start-ver=1.4
cd-journal=joma
no-vol=6
cd-vols=
no-issue=2
article-no=
start-page=284
end-page=293
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2026
dt-pub=20260201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Clinical Characteristics and Spatial Transcriptome Analysis of Non–Small Cell Lung Cancers Exhibiting Early Alectinib Resistance: A Retrospective OLCSG Study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Some anaplastic lymphoma kinase (ALK) gene rearrangement–positive lung cancers show early resistance, within 3 months, to alectinib. This study investigated the clinical and molecular characteristics of these patients. We analyzed patients with unresectable stage III/IV disease without indications for radical radiotherapy and recurrent ALK-positive lung cancer who received alectinib as the primary ALK tyrosine kinase inhibitor between 2013 and 2021 at nine hospitals. In total, 103 patients were included. The median age was 65 years; 44 were male and 22 had brain metastases. The median progression-free survival and overall survival (OS) were 28.7 and 80.6 months. Nineteen patients treated for ≤3 months and 84 treated for >3 months were categorized into the early resistance and responder groups, respectively. The early resistance group had significantly shorter OS (8.4 months vs. not estimable, P < 0.001) and was significantly more likely to have brain metastases (42% vs. 17%, P = 0.027). They also showed elevated inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR). Univariate analysis identified brain metastases and high NLR as significant predictors of early resistance. Spatial transcriptome analysis and immunohistochemical staining revealed upregulation of annexin A1 (ANXA1), a calcium-dependent phospholipid-binding protein involved in inflammation and cancer progression, in the early resistance group. Interleukin 6 stimulation, prompted by elevated inflammatory markers, increased ANXA1 expression and reduced alectinib sensitivity. Knockdown of ANXA1 improved alectinib sensitivity in alectinib-resistant cells. In conclusion, brain metastases and high NLR are associated with early resistance. ANXA1 may play an important role in mediating early resistance. New treatment options for the early resistance group are required.
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=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=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=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=InoueHirofumi
en-aut-sei=Inoue
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YokoyamaToshihide
en-aut-sei=Yokoyama
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=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=KudoKenichiro
en-aut-sei=Kudo
en-aut-mei=Kenichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HoritaNaokatsu
en-aut-sei=Horita
en-aut-mei=Naokatsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
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=11
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=12
ORCID=

en-aut-name=SugimotoKeisuke
en-aut-sei=Sugimoto
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
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=14
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=15
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=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=

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 Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital
kn-affil=

affil-num=7
en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center
kn-affil=

affil-num=8
en-affil=Department of Thoracic Oncology and Medicine, National Hospital Organization, Shikoku Cancer Center
kn-affil=

affil-num=9
en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center
kn-affil=

affil-num=10
en-affil=Department of Respiratory Medicine, Kure Kyosai Hospital
kn-affil=

affil-num=11
en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital
kn-affil=

affil-num=12
en-affil=Department of Chest Surgery, Shimonoseki City Hospital
kn-affil=

affil-num=13
en-affil=Department of Respiratory Medicine, Japanese Red Cross Kobe Hospital
kn-affil=

affil-num=14
en-affil=Center for Comprehensive Genomic 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=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=17
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=1
article-no=
start-page=1773
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20251216
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Single-cell and spatial transcriptomic characterization of pulmonary pleomorphic carcinoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Pulmonary pleomorphic carcinoma (PPC) is a rare subtype of lung cancer that comprises both epithelial and sarcomatoid components. The molecular basis of PPC, including the cellular dynamics of its components, remains largely unknown. To elucidate potential therapeutic targets for PPC, we perform a multi-omics analysis incorporating digital spatial profiling and single-cell RNA sequencing (scRNA-seq). PPC exhibits diverse driver gene alterations, including MET exon 14 skipping mutation (METex14) and ALK fusion. In spatial transcriptomics, MET gene and protein are overexpressed exclusively within the epithelial component and not in the sarcomatoid component, even in patients harboring METex14. Epithelial-mesenchymal transition (EMT)-related transcriptional changes, along with extracellular matrix (ECM) remodeling between the epithelial and sarcomatoid components, are observed. scRNA-seq identifies cell populations within the epithelial component that contribute to the malignant transformation and differentiation of the sarcomatoid component. They are characterized by an intermediate EMT state with ECM remodeling signature, suggesting their potential as novel therapeutic targets for PPC.
en-copyright=
kn-copyright=

en-aut-name=MatsuokaAtsushi
en-aut-sei=Matsuoka
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
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=OhkiMasayoshi
en-aut-sei=Ohki
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HisamatsuKazuya
en-aut-sei=Hisamatsu
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FujiwaraRyota
en-aut-sei=Fujiwara
en-aut-mei=Ryota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IshimuraKosei
en-aut-sei=Ishimura
en-aut-mei=Kosei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=FujiiRyunosuke
en-aut-sei=Fujii
en-aut-mei=Ryunosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=HigashiharaTomoaki
en-aut-sei=Higashihara
en-aut-mei=Tomoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HayashiNaohiro
en-aut-sei=Hayashi
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=OkadaKazuhiro
en-aut-sei=Okada
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=YoshichikaRyo
en-aut-sei=Yoshichika
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MukoharaFumiaki
en-aut-sei=Mukohara
en-aut-mei=Fumiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=YoshikawaMao
en-aut-sei=Yoshikawa
en-aut-mei=Mao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=FukumotoYuma
en-aut-sei=Fukumoto
en-aut-mei=Yuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=TomiokaYasuaki
en-aut-sei=Tomioka
en-aut-mei=Yasuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=TanakaShin
en-aut-sei=Tanaka
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=MiyoshiKentaroh
en-aut-sei=Miyoshi
en-aut-mei=Kentaroh
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=OkazakiMikio
en-aut-sei=Okazaki
en-aut-mei=Mikio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
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=21
ORCID=

en-aut-name=OtaniYusuke
en-aut-sei=Otani
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=TanakaAtsushi
en-aut-sei=Tanaka
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=InoueHirofumi
en-aut-sei=Inoue
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
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=25
ORCID=

en-aut-name=YamamotoHidetaka
en-aut-sei=Yamamoto
en-aut-mei=Hidetaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
ORCID=

en-aut-name=EnnishiDaisuke
en-aut-sei=Ennishi
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=27
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=28
ORCID=

affil-num=1
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=2
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=3
en-affil=
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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=6
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=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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=9
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=10
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=11
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=12
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=13
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=14
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=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=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=17
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=18
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=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 General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=21
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=22
en-affil=Department of Pathology, Beth Israel Deaconess Medical Center
kn-affil=

affil-num=23
en-affil=Department of Pathology, Beth Israel Deaconess Medical Center
kn-affil=

affil-num=24
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=

affil-num=25
en-affil=Department of Tumor Microenvironment, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=26
en-affil=Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=27
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=

affil-num=28
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=64
cd-vols=
no-issue=23
article-no=
start-page=3413
end-page=3418
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20251201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Prompt Diagnosis of Ascites and Dramatic Effect of Alectinib for Advanced Lung Adenocarcinoma Harboring EML4-ALK Fusion
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 75-year-old never-smoker woman presented with dyspnea and loss of appetite. A mass was identified in the left upper lobe of the lung, and the patient was referred to our hospital. Despite the diagnosis of lung adenocarcinoma via bronchoscopy, anaplastic lymphoma kinase (ALK) immunostaining was negative. Rapid weight gain and abdominal distension caused by ascites prompted fluid testing using the AmoyDx® Pan Lung Cancer PCR Panel. EML4-ALK fusion was confirmed, and alectinib therapy was initiated immediately. The tumor size had decreased significantly, and the patient was discharged on day 34. This case highlights the necessity of multiplex genetic testing even when ALK immunostaining is negative.
en-copyright=
kn-copyright=

en-aut-name=BabaTakahiro
en-aut-sei=Baba
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=InoueHirofumi
en-aut-sei=Inoue
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MatsuokaHiromi
en-aut-sei=Matsuoka
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KyakunoMio
en-aut-sei=Kyakuno
en-aut-mei=Mio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YoshinagaYusuke
en-aut-sei=Yoshinaga
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakeguchiTetsuya
en-aut-sei=Takeguchi
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=FujiwaraMiho
en-aut-sei=Fujiwara
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=YamadaKotaro
en-aut-sei=Yamada
en-aut-mei=Kotaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NakamuraEri
en-aut-sei=Nakamura
en-aut-mei=Eri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
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=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=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
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=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=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
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=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=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
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=22
ORCID=

affil-num=1
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Department of Medical Support, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Medical Support, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine
kn-affil=

