Updated on 2025/05/19

写真a

 
Yoshihiro Aizawa
 
Organization
School of Medicine Medical Course Otorhinolaryngology Head and Neck Surgery Assistant Professor
Title
Assistant Professor
External link

Research Interests

  • 患者腫瘍組織移植モデル

  • オルガノイド

  • 唾液腺癌

  • 頭頸部癌

  • バイオインフォマティクス

Research Areas

  • Life Science / Otorhinolaryngology

Papers

  • Establishment of experimental salivary gland cancer models using organoid culture and patient-derived xenografting. International journal

    Yoshihiro Aizawa, Kentaro Takada, Jun Aoyama, Daisuke Sano, Shoji Yamanaka, Masahide Seki, Yuta Kuze, Jordan A Ramilowski, Ryo Okuda, Yasuharu Ueno, Yusuke Nojima, Yoshiaki Inayama, Hiromitsu Hatakeyama, Takashi Hatano, Hideaki Takahashi, Goshi Nishimura, Satoshi Fujii, Yutaka Suzuki, Hideki Taniguchi, Nobuhiko Oridate

    Cellular oncology (Dordrecht)   46 ( 2 )   409 - 421   2023.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    PURPOSE: Depending on its histological subtype, salivary gland carcinoma (SGC) may have a poor prognosis. Due to the scarcity of preclinical experimental models, its molecular biology has so far remained largely unknown, hampering the development of new treatment modalities for patients with these malignancies. The aim of this study was to generate experimental human SGC models of multiple histological subtypes using patient-derived xenograft (PDX) and organoid culture techniques. METHODS: Tumor specimens from surgically resected SGCs were processed for the preparation of PDXs and patient-derived organoids (PDOs). Specimens from SGC PDXs were also processed for PDX-derived organoid (PDXO) generation. In vivo tumorigenicity was assessed using orthotopic transplantation of SGC organoids. The pathological characteristics of each model were compared to those of the original tumors using immunohistochemistry. RNA-seq was used to analyze the genetic traits of our models. RESULTS: Three series of PDOs, PDXs and PDXOs of salivary duct carcinomas, one series of PDOs, PDXs and PDXOs of mucoepidermoid carcinomas and PDXs of myoepithelial carcinomas were successfully generated. We found that PDXs and orthotopic transplants from PDOs/PDXOs showed similar histological features as the original tumors. Our models also retained their genetic traits, i.e., transcription profiles, genomic variants and fusion genes of the corresponding histological subtypes. CONCLUSION: We report the generation of SGC PDOs, PDXs and PDXOs of multiple histological subtypes, recapitulating the histological and genetical characteristics of the original tumors. These experimental SGC models may serve as a useful resource for the development of novel therapeutic strategies and for investigating the molecular mechanisms underlying the development of these malignancies.

    DOI： 10.1007/s13402-022-00758-6

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  • Effect of HER2-targeted therapy on PDX and PDX-derived organoids generated from HER2-positive salivary duct carcinoma. International journal

    Jun Aoyama, Yusuke Nojima, Daisuke Sano, Yuri Hirai, Natsumi Kijima, Yoshihiro Aizawa, Kentaro Takada, Takashi Hatano, Hideaki Takahashi, Goshi Nishimura, Nobuhiko Oridate

    Head & neck   45 ( 7 )   1801 - 1811   2023.7

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    Language：English   Publishing type：Research paper (scientific journal)  

    BACKGROUND: We previously established a patient-derived xenograft (PDX) model, patient-derived organoids (PDOs), and PDX-derived organoids (PDXOs) for salivary duct carcinoma (SDC). Using these models, this study examined the therapeutic effect of human epidermal growth factor receptor 2 (HER2) blockade on HER2-positive SDC. METHODS: The therapeutic effect of lapatinib was assessed in SDC PDXOs with regards to cell growth, receptor/downstream signaling molecule expression, phosphorylation levels, and apoptosis. Effect of lapatinib treatment was evaluated in vivo in SDC PDX mice. RESULTS: The siRNA knockdown of HER2 and lapatinib suppressed cell proliferation in SDC PDXOs. Lapatinib inhibited the phosphorylation of HER2 and its downstream targets, and induced apoptosis in SDC PDXOs. Lapatinib also significantly reduced tumor volumes compared with that of the control in SDC PDX mice. CONCLUSION: For the first time, we demonstrated the efficacy of anti-HER2 therapy in HER2-positive SDC using preclinical models of SDC PDX and PDXO.

