研究活動情報

• Association between bacteria detected in blood and the oral environment in patients with infective endocarditis.

  Yumi Muraki, Haruka Terawaki, Hana Okazaki, Mika Nishii, Masaya Akashi

  INTRODUCTION: Infective endocarditis (IE) is a rare disease with a high mortality rate. Although IE is often associated with dental treatment, poor oral hygiene has also been reported to contribute to development, even in the absence of dental procedures. Therefore, oral surgeons may play an important role in the prevention of IE through oral hygiene management and therapeutic interventions. Few studies have examined the relationship between the causative bacteria in patients with IE and their oral environment. We therefore retrospectively investigated the bacteria detected by blood culture and the oral environment of patients treated for IE. METHODS: The study sample comprised 48 patients who underwent IE treatment from October 2018 to April 2024. We evaluated the correlation between the number of teeth indicated for extraction, as determined by panoramic radiography and intraoral examination, and the bacteria detected in blood culture tests performed during IE treatment. RESULTS: The final study cohort comprised 31 patients. Among the bacteria detected by blood culture, seven were classified as intraoral and five as extraoral. The number of teeth indicated for extraction was significantly higher in patients with IE caused by intraoral bacteria than in those with IE caused by extraoral bacteria. CONCLUSIONS: Careful dental monitoring is essential to prevent deterioration of oral hygiene. When dental treatment is deemed necessary, early intervention before caries progresses is critically important.

  2026年04月, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy, 32(6) (6), 102971 - 102971, 英語, 国際誌

  研究論文（学術雑誌）


• Identifying the clinical indicator for surgical intervention in medication-related osteonecrosis of the jaw.

  Yoshiaki Tadokoro, Takumi Hasegawa, Daisuke Takeda, Junya Hirota, Kaito Uryu, Tatsuya Shirai, Yumi Muraki, Masaya Akashi

  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）

  神戸大学リポジトリ（Kernel）へのリンク


• Expression Analysis of JCAD and IL-33 in Gingival Cancer Tumor Angiogenesis.

  Tatsuya Shirai, Yasumasa Kakei, Yumi Muraki, Tatsuya Nagano, Ratoe Suraya, Kaito Uryu, Daisuke Takeda, Manabu Shigeoka, Akira Kimoto, Takumi Hasegawa, Tetsuya Hara, Noriaki Emoto, Masaya Akashi

  Head and neck cancer is the sixth most common malignant disease worldwide [...].

  2025年11月, Cancers, 17(23) (23), 英語, 国際誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Involvement of resistant bacteria in the severity of refractory osteonecrosis of the jaw.

  Junya Kusumoto, Yumi Muraki, Eiji Iwata, Megumi Matsumura, Shungo Furudoi, Masaya Akashi

  PURPOSE: Osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) are relatively rare and refractory, and there is no consensus regarding the bacteria associated with their development. This study was conducted to identify the bacteria associated with refractory ORN and MRONJ, including severe cases. METHODS: Patients who underwent surgery for osteonecrosis of the jaw were included in this study. Bacterial culture specimens were obtained from tissue as deeply as possible. Severe cases of ORN and MRONJ were defined as stage IV of Lyon's classification and stage III of the AAOMS classification, respectively. Demographic data, clinical features, antimicrobials usage, and bacteria detected were analysed to determine the factors associated with severe disease. RESULTS: Seventy-seven patients (ORN, n = 22; MRONJ, n = 55) were analysed. Penicillins were the most commonly used antimicrobials. A total of 311 bacterial strains were detected in tissue culture (detection rate = 100%). Streptococcus spp. were the most common bacteria (37.0%), followed by anaerobes (33.8%). Gram-negative rods were detected in 10.3% of the patients, antimicrobial-resistant bacteria in 78.4%, and ampicillin resistance in 60.8%. Factors associated with severe disease were ampicillin resistance and malignancy in MRONJ, with odds ratios of 8.74 (95% confidence interval, 1.20-63.4; p = 0.032) and 13.5 (1.09-168, p = 0.043), respectively. Enterobacter spp. were detected only in severe cases. CONCLUSION: Bacteria associated with osteonecrosis of the jaw are similar in composition to those responsible for common odontogenic infections, but with a higher proportion of gram-negative rods. Ampicillin-resistant bacteria, including Enterobacter spp., are implicated in severe disease.