affil-num=5
en-affil=Department of Respiratory Medicine, Okayama University Hospital
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 Respiratory Medicine, Okayama University Hospital
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 Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=12
en-affil=Center for Comprehensive Genomic 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=Department of Geriatric Medicine, Okayama University Hospital
kn-affil=

affil-num=15
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=

affil-num=16
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=

affil-num=17
en-affil=Department of Respiratory 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=Center for Clinical Oncology, Okayama University Hospital
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=

affil-num=22
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=lung adenocarcinoma
kn-keyword=lung adenocarcinoma
en-keyword=EML4-ALK
kn-keyword=EML4-ALK
en-keyword=AmoyDxⓇ Pan Lung Cancer PCR Panel
kn-keyword=AmoyDxⓇ Pan Lung Cancer PCR Panel
en-keyword=alectinib
kn-keyword=alectinib
END

start-ver=1.4
cd-journal=joma
no-vol=17
cd-vols=
no-issue=10
article-no=
start-page=e95808
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20251031
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Risk Stratification for the Prediction of Skeletal-Related Events in Patients With Bone Metastases From Non-small Cell Lung Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Skeletal-related events (SREs) frequently occur in patients with bone metastases from non-small cell lung cancer (NSCLC). This study aimed to identify risk factors for SREs in patients with NSCLC. Based on these factors, we also aimed to stratify patients into subgroups to facilitate the assessment of SRE risk. This retrospective analysis used medical records of 139 patients with NSCLC bone metastases who received treatment at our institution between 2011 and 2014. The incidence of SREs was assessed, and SRE-free survival was analyzed using the Kaplan-Meier method. Clinical information collected at registration was assessed to identify factors associated with the onset of SREs within six months. Univariate analysis was performed using Fisher’s exact test, and multivariate analysis was performed using Cox regression. Of the 139 patients, 36 (26%) developed SREs after registration. The SRE-free survival rates were 80% and 64% at 6 and 12 months, respectively. The univariate and multivariate analyses revealed that the absence of epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangement (hazard ratio (HR): 4.51, 95% confidence interval (CI): 1.32-15.7, p = 0.017) and a lactate dehydrogenase (LDH) level ≥400 U/L (HR: 8.08, 95% CI: 1.78-36.6, p = 0.0067) were risk factors for SRE presentation within six months. Patients were classified into the following three subgroups: with EGFR mutation or ALK rearrangement and LDH level <400 U/L; without EGFR mutation or ALK rearrangement and LDH level <400 U/L; with/without EGFR mutation or ALK rearrangement and LDH level ≥400 U/L. The corresponding six-month SRE-free survival rates were 92%, 69%, and 34%, respectively, showing significant differences (p < 0.001). Close monitoring is recommended for patients with LDH levels ≥400 U/L in daily clinical practice, particularly with the help of the proficiency of orthopedic and radiological experts, to prevent complications such as pathological fractures and paraplegia.
en-copyright=
kn-copyright=

en-aut-name=SakamotoYoshihiro
en-aut-sei=Sakamoto
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NakataEiji
en-aut-sei=Nakata
en-aut-mei=Eiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HamadaMasanori
en-aut-sei=Hamada
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KatayamaYoshimi
en-aut-sei=Katayama
en-aut-mei=Yoshimi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SugiharaShinsuke
en-aut-sei=Sugihara
en-aut-mei=Shinsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OzakiToshifumi
en-aut-sei=Ozaki
en-aut-mei=Toshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=2
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=3
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=4
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=5
en-affil=Department of Orthopedic Surgery, Shikoku Cancer Center
kn-affil=

affil-num=6
en-affil=Department of Orthopedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=anaplastic lymphoma kinase
kn-keyword=anaplastic lymphoma kinase
en-keyword=bone metastases
kn-keyword=bone metastases
en-keyword=epidermal growth factor receptor-tyrosine kinase
kn-keyword=epidermal growth factor receptor-tyrosine kinase
en-keyword=lactate dehydrogenase
kn-keyword=lactate dehydrogenase
en-keyword=non-small cell lung cancer
kn-keyword=non-small cell lung cancer
en-keyword=skeletal related events
kn-keyword=skeletal related events
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=2025
dt-pub=20250925
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=EGFRとMETを標的とする二重特異性抗体であるアミバンタマブのALK融合遺伝子陽性非小細胞肺癌細胞株に対する有効性
kn-title=Efficacy of amivantamab, a bi-specific antibody targeting EGFR and MET, in ALK-rearranged non-small-cell lung cancer cell lines
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=NISHITatsuya
en-aut-sei=NISHI
en-aut-mei=Tatsuya
kn-aut-name=西達也
kn-aut-sei=西
kn-aut-mei=達也
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=4
cd-vols=
no-issue=2
article-no=
start-page=e70091
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250427
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Olanzapine enabled rechallenge after lorlatinib-induced psychosis: A case report
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Lorlatinib is a third-generation tyrosine kinase inhibitor for anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). While it has a high intracranial lesion control rate, it can also cause central nervous system complications, including psychotic symptoms. We present a case of lorlatinib-induced psychosis successfully managed with olanzapine, enabling lorlatinib rechallenge.<br>
Case Presentation: A 32-year-old woman with ALK-positive NSCLC and brain metastases was started on lorlatinib. After 18 months, she developed hallucinations and delusions. Despite treatment with risperidone, her psychotic symptoms persisted, leading to hospitalization. Her symptoms resolved upon lorlatinib discontinuation while risperidone was continued. Given the critical role of lorlatinib in controlling brain metastases, rechallenge was considered. To mitigate concerns regarding drug interactions, risperidone was replaced with olanzapine. Following lorlatinib rechallenge with olanzapine, no recurrence of psychiatric symptoms was observed, allowing continued lorlatinib treatment. Additionally, no progression of lung cancer was noted.<br>
Conclusion: Lorlatinib is an essential drug for controlling brain metastases in ALK-positive NSCLC. However, it can induce psychotic symptoms. When psychiatrists are involved in managing adverse effects during cancer treatment, close collaboration among oncologists, psychiatrists, and patients is essential.
en-copyright=
kn-copyright=

en-aut-name=YokodeAkiyoshi
en-aut-sei=Yokode
en-aut-mei=Akiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FujiwaraMasaki
en-aut-sei=Fujiwara
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakamuraYuko
en-aut-sei=Nakamura
en-aut-mei=Yuko
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=SakamotoShinji
en-aut-sei=Sakamoto
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=TakakiManabu
en-aut-sei=Takaki
en-aut-mei=Manabu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Neuropsychiatry, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Department of Neuropsychiatry, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Neuropsychiatry, Okayama University Hospital
kn-affil=

affil-num=4
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of Neuropsychiatry, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of Neuropsychiatry, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=psycho-oncology
kn-keyword=psycho-oncology
en-keyword=lorlatinib
kn-keyword=lorlatinib
en-keyword=lung cancer
kn-keyword=lung cancer
en-keyword=medication-induced psychosis
kn-keyword=medication-induced psychosis
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=2024
dt-pub=20240325
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=ALK融合遺伝子陽性非小細胞肺癌に対するgilteritinibの有効性についての検討
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=
en-copyright=
kn-copyright=

en-aut-name=ANDOChihiro
en-aut-sei=ANDO
en-aut-mei=Chihiro
kn-aut-name=安東千裕
kn-aut-sei=安東
kn-aut-mei=千裕
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
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=23
cd-vols=
no-issue=17
article-no=
start-page=9782
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220829
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mutual Effects of Orexin and Bone Morphogenetic Proteins on Gonadotropin Expression by Mouse Gonadotrope Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Orexin plays a key role in the regulation of sleep and wakefulness and in feeding behavior in the central nervous system, but its receptors are expressed in various peripheral tissues including endocrine tissues. In the present study, we elucidated the effects of orexin on pituitary gonadotropin regulation by focusing on the functional involvement of bone morphogenetic proteins (BMPs) and clock genes using mouse gonadotrope L beta T2 cells that express orexin type 1 (OX1R) and type 2 (OX2R) receptors. Treatments with orexin A enhanced LH beta and FSH beta mRNA expression in a dose-dependent manner in the absence of GnRH, whereas orexin A in turn suppressed GnRH-induced gonadotropin expression in L beta T2 cells. Orexin A downregulated GnRH receptor expression, while GnRH enhanced OX1R and OX2R mRNA expression. Treatments with orexin A as well as GnRH increased the mRNA levels of Bmal1 and Clock, which are oscillational regulators for gonadotropin expression. Of note, treatments with BMP-6 and -15 enhanced OX1R and OX2R mRNA expression with upregulation of clock gene expression. On the other hand, orexin A enhanced BMP receptor signaling of Smad1/5/9 phosphorylation through upregulation of ALK-2/BMPRII among the BMP receptors expressed in L beta T2 cells. Collectively, the results indicate that orexin regulates gonadotropin expression via clock gene expression by mutually interacting with GnRH action and the pituitary BMP system in gonadotrope cells.
en-copyright=
kn-copyright=

