start-ver=1.4
cd-journal=joma
no-vol=326
cd-vols=
no-issue=2
article-no=
start-page=201
end-page=209
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20140815
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Everolimus prolonged survival in transgenic mice with EGFR-driven lung tumors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Everolimus is an orally administered mTOR inhibitor. The effect, and mechanism of action, of everolimus on lung cancers with an epidermal growth factor receptor (EGFR) mutation remain unclear. Four gefitinib-sensitive and -resistant cell lines were used in the present work. Growth inhibition was determined using the MTT assay. Transgenic mice carrying the EGFR L858R mutation were treated with everolimus (10 mg/kg/day), or vehicle alone, from 5 to 20 weeks of age, and were then sacrificed. To evaluate the efficacy of everolimus in prolonging survival, everolimus (10 mg/kg/day) or vehicle was administered from 5 weeks of age. The four cell lines were similarly sensitive to everolimus. Expression of phosphorylated (p) mTOR and pS6 were suppressed upon treatment with everolimus in vitro, whereas the pAKT level increased. The numbers of lung tumors with a long axis exceeding 1 mm in the everolimus-treated and control groups were 1.9 +/- 0.9 and 9.4 +/- 3.2 (t-test, p<0.001), respectively. pS6 was suppressed during everolimus treatment. Although apoptosis and autophagy were not induced in everolimus-treated EGFR transgenic mice, angiogenesis was suppressed. The median survival time in the everolimus-treated group (58.0 weeks) was significantly longer than that in the control group (31.2 weeks) (logrank test, p<0.001). These findings suggest that everolimus had an indirect effect on tumor formation by inhibiting angiogenesis and might be effective to treat lung tumors induced by an activating EGFR gene mutation.
en-copyright=
kn-copyright=
en-aut-name=YasugiMasayuki
en-aut-sei=Yasugi
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=TakigawaNagio
en-aut-sei=Takigawa
en-aut-mei=Nagio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OchiNobuaki
en-aut-sei=Ochi
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HaradaDaijiro
en-aut-sei=Harada
en-aut-mei=Daijiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NinomiyaTakashi
en-aut-sei=Ninomiya
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MurakamiToshi
en-aut-sei=Murakami
en-aut-mei=Toshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=HondaYoshihiro
en-aut-sei=Honda
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=TanimotoMitsune
en-aut-sei=Tanimoto
en-aut-mei=Mitsune
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=2
en-affil=
kn-affil=Kawasaki Hosp, Kawasaki Med Sch, Dept Gen Internal Med 4
affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=10
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=11
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
en-keyword=Non-small cell lung cancer
kn-keyword=Non-small cell lung cancer
en-keyword=Adenocarcinoma
kn-keyword=Adenocarcinoma
en-keyword=Everolimus
kn-keyword=Everolimus
en-keyword=mTOR
kn-keyword=mTOR
en-keyword=EGFR
kn-keyword=EGFR
END
start-ver=1.4
cd-journal=joma
no-vol=127
cd-vols=
no-issue=2
article-no=
start-page=127
end-page=132
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=20150803
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=A prospective cohort study to define the clinical and pathological features of lung cancers harboring HER2 gene aberrations (the HER2-CS Study) and a phase II study of trastuzumab emtansine (recombinant) in patients with HER2-positive non-small cell lung cancer who recurred, progressed after standard chemotherapy, or were primarily refractory to standard chemotherapy
kn-title=HER2異常等の低頻度の分子異常を有する非小細胞肺癌の臨床病理学的特徴を明らかにするための前向き観察研究（HER2-CS Study）と標準化学療法後再発・増悪または標準化学療法不応性のHER2陽性非小細胞肺癌患者を対象としたトラスツズマブエムタンシン（遺伝子組換え）の第2相試験
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=木浦勝行
kn-aut-sei=木浦
kn-aut-mei=勝行
aut-affil-num=1
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=堀田勝幸
kn-aut-sei=堀田
kn-aut-mei=勝幸
aut-affil-num=2
ORCID=
en-aut-name=SatoAkiko
en-aut-sei=Sato
en-aut-mei=Akiko
kn-aut-name=佐藤晃子
kn-aut-sei=佐藤
kn-aut-mei=晃子
aut-affil-num=3
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=大橋圭明
kn-aut-sei=大橋
kn-aut-mei=圭明
aut-affil-num=4
ORCID=
en-aut-name=NinomiyaTakashi
en-aut-sei=Ninomiya
en-aut-mei=Takashi
kn-aut-name=二宮崇
kn-aut-sei=二宮
kn-aut-mei=崇
aut-affil-num=5
ORCID=
en-aut-name=MinnamiDaisuke
en-aut-sei=Minnami
en-aut-mei=Daisuke
kn-aut-name=南大輔
kn-aut-sei=南
kn-aut-mei=大輔
aut-affil-num=6
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=田端雅弘
kn-aut-sei=田端
kn-aut-mei=雅弘
aut-affil-num=7
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=久保寿夫
kn-aut-sei=久保
kn-aut-mei=寿夫
aut-affil-num=8
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=加藤有加
kn-aut-sei=加藤
kn-aut-mei=有加
aut-affil-num=9
ORCID=
en-aut-name=HirataTaizo
en-aut-sei=Hirata
en-aut-mei=Taizo
kn-aut-name=平田泰三
kn-aut-sei=平田
kn-aut-mei=泰三
aut-affil-num=10
ORCID=
affil-num=1
en-affil=
kn-affil=岡山大学病院
affil-num=2
en-affil=
kn-affil=岡山大学病院
affil-num=3
en-affil=
kn-affil=岡山大学病院
affil-num=4
en-affil=
kn-affil=岡山大学病院
affil-num=5
en-affil=
kn-affil=岡山大学病院
affil-num=6
en-affil=
kn-affil=岡山大学病院
affil-num=7
en-affil=
kn-affil=岡山大学病院
affil-num=8
en-affil=
kn-affil=岡山大学病院
affil-num=9
en-affil=
kn-affil=岡山大学病院
affil-num=10
en-affil=
kn-affil=岡山大学病院
en-keyword=臨床研究中核病院
kn-keyword=臨床研究中核病院
en-keyword=国立研究開発法人日本医療研究開発機構
