Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2024.07

  -

  Now

  Department of Medical Oncology, Sapporo Medical University School of Medicine  

  教授

• 2016.11

  -

  2024.06

  札幌医科大学 医学部 腫瘍内科学講座  

  講師

• 2011.04

  -

  2016.10

  Sapporo Medical University   School of Medicine   助教

• 2009.03

  -

  2011.03

  Harvard University Dana-Farber Cancer Institute  

  リサーチ フェロー

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Gastroenterology  

• Life sciences   Hematology and oncology  

• Life sciences   Tumor diagnostics and therapeutics   がんゲノム医療

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University School of Medicine   Department of Medical Oncology  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• Medical Oncologist

• NASH

• 癌細胞における鉄代謝

• 新規大腸癌治療法開発

• 細胞標的治療

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Germline <scp><i>BRCA1</i></scp>‐Mutated Synchronous and Metachronous Pancreatic Acinar Cell Carcinoma With Long‐Term Survival

  Tomohiro Kubo, Yuki Ikeda, Joji Muramatu, Kazuma Ishikawa, Makoto Yoshida, Kazuharu Kukita, Masafumi Imamura, Shintaro Sugita, Akihiro Sakurai, Kohichi Takada

  Cancer Reports ( Wiley )  7 ( 8 )  2024.08

  　View Summary

  ABSTRACT Background Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic neoplasm. Recently, molecular analysis revealed that PACC shows a high frequency of the BRCA1/2 mutation and is likely to be considered a cancer associated with hereditary breast and ovarian cancer (HBOC). Hereditary cancers, including HBOC, are characterized by multifocal and/or metachronous tumors. However, no case reports exist of germline BRCA1‐mutated synchronous and metachronous PACC. Case A 58‐year‐old man was diagnosed with synchronous and metachronous PACC at the age of 56 and underwent two surgeries. Ten months after the second surgery, the patient developed multiple liver metastases. Gemcitabine plus nab‐paclitaxel therapy was administered as first‐line chemotherapy. After seven cycles, computed tomography examination revealed progressive disease (PD). Therefore, modified FOLFIRINOX (mFFX) was administered as second‐ line chemotherapy. After 19 cycles of mFFX, comprehensive cancer genomic profiling (CGP) identified a BRCA1 pathogenic variant that was confirmed to be germline origin. Accordingly, we treated the patient with olaparib; however, he was diagnosed with PD after 4 months. He subsequently died 5 years and 9 months after the initial surgery, and 3 years and 10 months after chemotherapy. Based on the genetic data of the patients, his family members received genetic counseling followed by cascade testing. Consequently, the same gBRCA1 pathogenic variant was detected in the son and his surveillance for HBOC‐related cancers was initiated. Conclusion We diagnosed a 58‐year‐old man with a synchronous and metachronous PACC with germline BRCA1 pathogenic variant. Considering that PACC is likely to have BRCA1/2 mutations responsible for HBOC, we need to be aware of the possible presence of multifocal and/or metachronous tumors in patients with PACC. Additionally, patients with PACC should undergo genetic examinations, which would be beneficial in determining treatment strategies and health care for blood relatives.

  DOI

• LMNA::NTRK1 Fusion-positive Leiomyosarcoma: Discrepancy between DNA-based Comprehensive Genomic Profiling and RNA Sequencing.

  Norito Suzuki, Masashi Idogawa, Makoto Emori, Kazuyuki Murase, Yohei Arihara, Hajime Nakamura, Makoto Usami, Tomohiro Kubo, Ichiro Kinoshita, Shintaro Sugita, Takashi Tokino, Tadashi Hasegawa, Akihiro Sakurai, Kohichi Takada

  Internal medicine (Tokyo, Japan)   63 ( 15 ) 2215 - 2219  2024.08  [Domestic journal]

  　View Summary

  A 26-year-old man presented with a tumor in the left soleus muscle. The tumor was diagnosed as a locally advanced leiomyosarcoma. The patient was treated with irradiation followed by wide resection. One year after surgery, the patient presented with multiple lung metastases. Despite aggressive sequential chemotherapy, systemic metastatic tumors continued to develop. To explore therapeutic options for the patient, we performed DNA-based CGP with FoundationOne® CDx (F1). F1 identified an out-of-strand rearrangement of the NOS1AP::NTRK1 gene, which has not been previously reported. In contrast, RNA sequencing revealed an in-frame LMNA::NTRK1 gene, which is an oncogenic fusion gene.

