Updated on 2024/04/08

写真a

 
TANAKA Ichidai
 
Organization
Nagoya University Hospital Respiratory Medicine Assistant Professor
Graduate School
Graduate School of Medicine
Title
Assistant Professor

Degree 1

  1. 医学博士 ( 2014.3   名古屋大学 ) 

Research Interests 8

  1. Lung Cancer

  2. Malignant Mesothelioma

  3. 分子生物学

  4. Mechanobiology

  5. Metabolomics

  6. Proteomics

  7. TTF-1陰性肺癌

  8. LKB1不活化肺癌

Research Areas 1

  1. Life Science / Respiratory medicine

Current Research Project and SDGs 3

  1. 悪性中皮腫に対する新規治療法開発のための基盤構築

  2. 肺癌・悪性中皮腫における腫瘍微小環境の解析

  3. 非小細胞肺に対する新規治療法の開発

Professional Memberships 8

  1. アジア太平洋呼吸器学会学術集会

    2022.3

  2. 日本呼吸器学会

  3. 日本呼吸器内視鏡学会

  4. 日本癌学会

  5. 日本臨床腫瘍学会

  6. 日本肺癌学会

  7. AACR

  8. 日本内科学会

▼display all

Awards 1

  1. 名大内科学研究奨励賞

    2013.7   名古屋大学  

     More details

    Country:Japan

 

Papers 47

  1. Benralizumab treatment in an elderly patient with eosinophilic esophagitis resulted in remission: a case report. Reviewed

    Ishii A, Shibata T, Tsunoda Y, Kayukawa T, Kobayashi M, Orinaka M, Miyamatsu S, Ryuge Y, Asano S, Tanaka I

    BMC geriatrics   Vol. 24 ( 1 ) page: 92   2024.1

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:BMC Geriatrics  

    Background: Interleukin-5 (IL-5) has recently been shown to play a crucial role in eosinophil-mediated diseases, implying that an IL-5 receptor alpha chain (IL-5Rα) antibody (benralizumab) can be effective against eosinophilic esophagitis (EoE). Here, we present a case in which benralizumab significantly improved the symptoms and signs of an elderly Asian woman with EoE who had inadequate response to existing treatments. Case presentation A 73-year-old woman with an 8-year history of bronchial asthma (BA) and a 7-year history of dysphagia presented to our hospital with worsening dysphagia, vomiting, chest pain, and difficulty in eating. Blood biochemical findings revealed an increase in the eosinophil fraction of white blood cells (42.2%), and a conventional chest computed tomography scan revealed esophageal wall thickening. An upper gastrointestinal endoscopy revealed mucosal edema as well as multiple esophageal rings, and esophageal biopsy specimens showed an eosinophilic infiltrate of more than 15 cells/ high power field. Based on these findings, she was diagnosed as EoE complicated by BA. We firstly administrated 20 mg/day of prednisolone, rabeprazole sodium and liquid budesonide oral suspension for 5 months; however, they were ineffective and her dysphagia worsened over time. Then, benralizumab treatment in combination with these drugs was started. Her dysphagia completely disappeared 2 weeks after starting benralizumab, and an upper endoscopy showed that the clinical findings had completely disappeared after another 6 weeks. Benralizumab was then given to her for 41 months, and her symptoms remained in remission. In addition, she had no EoE recurrence for more than 12 months after discontinuing benralizumab. Conclusions: Benralizumab in combination with other multiple drugs significantly improved the symptoms and examination findings of an elderly patients with EoE. Furthermore, she experienced no recurrence even after discontinuing benralizumab withdrawal, suggesting that benralizumab could be an appropriate therapeutic option for EoE.

    DOI: 10.1186/s12877-024-04683-1

    Scopus

    PubMed

  2. Metabolic barriers in non-small cell lung cancer with LKB1 and/or KEAP1 mutations for immunotherapeutic strategies. Reviewed

    Tanaka I, Koyama J, Itoigawa H, Hayai S, Morise M

    Frontiers in oncology   Vol. 13   page: 1249237   2023

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Frontiers in Oncology  

    Currently, immune checkpoint inhibitors (ICIs) are widely considered the standard initial treatment for advanced non-small cell lung cancer (NSCLC) when there are no targetable driver oncogenic alternations. NSCLC tumors that have two alterations in tumor suppressor genes, such as liver kinase B1 (LKB1) and/or Kelch-like ECH-associated protein 1 (KEAP1), have been found to exhibit reduced responsiveness to these therapeutic strategies, as revealed by multiomics analyses identifying immunosuppressed phenotypes. Recent advancements in various biological approaches have gradually unveiled the molecular mechanisms underlying intrinsic reprogrammed metabolism in tumor cells, which contribute to the evasion of immune responses by the tumor. Notably, metabolic alterations in glycolysis and glutaminolysis have a significant impact on tumor aggressiveness and the remodeling of the tumor microenvironment. Since glucose and glutamine are essential for the proliferation and activation of effector T cells, heightened consumption of these nutrients by tumor cells results in immunosuppression and resistance to ICI therapies. This review provides a comprehensive summary of the clinical efficacies of current therapeutic strategies against NSCLC harboring LKB1 and/or KEAP1 mutations, along with the metabolic alterations in glycolysis and glutaminolysis observed in these cancer cells. Furthermore, ongoing trials targeting these metabolic alterations are discussed as potential approaches to overcome the extremely poor prognosis associated with this type of cancer.

    DOI: 10.3389/fonc.2023.1249237

    Scopus

    PubMed

  3. Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis Reviewed

    Gen S., Tanaka I., Morise M., Koyama J., Kodama Y., Matsui A., Miyazawa A., Hase T., Hibino Y., Yokoyama T., Kimura T., Yoshida N., Sato M., Hashimoto N.

    BMC Cancer   Vol. 22 ( 1 )   2022.12

     More details

    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:BMC Cancer  

    Background: Osimertinib—the third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)—has been widely used as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib demonstrated central nervous system activity in patients with brain metastasis; however, its efficacy against other distant metastatic organs, including bone and liver, remains unclear. Therefore, we retrospectively analyzed the clinical efficacy of osimertinib in these patients in comparison to other EGFR-TKIs. Methods: Clinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n = 183), afatinib (n = 55), or osimertinib (n = 150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR). Results: In univariate and multivariate analyses, most distant metastases, including the brain and bone, were unrelated to the therapeutic efficacy of osimertinib, although liver metastasis and L858R mutation were independently associated with shorter PFS. PFS and OS in patients with liver metastases were significantly shorter than those in patients without liver metastases (PFS: 7.4 vs. 19.7 months, OS: 12.1 months vs. not reached, respectively). Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs. The PFS of patients with liver metastases was not significantly different among the three EGFR-TKI groups. Furthermore, the ORR of osimertinib in patients with liver metastases was significantly attenuated, and the effectiveness was similar to 1st- or 2nd -generation EGFR-TKIs. Conclusion: Osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion; however, its efficacy against liver metastasis was remarkably attenuated. New therapeutic developments for patients with EGFR-mutant NSCLC with liver metastases are needed.

    DOI: 10.1186/s12885-022-09741-8

    Scopus

  4. SRGN-Triggered Aggressive and Immunosuppressive Phenotype in a Subset of TTF-1-Negative Lung Adenocarcinomas. Reviewed International coauthorship

    Tanaka I, Dayde D, Tai MC, Mori H, Solis LM, Tripathi SC, Fahrmann JF, Unver N, Parhy G, Jain R, Parra ER, Murakami Y, Aguilar-Bonavides C, Mino B, Celiktas M, Dhillon D, Casabar JP, Nakatochi M, Stingo F, Baladandayuthapani V, Wang H, Katayama H, Dennison JB, Lorenzi PL, Do KA, Fujimoto J, Behrens C, Ostrin EJ, Rodriguez-Canales J, Hase T, Fukui T, Kajino T, Kato S, Yatabe Y, Hosoda W, Kawaguchi K, Yokoi K, Chen-Yoshikawa TF, Hasegawa Y, Gazdar AF, Wistuba II, Hanash S, Taguchi A

    Journal of the National Cancer Institute     2022.2

     More details

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

    DOI: 10.1093/jnci/djab183

    PubMed

  5. Current immunotherapeutic strategies targeting the PD-1/PD-L1 axis in non-small cell lung cancer with oncogenic driver mutations Reviewed

    Tanaka I., Morise M.

    International Journal of Molecular Sciences   Vol. 23 ( 1 )   2022.1

     More details

    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:International Journal of Molecular Sciences  

    Treatment strategies targeting programed cell death 1 (PD-1) or its ligand, PD-L1, have been developed as immunotherapy against tumor progression for various cancer types including non-small cell lung cancer (NSCLC). The recent pivotal clinical trials of immune-checkpoint inhibiters (ICIs) combined with cytotoxic chemotherapy have reshaped therapeutic strategies and established various first-line standard treatments. The therapeutic effects of ICIs in these clinical trials were analyzed according to PD-L1 tumor proportion scores or tumor mutational burden; however, these indicators are insufficient to predict the clinical outcome. Consequently, molecular biological approaches, including multi-omics analyses, have addressed other mechanisms of cancer immune escape and have revealed an association of NSCLC containing specific driver mutations with distinct immune phenotypes. NSCLC has been characterized by driver mutation-defined molecular subsets and the effect of driver mutations on the regulatory mechanism of PD-L1 expression on the tumor itself. In this review, we summarize the results of recent clinical trials of ICIs in advanced NSCLC and the association between driver alterations and distinct immune phenotypes. We further discuss the current clinical issues with a future perspective for the role of precision medicine in NSCLC.

