Updated on 2023/10/04

写真a

 
Taiji Hamada
 
Organization
Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Advanced Therapeutics Course Oncology Assistant Professor
Title
Assistant Professor

Degree

  • Doctor (philosophy in medical science) ( 2015.8   Kagoshima University )

Research Interests

  • genome editing

Research Areas

  • Life Science / Molecular biology

Research History

  • Kagoshima University   Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Advanced Therapeutics Course Oncology   Assistant Professor

    2018.1

  • Kagoshima University   Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area Graduate School of Medical and Dental Sciences Advanced Therapeutics Course Oncology

    2013.12 - 2017.12

Professional Memberships

 

Papers

  • Hamada T, Higashi M, Yokoyama S, Akahane T, Hisaoka M, Noguchi H, Furukawa T, Tanimoto A .  MALAT1 functions as a transcriptional promoter of MALAT1::GLI1 fusion for truncated GLI1 protein expression in cancer. .  BMC cancer23 ( 1 ) 424   2023.5MALAT1 functions as a transcriptional promoter of MALAT1::GLI1 fusion for truncated GLI1 protein expression in cancer.Reviewed

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

    DOI： 10.1186/s12885-023-10867-6

    PubMed

  • Taiji Hamada, Seiya Yokoyama, Toshiaki Akahane, Kei Matsuo, Akihide Tanimoto .  Genome Editing Using Cas9 Ribonucleoprotein Is Effective for Introducing PDGFRA Variant in Cultured Human Glioblastoma Cell Lines. .  International journal of molecular sciences24 ( 1 )   2022.12Genome Editing Using Cas9 Ribonucleoprotein Is Effective for Introducing PDGFRA Variant in Cultured Human Glioblastoma Cell Lines.Reviewed International journal

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    Many variants of uncertain significance (VUS) have been detected in clinical cancer cases using next-generation sequencing-based cancer gene panel analysis. One strategy for the elucidation of VUS is the functional analysis of cultured cancer cell lines that harbor targeted gene variants using genome editing. Genome editing is a powerful tool for creating desired gene alterations in cultured cancer cell lines. However, the efficiency of genome editing varies substantially among cell lines of interest. We performed comparative studies to determine the optimal editing conditions for the introduction of platelet-derived growth factor receptor alpha (PDGFRA) variants in human glioblastoma multiforme (GBM) cell lines. After monitoring the copy numbers of PDGFRA and the expression level of the PDGFRα protein, four GBM cell lines (U-251 MG, KNS-42, SF126, and YKG-1 cells) were selected for the study. To compare the editing efficiency in these GBM cell lines, the modes of clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) delivery (plasmid vs. ribonucleoprotein (RNP)), methods of transfection (lipofection vs. electroporation), and usefulness of cell sorting were then evaluated. Herein, we demonstrated that electroporation-mediated transfer of Cas9 with single-guide RNA (Cas9 RNP complex) could sufficiently edit a target nucleotide substitution, irrespective of cell sorting. As the Cas9 RNP complex method showed a higher editing efficiency than the Cas9 plasmid lipofection method, it was the optimal method for single-nucleotide editing in human GBM cell lines under our experimental conditions.

    DOI： 10.3390/ijms24010500

    PubMed

  • Hamada T. .  An oncogenic splice variant of PDGFRα in adult glioblastoma as a therapeutic target for selective CDK4/6 inhibitors .  Scientific Reports12 ( 1 ) 1275   2022.12Reviewed

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41598-022-05391-9

    Scopus

    PubMed

  • Sieya Yokoyama, Hiromichi Iwaya, Toshiaki Akahane, Taiji Hamada, Michiyo Higashi, Shinichi Hashimoto, Shiroh Tanoue, Takao Ohtsuka, Akio Ido, Akihide Tanimoto .  Sequential evaluation of MUC promoter methylation using next‐generation sequencing‐based custom‐made panels in liquid‐based cytology specimens of pancreatic cancer .  Diagnostic Cytopathology50 ( 11 ) 499 - 507   2022.8Reviewed International journal

