研究者詳細 - 田中　一大

論文 - 田中　一大

分割表示 47 件中 1 - 20 件目／全件表示 >>

Benralizumab treatment in an elderly patient with eosinophilic esophagitis resulted in remission: a case report. 査読有り

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

BMC geriatrics 24 巻 ( 1 ) 頁： 92 2024年1月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

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

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

Frontiers in oncology 13 巻頁： 1249237 2023年

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis 査読有り

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 22 巻 ( 1 ) 2022年12月

担当区分：筆頭著者,　責任著者記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：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

SRGN-Triggered Aggressive and Immunosuppressive Phenotype in a Subset of TTF-1-Negative Lung Adenocarcinomas. 査読有り国際共著

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年2月

Current immunotherapeutic strategies targeting the PD-1/PD-L1 axis in non-small cell lung cancer with oncogenic driver mutations 査読有り

Tanaka I., Morise M.

International Journal of Molecular Sciences 23 巻 ( 1 ) 2022年1月

担当区分：筆頭著者,　責任著者記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：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

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 招待有り査読有り

Tanaka Ichidai, Furukawa Taiki, Morise Masahiro

CANCER CELL INTERNATIONAL 21 巻 ( 1 ) 頁： 454 2021年8月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

Oxytocin receptor is a promising therapeutic target of malignant mesothelioma 査読有り

Cancer Sci. 2021年7月

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. 査読有り国際共著

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

Endocrine journal 68 巻 ( 5 ) 頁： 613 - 620 2021年5月

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

Potential Benefits of Bevacizumab Combined With Platinum-Based Chemotherapy in Advanced Non-Small-Cell Lung Cancer Patients With EGFR Mutation 査読有り国際共著国際誌

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 21 巻 ( 3 ) 頁： 273 - + 2020年5月

Potential for afatinib as an optimal treatment for advanced non-small cell lung carcinoma in patients with uncommon EGFR mutations 査読有り国際誌

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 127 巻頁： 169 - 171 2019年1月

The Subunit eIF2 ss of Translation- Initiation Factor EIF2 Is a Potential Therapeutic Target for Non-Small Cell Lung Cancer 査読有り国際共著

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 109 巻頁： 1181-1181 2018年12月

Aberrant tryptophan catabolism marked by high kynureninase expression contributes to immunosuppression and poor outcome in lung adenocarcinoma 査読有り国際共著

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 78 巻 ( 13 ) 2018年7月

A phase II trial of Ifosfamide combination with recommended supportive therapy for recurrent SCLC in second-line and heavily treated setting 査読有り国際共著国際誌

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

CANCER CHEMOTHERAPY AND PHARMACOLOGY 81 巻 ( 2 ) 頁： 339 - 345 2018年2月

Role of CPS1 in Cell Growth, Metabolism, and Prognosis in LKB1-Inactivated Lung Adenocarcinoma 査読有り国際共著国際誌

Celiktas Muge, Tanaka Ichidai, Tripathi Satyendra Chandra, Fahrmann Johannes F., Aguilar-Bonavides Clemente, Villalobos Pamela, Delgado Oliver, Dhillon Dilsher, Dennison Jennifer B., Ostrin Edwin J., Wang Hong, Behrens Carmen, Do Kim-Anh, Gazdar Adi F., Hanash Samir M., Taguchi Ayumu

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE 109 巻 ( 3 ) 頁： 1 - 9 2017年3月

LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade 査読有り国際誌

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

ONCOGENE 34 巻 ( 1 ) 頁： 73 - 83 2015年1月

Circulating microRNA Panel for Prediction of Recurrence and Survival in Early-Stage Lung Adenocarcinoma 査読有り

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 25 巻 ( 4 ) 2024年2月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

The oncogenic role of LGR6 overexpression induced by aberrant Wnt/β-catenin signaling in lung cancer. 査読有り

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 15 巻 ( 2 ) 頁： 131 - 141 2024年1月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

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

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 60 巻 ( 11 ) 頁： 2002 - 2013 2023年11月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

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

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 26 巻 ( 3 ) 頁： 391 2023年9月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

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

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年8月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

　前のページ - 次のページ　

<田中 一大>

論文 - 田中 一大

<田中　一大>

論文 - 田中　一大