小澤 宏之 (オザワ ヒロユキ)

Ozawa, Hiroyuki

写真a

所属(所属キャンパス)

医学部 耳鼻咽喉科・頭頸部外科学教室 (信濃町)

職名

教授

外部リンク

学位 【 表示 / 非表示

  • 博士(医学), 慶應義塾大学, 2010年01月

免許・資格 【 表示 / 非表示

  • 耳鼻咽喉科専門医, 2003年09月

  • 日本癌治療医認定医機構 癌治療認定医, 2008年04月

  • 日本頭頸部外科学会 頭頸部がん専門医, 2010年10月

 

研究分野 【 表示 / 非表示

  • ライフサイエンス / 腫瘍診断、治療学

  • ライフサイエンス / 耳鼻咽喉科学

研究キーワード 【 表示 / 非表示

  • 甲状腺腫瘍

  • 頭蓋底腫瘍

  • 頭頸部癌

  • 頸動脈小体腫瘍

研究テーマ 【 表示 / 非表示

  • 頸動脈小体腫瘍の発生、腫瘍進展の解明, 

    2014年
    -
    継続中

  • 頭頸部癌の転移メカニズムの解明, 

    2003年
    -
    継続中

 

論文 【 表示 / 非表示

  • Correlation between genotype and phenotype with special attention to hearing in 14 Japanese cases of NF2-related schwannomatosis

    Oishi N., Noguchi M., Fujioka M., Nara K., Wasano K., Mutai H., Kawakita R., Tamura R., Karatsu K., Morimoto Y., Toda M., Ozawa H., Matsunaga T.

    Scientific Reports (Scientific Reports)  13 ( 1 )  2023年12月

     概要を見る

    NF2-related schwannomatosis (NF2) is an autosomal dominant genetic disorder caused by variants in the NF2 gene. Approximately 50% of NF2 patients inherit pathogenic variants, and the remainder acquire de novo variants. NF2 is characterized by development of bilateral vestibular schwannomas. The genetic background of Japanese NF2 cases has not been fully investigated, and the present report performed a genetic analysis of 14 Japanese NF2 cases and examined genotype–phenotype correlations. DNA samples collected from peripheral blood were analyzed by next-generation sequencing, multiplex ligation-dependent probe amplification analysis, and in vitro electrophoresis. Ten cases had pathogenic or likely pathogenic variants in the NF2 gene, with seven truncating variants and three non-truncating variants. The age of onset in all seven cases with truncating variants was < 20 years. The age of onset significantly differed among cases with truncating NF2 variants, non-truncating NF2 variants, and no NF2 variants. However, the clinical course of tumor growth and hearing deterioration were not predicted only by germline pathogenic NF2 variants. The rate of truncating variants was higher in the present study than that of previous reports. Genotype–phenotype correlations in the age of onset were present in the analyzed Japanese NF2 cases.

  • Development of cochlear spiral ligament fibrocytes of the common marmoset, a nonhuman model animal

    Hosoya M., Iwabu K., Kitama T., Nishiyama T., Oishi N., Okano H., Ozawa H.

    Scientific Reports (Scientific Reports)  13 ( 1 )  2023年12月

     概要を見る

    Spiral ligament fibrocytes generate potassium gradients, which hair cells require to convert mechanical sound waves into electrical palsy. Together with the stria vascularis, they regulate endolymph electrolyte homeostasis. Developing spiral ligament fibrocytes and generating endocochlear potential with an appropriate endolymph ion composition are essential for hearing. Understanding spiral ligament fibrocyte development is useful for studying age-related and genetic hearing loss, as well as for regenerative therapy and cochlear immunology. Despite interspecies differences, most studies of cochlear development have been conducted in rodent models due to the difficulty of using human fetal samples. This study investigated the cochlear development of spiral ligament fibrocytes in a small New World monkey species, the common marmoset (Callithrix jacchus). We examined the developmental expression of specific genes in spiral ligament fibrocytes, including those essential for the generation of endolymphatic potential. Our results showed that this animal model of spiral ligament fibrocyte development is similar to that of humans and is a suitable alternative for the analysis of human cochlear development. The time course established in this study will be useful for studying the primate-specific developmental biology of the inner ear, which may lead to novel treatment strategies for human hearing loss.

  • Apoptosis of type I spiral ganglion neuron cells in Otof-mutant mice

    Tsuzuki N., Namba K., Saegusa C., Mutai H., Nishiyama T., Oishi N., Matsunaga T., Fujioka M., Ozawa H.