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

    BACKGROUND: As liquid-based cytology (LBC) specimens preserve high-quality DNA, clinical sequencing of LBC specimens using next-generation sequencing (NGS) is becoming a common strategy. This study aimed to evaluate the feasibility of NGS-based custom-made panels for evaluating MUC promoter methylation in LBC specimens. METHODS: Thirty-one patients with pancreatic cancer were enrolled in the study. Cancer tissue samples were obtained using endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB). LBC, formalin-fixed paraffin-embedded (FFPE), and fresh frozen specimens were prepared for DNA extraction after pathological diagnosis. These specimens were then subjected to NGS analysis using custom-made cancer gene screening and methylation panels comprising 28 cancer-related genes and 13 gene promoter regions, including MUC1, MUC2, and MUC4. RESULTS: The success rate of NGS using the cancer gene panel was comparable among the LBC, FFPE, and frozen specimens, and the presence of cancer cell-derived somatic mutations in each specimen was confirmed. The specimens were then tested using a methylation panel that revealed the sequential methylation status of CpG islands located in the promoter regions of MUC genes. The methylation status results obtained from LBC specimens were almost comparable with those from FFPE and frozen specimens. CONCLUSIONS: MUC and other gene methylation analyses using an NGS-based panel were successfully performed in residual LBC specimens obtained by EUS-FNA/FNB. Therefore, this approach provides an alternative source of molecular tests for gene mutations and methylation, especially in the pancreatic cancers, which are often unresectable and unsuitable for obtaining FFPE specimens.

    DOI： 10.1002/dc.25022

    PubMed

    Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/dc.25022

  • Nayuta Higa, Toshiaki Akahane, Seiya Yokoyama, Hajime Yonezawa, Hiroyuki Uchida, Tomoko Takajo, Ryosuke Otsuji, Taiji Hamada, Kei Matsuo, Mari Kirishima, Nobuhiro Hata, Ryosuke Hanaya, Akihide Tanimoto, Koji Yoshimoto .  Prognostic impact of <i>PDGFRA</i> gain/amplification and <i>MGMT</i> promoter methylation status in patients with <i>IDH</i> wild-type glioblastoma .  Neuro-Oncology Advances4 ( 1 ) vdac097   2022.6Reviewed International journal

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

    Abstract

    Background

    Platelet-derived growth factor receptor alpha (PDGFRA) is the second most frequently mutated tyrosine kinase receptor in glioblastoma (GBM). However, the prognostic impact of PDGFRA amplification on GBM patients remains unclear. Herein, we evaluated this impact by retrospectively analyzing outcomes of patients with IDH wild-type GBM.

    Methods

    Using a custom-made oncopanel, we evaluated PDGFRA gain/amplification in 107 GBM samples harboring wild-type IDH, along with MGMT promoter (MGMTp) methylation status.

    Results

    We detected PDGFRA gain/amplification in 31 samples (29.0%). PDGFRA gain/amplification predicted poor prognosis (P = .003). Compared to unamplified PDGFRA, PDGFRA gain/amplification in GBM was associated with higher patient age (P = .031), higher Ki-67 score (P = .019), and lower extent of surgical resection (P = .033). Unmethylated MGMTp also predicted poor prognosis (P = .005). As PDGFRA gain/amplification and unmethylated MGMTp were independent factors for poor prognosis in multivariate analyses, we grouped GBM cases based on PDGFRA and MGMTp status: poor (PDGFRA gain/amplification and unmethylated MGMTp), intermediate (PDGFRA gain/amplification or unmethylated MGMTp), and good (PDGFRA intact and methylated MGMTp) prognosis. The Kaplan-Meier survival analysis indicated that these groups significantly correlated with the OS of GBM patients (P &amp;lt; .001).

    Conclusions

    Here we report that PDGFRA gain/amplification is a predictor of poor prognosis in IDH wild-type GBM. Combining PDGFRA gain/amplification with MGMTp methylation status improves individual prognosis prediction in patients with IDH wild-type GBM.

