start-ver=1.4
cd-journal=joma
no-vol=124
cd-vols=
no-issue=3
article-no=
start-page=207
end-page=210
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20121203
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Liposomal delivery of microRNA-7-expressing plasmid overcomes epidermal growth factor receptor tyrosine kinase inhibitor resistance in lung cancer cells
kn-title=EGFR`VLi[[jQςΟ«xΰΧEΙΞ·ιmicroRNA-7»vX~hΜ|\[πp’½±όΙζιΜ’
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=₯Ό
kn-aut-sei=
kn-aut-mei=₯Ό
aut-affil-num=1
ORCID=
en-aut-name=TakigawaNagio
en-aut-sei=Takigawa
en-aut-mei=Nagio
kn-aut-name=λμή`v
kn-aut-sei=λμ
kn-aut-mei=ή`v
aut-affil-num=2
ORCID=
en-aut-name=ItoSachio
en-aut-sei=Ito
en-aut-mei=Sachio
kn-aut-name=Ι‘²qv
kn-aut-sei=Ι‘
kn-aut-mei=²qv
aut-affil-num=3
ORCID=
en-aut-name=KashiharaHiromi
en-aut-sei=Kashihara
en-aut-mei=Hiromi
kn-aut-name=΄Gό
kn-aut-sei=΄
kn-aut-mei=Gό
aut-affil-num=4
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=s΄pξ
kn-aut-sei=s΄
kn-aut-mei=pξ
aut-affil-num=5
ORCID=
en-aut-name=YasudaTatsuji
en-aut-sei=Yasuda
en-aut-mei=Tatsuji
kn-aut-name=Ϋc§ρ
kn-aut-sei=Ϋc
kn-aut-mei=§ρ
aut-affil-num=6
ORCID=
en-aut-name=ShimizuKenji
en-aut-sei=Shimizu
en-aut-mei=Kenji
kn-aut-name=΄
ρ
kn-aut-sei=΄
kn-aut-mei=ρ
aut-affil-num=7
ORCID=
en-aut-name=TanimotoMitsune
en-aut-sei=Tanimoto
en-aut-mei=Mitsune
kn-aut-name=J{υΉ
kn-aut-sei=J{
kn-aut-mei=υΉ
aut-affil-num=8
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=ΨYs
kn-aut-sei=ΨY
kn-aut-mei=s
aut-affil-num=9
ORCID=
affil-num=1
en-affil=
kn-affil=ͺRεwεw@γςw€Θ@tEξαEΔzνΰΘw
affil-num=2
en-affil=
kn-affil=ͺRεwεw@γςw€Θ@tEξαEΔzνΰΘw
affil-num=3
en-affil=
kn-affil=ͺRεwεw@γςw€Θ@ͺqβ`w
affil-num=4
en-affil=
kn-affil=ͺRεwεw@γςw€Θ@tEξαEΔzνΰΘw
affil-num=5
en-affil=
kn-affil=ͺRεwεw@γςw€Θ@tEξαEΔzνΰΘw
affil-num=6
en-affil=
kn-affil=ͺRεwεw@γςw€Θ@ΧE»w
affil-num=7
en-affil=
kn-affil=ͺRεwεw@γςw€Θ@ͺqβ`w
affil-num=8
en-affil=
kn-affil=ͺRεwεw@γςw€Θ@tEξαEΔzνΰΘw
affil-num=9
en-affil=
kn-affil=ͺRεwεw@γςw€Θ@tEξαEΔzνΰΘw
en-keyword=microRNA7
kn-keyword=microRNA7
en-keyword=EGFR
kn-keyword=EGFR
en-keyword=oncogene addiction
kn-keyword=oncogene addiction
en-keyword=lung cancer
kn-keyword=lung cancer
en-keyword=liposome
kn-keyword=liposome
END
start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=9
article-no=
start-page=1720
end-page=1727
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2011
dt-pub=201109
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Liposomal Delivery of MicroRNA-7-Expressing Plasmid Overcomes Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor-Resistance in Lung Cancer Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have been strikingly effective in lung cancers harboring activating EGFR mutations. Unfortunately, the cancer cells eventually acquire resistance to EGFR-TKI. Approximately 50% of the acquired resistance involves a secondary T790M mutation. To overcome the resistance, we focused on EGFR suppression using microRNA-7 (miR-7), targeting multiple sites in the 30-untranslated region of EGFR mRNA. Two EGFR-TKI-sensitive cell lines (PC-9 and H3255) and two EGFR-TKI-resistant cell lines harboring T790M (RPC-9 and H1975) were used. We constructed miR-7-2 containing miR-7-expressing plasmid. After transfection of the miR-7-expressing plasmid, using cationic liposomes, a quantitative PCR and dual luciferase assay were conducted to examine the efficacy. The antiproliferative effect was evaluated using a cell count assay and xenograft model. Protein expression was examined by Western blotting. The miR-7 expression level of the transfectants was approximately 30-fold higher, and the luciferase activity was ablated by 92%. miR-7 significantly inhibited cell growth not only in PC-9 and H3255 but also in RPC-9 and H1975. Expression of insulin receptor substrate-1 (IRS-1), RAF-1, and EGFR was suppressed in the four cell lines. Injection of the miR-7-expressing plasmid revealed marked tumor regression in a mouse xenograft model using RPC-9 and H1975. EGFR, RAF-1, and IRS-1 were suppressed in the residual tumors. These findings indicate promising therapeutic applications of miR-7-expressing plasmids against EGFR oncogene-addicted lung cancers including T790M resistance by liposomal delivery. Mol Cancer Ther; 10(9); 1720-7.
en-copyright=
kn-copyright=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
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=ItoSachio
en-aut-sei=Ito
en-aut-mei=Sachio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KashiharaHiromi
en-aut-sei=Kashihara
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=
en-aut-name=YasudaTatsuji
en-aut-sei=Yasuda
en-aut-mei=Tatsuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=ShimizuKenji
en-aut-sei=Shimizu
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TanimotoMitsune
en-aut-sei=Tanimoto
en-aut-mei=Mitsune
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Genet
affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Cell Chem
affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Mol Genet
affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
END
start-ver=1.4
cd-journal=joma
no-vol=104
cd-vols=
no-issue=1
article-no=
start-page=78
end-page=84
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=201301
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Subpopulation of small-cell lung cancer cells expressing CD133 and CD87 show resistance to chemotherapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Tumors are presumed to contain a small population of cancer stem cells (CSCs) that initiate tumor growth and promote tumor spreading. Multidrug resistance in CSCs is thought to allow the tumor to evade conventional therapy. This study focused on expression of CD133 and CD87 because CD133 is a putative marker of CSCs in some cancers including lung, and CD87 is associated with a stem-cell-like property in small-cell lung cancer (SCLC). Six SCLC cell lines were used. The expression levels of CD133 and CD87 were analyzed by real-time quantitative reverse transcription-polymerase chain reaction and flow cytometry. CD133+/- and CD87+/- cells were isolated by flow cytometry. The drug sensitivities were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Non-obese diabetic/severe combined immunodeficiency mice were used for the tumor formation assay. SBC-7 cells showed the highest expression levels of both CD133 and CD87 among the cell lines. CD133-/CD87-, CD133+/CD87-, and CD133-/CD87+ cells were isolated from SBC-7 cells; however, CD133+/CD87+ cells could not be obtained. Both CD133+/CD87- and CD133-/CD87+ subpopulations showed a higher resistance to etoposide and paclitaxel and greater re-populating ability than the CD133-/CD87- subpopulation. CD133+/CD87- cells contained more G0 quiescent cells than CD133-/CD87- cells. By contrast, CD133-/CD87- cells showed the highest tumorigenic potential. In conclusion, both CD133 and CD87 proved to be inadequate markers for CSCs; however, they might be beneficial for predicting resistance to chemotherapy. (Cancer Sci 2013; 104: 7884)
en-copyright=
kn-copyright=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
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=OsawaMasahiro
en-aut-sei=Osawa
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=HaradaDaijiro
en-aut-sei=Harada
en-aut-mei=Daijiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=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=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=YamaneHiromichi
en-aut-sei=Yamane
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol
affil-num=2
en-affil=
kn-affil=Kawasaki Med Univ, Dept Gen Internal Med 4
affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol
affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol
affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol
affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol
affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol
affil-num=8
en-affil=
kn-affil=Kawasaki Med Univ, Dept Gen Internal Med 4
affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol
affil-num=10
en-affil=
kn-affil=Okayama Univ Hosp, Dept Resp Med
END
start-ver=1.4
cd-journal=joma
no-vol=103
cd-vols=
no-issue=10
article-no=
start-page=1795
end-page=1802
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201210