kn-keyword=国立研究開発法人日本医療研究開発機構
en-keyword=文部科学省橋渡し研究加速ネットワークプログラム
kn-keyword=文部科学省橋渡し研究加速ネットワークプログラム
en-keyword=HER2-CS study
kn-keyword=HER2-CS study
en-keyword=trastuzumab emtansine
kn-keyword=trastuzumab emtansine
END
start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=4
article-no=
start-page=243
end-page=253
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=201608
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Effect of Vandetanib on Lung Tumorigenesis in Transgenic Mice Carrying an Activating Egfr Gene Mutation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Vandetanib (ZactimaTM) is a novel, orally available inhibitor of both vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinase. In the present study, a line of transgenic mice with a mouse Egfr gene mutation (delE748-A752) corresponding to a human EGFR mutation (delE746-A750) was established. The transgenic mice developed atypical adenomatous hyperplasia to adenocarcinoma of the lung at around 5 weeks of age and died of lung tumors at approximately 17 weeks of age. In the mice treated with vandetanib (6mg/kg/day), these lung tumors disappeared and the phosphorylations of EGFR and VEGFR-2 were reduced in lung tissues to levels comparable to those of non-transgenic control mice. The median overall survival time of the transgenic mice was 28 weeks in the vandetanib-treated group and 17 weeks in the vehicle-treated group. Vandetanib significantly prolonged the survival of the transgenic mice (log-rank test, p＜0.01); resistance to vandetanib occurred at 20 weeks of age and the animals died from their lung tumors at about 28 weeks of age. These data suggest that vandetanib could suppress the progression of tumors harboring an activating EGFR mutation.
en-copyright=
kn-copyright=
en-aut-name=OsawaMasahiro
en-aut-sei=Osawa
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TakataSaburo
en-aut-sei=Takata
en-aut-mei=Saburo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TakigawaNagio
en-aut-sei=Takigawa
en-aut-mei=Nagio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=Takata Minoru
en-aut-sei=Takata
en-aut-mei=Minoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TanimotoMitsune
en-aut-sei=Tanimoto
en-aut-mei=Mitsune
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of General Internal Medicine 4, Kawasaki Medical School
kn-affil=
affil-num=7
en-affil=Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University
kn-affil=
affil-num=8
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=vandetanib
kn-keyword=vandetanib
en-keyword=VEGFR
kn-keyword=VEGFR
en-keyword=EGFR
kn-keyword=EGFR
en-keyword=nonsmall cell lung cancer
kn-keyword=nonsmall cell lung cancer
en-keyword=transgenic mouse
kn-keyword=transgenic mouse
END
start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=11
article-no=
start-page=2009
end-page=2018
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190730
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction
The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples.
Methods
Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction.
Results
ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in vitro and in vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes.
Conclusions
High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy.
en-copyright=
kn-copyright=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MatsubaraTakehiro
en-aut-sei=Matsubara
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KayataniHiroe
en-aut-sei=Kayatani
en-aut-mei=Hiroe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SatoAkiko
en-aut-sei=Sato
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=NinomiyaTakashi
en-aut-sei=Ninomiya
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=TakataMinoru
en-aut-sei=Takata
en-aut-mei=Minoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Center of Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=17
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=18
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Graduate School of Biostudies, Radiation Biology Center, Kyoto University
kn-affil=
affil-num=20
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=21
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=ALK G1202R
kn-keyword=ALK G1202R
en-keyword=Alectinib
kn-keyword=Alectinib
en-keyword=Amphiregulin
kn-keyword=Amphiregulin
en-keyword=MET
kn-keyword=MET
en-keyword=NSCLC
kn-keyword=NSCLC
END
start-ver=1.4
cd-journal=joma
no-vol=28
cd-vols=
no-issue=
article-no=
start-page=100947
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=2019
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A case of axillary lymphadenitis caused by Mycobacterium intracellulare in an immunocompetent patient
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Axillary lymphadenitis caused by non-tuberculous mycobacteria is rare and has been reported in immunocompromised hosts. Herein, we report the case of a 67-year-old man without immunodeficiency who developed right axillary lymphadenitis caused by Mycobacterium intracellulare and showed a small nodular shadow in the left pulmonary apex. Biopsy of the right axillary lymph node revealed several epithelioid granulomas, and the culture of the lymph node aspirate yielded Mycobacterium intracellulare. The lymph node lesion and left lung apex shadow resolved spontaneously after careful outpatient monitoring. This case suggests that axillary lymphadenitis could be caused by Mycobacterium intracellulare in an immunocompetent patient.