    DOI： 10.1093/noajnl/vdac097

    Scopus

    PubMed

    Other Link： https://academic.oup.com/noa/article-pdf/4/1/vdac097/45178840/vdac097.pdf

  • Nayuta Higa, Toshiaki Akahane, Taiji Hamada, Hajime Yonezawa, Hiroyuki Uchida, Ryutaro Makino, Shoji Watanabe, Tomoko Takajo, Seiya Yokoyama, Mari Kirishima, Kei Matsuo, Shingo Fujio, Ryosuke Hanaya, Akihide Tanimoto, Koji Yoshimoto .  Distribution and favorable prognostic implication of genomic EGFR alterations in IDH-wildtype glioblastoma. .  Cancer medicine   2022.6Distribution and favorable prognostic implication of genomic EGFR alterations in IDH-wildtype glioblastoma.Reviewed International journal

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

    BACKGROUND: We aimed to evaluate the mutation profile, transcriptional variants, and prognostic impact of the epidermal growth factor receptor (EGFR) gene in isocitrate dehydrogenase (IDH)-wildtype glioblastomas (GBMs). METHODS: We sequenced EGFR, evaluated the EGFR splicing profile using a next-generation sequencing oncopanel, and analyzed the outcomes in 138 grade IV IDH-wildtype GBM cases. RESULTS: EGFR mutations were observed in 10% of GBMs. A total of 23.9% of the GBMs showed EGFR amplification. Moreover, 25% of the EGFR mutations occurred in the kinase domain. Notably, EGFR alterations were a predictor of good prognosis (p = 0.035). GBM with EGFR alterations was associated with higher Karnofsky Performance Scale scores (p = 0.014) and lower Ki-67 scores (p = 0.005) than GBM without EGFR alterations. EGFRvIII positivity was detected in 21% of EGFR-amplified GBMs. We identified two other EGFR variants in GBM cases with deletions of exons 6-7 (Δe 6-7) and exons 2-14 (Δe 2-14). In one case, the initial EGFRvIII mutation transformed into an EGFR Δe 2-14 mutation during recurrence. CONCLUSIONS: We found that the EGFR gene profiles of GBM differ among cohorts and that EGFR alterations are good prognostic markers of overall survival in patients with IDH-wildtype GBM. Additionally, we identified rare EGFR variants with longitudinal and temporal transformations of EGFRvIII.

    DOI： 10.1002/cam4.4939

    PubMed

  • Mari Kirishima, Seiya Yokoyama, Kei Matsuo, Taiji Hamada, Michiko Shimokawa, Toshiaki Akahane, Tomoyuki Sugimoto, Hirohito Tsurumaru, Matsujiro Ishibashi, Yuko Mataki, Takao Ootsuka, Mitsuharu Nomoto, Chihiro Hayashi, Akihiko Horiguchi, Michiyo Higashi, Akihide Tanimoto .  Gallbladder microbiota composition is associated with pancreaticobiliary and gallbladder cancer prognosis. .  BMC microbiology22 ( 1 ) 147 - 147   2022.5Gallbladder microbiota composition is associated with pancreaticobiliary and gallbladder cancer prognosis.Reviewed International journal

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

    BACKGROUND: The microbial population of the intestinal tract and its relationship to specific diseases has been extensively studied during the past decade. However, reports characterizing the bile microbiota are rare. This study aims to investigate the microbiota composition in patients with pancreaticobiliary cancers and benign diseases by 16S rRNA gene amplicon sequencing and to evaluate its potential value as a biomarker for the cancer of the bile duct, pancreas, and gallbladder. RESULTS: We enrolled patients who were diagnosed with cancer, cystic lesions, and inflammation of the pancreaticobiliary tract. The study cohort comprised 244 patients. We extracted microbiome-derived DNA from the bile juice in surgically resected gallbladders. The microbiome composition was not significantly different according to lesion position and cancer type in terms of alpha and beta diversity. We found a significant difference in the relative abundance of Campylobacter, Citrobacter, Leptotrichia, Enterobacter, Hungatella, Mycolicibacterium, Phyllobacterium and Sphingomonas between patients without and with lymph node metastasis. CONCLUSIONS: There was a significant association between the relative abundance of certain microbes and overall survival prognosis. These microbes showed association with good prognosis in cholangiocarcinoma, but with poor prognosis in pancreatic adenocarcinoma, and vice versa. Our findings suggest that pancreaticobiliary tract cancer patients have an altered microbiome composition, which might be a biomarker for distinguishing malignancy.