    DOI: 10.3390/ijms23010245

    Scopus

  6. The current issues and future perspective of artificial intelligence for developing new treatment strategy in non-small cell lung cancer: harmonization of molecular cancer biology and artificial intelligence Invited Reviewed

    Tanaka Ichidai, Furukawa Taiki, Morise Masahiro

    CANCER CELL INTERNATIONAL   Vol. 21 ( 1 ) page: 454   2021.8

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Cancer Cell International  

    Comprehensive analysis of omics data, such as genome, transcriptome, proteome, metabolome, and interactome, is a crucial technique for elucidating the complex mechanism of cancer onset and progression. Recently, a variety of new findings have been reported based on multi-omics analysis in combination with various clinical information. However, integrated analysis of multi-omics data is extremely labor intensive, making the development of new analysis technology indispensable. Artificial intelligence (AI), which has been under development in recent years, is quickly becoming an effective approach to reduce the labor involved in analyzing large amounts of complex data and to obtain valuable information that is often overlooked in manual analysis and experiments. The use of AI, such as machine learning approaches and deep learning systems, allows for the efficient analysis of massive omics data combined with accurate clinical information and can lead to comprehensive predictive models that will be desirable for further developing individual treatment strategies of immunotherapy and molecular target therapy. Here, we aim to review the potential of AI in the integrated analysis of omics data and clinical information with a special focus on recent advances in the discovery of new biomarkers and the future direction of personalized medicine in non-small lung cancer.

    DOI: 10.1186/s12935-021-02165-7

    Web of Science

    Scopus

    PubMed

  7. Oxytocin receptor is a promising therapeutic target of malignant mesothelioma Reviewed

    Cancer Sci.     2021.7

     More details

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

  8. Efficacies of programmed cell death 1 ligand 1 blockade in non-small cell lung cancer patients with acquired resistance to prior programmed cell death 1 inhibitor and development of diabetic ketoacidosis caused by two different etiologies: a retrospective case series. Reviewed International coauthorship

    Ishi A, Tanaka I, Iwama S, Sakakibara T, Mastui T, Kobayashi T, Hase T, Morise M, Sato M, Arima H, Hashimoto N

    Endocrine journal   Vol. 68 ( 5 ) page: 613 - 620   2021.5

     More details

    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:一般社団法人 日本内分泌学会  

    <p>The programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis is vital for immune resistance during tumor development, while PD-L1 inhibitors can also inhibit the PD-L1/B7-1 (CD80) interaction, indicating one of the molecular differences between PD-1 and PD-L1 inhibitors. However, the clinical benefits of PD-L1 inhibitors in patients previously treated with PD-1 inhibitors remain unknown. In this study, we retrospectively analyzed the clinical data of eight patients with non-small cell lung cancer who received the PD-L1 inhibitor atezolizumab and previously treated with the PD-1 inhibitor nivolumab. The median progression-free survival was 2.1 months (1.8–18.7 months), and 4 of 8 patients achieved at least stable disease. In two of these patients, atezolizumab treatment resulted in longer progression-free survival (PFS) compared with that of nivolumab. Conversely, one patient exhibited grade 4 diabetic ketoacidosis (DKA) within 2 weeks after the initial administration of atezolizumab. Another patient had developed type 1 diabetes mellitus (T1DM) during the prior nivolumab treatment and then developed DKA due to an infection after the initiation of atezolizumab. Both of them had high-risk human leukocyte antigen-DR/DQ types relevant to T1DM. These results demonstrate the potential efficacy of PD-L1 inhibitors to some tumors that have acquired resistance to PD-1 inhibitors and suggest that appropriate managements are required for not only a newly onset of T1DM but also blood glucose control after the development of T1DM during a reiteration of the PD-1/PD-L1 blockade.</p>

    DOI: 10.1507/endocrj.EJ20-0769

    Scopus

    PubMed

  9. Potential Benefits of Bevacizumab Combined With Platinum-Based Chemotherapy in Advanced Non-Small-Cell Lung Cancer Patients With EGFR Mutation Reviewed International coauthorship International journal

    Tanaka Ichidai, Morise Masahiro, Miyazawa Ayako, Kodama Yuta, Tamiya Yutaro, Gen Soei, Matsui Akira, Hase Tetsunari, Hashimoto Naozumi, Sato Mitsuo, Hasegawa Yoshinori

    CLINICAL LUNG CANCER   Vol. 21 ( 3 ) page: 273 - +   2020.5

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Clinical Lung Cancer  

    DOI: 10.1016/j.cllc.2020.01.011

    Web of Science

    Scopus

    PubMed

  10. Potential for afatinib as an optimal treatment for advanced non-small cell lung carcinoma in patients with uncommon EGFR mutations Reviewed International journal

    Tanaka Ichidai, Morise Masahiro, Kodama Yuta, Matsui Akira, Ozawa Naoya, Ozone Sachiko, Goto Daiki, Miyazawa Ayako, Hase Tetsunari, Hashimoto Naozumi, Sato Mitsuo, Hasegawa Yoshinori

    LUNG CANCER   Vol. 127   page: 169 - 171   2019.1

     More details

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

    DOI: 10.1016/j.lungcan.2018.11.018

    Web of Science

    Scopus

    PubMed

  11. The Subunit eIF2 ss of Translation- Initiation Factor EIF2 Is a Potential Therapeutic Target for Non-Small Cell Lung Cancer Reviewed International coauthorship

    Tanaka Ichidai, Sato Mitsuo,Goto Daiki, Kato Toshio, Kakumu Tomohiko, Miyazawa Ayako, Yogo Naoyuki, Hase Tetsunari, Morise Masahiro, Sekido Yoshitaka, Kondo Masashi, Hasegawa Yoshinori

    CANCER SCIENCE   Vol. 109   page: 1181-1181   2018.12

     More details

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

    Web of Science

  12. Aberrant tryptophan catabolism marked by high kynureninase expression contributes to immunosuppression and poor outcome in lung adenocarcinoma Reviewed International coauthorship

    Ostrin Edwin J., Fahrmann Johannes F., Tanaka Ichidai, Celiktas Muge, Aguilar Clemente, Aguilar Mitzi, Dennison Jennifer B., Murage Eunice, Tripathi Satyendra C., Delgado Oliver, Wang Hong, Rodriguez-Canales Jaime, Behrens Carmen, Wistuba Ignacio I., Taguchi Ayumu, Hanash Samir M.

    CANCER RESEARCH   Vol. 78 ( 13 )   2018.7

     More details

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

    DOI: 10.1158/1538-7445.AM2018-1447

    Web of Science

  13. A phase II trial of Ifosfamide combination with recommended supportive therapy for recurrent SCLC in second-line and heavily treated setting Reviewed International coauthorship International journal

    Tanaka Ichidai, Kawada Kenji, Morise Masahiro, Hase Tetsunari, Hayashi Hiroaki, Sokai Akihiko, Fukatsu Asuki, Kondo Masashi, Nomura Fumio, Hasegawa Yoshinori

    CANCER CHEMOTHERAPY AND PHARMACOLOGY   Vol. 81 ( 2 ) page: 339 - 345   2018.2

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Cancer Chemotherapy and Pharmacology  

    DOI: 10.1007/s00280-017-3497-0

    Web of Science

    Scopus

    PubMed

  14. Role of CPS1 in Cell Growth, Metabolism and Prognosis in LKB1-Inactivated Lung Adenocarcinoma. Reviewed International coauthorship International journal

    Journal of the National Cancer Institute   Vol. 109 ( 3 ) page: 1 - 9   2017.3

     More details

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

    DOI: 10.1093/jnci/djw231

    Web of Science

    Scopus

    PubMed

  15. LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade. Reviewed International journal

    Tanaka I, Osada H, Fujii M, Fukatsu A, Hida T, Horio Y, Kondo Y, Sato A, Hasegawa Y, Tsujimura T, Sekido Y

    Oncogene   Vol. 34 ( 1 ) page: 73 - 83   2015.1

     More details

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

    DOI: 10.1038/onc.2013.528

    Web of Science

    Scopus

    PubMed

  16. Circulating microRNA Panel for Prediction of Recurrence and Survival in Early-Stage Lung Adenocarcinoma Reviewed

    Tai, MC; Bantis, LE; Parhy, G; Kato, T; Tanaka, I; Chow, CW; Fujimoto, J; Behrens, C; Hase, T; Kawaguchi, K; Fahrmann, JF; Ostrin, EJ; Yokoi, K; Chen-Yoshikawa, TF; Hasegawa, Y; Hanash, SM; Wistuba, II; Taguchi, A

    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES   Vol. 25 ( 4 )   2024.2

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:International Journal of Molecular Sciences  

    Early-stage lung adenocarcinoma (LUAD) patients remain at substantial risk for recurrence and disease-related death, highlighting the unmet need of biomarkers for the assessment and identification of those in an early stage who would likely benefit from adjuvant chemotherapy. To identify circulating miRNAs useful for predicting recurrence in early-stage LUAD, we performed miRNA microarray analysis with pools of pretreatment plasma samples from patients with stage I LUAD who developed recurrence or remained recurrence-free during the follow-up period. Subsequent validation in 85 patients with stage I LUAD resulted in the development of a circulating miRNA panel comprising miR-23a-3p, miR-320c, and miR-125b-5p and yielding an area under the curve (AUC) of 0.776 in predicting recurrence. Furthermore, the three-miRNA panel yielded an AUC of 0.804, with a sensitivity of 45.8% at 95% specificity in the independent test set of 57 stage I and II LUAD patients. The miRNA panel score was a significant and independent factor for predicting disease-free survival (p < 0.001, hazard ratio [HR] = 1.64, 95% confidence interval [CI] = 1.51–4.22) and overall survival (p = 0.001, HR = 1.51, 95% CI = 1.17–1.94). This circulating miRNA panel is a useful noninvasive tool to stratify early-stage LUAD patients and determine an appropriate treatment plan with maximal efficacy.