  2025年09月, Clinical oral investigations, 29(10) (10), 454 - 454, 英語, 国際誌

  研究論文（学術雑誌）


• Potential of zoledronate for treating diffuse sclerosing osteomyelitis of the mandible in adult patients.

  Junya Kusumoto, Shungo Furudoi, Yumi Muraki, Moeka Warabi, Daisuke Takeda, Masaya Akashi

  INTRODUCTION: Diffuse sclerosing osteomyelitis (DSO) is a rare nonbacterial bone disease associated with recurrent pain and swelling, and its pathogenesis remains unknown. Despite the absence of an established treatment for DSO, bisphosphonates have recently been considered effective in managing this condition. However, the use of zoledronate is off-label, with limited reported cases. Therefore, this study aimed to investigate the effects of zoledronate on pain suppression in DSO. METHODS: This single-arm retrospective study evaluated adult patients diagnosed with mandibular DSO and treated with zoledronate. Patient demographics, pain suppression effect, recurrence, number of zoledronate administration, adverse reactions to zoledronate, and imaging findings were investigated. RESULTS: The study included 18 patients (median age of 59.5 years). Zoledronate effectively suppressed pain in all patients, with a median duration of effect onset of 1 day. Symptom recurrence was observed in 66.7% of patients, with a median time of 29 months from the first zoledronate administration to recurrence. Zoledronate was administered multiple times to 44.7% of patients. The median duration of response was 80 months for patients who experienced relief after a single administration of zoledronate compared to 32 months for those who received multiple administrations (p < 0.001). Adverse reactions, including flu-like symptoms, were observed in 72.2% of the patients, and no medication-related osteonecrosis of the jaw was observed during the follow-up period. CONCLUSIONS: Zoledronate is a relatively safe and effective treatment option for DSO of the mandible. Key Points • Zoledronate effectively suppresses pain in mandibular diffuse sclerosing osteomyelitis. • All condylar lesions recurred after zoledronate administration. • Patients with mandibular canal enlargement required multiple doses of zoledronate. • Adverse reactions to zoledronate administration were minor.

  2025年04月, Clinical rheumatology, 44(6) (6), 2463 - 2475, 英語, 国際誌

  研究論文（学術雑誌）


• Oral Health and Cardiovascular Disease - A Scoping Review of Assessment Methods, Risk Factors, and Prognosis.

  Masato Ogawa, Masatsugu Okamura, Takuma Yagi, Kenichiro Maekawa, Kota Amakasu, Tatsuro Inoue, Seimi Satomi-Kobayashi, Megumi Katayama, Yumi Muraki, Masaya Akashi

  Oral frailty, which encompasses decline in oral health and function with aging, has broader health implications. However, its specific role in individuals with cardiovascular disease (CVD) remains poorly understood. In this scoping review we investigated the prevalence, assessment tools, and potential intervention strategies for oral frailty in patients with CVD. We used the Population, Concept, and Context framework as follows: Population: Patients with CVD; Concept: Existing literature on oral frailty in the context of CVD; Context: Not restricted. Extracted data were synthesized qualitatively. From an initial pool of 3,199 studies, 70 were included in the final analysis, with a cumulative sample size of 891,450 individuals. Among the assessment tools for oral frailty, the number of teeth was the most commonly used measure in 39 studies, followed by the Decayed, Missing, Filled Index. Of the studies, 5 studies indicated that coronary artery disease and diabetes are risk factors for oral frailty, and 8 identified poor oral health as a predictor of cardiac events. However, no study clearly defined oral frailty in the context of CVD. Additionally, only 2 studies explored the relationship between oral health and physical frailty. This results of this review underscore the lack of a standardized definition for oral frailty in CVD. Although associations between oral health and prognosis were observed, further research is needed to clarify the definitions and explore causal relationships.

  2025年04月, Circulation reports, 7(4) (4), 223 - 230, 英語, 国内誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Effect of Statins on Patients With Osteoradionecrosis of the Jaw.