en-aut-name=SoejimaYoshiaki
en-aut-sei=Soejima
en-aut-mei=Yoshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IwataNahoko
en-aut-sei=Iwata
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NakayamaNanako
en-aut-sei=Nakayama
en-aut-mei=Nanako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HirataShinichi
en-aut-sei=Hirata
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NakanoYasuhiro
en-aut-sei=Nakano
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=YamamotoKoichiro
en-aut-sei=Yamamoto
en-aut-mei=Koichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SuyamaAtsuhito
en-aut-sei=Suyama
en-aut-mei=Atsuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OguniKohei
en-aut-sei=Oguni
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NadaTakahiro
en-aut-sei=Nada
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FujisawaSatoshi
en-aut-sei=Fujisawa
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=OtsukaFumio
en-aut-sei=Otsuka
en-aut-mei=Fumio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=7
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=8
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=9
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=11
en-affil=Department of General Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=bone morphogenetic protein (BMP)
kn-keyword=bone morphogenetic protein (BMP)
en-keyword=clock
kn-keyword=clock
en-keyword=gonadotropin
kn-keyword=gonadotropin
en-keyword=orexin
kn-keyword=orexin
en-keyword=pituitary
kn-keyword=pituitary
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=2022
dt-pub=20220325
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=治療歴のないALK、ROS1、またはEGFR陽性非小細胞肺癌の前臨床モデルにおいてSHP2阻害はチロシンキナーゼ阻害剤の効果を増強する
kn-title=SHP2 Inhibition Enhances the Effects of Tyrosine Kinase Inhibitors in Preclinical Models of Treatment-naïve ALK-, ROS1-, or EGFR-altered Non-small Cell Lung Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=狩野裕久
kn-aut-sei=狩野
kn-aut-mei=裕久
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
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=20210920
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=This prespecified subanalysis of the global, randomized controlled phase Ill KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death-ligand 1 (PD-L1) tumor proportion score of 50% or greater evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety. Of 305 patients randomized in KEYNOTE-024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). The hazard ratio (HR) for progression-free survival by independent central review (data cut-off date, 10 July 2017) was 0.25 (95% confidence interval [CI], 0.10-0.64; one-sided, nominal P = .001). The HR for overall survival (data cut-off date, 15 February 2019) was 0.39 (95% CI, 0.17-0.91; one-sided, nominal P = .012). Treatment-related adverse events occurred in 21/21 (100%) pembrolizumab-treated and 18/19 (95%) chemotherapy-treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3-5 events. Immune-mediated adverse events and infusion reactions occurred in 11 patients (52%) and four patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3-5 events. Consistent with results from KEYNOTE-024 overall, first-line pembrolizumab improved progression-free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non-small-cell lung cancer without EGFRIALK alterations and a PD-L1 tumor proportion score of 50% or greater.
en-copyright=
kn-copyright=

en-aut-name=SatouchiMiyako
en-aut-sei=Satouchi
en-aut-mei=Miyako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NosakiKaname
en-aut-sei=Nosaki
en-aut-mei=Kaname
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakahashiToshiaki
en-aut-sei=Takahashi
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NakagawaKazuhiko
en-aut-sei=Nakagawa
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=AoeKeisuke
en-aut-sei=Aoe
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KurataTakayasu
en-aut-sei=Kurata
en-aut-mei=Takayasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SekineAkimasa
en-aut-sei=Sekine
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HoriikeAtsushi
en-aut-sei=Horiike
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FukuharaTatsuro
en-aut-sei=Fukuhara
en-aut-mei=Tatsuro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SugawaraShunichi
en-aut-sei=Sugawara
en-aut-mei=Shunichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UmemuraShigeki
en-aut-sei=Umemura
en-aut-mei=Shigeki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SakaHideo
en-aut-sei=Saka
en-aut-mei=Hideo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OkamotoIsamu
en-aut-sei=Okamoto
en-aut-mei=Isamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=YamamotoNobuyuki
en-aut-sei=Yamamoto
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=SakaiHiroshi
en-aut-sei=Sakai
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KishiKazuma
en-aut-sei=Kishi
en-aut-mei=Kazuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=KatakamiNobuyuki
en-aut-sei=Katakami
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=HorinouchiHidehito
en-aut-sei=Horinouchi
en-aut-mei=Hidehito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=HidaToyoaki
en-aut-sei=Hida
en-aut-mei=Toyoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=OkamotoHiroaki
en-aut-sei=Okamoto
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=AtagiShinji
en-aut-sei=Atagi
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=OhiraTatsuo
en-aut-sei=Ohira
en-aut-mei=Tatsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=HanShi Rong
en-aut-sei=Han
en-aut-mei=Shi Rong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=NoguchiKazuo
en-aut-sei=Noguchi
en-aut-mei=Kazuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=EbianaVictoria
en-aut-sei=Ebiana
en-aut-mei=Victoria
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
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=26
ORCID=

affil-num=1
en-affil=Department of Thoracic Oncology, Hyogo Cancer Center
kn-affil=

affil-num=2
en-affil=Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center
kn-affil=

affil-num=3
en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center
kn-affil=

affil-num=4
en-affil=Department of Medical Oncology, Faculty of Medicine, Kindai University
kn-affil=

affil-num=5
en-affil=Department of Medical Oncology, National Hospital Organization Yamaguchi Ube Medical Center
kn-affil=

affil-num=6
en-affil=Department of Thoracic Oncology, Kansai Medical University Hospital
kn-affil=

affil-num=7
en-affil=Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center
kn-affil=

affil-num=8
en-affil=Department of Thoracic Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research
kn-affil=

affil-num=9
en-affil=Miyagi Cancer Center
kn-affil=

affil-num=10
en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital
kn-affil=

affil-num=11
en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East
kn-affil=

affil-num=12
en-affil=Department of Respiratory Medicine and Medical Oncology, National Hospital Organization Nagoya Medical Center
kn-affil=

affil-num=13
en-affil=Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University
kn-affil=

affil-num=14
en-affil=Internal Medicine III, Wakayama Medical University
kn-affil=

affil-num=15
en-affil=Department of Thoracic Oncology, Saitama Cancer Center
kn-affil=

affil-num=16
en-affil=Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital
kn-affil=

affil-num=17
en-affil=Division of Integrated Oncology, Institute of Biomedical Research and Innovation Hospital
kn-affil=

affil-num=18
en-affil=Department of Thoracic Oncology, National Cancer Center Hospital
kn-affil=

affil-num=19
en-affil=Department of Thoracic Oncology, Aichi Cancer Center
kn-affil=

affil-num=20
en-affil=Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen’s Hospital
kn-affil=

affil-num=21
en-affil=Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center
kn-affil=

affil-num=22
en-affil=Department of Surgery, Tokyo Medical University
kn-affil=

affil-num=23
en-affil=MSD K.K.
kn-affil=

affil-num=24
en-affil=MSD K.K.
kn-affil=

affil-num=25
en-affil=Merck & Co., Inc.
kn-affil=

affil-num=26
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
en-keyword=Japan
kn-keyword=Japan
en-keyword=non-small-cell lung carcinoma
kn-keyword=non-small-cell lung carcinoma
en-keyword=PD-L1 protein
kn-keyword=PD-L1 protein
en-keyword=pembrolizumab
kn-keyword=pembrolizumab
en-keyword=treatment outcome
kn-keyword=treatment outcome
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=12
cd-vols=
no-issue=5
article-no=
start-page=643
end-page=649
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210120
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Crizotinib for recurring non-small-cell lung cancer with EML4-ALK fusion genes previously treated with alectinib: A phase II trial
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background</br>
The efficacy of crizotinib treatment for recurring EML4‐ALK‐positive non‐small cell lung cancer (NSCLC) previously treated with alectinib is unclear. Based on our preclinical findings regarding hepatocyte growth factor/mesenchymal epithelial transition (MET) pathway activation as a potential mechanism of acquired resistance to alectinib, we conducted a phase II trial of the anaplastic lymphoma kinase/MET inhibitor, crizotinib, in patients with alectinib‐refractory, EML4‐ALK‐positive NSCLC. </br>
Methods</br>
Patients with ALK‐rearranged tumors treated with alectinib immediately before enrolling in the trial received crizotinib monotherapy. The objective response rate was the primary outcome of interest. </br>
Results</br>
Nine (100%) patients achieved a partial response with alectinib therapy with a median treatment duration of 6.7 months. Crizotinib was administered with a median treatment interval of 50 (range, 20–433) days. The overall response rate was 33.3% (90% confidence interval [CI]: 9.8–65.5 and 95% CI: 7.5–70.1), which did not reach the predefined criteria of 50%. Two (22%) patients who achieved a partial response had brain metastases at baseline. Progression‐free survival (median, 2.2 months) was not affected by the duration of treatment with alectinib. The median survival time was 24.1 months. The most common adverse events were an increased aspartate transaminase/alanine transaminase (AST/ALT) ratio (44%) and appetite loss (33%); one patient developed transient grade 4 AST/ALT elevation, resulting in treatment discontinuation. Other adverse events were consistent with those previously reported; no treatment‐related deaths occurred.</br>
Conclusions</br>
Although the desired response rate was not achieved, crizotinib monotherapy following treatment with alectinib showed efficacy alongside previously described adverse events.
en-copyright=
kn-copyright=