    DOI： 10.1002/hed.27395

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  • 当院における下顎歯肉癌に対する下顎骨区域切除術後の早期退院への試み

    古川 駿, 中山 明仁, 田中 久美子, 逆井 清, 相澤 圭洋, 百束 紘, 森 義明, 折舘 伸彦

    神奈川医学会雑誌   50 ( 2 )   57 - 57   2023.7

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  • P4HA1 Promotes Cell Migration and Colonization in Hypopharyngeal Squamous Cell Carcinoma. International journal

    Kaname Sato, Daisuke Sano, Hideaki Takahashi, Tatsu Kuwahara, Yoshihiro Aizawa, Jun Aoyama, Yusuke Nojima, Takashi Hatano, Yasuhiro Arai, Goshi Nishimura, Hiromitsu Hatakeyama, Nobuhiko Oridate

    Anticancer research   43 ( 6 )   2571 - 2582   2023.6

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    BACKGROUND/AIM: This study aimed to identify key molecules associated with the survival of patients with hypopharyngeal squamous cell carcinoma (HpSCC) by combining in silico and in vitro analyses. MATERIALS AND METHODS: Differentially expressed genes (DEGs) were screened using the Gene Expression Omnibus database. For DEGs, we performed functional enrichment and protein-protein interaction network analyses to identify potential biological functions and hub genes. Functional analysis of HpSCC cell lines verified the critical roles of the hub genes. RESULTS: DEGs were associated with the extracellular matrix. Among the hub genes, high expression of prolyl 4-hydroxylase subunit alpha 1 (P4HA1) was significantly associated with shorter survival. In addition, P4HA1 knockdown inhibited cell migration and colonization. Suppression of cell proliferation was demonstrated using P4HA1-selective inhibitors. CONCLUSION: P4HA1 may be a useful therapeutic target for the treatment of HpSCC.

    DOI： 10.21873/anticanres.16424

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  • オルガノイド培養技術とPatient-derived xenograftモデルを用いた唾液腺癌モデル作製

    佐野 大佑, 相澤 圭洋, 青山 準, 野島 雄介, 高田 顕太郎, 高橋 秀聡, 折舘 伸彦

    日本唾液腺学会誌   62   37 - 37   2022.11

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  • ヒトHER2陽性唾液腺導管癌由来オルガノイドによるin vitro/in vivoでの薬効評価(Drug evaluation using patient-derived organoid of HER2-positive salivary duct carcinoma in vitro and in vivo)

    青山 準, 野島 雄介, 相澤 圭洋, 高田 顕太郎, 鬼島 菜摘, 平井 友梨, 波多野 孝, 高橋 秀聡, 佐野 大佑, 藤井 誠志, 折舘 伸彦

    日本癌学会総会記事   81回   P - 1287   2022.9

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  • FosL1 Regulates Regional Metastasis of Head and Neck Squamous Cell Carcinoma by Promoting Cell Migration, Invasion, and Proliferation. International journal

    Hiroshi Hyakusoku, Kae Sawakuma, Daisuke Sano, Hideaki Takahashi, Takashi Hatano, Kaname Sato, Yasuhiro Isono, Shoko Shimada, Kentaro Takada, Tatsu Kuwahara, Yoshihiro Aizawa, Nobuhiko Oridate

    Anticancer research   41 ( 7 )   3317 - 3326   2021.7

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    BACKGROUND/AIM: We evaluated the impact of FosL1, a member of the activated protein-1 family, on the pathways leading to regional metastasis of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: We examined the influence of small interfering RNA (siRNA) and short heparin RNA (shRNA) mediated knockdown of FosL1 on cell migration, invasion, and proliferation in vitro as well as on regional metastasis in vivo. The prognostic significance of FosL1 was also analyzed using the Kaplan- Meier plotter using data from an HNSCC patient database. RESULTS: Down-regulation of FosL1 inhibited cell migration, invasion, and proliferation in vitro, decreased the incidence of regional metastases, and prolonged the survival of mice in vivo. We also determined that HNSCC patients with higher expression levels of FosL1 had a significantly shorter survival time than those with low expression of FosL1. CONCLUSION: FosL1 plays a crucial role in promoting cell migration, invasion, and proliferation in HNSCC.