  Junya Kusumoto, Yumi Muraki, Akiko Sakakibara, Shungo Furudoi, Masaya Akashi

  BACKGROUND: Osteoradionecrosis of the jaw (ORN) is a late complication of radiation therapy. Radiation-induced fibrosis is the most likely mechanism for developing ORN, and statins are effective against radiation-induced fibrosis. However, no reports have indicated the direct effectiveness of statins in treating ORN. PURPOSE: This study aimed to measure the association between statin exposure and ORN disease resolution. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study included patients with ORN diagnosed between January 2008 and December 2020 at the Hospital's Department of Oral and Maxillofacial Surgery. Patients who were immunocompromised or followed up for < 6 months were excluded. PREDICTOR VARIABLE: The predictor variable was statin exposure, which was defined as the use of statins for dyslipidemia. MAIN OUTCOME VARIABLE: The main outcome variable was ORN disease progression status (good prognosis). Patients who showed full recovery and improvement were included in the good prognosis group, and those who showed invariance and deterioration were included in the poor prognosis group. COVARIATES: We analyzed the clinicodemographic including the age of onset, sex, history of smoking, alcohol consumption, history of chemotherapy, tumor site, association with dental treatment, location (maxilla or mandible), the time to ORN onset from radiation therapy, and stage of ORN, and treatment characteristics including hyperbaric oxygen therapy, long-term macrolide administration, and sequestrectomy. ANALYSES: We analyzed the association between statin exposure or covariates and time to ORN improvement using bivariate and multivariate Cox regression. The significance level was set at P = .05. RESULTS: We analyzed 102 patients, and the improvement rate was 32.4%. The favorable prognostic factors were statin exposure (adjusted hazard ratio [HR], 3.71; 95% confidence interval [CI], 1.62 to 8.50; P = .002), onset in the maxilla (HR, 2.15; 95% CI, 1.02 to 4.55; P = .045), and stage 1 of ORN (HR, 2.65; 95% CI, 1.20 to 5.83; P = .016). CONCLUSION AND RELEVANCE: In this study, statin exposure, onset in the maxilla, and stage 1 of Lyons's classification were favorable prognostic factors for ORN. Although this study's findings were insufficient to recommend statin use for ORN, statins may be a novel and effective treatment for ORN.

  2024年12月, Journal of oral and maxillofacial surgery : official journal of the American Association of Oral and Maxillofacial Surgeons, 82(12) (12), 1585 - 1595, 英語, 国際誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Dental dysplasia in childhood cancer survivors: a case series of permanent tooth abnormalities.

  Yumi Muraki, Atsushi Shioyasono, Mika Nishii, Daisuke Takeda, Junya Kusumoto, Masaya Akashi

  PURPOSE: This study was performed to investigate the association of dental dysplasia with childhood cancer. We examined the occurrence of agenesis, microdontia, and enamel changes of permanent teeth in pediatric cancer survivors. METHODS: Seventy-six patients with pediatric cancer and hematologic diseases were referred to our department for the first time from October 2005 to December 2019. Of these, 17 patients who presented for a checkup in our department fulfilled the study criteria and were analyzed. Clinical examinations and panoramic radiographs were performed to investigate dental dysplasia of permanent teeth. A total of 34 developmental abnormalities (18 missing teeth, 16 cases of microdontia) occurred in 5 patients. The patients' medical records were also analyzed to assess the relationships of specific types of dysplasia with the treatment duration and cumulative drug dose administered. RESULTS: All five pediatric cancer survivors had dental dysplasia; all five had tooth agenesis, and four had microdontia. All five patients were < 4 years of age and had undergone high-dose chemotherapy. CONCLUSION: In this study, childhood cancer survivors who received high-dose chemotherapy before age 4 years experienced the dental dysplasia, including tooth agenesis, microdontia. These findings highlight the need for careful dental monitoring and early intervention in pediatric patients undergoing high-dose chemotherapy. CLINICAL TRIAL NUMBER: This research was conducted in accordance with the Declaration of Helsinki and approved by the Medical Ethics Committee of the Medical University of Kobe (protocol code No. B230066, 1 September 2023).

