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• Biomarkers for Predicting Anti-Programmed Cell Death-1 Antibody Treatment Effects in Head and Neck Cancer.

  Katsunori Tanaka, Hitoshi Hirakawa, Mikio Suzuki, Teruyuki Higa, Shinya Agena, Narumi Hasegawa, Junko Kawakami, Masatomo Toyama, Tomoyo Higa, Hidetoshi Kinjyo, Norimoto Kise, Shunsuke Kondo, Hiroyuki Maeda, Taro Ikegami

  Current oncology (Toronto, Ont.)   30 ( 6 ) 5409 - 5424   2023.06 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  In recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC), survival outcomes are significantly better in patients who receive anti-programmed cell death-1 (PD-1) monoclonal antibody therapy than in those who receive standard therapy. However, there is no established biomarker that can predict the anti-PD-1 antibody treatment effect and immune-related adverse events (irAEs) in these patients. This study investigated the inflammatory and nutritional status in 42 patients with R/M-HNSCC and programmed cell death ligand-1 (PD-L1) polymorphisms (rs4143815 and rs2282055) in 35 of the 42 patients. The 1- and 2-year overall survival was 59.5% and 28.6%, respectively; the 1- and 2-year first progression-free survival was 19.0% and 9.5%, respectively, and the respective second progression-free survival was 50% and 27.8%. Performance status and inflammatory and nutritional status (assessed by the geriatric nutritional risk index, modified Glasgow prognostic score, and prognostic nutritional index) were identified as significant indicators of survival outcomes in multivariate analysis. Patients with ancestral alleles in PD-L1 polymorphisms had less frequent irAEs. Performance status and inflammatory and nutritional status before treatment were closely related to survival outcomes after PD-1 therapy. These indicators can be calculated using routine laboratory data. PD-L1 polymorphisms may be biomarkers for predicting irAEs in patients receiving anti-PD-1 therapy.

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• Human papillomavirus infection and EGFR exon 20 insertions in sinonasal inverted papilloma and squamous cell carcinoma

  Hitoshi Hirakawa, Taro Ikegami, Norimoto Kise, Hidetoshi Kinjyo, Shunsuke Kondo, Shinya Agena, Narumi Hasegawa, Junko Kawakami, Hiroyuki, Maeda, Mikio Suzuki

  Journal of Personalized Medicine   13 ( 4 ) 657   2023.04 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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• p16 Overexpression in Sinonasal Squamous Cell Carcinoma: Association with Human Papillomavirus and Prediction of Survival Outcomes

  Hitoshi Hirakawa , Taro Ikegami, Mikio Suzuki

  Journal of Clinical Medicine     2023 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

• Prospective Analysis of Squamous Cell Carcinoma Antigen-1 and -2 for Diagnosing Sinonasal Inverted Papilloma

  Katsunori Tanaka, Hitoshi Hirakawa, Mikio Suzuki, Taro Ikegami

  Current Oncology ( MDPI )  ( 30 ) 5409 - 5424   2023 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

• Development of Antibodies against HPV-6 and HPV-11 for the Study of Laryngeal Papilloma.

  Taro Ikegami, Norimoto Kise, Hidetoshi Kinjyo, Shunsuke Kondo, Mikio Suzuki, Narutoshi Tsukahara, Akikazu Murakami, Asanori Kiyuna, Shinya Agena, Katsunori Tanaka, Narumi Hasegawa, Junko Kawakami, Akira Ganaha, Hiroyuki Maeda, Hitoshi Hirakawa

  Viruses   13 ( 10 )   2021.10 [ Peer Review Accepted ]

  Type of publication: Research paper (scientific journal)

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  Laryngeal papilloma (LP), which is associated with infection by human papillomavirus (HPV)-6 or -11, displays aggressive growth. The precise molecular mechanism underlying the tumorigenesis of LP has yet to be uncovered. Building on our earlier research into HPV-6, in this study, the viral gene expression of HPV-11 was investigated by quantitative PCR and DNA/RNA in situ hybridization. Additionally, newly developed antibodies against the E4 protein of HPV-6 and HPV-11 were evaluated by immunohistochemistry. The average viral load of HPV-11 in LP was 1.95 ± 0.66 × 105 copies/ng DNA, and 88% of HPV mRNA expression was found to be E4, E5a, and E5b mRNAs. According to RNA in situ hybridization, E4 and E5b mRNAs were expressed from the middle to upper part of the epithelium. E4 immunohistochemistry revealed a wide positive reaction in the upper cell layer in line with E4 mRNA expression. Other head and neck lesions with HPV-11 infection also showed a positive reaction in E4 immunohistochemistry. The distribution pattern of HPV DNA, viral mRNA, and E4 protein in LP with HPV-11 infection was quite similar to that of HPV-6. Therefore, it might be possible to apply these E4-specific antibodies in other functional studies as well as clinical applications, including targeted molecular therapies in patients with HPV-6 and HPV-11 infection.

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