    DOI: 10.3390/ijms25042331

    Web of Science

    Scopus

    PubMed

  17. The oncogenic role of LGR6 overexpression induced by aberrant Wnt/β-catenin signaling in lung cancer. Reviewed

    Sunaga N, Kaira K, Shimizu K, Tanaka I, Miura Y, Nakazawa S, Ohtaki Y, Kawabata-Iwakawa R, Sato M, Girard L, Minna JD, Hisada T

    Thoracic cancer   Vol. 15 ( 2 ) page: 131 - 141   2024.1

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Thoracic Cancer  

    Background: Molecular abnormalities in the Wnt/β-catenin pathway confer malignant phenotypes in lung cancer. Previously, we identified the association of leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6) with oncogenic Wnt signaling, and its downregulation upon β-catenin knockdown in non-small cell lung cancer (NSCLC) cells carrying CTNNB1 mutations. The aim of this study was to explore the mechanisms underlying this association and the accompanying phenotypes. Methods: LGR6 expression in lung cancer cell lines and surgical specimens was analyzed using quantitative RT-PCR and immunohistochemistry. Cell growth was assessed using colony formation assay. Additionally, mRNA sequencing was performed to compare the expression profiles of cells subjected to different treatments. Results: LGR6 was overexpressed in small cell lung cancer (SCLC) and NSCLC cell lines, including the CTNNB1-mutated NSCLC cell lines HCC15 and A427. In both cell lines, LGR6 knockdown inhibited cell growth. LGR6 expression was upregulated in spheroids compared to adherent cultures of A427 cells, suggesting that LGR6 participates in the acquisition of cancer stem cell properties. Immunohistochemical analysis of lung cancer specimens revealed that the LGR6 protein was predominantly overexpressed in SCLCs, large cell neuroendocrine carcinomas, and lung adenocarcinomas, wherein LGR6 overexpression was associated with vascular invasion, the wild-type EGFR genotype, and an unfavorable prognosis. Integrated mRNA sequencing analysis of HCC15 and A427 cells with or without LGR6 knockdown revealed LGR6-related pathways and genes associated with cancer development and stemness properties. Conclusions: Our findings highlight the oncogenic roles of LGR6 overexpression induced by aberrant Wnt/β-catenin signaling in lung cancer.

    DOI: 10.1111/1759-7714.15169

    Scopus

    PubMed

  18. Inhalation adherence for asthma and COPD improved during the COVID-19 pandemic: a questionnaire survey at a university hospital in Japan. Reviewed

    Fukutani E, Wakahara K, Nakamura S, Yokoi E, Yoshimi A, Miyazaki M, Nakamura M, Shindo Y, Sakamoto K, Okachi S, Tanaka I, Hamajima N, Noda Y, Hashimoto N, Ishii M

    The Journal of asthma : official journal of the Association for the Care of Asthma   Vol. 60 ( 11 ) page: 2002 - 2013   2023.11

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Asthma  

    Background: Good adherence to an inhaled medication protocol is necessary for the management of asthma and chronic obstructive pulmonary disease (COPD), and several interventions to improve adherence have been reported. However, the impact of patient life changes and psychological aspects on treatment motivation is obscure. Here, we investigated changes in inhaler adherence during the COVID-19 pandemic and how lifestyle and psychological changes affected it. Methods: Seven-hundred sixteen adult patients with asthma and COPD who had visited Nagoya University Hospital between 2015 and 2020 were selected. Among them, 311 patients had received instruction at a pharmacist-managed clinic (PMC). We distributed one-time cross-sectional questionnaires from January 12 to March 31, 2021. The questionnaire covered the status of hospital visits, inhalation adherence before and during the COVID-19 pandemic, lifestyles, medical conditions, and psychological stress. The Adherence Starts with Knowledge-12 (ASK-12) was used to assess adherence barriers. Results: Four-hundred thirty-three patients answered the questionnaire. Inhalation adherence was significantly improved in both diseases during the COVID-19 pandemic. The most common reason for improved adherence was fear of infection. Patients with improved adherence were more likely to believe that controller inhalers could prevent COVID-19 from becoming more severe. Improved adherence was more common in patients with asthma, those not receiving counseling at PMC, and those with poor baseline adherence. Conclusions: Inhalation adherence for asthma and COPD improved in the COVID-19 pandemic. The patients seemed to realize the necessity and benefits of the medication more strongly than before the pandemic, which motivated them to improve adherence.

    DOI: 10.1080/02770903.2023.2209173

    Scopus

    PubMed

  19. Silencing of GRHL2 induces epithelial‑to‑mesenchymal transition in lung cancer cell lines with different effects on proliferation and clonogenic growth. Reviewed

    Kawabe N, Matsuoka K, Komeda K, Muraki N, Takaba M, Togami Y, Ito Y, Yamada M, Sunaga N, Girard L, Minna JD, Cai L, Xie Y, Tanaka I, Morise M, Sato M

    Oncology letters   Vol. 26 ( 3 ) page: 391   2023.9

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oncology Letters  

    Grainyhead-like 2 (GRHL2) is a transcription factor that suppresses epithelial-to-mesenchymal transition (EMT). It has been previously shown that GRHL2 can confer both oncogenic and tumor-suppressive roles in human cancers, including breast, pancreatic and colorectal cancers. However, its role in lung cancer remains elusive. In the present study, a meta-analysis of multiple gene expression datasets with clinical data revealed that GRHL2 expression was increased in lung cancer compared with that in the normal tissues. Copy number analysis of GRHL2, performed using datasets of whole exome sequencing involving 151 lung cancer cell lines, revealed frequent amplifications, suggesting that the increased GRHL2 expression may have resulted from gene amplification. A survival meta-analysis of GRHL2 using The Cancer Genome Atlas (TCGA) dataset showed no association of GRHL2 expression with overall survival. GRHL2 expression was found to be associated with EMT status in lung cancer in TCGA dataset and lung cancer cell lines. GRHL2 knockdown induced partial EMT in the hTERT/Cdk4-immortalized normal lung epithelial cell line HBEC4KT without affecting proliferation measured by CCK-8 assays. In addition, GRHL2 silencing caused three lung cancer cell lines, H1975, H2009 and H441, to undergo partial EMT. However, the proliferative effects differed significantly. GRHL2 silencing promoted proliferation but not colony formation in H1975 cells whilst suppressing colony formation without affecting proliferation in H2009 cells, but it did not affect proliferation in H441 cells. These results suggest cell type-dependent effects of GRHL2 knockdown. Downstream, GRHL2 silencing enhanced the phosphorylation of AKT and ERK, assessed by western blotting with phospho-specific antibodies, in HBEC4KT, H1975 and H2009 cell lines but not in the H441 cell line. By contrast, transient GRHL2 overexpression did not affect A549 cell proliferation, which lack detectable endogenous expression of the GRHL2 protein. However, GRHL2 overexpression did suppress E-cadherin expression in A549 cells. These results suggested that GRHL2 does not only function as a tumor suppressor of EMT but can also behave as an oncogene depending on the lung cancer cell-type context.

    DOI: 10.3892/ol.2023.13977

    Scopus

    PubMed

  20. Non-invasive early prediction of immune checkpoint inhibitor efficacy in non-small-cell lung cancer patients using on-treatment serum CRP and NLR. Reviewed

    Matsuzawa R, Morise M, Kinoshita F, Tanaka I, Koyama J, Kimura T, Kondoh Y, Tanaka T, Shima K, Hase T, Wakahara K, Ishii M, Hashimoto N

    Journal of cancer research and clinical oncology     2022.8

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Journal of Cancer Research and Clinical Oncology  

    Purpose: We determined the clinical relevance of early C-reactive protein (CRP) and neutrophil–lymphocyte ratio (NLR) change in blood as surrogate markers of pro-tumor inflammation (PTI) for predicting clinical outcome of programmed cell death (PD)-1/programmed cell death ligand (PD-L) 1 inhibitor treatment in non-small-cell lung carcinoma (NSCLC). Methods: We retrospectively reviewed NSCLC patients treated with anti-PD-1 or PD-L1 inhibitors. Early CRP change was defined as the ratio of 6 weeks CRP to baseline CRP, and early NLR change was defined as that of the 6 weeks NLR to baseline NLR. PTI index was determined by combinatorial evaluation of early CRP change and early NLR change, PTI index low: both of these were low, intermediate: either of these was low, high; both of these were high. Results: The study included 217 patients. Early CRP change and early NLR change were both associated with PFS and OS. The combinatorial evaluation using these two markers enabled the clear stratification of PFS and OS. The median PFS in patient with PTI index low was 13.9 months, while the median PFS in those with PTI index high was 2.5 months (p < 0.01, log-rank test). The median OS in patients with PTI index low was not reached; the median OS in those with PTI index high was only 15.4 months (p < 0.01, log-rank test). Conclusions: The combinatorial early CRP change and early NLR change as PTI biomarkers have clinical potential in identifying NSCLC patients who can achieve a durable response and long-term survival using PD-1/PD-L1 inhibitors.

    DOI: 10.1007/s00432-022-04300-x

    Scopus

    PubMed

  21. Resistance to mutant KRAS<sup>V12</sup>-induced senescence in an hTERT/Cdk4-immortalized normal human bronchial epithelial cell line Reviewed

    Muraki N., Yamada M., Doki H., Nakai R., Komeda K., Goto D., Kawabe N., Matsuoka K., Matsushima M., Kawabe T., Tanaka I., Morise M., Shay J.W., Minna J.D., Sato M.

    Experimental Cell Research   Vol. 414 ( 1 )   2022.5

     More details

    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Experimental Cell Research  

    Mutant KRAS, the most frequently occurring (∼30%) driver oncogene in lung adenocarcinoma, induces normal epithelial cells to undergo senescence. This phenomenon, called “oncogene-induced senescence (OIS)”, prevents mutant KRAS-induced malignant transformation. We have previously reported that mutant KRASV12 induces OIS in a subset of normal human bronchial epithelial cell line immortalized with hTERT and Cdk4. Understanding the mechanism and efficacy of this important cancer prevention mechanism is a key knowledge gap. Therefore, this study investigates mutant KRASV12-induced OIS in upregulated telomerase combined with the p16/RB pathway inactivation in normal bronchial epithelial cells. The normal (non-transformed and non-tumorigenic) human bronchial epithelial cell line HBEC3 (also called “HBEC3KT”), immortalized with hTERT (“T”) and Cdk4 (“K”), was used in this study. HBEC3 that expressed mutant KRASV12 in a doxycycline-regulated manner was established (designated as HBEC3-RIN2). Controlled induction of mutant KRASV12 expression induced partial epithelial-to-mesenchymal transition in HBEC3-RIN2 cells, which was associated with upregulated expression of ZEB1 and SNAIL. Mutant KRASV12 caused the majority of HBEC3-RIN2 to undergo morphological changes; suggestive of senescence, which was associated with enhanced autophagic flux. Upon mutant KRASV12 expression, only a small HBEC3-RIN2 cell subset underwent senescence, as assessed by a senescence-associated β-galactosidase staining (SA-βG) method. Furthermore, mutant KRASV12 enhanced cell growth, evaluated by colorimetric proliferation assay, and liquid and soft agar colony formation assays, partially through increased phosphorylated AKT and ERK expression but did not affect cell division, or cell cycle status. Intriguingly, mutant KRASV12 reduced p53 protein expression but increased p21 protein expression by prolonging its half-life. These results indicate that an hTERT/Cdk4 -immortalized normal bronchial epithelial cell line is partially resistant to mutant KRASV12-induced senescence. This suggests that OIS does not efficiently suppress KRASV12-induced transformation in the context of the simultaneous occurrence of telomerase upregulation and inactivation of the p16/Rb pathway.