  2024年11月, Oral and maxillofacial surgery, 29(1) (1), 9 - 9, 英語, 国際誌

  研究論文（学術雑誌）


• 周術期のオーラルマネジメントによる外科感染症の予防 歯とHeartとの関連

  楠元 順哉, 片山 めぐみ, 村木 友美, 明石 昌也

  (一社)日本外科感染症学会, 2024年10月, 日本外科感染症学会雑誌, 21(1) (1), 198 - 198, 日本語


• Dental intervention against osteoradionecrosis of the jaws in irradiated patients with head and neck malignancy: a single-arm prospective study.

  Yumi Muraki, Masaya Akashi, Yasuo Ejima, Takumi Hasegawa, Daisuke Miyawaki, Hirotaka Shinomiya, Mika Nishii, Naoki Otsuki, Ryohei Sasaki, Ken-Ichi Nibu, Takahide Komori

  BACKGROUND: The purpose of this study was to investigate the effectiveness of dental intervention before and after radiation therapy (RT) for head and neck malignancy on prevention of osteoradionecrosis (ORN) of the jaws. METHODS: This is a single-arm prospective study according to intervention protocol of prophylactic dental extraction before RT and routine follow-up after RT. The primary endpoint was the occurrence of jawbone exposure during the first 2 years after RT. RESULTS: Sixty-seven patients were assessed. Before RT, 144 teeth among 39 patients (58%) were prophylactically extracted. The occurrence of transient jawbone exposure during the first 2 years after RT was 7%. Because those jawbone exposures healed with intervention after RT, no jawbone exposure was found at 2 years after RT. CONCLUSIONS: Dental intervention both before and after RT seemed to be important to prevent ORN development. Further studies in larger cohorts are necessary.

  2019年09月, Oral and maxillofacial surgery, 23(3) (3), 297 - 305, 英語, 国際誌

  研究論文（学術雑誌）


• Induced Pluripotent Stem Cell-related Genes Correlate With Poor Prognoses of Oral Squamous Cell Carcinoma.

  Yumi Muraki, Takumi Hasegawa, Daisuke Takeda, Takeshi Ueha, Eiji Iwata, Izumi Saito, Rika Amano, Akiko Sakakibara, Masaya Akashi, Takahide Komori

  BACKGROUND/AIM: We recently investigated the contribution of the iPS-related genes SOX2, OCT4, and Nanog to de-differentiation by assaying for their mRNA levels. Given that mRNA expression does not always correlate with the protein levels, the aim of this study was to retrospectively determine the expression of these four iPS-related factors in human OSCC specimens by immunohistochemistry and examine their association with patient prognosis. MATERIALS AND METHODS: iPS cell-related gene expression in 89 OSCC patients by tissue microarray, and its correlation with clinicopathological factors, differentiation, metastasis, and poor prognoses were investigated. RESULTS: No evidence of statistically significant relationships was found between the expression of iPS cell-related genes and clinicopathological parameters. However, our data indicated that KLF4 expression was associated with survival, and poor tumor differentiation. In addition, high expression of KLF4 was an independent poor prognostic factor (p=0.004) for OSCC patients. CONCLUSION: In preoperative biopsies, higher KLF4 and poor differentiation may be clinically effective predictors for the prognosis of oral cancer.

  2019年03月, Anticancer research, 39(3) (3), 1205 - 1216, 英語, 国際誌

  研究論文（学術雑誌）

• 下顎びまん性硬化性骨髄炎に対してゾレドロン酸は有効な治療薬となりうるか?

  楠元 順哉, 古土井 春吾, 村木 友美, 武田 大介, 明石 昌也

  (NPO)日本口腔科学会, 2024年09月, 日本口腔科学会雑誌, 73(2) (2), 195 - 195, 日本語


• オーラルフレイル:循環器領域と歯科口腔領域の診療連携 歯科医師の立場から

  村木 友美

  (一社)日本循環器学会, 2024年03月, 日本循環器学会学術集会抄録集, 88回, CE4 - 1, 日本語


• 歯とHeartとの関連

  楠元順哉, 片山めぐみ, 村木友美, 明石昌也

  2024年, 日本外科感染症学会雑誌(Web), 21(1) (1)