    DOI： 10.21873/anticanres.15119

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  • 癌細胞のp53喪失は癌微小環境における神経の成長と再プログラムを通じて癌の進展を促す

    高橋 秀聡, 佐野 大佑, 波多野 孝, 佐藤 要, 桑原 達, 相澤 圭洋, 青山 準, 折舘 伸彦

    日本癌学会総会記事   79回   OE11 - 8   2020.10

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  • FOSL1 promotes regional metastasis of head and neck squamous cell carcinoma Reviewed

    Sano Daisuke, Sawakuma Kae, Hyakusoku Hiroshi, Hatano Takashi, Isono Yasuhiro, Takada Kentaro, Sato Kaname, Kuwahara Tatsu, Aizawa Yoshihiro, Oridate Nobuhiko

    CANCER SCIENCE   109   526   2018.12

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MISC

  • 日本人難聴患者より認められた新規OTOGバリアントおよび臨床的特徴

    荒井 康裕, 和田 昂, 高田 顕太郎, 相澤 圭洋, 逆井 清, 森下 大樹, 折舘 伸彦, 西尾 信哉, 宇佐美 真一

    日本耳科学会総会・学術講演会抄録集   34回   181 - 181   2024.10

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    Language：Japanese   Publisher：(一社)日本耳科学会  

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  • 外側半規管瘻孔を生じた術後性乳突腔障害の1例

    和田 昂, 荒井 康裕, 高田 顕太郎, 森下 大樹, 相澤 圭洋, 逆井 清, 折舘 伸彦

    日本耳科学会総会・学術講演会抄録集   34回   384 - 384   2024.10

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  • 当科で経験した悪性外耳道炎5症例

    相澤 圭洋, 和田 昴, 荒井 康裕, 折舘 伸彦

    日本耳科学会総会・学術講演会抄録集   34回   336 - 336   2024.10

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  • 人工内耳装用を長期間中止した後に再装用した症例

    蜂谷 純, 吉田 佳那, 松永 由, 相澤 圭洋, 荒井 康裕, 畠山 博充

    言語聴覚研究   21 ( 3 )   325 - 325   2024.9

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  • 当院における深頸部膿瘍57例の臨床的検討

    足立 和斗, 佐久間 巴, 福井 健太, 吉田 興平, 大氣 大和, 相澤 圭洋, 勝又 徳行, 波多野 孝, 畠山 博充, 折舘 伸彦

    神奈川医学会雑誌   51 ( 2 )   89 - 90   2024.7

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  • 喉頭截開により摘出した喉頭横紋筋腫の一例

    足立 和斗, 畠山 博充, 波多野 孝, 勝又 徳行, 相澤 圭洋, 大氣 大和, 吉田 興平, 佐久間 巴, 福井 健太, 折舘 伸彦

    神奈川医学会雑誌   51 ( 1 )   55 - 55   2024.1

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  • 両側外耳道閉鎖症に対して両側骨固定型補聴器埋め込みを行った症例

    相澤 圭洋, 高田 顕太郎, 荒井 康裕, 和田 昂, 折舘 伸彦

    日本耳科学会総会・学術講演会抄録集   33回   375 - 375   2023.11

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  • 同胞症例における遺伝性難聴の検討

    荒井 康裕, 高田 顕太郎, 和田 昂, 森下 大樹, 相澤 圭洋, 逆井 清, 西尾 信哉, 宇佐美 真一, 折舘 伸彦

    日本耳科学会総会・学術講演会抄録集   33回   380 - 380   2023.11

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    Language：Japanese   Publisher：(一社)日本耳科学会  