    DOI: 10.1016/j.yexcr.2022.113053

    Scopus

  22. Mutational Activation of the NRF2 Pathway Upregulates Kynureninase Resulting in Tumor Immunosuppression and Poor Outcome in Lung Adenocarcinoma Reviewed

    Fahrmann Johannes F., Tanaka Ichidai, Irajizad Ehsan, Mao Xiangying, Dennison Jennifer B., Murage Eunice, Casabar Julian, Mayo Jeffrey, Peng Qian, Celiktas Muge, Vykoukal Jody V., Park Soyoung, Taguchi Ayumu, Delgado Oliver, Tripathi Satyendra C., Katayama Hiroyuki, Soto Luisa Maren Solis, Rodriguez-Canales Jaime, Behrens Carmen, Wistuba Ignacio, Hanash Samir, Ostrin Edwin J.

    CANCERS   Vol. 14 ( 10 )   2022.5

     More details

    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Cancers  

    Activation of the NRF2 pathway through gain-of-function mutations or loss-of-function of its suppressor KEAP1 is a frequent finding in lung cancer. NRF2 activation has been reported to alter the tumor microenvironment. Here, we demonstrated that NRF2 alters tryptophan metabolism through the kynurenine pathway that is associated with a tumor-promoting, immune suppressed microenvironment. Specifically, proteomic profiles of 47 lung adenocarcinoma (LUAD) cell lines (11 KEAP1 mutant and 36 KEAP1 wild-type) revealed the tryptophan-kynurenine enzyme kynureninase (KYNU) as a top overexpressed protein associated with activated NRF2. The siRNA-mediated knockdown of NFE2L2, the gene encoding for NRF2, or activation of the NRF2 pathway through siRNA-mediated knockdown of KEAP1 or via chemical induction with the NRF2-activator CDDO-Me confirmed that NRF2 is a regulator of KYNU expression in LUAD. Metabolomic analyses confirmed KYNU to be enzymatically functional. Analysis of multiple independent gene expression datasets of LUAD, as well as a LUAD tumor microarray demonstrated that elevated KYNU was associated with immunosuppression, including potent induction of T-regulatory cells, increased levels of PD1 and PD-L1, and resulted in poorer survival. Our findings indicate a novel mechanism of NRF2 tumoral immunosuppression through upregulation of KYNU.

    DOI: 10.3390/cancers14102543

    Web of Science

    Scopus

  23. Amelanotic Malignant Melanoma with a BRAF V600E Mutation Mimicking Primary Lung Cancer. Reviewed

    Matsuzawa R, Morise M, Tanaka I, Hayai S, Tamiya Y, Koyama J, Hase T, Wakahara K, Deoksu K, Shimoyama Y, Hashimoto N

    Internal medicine (Tokyo, Japan)     2021.8

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:一般社団法人 日本内科学会  

    <p>Amelanotic melanoma is a rare type of melanoma that shows little or no melanin pigmentation. When tumor lesions are not detected in cutaneous sites, the presence of melanin is the hallmark sign of malignant melanoma. We herein report a case of amelanotic melanoma with a <i>BRAF V600E</i> mutation mimicking primary lung cancer that was finally diagnosed on an autopsy. The current case suggests important caveats for the differential diagnosis of patients with <i>BRAF V600E</i> mutation-positive poorly differentiated lung tumors. In terms of the pathological diagnosis, routine immunohistochemical staining may be useful, especially in patients with a poorly differentiated lung tumor without TTF-1 expression. </p>

    DOI: 10.2169/internalmedicine.6657-20

    PubMed

  24. Is area under the curve the best parameter for carboplatin induced emetic risk stratification? Reviewed

    Ozone S., Ichikawa K., Morise M., Matsui A., Kinoshita F., Matsuzawa R., Koyama J., Tanaka I., Hashimoto N.

    Nagoya Journal of Medical Science   Vol. 83 ( 4 ) page: 773 - 785   2021

     More details

    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Nagoya Journal of Medical Science  

    Carboplatin (CBDCA)-induced emetic risk is currently classified on the basis of CBDCA-area under the curve (CBDCA-AUC). We investigated the utility of three CBDCA dosage parameters for predicting emesis by CBDCA. Patients with thoracic cancer treated with CBDCA were included. The endpoints were complete response (CR) and total control (TC). CR was defined as no vomiting and no use of rescue medication during the overall assessment period, whereas TC was defined as no vomiting, nausea, nor use of rescue medication during the overall assessment period. The parameters of CBDCA were defined as follows: (1) CBDCA-AUC; (2) CBDCA/body surface area (BSA): the administered dose of CBDCA per body surface area (mg/m2); and (3) total CBDCA/body: the total administered dose of CBDCA (mg). Eighty-five patients were evaluated. The median CBDCA/BSA but not CBDCA-AUC was higher in patients with non-CR compared to those with CR. Receiver operating characteristic curve analysis revealed that the AUC of CBDCA/BSA for predicting non-CR was higher than that of CBDCA-AUC. CBDCA/BSA shows greater potential for predicting CBDCA-induced emetic risk compared with CBDCA-AUC, which is the parameter in current antiemetic guidelines.

    DOI: 10.18999/nagjms.83.4.773

    Scopus

  25. Primary Prophylaxis Indication for Docetaxel Induced Febrile Neutropenia in Elderly Patients with Non-Small Cell Lung Cancer Reviewed International journal

    Matsui Akira, Morise Masahiro, Tanaka Ichidai, Ozone Sachiko, Matsuzawa Reiko, Koyama Junji, Hase Tetsunari, Hashimoto Naozumi, Sato Mitsuo, Hasegawa Yoshinori

    CANCER INVESTIGATION   Vol. 38 ( 7 ) page: 424 - 430   2020.8

     More details

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

    DOI: 10.1080/07357907.2020.1793350

    Web of Science

    Scopus

    PubMed

  26. Plasma-Derived Extracellular Vesicles Convey Protein Signatures That Reflect Pathophysiology in Lung and Pancreatic Adenocarcinomas Reviewed International coauthorship International journal

    Fahrmann Johannes F., Mao Xiangying, Irajizad Ehsan, Katayama Hiroyuki, Capello Michela, Tanaka Ichidai, Kato Taketo, Wistuba Ignacio I., Maitra Anirban, Ostrin Edwin J., Hanash Samir M., Vykoukal Jody

    CANCERS   Vol. 12 ( 5 )   2020.5

     More details

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

    DOI: 10.3390/cancers12051147

    Web of Science

    Scopus

    PubMed

  27. UHRF1, a Regulator of Methylation, as a Diagnostic and Prognostic Marker for Lung Cancer Reviewed

    Goto D., Komeda K., Uwatoko N., Nakashima M., Koike M., Kawai K., Kodama Y., Miyazawa A., Tanaka I., Hase T., Morise M., Hasegawa Y., Kawabe T., Sato M.

    Cancer Investigation   Vol. 38 ( 4 ) page: 240 - 249   2020.4

     More details

    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Cancer Investigation  

    We evaluated the value of UHRF1, a regulator of methylation, as a biomarker for lung cancer. UHRF1 is expressed at higher levels in both lung adenocarcinoma (AD) and squamous cell carcinoma (SQ); however, a meta-analysis showed that UHRF1 expression is correlated with worse survival in patients with AD but not in those with SQ. UHRF1 knockdown suppressed the growth of lung cancer cell lines through G1 cell cycle arrest in some cell lines. These results suggest that UHRF1 may server as a diagnostic marker for AD and SQ and as a prognostic marker for AD in lung cancer.

    DOI: 10.1080/07357907.2020.1747483

    Scopus

  28. Impact of Combined Evaluation Using Tumor Volume and Metastatic Nodal Extent in Stage III NSCLC Treated with CRT Reviewed International journal

    Tamiya Y., Morise M., Matsuzawa R., Tanaka I., Okada T., Iwano S., Hase T., Hashimoto N., Sato M., Itoh Y., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 14 ( 10 ) page: S909 - S910   2019.10

     More details

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

    Web of Science

  29. UHRF1 as a Potential Therapeutic Target for KRAS Mutated Non-Small Cell Lung Cancer Reviewed International journal

    Goto D., Kizuki M., Uwatoko N., Kawai K., Koike M., Nakashima M., Miyazawa A., Tanaka I., Hase T., Morise M., Hasegawa Y., Minna J., Sato M.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 14 ( 10 ) page: S692 - S692   2019.10

     More details

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

    Web of Science

  30. Impact of Combined Evaluation Using Tumor Volume and Metastatic Nodal Extent in Stage III NSCLC Treated with CRT Reviewed International journal

    Tamiya Y, Morise M, Matsuzawa R, Tanaka I, Okada T, Iwano S, Hase T, Hashimoto N, Sato M, Itoh Y, Hasegawa Y

    JOURNAL OF THORACIC ONCOLOGY   Vol. 14 ( 10 ) page: S909 - S910   2019.10

     More details

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

  31. CADM1 associates with Hippo pathway core kinases; membranous co-expression of CADM1 and LATS2 in lung tumors predicts good prognosis Reviewed International journal

    Ito Takeshi, Nakamura Atsuko, Tanaka Ichidai, Tsuboi Yumi, Morikawa Teppei, Nakajima Jun, Takai Daiya, Fukayama Masashi, Sekido Yoshitaka, Niki Toshiro, Matsubara Daisuke, Murakami Yoshinori

    CANCER SCIENCE   Vol. 110 ( 7 ) page: 2284 - 2295   2019.7

     More details

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

    DOI: 10.1111/cas.14040

    Web of Science

    Scopus

    PubMed

  32. Mechanobiology of Lung Cancer Cells: Regulation of PD-L1 Expression by Matrix Stiffness

    Miyazawa A., Ito S., Asano S., Tanaka I., Sato M., Kondo M., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 13 ( 10 ) page: S518-S518   2018.10

     More details

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

    Web of Science

  33. eIF2 beta, A Subunit of Translation-Initiation Factor EIF2, as a Potential Therapeutic Target for Non-Small Cell Lung Cancer

    Goto D., Tanaka I., Sato M., Kato T., Miyazawa A., Hase T., Morise M., Sekido Y., Girard L., Minna J., Byers L., Heymach J., Coombes K., Kondo M., Hasegawa Y.