• 歯科衛生士が口腔衛生管理を行った患者に対するCOVID-19発症状況について

  岡崎 葉菜, 武田 大介, 片山 めぐみ, 西井 美佳, 村木 友美, 長谷川 巧実, 明石 昌也

  (一社)日本口腔ケア学会, 2023年04月, 日本口腔ケア学会雑誌, 17(3) (3), 172 - 172, 日本語


• COVID-19感染が契機と考えられたスティーブンスジョンソン症候群患者への口腔衛生管理の1例

  片山 めぐみ, 村木 友美, 岡崎 葉菜, 西井 美佳, 武田 大介, 長谷川 巧実, 明石 昌也

  (一社)日本口腔ケア学会, 2023年04月, 日本口腔ケア学会雑誌, 17(3) (3), 229 - 229, 日本語


• 当科における矯正用アンカープレートの臨床統計学的検討

  山下淳也, 鈴木泰明, 塩屋園敦, 筧康正, 江崎友美, 木本明, 南川勉, 古森孝英

  2018年, 日本口腔科学会雑誌(Web), 67(2) (2)


• 急速に増大し巨舌を呈した多発性骨髄腫に伴うアミロイドーシスの1例

  藤田 剛史, 井堂 信二郎, 大槻 有美, 江崎 友美, 長谷川 巧実, 古森 孝英

  症例は81歳女性で、舌縁部の無痛性腫瘤に気づき、近医歯科でhypertrophic scarと診断されたが、徐々に増大傾向を示した。左右舌縁にび漫性の弾性軟の腫脹と圧痕を認め、頬粘膜、下唇は浮腫様で内出血斑がみられた。検査所見では貧血以外に異常はなく、画像検査で腫瘍性病変は認めなかった。舌尖部より生検を行い、アミロイドの沈着を認めたため腫瘍血液科に対診し、骨髄穿刺で多発性骨髄腫(IgGλtype、ISS III期)と診断された。メルファランとデキサメタゾン(DEX)による化学療法が施行されたが、マーカーのβ2マイクログロブリンは減少後増加し、舌の腫大は進行して口唇に多発性の腫瘤を認めた。ボルテゾミブとDEXに変更されたが、口腔内のアミロイド沈着は進行し、粘膜からの出血、血腫を広範に認めた。治療開始4ヵ月で患者・家族はこれ以上の治療を希望されず、自宅療養となったが、退院3日後に多臓器不全により死亡した。

  (公社)日本口腔外科学会, 2015年01月, 日本口腔外科学会雑誌, 61(1) (1), 25 - 30, 日本語


• 顎関節障害を認めた混合性結合組織病の1例

  江崎 友美, 渋谷 恭之, 鈴木 泰明, 古森 孝英

  症例は30歳女性で、幼少期よりアトピー性皮膚炎、23歳時に混合性結合組織病(MCTD)と診断された。両側顎関節部の疼痛と開口障害が悪化し、当科に紹介となった。両側顎関節部に開口時痛と圧痛を認め、両側咬筋、側頭筋、顎二腹筋に圧痛を認め、自力・強制開口位での切歯間距離は24mm、最大開口位保持時間は数秒であった。パノラマX線で両側下顎頭の変形や筋突起過形成は認めず、NRIで両側の復位しない関節円板前方転位、両側下顎頭の骨皮質の菲薄化と断裂、下顎頭上面の凹凸不整、左側の下顎頭から下顎頸部にかけて脂肪髄の消失が認められた。MCTDに併発した顎関節炎と診断した。筋のマッサージを指導し、塩酸チザニジン投与を開始した。徒手による開口訓練を指示し、スタビライゼーション型スプリント療法で顎関節部の疼痛は軽減し、開口量に変化はないが、開口保持時間の延長が認められた。初診より2年7ヵ月経過で顎関節症状は安定し、開口訓練継続で経過観察中である。

  (公社)日本口腔外科学会, 2013年01月, 日本口腔外科学会雑誌, 59(1) (1), 43 - 47, 日本語


• 放射線性下顎骨壊死からの病的骨折に対して下顎骨区域切除を行った2例

  江崎 友美, 古土井 春吾, 竹内 純一郎, 高橋 英哲, 三浦 加織, 古森 孝英

  (NPO)日本口腔科学会, 2012年01月, 日本口腔科学会雑誌, 61(1) (1), 132 - 132, 日本語


• 他科悪性腫瘍患者に対する口腔ケア施行例の臨床的検討 経過不良例を中心に

  村田 真穂, 梅田 正博, 奥田 美穂子, 西井 美佳, 澤田 麻衣子, 江崎 友美, 四宮 玲奈, 白神 翔, 高橋 佑豪, 松井 太輝, 高橋 英哲, 浅井 知子, 竹内 純一郎, 南川 勉, 古土井 春吾, 渋谷 恭之, 古森 孝英