    DOI： 10.1186/s12866-022-02557-3

    PubMed

  • Michiyo Higashi, Taiji Hamada, Ken Sasaki, Yusuke Tsuruda, Masataka Shimonosono, Ikumi Kitazono, Mari Kirishima, Takashi Tasaki, Hirotsugu Noguchi, Kazuhiro Tabata, Masanori Hisaoka, Yoshihiko Fukukura, Takao Ohtsuka, Akihide Tanimoto .  Esophageal plexiform fibromyxoma: A case report with molecular analysis for MALAT1-GLI1 fusion. .  Pathology, research and practice233   153878 - 153878   2022.5Esophageal plexiform fibromyxoma: A case report with molecular analysis for MALAT1-GLI1 fusion.Reviewed International journal

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

    Plexiform fibromyxoma (PFM) is a rare gastrointestinal tract tumor that develops in the stomach in most cases. Here, we report an extremely rare case of esophageal PFM. A female in her mid-30 s presented with difficulty in swallowing and breathing. Endoscopic examination revealed a submucosal tumor measuring approximately 45 × 50 mm in the upper thoracic esophagus. The biopsied specimen did not show definite histological evidence of gastrointestinal stromal tumors (GISTs). Since imatinib administration based on a clinical diagnosis of GIST did not show a therapeutic effect for tumor reduction, tumor resection was performed. The resected tumor exhibited proliferation of spindle tumor cells with abundant myxoid and vascular stroma separated by a muscular layer, indicating a plexiform arrangement. Immunohistochemical analysis demonstrated that the tumor cells diffusely expressed vimentin and alpha-smooth muscle actin, but not desmin, c-kit, DOG1, and CD34. MALAT1-GLI1 fusion was detected in formalin-fixed paraffin-embedded tissue using RT-PCR and Sanger sequencing. The results suggested that a fibromyxoid tumor can develop in the esophagus, showing an identical histology and MALAT1-GLI1 fusion to gastric PFM.

    DOI： 10.1016/j.prp.2022.153878

    PubMed

  • Kitazono I, Hamada T, Yoshimura T, Kirishima M, Yokoyama S, Akahane T, Tanimoto A .  PCP4/PEP19 downregulates neurite outgrowth via transcriptional regulation of Ascl1 and NeuroD1 expression in human neuroblastoma M17 cells. .  Laboratory investigation; a journal of technical methods and pathology100 ( 12 ) 1551 - 1563   2020.12PCP4/PEP19 downregulates neurite outgrowth via transcriptional regulation of Ascl1 and NeuroD1 expression in human neuroblastoma M17 cells.

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  • Nayuta Higa, Toshiaki Akahane, Seiya Yokoyama, Hajime Yonezawa, Hiroyuki Uchida, Tomoko Takajo, Mari Kirishima, Taiji Hamada, Kei Matsuo, Shingo Fujio, Tomoko Hanada, Hiroshi Hosoyama, Masanori Yonenaga, Akihisa Sakamoto, Tsubasa Hiraki, Akihide Tanimoto, Koji Yoshimoto. .  A tailored next-generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas. .  Cancer Science   2020.8A tailored next-generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas.Reviewed

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

  • Ikumi Kitazono, Taiji Hamada, Takuya Yoshimura, Mari Kirishima, Seiya Yokoyama, Toshiaki Akahane, Akihide Tanimoto. .  PCP4/PEP19 downregulates neurite outgrowth via transcriptional regulation of Ascl1 and NeuroD1 expression in human neuroblastoma M17 cells. .  Laboratory Investigation   2020.7PCP4/PEP19 downregulates neurite outgrowth via transcriptional regulation of Ascl1 and NeuroD1 expression in human neuroblastoma M17 cells.Reviewed

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Nature Limited  

    DOI： 10.1038/s41374-020-0462-z.

  • Yokoyama S, Hamada T, Higashi M, Matsuo K, Maemura K, Kurahara H, Horinouchi M, Hiraki T, Sugimoto T, Akahane T, Yonezawa S, Kornmann M, Batra SK, Hollingsworth MA, Tanimoto A .  Predicted Prognosis of Patients with Pancreatic Cancer by Machine Learning. .  Clinical cancer research : an official journal of the American Association for Cancer Research26 ( 10 ) 2411 - 2421   2020.5Predicted Prognosis of Patients with Pancreatic Cancer by Machine Learning.