    JOURNAL OF THORACIC ONCOLOGY   Vol. 13 ( 10 ) page: S516 - S517   2018.10

     More details

    Publishing type:Research paper (scientific journal)  

    Web of Science

  34. eIF2 beta, a subunit of translation-initiation factor EIF2, is a potential therapeutic target for non-small cell lung cancer Reviewed International journal

    Tanaka Ichidai, Sato Mitsuo, Kato Toshio, Goto Daiki, Kakumu Tomohiko, Miyazawa Ayako, Yogo Naoyuki, Hase Tetsunari, Morise Masahiro, Sekido Yoshitaka, Girard Luc, Minna John D., Byers Lauren A., Heymach John V., Coombes Kevin R., Kondo Masashi, Hasegawa Yoshinori

    CANCER SCIENCE   Vol. 109 ( 6 ) page: 1843 - 1852   2018.6

     More details

    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Cancer Science  

    DOI: 10.1111/cas.13602

    Web of Science

    Scopus

    PubMed

  35. Regulation of PD-L1 expression by matrix stiffness in lung cancer cells Reviewed International journal

    Miyazawa Ayako, Ito Satoru, Asano Shuichi, Tanaka Ichidai, Sato Mitsuo, Kondo Masashi, Hasegawa Yoshinori

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   Vol. 495 ( 3 ) page: 2344 - 2349   2018.1

     More details

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

    DOI: 10.1016/j.bbrc.2017.12.115

    Web of Science

    Scopus

    PubMed

  36. An EGFR-mutated Lung Adenocarcinoma Undergoing Squamous Cell Carcinoma Transformation Exhibited a Durable Response to Afatinib Reviewed International journal

    Sato Mitsuo, Matsui Akira, Shimoyama Yoshie, Omote Norihito, Morise Masahiro, Hase Tetsunari, Tanaka Ichidai, Suzuki Kojiro, Hasegawa Yoshinori

    INTERNAL MEDICINE   Vol. 57 ( 23 ) page: 3429 - 3432   2018

     More details

    Language:English   Publishing type:Research paper (scientific journal)   Publisher:一般社団法人 日本内科学会  

    <p>Squamous cell carcinoma (SCC) transformation has been identified as a mechanism of resistance to first-generation epidermal growth factor receptor tyrosine kinase inhibitors (<i>EGFR</i>-TKIs), gefitinib or erlotinib, in <i>EGFR</i>-mutated lung cancer. However, whether second- or third-generation TKIs can overcome resistance due to SCC transformation remains unclear. We herein report an <i>EGFR</i>-mutated lung adenocarcinoma undergoing transformation into SCC that exhibited a durable response to afatinib, which is a second-generation irreversible <i>EGFR</i>-TKI. We suggest that afatinib can be considered as a treatment option for <i>EGFR</i>-mutated tumor undergoing SCC transformation, particularly in the absence of a <i>T790M</i> mutation. </p>

    DOI: 10.2169/internalmedicine.0999-18

    Web of Science

    Scopus

    PubMed

  37. A phase II trial of Ifosfamide combination with recommended supportive therapy for recurrent SCLC in second-line and heavily treated setting Reviewed

    Ichidai Tanaka Kenji Kawada Masahiro Morise Tetsunari Hase Hiroaki Hayashi Akihiko Sokai Asuki Fukatsu Masashi Kondo Fumio Nomura Yoshinori Hasegawa

    Cancer Chemotherapy and Pharmacology     2017.12

     More details

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

    DOI: doi.org/10.1007/s00280-017-3497-0

  38. Plasma-derived extracellular vesicle proteins as a source of biomarkers for lung adenocarcinoma Reviewed International coauthorship International journal

    Vykoukal Jody, Sun Nan, Aguilar-Bonavides Clemente, Katayama Hiroyuki, Tanaka Ichidai, Fahrmann Johannes F., Capello Michela, Fujimoto Junya, Aguilar Mitzi, Wistuba Ignacio I., Taguchi Ayumu, Ostrin Edwin J., Hanash Samir M.

    ONCOTARGET   Vol. 8 ( 56 ) page: 95466 - 95480   2017.11

     More details

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

    DOI: 10.18632/oncotarget.20748

    Web of Science

    Scopus

    PubMed

  39. Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer. Reviewed International journal

    Dayde D, Tanaka I, Jain R, Tai MC, Taguchi A

    International journal of molecular sciences   Vol. 18 ( 3 )   2017.3

     More details

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

    DOI: 10.3390/ijms18030573

    Web of Science

    Scopus

    PubMed

  40. Mechanobiology and functional role of YAP/TAZ in lung cancer and malignant mesothelioma Reviewed

    Tanaka Ichidai

    Japanese Open Journal of Respiratory Medicine   Vol. 1 ( 2 )   2017

     More details

    Authorship:Lead author, Corresponding author   Language:Japanese   Publishing type:Part of collection (book)   Publisher:COSMIC  

    DOI: 10.24557/kokyurinsho.1.e00020

  41. Loss of YAP1 defines neuroendocrine differentiation of lung tumors. Reviewed International journal

    Ito T, Matsubara D, Tanaka I, Makiya K, Tanei ZI, Kumagai Y, Shiu SJ, Nakaoka HJ, Ishikawa S, Isagawa T, Morikawa T, Shinozaki-Ushiku A, Goto Y, Nakano T, Tsuchiya T, Tsubochi H, Komura D, Aburatani H, Dobashi Y, Nakajima J, Endo S, Fukayama M, Sekido Y, Niki T, Murakami Y

    Cancer science   Vol. 107 ( 10 ) page: 1527 - 1538   2016.10

     More details

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

    DOI: 10.1111/cas.13013

    Web of Science

    Scopus

    PubMed

  42. Activation of Yes-Associated Protein in Low-Grade Meningiomas Is Regulated by Merlin, Cell Density, and Extracellular Matrix Stiffness. Reviewed International journal

    Tanahashi K, Natsume A, Ohka F, Motomura K, Alim A, Tanaka I, Senga T, Harada I, Fukuyama R, Sumiyoshi N, Sekido Y, Wakabayashi T

    Journal of neuropathology and experimental neurology   Vol. 74 ( 7 ) page: 704 - 709   2015.7

     More details

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

    DOI: 10.1097/NEN.0000000000000211

    Web of Science

    Scopus

    PubMed

  43. RASSF3 downregulation increases malignant phenotypes of non-small cell lung cancer. Reviewed International journal

    Fukatsu A, Ishiguro F, Tanaka I, Kudo T, Nakagawa K, Shinjo K, Kondo Y, Fujii M, Hasegawa Y, Tomizawa K, Mitsudomi T, Osada H, Hata Y, Sekido Y

    Lung cancer (Amsterdam, Netherlands)   Vol. 83 ( 1 ) page: 23 - 29   2014.1

     More details

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

    DOI: 10.1016/j.lungcan.2013.10.014

    Web of Science

    Scopus

    PubMed

  44. DYSREGULATION OF HIPPO TUMOR-SUPPRESSIVE PATHWAY IN MALIGNANT MESOTHELIOMA Reviewed International journal

    Sekido Yoshitaka, Tanaka Ichidai, Fujii Makiko, Osada Hirotaka

    JOURNAL OF THORACIC ONCOLOGY   Vol. 8   page: S1045 - S1046   2013.11

     More details

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

    Web of Science

  45. YAP induces malignant mesothelioma cell proliferation by upregulating transcription of cell cycle-promoting genes. Reviewed International journal

    Mizuno T, Murakami H, Fujii M, Ishiguro F, Tanaka I, Kondo Y, Akatsuka S, Toyokuni S, Yokoi K, Osada H, Sekido Y

    Oncogene   Vol. 31 ( 49 ) page: 5117 - 5122   2012.12

     More details

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

    DOI: 10.1038/onc.2012.5

    Web of Science

    Scopus

    PubMed

  46. Convergent signaling in the regulation of connective tissue growth factor in malignant mesothelioma TGF beta signaling and defects in the Hippo signaling cascade Reviewed International journal

    Fujii Makiko, Nakanishi Hayao, Toyoda Takeshi, Tanaka Ichidai, Kondo Yutaka, Osada Hirotaka, Sekido Yoshitaka

    CELL CYCLE   Vol. 11 ( 18 ) page: 3373 - 3379   2012.9

     More details

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

    DOI: 10.4161/cc.21397

    Web of Science

    Scopus

    PubMed

  47. Interstitial pneumonia and nodular regenerative hyperplasia of the liver as initial manifestations of polyarteritis nodosa. Reviewed International journal

    Tanaka I, Imaizumi K, Hashimoto I, Asai N, Yokoi T, Matsuno T, Hasegawa Y

    Internal medicine (Tokyo, Japan)   Vol. 51 ( 6 ) page: 635 - 638   2012

     More details

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

    DOI: 10.2169/internalmedicine.51.5638

    Web of Science

    Scopus

    PubMed

▼display all

Books 3

  1. 大気・室内環境関連疾患 予防と対策の手引き 2019

    長谷川好規、佐藤光夫、森瀬昌宏、田中一大( Role: Joint author)