  (一社)日本有病者歯科医療学会, 2010年12月, 有病者歯科医療, 19(3) (3), 189 - 190, 日本語

• 感染性心内膜炎患者における検出菌と口腔内環境に関する調査

  寺脇遥, 村木友美, 岡崎葉菜, 西井美佳, 明石昌也

  第69回日本口腔外科学会総会・学術大会, 2024年11月


• チーム医療セッション 教育講演4 オーラルフレイル：循環器領域と歯科口腔領域の診療連携～歯科医師の立場から～

  村木友美

  第88回日本循環器学会学術集会, 2024年03月


• 小児がん経験患者と歯の発育不全の関連性

  村木 友美・塩屋園 敦・西井 美佳・武田 大介・楠元 順哉・明石 昌也

  第68回公益社団法人 日本口腔外科学会総会・学術大会, 2023年11月


• 口腔扁平上皮癌におけるiPS細胞関連因子の発現率と予後の関連性

  江崎友美, 長谷川巧実, 武田大介, 筧 康正, 明石昌也, 南川 勉, 古森孝英

  第63回（公社）日本口腔外科学会総会・学術大会, 2018年11月


• 放射線性下顎骨壊死からの病的骨折に対して下顎骨区域切除術を行った2例

  江崎友美, 古土井春吾, 竹内純一郎, 高橋英哲, 三浦加織, 古森孝英

  第65回口腔科学会総会・学術集会, 2011年04月


• 混合性結合組織病から開口障害および顎関節症を発症した1例

  江崎友美, 渋谷恭之, 井川恵理, 鈴木泰明, 古森孝英

  第41回口腔外科学会 近畿地方会学術集会, 2010年06月

• 移植筋弁の経年萎縮を予防しうる治療法開発

  村木 友美

  日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 2025年04月01日 - 2029年03月31日


• 生体に害の少ない口腔癌に有効な新規抗癌剤候補分子の探索

  村木 友美

  日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 2021年04月01日 - 2025年03月31日

  分子標的薬や免疫チェック阻害薬の登場により，従来にない発想に基づいた新たな抗癌剤の開発が期待されています。現在歯科口腔外科領域のみならず，日常臨床の現場で頻用されている抗癌剤の代表的なものは、多くは多様で深刻な副作用を伴います。よって「副作用の少ない人体に無害な抗癌剤の開発」は患者さんの苦痛の除去に大きく貢献します。 抗癌剤はDNAの複製・転写の抑制や、成長因子の活性阻害等人体において極めて重要な機能を阻害することで成り立っていることがほとんどです。一方で、副作用の少ない人体に可能な限り無害な抗癌剤を探索する上で一つのきっかけとなるのは正常時における生命維持にそれ程は重要な機能を果たしていない分子であり、かつ病的な状態においてのみ際立って機能する可能性がある分子であると言えます。本申請研究では病的な環境下でのみ機能している可能性がある分子のヒトの癌組織における発現様式や、この病的血管関連分子（JCAD）の遺伝子発現を抑えたノックアウトマウスを用いて研究を行い、病的血管関連分子JCADの癌、特に癌脈管新生における役割を明らかにし、新たな抗癌剤開発のきっかけとすることを目的としています。当該年度は本申請研究の初年度で、まずヒトの口腔癌の中でも歯肉癌にしぼってJCADと血管のマーカーであるCD31とで免疫染色を施行しました。その結果、興味深い結果が得られつつあり、現在解析を進めています。並行してノックアウトマウスを用いた研究も行いました。病的な環境下でも血管新生、および病的血管新生が抑制されているとどのような変化を示すかを調べるため創傷治癒アッセイを行い、現在結果を解析中です。また、本申請研究の主たる目的は癌新生血管におけるJCADの役割を明らかにすることなので、JCADノックアウトマウスを用いて腫瘍移植実験を行い、今後さらに実験回数を増やして解析を進めていく所存です。