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  • 経蝶形骨洞アプローチ下腫瘍摘出術における当院提案鼻中隔切開法の有用性

    大氣 大和, 中村 大志, 桑原 達, 福井 健太, 足立 和斗, 佐久間 巴, 吉田 興平, 相澤 圭洋, 勝又 徳行, 波多野 孝, 畠山 博充, 坂田 勝巳, 折舘 伸彦

    日本鼻科学会会誌   62 ( 3 )   514 - 514   2023.9

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  • 急性進行性感音難聴を呈した小児小脳橋角部海綿状血管腫の一例

    百束 紘, 逆井 清, 相澤 圭洋, 古川 駿, 森 義明, 中山 明仁

    日本耳鼻咽喉科頭頸部外科学会会報   126 ( 4 )   635 - 635   2023.4

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  • 6cm小切開喉頭亜全摘出術 手技の開発と初期臨床治験

    中山 明仁, 森 義明, 百束 紘, 古川 駿, 相澤 圭洋, 逆井 清, 折舘 伸彦

    日本耳鼻咽喉科頭頸部外科学会会報   126 ( 4 )   564 - 564   2023.4

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  • 化学療法が有効であった気管扁平上皮癌の1例

    森 義明, 相澤 圭洋, 逆井 清, 古川 駿, 百束 紘, 中山 明仁, 吉村 太一

    日本気管食道科学会会報   74 ( 2 )   s29 - s29   2023.4

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  • 高齢・高リスク患者の進行喉頭癌に対して6cm皮膚切開で喉頭全摘出術を施行した一例

    逸見 真弘, 中山 明仁, 森 義明, 百足 紘, 古川 駿, 相澤 圭洋, 逆井 清, 折舘 伸彦

    神奈川医学会雑誌   50 ( 1 )   34 - 34   2023.1

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  • Empty nose syndromeの3症例

    中山 明仁, 森 義明, 百束 紘, 古川 駿, 相澤 圭洋, 逆井 清, 田中 久美子, 折舘 伸彦

    神奈川医学会雑誌   50 ( 1 )   36 - 37   2023.1

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  • オルガノイド培養技術とPatient-derived xenograftモデルを用いた唾液腺癌モデル作製

    佐野 大佑, 相澤 圭洋, 青山 準, 野島 雄介, 高田 顕太郎, 高橋 秀聡, 折舘 伸彦

    日本唾液腺学会誌   62   37 - 37   2022.11

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  • ヒトHER2陽性唾液腺導管癌由来オルガノイドによるin vitro/in vivoでの薬効評価(Drug evaluation using patient-derived organoid of HER2-positive salivary duct carcinoma in vitro and in vivo)

    青山 準, 野島 雄介, 相澤 圭洋, 高田 顕太郎, 鬼島 菜摘, 平井 友梨, 波多野 孝, 高橋 秀聡, 佐野 大佑, 藤井 誠志, 折舘 伸彦

    日本癌学会総会記事   81回   P - 1287   2022.9

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  • Establishment of PDX-derived salivary adenoid cystic carcinoma cell lines using organoid culture method. International journal

    Kentaro Takada, Yoshihiro Aizawa, Daisuke Sano, Ryo Okuda, Keisuke Sekine, Yasuharu Ueno, Shoji Yamanaka, Jun Aoyama, Kaname Sato, Tatsu Kuwahara, Takashi Hatano, Hideaki Takahashi, Yasuhiro Arai, Goshi Nishimura, Hideki Taniguchi, Nobuhiko Oridate

    International journal of cancer   148 ( 1 )   193 - 202   2021.1

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    Language：English   Publisher：(一社)日本癌学会  