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=JAK2-related pathway induces acquired erlotinib resistance in lung cancer cells harboring an epidermal growth factor receptor-activating mutation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as gefitinib and erlotinib, are effective for non-small cell lung cancer with activating EGFR mutations. However, even in patients with an initial dramatic response to such a drug, acquired resistance develops after 612 similar to months. A secondary mutation of T790M in EGFR and amplification of the MET gene account for this resistance; however, the mechanism(s) of approximately 30% of acquired resistance cases remain unknown. We established an erlotinib-resistant lung cancer cell line named PC-9/ER3 that harbors an EGFR mutation after continuously exposing PC-9 cells to erlotinib. PC-9/ER3 cells were 136-fold more resistant to erlotinib than the parental cells. Although the PC-9/ER3 cells did not carry the T790M mutation or MET amplification and had similar levels of phosphorylated (p) STAT3, pJAK2 increased in the resistant cells. It was found in the present study that 312 similar to h of exposure to erlotinib in both cell lines did not affect pJAK2 expression, but did result in increased pSTAT3 expression. pAkt in PC-9/ER3 cells was less suppressed than in PC-9 cells, although pEGFR and pMAPK were markedly suppressed in both cell lines. The combined treatment of erlotinib plus a JAK2 inhibitor (JSI-124) suppressed pAkt in PC-9/ER3 cells. Similarly, the combination of erlotinib plus JSI-124 or siRNA against JAK2 restored sensitivity to erlotinib in PC-9/ER3 cells. The combination of erlotinib plus JSI-124 was also effective for reducing PC-9/ER3 tumors in a murine xenograft model. Our results suggest that the activation of JAK2 partially accounts for acquired erlotinib resistance.(Cancer Sci, doi: 10.1111/j.1349-7006.2012.02363.x, 2012)
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=TakigawaNagio
en-aut-sei=Takigawa
en-aut-mei=Nagio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OchiNobuaki
en-aut-sei=Ochi
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=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=YasugiMasayuki
en-aut-sei=Yasugi
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=
en-aut-name=TakedaHiromasa
en-aut-sei=Takeda
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=TakataSaburo
en-aut-sei=Takata
en-aut-mei=Saburo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
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=11
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=12
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=2
en-affil=
kn-affil=Kawasaki Med Univ, Dept Gen Internal Med 4
affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol
affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=8
en-affil=
kn-affil=Okayama Univ Hosp, Dept Resp Med
affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=10
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=11
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Hematol Oncol & Resp Med
affil-num=12
en-affil=
kn-affil=Okayama Univ Hosp, Dept Resp Med
END
start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=4
article-no=
start-page=243
end-page=253
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=201608
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Effect of Vandetanib on Lung Tumorigenesis in Transgenic Mice Carrying an Activating Egfr Gene Mutation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Vandetanib (ZactimaTM) is a novel, orally available inhibitor of both vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinase. In the present study, a line of transgenic mice with a mouse Egfr gene mutation (delE748-A752) corresponding to a human EGFR mutation (delE746-A750) was established. The transgenic mice developed atypical adenomatous hyperplasia to adenocarcinoma of the lung at around 5 weeks of age and died of lung tumors at approximately 17 weeks of age. In the mice treated with vandetanib (6mg/kg/day), these lung tumors disappeared and the phosphorylations of EGFR and VEGFR-2 were reduced in lung tissues to levels comparable to those of non-transgenic control mice. The median overall survival time of the transgenic mice was 28 weeks in the vandetanib-treated group and 17 weeks in the vehicle-treated group. Vandetanib significantly prolonged the survival of the transgenic mice (log-rank test, p0.01); resistance to vandetanib occurred at 20 weeks of age and the animals died from their lung tumors at about 28 weeks of age. These data suggest that vandetanib could suppress the progression of tumors harboring an activating EGFR mutation.
en-copyright=
kn-copyright=
en-aut-name=OsawaMasahiro
en-aut-sei=Osawa
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TakataSaburo
en-aut-sei=Takata
en-aut-mei=Saburo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TakigawaNagio
en-aut-sei=Takigawa
en-aut-mei=Nagio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=Takata Minoru
en-aut-sei=Takata
en-aut-mei=Minoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TanimotoMitsune
en-aut-sei=Tanimoto
en-aut-mei=Mitsune
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of General Internal Medicine 4, Kawasaki Medical School
kn-affil=
affil-num=7
en-affil=Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Radiation Biology Center, Kyoto University
kn-affil=
affil-num=8
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Haematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=vandetanib
kn-keyword=vandetanib
en-keyword=VEGFR
kn-keyword=VEGFR
en-keyword=EGFR
kn-keyword=EGFR
en-keyword=nonsmall cell lung cancer
kn-keyword=nonsmall cell lung cancer
en-keyword=transgenic mouse
kn-keyword=transgenic mouse
END
start-ver=1.4
cd-journal=joma
no-vol=71
cd-vols=
no-issue=5
article-no=
start-page=453
end-page=457
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2017
dt-pub=201710
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Protective Effects of Bisoprolol against Acute Exacerbation in Moderate-to-Severe Chronic Obstructive Pulmonary Disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Although recent retrospective studies suggested that the use of ΐ-blockers appears to help improve the mortality rate and decrease the rate of exacerbation in chronic obstructive pulmonary disease (COPD) patients with heart failure, the effects of ΐ-blockers on COPD patients without heart failure have not been established. Based on previous reports, we have launched a multicenter, prospective, single-arm phase II study to evaluate the preventive effect of the cardioselective ΐ-blocker bisoprolol in COPD exacerbation, in Japanese individuals with moderate-to-severe COPD who do not have heart failure but do have hypertension requiring the use of medication. The primary endpoint is the rate of mild-to-severe COPD exacerbation. The results of this study will clarify whether bisoprolol can prevent exacerbation in COPD patients without heart failure.
en-copyright=
kn-copyright=
en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OdaNaohiro
en-aut-sei=Oda
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MorichikaDaisuke
en-aut-sei=Morichika
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=
en-aut-name=OzeIsao
en-aut-sei=Oze
en-aut-mei=Isao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TanimotoYasushi
en-aut-sei=Tanimoto
en-aut-mei=Yasushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=IchikawaHirohisa
en-aut-sei=Ichikawa
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=FujiiUtako
en-aut-sei=Fujii
en-aut-mei=Utako
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=KanehiroArihiko
en-aut-sei=Kanehiro
en-aut-mei=Arihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
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=Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute
kn-affil=
affil-num=7
en-affil=National Hospital Organization Minami-Okayama Medical Center
kn-affil=
affil-num=8
en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital
kn-affil=
affil-num=9
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=chronic obstructive pulmonary disease
kn-keyword=chronic obstructive pulmonary disease
en-keyword=ΐ-blocker
kn-keyword=ΐ-blocker
en-keyword=bisoprolol
kn-keyword=bisoprolol
en-keyword=exacerbation
kn-keyword=exacerbation
en-keyword=heart failure
kn-keyword=heart failure
END
start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=11
article-no=
start-page=2009
end-page=2018
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190730
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction
The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples.
Methods
Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction.
Results
ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in?vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in?vitro and in?vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes.