en-aut-name=HaradaDaijiro
en-aut-sei=Harada
en-aut-mei=Daijiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=IsozakiHideko
en-aut-sei=Isozaki
en-aut-mei=Hideko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KozukiToshiyuki
en-aut-sei=Kozuki
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YokoyamaToshihide
en-aut-sei=Yokoyama
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=YoshiokaHiroshige
en-aut-sei=Yoshioka
en-aut-mei=Hiroshige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=BesshoAkihiro
en-aut-sei=Bessho
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=HosokawaShinobu
en-aut-sei=Hosokawa
en-aut-mei=Shinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
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=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=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=Okayama Lung Cancer Study Group
en-aut-sei=Okayama Lung Cancer Study Group
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

affil-num=1
en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center
kn-affil=

affil-num=2
en-affil=Department of Clinical Pharmaceutics, Okayama University Hospital
kn-affil=

affil-num=3
en-affil=Department of Thoracic Oncology, National Hospital Organization Shikoku Cancer Center
kn-affil=

affil-num=4
en-affil=Department of Respiratory Medicine, Kurashiki Central Hospital
kn-affil=

affil-num=5
en-affil=Department of Respiratory Medicine, Kurashiki Central Hospital
kn-affil=

affil-num=6
en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital
kn-affil=

affil-num=7
en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital
kn-affil=

affil-num=8
en-affil=Department of Internal Medicine, Fukuyama City Hospital
kn-affil=

affil-num=9
en-affil=
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=
kn-affil=
en-keyword=Alectinib
kn-keyword=Alectinib
en-keyword=anaplastic lymphoma kinase
kn-keyword=anaplastic lymphoma kinase
en-keyword=crizotinib
kn-keyword=crizotinib
en-keyword=drug therapy
kn-keyword=drug therapy
en-keyword=non-small cell lung carcinoma
kn-keyword=non-small cell lung carcinoma
END

start-ver=1.4
cd-journal=joma
no-vol=132
cd-vols=
no-issue=2
article-no=
start-page=54
end-page=56
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200803
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=The 2019 Incentive Awards of the Okayama Medical Association in Cancer Research (2019 Hayashibara Prize and Yamada Prize)
kn-title=令和元年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞）
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=槇本剛
kn-aut-sei=槇本
kn-aut-mei=剛
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Department of Respiratory Medicine, National Hospital Organization Iwakuni Clinical Center 
kn-affil=岩国医療センター　呼吸器内科
END

start-ver=1.4
cd-journal=joma
no-vol=111
cd-vols=
no-issue=12
article-no=
start-page=4480
end-page=4489
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200914
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE‐024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a programmed death ligand 1 (PD‐L1) tumor proportion score of 50% or higher evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum‐based chemotherapy (four to six cycles). The primary end‐point was progression‐free survival; secondary end‐points included overall survival and safety. Of 305 patients randomized in KEYNOTE‐024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). Median progression‐free survival was 41.4 (95% confidence interval [CI], 4.2‐42.5) months with pembrolizumab and 4.1 (95% CI, 2.8‐8.3) months with chemotherapy (hazard ratio [HR], 0.27 [95% CI, 0.11‐0.65]; one‐sided, nominal P = .001). Median overall survival was not reached (NR) (95% CI, 22.9‒NR) and 21.5 (95% CI, 5.2‐35.0) months, respectively (HR, 0.39 [95% CI, 0.17‐0.91]; one‐sided, nominal P = .012). Treatment‐related adverse events occurred in 21/21 (100%) pembrolizumab‐treated and 18/19 (95%) chemotherapy‐treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3‐5 events. Immune‐mediated adverse events and infusion reactions occurred in 11 pembrolizumab‐treated patients (52%) and four chemotherapy‐treated patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3‐5 events. Consistent with results from KEYNOTE‐024 overall, first‐line pembrolizumab improved progression‐free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non‐small‐cell lung cancer without EGFR/ALK alterations and a PD‐L1 tumor proportion score of 50% or higher. The trial is registered with Clinicaltrials.gov: NCT02142738.
en-copyright=
kn-copyright=

en-aut-name=SatouchiMiyako
en-aut-sei=Satouchi
en-aut-mei=Miyako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=NosakiKaname
en-aut-sei=Nosaki
en-aut-mei=Kaname
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakahashiToshiaki
en-aut-sei=Takahashi
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NakagawaKazuhiko
en-aut-sei=Nakagawa
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=AoeKeisuke
en-aut-sei=Aoe
en-aut-mei=Keisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KurataTakayasu
en-aut-sei=Kurata
en-aut-mei=Takayasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SekineAkimasa
en-aut-sei=Sekine
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=HoriikeAtsushi
en-aut-sei=Horiike
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FukuharaTatsuro
en-aut-sei=Fukuhara
en-aut-mei=Tatsuro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SugawaraShunichi
en-aut-sei=Sugawara
en-aut-mei=Shunichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=UmemuraShigeki
en-aut-sei=Umemura
en-aut-mei=Shigeki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SakaHideo
en-aut-sei=Saka
en-aut-mei=Hideo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=OkamotoIsamu
en-aut-sei=Okamoto
en-aut-mei=Isamu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=YamamotoNobuyuki
en-aut-sei=Yamamoto
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=SakaiHiroshi
en-aut-sei=Sakai
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KishiKazuma
en-aut-sei=Kishi
en-aut-mei=Kazuma
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=KatakamiNobuyuki
en-aut-sei=Katakami
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=

en-aut-name=HorinouchiHidehito
en-aut-sei=Horinouchi
en-aut-mei=Hidehito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=

en-aut-name=HidaToyoaki
en-aut-sei=Hida
en-aut-mei=Toyoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=

en-aut-name=OkamotoHiroaki
en-aut-sei=Okamoto
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=

en-aut-name=AtagiShinji
en-aut-sei=Atagi
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=

en-aut-name=OhiraTatsuo
en-aut-sei=Ohira
en-aut-mei=Tatsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=

en-aut-name=HanShi Rong
en-aut-sei=Han
en-aut-mei=Shi Rong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=

en-aut-name=NoguchiKazuo
en-aut-sei=Noguchi
en-aut-mei=Kazuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=

en-aut-name=EbianaVictoria
en-aut-sei=Ebiana
en-aut-mei=Victoria
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
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=26
ORCID=

affil-num=1
en-affil=Department of Thoracic Oncology, Hyogo Cancer Center
kn-affil=

affil-num=2
en-affil=Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center
kn-affil=

affil-num=3
en-affil=Division of Thoracic Oncology, Shizuoka Cancer Center
kn-affil=

affil-num=4
en-affil=Department of Medical Oncology, Kindai University Faculty of Medicine
kn-affil=

affil-num=5
en-affil=Department of Medical Oncology, National Hospital Organization Yamaguchi Ube Medical Center
kn-affil=

affil-num=6
en-affil=Department of Thoracic Oncology, Kansai Medical University
kn-affil=

affil-num=7
en-affil=Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center
kn-affil=

affil-num=8
en-affil=Department of Thoracic Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research
kn-affil=

affil-num=9
en-affil=Department of Respiratory Medicine, Miyagi Cancer Center
kn-affil=

affil-num=10
en-affil=Department of Pulmonary Medicine, Sendai Kousei Hospital
kn-affil=

affil-num=11
en-affil=Department of Thoracic Oncology, National Cancer Center Hospital East
kn-affil=