en-copyright=
kn-copyright=
en-aut-name=ItanoJunko
en-aut-sei=Itano
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=SenooSatoru
en-aut-sei=Senoo
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OdaNaohiro
en-aut-sei=Oda
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=Axillary lymphadenitis
kn-keyword=Axillary lymphadenitis
en-keyword=Mycobacterium avium complex infection
kn-keyword=Mycobacterium avium complex infection
en-keyword=Mycobacterium intracellulare
kn-keyword=Mycobacterium intracellulare
END
start-ver=1.4
cd-journal=joma
no-vol=28
cd-vols=
no-issue=
article-no=
start-page=100938
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=2019
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Long-term spontaneous remission with active surveillance in IgG4-related pleuritis: A case report and literature review
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Pleural effusion is a relatively rare feature of IgG4-related disease (IgG4-RD). Here, we report a case of a 72-year-old woman who presented with pleural effusion. Although the pleural adenosine deaminase level was increased, surgical biopsy of the pleura and left inguinal lymph node indicated that the effusion was due to IgG4-RD. Active surveillance was initiated because serum IgG4 and pleural effusion naturally decreased and then completely disappeared. The patient has shown no recurrence for >4 years. This case suggests that pleural biopsy can be used to distinguish IgG4-RD from tuberculosis; moreover, some cases with pleural effusion could improve without treatment.
en-copyright=
kn-copyright=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TaniguchiKohei
en-aut-sei=Taniguchi
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=SohJunichi
en-aut-sei=Soh
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=YoshinoTadashi
en-aut-sei=Yoshino
en-aut-mei=Tadashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences
kn-affil=
affil-num=7
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=IgG4-related disease
kn-keyword=IgG4-related disease
en-keyword=Pleural effusion
kn-keyword=Pleural effusion
en-keyword=Adenosine deaminase
kn-keyword=Adenosine deaminase
en-keyword=Pleural biopsy
kn-keyword=Pleural biopsy
en-keyword=Spontaneous remission
kn-keyword=Spontaneous remission
END
start-ver=1.4
cd-journal=joma
no-vol=59
cd-vols=
no-issue=6
article-no=
start-page=823
end-page=828
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200315
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Successful Re-administration of Osimertinib in Osimertinib-induced Interstitial Lung Disease with an Organizing Pneumonia Pattern: A Case Report and Literature Review
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Osimertinib is the standard therapy for epidermal-growth-factor-receptor (EGFR)-mutant lung cancers. We herein report a case of osimertinib-induced interstitial lung disease (OsiILD) with an organizing pneumonia (OP) pattern and provide a literature-based review. Six months after osimertinib administration, a 75-year-old woman with right pleural carcinomatosis developed ILD with an OP pattern. After salvage chemotherapy, osimertinib with corticosteroid was successfully re-administered. A literature review suggested that 1) OsiILD with an OP pattern was rare but should be recognized, and 2) re-administration of osimertinib in OsiILD was successful in select patients. A criterion that determines whether a patient would benefit from re-administration is warranted.
en-copyright=
kn-copyright=
en-aut-name=ItanoJunko
en-aut-sei=Itano
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=osimertinib
kn-keyword=osimertinib
en-keyword=drug-induced ILD
kn-keyword=drug-induced ILD
en-keyword=reversed halo sign
kn-keyword=reversed halo sign
en-keyword=organizing pneumonia pattern
kn-keyword=organizing pneumonia pattern
en-keyword=re-administration
kn-keyword=re-administration
END
start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=5
article-no=
start-page=371
end-page=379
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202010
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Anaplastic Lymphoma Kinase Fusion: A Review of Therapeutic Drugs and Treatment Strategies
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The prognosis of advanced non-small cell lung cancer (NSCLC) patients has improved in recent decades, especially for patients with an oncogenic driver mutation. Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are effective for patients with the echinoderm microtubule-associated protein-like 4-ALK fusion gene. Several ALK-TKIs have been established: the first-generation ALK-TKI, crizotinib; second-generation ALK-TKIs, alectinib and ceritinib; and third-generation ALK-TKI, lorlatinib. Some ALK-TKIs are effective for tumors that are resistant to other ALK-TKIs; however, as is known in epidermal growth factor receptormutant lung cancer, tumor resistance is inevitable. ALK-positive NSCLCs acquire resistance via various mechanisms, making it a heterogeneous disease. Therefore, it is necessary to develop next-generation treatment strategies, such as the use of next-generation ALK-TKIs for secondary mutations, or combination therapies with ALK-TKIs and other TKIs. In this review, we summarize the development and use of ALK-TKIs, prior pivotal clinical trials, and resistance mechanisms.
