Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2014.04

  -

  Now

  Sapporo Medical University   School of Medicine   講師

• 2013.01

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  2013.12

  Sapporo Medical University   医学部口腔外科学講座   訪問研究員

• 2007.04

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  2012.12

  Sapporo Medical University   医学部口腔外科学講座   助教

• 2005.04

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  2007.03

  ペンシルベニア大学   医学部   訪問研究員

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   講師  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• 臨床腫瘍学

• 薬剤感受性

• 低酸素応答

• ユビキチンリガーゼ

• チェックポイント

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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

• 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]

  　View Summary

  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

• A rare case report of diverticulum of the buccal mucosa

  Kazushige Koike, Hinako Mori, Kazuhiro Ogi, Makiya Jin, Satoshi Ohwada, Takahiro Iwamoto, Shintaro Sugita, Tadashi Hasegawa, Akihiro Miyazaki

  Clinical Case Reports ( Wiley )  11 ( 7 )  2023.07

  DOI

• Exploring olfactory receptor family 7 subfamily C member 1 as a novel oral cancer stem cell target for immunotherapy.

  Sho Miyamoto, Yoshihiko Hirohashi, Rena Morita, Akihiro Miyazaki, Kazuhiro Ogi, Takayuki Kanaseki, Kentaro Ide, Jumpei Shirakawa, Tomohide Tsukahara, Aiko Murai, Takashi Sasaya, Kazushige Koike, Shinichiro Kina, Toshihiro Kawano, Takahiro Goto, Edward Hosea Ntege, Yusuke Shimizu, Toshihiko Torigoe

  Cancer science   114 ( 9 ) 3496 - 3508  2023.06  [International journal]

  　View Summary

  The mortality rate of oral cancer has not improved over the past three decades despite remarkable advances in cancer therapies. Oral cancers contain a subpopulation of cancer stem cells (CSCs) that share characteristics associated with normal stem cells, including self-renewal and multi-differentiation potential. CSCs are tumorigenic, play a critical role in cancer infiltration, recurrence, and distant metastasis, and significantly contribute to drug resistance to current therapeutic strategies, including immunotherapy. Cytotoxic CD8+ T lymphocytes (CTLs) are key immune cells that effectively recognize peptide antigens presented by the major histocompatibility complex class I molecules. Increasing evidence suggests that cancer antigen-specific targeting by CTLs effectively regulates CSCs that drive cancer progression. In this study, we utilized data from public domains and performed various bioassays on human oral squamous cell carcinoma clinical samples and cell lines, including HSC-2 and HSC-3, to investigate the potential role of olfactory receptor family 7 subfamily C member 1 (OR7C1), a seven transmembrane G-protein-coupled olfactory receptor that is also expressed in nonolfactory tissues and was previously reported as a novel marker and target of colon cancer initiating cell-targeted immunotherapy, in CSC-targeted treatment against oral cancer. We found that the OR7C1 gene was expressed only in oral CSCs, and that CTLs reacted with human leukocyte antigen-A24-restricted OR7C1 oral CSC-specific peptides. Taken together, our findings suggest that OR7C1 represents a novel target for potent CSC-targeted immunotherapy 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]

  　View Summary

  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

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• A study on the association between distribution of immunocompetent cells and prognosis in patients with oral cancer

  Kazushige Koike, Koyo Nishiyama, Hironari Dehari, Kazuhiro Ogi

  CANCER SCIENCE ( WILEY )  113   1613 - 1613  2022.02

  Research paper, summary (international conference)  

• Stage III・IVの口腔扁平上皮癌に対する動注化学療法併用放射線治療の治療効果に関する検討

  小池和茂, 岡本準也, 西山廣陽, 佐々木敬則, 荻和弘, 出張裕也, 宮崎晃亘

  頭頸部癌   47 ( 2 )  2021

  J-GLOBAL

• 再発または遠隔転移を有する口腔癌に対しニボルマブ投与は遺伝子変異が指標となるか

  荻和弘, 小林淳一, 小林淳一, 西山廣陽, 小池和茂, 高田弘一, 染谷正則, 宮崎晃亘

  日本癌治療学会学術集会(Web)   58th  2020

  J-GLOBAL

• Cancer immunotherapy for oral cancer: Research toward clinical applications of personalized combination immunotherapy

  宮崎晃亘, 荻和弘, 小池和茂, 岡本準也, 出張裕也, 中井裕美

  月刊Precision Medicine   3 ( 14 )  2020

  J-GLOBAL

• Prognostic impact of HLA class Ι expression and its association with CD8⁺T-cell density in oral squamous cell carcinoma