    To generate a reliable preclinical model system exhibiting the molecular features of salivary adenoid cystic carcinoma (ACC) whose biology is still unclear due to the paucity of stable cell cultures. To develop new in vitro and in vivo models of ACC, the techniques of organoid culture and patient-derived tumor xenograft (PDX), which have attracted attention in other malignancies in recent years, were applied. Tumor specimens from surgically resected salivary ACC were proceeded for the preparation of PDX and organoid culture. The orthotopic transplantation of patient-derived or PDX-derived organoids was demonstrated into submandibular glands of NSG mice and those histology was evaluated. PDX-derived organoid cells were evaluated for the presence of MYB-mediated fusion genes and proceeded for in vitro drug sensitivity assay. Human ACC-derived organoids were successfully generated in three-dimensional culture and confirmed the ability of these cells to form tumors by orthotopic injection. Short-term organoid cell cultures from two individual ACC PDX tumors were also established that maintain the characteristic MYBL1 translocation and histological features of the original parent and PDX tumors. Finally, the establishment of drug sensitivity tests on these short-term cultured cells was confirmed using three different agents. This is the first to report an approach for the generation of human ACC-derived organoids as in vitro and in vivo cancer models, providing insights into understanding of the ACC biology and creating personalized therapy design for patients with ACC.

    DOI： 10.1002/ijc.33315

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  • 癌細胞のp53喪失は癌微小環境における神経の成長と再プログラムを通じて癌の進展を促す

    高橋 秀聡, 佐野 大佑, 波多野 孝, 佐藤 要, 桑原 達, 相澤 圭洋, 青山 準, 折舘 伸彦

    日本癌学会総会記事   79回   OE11 - 8   2020.10

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  • 共発現解析を用いた唾液腺腺様嚢胞癌の遠隔転移に関わる遺伝子の同定(Identifying hub genes associated with distant metastasis of salivary adenoid cystic carcinoma by co-expression analysis)

    相澤 圭洋, 高田 顕太郎, 佐野 大佑, 折舘 伸彦

    日本癌学会総会記事   78回   P - 2155   2019.9

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  • オルガノイド培養法を用いたPDX由来唾液腺腺様嚢胞癌の癌細胞株作製(Establishment of PDX-derived salivary gland adenoid cystic carcinoma cell lines using organoid culture method)

    高田 顕太郎, 相澤 圭洋, 佐野 大佑, 奥田 諒, 関根 圭輔, 上野 康晴, 青山 準, 波多野 孝, 荒井 康裕, 谷口 英樹, 折舘 伸彦

    日本癌学会総会記事   78回   P - 1292   2019.9

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  • 共発現解析を用いた唾液腺腺様嚢胞癌の遠隔転移に関わる遺伝子の同定(Identifying hub genes associated with distant metastasis of salivary adenoid cystic carcinoma by co-expression analysis)

    相澤 圭洋, 高田 顕太郎, 佐野 大佑, 折舘 伸彦

    日本癌学会総会記事   78回   P - 2155   2019.9

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  • 頭頸部癌の頸部リンパ節転移機構におけるFOSL1の関与について(FOSL1 promotes regional metastasis of head and neck squamous cell carcinoma)

    佐野 大佑, 澤熊 香衣, 百束 紘, 波多野 孝, 磯野 泰大, 高田 顕太郎, 佐藤 要, 桑原 達, 相澤 圭洋, 折舘 伸彦

    日本癌学会総会記事   77回   774 - 774   2018.9

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  • 当科における高齢者頭頸部癌症例の治療選択

    池宮城 秀崇, 西村 剛志, 佐野 大佑, 矢吹 健一郎, 荒井 康裕, 千葉 欣大, 田辺 輝彦, 森下 大樹, 柊 陽平, 相澤 圭洋, 高尾 なつみ, 野島 雄介, 折舘 伸彦

    日本耳鼻咽喉科学会会報   121 ( 4 )   589 - 589   2018.4

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  • 下位脳神経麻痺を呈した悪性外耳道炎の一例

    相澤 圭洋, 荒井 康裕, 高橋 優宏, 青木 登志将, 田辺 輝彦, 佐野 大佑, 塩野 理, 西村 剛志, 折舘 伸彦

    神奈川医学会雑誌   44 ( 1 )   59 - 60   2017.1

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Research Projects

  • Exploring therapeutic targets for salivary gland cancer using gene network analysis.

    Grant number：24K19775  2024.4 - 2027.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Early-Career Scientists

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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