en-copyright=
kn-copyright=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
affil-num=1
en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=lung cancer
kn-keyword=lung cancer
en-keyword=anaplastic lymphoma kinase
kn-keyword=anaplastic lymphoma kinase
en-keyword=tyrosine kinase inhibitors
kn-keyword=tyrosine kinase inhibitors
en-keyword=resistance mechanism
kn-keyword=resistance mechanism
END
start-ver=1.4
cd-journal=joma
no-vol=20
cd-vols=
no-issue=6
article-no=
start-page=393
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202012
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Detection of epidermal growth factor receptor mutations in exhaled breath condensate using droplet digital polymerase chain reaction
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The detection of certain oncogenic driver mutations, including those of epidermal growth factor receptor (EGFR), is essential for determining treatment strategies for advanced non‑small cell lung cancer (NSCLC). The current study assessed the feasibility of testing exhaled breath condensate (EBC) for EGFR mutations by droplet digital PCR (ddPCR). Samples were collected from 12 patients with NSCLC harboring EGFR mutations that were admitted to Okayama University Hospital between June 1, 2014 and December 31, 2017. A total of 21 EBC samples were collected using the RTube™ method and EGFR mutations (L858R, exon 19 deletions or T790M) were assessed through ddPCR analysis (EBC‑ddPCR). A total of 3 healthy volunteer samples were also tested to determine a threshold value for each mutation. Various patient characteristics were determined, including sex (3 males and 9 females), age (range 54‑81 years; median, 66 years), smoking history (10 had never smoked; 2 were former smokers), histology (12 patients exhibited adenocarcinoma), clinical stage (9 patients were stage IV; 3 exhibited post‑operative recurrence) and EGFR mutation type (4 had L858R; 8 had exon 19 deletions; 8 had T790M). EBC‑ddPCR demonstrated positive droplets in 8 of the 12 patients. The sensitivity and specificity of each mutation was as follows: 27.3 and 80.0% for EGFR L858R, 30.0 and 90.9% for EGFR Ex19del, and 22.2 and 100% for EGFR T790M. EBC‑ddPCR analysis of EGFR mutations exhibited modest sensitivity and acceptable specificity. EBC‑ddPCR is a minimally invasive and replicable procedure and may be a complementary method for EGFR testing in patients where blood or tissue sampling proves difficult.
en-copyright=
kn-copyright=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TamuraTomoki
en-aut-sei=Tamura
en-aut-mei=Tomoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MatsubaraTakehiro
en-aut-sei=Matsubara
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SenooSatoru
en-aut-sei=Senoo
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=OdaNaohiro
en-aut-sei=Oda
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=NinomiyaTakashi
en-aut-sei=Ninomiya
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Okayama University Hospital Biobank
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Okayama University Hospital Biobank
kn-affil=
affil-num=17
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=18
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=20
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=21
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=non-small cell lung cancer
kn-keyword=non-small cell lung cancer
en-keyword=epidermal growth factor receptor mutations
kn-keyword=epidermal growth factor receptor mutations
en-keyword=droplet digital PCR
kn-keyword=droplet digital PCR
en-keyword=exhaled breath condensate
kn-keyword=exhaled breath condensate
en-keyword=EGFR-TKIs
kn-keyword=EGFR-TKIs
END
start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210107
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene-driven non-small-cell lung cancers
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Molecular agents targeting the epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)- or c-ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene-driven non-small-cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti-vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti-tumor effects of these agents in xenograft mouse models of EGFR-, ALK-, or ROS1-altered NSCLC. The numbers of CD31-positive blood vessels were significantly lower in the tumors of mice treated with an anti-VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR-, ALK-, or ROS1-altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti-tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti-tumor effects of molecular targeted agents in various oncogene-driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti-VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene-driven NSCLC.
en-copyright=
kn-copyright=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KayataniHiroe
en-aut-sei=Kayatani
en-aut-mei=Hiroe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=HaraNaofumi
en-aut-sei=Hara
en-aut-mei=Naofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=HirabaeAtsuko
en-aut-sei=Hirabae
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=NinomiyaTakashi
en-aut-sei=Ninomiya
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=17
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=18
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=20
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=21
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=22
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=3
article-no=
start-page=639
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202177
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Triple therapy with osimertinib, bevacizumab and cetuximab in EGFR‑mutant lung cancer with HIF‑1α/TGF‑α expression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Osimertinib, a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is the standard treatment for patients with lung cancer harboring EGFR T790M; however, acquired resistance is inevitable due to genetic and epigenetic changes in cancer cells. In addition, a recent randomized clinical trial revealed that the combination of osimertinib and bevacizumab failed to exhibit superior progression‑free survival compared with osimertinib alone. The present study aimed to investigate the effect of triple therapy with osimertinib, bevacizumab and cetuximab in xenograft tumors with different initial tumor volumes (conventional model, 200 mm3 and large model, 500 mm3). The results demonstrated that osimertinib significantly inhibited tumor growth in both the conventional and large models; however, maximum tumor regression was attenuated in the large model in which hypoxia‑inducible factor‑1α (HIF‑1α) and transforming growth factor‑α (TGF‑α) expression levels increased. Although the combination of osimertinib and bevacizumab exerted a greater inhibitory effect on tumor growth compared with osimertinib in the conventional model, the effect of this combination therapy was attenuated in the large model. TGF‑α attenuated sensitivity to osimertinib in vitro; however, this negative effect was counteracted by the combination of osimertinib and cetuximab, but not osimertinib and bevacizumab. In the large xenograft tumor model, the triple therapy induced the greatest inhibitory effect on tumor growth compared with osimertinib alone and its combination with bevacizumab. Clinical trials of the triple therapy are required for patients with lung cancer with EGFR mutations and HIF‑1α/TGF‑α.