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  • Seiya Yokoyama, Taiji Hamada, Michiyo Higashi, Kei Matsuo, Kosei Maemura, Hiroshi Kurahara, Michiko Horinouchi, Tsubasa Hiraki, Tomoyuki Sugimoto, Toshiaki Akahane, Suguru Yonezawa, Marko Kornmann, Surinder K Batra, Michael A Hollingsworth, Akihide Tanimoto. .  Predicted Prognosis of Patients With Pancreatic Cancer by Machine Learning. .  Clinical Cancer Research   2020.5Predicted Prognosis of Patients With Pancreatic Cancer by Machine Learning.Reviewed

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

  • Guo X, Noguchi H, Ishii N, Homma T, Hamada T, Hiraki T, Zhang J, Matsuo K, Yokoyama S, Ishibashi H, Fukushige T, Kanekura T, Fujii J, Uramoto H, Tanimoto A, Yamada S .  The Association of Peroxiredoxin 4 with the Initiation and Progression of Hepatocellular Carcinoma. .  Antioxidants & redox signaling30 ( 10 ) 1271 - 1284   2019.4The Association of Peroxiredoxin 4 with the Initiation and Progression of Hepatocellular Carcinoma.

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  • Akahane T, Yamaguchi T, Kato Y, Yokoyama S, Hamada T, Nishida Y, Higashi M, Nishihara H, Suzuki S, Ueno S, Tanimoto A .  Comprehensive validation of liquid-based cytology specimens for next-generation sequencing in cancer genome analysis. .  PloS one14 ( 6 ) e0217724   2019Comprehensive validation of liquid-based cytology specimens for next-generation sequencing in cancer genome analysis.Invited Reviewed

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

    DOI： 10.1371/journal.pone.0217724

    PubMed

  • Zhang J, Guo X, Hamada T, Yokoyama S, Nakamura Y, Zheng J, Kurose N, Ishigaki Y, Uramoto H, Tanimoto A, Yamada S .  Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury. .  International journal of molecular sciences19 ( 9 )   2018.8Protective Effects of Peroxiredoxin 4 (PRDX4) on Cholestatic Liver Injury.

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  • Onishi S, Kaji T, Yamada W, Nakame K, Machigashira S, Kawano M, Yano K, Harumatsu T, Yamada K, Masuya R, Kawano T, Mukai M, Hamada T, Souda M, Yoshioka T, Tanimoto A, Ieiri S .  Ghrelin stimulates intestinal adaptation following massive small bowel resection in parenterally fed rats. .  Peptides106   59 - 67   2018.8Ghrelin stimulates intestinal adaptation following massive small bowel resection in parenterally fed rats.

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  • Honjo K, Hamada T, Yoshimura T, Yokoyama S, Yamada S, Tan YQ, Leung LK, Nakamura N, Ohi Y, Higashi M, Tanimoto A .  PCP4/PEP19 upregulates aromatase gene expression via CYP19A1 promoter I.1 in human breast cancer SK-BR-3 cells. .  Oncotarget9 ( 51 ) 29619 - 29633   2018.7PCP4/PEP19 upregulates aromatase gene expression via CYP19A1 promoter I.1 in human breast cancer SK-BR-3 cells.Invited Reviewed

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Impact Journals, LLC  

    DOI： 10.18632/oncotarget.25651

    PubMed

  • Yamada S, Kawaguchi H, Yamada T, Guo X, Matsuo K, Hamada T, Miura N, Tasaki T, Tanimoto A .  Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty Liver Disease in Microminipigs. .  Journal of atherosclerosis and thrombosis24 ( 11 ) 1150 - 1166   2017.11Cholic Acid Enhances Visceral Adiposity, Atherosclerosis and Nonalcoholic Fatty Liver Disease in Microminipigs.

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  • Yokoyama S, Higashi M, Tsutsumida H, Wakimoto J, Hamada T, Wiest E, Matsuo K, Kitazono I, Goto Y, Guo X, Hamada T, Yamada S, Hiraki T, Yonezawa S, Batra SK, Hollingsworth MA, Tanimoto A .  TET1-mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer. .  Genes & cancer8 ( 3-4 ) 517 - 527   2017.3TET1-mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer.

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Research Projects

  • PDGFRA遺伝子変異の抗がん剤感受性マップの作製

    Grant number：22K07305  2022.4 - 2025.3

    日本学術振興会  科学研究費助成事業  基盤研究（C）

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    Authorship：Principal investigator  Grant type：Competitive

    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

  • 乳癌を標的とした新規アロマターゼ阻害剤の開発に向けた基盤研究

    2018.4 - 2021.3

    科学研究費補助金  基盤研究(C)