  小池和茂, 出張裕也, 西山廣陽, 荻和弘, 笹谷聖, 土橋恵, 畠中柚衣, 畠中柚衣, 塚原智英, 鳥越俊彦, 宮崎晃亘

  日本癌学会学術総会抄録集(Web)   79th  2020

  J-GLOBAL

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 遺伝子変異とがん免疫環境は口腔癌の免疫チェックポイント阻害薬の奏効率の指標となる

  基盤研究(C)

  Project Year :

  2022.04

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  2025.03

   

  荻 和弘, 笹谷 聖, 西山 廣陽, 岩本 空大

• p53の機能獲得変異は口腔扁平上皮癌の治療標的となり得るか

  基盤研究(C)

  Project Year :

  2022.04

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  2025.03

   

  松田 亜沙実, 佐々木 泰史, 荻 和弘

• 再発口腔がんに対する遺伝子変異量が免疫チェックポイント阻害剤の有効性を検証する

  基盤研究(C)

  Project Year :

  2019.04

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  2023.03

   

  荻 和弘, 西山 廣陽, 宮本 昇

  　View Summary

  Nivolumabの治療効果はCD8陽性T細胞(CTL)の腫瘍内浸潤とPD-L1の発現に依存しており、CPS（Combined Positive Score）が20以上の症例ではPFSが有意に延長された事が報告されている。しかしながら治療奏効例で腫瘍浸潤エフェクターT細胞上のPD-1発現が有意に高かったものの、一部の症例では腫瘍浸潤エフェクターT細胞上のPD-1発現が高いにもかかわらずPD-1／PD-L1阻害剤治療が奏功しなかったため、さらなるバイオマーカー探索をすすめ、口腔がん特異的な網羅的なドライバー遺伝子に着目した。変異解析の結果、p53、CCND1の他に、遺伝子変異の頻度の少ないNOTCH１の遺伝子変異を認めた。 NOTCH１の遺伝子変異を認めた症例においては、CD8陽性/PD-L1陽性で、Nivolumab 投与後にpsuedo-progressionを示し、その後の救済化学療法が著効しCR（Complete Response）評価となった。また他のCD8陽性/PD-L1陽性の症例においても、Notchシグナル伝達系の異常を認めた。 口腔がん患者の生検検体と治療前の血漿からcDNAを抽出し、次世代シークエンス（NGS）をもちいて全エクソーム解析を行った。化学放射線治療後にPD（Progression disease)評価をした症例で、NOTCH2NLB遺伝子のフレームシフト変異を認めた。以上からNotch経路の異常はCD8+T細胞の発現を制御しているとの仮説を立て検証している。 現在、様々な口腔がん細胞株からcDNAを抽出し、Notch1-4遺伝子の発現量についてreal-time PCRによる解析を行っている。Notch 3,4の発現は乏しく、Notch 1,2遺伝子の発現は細胞株によって異なることが明らかにされた。

• The elucidation of tumor microenvironment in invasive front of oral cancer and its application to therapy

  Grant-in-Aid for Challenging Exploratory Research

  Project Year :

  2016.04

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  2018.03

   

  Hiratsuka Hiroyoshi

  　View Summary

  91 cases of cT1,2N0M0 OSCC treated with transoral resection of the primary tumor were assessed based on 3 types of invasive tumor patterns on histopathologic and pancytokeratin-stained immunohistological sections: the mode of invasion, worst pattern of invasion (WPOI), and tumor budding. The correlations among invasive tumor patterns, regional metastasis, and disease-free survival were analyzed. Of the 91 cases, 22 had pathologically proven regional metastasis. The mode of invasion and tumor budding were associated with regional metastasis as well as lymphovascular invasion in univariate analysis. All three invasive patterns, the mode of invasion, WPOI, and tumor budding, were found to be significant predictors of 5-year disease-free survivalas well as lymphovascular invasion and perineural invasion. Our results indicate that the intensity of tumor budding may be a novel diagnostic biomarker, as well as a therapeutic tool, for regional metastasis in patients with cT1,2N0M0 OSCC.

• A novel design of metabolic target therapy in oral cancer cells

  Grant-in-Aid for Challenging Exploratory Research

  Project Year :

  2014.04

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  2017.03

   

  Ogi Kazuhiro

  　View Summary

  2 - DG (2 - deoxy - D - glucose), a glucose metabolism inhibitor takes into tumor cells, but the amount of uptakes are depending on the phenotype of tumor cells. In our study, we established mice xenograft models with oral squamous cell carcinoma cell line , and we examined the antitumor effect by the combination of radiotherapy with 2-DG. As a result, in the group of the combination of radiotherapy with 2-DG, there is a significant tumor growth suppression compared with the control group and 2-DG alone. Our study suggested that 2-DG has synergistic effects when combined with radiotherapy, which might lead to the design of an effective metabolic target therapy.

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