en-copyright=
kn-copyright=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=epidermal growth factor receptor
kn-keyword=epidermal growth factor receptor
en-keyword=osimertinib
kn-keyword=osimertinib
en-keyword=bevacizumab
kn-keyword=bevacizumab
en-keyword=cetuximab
kn-keyword=cetuximab
en-keyword=hypoxia‑inducible factor‑1α
kn-keyword=hypoxia‑inducible factor‑1α
en-keyword=transforming growth factor‑α
kn-keyword=transforming growth factor‑α
END
start-ver=1.4
cd-journal=joma
no-vol=60
cd-vols=
no-issue=17
article-no=
start-page=2831
end-page=2837
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210901
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Marginal Zone Lymphoma and Lung Adenocarcinoma with an EGFR Exon 19 E746-S752del Mutation in a Patient with IgG4-related Disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 68-year-old man presented with a solid mass at the left renal pelvis and ureter with multiple systemic lymphadenopathies and a mass with a cavity in the right lower lobe of the lung. While a transbronchial lung biopsy revealed no malignancy, a biopsy of the renal pelvis showed marginal zone lymphoma with polyclonal IgG4-positive cells. The serum IgG4 level and presence of a bilateral orbital mass suggested Mikulicz disease. The lesions shrank following the administration of steroids. A rebiopsy confirmed lung adenocarcinoma, and its background showed IgG4-positive cells a year later. IgG4-related diseases require careful follow-up because they can be complicated by malignancy.
en-copyright=
kn-copyright=
en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=FujiiNobuharu
en-aut-sei=Fujii
en-aut-mei=Nobuharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=GionYuka
en-aut-sei=Gion
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=EGFR
kn-keyword=EGFR
en-keyword=IgG4-related disease
kn-keyword=IgG4-related disease
en-keyword=marginal zone lymphoma
kn-keyword=marginal zone lymphoma
en-keyword=osimertinib
kn-keyword=osimertinib
END
start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=1
article-no=
start-page=20
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220207
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Identification of targetable kinases in idiopathic pulmonary fibrosis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF). Methods Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC). Results Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions. Conclusions We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF.
en-copyright=
kn-copyright=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SugimotoSeiichiro
en-aut-sei=Sugimoto
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SenooSatoru
en-aut-sei=Senoo
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=5
en-affil=Department of Thoracic Surgery, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Organ Transplant Center, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=12
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=17
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=18
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=19
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=Idiopathic pulmonary fibrosis
kn-keyword=Idiopathic pulmonary fibrosis
en-keyword=RNA sequencing
kn-keyword=RNA sequencing
en-keyword=Molecular therapeutic target
kn-keyword=Molecular therapeutic target
en-keyword=Personalized therapy
kn-keyword=Personalized therapy
END
start-ver=1.4
cd-journal=joma
no-vol=61
cd-vols=
no-issue=3
article-no=
start-page=379
end-page=383
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Pulmonary Aspergilloma and Allergic Bronchopulmonary Aspergillosis Following the 2018 Heavy Rain Event in Western Japan
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 16-year-old boy with asthma participated in recovery volunteer work following the 2018 heavy rains in Japan. One month later, he experienced chest pain and dyspnea. Chest computed tomography revealed a cavity with a fungal ball, and Aspergillus fumigatus was detected in his bronchoalveolar lavage fluid. He was treated with voriconazole, but new consolidations appeared rapidly. He also experienced allergic bronchopulmonary aspergillosis. After prednisolone prescription, the consolidations improved; however, his asthma worsened. He underwent partial lung resection to avoid allergens, and his symptoms improved. We must recognize cases of infection after a disaster, especially in patients with chronic respiratory diseases.
en-copyright=
kn-copyright=
en-aut-name=AndoEri
en-aut-sei=Ando
en-aut-mei=Eri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YamaneMasaomi
en-aut-sei=Yamane
en-aut-mei=Masaomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Center for Graduate Medical Education, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Departments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=pulmonary aspergilloma
kn-keyword=pulmonary aspergilloma
en-keyword=allergic bronchopulmonary aspergillosis
kn-keyword=allergic bronchopulmonary aspergillosis
en-keyword=disaster
kn-keyword=disaster
END
start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=2
article-no=
start-page=494
end-page=498
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=2022
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Successful and Prompt Treatment with Tepotinib for Lung Adenocarcinoma Harboring MET Exon 14 Skipping Mutation Combined with Lung Abscess Formation: A Case Report
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Tepotinib, the novel MET-tyrosine kinase inhibitor, shows an antitumor effect for patients with non-small-cell lung cancer (NSCLC) harboring MET exon 14 skipping mutation. In January 2022, the AmoyDx (R) Pan Lung Cancer polymerase chain reaction Panel (AmoyDx (R) panel), which had a shorter turnaround time than the conventional test, was launched in Japan as a tepotinib companion test. We report a patient with an advanced MET-mutant NSCLC promptly diagnosed using the AmoyDx (R) panel and successfully treated with tepotinib. Although the patient's performance status (PS) worsened due to the rapid tumor progression and lung abscess formation, the tumor shrank immediately after tepotinib treatment with marked PS improvement.