Conclusions
High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy.
en-copyright=
kn-copyright=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MatsubaraTakehiro
en-aut-sei=Matsubara
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KayataniHiroe
en-aut-sei=Kayatani
en-aut-mei=Hiroe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SatoAkiko
en-aut-sei=Sato
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=NinomiyaTakashi
en-aut-sei=Ninomiya
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=TakataMinoru
en-aut-sei=Takata
en-aut-mei=Minoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Center of Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=17
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=18
en-affil=Okayama University Hospital Biobank, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Graduate School of Biostudies, Radiation Biology Center, Kyoto University
kn-affil=
affil-num=20
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=21
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=ALK G1202R
kn-keyword=ALK G1202R
en-keyword=Alectinib
kn-keyword=Alectinib
en-keyword=Amphiregulin
kn-keyword=Amphiregulin
en-keyword=MET
kn-keyword=MET
en-keyword=NSCLC
kn-keyword=NSCLC
END
start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=2
article-no=
start-page=129
end-page=135
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=202004
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Association between Histological Types and Enhancement of Dynamic CT for Primary Lung Cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= The aim of this study was to explore enhancement patterns of different types of primary lung cancers on 2-phase dynamic computed tomography (CT). This study included 217 primary lung cancer patients (141 adenocarcinomas [ADs], 48 squamous cell carcinomas [SCCs], 20 small cell lung carcinomas [SCLCs], and 8 others) who were examined using a 2-phase dynamic scan. Regions of interest were identified and mean enhancement values were calculated. After excluding the 20 SCLCs because these lesions had different clinical stages from the other cancer types, the mean attenuation values and subtractions between phases were compared between types of non-small cell lung carcinomas (NSCLCs) using the Kruskal?Wallis test. Late phase attenuation and attenuation of the late minus unenhanced phase (LMU) of SCCs were significantly higher than those of ADs (p<0.05). To differentiate SCC and AD in the late phase, a threshold of 80.21 Hounsfield units (HU) gave 52.9% accuracy. In LMU, a threshold of 52.16 HU gave 59.3% accuracy. Dynamic lung CT has the potential to aid in differentiating among NSCLC types.
en-copyright=
kn-copyright=
en-aut-name=FukumaShogo
en-aut-sei=Fukuma
en-aut-mei=Shogo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ShinyaTakayoshi
en-aut-sei=Shinya
en-aut-mei=Takayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=
en-aut-name=FukuharaRyuichiro
en-aut-sei=Fukuhara
en-aut-mei=Ryuichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=OgawaNanako
en-aut-sei=Ogawa
en-aut-mei=Nanako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=HigakiFumiyo
en-aut-sei=Higaki
en-aut-mei=Fumiyo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=HirakiTakao
en-aut-sei=Hiraki
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=
en-aut-name=KanazawaSusumu
en-aut-sei=Kanazawa
en-aut-mei=Susumu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
affil-num=1
en-affil=Department of Radiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Radiology, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Pediatric Radiology, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of Radiology, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Department of Radiology, Okayama City General Medical Center
kn-affil=
affil-num=7
en-affil=Department of Pathology, 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=Department of Radiology, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of General Thoracic Surgery, Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Radiology, Okayama University Hospital
kn-affil=
en-keyword=differentiation
kn-keyword=differentiation
en-keyword=dynamic computed tomography
kn-keyword=dynamic computed tomography
en-keyword=primary lung cancer
kn-keyword=primary lung cancer
en-keyword=enhancement pattern
kn-keyword=enhancement pattern
END
start-ver=1.4
cd-journal=joma
no-vol=21
cd-vols=
no-issue=
article-no=
start-page=113
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200331
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Pembrolizumab-induced hypothyroidism caused reversible increased serum creatinine levels: a case report
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background
The advent of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with advanced malignancies. On the other hand, these drugs might cause immune-related adverse events (irAEs) including endocrinopathies and nephropathies. Thyroid dysfunction is one of the most common irAEs. For ICIs-induced nephropathies, most cases are due to tubulointerstitial nephritis, which might require steroid treatment. Here, we report a patient with non-small cell lung cancer treated with ICI who developed increased serum creatinine (s-Cr) levels due to ICIs-induced hypothyroidism.
Case presentation
A 57-year-old Asian man with refractory non-small cell lung cancer under ICIs therapy (pembrolizumab, an anti-programmed cell death-1 monoclonal antibody) developed increased s-Cr levels 5 months after the pembrolizumab initiation. His laboratory data, renal biopsy, and Gallium-67 scintigraphy findings denied pembrolizumab-induced tubulointerstitial nephritis. His renal function was correlated with thyroid function. Despite the increase of s-Cr levels, serum cystatin C levels were normal, which could be explained by the hypothyroidism. Levothyroxine treatment improved renal function as well as thyroid function. Then pembrolizumab was resumed, and both his thyroid and renal function remained normal level. Ultimately, we concluded that the increased s-Cr levels were caused by pembrolizumab-induced hypothyroidism.
Conclusion
All clinicians involved in ICI treatment need to recognize the possible increase in s-Cr levels caused by ICIs-induced hypothyroidism, and we propose monitoring serum cystatin C levels to differentiate ICIs-induced hypothyroidism from tubulointerstitial nephritis before invasive renal biopsies or steroid treatment, which are recommended by the prescribing information for pembrolizumab, are performed.
en-copyright=
kn-copyright=
en-aut-name=MatsuokaNatsumi
en-aut-sei=Matsuoka
en-aut-mei=Natsumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=TsujiKenji
en-aut-sei=Tsuji
en-aut-mei=Kenji
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=HaraTakayuki
en-aut-sei=Hara
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=FukushimaKazuhiko
en-aut-sei=Fukushima
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TomaKishio
en-aut-sei=Toma
en-aut-mei=Kishio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KitamuraShinji
en-aut-sei=Kitamura
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=InagakiKenichi
en-aut-sei=Inagaki
en-aut-mei=Kenichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SugiyamaHitoshi
en-aut-sei=Sugiyama
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology, Allergy and Respiratory Medicine,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism,Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Pembrolizumab
kn-keyword=Pembrolizumab
en-keyword=Hypothyroidism
kn-keyword=Hypothyroidism
en-keyword=Creatinine
kn-keyword=Creatinine
en-keyword=Cystatin C
kn-keyword=Cystatin C
END
start-ver=1.4
cd-journal=joma
no-vol=111
cd-vols=
no-issue=10
article-no=
start-page=3739
end-page=3746
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200729
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Utility of immune checkpoint inhibitors in non-small-cell lung cancer patients with poor performance status
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Most clinical trials of non-small-cell lung cancer (NSCLC) exclude patients with poor ECOG performance status (PS). Thus, the efficacy of immune checkpoint inhibitors (ICIs) in patients with poor PS remains unclear. Herein, we used data from a retrospective cohort to assess the potential clinical benefits of ICIs in NSCLC patients with poor PS. Data from NSCLC patients who received ICI monotherapy at 9 institutions between December 2015 and May 2018 were retrospectively analyzed. After excluding 4 patients who lacked PS data, a total of 527 ICI-treated patients, including 79 patients with PS 2 or higher, were used for our analyses. The progression-free survival (PFS) and overall survival (OS) of patients with PS 2 or higher were significantly shorter compared with those of PS 0-1 patients (median PFS, 4.1 vs 2.0 months;P < .001 and median OS, 17.4 vs 4.0 months;P < .001). Among NSCLC patients with programmed cell death protein-ligand 1 (PD-L1) expression of 50% or higher who were treated with pembrolizumab as first-line therapy, the median PFS times of patients with PS 2 and 0-1 were 7.3 and 8.1 months, respectively. There was no significant difference in PFS between patients with PS 2 and 0-1 (P = .321). Although poor PS was significantly associated with worse outcomes in NSCLC patients treated with ICIs, pembrolizumab as a first-line treatment in NSCLC patients expressing high levels of PD-L1 could provide a clinical benefit, even in patients with PS 2.
en-copyright=
kn-copyright=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
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=HaradaDaijiro
en-aut-sei=Harada
en-aut-mei=Daijiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=InoueKoji
en-aut-sei=Inoue
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
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=6
ORCID=
en-aut-name=KishinoDaizo
en-aut-sei=Kishino
en-aut-mei=Daizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=WatanabeKazuhiko
en-aut-sei=Watanabe
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=
en-aut-name=OdaNaohiro
en-aut-sei=Oda
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=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=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, 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, Ehime Prefectural Central Hospital
kn-affil=
affil-num=5
en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center
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, Himeji Red Cross Hospital
kn-affil=
affil-num=8
en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital
kn-affil=
affil-num=9
en-affil=Department of General Internal Medicine 4, Kawasaki Medical School
kn-affil=
affil-num=10
en-affil=Department of Internal Medicine, Fukuyama City Hospital
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=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Hematology, Oncology, and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=non-small cell-lung cancer
kn-keyword=non-small cell-lung cancer
en-keyword=PD-L1
kn-keyword=PD-L1
en-keyword=pembrolizumab
kn-keyword=pembrolizumab
en-keyword=poor performance status
kn-keyword=poor performance status
END
start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=5
article-no=
start-page=423
end-page=425
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=Rapid Disease Progression of Advanced Non-small Cell Lung Cancer Five Months after Cessation of Pembrolizumab
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We report a case of late-onset hyperprogressive disease after cessation of a PD-1 inhibitor. A male was diagnosed with metastatic lung adenocarcinoma with little progression for 2 months before treatment. He received pembrolizumab as a second-line treatment and was subsequently prescribed docetaxel for 3 months until a slight increase in pleural effusion. At the time of progression to docetaxel, he commenced prednisolone because of immune-system-related diarrhea. After that, his general condition rapidly worsened with severe fatigue and hypoxia. Computed tomography revealed a massive increase of pleural effusion and replacement of almost the entire liver with cancer over a period of 5 weeks.