affil-num=12
en-affil=Department of Respiratory Medicine and Medical Oncology, National Hospital Organization Nagoya Medical Center
kn-affil=

affil-num=13
en-affil=Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University
kn-affil=

affil-num=14
en-affil=Internal Medicine III, Wakayama Medical University
kn-affil=

affil-num=15
en-affil=Department of Thoracic Oncology, Saitama Cancer Center
kn-affil=

affil-num=16
en-affil=Department of Respiratory Medicine, Respiratory Center, Totanomon Hospital
kn-affil=

affil-num=17
en-affil=Division of Integrated Oncology, Institute of Biomedical Research and Innovation Hospital
kn-affil=

affil-num=18
en-affil=Department of Thoracic Oncology, National Cancer Center Hospital
kn-affil=

affil-num=19
en-affil=Department of Thoracic Oncology, Aichi Cancer Center
kn-affil=

affil-num=20
en-affil=Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen’s Hospital
kn-affil=

affil-num=21
en-affil=Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center
kn-affil=

affil-num=22
en-affil=Department of Surgery, Tokyo Medical University
kn-affil=

affil-num=23
en-affil=MSD, K.K.
kn-affil=

affil-num=24
en-affil=MSD, K.K.
kn-affil=

affil-num=25
en-affil=Merck & Co., Inc.
kn-affil=

affil-num=26
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
en-keyword=Japan
kn-keyword=Japan
en-keyword=non-small-cell lung carcinoma
kn-keyword=non-small-cell lung carcinoma
en-keyword=PD-L1 protein
kn-keyword=PD-L1 protein
en-keyword=pembrolizumab
kn-keyword=pembrolizumab
en-keyword=treatment outcome
kn-keyword=treatment outcome
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=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20191227
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Tumor Mutation Burden高値のALK陽性肺癌におけるアレクチニブ早期耐性機序について
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=
en-copyright=
kn-copyright=

en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=槇本剛
kn-aut-sei=槇本
kn-aut-mei=剛
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学大学院医歯薬学総合研究科
END

start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=1
article-no=
start-page=89
end-page=94
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202002
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Multicenter, Open-label, Clinical Trial to Assess the Effectiveness and Safety of Allogeneic Hematopoietic Stem Cell Transplantation Using Reduced-intensity Conditioning in Relapsed/refractory Anaplastic Large-cell Lymphoma in Children
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= No standard treatment for relapsed or refractory anaplastic large-cell lymphoma (ALCL) has been established. This study is a multicenter, open-label trial to examine the effectiveness and safety of transplantation with reduced-intensity conditioning (RIC) for patients under 20 years old with relapsed or refractory ALCL. We defined RIC as the administration of fludarabine (30 mg/m2/day) for five days plus melphalan (70 mg/m2/day) for two days and total body irradiation at 4 Gy, followed by allogeneic hematopoietic stem cell transplantation.
en-copyright=
kn-copyright=

en-aut-name=KadaAkiko
en-aut-sei=Kada
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=FukanoReiji
en-aut-sei=Fukano
en-aut-mei=Reiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MoriTetsuya
en-aut-sei=Mori
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KameiMichi
en-aut-sei=Kamei
en-aut-mei=Michi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TanakaFumiko
en-aut-sei=Tanaka
en-aut-mei=Fumiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=UeyamaJunichi
en-aut-sei=Ueyama
en-aut-mei=Junichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SekimizuMasahiro
en-aut-sei=Sekimizu
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=OsumiTomoo
en-aut-sei=Osumi
en-aut-mei=Tomoo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MoriTakeshi
en-aut-sei=Mori
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KogaYuhki
en-aut-sei=Koga
en-aut-mei=Yuhki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=OhkiKentaro
en-aut-sei=Ohki
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FujitaNaoto
en-aut-sei=Fujita
en-aut-mei=Naoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=MitsuiTetsuo
en-aut-sei=Mitsui
en-aut-mei=Tetsuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=SaitoAkiko M.
en-aut-sei=Saito
en-aut-mei=Akiko M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=HashimotoHiroya
en-aut-sei=Hashimoto
en-aut-mei=Hiroya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=KobayashiRyoji
en-aut-sei=Kobayashi
en-aut-mei=Ryoji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

affil-num=1
en-affil=Clinical Research Center, NHO Nagoya Medical Center
kn-affil=

affil-num=2
en-affil=Department of Pediatrics, Yamaguchi University Graduate School of Medicine
kn-affil=

affil-num=3
en-affil=Department of Pediatrics, St. Marianna University School of Medicine Hospital
kn-affil=

affil-num=4
en-affil=Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences
kn-affil=

affil-num=5
en-affil=Department of Pediatrics, Saiseikai Yokohamashi Nanbu Hospital
kn-affil=

affil-num=6
en-affil=Department of Pediatrics, Tottori University Hospital,
kn-affil=

affil-num=7
en-affil=Department of Pediatrics, NHO Nagoya Medical Center
kn-affil=

affil-num=8
en-affil=Children’s Cancer Center, National Center for Child Health and Development
kn-affil=

affil-num=9
en-affil=Department of Hematology and Oncology, Children’s Cancer Center, Kobe Children’s Hospital
kn-affil=

affil-num=10
en-affil=Department of Pediatrics, Graduate School of Medical Sciences Kyushu University
kn-affil=

affil-num=11
en-affil=Department of Pediatric Hematology and Oncology Research, National Center for Child Health and Development
kn-affil=

affil-num=12
en-affil=Department of Pediatrics, Hiroshima Red Cross Hospital and Atomic-Bomb Survivors Hospital
kn-affil=

affil-num=13
en-affil=Department of Pediatrics, Yamagata University Hospital
kn-affil=

affil-num=14
en-affil=Clinical Research Center, NHO Nagoya Medical Center
kn-affil=

affil-num=15
en-affil=Clinical Research Center, NHO Nagoya Medical Center
kn-affil=

affil-num=16
en-affil=Department of Pediatrics and Adolescence, Sapporo Hokuyu Hospital
kn-affil=
en-keyword=anaplastic large-cell lymphoma
kn-keyword=anaplastic large-cell lymphoma
en-keyword=relapsed/refractory
kn-keyword=relapsed/refractory
en-keyword=fludarabine
kn-keyword=fludarabine
en-keyword=melphalan
kn-keyword=melphalan
en-keyword=total body irradiation
kn-keyword=total body irradiation
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<br/>
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. <br/>
Methods<br/>
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. <br/>Results<br/>
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. <br/>Conclusions<br/>
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=72
cd-vols=
no-issue=4
article-no=
start-page=431
end-page=436
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2018
dt-pub=201808
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Phase I/II Study of Crizotinib for Recurrent or Refractory Anaplastic Lymphoma Kinase-Positive Anaplastic Large Cell Lymphoma and a Phase I Study of Crizotinib for Recurrent or Refractory Neuroblastoma : Study Protocol for a Multicenter Single-arm Open-label Trial
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Crizotinib is an inhibitor of multiple tyrosine kinases, including the anaplastic lymphoma kinase (ALK). Responses to crizotinib have also been reported in patients with ALK-positive anaplastic large-cell lymphoma (ALCL) and solid tumors with ALK-mutation, including neuroblastoma. Optimal treatment for patients with recurrent or refractory ALK-positive ALCL and neuroblastoma has not been established. There is a need to develop new drugs for these patients. The objectives of this trial are to evaluate the tolerability and safety of crizotinib in Japanese patients with recurrent/refractory ALK-positive ALCL or neuroblastoma (phase I) and its efficacy in recurrent/refractory ALK-positive ALCL (phase II).
en-copyright=
kn-copyright=

en-aut-name=SekimizuMasahiro
en-aut-sei=Sekimizu
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OsumiTomoo
en-aut-sei=Osumi
en-aut-mei=Tomoo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=FukanoReiji
en-aut-sei=Fukano
en-aut-mei=Reiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KogaYuhki
en-aut-sei=Koga
en-aut-mei=Yuhki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KadaAkiko
en-aut-sei=Kada
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SaitoAkiko  M.
en-aut-sei=Saito
en-aut-mei=Akiko  M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MoriTetsuya
en-aut-sei=Mori
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Pediatrics, Nagoya Medical Center
kn-affil=

affil-num=2
en-affil=Children’s Cancer Center, National Center for Child Health and Development
kn-affil=

affil-num=3
en-affil=Department of Pediatrics, Yamaguchi University Hospital
kn-affil=

affil-num=4
en-affil=Department of Pediatrics, Kyushu University Hospital
kn-affil=

affil-num=5
en-affil=Department of Clinical Research Center, Nagoya Medical Center
kn-affil=