en-copyright=
kn-copyright=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ShimonishiAtsushi
en-aut-sei=Shimonishi
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
affil-num=1
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=MET
kn-keyword=MET
en-keyword=Tepotinib
kn-keyword=Tepotinib
en-keyword=Non-small-cell lung cancer
kn-keyword=Non-small-cell lung cancer
END
start-ver=1.4
cd-journal=joma
no-vol=178
cd-vols=
no-issue=
article-no=
start-page=1
end-page=10
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202304
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PD-1 blockade augments CD8+ T cell dependent antitumor immunity triggered by Ad-SGE-REIC in Egfr-mutant lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objectives: No immunotherapeutic protocol has yet been established in never-smoking patients with lung cancer harboring driver oncogenic mutations, such as epidermal growth factor receptor (EGFR) mutations. The immunostimulatory effect of Ad-REIC, a genetically engineered adenovirus vector expressing a tumor suppressor gene, reduced expression in immortalized cells (REIC), has been investigated in clinical trials for various solid tumors. However, the immunostimulatory effect of the Ad-REIC in EGFR-mutant lung cancer with a non-inflamed tumor microenvironment (TME) has not been explored.
Materials and methods: We used a syngeneic mouse model developed by transplanting Egfr-mutant lung cancer cells into single or double flanks of C57BL/6J mice. Ad-SGE-REIC, a 2nd-generation vector with an enhancer sequence, was injected only into the tumors from one flank, and its antitumor effects were assessed. Tumor-infiltrating cells were evaluated using immunohistochemistry or flow cytometry. The synergistic effects of Ad-SGE-REIC and PD-1 blockade were also examined.
Results: Injection of Ad-SGE-REIC into one side of the tumor induced not only a local antitumor effect but also a bystander abscopal effect in the non-injected tumor, located on the other flank. The number of PD-1+CD8+ T cells increased in both injected and non-injected tumors. PD-1 blockade augmented the local and abscopal antitumor effects of Ad-SGE-REIC by increasing the number of CD8+ T cells in the TME of Egfr-mutant tumors. Depletion of CD8+ cells reverted the antitumor effect, suggesting they contribute to antitumor immunity.
Conclusion: Ad-SGE-REIC induced systemic antitumor immunity by modifying the TME status from non-inflamed to inflamed, with infiltration of CD8+ T cells. Additionally, in Egfr-mutant lung cancer, this effect was enhanced by PD-1 blockade. These findings pave the way to establish a novel combined immunotherapy strategy with Ad-SGE-REIC and anti-PD-1 antibody for lung cancer with a non-inflamed TME.
en-copyright=
kn-copyright=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=HirabaeAtsuko
en-aut-sei=Hirabae
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TakadaKenji
en-aut-sei=Takada
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=KumonHiromi
en-aut-sei=Kumon
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine
kn-affil=
affil-num=12
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=17
en-affil=Innovation Center Okayama for Nanobio-targeted Therapy, Okayama University
kn-affil=
affil-num=18
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=19
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=EGFR mutation
kn-keyword=EGFR mutation
en-keyword=Non-small cell lung cancer
kn-keyword=Non-small cell lung cancer
en-keyword=Antitumor immunity
kn-keyword=Antitumor immunity
en-keyword=Non-inflamed tumor
kn-keyword=Non-inflamed tumor
en-keyword=Ad-SGE-REIC
kn-keyword=Ad-SGE-REIC
en-keyword=Gene therapy
kn-keyword=Gene therapy
en-keyword=PD-1
kn-keyword=PD-1
END
start-ver=1.4
cd-journal=joma
no-vol=114
cd-vols=
no-issue=11
article-no=
start-page=4343
end-page=4354
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230915
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.
en-copyright=
kn-copyright=
en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=NishiTatsuya
en-aut-sei=Nishi
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MoritaAyako
en-aut-sei=Morita
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HaraNaofumi
en-aut-sei=Hara
en-aut-mei=Naofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TakadaKenji
en-aut-sei=Takada
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=KondoTakumi
en-aut-sei=Kondo
en-aut-mei=Takumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=MatsuokaKen-Ichi
en-aut-sei=Matsuoka
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=17
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=18
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=20
en-affil=Department of Hematology, Oncology and Respiratory Medicine
kn-affil=
affil-num=21
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=alectinib
kn-keyword=alectinib
en-keyword=ALK
kn-keyword=ALK
en-keyword=gilteritinib
kn-keyword=gilteritinib
en-keyword=non-small cell lung cancer
kn-keyword=non-small cell lung cancer
en-keyword=TKI
kn-keyword=TKI
END
start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230823
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Intracranial metastases are common in nonsmall-cell lung cancer (NSCLC) patients, whose prognosis is very poor. In addition, intracranial progression is common during systemic treatments due to the inability to penetrate central nervous system (CNS) barriers, whereas the intracranial effects of cancer immunotherapies remain unclear. We analyzed clinical data to evaluate the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies compared with those treated without PD-1 blockade therapies, and found that the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies was significantly lower than that in patients treated with cytotoxic chemotherapies. In murine models, intracranial rechallenged tumors after initial rejection by PD-1 blockade were suppressed. Accordingly, long-lived memory precursor effector T cells and antigen-specific T cells were increased by PD-1 blockade in intracranial lesions. However, intracranial rechallenged different tumors are not suppressed. Our results indicate that cancer immunotherapies can prevent intracranial progression, maintaining long-term effects intracranially as well as systemically. If intracranial recurrence occurs during the treatment with PD-1 blockade therapies, aggressive local therapies could be worthwhile.