en-copyright=
kn-copyright=
en-aut-name=HirabaeAtsuko
en-aut-sei=Hirabae
en-aut-mei=Atsuko
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=SunamiRyota
en-aut-sei=Sunami
en-aut-mei=Ryota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OtaMoeko
en-aut-sei=Ota
en-aut-mei=Moeko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=IwamotoYoshitaka
en-aut-sei=Iwamoto
en-aut-mei=Yoshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
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=7
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 Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=lung cancer
kn-keyword=lung cancer
en-keyword=immune checkpoint inhibitors
kn-keyword=immune checkpoint inhibitors
en-keyword=pembrolizumab
kn-keyword=pembrolizumab
en-keyword=hyperprogression
kn-keyword=hyperprogression
END
start-ver=1.4
cd-journal=joma
no-vol=59
cd-vols=
no-issue=2
article-no=
start-page=163
end-page=167
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200115
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Managing Lung Cancer with Comorbid Interstitial Pneumonia
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Systemic therapy for advanced non-small cell lung cancer (NSCLC) has dramatically changed in the latest 15 years. Molecular-targeted therapy has brought about an era of precision medicine, and immune checkpoint inhibitors have brought hope for a cure for advanced NSCLC. In the wake of this remarkable advancement, lung cancer with comorbid interstitial pneumonia (IP) has been completely left behind, as most clinical trials exclude patients with comorbid IP. IP, especially idiopathic pulmonary fibrosis (IPF), is often accompanied by lung cancer, and acute exacerbation can develop during various cancer therapies, including surgery, radiotherapy and pharmacotherapy. In this review, we focus on the clinical questions concerning pharmacotherapy in cases of advanced lung cancer with comorbid IP and discuss what we can do with the currently available data.
en-copyright=
kn-copyright=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=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 Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Department of Medical Technology, Okayama University Graduate School of Health Sciences
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=lung cancer
kn-keyword=lung cancer
en-keyword=interstitial pneumonia
kn-keyword=interstitial pneumonia
END
start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210107
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene-driven non-small-cell lung cancers
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Molecular agents targeting the epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)- or c-ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene-driven non-small-cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti-vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti-tumor effects of these agents in xenograft mouse models of EGFR-, ALK-, or ROS1-altered NSCLC. The numbers of CD31-positive blood vessels were significantly lower in the tumors of mice treated with an anti-VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR-, ALK-, or ROS1-altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti-tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti-tumor effects of molecular targeted agents in various oncogene-driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti-VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene-driven NSCLC.
en-copyright=
kn-copyright=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KayataniHiroe
en-aut-sei=Kayatani
en-aut-mei=Hiroe
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=HaraNaofumi
en-aut-sei=Hara
en-aut-mei=Naofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=HirabaeAtsuko
en-aut-sei=Hirabae
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=NinomiyaTakashi
en-aut-sei=Ninomiya
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=17
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=18
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=20
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=21
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=22
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=3
article-no=
start-page=639
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=202177
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Triple therapy with osimertinib, bevacizumab and cetuximab in EGFR?mutant lung cancer with HIF?1Ώ/TGF?Ώ expression
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Osimertinib, a third generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is the standard treatment for patients with lung cancer harboring EGFR T790M; however, acquired resistance is inevitable due to genetic and epigenetic changes in cancer cells. In addition, a recent randomized clinical trial revealed that the combination of osimertinib and bevacizumab failed to exhibit superior progression?free survival compared with osimertinib alone. The present study aimed to investigate the effect of triple therapy with osimertinib, bevacizumab and cetuximab in xenograft tumors with different initial tumor volumes (conventional model, 200 mm3 and large model, 500 mm3). The results demonstrated that osimertinib significantly inhibited tumor growth in both the conventional and large models; however, maximum tumor regression was attenuated in the large model in which hypoxia?inducible factor?1Ώ (HIF?1Ώ) and transforming growth factor?Ώ (TGF?Ώ) expression levels increased. Although the combination of osimertinib and bevacizumab exerted a greater inhibitory effect on tumor growth compared with osimertinib in the conventional model, the effect of this combination therapy was attenuated in the large model. TGF?Ώ attenuated sensitivity to osimertinib in vitro; however, this negative effect was counteracted by the combination of osimertinib and cetuximab, but not osimertinib and bevacizumab. In the large xenograft tumor model, the triple therapy induced the greatest inhibitory effect on tumor growth compared with osimertinib alone and its combination with bevacizumab. Clinical trials of the triple therapy are required for patients with lung cancer with EGFR mutations and HIF?1Ώ/TGF?Ώ.
en-copyright=
kn-copyright=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=epidermal growth factor receptor
kn-keyword=epidermal growth factor receptor
en-keyword=osimertinib
kn-keyword=osimertinib
en-keyword=bevacizumab
kn-keyword=bevacizumab
en-keyword=cetuximab
kn-keyword=cetuximab
en-keyword=hypoxia?inducible factor?1Ώ
kn-keyword=hypoxia?inducible factor?1Ώ
en-keyword=transforming growth factor?Ώ
kn-keyword=transforming growth factor?Ώ
END
start-ver=1.4
cd-journal=joma
no-vol=60
cd-vols=
no-issue=17
article-no=
start-page=2831
end-page=2837
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210901
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Marginal Zone Lymphoma and Lung Adenocarcinoma with an EGFR Exon 19 E746-S752del Mutation in a Patient with IgG4-related Disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 68-year-old man presented with a solid mass at the left renal pelvis and ureter with multiple systemic lymphadenopathies and a mass with a cavity in the right lower lobe of the lung. While a transbronchial lung biopsy revealed no malignancy, a biopsy of the renal pelvis showed marginal zone lymphoma with polyclonal IgG4-positive cells. The serum IgG4 level and presence of a bilateral orbital mass suggested Mikulicz disease. The lesions shrank following the administration of steroids. A rebiopsy confirmed lung adenocarcinoma, and its background showed IgG4-positive cells a year later. IgG4-related diseases require careful follow-up because they can be complicated by malignancy.
en-copyright=
kn-copyright=
en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=FujiiNobuharu
en-aut-sei=Fujii
en-aut-mei=Nobuharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=GionYuka
en-aut-sei=Gion
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Division of Pathophysiology, Okayama University Graduate School of Health Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=EGFR
kn-keyword=EGFR
en-keyword=IgG4-related disease
kn-keyword=IgG4-related disease
en-keyword=marginal zone lymphoma
kn-keyword=marginal zone lymphoma
en-keyword=osimertinib
kn-keyword=osimertinib
END
start-ver=1.4
cd-journal=joma
no-vol=23
cd-vols=
no-issue=1
article-no=
start-page=20
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220207
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Identification of targetable kinases in idiopathic pulmonary fibrosis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF). Methods Thirteen samples from five patients with IPF (Cases 1-5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC). Results Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions. Conclusions We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF.