    一般社団法人 日本呼吸器学会  2019.1 

     More details

    Language:Japanese Book type:Scholarly book

  2. 嚢胞性線維症の診療の手引き(改訂第2版)

    厚生労働科学研究費補助金 難治性膵疾患に関する調査研究班( Role: Contributor)

    2018.3 

     More details

    Language:Japanese

  3. 嚢胞性線維症の診療の手引き

    厚生労働科学研究費補助金 難治性膵疾患に関する調査研究班( Role: Contributor)

    2008.3 

Presentations 22

  1. オキシトシン受容体を標的とした悪性中皮腫に対する新規治療法の開発 International coauthorship

    田中 一大、小玉 勇太、佐藤 龍洋, 玄 宗栄、森瀬 昌宏、佐藤 光夫, 関戸 好孝、石井 誠

    1. 第63回日本呼吸器学会学術総会  2023.4.29  日本呼吸器学会

     More details

    Event date: 2023.4

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:東京   Country:Japan  

  2. 当院における高齢EGFR陽性非小細胞肺癌に対する一次治療でのOsimertinib療法の有効性と安全性 International coauthorship

    南谷 有香, 稲葉 慈, 佐久間 健太、森下 拓斗、中垣 しおり、滝 俊一、宮沢 亜矢子、林 信之、日比野 佳孝、玄 宗栄、田中 一大

    第63回日本呼吸器学会学術総会  2023.4.29  日本呼吸器学会

     More details

    Event date: 2023.4

    Language:Japanese   Presentation type:Poster presentation  

    Venue:東京   Country:Japan  

  3. Oxytocin receptor is a promising therapeutic target of malignant mesothelioma International conference

    田中一大

    第25回アジア太平洋呼吸器学会学術集会  2021.11.20 

     More details

    Event date: 2021.11

    Language:English   Presentation type:Poster presentation  

    Venue:京都  

  4. Potential benefits of bevacizumab plus platinum-based chemotherapy in advanced non-small-cell lung cancer patients with EGFR mutation

    Ichidai tanaka

    2020.9.23 

     More details

    Event date: 2020.9

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  5. SRGN triggered aggressive and immunosuppressive phenotype in TTF-1 negative lung adenocarcinomas International coauthorship

    Ichidai tanaka

    2020.9.23 

     More details

    Event date: 2020.9

    Language:English  

    Country:Japan  

  6. eIF2b is a Potential Therapeutic Target for Nonsmall Cell Lung Cancer International conference

     More details

    Event date: 2018.11 - 2018.12

    Language:English   Presentation type:Poster presentation  

    Country:Japan  

  7. Uncommon EGFR遺伝子変異陽性肺癌 に対するアファチニブの臨床効果の検討 International coauthorship

    田中一大

    第 116 回 日本内科学会学講演会 

     More details

    Language:Japanese  

  8. Gene A, upregulated by mutant KRAS, is a potential therapeutic target for lung cancer

    2023.9.23 

     More details

    Event date: 2023.9

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

  9. LOX has a possibility of being a therapeutic target through the mechanism of oncogene-induced cellular senescence.

    2023.9.22 

     More details

    Event date: 2023.9

    Language:Japanese  

    Country:Japan  

  10. A LIM protein ajuba suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade. International conference

    Ichidai Tanaka, Hirotaka Osada, Makiko Fujii and Yoshitaka Sekido

    AACR 104th Annual Meeting 2013 

     More details

    Event date: 2013.4

    Language:English   Presentation type:Poster presentation  

    Country:United States  

  11. Interstitial Pneumonia and Nodular Regenerative Hyperplasia of the Liver as Initial Manifestations of Polyarteritis Nodosa International conference

    Tanaka Ichidai, Imaizumi Kazuyoshi, Hashimoto Izumi, Asai Naoya, Yokoi Toyoharu, Matsuno Tadakatsu, Hasegawa Yoshinori

    The Japanese Society of Internal Medicine 

     More details

    Event date: 2012

    Language:English   Presentation type:Oral presentation (general)  

    Country:Japan  

    A 65-year-old man was admitted to our hospital because of progressive dyspnea. A laboratory examination and high-resolution computed tomography (HRCT) revealed that he had interstitial pneumonia (IP) with liver dysfunction. Myeloperoxidase-ANCA (MPO-ANCA) was negative. Although his respiratory condition had become stable after initiation of steroid therapy, liver dysfunction had worsened with progressive portal hypertension. He died of hepatic insufficiency about three years after the first medical examination.<br> Autopsy showed that he had vasculitis of medium and small blood vessels of the spleen, lungs, and liver. The final diagnosis was classical polyarteritis nodosa (PAN). Microscopically, non-specific interstitial pneumonia was identified in the autopsied lung. The pathological findings of the liver were consistent with nodular regenerative hyperplasia (NRH). We report a case of PAN with IP and NRH preceding findings of systemic vasculitis.<br>

  12. P11-4 当院でEBUS-TBNAを施行し,偽陰性診断であった5症例の検討(EBUS2,ポスター11,第35回日本呼吸器内視鏡学会学術集会) International conference

    麻生 裕紀, 村田 直彦, 高嶋 浩司, 岡地 祥太郎, 丸山 英一, 深津 明日樹, 木村 元宏, 梶川 茂久, 進藤 有一郎, 森瀬 昌宏, 犬飼 朗博, 今井 直幸, 佐藤 光夫, 近藤 征史, 長谷川 好規, 橋本 泉, 今泉 和良, 魚津 桜子, 田中 一大, 青山 大輔, 伊藤 亮太, 小林 大介

    気管支学  2012  特定非営利活動法人 日本呼吸器内視鏡学会

     More details

    Event date: 2012

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  13. O24-4 EBUS-GS下生検に通常鉗子生検を追加することの有用性の検討(EBUS1,一般口演24,第35回日本呼吸器内視鏡学会学術集会) International conference

    今井 直幸, 深津 明日樹, 高嶋 浩司, 木村 元宏, 梶川 茂久, 丸山 英一, 岡地 祥太郎, 橋本 直純, 進藤 有一郎, 森瀬 昌宏, 犬飼 朗博, 今泉 和良, 佐藤 光夫, 近藤 征史, 長谷川 好規, 橋本 泉, 魚津 桜子, 青山 大輔, 田中 一大, 小林 大介, 伊藤 亮太, 村田 直彦

    気管支学  2012  特定非営利活動法人 日本呼吸器内視鏡学会

     More details

    Event date: 2012

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  14. 6.EBUS-TBNAが診断に有用であった子宮頸癌肺転移の1例(第40回 日本呼吸器内視鏡学会中部支部会) International conference

    橋本 泉, 橋本 直純, 佐藤 光夫, 近藤 征史, 今泉 和良, 長谷川 好規, 今井 直幸, 犬飼 朗博, 岩木 舞, 下方 智也, 森瀬 昌宏, 小川 知美, 山下 良, 田中 一大

    気管支学  2011  特定非営利活動法人 日本呼吸器内視鏡学会

     More details

    Event date: 2011

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  15. O27-2 当院での気管支内視鏡検査における鉗子洗浄検査結果の解析(気管支鏡検査2,一般口演27,第34回日本呼吸器内視鏡学会学術集会) International conference

    今井 直幸, 楠瀬 公章, 近藤 征史, 橋本 泉, 今泉 和良, 長谷川 好規, 田中 一大, 小川 知美, 青山 大輔, 橋本 直純, 犬飼 朗博, 森瀬 昌宏, 岩木 舞, 山下 良

    気管支学  2011  特定非営利活動法人 日本呼吸器内視鏡学会

     More details

    Event date: 2011

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  16. O25-2 気管支鏡検査時の鎮静術におけるミダゾラム標準投与法確立へのアプローチ(気管支鏡検査/麻酔・前処置,一般口演25,第34回日本呼吸器内視鏡学会学術集会) International conference

    小川 知美, 橋本 泉, 橋本 直純, 近藤 征史, 今泉 和良, 長谷川 好規, 進藤 有一郎, 今井 直幸, 犬飼 朗博, 小栗 知世, 楠瀬 公章, 山下 良, 田中 一大, 岩木 舞

    気管支学  2011  特定非営利活動法人 日本呼吸器内視鏡学会

     More details

    Event date: 2011

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  17. O12-3 肺内の腫瘤性病変に対するEBUS-TBNAあるいはTBNA穿刺生検時における発熱性合併症(EBUS/EUS,一般口演12,第34回日本呼吸器内視鏡学会学術集会) International conference

    小栗 知世, 橋本 直純, 近藤 征史, 今泉 和良, 長谷川 好規, 今井 直幸, 犬飼 朗博, 山下 良, 田中 一大, 楠瀬 公章, 小川 知美, 岩木 舞, 橋本 泉

    気管支学  2011  特定非営利活動法人 日本呼吸器内視鏡学会

     More details

    Event date: 2011

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  18. O10-3 当院における肺末梢病変に対するEBUS-GS検査結果の解析(EBUS-GS,一般口演10,第34回日本呼吸器内視鏡学会学術集会) International conference

    田中 一大, 近藤 征史, 今泉 和良, 長谷川 好規, 小川 知美, 今井 直幸, 犬飼 朗博, 青山 大輔, 楠瀬 公章, 山下 良, 岩木 舞, 橋本 直純

    気管支学  2011  特定非営利活動法人 日本呼吸器内視鏡学会

     More details

    Event date: 2011

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  19. 8.局所麻酔下胸腔鏡が診断に有用であった肺扁平上皮癌の1例(第36回日本呼吸器内視鏡学会中部支部会) International conference

    林 浩昭, 祖開 暁彦, 伊藤 亮太, 加藤 理紗, 田中 一大, 横山 俊彦, 野村 史郎, 酒井 秀造

    特定非営利活動法人 日本呼吸器内視鏡学会 

     More details

    Event date: 2009

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  20. 3.PETにて術前より異なる性格の腫瘍と予想された同時多発肺癌の1例(第93回日本肺癌学会中部支部会,中部支部,支部活動) International conference