en-copyright=
kn-copyright=
en-aut-name=KemmotsuNaoya
en-aut-sei=Kemmotsu
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KunimasaKei
en-aut-sei=Kunimasa
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=IshinoTakamasa
en-aut-sei=Ishino
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=OtaniYoshihiro
en-aut-sei=Otani
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MichiueHiroyuki
en-aut-sei=Michiue
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=InoueTakako
en-aut-sei=Inoue
en-aut-mei=Takako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=TamiyaMotohiro
en-aut-sei=Tamiya
en-aut-mei=Motohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=SakaiKazuko
en-aut-sei=Sakai
en-aut-mei=Kazuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=DansakoHiromichi
en-aut-sei=Dansako
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=NishioKazuto
en-aut-sei=Nishio
en-aut-mei=Kazuto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=DateIsao
en-aut-sei=Date
en-aut-mei=Isao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
affil-num=1
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute
kn-affil=
affil-num=4
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=10
en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute
kn-affil=
affil-num=11
en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute
kn-affil=
affil-num=12
en-affil=Department of Genome Biology, Kindai University Faculty of Medicine
kn-affil=
affil-num=13
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=14
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=15
en-affil=Department of Genome Biology, Kindai University Faculty of Medicine
kn-affil=
affil-num=16
en-affil=Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=17
en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=18
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=cancer immunotherapy
kn-keyword=cancer immunotherapy
en-keyword=intracranial metastasis
kn-keyword=intracranial metastasis
en-keyword=intracranial progression
kn-keyword=intracranial progression
en-keyword=memory precursor effector T cell
kn-keyword=memory precursor effector T cell
en-keyword=nonsmall-cell lung cancer
kn-keyword=nonsmall-cell lung cancer
END
start-ver=1.4
cd-journal=joma
no-vol=38
cd-vols=
no-issue=
article-no=
start-page=101669
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=2022
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Massive hemoptysis in a post-operative patient with recurrent lung cancer successfully treated by the combination therapy of Endobronchial Watanabe Spigot and bronchial artery embolization
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 76-year-old woman who was treated with lorlatinib for postoperative recurrent anaplastic lymphoma kinase-positive lung adenocarcinoma visited our hospital with massive hemoptysis. Chest computed tomography showed massive bleeding from the right upper lobe; however, the cause of bleeding was unclear. After bronchial artery embolization (BAE), bronchial occlusion was performed using an Endobronchial Watanabe Spigot (EWS) that was easily placed because BAE had reduced the bleeding volume. Treatment with BAE alone was inadequate; however, additional therapy with EWS after BAE successfully controlled the massive hemoptysis, especially in this patient who underwent lobectomy to prevent respiratory dysfunction.
en-copyright=
kn-copyright=
en-aut-name=TaokaMasataka
en-aut-sei=Taoka
en-aut-mei=Masataka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=UmakoshiNoriyuki
en-aut-sei=Umakoshi
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Radiology, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=Hemoptysis
kn-keyword=Hemoptysis
en-keyword=Bronchial artery embolization
kn-keyword=Bronchial artery embolization
en-keyword=Endoscopic bronchial occlusion
kn-keyword=Endoscopic bronchial occlusion
en-keyword=Endobronchial Watanabe Spigot
kn-keyword=Endobronchial Watanabe Spigot
END
start-ver=1.4
cd-journal=joma
no-vol=150
cd-vols=
no-issue=2
article-no=
start-page=89
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240212
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Clinical characteristics of patients treated with immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: CS-Lung-003 prospective observational registry study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose Immune checkpoint inhibitors (ICIs) are ineffective against epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics of patients who were treated or not treated with ICIs, and of those who benefit from immunotherapy in EGFR-mutant NSCLC.
Methods We analyzed patients with unresectable stage III/IV or recurrent NSCLC harboring EGFR mutations using a prospective umbrella-type lung cancer registry (CS-Lung-003).