en-copyright=
kn-copyright=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomidaShuta
en-aut-sei=Tomida
en-aut-mei=Shuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=YamamotoHiromasa
en-aut-sei=Yamamoto
en-aut-mei=Hiromasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SugimotoSeiichiro
en-aut-sei=Sugimoto
en-aut-mei=Seiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SenooSatoru
en-aut-sei=Senoo
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Center for Comprehensive Genomic Medicine, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=5
en-affil=Department of Thoracic Surgery, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Organ Transplant Center, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=12
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=17
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=18
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=19
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=Idiopathic pulmonary fibrosis
kn-keyword=Idiopathic pulmonary fibrosis
en-keyword=RNA sequencing
kn-keyword=RNA sequencing
en-keyword=Molecular therapeutic target
kn-keyword=Molecular therapeutic target
en-keyword=Personalized therapy
kn-keyword=Personalized therapy
END
start-ver=1.4
cd-journal=joma
no-vol=61
cd-vols=
no-issue=3
article-no=
start-page=379
end-page=383
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Pulmonary Aspergilloma and Allergic Bronchopulmonary Aspergillosis Following the 2018 Heavy Rain Event in Western Japan
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 16-year-old boy with asthma participated in recovery volunteer work following the 2018 heavy rains in Japan. One month later, he experienced chest pain and dyspnea. Chest computed tomography revealed a cavity with a fungal ball, and Aspergillus fumigatus was detected in his bronchoalveolar lavage fluid. He was treated with voriconazole, but new consolidations appeared rapidly. He also experienced allergic bronchopulmonary aspergillosis. After prednisolone prescription, the consolidations improved; however, his asthma worsened. He underwent partial lung resection to avoid allergens, and his symptoms improved. We must recognize cases of infection after a disaster, especially in patients with chronic respiratory diseases.
en-copyright=
kn-copyright=
en-aut-name=AndoEri
en-aut-sei=Ando
en-aut-mei=Eri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=RaiKammei
en-aut-sei=Rai
en-aut-mei=Kammei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=YamaneMasaomi
en-aut-sei=Yamane
en-aut-mei=Masaomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=MiyaharaNobuaki
en-aut-sei=Miyahara
en-aut-mei=Nobuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Center for Graduate Medical Education, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Departments of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=pulmonary aspergilloma
kn-keyword=pulmonary aspergilloma
en-keyword=allergic bronchopulmonary aspergillosis
kn-keyword=allergic bronchopulmonary aspergillosis
en-keyword=disaster
kn-keyword=disaster
END
start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=2
article-no=
start-page=494
end-page=498
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=2022
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Successful and Prompt Treatment with Tepotinib for Lung Adenocarcinoma Harboring MET Exon 14 Skipping Mutation Combined with Lung Abscess Formation: A Case Report
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Tepotinib, the novel MET-tyrosine kinase inhibitor, shows an antitumor effect for patients with non-small-cell lung cancer (NSCLC) harboring MET exon 14 skipping mutation. In January 2022, the AmoyDx (R) Pan Lung Cancer polymerase chain reaction Panel (AmoyDx (R) panel), which had a shorter turnaround time than the conventional test, was launched in Japan as a tepotinib companion test. We report a patient with an advanced MET-mutant NSCLC promptly diagnosed using the AmoyDx (R) panel and successfully treated with tepotinib. Although the patient's performance status (PS) worsened due to the rapid tumor progression and lung abscess formation, the tumor shrank immediately after tepotinib treatment with marked PS improvement.
en-copyright=
kn-copyright=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ShimonishiAtsushi
en-aut-sei=Shimonishi
en-aut-mei=Atsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
affil-num=1
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=MET
kn-keyword=MET
en-keyword=Tepotinib
kn-keyword=Tepotinib
en-keyword=Non-small-cell lung cancer
kn-keyword=Non-small-cell lung cancer
END
start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=24
article-no=
start-page=6184
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221214
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Effect of Pleural Effusion on Prognosis in Patients with Non-Small Cell Lung Cancer Undergoing Immunochemotherapy: A Retrospective Observational Study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Simple Summary Minimal data exists on pleural effusion (PE) for non-small cell lung cancer (NSCLC) patients undergoing combined ICI and chemotherapy. We retrospectively investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival and overall survival than those without PE. In addition, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. In conclusion, PE was associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy. Objectives: Combined immune checkpoint inhibitor (ICI) therapy and chemotherapy has become the standard treatment for advanced non-small-cell lung cancer (NSCLC). Pleural effusion (PE) is associated with poor outcomes among patients with NSCLC undergoing chemotherapy. However, minimal data exists on PE for patients undergoing combined ICI and chemotherapy. Therefore, we investigated how PE affects survival outcomes in patients with NSCLC undergoing this combined therapy. Methods: We identified patients with advanced NSCLC undergoing chemotherapy and ICI therapy from the Okayama Lung Cancer Study Group-Immune Chemotherapy Database (OLCSG-ICD) between December 2018 and December 2020; the OLCSG-ICD includes the clinical data of patients with advanced NSCLC from 13 institutions. Then, we analyzed the treatment outcomes based on the presence of PE. Results: We identified 478 patients who underwent combined ICI therapy and chemotherapy; 357 patients did not have PE, and 121 patients did have PE. Patients with PE had significantly shorter progression-free survival (PFS) and overall survival (OS) than those without PE (median PFS: 6.2 months versus 9.1 months; p < 0.001; median OS: 16.4 months versus 27.7 months; p < 0.001). The negative effect of PE differed based on the patient's programmed cell death-ligand 1 (PD-L1) expression status; with the effect being more evident in patients with high PD-L1 expression. In addition, PFS and OS did not differ between patients who did and did not undergo bevacizumab treatment; thus, bevacizumab-containing regimens did not improve the survival outcomes for patients with PE. Conclusion: PE is associated with poor outcomes among patients with NSCLC undergoing combined ICI therapy and chemotherapy.
en-copyright=
kn-copyright=
en-aut-name=NishimuraTomoka
en-aut-sei=Nishimura
en-aut-mei=Tomoka
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=YokoyamaToshihide
en-aut-sei=Yokoyama
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=InoueKoji
en-aut-sei=Inoue
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TamuraTomoki
en-aut-sei=Tamura
en-aut-mei=Tomoki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SatoKen
en-aut-sei=Sato
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=OdaNaohiro
en-aut-sei=Oda
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=
en-aut-name=KishinoDaizo
en-aut-sei=Kishino
en-aut-mei=Daizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KawaiHaruyuki
en-aut-sei=Kawai
en-aut-mei=Haruyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
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=11
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=12
ORCID=
en-aut-name=FujimotoNobukazu
en-aut-sei=Fujimoto
en-aut-mei=Nobukazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=IchikawaHirohisa
en-aut-sei=Ichikawa
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
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=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=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
affil-num=1
en-affil=Department of Hematology and Oncology, 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 Respiratory Medicine, Ohara Healthcare Foundation, Kurashiki Central Hospital
kn-affil=
affil-num=4
en-affil=Department of Respiratory Medicine, Ehime Prefectural Central Hospital
kn-affil=
affil-num=5
en-affil=Department of Respiratory Medicine, NHO Iwakuni Clinical Center
kn-affil=
affil-num=6
en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center
kn-affil=
affil-num=7
en-affil=Department of Internal Medicine, Fukuyama City Hospital
kn-affil=
affil-num=8
en-affil=Department of Respiratory Medicine, Japanese Red Cross Okayama Hospital
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, Japanese Red Cross Society Himeji Hospital
kn-affil=
affil-num=10
en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital
kn-affil=
affil-num=11
en-affil=Department of Chest Surgery, Shimonoseki City Hospital
kn-affil=
affil-num=12
en-affil=Department of General Internal Medicine 4, Kawasaki Medical School
kn-affil=
affil-num=13
en-affil=Department of Respiratory Medicine, Okayama Rosai Hospital
kn-affil=
affil-num=14
en-affil=Department of Respiratory Medicine, KKR Takamatsu Hospital
kn-affil=
affil-num=15
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=17
en-affil=Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=18
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=pleural effusion
kn-keyword=pleural effusion
en-keyword=non-small cell carcinoma
kn-keyword=non-small cell carcinoma
en-keyword=immune checkpoint inhibitors
kn-keyword=immune checkpoint inhibitors
END
start-ver=1.4
cd-journal=joma
no-vol=178
cd-vols=
no-issue=
article-no=
start-page=1
end-page=10
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202304
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PD-1 blockade augments CD8+ T cell dependent antitumor immunity triggered by Ad-SGE-REIC in Egfr-mutant lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objectives: No immunotherapeutic protocol has yet been established in never-smoking patients with lung cancer harboring driver oncogenic mutations, such as epidermal growth factor receptor (EGFR) mutations. The immunostimulatory effect of Ad-REIC, a genetically engineered adenovirus vector expressing a tumor suppressor gene, reduced expression in immortalized cells (REIC), has been investigated in clinical trials for various solid tumors. However, the immunostimulatory effect of the Ad-REIC in EGFR-mutant lung cancer with a non-inflamed tumor microenvironment (TME) has not been explored.