affil-num=6
en-affil=Department of Clinical Research Center, Nagoya Medical Center
kn-affil=

affil-num=7
en-affil=Department of Pediatrics, St. Marianna University School of Medicine Hospital
kn-affil=
en-keyword=crizotinib
kn-keyword=crizotinib
en-keyword=recurrent
kn-keyword=recurrent
en-keyword=refractory
kn-keyword=refractory
en-keyword=anaplastic large cell lymphoma
kn-keyword=anaplastic large cell lymphoma
en-keyword=neuroblastoma
kn-keyword=neuroblastoma
END

start-ver=1.4
cd-journal=joma
no-vol=71
cd-vols=
no-issue=6
article-no=
start-page=505
end-page=512
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2017
dt-pub=201712
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Effects of (−)-epigallocatechin-3-gallate on EGFR- or Fusion Gene-driven Lung Cancer Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= (−)-Epigallocatechin-3-gallate (EGCG) has been shown to bind to several receptors including epidermal growth factor receptor (EGFR). EGFR tyrosine kinase inhibitors and anaplastic lymphoma kinase (ALK) inhibitors are effective for non-small cell lung cancers harboring activating EGFR mutations and ALK or c-ros oncogene 1 (ROS1) fusion genes, respectively. We investigated the effects of EGCG on EGFR- or fusion gene-driven lung cancer cells such as PC-9, RPC-9, H1975, H2228 and HCC78. The five cell lines had similar sensitivity to EGCG. Phosphorylated (p)EGFR, pAkt and pErk in PC-9, RPC-9 and H1975 cells were suppressed by EGCG (50 or 100 μM). EGCG also inhibited pALK in H2228, pROS1 in HCC78, and pErk and pAkt in both cell lines. All the xenograft tumors established using the 5 cell lines in EGCG-treated groups were significantly smaller than the tumors in the vehicle-treated groups. The numbers of tumor blood vessels of xenograft tissues in EGCG-treated mice were significantly lower than those in vehicle-treated mice. In conclusion, EGCG may be effective for EGFR-driven lung tumors irrespective of the presence of T790M, and for ALK or ROS1 fusion gene-driven lung tumors.
en-copyright=
kn-copyright=

en-aut-name=HondaYoshihiro
en-aut-sei=Honda
en-aut-mei=Yoshihiro
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=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
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=5
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=6
ORCID=

en-aut-name=YasugiMasayuki
en-aut-sei=Yasugi
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=

en-aut-name=YamaneHiromichi
en-aut-sei=Yamane
en-aut-mei=Hiromichi
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=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=Department of Allergy and Respiratory 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=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=General Internal Medicine 4, Kawasaki Medical School
kn-affil=

affil-num=10
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=

affil-num=11
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=epigallocatechin-3-gallate
kn-keyword=epigallocatechin-3-gallate
en-keyword=lung cancer
kn-keyword=lung cancer
en-keyword=EGFR
kn-keyword=EGFR
en-keyword=ALK
kn-keyword=ALK
en-keyword=ROS1
kn-keyword=ROS1
END

start-ver=1.4
cd-journal=joma
no-vol=129
cd-vols=
no-issue=1
article-no=
start-page=5
end-page=8
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2017
dt-pub=20170403
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=The 2015 Incentive Award of the Okayama Medical Association in Cancer Research (2015 Hayashibara Prize and Yamada Prize)
kn-title=平成27年度岡山医学会賞　がん研究奨励賞（林原賞・山田賞）
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=IsozakiHideko
en-aut-sei=Isozaki
en-aut-mei=Hideko
kn-aut-name=磯崎英子
kn-aut-sei=磯崎
kn-aut-mei=英子
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Department of Clinical Pharmaceutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=岡山大学大学院医歯薬学総合研究科　臨床薬剤学
END

start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=6
article-no=
start-page=503
end-page=506
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=201612
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Two Relapsed Stage III Childhood Anaplastic Large Cell Lymphoma Patients with NPM-ALK Fusion in Bone Marrow from Initial Diagnosis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Childhood anaplastic large cell lymphoma (ALCL) accounts for approx. 10–30 of cases of non-Hodgkin lymphoma, and the ALCL99 study reported 60–75 disease-free survival; however, a relatively high relapse rate was observed (25–30 ). We report 2 patients with Stage III ALCL who relapsed 6–18 months after the end of ALCL99 chemotherapy. A retrospective molecular analysis identified the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) fusion gene in the first diagnostic bone marrow samples taken from both patients. However, antibodies against the ALK protein appeared to be relatively low in the serum of both patients (×100 and ×750). An increase in chemotherapy intensity may be beneficial if Stage III ALCL patients are shown to be NPM-ALK chimera-positive in the first diagnostic bone marrow sample.
en-copyright=
kn-copyright=

en-aut-name=KanazawaYui
en-aut-sei=Kanazawa
en-aut-mei=Yui
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YamashitaYuka
en-aut-sei=Yamashita
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=FujiwaraMitsuhiro
en-aut-sei=Fujiwara
en-aut-mei=Mitsuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MuraokaMichiko
en-aut-sei=Muraoka
en-aut-mei=Michiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WashioKana
en-aut-sei=Washio
en-aut-mei=Kana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KanamitsuKiichiro
en-aut-sei=Kanamitsu
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=IshidaHisashi
en-aut-sei=Ishida
en-aut-mei=Hisashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NakanoTakae
en-aut-sei=Nakano
en-aut-mei=Takae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=YamadaMiho
en-aut-sei=Yamada
en-aut-mei=Miho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=HoribeKeizo
en-aut-sei=Horibe
en-aut-mei=Keizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TanakaTakehiro
en-aut-sei=Tanaka
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
ORCID=

en-aut-name=ShimadaAkira
en-aut-sei=Shimada
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of aPediatrics, Okayama University Hospital
kn-affil=

affil-num=2
en-affil=Clinical Research Center, Nagoya Medical Center
kn-affil=

affil-num=3
en-affil=Department of Pediatrics, Kurashiki Central Hospital
kn-affil=

affil-num=4
en-affil=Department of aPediatrics, Okayama University Hospital
kn-affil=

affil-num=5
en-affil=Department of aPediatrics, Okayama University Hospital
kn-affil=

affil-num=6
en-affil=Department of aPediatrics, Okayama University Hospital
kn-affil=

affil-num=7
en-affil=Department of aPediatrics, Okayama University Hospital
kn-affil=

affil-num=8
en-affil=Department of aPediatrics, Okayama University Hospital
kn-affil=

affil-num=9
en-affil=Clinical Research Center, Nagoya Medical Center
kn-affil=

affil-num=10
en-affil=Clinical Research Center, Nagoya Medical Center
kn-affil=

affil-num=11
en-affil=Department of Pathology, Okayama University Hospital
kn-affil=

affil-num=12
en-affil=Department of Pathology, Okayama University Hospital
kn-affil=

affil-num=13
en-affil=Department of aPediatrics, Okayama University Hospital
kn-affil=
en-keyword=ALCL
kn-keyword=ALCL
en-keyword=NPM-ALK fusion
kn-keyword=NPM-ALK fusion
en-keyword=lymphoma
kn-keyword=lymphoma
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=2016
dt-pub=20160630
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=非小細胞肺癌細胞は代替受容体チロシンキナーゼの活性化によってALK阻害剤アレクチニブに耐性を獲得する
kn-title=Non–Small Cell Lung Cancer Cells Acquire Resistance to the ALK Inhibitor Alectinib by Activating Alternative Receptor Tyrosine Kinases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=IsozakiHideko
en-aut-sei=Isozaki
en-aut-mei=Hideko
kn-aut-name=磯崎英子
kn-aut-sei=磯崎
kn-aut-mei=英子
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学
END

start-ver=1.4
cd-journal=joma
no-vol=128
cd-vols=
no-issue=2
article-no=
start-page=141
end-page=146
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=20160801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Drug interaction (36. Combination with oral molecular target drugs in lung cancer)
kn-title=薬物相互作用（36―肺癌領域における経口分子標的治療薬）
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=HigashionnaTsukasa
en-aut-sei=Higashionna
en-aut-mei=Tsukasa
kn-aut-name=東恩納司
kn-aut-sei=東恩納
kn-aut-mei=司
aut-affil-num=1
ORCID=

en-aut-name=EsumiSatoru
en-aut-sei=Esumi
en-aut-mei=Satoru
kn-aut-name=江角悟
kn-aut-sei=江角
kn-aut-mei=悟
aut-affil-num=2
ORCID=

