Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Surgical dentistry  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   医学部   助教  

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Notch signaling genes and CD8+ T-cell dynamics: Their contribution to immune-checkpoint inhibitor therapy in oral squamous cell carcinoma: A retrospective study.

  Kazuhiro Ogi, Takahiro Iwamoto, Takashi Sasaya, Koyo Nishiyama, Takaaki Tokura, Takanori Sasaki, Hironari Dehari, Yohei Arihara, Kazuyuki Murase, Masato Saito, Masanori Someya, Kohichi Takada, Akihiro Miyazaki

  Cancer medicine   13 ( 5 ) e6985  2024.03  [International journal]

  　View Summary

  BACKGROUND: Aberrant Notch signaling pathway has been related with the tumorigenesis in head and neck region, involving oral cavity. Here, we report the correlation between mutations in the Notch signaling pathway and CD8+ T-cell infiltration via PD-L1, which lead to enhanced antitumor immunity and may target for immune-checkpoint inhibitors (ICIs) therapy. METHODS: This retrospective study analyzed the results of immunohistochemical staining for PD-L1 and CD8+ T-cell infiltration in 10 patients and whole-exome sequencing (WES) was conducted on five of these patients to identify frequently mutated genes. RESULTS: Four of 10 patients were positive for PD-L1 and CD8+ T. By analyzing WES in three of these four patients, we notably identified the mutations of NOTCH1, FBXW7, and noncoding RNA intronic mutation in NOTCH2NLR in two of these three patients. This study may enable better selection of ICI therapy with CD8+ T-cell infiltration via PD-L1 expression for oral squamous cell carcinoma patients with mutations in Notch signaling pathway.

  DOI PubMed

• 広範囲顎骨支持型補綴治療における当科での非可動粘膜獲得のための一工夫

  都倉 尭明, 出張 裕也, 西山 廣陽, 宮本 昇, 大橋 伸英, 佐々木 敬則, 宮崎 晃亘

  Japanese Journal of Maxillo Facial Implants ( (公社)日本顎顔面インプラント学会 )  22 ( 3 ) 177 - 177  2023.11

• Immunohistological evaluation of patients treated with intra-arterial chemoradiotherapy and surgery for oral cancer.

  Yutaro Ikeuchi, Masanori Someya, Tomokazu Hasegawa, Masato Saito, Shoh Mafune, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Hironari Dehari, Kazuhiro Ogi, Takanori Sasaki, Yoshihiko Hirohashi, Toshihiko Torigoe, Naoki Hirokawa, Akihiro Miyazaki, Koh-Ichi Sakata

  Medical molecular morphology    2023.07  [Domestic journal]

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  Preoperative intra-arterial chemoradiotherapy (IACRT) can improve the outcome and reduce the extent of surgery in patients with advanced oral cancer. However, the response to this regimen varies among patients, which may be related to the immune status of the tumor. We investigated the effects of proteins involved in tumor immunity on the outcomes of combined IACRT and surgery for oral cancer. We examined CD8 + and FoxP3 + tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on immune cells and tumor cells in pretreatment biopsy samples from 69 patients diagnosed with oral cancer treated with IACRT at our institution during 2000-2020. Patients with abundant CD8 + TILs had significantly better 5-year disease-specific survival (DSS) compared to that of patients with less infiltration of these cells (P = 0.016). Patients with higher FoxP3 + T-cells invasion had significantly better DSS compared to that of less FoxP3 (P = 0.005). Patients with high PD-L1 expression in tumor cells and immune cells had significantly better DSS than that of patients with low PD-L1 expression in these cells (P = 0.009 and P = 0.025, respectively). Collectively, these results suggest that the tumor immune microenvironment could affect outcomes of IACRT treatment in oral cancer.

  DOI PubMed

• Accurate estimation of skeletal muscle mass by comparison of computed tomographic images of the third lumbar and third cervical vertebrae in Japanese patients with oral squamous cell carcinoma.

  Nobuhide Ohashi, Kazushige Koike, Kurumi Sakai, Koyo Nishiyama, Takanori Sasaki, Kazuhiro Ogi, Hironari Dehari, Nobumichi Kobayashi, Akihiro Miyazaki

  Oral radiology   39 ( 2 ) 408 - 417  2022.09  [Domestic journal]

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  OBJECTIVES: We evaluated the accuracy of estimating the cross-sectional area (CSA) at the third lumbar vertebra (L3) based on the CSA at the third cervical vertebra (C3) using computed tomographic images, and we identified the sources of error and bias using the evaluation of absolute reliability in 89 Japanese patients with oral squamous cell carcinoma. METHODS: Skeletal muscle CSA was measured at the C3 and L3 on pretreatment computed tomographic images. We used the CSA at the C3 to estimate CSA at the L3 in an existing prediction formula. Correlation coefficients were used to evaluate the relative reliability of the estimate, and Bland-Altman analysis and minimum detectable change (MDC) were used to evaluate its absolute reliability. RESULTS: Estimated and actual CSAs at L3 were strongly correlated (r = 0.885, p < 0.001). The mean difference between the estimated and actual CSAs was - 1.0887 cm2, the 95% confidence interval was - 4.09 to 1.91 cm2 (p = 0.472), and the 95% limits of agreement were - 29.0 and 26.8 cm2. The MDC at the 95% level of confidence in estimated and actual CSAs was 27.9 cm2. CONCLUSIONS: The estimation of CSA at the L3 from the existing prediction formula with the CSA at the C3 had no systematic biases, but it did have random errors. Random errors resulted from measurement errors and biological variation. Usefulness of the existing formula is limited by physical differences in populations.