Materials and methods: We used a syngeneic mouse model developed by transplanting Egfr-mutant lung cancer cells into single or double flanks of C57BL/6J mice. Ad-SGE-REIC, a 2nd-generation vector with an enhancer sequence, was injected only into the tumors from one flank, and its antitumor effects were assessed. Tumor-infiltrating cells were evaluated using immunohistochemistry or flow cytometry. The synergistic effects of Ad-SGE-REIC and PD-1 blockade were also examined.
Results: Injection of Ad-SGE-REIC into one side of the tumor induced not only a local antitumor effect but also a bystander abscopal effect in the non-injected tumor, located on the other flank. The number of PD-1+CD8+ T cells increased in both injected and non-injected tumors. PD-1 blockade augmented the local and abscopal antitumor effects of Ad-SGE-REIC by increasing the number of CD8+ T cells in the TME of Egfr-mutant tumors. Depletion of CD8+ cells reverted the antitumor effect, suggesting they contribute to antitumor immunity.
Conclusion: Ad-SGE-REIC induced systemic antitumor immunity by modifying the TME status from non-inflamed to inflamed, with infiltration of CD8+ T cells. Additionally, in Egfr-mutant lung cancer, this effect was enhanced by PD-1 blockade. These findings pave the way to establish a novel combined immunotherapy strategy with Ad-SGE-REIC and anti-PD-1 antibody for lung cancer with a non-inflamed TME.
en-copyright=
kn-copyright=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
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kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=HirabaeAtsuko
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kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=OkawaSachi
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kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TomonobuNahoko
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en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TakadaKenji
en-aut-sei=Takada
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
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kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=KumonHiromi
en-aut-sei=Kumon
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine
kn-affil=
affil-num=12
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=17
en-affil=Innovation Center Okayama for Nanobio-targeted Therapy, Okayama University
kn-affil=
affil-num=18
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=19
en-affil=Department of Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=EGFR mutation
kn-keyword=EGFR mutation
en-keyword=Non-small cell lung cancer
kn-keyword=Non-small cell lung cancer
en-keyword=Antitumor immunity
kn-keyword=Antitumor immunity
en-keyword=Non-inflamed tumor
kn-keyword=Non-inflamed tumor
en-keyword=Ad-SGE-REIC
kn-keyword=Ad-SGE-REIC
en-keyword=Gene therapy
kn-keyword=Gene therapy
en-keyword=PD-1
kn-keyword=PD-1
END
start-ver=1.4
cd-journal=joma
no-vol=2
cd-vols=
no-issue=7
article-no=
start-page=739
end-page=753
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220728
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Mixed Response to Cancer Immunotherapy is Driven by Intratumor Heterogeneity and Differential Interlesion Immune Infiltration
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Some patients experience mixed response to immunotherapy, whose biological mechanisms and clinical impact have been obscure. We obtained two tumor samples from lymph node (LN) metastatic lesions in a same patient. Whole exome sequencing for the both tumors and single-cell sequencing for the both tumor-infiltrating lymphocytes (TIL) demonstrated a significant difference in tumor clonality and TILs' characteristics, especially exhausted T-cell clonotypes, although a close relationship between the tumor cell and T-cell clones were observed as a response of an overlapped exhausted T-cell clone to an overlapped neoantigen. To mimic the clinical setting, we generated a mouse model of several clones from a same tumor cell line. Similarly, differential tumor clones harbored distinct TILs, and one responded to programmed cell death protein 1 (PD-1) blockade but the other did not in this model. We further conducted cohort study (n = 503) treated with PD-1 blockade monotherapies to investigate the outcome of mixed response. Patients with mixed responses to PD-1 blockade had a poor prognosis in our cohort. Particularly, there were significant differences in both tumor and T-cell clones between the primary and LN lesions in a patient who experienced tumor response to anti-PD-1 mAb followed by disease progression in only LN metastasis. Our results underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome.
Significance: Several patients experience mixed responses to immunotherapies, but the biological mechanisms and clinical significance remain unclear. Our results from clinical and mouse studies underscore that intertumoral heterogeneity alters characteristics of TILs even in the same patient, leading to mixed response to immunotherapy and significant difference in the outcome.
en-copyright=
kn-copyright=
en-aut-name=MorinagaTakao
en-aut-sei=Morinaga
en-aut-mei=Takao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=InozumeTakashi
en-aut-sei=Inozume
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KawazuMasahito
en-aut-sei=Kawazu
en-aut-mei=Masahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=SaxNicolas
en-aut-sei=Sax
en-aut-mei=Nicolas
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=YamashitaKazuo
en-aut-sei=Yamashita
en-aut-mei=Kazuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KawashimaShusuke
en-aut-sei=Kawashima
en-aut-mei=Shusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=UenoToshihide
en-aut-sei=Ueno
en-aut-mei=Toshihide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=LinJason
en-aut-sei=Lin
en-aut-mei=Jason
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=OharaYuuki
en-aut-sei=Ohara
en-aut-mei=Yuuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=KuwataTakeshi
en-aut-sei=Kuwata
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=YukamiHiroki
en-aut-sei=Yukami
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KawazoeAkihito
en-aut-sei=Kawazoe
en-aut-mei=Akihito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=ShitaraKohei
en-aut-sei=Shitara
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=Honobe-TabuchiAkiko
en-aut-sei=Honobe-Tabuchi
en-aut-mei=Akiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=OhnumaTakehiro
en-aut-sei=Ohnuma
en-aut-mei=Takehiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=KawamuraTatsuyoshi
en-aut-sei=Kawamura
en-aut-mei=Tatsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=UmedaYoshiyasu
en-aut-sei=Umeda
en-aut-mei=Yoshiyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=KawaharaYu
en-aut-sei=Kawahara
en-aut-mei=Yu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=NakamuraYasuhiro
en-aut-sei=Nakamura
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=KiniwaYukiko
en-aut-sei=Kiniwa
en-aut-mei=Yukiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
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=23
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=24
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=25
ORCID=
en-aut-name=EnokidaTomohiro
en-aut-sei=Enokida
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
ORCID=
en-aut-name=TaharaMakoto
en-aut-sei=Tahara
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=27
ORCID=
en-aut-name=HasegawaYoshinori
en-aut-sei=Hasegawa
en-aut-mei=Yoshinori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=28
ORCID=
en-aut-name=ManoHiroyuki
en-aut-sei=Mano
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=29
ORCID=
en-aut-name=SuzukiYutaka
en-aut-sei=Suzuki
en-aut-mei=Yutaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=30
ORCID=
en-aut-name=NishikawaHiroyoshi
en-aut-sei=Nishikawa
en-aut-mei=Hiroyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=31
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=32
ORCID=
affil-num=1
en-affil=Chiba Cancer Center, Research Institute
kn-affil=
affil-num=2
en-affil=Chiba Cancer Center, Research Institute
kn-affil=
affil-num=3
en-affil=Chiba Cancer Center, Research Institute
kn-affil=
affil-num=4
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=KOTAI Biotechnologies Inc
kn-affil=
affil-num=6
en-affil=KOTAI Biotechnologies Inc
kn-affil=
affil-num=7
en-affil=Chiba Cancer Center, Research Institute
kn-affil=
affil-num=8
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=
affil-num=10
en-affil=Chiba Cancer Center, Research Institute
kn-affil=
affil-num=11
en-affil=Department of Pathology, National Cancer Center Hospital East
kn-affil=
affil-num=12
en-affil=Department of Genetic Medicineand Services, National Cancer Center Hospital East
kn-affil=
affil-num=13
en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East
kn-affil=
affil-num=14
en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East
kn-affil=
affil-num=15
en-affil=Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East
kn-affil=
affil-num=16
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=
affil-num=17
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=
affil-num=18
en-affil=Department of Dermatology, University of Yamanashi
kn-affil=
affil-num=19
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=
affil-num=20
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=
affil-num=21
en-affil=Department of Skin Oncology/Dermatology, Saitama Medical University International Medical Center
kn-affil=
affil-num=22
en-affil=Department of Dermatology, Shinshu University School of Medicine
kn-affil=
affil-num=23
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=24
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=25
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=26
en-affil=Department of Head and Neck Medical Oncology, National Cancer Center Hospital East
kn-affil=
affil-num=27
en-affil=Department of Head and Neck Medical Oncology, National Cancer Center Hospital East
kn-affil=
affil-num=28
en-affil=Department of Applied Genomics, Kazusa DNA Research Institute
kn-affil=
affil-num=29
en-affil=Division of Cellular Signaling, National Cancer Center Research Institute
kn-affil=
affil-num=30
en-affil=Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo
kn-affil=
affil-num=31
en-affil=Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center
kn-affil=
affil-num=32
en-affil=Department of Tumor Microenvironment, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=114
cd-vols=
no-issue=11
article-no=
start-page=4343
end-page=4354
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230915