    渡部 俊也, 石黒 太志, 森 正一, 林 浩昭, 租開 暁彦, 加藤 理紗, 伊藤 亮太, 田中 一大, 横山 俊彦, 野村 史郎, 酒井 秀造

    日本肺癌学会 

     More details

    Event date: 2008.12

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  21. 26.EGFR FISH法とGefitinibの効果に関する検討(第92回日本肺癌学会中部支部会,中部支部,支部活動) International conference

    濱田 努, 伊藤 亮太, 田中 一大, 小川 知美, 横山 俊彦, 野村 史郎, 酒井 秀造, 伊藤 雅文

    日本肺癌学会 

     More details

    Event date: 2008.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

  22. 29. 当院での化学療法におけるリスクマネージメントの試み(第90回 日本肺癌学会中部支部会,支部活動) International conference

    小川 知美, 田中一大, 伊奈 孝一郎, 濱田 努, 楠瀬 公章, 小川 紫都, 野村 史郎, 酒井 秀造

    日本肺癌学会 

     More details

    Event date: 2007.4

    Language:Japanese   Presentation type:Oral presentation (general)  

    Country:Japan  

▼display all

Other research activities 1

  1. Associate Editor of Cancer Cell International

    2020.7

Research Project for Joint Research, Competitive Funding, etc. 11

  1. 悪性中皮腫に対する新規ドラッグデリバリーシステムを用いた個別化治療の開発

    Grant number:23ak0101212h0001  2023.4 - 2026.3

    AMED創薬基盤推進研究事業  悪性中皮腫

    田中一大

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\55792776 ( Direct Cost: \42917920 、 Indirect Cost:\12875256 )

  2. 分泌タンパク質SMOC1を標的としたLKB1不活化肺癌における新規治療戦略の構築

    Grant number:21cm0106187h0001  2021.5 - 2023.3

    次世代がん医療創生研究事業 

      More details

    Authorship:Principal investigator  Grant type:Competitive

  3. LKB1不活化肺癌に対する人工核酸を用いた新規個別化治療の構築

    Grant number:A173  2024.4 - 2025.3

    橋渡し研究戦略的推進プログラム  肺癌

    田中一大

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\5000000

  4. LKB1不活化肺癌に対する人工核酸を用いた新規個別化治療の構築

    Grant number:A173  2023.7 - 2024.3

    橋渡し研究戦略的推進プログラム (世界を展望できる地域に合った持続的に成長する機関の創成を目指した研究)  肺癌

    田中一大

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\29200000

  5. LKB1不活化肺癌に対する人工核酸を用いた新規個別化治療の構築

    Grant number:A173  2023.4 - 2024.3

    橋渡し研究戦略的推進プログラム  肺癌

    田中一大

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\5000000

  6. オキシトシン受容体を標的とした悪性中皮腫における新規個別化治療の確立 International coauthorship

    Grant number:A112  2022.7 - 2023.3

    橋渡し研究戦略的推進プログラム  悪性中皮腫

    田中一大

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\17060000 ( Direct Cost: \16563107 、 Indirect Cost:\496893 )

  7. オキシトシン受容体を標的とした悪性中皮腫における新規個別化治療の確立 International coauthorship

    Grant number:A112  2020.4 - 2021.3

    橋渡し研究戦略的推進プログラム  悪性中皮腫

    田中一大

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\5000000

  8. LKB1不活化肺癌に対する新規治療戦略の構築

    2021.4 - 2022.3

    先端研究支援  肺癌

    田中一大

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\3000000

  9. LKB1不活化肺癌におけるピリミジン塩基合成経路を標的とした新規治療法の確立

    2021.4 - 2022.3

    堀科学芸術振興財団 研究費助成事業  肺癌

    田中一大

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\1000000

  10. 悪性中皮腫に対する新規治療法の開発に向けたPatient-derived xenograft (PDX) マウスモデルの作成

    2019.4 - 2020.3

    日東学術振興財団 研究助成  悪性中皮腫

    田中一大

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\1000000

  11. LKB1が不活化した肺癌におけるSMOC1を標的とした新規治療戦略の構築

    2018.4 - 2019.3

    がんその他の悪性新生物研究助成金  肺癌

    田中一大

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\500000

▼display all

KAKENHI (Grants-in-Aid for Scientific Research) 8

  1. ピリミジン塩基合成経路を標的としたLKB1不活化肺癌に対する新規治療法の開発

    Grant number:23H02920  2023.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(B)

    田中 一大, 関戸 好孝, 田口 歩, 佐藤 光夫, 佐藤 龍洋

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\18720000 ( Direct Cost: \14400000 、 Indirect Cost:\4320000 )

    非小細胞肺癌の約20%は、腫瘍抑制遺伝子であるLiver kinaseB1(LKB1)の不活化変異をきたしており、免疫チェックポイント阻害剤に不応性で極めて予後が悪い。申請者は、サルベージ経路でピリミジン塩基合成を促進する酵素が、LKB1不活化肺癌で高発現していることを新たに発見した。さらに、同因子をノックダウンすると、LKB1不活化肺癌細胞株の増殖が有意に抑制されることを見出し有望な治療標的になるという着想に至った。本研究では、LKB1不活化肺癌におけるピリミジン塩基のサルベージ経路が腫瘍増殖に果たす役割を解明すると同時に、同経路を標的とする新規治療法の開発を目指す。

  2. 長鎖非翻訳RNAを標的とする変異KRAS肺癌の合成致死治療の開発

    Grant number:22K19522  2022.6 - 2024.3

    科学研究費助成事業  挑戦的研究(萌芽)

    佐藤 光夫, 田中 一大

      More details

    Authorship:Coinvestigator(s)  Grant type:Competitive

    変異KRASは固形癌において最も高頻度に認められるドライバー癌遺伝子であるが、薬物的なシグナルの直接遮断が難しく、治療薬開発は難航している。別のアプローチとして合成致死が期待されるが、従来の報告は変異KRAS癌の合成致死遺伝子が存在する可能性は低いことを示す。そこで、本課題は合成致死に導く標的として遺伝子ではなく長鎖非翻訳RNA (lncRNA)に着目する。lncRNAは最も多い転写物であり、多彩な機能を持つとされるが個々のlncRNAの機能は大部分が未解明である。したがって、合成致死の標的としての高い可能性を持つと考えた。以上から本課題はlncRNAを標的とする変異KRAS肺癌の合成致死治療開発を目的とする。

  3. 悪性中皮腫におけるオキシトシン受容体を標的とした新規治療法の開発

    Grant number:20H03689  2020.4 - 2023.3

    科学研究費助成事業 

    田中 一大

      More details

    Authorship:Principal investigator  Grant type:Competitive

    Grant amount:\17810000 ( Direct Cost: \13700000 、 Indirect Cost:\4110000 )

    悪性中皮腫は希少な腫瘍であるが極めて予後不良であり、新規治療法の開発が切望されている。研究代表者はこれまでの解析で、約40%の悪性中皮腫において著しく高発現している受容体に着眼し、独立した予後予測因子であることを発見した。さらにin vitro の解析で、同遺伝子をノックダウンすると、中皮腫細胞株の増殖が有意に抑制されることを見出した。これらの結果を基軸に、本研究では1)悪性中皮腫における同受容体下流の細胞内シグナル経路の解明、2)同受容体阻害剤の抗腫瘍効果の検証、3)さらに悪性中皮腫の組織検体を用いて免疫染色を施行し、同受容体を標的とした治療対象を選出するプロトコルの最適化を行う。

  4. Elucidation of the molecular mechanisms of tumor progression in LKB1-inactivated lung cancer

    Grant number:18K15949  2018.4 - 2020.3

    Grant-in-Aid for Early-Career Scientists

    Tanaka Ichidai

      More details

    Authorship:Principal investigator 

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

    Liver kinase B1 (LKB1) is a tumor suppressor frequently inactivated in some human cancers, and non-small lung cancer (NSCLC) with LKB1 inactivation is one of the most aggressive neoplasms. To identify molecular features associated with LKB1 inactivation, bioinformatic analysis was initially conducted using lung cancer omics datasets such as mRNA and protein expression. Eventually, SPARC Related Modular Calcium Binding 1 (SMOC1), which plays essential roles in both eye and limb development, was identified as a markedly increased secreted protein in LKB1-inactivated NSCLC. SMOC1 knockdown reduced cancer cell migration and tumor angiogenesis in NSCLC with LKB1 inactivation. Furthermore, SMOC1 expression was significantly associated with poor overall survival, indicating that SMOC1 expression would be one of a prognostic biomarker in MSCLC. Our findings suggest that SMOC1 plays a crucial role in the development of NSCLC with LKB1 inactivation.