  DOI PubMed

• Clinical and histopathologic effects of neoadjuvant intra-arterial chemoradiotherapy with cisplatin in combination with oral S-1 on stage III and IV oral cancer.

  Kazushige Koike, Nobuhide Ohashi, Koyo Nishiyama, Junya Okamoto, Takanori Sasaki, Kazuhiro Ogi, Hironari Dehari, Naoki Hirokawa, Masanori Someya, Masato Saito, Hiroki Okuda, Akemi Otani, Tomoko Sonoda, Taro Sugawara, Tadashi Hasegawa, Hiroyoshi Hiratsuka, Koh-Ichi Sakata, Akihiro Miyazaki

  Oral surgery, oral medicine, oral pathology and oral radiology   134 ( 3 ) 347 - 353  2022.09  [International journal]

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  OBJECTIVE: The aim of this study was to examine the clinical and histopathologic effects of neoadjuvant intra-arterial chemoradiotherapy (IACRT) using cisplatin in combination with oral S-1 (tegafur/gimeracil/oteracil potassium) on stage III and IV oral squamous cell carcinoma. STUDY DESIGN: Thirty patients received infusions of superselective intra-arterial cisplatin 60 mg/m2 by the Seldinger method and conventional external beam radiotherapy (total 40 Gy) combined with oral S-1 on the day of irradiation. Curative surgery and neck dissection were performed 4 to 6 weeks after IACRT. The clinical response of the primary lesion was evaluated approximately 4 weeks after IACRT. The surgically resected specimens were examined for histologic features according to the grading system for histologic evaluation and for residual tumor grade (RGrades). RESULTS: Histopathologic evaluation of the therapeutic effect was grade 2 in 10 patients and grade 3 in 16 patients. According to the distribution of RGrades, the remaining tumor cells were mostly in the central area of the primary lesion, as seen in 24 patients. CONCLUSIONS: These findings indicate that neoadjuvant IACRT with cisplatin and oral S-1 was an effective treatment, suggesting the possibility of reducing the extent of curative surgery based on RGrades.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 第VII因子欠乏症患者に対して顎矯正手術を行った1例