    Neuroscience Letters (Neuroscience Letters)  803 2023年04月

    ISSN  03043940

     概要を見る

    Otof, which encodes otoferlin, knockout mice are considered model mice for auditory neuropathy spectrum disorder, which is characterized by an absent auditory brainstem response (ABR) despite preserved distortion product otoacoustic emission (DPOAE). Although otoferlin-deficient mice lack neurotransmitter release at the inner hair cell (IHC) synapse, it remains unclear how the Otof mutation affects spiral ganglions. Thus, we used Otof-mutant mice carrying the Otoftm1a(KOMP)Wtsi allele (Otoftm1a) and analyzed spiral ganglion neurons (SGNs) in Otoftm1a/tm1a mice by immunolabeling type Ⅰ SGNs (SGN-Ⅰ) and type II SGNs (SGN-II). We also examined apoptotic cells in SGNs. Four-week-old Otoftm1a/tm1a mice had an absent ABR but normal DPOAEs. The number of SGNs was significantly lower in Otoftm1a/tm1a mice on postnatal day 7 (P7), P14, and P28 compared with that of wild-type mice. Moreover, significantly more apoptotic SGNs were observed in Otoftm1a/tm1a mice than in wild-type mice on P7, P14, and P28. SGN-IIs were not significantly reduced in Otoftm1a/tm1a mice on P7, P14, and P28. No apoptotic SGN-IIs were observed under our experimental conditions. In summary, Otoftm1a/tm1a mice showed a reduction in SGNs accompanied by apoptosis of SGN-Ⅰs even before the onset of hearing. We speculate that the reduction in SGNs with apoptosis is a secondary defect caused by a lack of otoferlin in IHCs. Appropriate glutamatergic synaptic inputs may be important for the survival of SGNs.

  • Molecular basis of carotid body tumor and associated clinical features in Japan identified by genomic, immunohistochemical, and clinical analyses

    Yoshihama K., Mutai H., Sekimizu M., Ito F., Saito S., Nakamura S., Mikoshiba T., Nagai R., Takebayashi A., Miya F., Kosaki K., Ozawa H., Matsunaga T.

    Clinical Genetics (Clinical Genetics)  103 ( 4 ) 466 - 471 2023年04月

    ISSN  00099163

     概要を見る

    Carotid body tumor (CBT) is classified as a paraganglioma (PGL). Here, we report the genetic background, protein expression pattern, and clinical findings of 30 Japanese CBT cases. Germline pathogenic or likely pathogenic (P/LP) variants of genes encoding succinate dehydrogenase subunits (SDHs) were detected in 15 of 30 cases (50%). The SDHB variants were the most frequently detected, followed by SDHA and SDHD variants. One case with SDHAF2 variant was bilateral CBT, and other two multiple PGL cases were not detected P/LP variants. The three cases with germline variants that could be tested did not have somatic P/LP variants of the same genes. Immunohistochemical analysis showed negative SDHB signals in CBT tissues in five cases with germline P/LP variants of SDHB, SDHD, or SDHA. In addition, SDHB signals in CBT tissues were negative in four of nine cases without germline P/LP variants of SDHs. These findings suggest the involvement of unidentified molecular mechanisms affecting SDHs.

  • Generation of two induced pluripotent stem cell lines from individuals without auditory disorders

    Okura S., Ishii H., Suzuki A., Saegusa C., Fujiki K., Sugano K., Suzuki N., Saeki T., Matsuzaki S., Ozawa H., Fujioka M., Hosoya M., Okano H.

    Stem Cell Research (Stem Cell Research)  67 2023年03月

    ISSN  18735061

     概要を見る

    We report the establishment of two human induced pluripotent stem cell (iPSC) lines from individuals without auditory disorders. Extensive audiometry tests were performed to confirm normal hearing. The generated iPSC lines expressed pluripotency genes and showed differentiation capability into the three germ layers. The iPSC lines will be used as controls for pathological analysis and drug screening for ear disorders.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

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競争的研究費の研究課題 【 表示 / 非表示

  • 頭頸部癌における低酸素応答因子の免疫応答への影響の解析とその臨床応用

    2020年04月
    -
    2023年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 小澤 宏之, 基盤研究(C), 補助金,  研究代表者

  • 低酸素応答因子を標的とした頭頸部癌転移治療の開発

    2017年04月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 小澤 宏之, 基盤研究(C), 補助金,  研究代表者

  • 頭頸部癌における低酸素誘導因子発現の転移への影響とその臨床応用に関する研究

    2014年04月
    -
    2017年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 小澤 宏之, 基盤研究(C), 補助金,  研究代表者

     研究概要を見る

    頭頸部癌症例のHIF1-α発現について検討を行った。早期舌癌25症例の免疫染色ではHIF1-αの核内発現と遅発性頸部転移との関係が示された。また経口的腫瘍切除の適応となった早期下咽頭癌症例においてリンパ節転移の有無とHIF1-α発現との間に相関を認めた。
    さらにHIF1-α阻害薬を用いて下流シグナルの変化をReal Time PCRで測定した。頭頸部癌細胞株にHIF1-α阻害薬を投与することにより、EMT関連遺伝子のなかではTWISTが、また癌幹細胞に関係するNANOGおよびOCT3/4遺伝子の発現が低下し、これらの遺伝子発現がHIF1-αにより制御され転移病巣形成に関与していることが示された。

 

担当授業科目 【 表示 / 非表示

  • 耳鼻咽喉科学演習

    2024年度

  • 耳鼻咽喉科学実習

    2024年度

  • 耳鼻咽喉科学

    2024年度

  • 耳鼻咽喉科学講義

    2024年度

  • 耳鼻咽喉科学臨床実習

    2024年度

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担当経験のある授業科目 【 表示 / 非表示

  • 頭頸部癌の基礎と臨床

    慶應義塾

    2017年04月
    -
    2018年03月

  • 鼻副鼻腔腫瘍・前頭蓋底腫瘍・下垂体腫瘍

    慶應義塾

    2017年04月
    -
    2018年03月

 

所属学協会 【 表示 / 非表示

  • 日本耳鼻咽喉科学会

     
  • 日本頭頸部癌学会

     
  • 日本頭頸部外科学会

     
  • 日本頭蓋底外科学会

     
  • 耳鼻咽喉科臨床学会

     

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