  DOI PubMed

• Marked Response to Nivolumab by a Patient With <scp>SMARCA4</scp>‐Deficient Undifferentiated Urothelial Carcinoma Showing High <scp>PD</scp>‐<scp>L1</scp> Expression: A Case Report

  Yohei Arihara, Ginji Omori, Ko Kobayashi, Shintaro Sugita, Kazuyuki Murase, Tomohiro Kubo, Masashi Idogawa, Tadashi Hasegawa, Kohichi Takada

  Cancer Reports ( Wiley )  7 ( 6 )  2024.06

  　View Summary

  ABSTRACT Background SMARCA4 is a component gene of the SWI/SNF (SWItch/Sucrose NonFermentable) chromatin remodeling complex; undifferentiated tumors associated with its functional deletion have been described in several organs. However, no established treatment for these tumors currently exists. Case In this study, we report a case of a SMARCA4‐deficient undifferentiated urothelial carcinoma with high PD‐L1 expression that was effectively treated with nivolumab after early relapse following treatment for non‐invasive bladder cancer. The histological morphology of the rhabdoid‐like undifferentiated tumor of unknown primary led us to suspect a SWI/SNF‐deficient tumor, and subsequent immunostaining led to the diagnosis of a SMARCA4‐deficient undifferentiated tumor. This effort also led to the identification of the developmental origin of this SMARCA4‐deficient undifferentiated tumor as a non‐invasive bladder cancer. We also carried out a detailed immune phenotypic assay on peripheral T cells. In brief, a phenotypic change of CD8+T cells from naive to terminally differentiated effector memory cells was observed. Conclusion Regardless of the organ of cancer origin or cancer type, SWI/SNF‐deficient tumors should be suspected in undifferentiated and dedifferentiated tumors, and immune checkpoint inhibitors may be considered as a promising treatment option for this type of tumor. The pathogenesis of SMARCA4‐deficient anaplastic tumors awaits further elucidation for therapeutic development.

  DOI

• Crizotinib therapy for congenital embryonal rhabdomyosarcoma associated with an <i>ATIC–ALK</i> gene fusion

  Yusuke Akane, Masaki Yamamoto, Akira Takebayashi, Ryo Hamada, Keita Igarashi, Makoto Emori, Shintaro Sugita, Kohichi Takada, Tadashi Hasegawa, Takeshi Tsugawa

  Pediatric Blood &amp; Cancer ( Wiley )   2024.06

  DOI

• 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

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 食道癌 診断と治療のup to date 食道腺癌を含めて 切除可能進行食道癌に対する三剤併用療法ベースの化学放射線療法は手術療法を代替できるか?:傾向スコアマッチング分析

  大沼 啓之, 小野山 直輝, 濱口 孝太, 早坂 尚貴, 佐藤 昌則, 村瀬 和幸, 高田 弘一, 宮西 浩嗣, 村上 武志, 伊東 竜哉, 信岡 隆幸, 竹政 伊知朗, 土屋 高旭, 長谷川 智一, 堀 正和, 染谷 正則, 坂田 耕一, 加藤 淳二

  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 )  128回・122回   35 - 35  2021.03

• Targeting Wnt/β-Catenin Pathway for Drug Therapy

  Chenglong Liu, Kohichi Takada, Di Zhu

  Medicine in Drug Discovery ( Elsevier B.V. )  8  2020.12

  Book review, literature introduction, etc.  

  　View Summary

  The Wnt/β-catenin signaling pathway, including canonical or noncanonical pathway, is a highly conserved pathway which can regulate cell proliferation, migration, differentiation, and apoptosis. The Wnt pathway has been shown to undergo aberrant activation in various cancers, particularly colorectal cancer. Wnt-targeted therapy attracted attention in a significant area of developmental therapeutics. Extensive efforts have been made to develop small-molecule drugs to inhibit the pathway for the treatment of various diseases. These small molecules disrupt protein-protein interactions in key parts of the pathway. Here, we review current indications for drug therapy and some problems in the treatment process that may be addressed in future investigations.

  DOI

• 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

• 低用量IL2はBCL2の発現を誘導することでCD4制御性T細胞のアポトーシスを抑制する(Low-close interleukin-2 induces BCL2 expression and resistance to apoptosis in CD4 regulatory T Cells)

  松野 鉄平, 村瀬 和幸, 高田 弘一, 河野 豊, 平川 昌宏, 宮西 浩嗣, 小船 雅義, 加藤 淳二

  札幌医学雑誌 ( 札幌医科大学 )  87 ( 1-6 ) 49 - 61  2018.12

  　View Summary

  制御性T細胞(Treg)は自己免疫寛容や恒常性の維持に重要な役割を果たしている。インターロイキン2(IL-2)はTregの増加、活動、生存に非常に重要である。既報では低用量IL-2はTregの増加に選択的に作用し、自己免疫疾患の臨床症状を改善させると報告されている。IL-2がTregの内因性アポトーシスにどのように作用するのかを調べるために、我々はBH3プロファイリングを用い、ミトコンドリアのアポトーシスプライミングを定量的に測定した。BH3ペプチドパターンではTregのプライミングがTconより多く、それがBCL2に依存していることを示した。実際に、TregではTconよりもBCL2の発現が低かった。IL-2の作用を調べるために、TregとTconに分け、異なった用量のIL-2で培養した。Tregでは低用量のIL-2(10 IU/ml)でプライミングは低下しBCL2発現は増加したが、Tconではプライミングの低下とBCL2発現の増加には高用量のIL-2(>100 IU/ml)が必要であった。また、低用量IL-2はTregにおいてのみアポトーシスへの感受性を減らすことがアポトーシスアッセイによって判明した。ABT-199というBCL2選択的阻害剤はTregとTcon両者のプライミングとアポトーシスを増加させる。IL2はTregにおいてのみこのABT-199の効果を打ち消した。このことからTregにおけるIL2による内因性アポトーシスの阻害がBCL2に依存していることが判明した。(著者抄録)