en-aut-name=KitamuraYoshihisa
en-aut-sei=Kitamura
en-aut-mei=Yoshihisa
kn-aut-name=北村佳久
kn-aut-sei=北村
kn-aut-mei=佳久
aut-affil-num=3
ORCID=

en-aut-name=SendoToshiaki
en-aut-sei=Sendo
en-aut-mei=Toshiaki
kn-aut-name=千堂年昭
kn-aut-sei=千堂
kn-aut-mei=年昭
aut-affil-num=4
ORCID=

affil-num=1
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=岡山大学病院　薬剤部

affil-num=2
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=岡山大学病院　薬剤部

affil-num=3
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=岡山大学病院　薬剤部

affil-num=4
en-affil=Department of Pharmacy, Okayama University Hospital
kn-affil=岡山大学病院　薬剤部
END

start-ver=1.4
cd-journal=joma
no-vol=126
cd-vols=
no-issue=3
article-no=
start-page=191
end-page=194
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20141201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=The 2013 Incentive Award of the Okayama Medical Association in Cancer Research (2013 Hayashibara Prize and Yamada Prize)
kn-title=平成25年度岡山医学会賞 がん研究奨励賞（林原賞・山田賞）
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=受賞対象論文: Shien K, Toyooka S, Yamamoto H, Soh J, Jida M, Thu KL, Hashida S, Maki Y, Ichihara E, Asano H, Tsukuda K, Takigawa N, Kiura K, Gazdar AF, Lam WL, Miyoshi S：Acquired resistance to EGFR inhibitors is associated with a manifestation of stem cell-like properties in cancer cells. Cancer Res (2013) 73, 3051-3061.
en-copyright=
kn-copyright=

en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=枝園和彦
kn-aut-sei=枝園
kn-aut-mei=和彦
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科 臨床遺伝子医療学，呼吸器・乳腺内分泌外科学
END

start-ver=1.4
cd-journal=joma
no-vol=126
cd-vols=
no-issue=2
article-no=
start-page=103
end-page=107
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20140801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Induction therapy followed by surgery for non small-cell lung cancer
kn-title=非小細胞肺癌に対する術前治療後外科切除療法
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=豊岡伸一
kn-aut-sei=豊岡
kn-aut-mei=伸一
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　臨床遺伝子医療学
en-keyword=非小細胞肺癌
kn-keyword=非小細胞肺癌
en-keyword=導入療法
kn-keyword=導入療法
en-keyword=放射線化学療法
kn-keyword=放射線化学療法
en-keyword=外科切除
kn-keyword=外科切除
END

start-ver=1.4
cd-journal=joma
no-vol=125
cd-vols=
no-issue=1
article-no=
start-page=57
end-page=66
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20130401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Lung cancer and molecular targeted drugs
kn-title=肺癌と分子標的薬
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=TanimotoMitsune
en-aut-sei=Tanimoto
en-aut-mei=Mitsune
kn-aut-name=谷本光音
kn-aut-sei=谷本
kn-aut-mei=光音
aut-affil-num=2
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学病院　呼吸器・アレルギー内科

affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　血液・腫瘍・呼吸器内科学
en-keyword=肺癌
kn-keyword=肺癌
en-keyword=分子プロファイリング
kn-keyword=分子プロファイリング
en-keyword=分子標的薬
kn-keyword=分子標的薬
en-keyword=EGFR遺伝子変異
kn-keyword=EGFR遺伝子変異
en-keyword=ALK融合遺伝子
kn-keyword=ALK融合遺伝子
END

start-ver=1.4
cd-journal=joma
no-vol=67
cd-vols=
no-issue=1
article-no=
start-page=19
end-page=24
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201302
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Silenced Expression of NFKBIA in Lung Adenocarcinoma Patients with a Never-smoking History
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Nuclear factor of κ-light polypeptide gene enhancer in B cells inhibitor α (NFKBIA), which is a tumor suppressor gene, was found to be silenced in lung adenocarcinomas. We examined NFKBIA expression, mutations in the EGFR and K-ras genes, and EML4-ALK fusion in 101 resected lung adenocarcinoma samples from never-smokers. NFKBIA expression was evaluated using immunohistochemistry. NFKBIA expression was negative in 16 of the 101 samples (15.8%). EGFR and K-ras mutations and EML4-ALK fusion were detected in 61 (60.5%), 1 (1.0%), and 2 (2.0%) of the 101 samples, respectively, in a completely mutually exclusive manner. Negative NFKBIA expression was observed significantly more frequently among the tumors with none of the three genetic alterations compared to those with such alterations (p＝0.009). In addition, negative NFKBIA expression was significantly more frequent among the EGFR-wild type samples compared to the EGFR-mutant samples (p＝0.013). In conclusion, NFKBIA expression was silenced in adenocarcinomas without EGFR/K-ras mutations or EML4-ALK fusion, suggesting that the silencing of NFKBIA may play an important role in the carcinogenesis of adenocarcinomas independent of EGFR/K-ras mutations or EML4-ALK fusion.
en-copyright=
kn-copyright=

en-aut-name=FurukawaMasashi
en-aut-sei=Furukawa
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
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=3
ORCID=

en-aut-name=IchimuraKouichi
en-aut-sei=Ichimura
en-aut-mei=Kouichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MakiYuho
en-aut-sei=Maki
en-aut-mei=Yuho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MuraokaTakayuki
en-aut-sei=Muraoka
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=TanakaNorimitsu
en-aut-sei=Tanaka
en-aut-mei=Norimitsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=UenoTsuyoshi
en-aut-sei=Ueno
en-aut-mei=Tsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=AsanoHiroaki
en-aut-sei=Asano
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=TsukudaKazunori
en-aut-sei=Tsukuda
en-aut-mei=Kazunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
ORCID=

en-aut-name=MiyoshiShinichiro
en-aut-sei=Miyoshi
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital

affil-num=2
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital

affil-num=3
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital

affil-num=4
en-affil=
kn-affil=Department of Pathology, Okayama University Hospital

affil-num=5
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital

affil-num=6
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital

affil-num=7
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital

affil-num=8
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital

affil-num=9
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital

affil-num=10
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital

affil-num=11
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital

affil-num=12
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital

affil-num=13
en-affil=
kn-affil=Department of Thoracic Surgery, Okayama University Hospital
en-keyword=never-smoker
kn-keyword=never-smoker
en-keyword=lung cancer
kn-keyword=lung cancer
en-keyword=adenocarcinoma
kn-keyword=adenocarcinoma
en-keyword=nuclear factor of κ-light polypeptide gene enhancer in B cells inhibitor α
kn-keyword=nuclear factor of κ-light polypeptide gene enhancer in B cells inhibitor α
en-keyword=epidermal growth factor receptor
kn-keyword=epidermal growth factor receptor
END

start-ver=1.4
cd-journal=joma
no-vol=71
cd-vols=
no-issue=7-1
article-no=
start-page=3661
end-page=3669
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=1959
dt-pub=19590630
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Studies on Behavior of Fluorine for Animal Organs part 2. Effect of administration of NaF+CaCO(3) and NaF+AlK(SO(4))(2) to rabbit on fluorine contents in bone and organs
kn-title=動物臓器に対するフッ素の挙動の研究 第2編 NaF+CaCO(3)並びにNaF+AlK(SO(4))(2)の投与家兎の骨および臓器中のフッ素含量について
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Rabbits were used as experimental animals. It was investigated how much fluorine was accumulated in their bones and organs, when NaF, CaCO(3)+NaF, and AlK(SO(4))(2)+NaF were respectively administered to them. (1) Amounts of fluorine contained in organs of non administered rabbits were considered to be the physiological required amounts which was taken as food from natural source. (2) When 1 mg/kg, and 10 mg/kg of NaF were respectively administered. amounts of fluorine in bones and organs did not increase so remarkably, but when 20 mg/kg of NaF, fluorine contents increased suddenly in all bones and organs. (3) When both CaCO(3) and NaF were administered in the same amount of fluorine, fluorine was much more accumulated in bones and less in all organs than when NaF alone was administered. (4) When both AlK(SO(4))(2) and NaF were administered, it showed a reverse result as that of CaCO3 and NaF namely, fluorine was more or less accumulated in bones, but much more in organs than amounts of fluorine which was accumulated when the same amount of fluorine alone was administred.
en-copyright=
kn-copyright=

en-aut-name=HayamiTadashi
en-aut-sei=Hayami
en-aut-mei=Tadashi
kn-aut-name=速水〓
kn-aut-sei=速水
kn-aut-mei=〓
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学理学部化学教室
END