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Efficacy of gilteritinib in comparison with alectinib for the treatment of ALK-rearranged non-small cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Gilteritinib is a multitarget tyrosine kinase inhibitor (TKI), approved for the treatment of FLT3-mutant acute myeloid leukemia, with a broad range of activity against several tyrosine kinases including anaplastic lymphoma kinase (ALK). This study investigated the efficacy of gilteritinib against ALK-rearranged non-small cell lung cancers (NSCLC). To this end, we assessed the effects of gilteritinib on cell proliferation, apoptosis, and acquired resistance responses in several ALK-rearranged NSCLC cell lines and mouse xenograft tumor models and compared its efficacy to alectinib, a standard ALK inhibitor. Gilteritinib was significantly more potent than alectinib, as it inhibited cell proliferation at a lower dose, with complete attenuation of growth observed in several ALK-rearranged NSCLC cell lines and no development of drug tolerance. Immunoblotting showed that gilteritinib strongly suppressed phosphorylated ALK and its downstream effectors, as well as mesenchymal-epithelial transition factor (MET) signaling. By comparison, MET signaling was enhanced in alectinib-treated cells. Furthermore, gilteritinib was found to more effectively abolish growth of ALK-rearranged NSCLC xenograft tumors, many of which completely receded. Interleukin-15 (IL-15) mRNA levels were elevated in gilteritinib-treated cells, together with a concomitant increase in the infiltration of tumors by natural killer (NK) cells, as assessed by immunohistochemistry. This suggests that IL-15 production along with NK cell infiltration may constitute components of the gilteritinib-mediated antitumor responses in ALK-rearranged NSCLCs. In conclusion, gilteritinib demonstrated significantly improved antitumor efficacy compared with alectinib against ALK-rearranged NSCLC cells, which can warrant its candidacy for use in anticancer regimens, after further examination in clinical trial settings.
en-copyright=
kn-copyright=
en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=NishiTatsuya
en-aut-sei=Nishi
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MoritaAyako
en-aut-sei=Morita
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HaraNaofumi
en-aut-sei=Hara
en-aut-mei=Naofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TakadaKenji
en-aut-sei=Takada
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=WatanabeHiromi
en-aut-sei=Watanabe
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NishiiKazuya
en-aut-sei=Nishii
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=KondoTakumi
en-aut-sei=Kondo
en-aut-mei=Takumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=MatsuokaKen-Ichi
en-aut-sei=Matsuoka
en-aut-mei=Ken-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
affil-num=1
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Department of Hematology and Oncology, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=14
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=15
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=17
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=18
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=20
en-affil=Department of Hematology, Oncology and Respiratory Medicine
kn-affil=
affil-num=21
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=alectinib
kn-keyword=alectinib
en-keyword=ALK
kn-keyword=ALK
en-keyword=gilteritinib
kn-keyword=gilteritinib
en-keyword=non-small cell lung cancer
kn-keyword=non-small cell lung cancer
en-keyword=TKI
kn-keyword=TKI
END
start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230823
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Intracranial metastases are common in nonsmall-cell lung cancer (NSCLC) patients, whose prognosis is very poor. In addition, intracranial progression is common during systemic treatments due to the inability to penetrate central nervous system (CNS) barriers, whereas the intracranial effects of cancer immunotherapies remain unclear. We analyzed clinical data to evaluate the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies compared with those treated without PD-1 blockade therapies, and found that the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies was significantly lower than that in patients treated with cytotoxic chemotherapies. In murine models, intracranial rechallenged tumors after initial rejection by PD-1 blockade were suppressed. Accordingly, long-lived memory precursor effector T cells and antigen-specific T cells were increased by PD-1 blockade in intracranial lesions. However, intracranial rechallenged different tumors are not suppressed. Our results indicate that cancer immunotherapies can prevent intracranial progression, maintaining long-term effects intracranially as well as systemically. If intracranial recurrence occurs during the treatment with PD-1 blockade therapies, aggressive local therapies could be worthwhile.
en-copyright=
kn-copyright=
en-aut-name=KemmotsuNaoya
en-aut-sei=Kemmotsu
en-aut-mei=Naoya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KunimasaKei
en-aut-sei=Kunimasa
en-aut-mei=Kei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=IshinoTakamasa
en-aut-sei=Ishino
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NagasakiJoji
en-aut-sei=Nagasaki
en-aut-mei=Joji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=OtaniYoshihiro
en-aut-sei=Otani
en-aut-mei=Yoshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MichiueHiroyuki
en-aut-sei=Michiue
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=InoueTakako
en-aut-sei=Inoue
en-aut-mei=Takako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=TamiyaMotohiro
en-aut-sei=Tamiya
en-aut-mei=Motohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=SakaiKazuko
en-aut-sei=Sakai
en-aut-mei=Kazuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=DansakoHiromichi
en-aut-sei=Dansako
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=NishioKazuto
en-aut-sei=Nishio
en-aut-mei=Kazuto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=DateIsao
en-aut-sei=Date
en-aut-mei=Isao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=TogashiYosuke
en-aut-sei=Togashi
en-aut-mei=Yosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
affil-num=1
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute
kn-affil=
affil-num=4
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=10
en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute
kn-affil=
affil-num=11
en-affil=Department of Thoracic Oncology, Osaka International Cancer Institute
kn-affil=
affil-num=12
en-affil=Department of Genome Biology, Kindai University Faculty of Medicine
kn-affil=
affil-num=13
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=14
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=15
en-affil=Department of Genome Biology, Kindai University Faculty of Medicine
kn-affil=
affil-num=16
en-affil=Department of Respiratory Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=17
en-affil=Department of Neurological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=18
en-affil=Department of Tumor Microenvironment, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=cancer immunotherapy
kn-keyword=cancer immunotherapy
en-keyword=intracranial metastasis
kn-keyword=intracranial metastasis
en-keyword=intracranial progression
kn-keyword=intracranial progression
en-keyword=memory precursor effector T cell
kn-keyword=memory precursor effector T cell
en-keyword=nonsmall-cell lung cancer
kn-keyword=nonsmall-cell lung cancer
END
start-ver=1.4
cd-journal=joma
no-vol=38
cd-vols=
no-issue=
article-no=
start-page=101669
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=2022
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Massive hemoptysis in a post-operative patient with recurrent lung cancer successfully treated by the combination therapy of Endobronchial Watanabe Spigot and bronchial artery embolization
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 76-year-old woman who was treated with lorlatinib for postoperative recurrent anaplastic lymphoma kinase-positive lung adenocarcinoma visited our hospital with massive hemoptysis. Chest computed tomography showed massive bleeding from the right upper lobe; however, the cause of bleeding was unclear. After bronchial artery embolization (BAE), bronchial occlusion was performed using an Endobronchial Watanabe Spigot (EWS) that was easily placed because BAE had reduced the bleeding volume. Treatment with BAE alone was inadequate; however, additional therapy with EWS after BAE successfully controlled the massive hemoptysis, especially in this patient who underwent lobectomy to prevent respiratory dysfunction.
en-copyright=
kn-copyright=
en-aut-name=TaokaMasataka
en-aut-sei=Taoka
en-aut-mei=Masataka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=UmakoshiNoriyuki
en-aut-sei=Umakoshi
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HigoHisao
en-aut-sei=Higo
en-aut-mei=Hisao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoYuka
en-aut-sei=Kato
en-aut-mei=Yuka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KuboToshio
en-aut-sei=Kubo
en-aut-mei=Toshio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OhashiKadoaki
en-aut-sei=Ohashi
en-aut-mei=Kadoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KiuraKatsuyuki
en-aut-sei=Kiura
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=3
en-affil=Department of Radiology, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=5
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=10
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=11
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=Hemoptysis
kn-keyword=Hemoptysis
en-keyword=Bronchial artery embolization
kn-keyword=Bronchial artery embolization
en-keyword=Endoscopic bronchial occlusion
kn-keyword=Endoscopic bronchial occlusion
en-keyword=Endobronchial Watanabe Spigot
kn-keyword=Endobronchial Watanabe Spigot
END
start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=10
article-no=
start-page=e0287501
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231026
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A randomized controlled trial of teprenone in terms of preventing worsening of COVID-19 infection
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background
Some COVID-19 patients develop life-threatening disease accompanied by severe pneumonitis. Teprenone induces expression of heat-shock proteins (HSPs) that protect against interstitial pneumonia in preclinical models. We explored whether teprenone prevented worsening of COVID-19 infections.