Results A total of 303 patients who met the eligibility criteria were analyzed. The median age was 69 years; 116 patients were male, 289 had adenocarcinoma, 273 had major mutations, and 67 were treated with ICIs. The duration of EGFR-TKI treatment was longer in the Non-ICI group than in the ICI group (17.1 vs. 12.7 months, p < 0.001). Patients who received ICIs for more than 6 months were categorized into the durable clinical benefit (DCB) group (24 patients), and those who received ICIs for less than 6 months into the Non-DCB group (43 patients). The overall survival in the DCB group exhibited longer than the Non-DCB group (69.3 vs. 47.1 months), and an equivalent compared to that in the Non-ICI group (69.3 vs. 68.9 months). Multivariate analysis for time to next treatment (TTNT) of ICIs showed that a poor PS was associated with a shorter TTNT [hazard ratio (HR) 3.309; p < 0.001]. Patients who were treated with ICIs and chemotherapy combination were associated with a longer TTNT (HR 0.389; p = 0.003). In addition, minor EGFR mutation was associated with a long TTNT (HR 0.450; p = 0.046).
Conclusion ICIs were administered to only 22% of patients with EGFR-mutated lung cancer, and they had shorter TTNT of EGFR-TKI compared to other patients. ICI treatment should be avoided in EGFR mutated lung cancer with poor PS but can be considered for lung cancer with EGFR minor mutations. Pathological biomarker to predict long-term responders to ICI are needed.
en-copyright=
kn-copyright=
en-aut-name=KuribayashiTadahiro
en-aut-sei=Kuribayashi
en-aut-mei=Tadahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TsubataYukari
en-aut-sei=Tsubata
en-aut-mei=Yukari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=IshikawaNobuhisa
en-aut-sei=Ishikawa
en-aut-mei=Nobuhisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KodaniMasahiro
en-aut-sei=Kodani
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KanajiNobuhiro
en-aut-sei=Kanaji
en-aut-mei=Nobuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=YamasakiMasahiro
en-aut-sei=Yamasaki
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=FujitakaKazunori
en-aut-sei=Fujitaka
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KuyamaShoichi
en-aut-sei=Kuyama
en-aut-mei=Shoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TakigawaNagio
en-aut-sei=Takigawa
en-aut-mei=Nagio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=FujimotoNobukazu
en-aut-sei=Fujimoto
en-aut-mei=Nobukazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KubotaTetsuya
en-aut-sei=Kubota
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=InoueMasaaki
en-aut-sei=Inoue
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=FujiwaraKeiichi
en-aut-sei=Fujiwara
en-aut-mei=Keiichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=HaritaShingo
en-aut-sei=Harita
en-aut-mei=Shingo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=TakataIchiro
en-aut-sei=Takata
en-aut-mei=Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=TakadaKenji
en-aut-sei=Takada
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Faculty of Medicine, Shimane University
kn-affil=
affil-num=6
en-affil=Department of Respiratory Medicine, Hiroshima Prefectural Hospital
kn-affil=
affil-num=7
en-affil=Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University
kn-affil=
affil-num=8
en-affil=Department of Internal Medicine, Division of Hematology, Rheumatology, and Respiratory Medicine, Faculty of Medicine, Kagawa University
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital
kn-affil=
affil-num=10
en-affil=Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences
kn-affil=
affil-num=11
en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center
kn-affil=
affil-num=12
en-affil=Department of Internal Medicine 4, Kawasaki Medical School
kn-affil=
affil-num=13
en-affil=Department of Medical Oncology, Okayama Rosai Hospital
kn-affil=
affil-num=14
en-affil=Department of Respiratory Medicine and Allergology, Kochi University Hospital
kn-affil=
affil-num=15
en-affil=Department of Chest Surgery, Shimonoseki City Hospital
kn-affil=
affil-num=16
en-affil=Department of Respiratory Medicine, NHO Okayama Medical Center
kn-affil=
affil-num=17
en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital
kn-affil=
affil-num=18
en-affil=Internal Medicine, Fukuyama City Hospital
kn-affil=
affil-num=19
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=20
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=21
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=22
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=EGFR
kn-keyword=EGFR
en-keyword=EGFR-TKI
kn-keyword=EGFR-TKI
en-keyword=Lung cancer
kn-keyword=Lung cancer
en-keyword=Immune checkpoint inhibitors
kn-keyword=Immune checkpoint inhibitors
en-keyword=Performance status
kn-keyword=Performance status
END
start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=10
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231031
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance.
Methods: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC.
Results: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation.
Conclusions: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-naïve EGFR-mutant NSCLC.
en-copyright=
kn-copyright=
en-aut-name=HaraNaofumi
en-aut-sei=Hara
en-aut-mei=Naofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MoritaAyako
en-aut-sei=Morita
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NishiTatsuya
en-aut-sei=Nishi
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=HirabaeAtsuko
en-aut-sei=Hirabae
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=AbeMasaya
en-aut-sei=Abe
en-aut-mei=Masaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=AsadaNoboru
en-aut-sei=Asada
en-aut-mei=Noboru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
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en-aut-name=OhashiKadoaki
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en-aut-name=HottaKatsuyuki
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en-aut-name=TabataMasahiro
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en-aut-name=MaedaYoshinobu
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en-aut-name=KiuraKatsuyuki
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en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital
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affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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affil-num=13
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affil-num=15
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=17
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=18
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
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affil-num=20
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=Epidermal growth factor receptor (EGFR)
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en-keyword=cell cycle
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en-keyword=CDK4/6 inhibitor
kn-keyword=CDK4/6 inhibitor
END