start-ver=1.4
cd-journal=joma
no-vol=41
cd-vols=
no-issue=5
article-no=
start-page=187
end-page=193
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=1987
dt-pub=198710
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Radioprotective effects of thiomethylhydantoin derivatives on Escherichia coli and mice.
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=<p>Protection of Escherichia coli NIHJ and C57BL mice from the effects of 60Co gamma-rays provided by S-alk(en)yl-L-cysteines and their hydantoin derivatives was examined. E. coli (10(6) cells/ml) suspended in a 20 mM aqueous solution of one of the drugs was irradiated with 60 Gy of gamma-rays. Five week-old male mice were exposed to 5.0-9.5 Gy of gamma-rays after a single intraperitoneal injection of 0.75 mmol/kg body weight of each compound. In both E. coli and mice, S-allyl compounds afforded more effective radioprotection than S-propyl compounds. The replacement of the alpha-hydrogen of S-substituted cysteines by methyl groups decreased the radioprotective effect. Hydantoin derivatives were much more radioprotective than the original sulfur-containing amino acids. Especially, DL-5-allylthiomethyl-5-methylhydantoin had a remarkable radioprotective effect in mice. The gamma-radiolysis mechanism of thiomethylhydantoin derivatives was discussed in connection with the radioprotective effect of the drugs.</p>

en-copyright=
kn-copyright=

en-aut-name=NishimuraAkihisa
en-aut-sei=Nishimura
en-aut-mei=Akihisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AonoKaname
en-aut-sei=Aono
en-aut-mei=Kaname
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

affil-num=1
en-affil=
kn-affil=Kawasaki College of Allied Health Professions

affil-num=2
en-affil=
kn-affil=Okayama  University
en-keyword=radioprotector
kn-keyword=radioprotector
en-keyword=thiomethylhydantoin
kn-keyword=thiomethylhydantoin
en-keyword=sulfur amino acids
kn-keyword=sulfur amino acids
en-keyword=dose reduction factor
kn-keyword=dose reduction factor
en-keyword= ?-radiolysis
kn-keyword= ?-radiolysis
END

start-ver=1.4
cd-journal=joma
no-vol=118
cd-vols=
no-issue=1
article-no=
start-page=17
end-page=21
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2006
dt-pub=20060501
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=原発性肺高血圧症の病態形成における骨形成蛋白（BMP）Ⅰ型受容体の関与とその意義：肺動脈血管平滑筋細胞を用いた検討
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=武田昌也
kn-aut-sei=武田
kn-aut-mei=昌也
aut-affil-num=1
ORCID=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=大塚文男
kn-aut-sei=大塚
kn-aut-mei=文男
aut-affil-num=2
ORCID=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=中村一文
kn-aut-sei=中村
kn-aut-mei=一文
aut-affil-num=3
ORCID=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=稲垣兼一
kn-aut-sei=稲垣
kn-aut-mei=兼一
aut-affil-num=4
ORCID=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=鈴木二郎
kn-aut-sei=鈴木
kn-aut-mei=二郎
aut-affil-num=5
ORCID=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=三浦大志
kn-aut-sei=三浦
kn-aut-mei=大志
aut-affil-num=6
ORCID=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=藤尾栄起
kn-aut-sei=藤尾
kn-aut-mei=栄起
aut-affil-num=7
ORCID=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=松原広己
kn-aut-sei=松原
kn-aut-mei=広己
aut-affil-num=8
ORCID=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=伊達洋至
kn-aut-sei=伊達
kn-aut-mei=洋至
aut-affil-num=9
ORCID=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=大江透
kn-aut-sei=大江
kn-aut-mei=透
aut-affil-num=10
ORCID=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=槇野博史
kn-aut-sei=槇野
kn-aut-mei=博史
aut-affil-num=11
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　腎・免疫・内分泌代謝内科学

affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　腎・免疫・内分泌代謝内科学

affil-num=3
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　循環器内科学

affil-num=4
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　腎・免疫・内分泌代謝内科学

affil-num=5
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　腎・免疫・内分泌代謝内科学

affil-num=6
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　循環器内科学

affil-num=7
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　循環器内科学

affil-num=8
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　循環器内科学

affil-num=9
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　腫瘍・胸部外科学

affil-num=10
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　循環器内科学

affil-num=11
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科　腎・免疫・内分泌代謝内科学
en-keyword=原発性肺高血圧症 (PPH)
kn-keyword=原発性肺高血圧症 (PPH)
en-keyword=骨形成蛋白 (BMP)
kn-keyword=骨形成蛋白 (BMP)
en-keyword=肺動脈血管平滑筋細胞
kn-keyword=肺動脈血管平滑筋細胞
en-keyword=TGF-β スーパーファミリー
kn-keyword=TGF-β スーパーファミリー
en-keyword=BMP IＢ型受容体 (ALK-6)
kn-keyword=BMP IＢ型受容体 (ALK-6)
END

start-ver=1.4
cd-journal=joma
no-vol=1
cd-vols=
no-issue=1
article-no=
start-page=199
end-page=204
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=1996
dt-pub=199603
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Selective reduction of nitrogen oxide with propylene on alumina-zirconia prepared from Al chelate compound and Zr alkoxide
kn-title=Alキレート化合物とZrアルコキシドより作製したアルミナージルコニアのプロピレンによるNO選択還元活性
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=An alumina-zirconia (AZ) composite powder was prepared by thermal decomposition of the organic precursors, which were synthesized from ethyl acetoacetate aluminium diisopropylate and zirconium n-butoxide. Specific surface area of AZ was higher than that of alumina-zirconia (ALK) prepared from aluminium sec-butoxide and zirconium nbutoxide. True density of AZ was lower than that of ALK. Selective reduction of nitrogen oxide with propylene in oxygen-rich atmosphere on AZ was superior to that on ALK.
en-copyright=
kn-copyright=

en-aut-name=KawabataKoji
en-aut-sei=Kawabata
en-aut-mei=Koji
kn-aut-name=川端浩二
kn-aut-sei=川端
kn-aut-mei=浩二
aut-affil-num=1
ORCID=

en-aut-name=YoshimatsuHideyuki
en-aut-sei=Yoshimatsu
en-aut-mei=Hideyuki
kn-aut-name=吉松英之
kn-aut-sei=吉松
kn-aut-mei=英之
aut-affil-num=2
ORCID=

en-aut-name=YabukiTatsumi
en-aut-sei=Yabuki
en-aut-mei=Tatsumi
kn-aut-name=矢吹達美
kn-aut-sei=矢吹
kn-aut-mei=達美
aut-affil-num=3
ORCID=

en-aut-name=OsakaAkiyoshi
en-aut-sei=Osaka
en-aut-mei=Akiyoshi
kn-aut-name=尾坂明義
kn-aut-sei=尾坂
kn-aut-mei=明義
aut-affil-num=4
ORCID=

en-aut-name=MiuraYoshinari
en-aut-sei=Miura
en-aut-mei=Yoshinari
kn-aut-name=三浦嘉也
kn-aut-sei=三浦
kn-aut-mei=嘉也
aut-affil-num=5
ORCID=

affil-num=1
en-affil=
kn-affil=岡山県工業技術センター

affil-num=2
en-affil=
kn-affil=岡山大学

affil-num=3
en-affil=
kn-affil=岡山県工業技術センター

affil-num=4
en-affil=
kn-affil=岡山大学

affil-num=5
en-affil=
kn-affil=岡山大学
en-keyword=Al chelate compound
kn-keyword=Al chelate compound
en-keyword=Zr alkoxide
kn-keyword=Zr alkoxide
en-keyword=alumina-zirconia
kn-keyword=alumina-zirconia
en-keyword=specific surface area
kn-keyword=specific surface area
en-keyword=true density
kn-keyword=true density
en-keyword=selective reduction of nitrogen oxide
kn-keyword=selective reduction of nitrogen oxide
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=2005
dt-pub=20050630
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=原発性肺高血圧症の散発例から単離した肺動脈血管平滑筋細胞を用いた,骨形成蛋白(BMP)システムの分子解析:BMP IB型受容体(ALK-6)の細胞増殖作用における役割
kn-title=Characterization of the Bone Morphogenetic Protein (BMP) System in Human Pulmonary Arterial Smooth Muscle Cells Isolated from a Sporadic Case of Primary Pulmonary Hypertension: Roles of BMP Type IB Receptor (Activin Receptor-Like Kinase-6) in the Mitotic Action
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=TakedaMasaya
en-aut-sei=Takeda
en-aut-mei=Masaya
kn-aut-name=武田昌也
kn-aut-sei=武田
kn-aut-mei=昌也
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学
END