Methods
This open-label, randomized, pilot phase 2 clinical trial was conducted at five institutions in Japan. We randomized patients hospitalized for COVID-19 with fever to teprenone or noteprenone groups in a 1:1 ratio. We stratified patients by sex, age < and >= 70 years and the existence (or not) of complications (hypertension, diabetes, ischemic heart disease, chronic pulmonary disease and active cancer). No limitation was imposed on other COVID-19 treatments. The primary endpoint was the intubation rate.
Results
One hundred patients were included, 51 in the teprenone and 49 in the no- teprenone groups. The intubation rate did not differ significantly between the two groups: 9.8% (5/51) vs. 2.0% (1/49) (sub-hazard ratio [SHR] 4.99, 95% confidence interval [CI]: 0.59-42.1; p = 0.140). The rates of intra-hospital mortality and intensive care unit (ICU) admission did not differ significantly between the two groups: intra-hospital mortality 3.9% (2/51) vs. 4.1% (2/ 49) (hazard ratio [HR] 0.78, 95%CI: 0.11-5.62; p = 0.809); ICU admission 11.8% (6/51) vs. 6.1% (3/49) (SHR 1.99, 95%CI: 0.51-7.80; p = 0.325).
Conclusion
Teprenone afforded no clinical benefit.
en-copyright=
kn-copyright=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=HasegawaKou
en-aut-sei=Hasegawa
en-aut-mei=Kou
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
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=3
ORCID=
en-aut-name=TanimotoYasushi
en-aut-sei=Tanimoto
en-aut-mei=Yasushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NousoKazuhiro
en-aut-sei=Nouso
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=OdaNaohiro
en-aut-sei=Oda
en-aut-mei=Naohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MitsumuneSho
en-aut-sei=Mitsumune
en-aut-mei=Sho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=YamadaHaruto
en-aut-sei=Yamada
en-aut-mei=Haruto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=
en-aut-name=HagiyaHideharu
en-aut-sei=Hagiya
en-aut-mei=Hideharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=MitsuhashiToshiharu
en-aut-sei=Mitsuhashi
en-aut-mei=Toshiharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TaniguchiAkihiko
en-aut-sei=Taniguchi
en-aut-mei=Akihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=ToyookaShinichi
en-aut-sei=Toyooka
en-aut-mei=Shinichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=TsukaharaKohei
en-aut-sei=Tsukahara
en-aut-mei=Kohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=AokageToshiyuki
en-aut-sei=Aokage
en-aut-mei=Toshiyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=TsukaharaHirokazu
en-aut-sei=Tsukahara
en-aut-mei=Hirokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
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=17
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
affil-num=1
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center
kn-affil=
affil-num=4
en-affil=Department of Allergy and Respiratory Medicine, National Hospital Organization Minami-Okayama Medical Center
kn-affil=
affil-num=5
en-affil=Department of Gastroenterology, Okayama City Hospital
kn-affil=
affil-num=6
en-affil=Department of Internal Medicine, Fukuyama City Hospital
kn-affil=
affil-num=7
en-affil=Department of Respiratory Medicine, National Hospital Organization Okayama Medical Center
kn-affil=
affil-num=8
en-affil=Department of Infectious Disease, Okayama City Hospital
kn-affil=
affil-num=9
en-affil=Department of Internal Medicine, Fukuyama City Hospital
kn-affil=
affil-num=10
en-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=12
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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 Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=10
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231031
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in EGFR-mutant non-small cell lung cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion and exon 21 L858R, are driver oncogenes of non-small cell lung cancer (NSCLC), with EGFR tyrosine kinase inhibitors (TKIs) being effective against EGFR-mutant NSCLC. However, the efficacy of EGFR-TKIs is transient and eventually leads to acquired resistance. Herein, we focused on the significance of cell cycle factors as a mechanism to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC before the emergence of acquired resistance.
Methods: Using several EGFR-mutant cell lines, we investigated the significance of cell cycle factors to attenuate the effect of EGFR-TKIs in EGFR-mutant NSCLC.
Results: In several EGFR-mutant cell lines, certain cancer cells continued to proliferate without EGFR signaling, and the cell cycle regulator retinoblastoma protein (RB) was not completely dephosphorylated. Further inhibition of phosphorylated RB with cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with the EGFR-TKI osimertinib, enhanced G0/G1 cell cycle accumulation and growth inhibition of the EGFR-mutant NSCLC in both in vitro and in vivo models. Furthermore, residual RB phosphorylation without EGFR signaling was maintained by extracellular signal-regulated kinase (ERK) signaling, and the ERK inhibition pathway showed further RB dephosphorylation.
Conclusions: Our study demonstrated that the CDK4/6-RB signal axis, maintained by the MAPK pathway, attenuates the efficacy of EGFR-TKIs in EGFR-mutant NSCLC, and targeting CDK4/6 enhances this efficacy. Thus, combining CDK4/6 inhibitors and EGFR-TKI could be a novel treatment strategy for TKI-na?ve EGFR-mutant NSCLC.
en-copyright=
kn-copyright=
en-aut-name=HaraNaofumi
en-aut-sei=Hara
en-aut-mei=Naofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=IchiharaEiki
en-aut-sei=Ichihara
en-aut-mei=Eiki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KanoHirohisa
en-aut-sei=Kano
en-aut-mei=Hirohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=AndoChihiro
en-aut-sei=Ando
en-aut-mei=Chihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MoritaAyako
en-aut-sei=Morita
en-aut-mei=Ayako
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NishiTatsuya
en-aut-sei=Nishi
en-aut-mei=Tatsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=OkawaSachi
en-aut-sei=Okawa
en-aut-mei=Sachi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NakasukaTakamasa
en-aut-sei=Nakasuka
en-aut-mei=Takamasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=HirabaeAtsuko
en-aut-sei=Hirabae
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=AbeMasaya
en-aut-sei=Abe
en-aut-mei=Masaya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=AsadaNoboru
en-aut-sei=Asada
en-aut-mei=Noboru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=NinomiyaKiichiro
en-aut-sei=Ninomiya
en-aut-mei=Kiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=MakimotoGo
en-aut-sei=Makimoto
en-aut-mei=Go
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=FujiiMasanori
en-aut-sei=Fujii
en-aut-mei=Masanori
kn-aut-name=
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=HottaKatsuyuki
en-aut-sei=Hotta
en-aut-mei=Katsuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=TabataMasahiro
en-aut-sei=Tabata
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=MaedaYoshinobu
en-aut-sei=Maeda
en-aut-mei=Yoshinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
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=20
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 Respiratory Medicine, Japanese Red Cross Okayama Hospital
kn-affil=
affil-num=4
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of 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 and Oncology, 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=Center for Clinical Oncology, 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=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=18
en-affil=Center for Clinical Oncology, Okayama University Hospital
kn-affil=
affil-num=19
en-affil=Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=20
en-affil=Department of Allergy and Respiratory Medicine, Okayama University Hospital
kn-affil=
en-keyword=Epidermal growth factor receptor (EGFR)
kn-keyword=Epidermal growth factor receptor (EGFR)
en-keyword=non-small cell lung cancer (NSCLC)
kn-keyword=non-small cell lung cancer (NSCLC)
en-keyword=cell cycle
kn-keyword=cell cycle
en-keyword=CDK4/6 inhibitor
kn-keyword=CDK4/6 inhibitor
END