  都倉 尭明, 出張 裕也, 桜田 奈保, 橋 雄馬, 木山 望, 上田 愛, 大橋 伸英, 佐々木 敬則, 宮崎 晃亘

  日本顎変形症学会雑誌 ( (NPO)日本顎変形症学会 )  34 ( 2 ) 114 - 114  2024.05

• 超高齢者に発症した下顎骨骨髄炎に起因する壊死性筋膜炎の1例

  榎本 隆久, 佐々木 敬則, 大和田 哲志, 桜田 奈保, 上野 智史, 都倉 尭明, 岡本 準也, 荻 和弘, 出張 裕也, 宮崎 晃亘

  日本口腔科学会雑誌 ( (NPO)日本口腔科学会 )  73 ( 1 ) 38 - 38  2024.03

• NOTCHシグナル伝達系の遺伝子変異は,再発口腔癌における免疫チェックポイント阻害剤の治療効果に影響する

  荻 和弘, 岩本 空大, 笹谷 聖, 都倉 尭明, 佐々木 敬則, 平塚 博義, 宮崎 晃亘

  頭頸部癌 ( (一社)日本頭頸部癌学会 )  49 ( 2 ) 156 - 156  2023.05

• ProPlan CMFを用いた,簡便な3Dサージカルガイドの作製の試み

  都倉 尭明, 出張 裕也, 橋 雄馬, 木山 望, 上田 愛, 大橋 伸英, 佐々木 敬則, 宮崎 晃亘

  日本顎変形症学会雑誌 ( (NPO)日本顎変形症学会 )  33 ( 2 ) 154 - 154  2023.05

• 超選択的動注化学療法施行後にコレステロール塞栓症を発症した口底癌の1例

  佐々木 敬則, 都倉 尭明, 岡本 準也, 中井 裕美, 土橋 恵, 笹谷 聖, 荻 和弘, 出張 裕也, 宮崎 晃亘

  日本口腔腫瘍学会誌 ( (一社)日本口腔腫瘍学会 )  34 ( 4 ) 183 - 189  2022.12

  　View Summary

  コレステロール塞栓症は,大血管壁にある粥腫が破綻し,コレステロール結晶が血中に流出することで末梢に塞栓をきたす疾患であり,カテーテル検査や心臓血管手術などが原因で発症する。今回,われわれは超選択的動注化学療法施行後にコレステロール塞栓症を発症した口底癌の1例を経験したので,その概要を報告する。症例は81歳男性,右側口底癌(T2N1M0,Stage III)。臓器機能温存を強く希望したため,放射線治療(66Gy)併用で計4回のSeldinger法による超選択的動注化学療法(CDDP)を施行した。5回目の超選択的動注化学療法を行う前に,右足趾の疼痛,紫紅色斑の出現と急激な腎機能低下(血清Cr値:1.92mg/dl,eGFR値:26.9ml/min)を認め,当院皮膚科で施行した組織生検でコレステロール塞栓症の病理組織学的診断を得た。ステロイドおよびプロスタサイクリン(PGI2)製剤経口投与により右足趾の疼痛は改善を認めたが,腎機能は改善しなかった。ステロイド治療終了後,外来で経過観察を行っていたところ,3ヵ月後に頸部リンパ節の再増大を認め,全身薬物療法を開始したが,10ヵ月後に肺炎により他病死した。Seldinger法では1%程度で脳梗塞が発症すると報告されている。一方,コレステロール塞栓症の発症は非常にまれではあるものの,血液透析に移行する可能性の高い予後不良な疾患である。治療法選択の際には十分に念頭に置くべき疾患の1つと考えられた。(著者抄録)

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• 若手研究奨励賞

  2011   日本がん免疫学会  

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• Elucidation of the mechanisms relating to immunoregulation in oral tumor microenvironment and development of novel treatments

  Grant-in-Aid for Scientific Research (B)

  Project Year :

  2023.04

  -

  2026.03

   

  宮崎 晃亘, 佐々木 敬則, 宮本 昇, 笹谷 聖, 加藤 大貴

• 口腔がん免疫療法に抗NKG2A抗体を併用した新たな機能温存治療の開発

  若手研究

  Project Year :

  2020.04

  -

  2023.03

   

  佐々木 敬則

  　View Summary

  令和3年度は口腔がん患者の組織検体でHLA-EおよびNKG2Aの免疫染色を行った。現在、解析を行っている。また樹立した癌細胞株のHLA-E発現とTILのNKG2A発現をフローサイトメトリーで確認し、解析を行っている。

• Basic and clinical study of new peptide vaccine therapy for patients with oral cancer

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2013.04

  -

  2016.03

   

  Miyazaki Akihiro, KOBAYASHI Jun-ichi, SASAKI Takanori, FUJINO Junki, MICHIFURI Yoshitaka

  　View Summary

  We described a sequential clinical trial of SVN-2B peptide vaccine therapy in combination with incomplete Freund’s adjuvant (IFA) and interferon (IFN)-alpha for patients with oral cancer. Results indicated that the combination therapy increased the frequency of peptide specific cytotoxic T lymphocytes (CTLs) more effectively than the peptide alone. This regimen may be useful as a new therapeutic modality. We isolated oral cancer stem-like cells (CSCs) as aldehyde dehydrogenase 1 bright (ALDH1br) cells. SPRR1B gene was shown to be overexpressed in the ALDH1br cells, indicating that it has a role in cell growth and maintenance by suppression of RASSF4. Furthermore, we established an oral cancer cell line and an autologous CTL line. It was shown that the CTL line recognized autologous tumor cells in an HLA-A24-restricted manner. Precise analyses of the CTL-recognized antigens may provide us with substantial strategies toward developing a more effective cancer peptide vaccine.

• Analysis of the β catenin gene abnormality and therapeutic application for oral cancer.

  Grant-in-Aid for Scientific Research (B)

  Project Year :

  2010

  -

  2012

   

  HIRATSUKA Hiroyoshi, DEHARI Hironari, MIYAZAKI Akihiro, OGI Kazuhiro, SASAKI Takanori, NAKAMORI Kenji, KOBAYASHI Jyunichi, SOGABE Youhei, YAMAMOTO Takashi, SHIMANISHI Makoto

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  Hypoxic regions in solid tumors mediate malignant transformation, cancer cell proliferation, resistance to anti-cancer agents, and enhanced cellular invasion and metastasis. In this study, we found that the wnt/β-catenin pathway activation mediates the acquisition of invasion and metastatic potential in oral squamous cell carcinoma cells. Hypoxia enhances the expression of glucose transporter 1 (GLUT1) and anticancer drug resistance, and activates NF-κB/p65 to trigger cell proliferation.

• Development of cancer peptide vaccine therapy for oral cancer

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2010

  -

  2012

   

  MIYAZAKI Akihiro, YAMAGUCHI Akira, KOBAYASHI Jyunichi, YAMAMOTO Takashi

  　View Summary

  We have confirmed the safety and efficacy of a cancer peptide vaccine therapy using a survivin2B-derived peptide decomposed from a survivin protein that is highly expressed in many malignancies. Furthermore, a clinical trial indicated that when using the peptide in conjunction with stimulants, a stronger immune effect could be obtained than from the peptide alone. The trial also confirmed the safety of the vaccine therapy. In the quest to develop a cancer peptide vaccine other than survivin, we have identified molecules that are highly expressed in cancer stem cells of the oral cavity, and established a foundation towards a more effective clinical application of cancer peptide vaccine therapy.