• A multidisciplinary treatment approach using docetaxel, nedaplatin, and 5-FU for advanced esophageal cancer

  Hiroyuki Ohnuma, Masahiro Hirakawa, Shohei Kikuchi, Yasushi Sato, Koichi Takada, Koji Miyanishi, Junji Kato

  ANNALS OF ONCOLOGY ( OXFORD UNIV PRESS )  28  2017.10

  Research paper, summary (international conference)  

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• 浜名湖シンポジウム研究助成演題

  2011.12  

• 日本肝臓学会 AASLD Travel Award

  2008.10  

• 浜名湖シンポジウム研究助成演題

  2006.12  

• 酸化ストレスと肝研究会 奨励賞

  2006.11  

• 第26回アルコール医学生物学研究会 優秀演題

  2006.03  

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• Development a novel immunotherapy for HCC targeted by BRG1

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2022.04

  -

  2025.03

   

  高田 弘一

  Authorship： Principal investigator

• MAGE-A4抗原を発現する切除不能進行・再発腫瘍に対するCAR-T細胞療法の医師主導第I相治験

  Project Year :

  2021.08

  -

  2024.03

   

  Authorship： Coinvestigator(s)

• Development a novel therapy for hepatocellular carcinoma by targeting STEAP1

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2019.04

  -

  2022.03

   

  Takada Kohichi

  　View Summary

  STEAP1 has emerged as an ideal target in cancer therapeutics. However, the functions of STEAP1 in hepatocellular carcinoma (HCC) remain unexplored. In the current study, we sought to characterize the biological roles of STEAP1 in HCC. STEAP1 transcripts are over-expressed and associated with poor clinical outcomes in patients with HCC in several publicly available datasets. STEAP1 silencing using small interfering RNA inhibited cell growth and was accompanied by G1 arrest induced by the suppression of cyclin D1 and the promotion of p27. STEAP1 silencing suppressed the expression of c-Myc, which we identified as a component in STEAP1 signal transduction by mining publicly available datasets, and confirmed this by PCR array. In conclusion, the knockdown of STEAP1 in HCC cells led to cell-growth inhibition involving G1 arrest by targeting the suppression of c-Myc. This study suggests a preclinical concept for STEAP1 as a druggable target in HCC.

• Development of a new treatment for colorectal cancer using the glucose metabolism characteristics.

  Grant-in-Aid for Scientific Research (B)

  Project Year :

  2017.04

  -

  2020.03

   

  Kato Junji

  　View Summary

  Metastatic / recurrent colorectal cancer is a disease with a poor prognosis, and the number of deaths continues to increase, and the development of more effective treatment methods is awaited. The FDG-PET examination, which utilizes the characteristics of increased sugar uptake in colorectal cancer, is useful for diagnosing colorectal cancer. Therefore, anticancer drugs using FDG as a carrier are promising as therapeutic agents for colorectal cancer. Therefore, we aimed to prepare an FDG-binding anticancer drug and examine its effect. A fluorescent reagent directly bound to FDG was prepared and examined, but no difference of anticancer effect from other sugar was observed. Considering that the stability of the reagent was a problem, we prepared a fluorescent reagent in which FDG was bound to liposomes, and found that it was taken up by cancer cells. In the future, we would like to promote the development of new anticancer agents that utilize this mechanism using FDG-binding liposomes.

• Reactive oxygen species play roles in multiple myeloma pathogenesis

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2016.04

  -

  2019.03

   

  Kohichi Takada

  　View Summary

  Six-transmembrane epithelial antigen of the prostate 1 (STEAP1), identified in prostate cancer cells as a cell surface protein, is over-expressed in a subset of human cancers. In cases of Ewing sarcoma, STEAP1 augmented cell proliferation and invasion and was accompanied by increased reactive oxygen spices (ROS) levels. Here, we characterized the biological impact of STEAP1 and ROS in multiple myeloma (MM) pathogenesis. STEAP1 expression negatively correlated with OS as determined from a publicly accessible gene expression profile data set. A loss-of-function approach in cultured MM cell lines revealed that STEAP1 silencing suppressed migration, invasion and bone marrow homing through inhibition of ROS production. Mechanistically, the inhibition of STEAP1 was associated with increased expression of anti-oxidant molecules regulated by the transcription factor, nuclear erythroid 2-related factor (NRF2), in MM cells. This study identified STEAP1 as a therapeutic target for MM.

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