) (6)新組織学シリーズV:脂肪 I.脂肪細胞の基礎 脂肪組織とイメージング
- 2023年, 日本口腔腫瘍学会総会・学術大会プログラム・抄録集, 41st放射線性顎骨壊死患者の予後不良となるリスク因子および病理組織学的特徴に関する後ろ向き観察研究
- 2022年, 日本口腔科学会学術集会プログラム・抄録集, 76th放射線性顎骨壊死患者を対象とした予後とリスク因子に関する後ろ向き観察研究