  5. ドライバー癌遺伝子誘導性の細胞老化を作用機序とする変異KRAS肺癌の創薬研究

    Grant number:21H02924  2021.4 - 2024.3

    科学研究費助成事業  基盤研究(B)

    佐藤 光夫, 芳川 豊史, 長谷 哲成, 湯川 博, 田中 一大, 松井 佑介

      More details

    Authorship:Coinvestigator(s) 

    変異KRAS癌の創薬を目的とする。代表者は自身開発の正常気管支上皮細胞モデルHBECにおいて、変異KRASの導入が細胞の悪性度を増強する一方で、細胞の増殖を停止させる癌遺伝子誘導細胞老化(oncogene-induced senescence; OIS)という現象に着目した。HBECモデルを用いたOIS回避機能に基づくプールshRNAライブラリースクリーニングを実施し、遺伝子Xを有望な治療標的候補として特定した。本課題では世界初のOIS誘導機序による肺癌治療薬の開発を目標とする。

  6. 部分的上皮間葉細胞転換(ハイブリッドEMT)の安定化因子を標的とする肺癌治療

    Grant number:19K22617  2019.6 - 2021.3

    科学研究費助成事業   挑戦的研究(萌芽)

    佐藤 光夫

      More details

    Authorship:Coinvestigator(s) 

    上皮間葉細胞転換(EMT)は癌細胞が上皮系から間葉系へ転換し悪性度を増強する現象である。これまではEMTを完了した細胞の悪性度が最も高いとされてきた。しかし、応募者の準備データは部分的なEMT細胞の方が完全なEMT細胞に比べ悪性形質が高いことを示唆する。また、部分的EMTを安定化する未知の因子の存在が推測され、これは癌の悪性形質を決定する有望な治療標的の可能性がある。以上より、本研究は肺癌治療標的として期待される部分的EMTの“安定化因子”の発見およびそれらを標的とする創薬を目的とする。方法として、応募者開発の正常気管支上皮細胞モデル(HBEC)を用いた機能的なスクリーニングなどを実施する。
    上皮間葉細胞転換(epithelial to mesenchymal transition, EMT)は癌細胞が上皮系から間葉系へ転換し悪性度を増強する現象である。これまでは、完全にEMTを完了した細胞の悪性度が最も高いと信じられてきた。しかし、最近の報告と応募者の準備データは予想に反し、部分的なEMT細胞、すなわちハイブリッドEMTの方が完全なEMT細胞に比べ癌幹細胞性質などの悪性形質が高いと示唆する。また、ハイブリッドEMTを安定化する未知の因子の存在が推測され、これは癌の悪性形質を決定している有望な治療標的の可能性がある。本研究は肺癌治療標的として期待されるハイブリッドEMTの“安定化因子”の発見を目的とする。2019年度はEMT安定化因子候補である遺伝子A(論文未発表にてAとする)の肺癌細胞における機能を評価した。複数の肺癌細胞株を使用し、RNA干渉によって遺伝子Aノックダウンを実施した。遺伝子ノックダウンの効率をウエスタンブロットで評価した。癌細胞の増殖を足場依存性および足場非依存性条件の両者において評価した。足場非依存性増殖能は軟寒天中のコロニー形成にて評価した。我々はある肺癌細胞株において、遺伝子Aノックダウン足場依存性増殖にはほとんど影響がなく、足場非依存性増殖能を強く抑制する結果を得た。足場非依存性増殖は細胞が細胞外のマトリックス等への接着を失った状態での増殖である。正常細胞は足場非依存性の状態では通常、細胞死に至る。対照的に癌細胞は足場非依存性増殖能を獲得していることが多く、その能力は浸潤能や転移能と深く関係しており、癌細胞の重要な悪性形質の一つである。したがって、我々の結果は遺伝子Aが肺癌の有望な治療標的となりうることを示唆した。今後は、足場非依存性増殖能を別のアッセイ系で評価し結果の確認を実施する。確認された場合は、遺伝子Aノックダウンによる足場非依存性増殖の抑制機序を明らかとする。
    2019年度はEMT安定化因子候補である遺伝子A(論文未発表にてAとする)の肺癌細胞における機能を評価した。複数の肺癌細胞株を使用し、RNA干渉によって遺伝子Aノックダウンを実施した。遺伝子ノックダウンの効率をウエスタンブロットで評価した。癌細胞の増殖を足場依存性および足場非依存性条件の両者において評価した。足場非依存性増殖能は軟寒天中のコロニー形成にて評価した。我々はある肺癌細胞株において、遺伝子Aノックダウン足場依存性増殖にはほとんど影響がなく、足場非依存性増殖能を強く抑制する結果を得た。今後は、足場非依存性増殖能を別のアッセイ系で評価し結果の確認を実施する。確認された場合は、遺伝子Aノックダウンによる足場非依存性増殖の抑制機序を明らかとする。また、遺伝子Aを含む候補遺伝子ならびにEMT関連遺伝子のタンパク発現をウエスタンブロットによって肺癌細胞パネルを使用して実施予定である。そのために、肺癌細胞パネルからのタンパク、RNA、DNAの抽出をほぼ完了した。2020年度も継続して実施する。
    肺癌の治療標的としての可能性を持つ遺伝子Aの機能評価を軸に研究を推進する。具体的には、複数のEMT状態の異なる肺癌細胞における遺伝子Aのがん促進作用を評価する。これによって、遺伝子Aの機能がEMT状態依存性であるかどうかを明らかとする。また、遺伝子Aノックダウンによる足場非依存性増殖能の抑制作用の機序を明らかとしていく。さらに、in vivo実験を追加し、遺伝子A標的治療の臨床応用への可能性も評価する。

  7. ドライバー癌遺伝子により誘導される細胞老化 (OIS) を利用した肺癌治療の開発

    Grant number:18H02819  2018.4 - 2021.3

    科学研究費助成事業  

    佐藤 光夫

      More details

    Authorship:Coinvestigator(s) 

    【本課題の目的】肺癌のドライバー癌遺伝子の一つ変異KRASは腺癌の20%程度に認められるが、その標的治療の開発は未成功である。これは変異KRASの癌化シグナルの薬物的な遮断が困難なためである。応募者は正常気管支モデルであるHBEC実験系を確立し(Sato, Cancer Res 2006)、さらに、変異KRASをHBECに導入すると悪性度の増強にもかかわらず細胞分裂を停止する現象を発見した(Sato, Mol Cancer Res 2013)。これは正常細胞が癌化を防御する機構の一つ癌遺伝子誘導細胞老化(oncogene-induced senescence; OIS)である。以上より、応募者は変異KRAS肺癌の新たな治療として変異KRASシグナルの遮断ではなく、OISを活用する治療を着想した。その実現のために、まず、HBECを用いて、OIS抑制作用を表現型とする機能的なプールshRNAスクリーニングを実施し、複数の標的候補を特定した。特に、肺癌細胞株が高発現する遺伝子Xは小分子化合物による治療標的となる可能性があるため、学内創薬産学協同研究センター(ラクオリア創薬株式会社)化合物スクリーニングを予定した(機密保持契約締結済み)。本研究はこれらの研究を発展させ、変異KRASならびに変異EGFRやALK遺伝子によるOIS誘導治療の開発を目的とする。
    <BR>
    【2019年度の成果】
    これまでに、複数の化合物ライブラリーを使用したハイスループットスクリーニング(HTS)を実施した。初期に同定したヒット化合物の活性が再現できなかったため、化合物選択基準の見直しを行い、ヒット化合物を選び直した。ヒット化合物の再現性、選択性、構造活性相関(Structure-Activity Relationship: SAR)解析の結果に基づき、数個のシーズ化合物に絞り込んだ。
    これまでに、複数の化合物ライブラリーを使用したハイスループットスクリーニング(HTS)を実施した。初期に同定したヒット化合物の活性が再現できなかったため、化合物選択基準の見直しを行い、ヒット化合物を選び直した。ヒット化合物の再現性、選択性、構造活性相関(Structure-Activity Relationship: SAR)解析の結果に基づき、数個のシーズ化合物に絞り込んだ。ヒット化合物の再現性ができなかったことなどにより当初の計画よりやや遅れている。
    これまでの研究成果に基づいて2020年度は以下を計画する。①SARの結果に基づいて新規化合物(リード化合物)を合成する。②リード化合物および遺伝子X産物との結晶構造解析を外部委託に実施する。③新規化合物に対して評価・解析およびデザイン・合成のステップを繰り返し実施し、さらに薬効の優れるリード化合物を合成する。④前記と併行して、遺伝子Xノックアウト肺癌細胞クローンを用いて、遺伝子X阻害の癌細胞の増殖抑制機序の解明を継続して実施する。⑤2020年度までに合成されるリード化合物に対して、各種非臨床試験(薬理、毒性、薬物動態試験など)に必要な予備的試験を実施する。具体的には、複数の化合物の薬効(XenograftやPDXモデル)、薬物動態(経口吸収率、血中半減期、代謝・排出経路、代謝物)、短期毒性(心血管作用、中枢作用、病理)、物性(溶解性、固体安定性)を評価する。以上の結果に基づいて、2020年度末までにリード化合物の基本特許申請を目標とする。

  8. 肺腺癌、悪性中皮腫におけるCADM1 によるHippo pathway 制御機構の解明

    2013.1 - 2014.12

    科学研究費補助金  新学術領域研究

    松原 大祐

      More details

    Authorship:Coinvestigator(s) 

▼display all

 

Teaching Experience (On-campus) 5

  1. 系統講義 (閉塞性肺疾患)

    2023

     詳細を見る

    閉塞性肺疾患に関する病態・概要

  2. 選択特別講義 難治性呼吸器疾患の克服に向けて

    2022

     詳細を見る

    選択特別講義「難治性呼吸器疾患の克服に向けて」の中で、肺癌におけるがん遺伝子変異に基づいだ個別化治療戦略の現状について講義を行った。

  3. 選択特別講義 難治性呼吸器疾患の克服に向けて

    2021

     詳細を見る

    選択特別講義「難治性呼吸器疾患の克服に向けて」の中で、肺癌におけるがん遺伝子変異に基づいだ個別化治療戦略の現状について講義を行った。

  4. 選択特別講義 難治性呼吸器疾患の克服に向けて

    2023

     詳細を見る

    選択特別講義「難治性呼吸器疾患の克服に向けて」の中で、肺癌におけるがん遺伝子変異に基づいだ個別化治療戦略の現状について講義を行った。

  5. ポリクリ実習 胸部レントゲンの読影について

    2021

     詳細を見る

    ポリクリIの実習指導において、胸部レントゲンの読影の仕方について1年を通じて講義を行った。

 

Social Contribution 3

  1. 名古屋市公害健康被害認定審査員

    Role(s):Investigater

    名古屋市  2018.4 - 2021.3

  2. 日本呼吸器学会東海地方会研修医向けセミナー 世話人会委員

    Role(s):Presenter, Planner, Organizing member, Demonstrator

    日本呼吸器学会東海地方会  呼吸器研修医向けセミナー  2017.9

  3. 愛知県がん診療連携協議会地域連携クリニカルパス部会

    Role(s):Organizing member

    愛知県がん診療連携協議会  地域連携クリニカルパス部会肺がんWG  2018.4

Academic Activities 1

  1. 第120回日本肺癌学会中部支部学術集会

    Role(s):Panel moderator, session chair, etc.

    関戸義孝  2021.2

     More details

    Type:Academic society, research group, etc.