start-ver=1.4
cd-journal=joma
no-vol=74
cd-vols=
no-issue=3
article-no=
start-page=96
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250204
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cancer-associated fibroblasts promote pro-tumor functions of neutrophils in pancreatic cancer via IL-8: potential suppression by pirfenidone
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background The mechanisms by which neutrophils acquire pro-tumor properties remain poorly understood. In pancreatic cancer, cancer-associated fibroblasts (CAFs) may interact with neutrophils, directing them to promote tumor progression.
Methods To validate the association between CAFs and neutrophils, the localization of neutrophils was examined in clinically resected pancreatic cancer specimens. CAFs were produced by culturing in cancer-conditioned media, and the effects of these CAFs on neutrophils were examined. In vitro migration and invasion assays assess the effect of CAF-activated neutrophils on cancer cells. The factors secreted by the activated neutrophils were also explored. Finally, pirfenidone (PFD) was tested to determine whether it could suppress the pro-tumor functions of activated neutrophils.
Results In pancreatic cancer specimens, neutrophils tended to co-localize with IL-6-positive CAFs. Neutrophils co-cultured with CAFs increased migratory capacity and prolonged life span. CAF-affected neutrophils enhance the migratory and invasive activities of pancreatic cancer cells. IL-8 is the most upregulated cytokine secreted by the neutrophils. PFD suppresses IL-8 secretion from CAF-stimulated neutrophils and mitigates the malignant traits of pancreatic cancer cells.
Conclusion CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach.
en-copyright=
kn-copyright=
en-aut-name=YagiTomohiko
en-aut-sei=Yagi
en-aut-mei=Tomohiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=NogiShohei
en-aut-sei=Nogi
en-aut-mei=Shohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TaniguchiAtsuki
en-aut-sei=Taniguchi
en-aut-mei=Atsuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=YoshimotoMasashi
en-aut-sei=Yoshimoto
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SuemoriKanto
en-aut-sei=Suemori
en-aut-mei=Kanto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NagaiYasuo
en-aut-sei=Nagai
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=FujitaShuto
en-aut-sei=Fujita
en-aut-mei=Shuto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KakiuchiYoshihiko
en-aut-sei=Kakiuchi
en-aut-mei=Yoshihiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TeraishiFuminori
en-aut-sei=Teraishi
en-aut-mei=Fuminori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=TakagiKosei
en-aut-sei=Takagi
en-aut-mei=Kosei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Cancer-associated fibroblasts
kn-keyword=Cancer-associated fibroblasts
en-keyword=Neutrophil
kn-keyword=Neutrophil
en-keyword=Anti-fibrotic agent
kn-keyword=Anti-fibrotic agent
en-keyword=Pirfenidone
kn-keyword=Pirfenidone
END
start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=1
article-no=
start-page=3267
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250125
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Novel treatment strategy targeting interleukin-6 induced by cancer associated fibroblasts for peritoneal metastasis of gastric cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer-associated fibroblasts (CAFs) are a crucial component in the tumor microenvironment (TME) of peritoneal metastasis (PM), where they contribute to tumor progression and metastasis via secretion of interleukin-6 (IL-6). Here, we investigated the role of IL-6 in PM of gastric cancer (GC) and assessed whether anti-IL-6 receptor antibody (anti-IL-6R Ab) could inhibit PM of GC. We conducted immunohistochemical analysis of IL-6 and alpha-smooth muscle (alpha-SMA) expressions in clinical samples of GC and PM, and investigated the interactions between CAFs and GC cells in vitro. Anti-tumor effects of anti-IL-6R Ab on PM of GC were investigated in an orthotopic murine PM model. IL-6 expression was significantly correlated with alpha-SMA expression in clinical samples of GC, and higher IL-6 expression in the primary tumor was associated with poor prognosis of GC. Higher IL-6 and alpha-SMA expressions were also observed in PM of GC. In vitro, differentiation of fibroblasts into CAFs and chemoresistance were observed in GC cells cocultured with fibroblasts. Anti-IL-6R Ab inhibited the progression of PM in GC cells cocultured with fibroblasts in the orthotopic mouse model but could not inhibit the progression of PM consisting of GC cells alone. IL-6 expression in the TME was associated with poor prognosis of GC, and CAFs were associated with establishment and progression of PM via IL-6. Anti-IL-6R Ab could inhibit PM of GC by the blockade of IL-6 secreted by CAFs, which suggests its therapeutic potential for PM of GC.
en-copyright=
kn-copyright=
en-aut-name=MitsuiEma
en-aut-sei=Mitsui
en-aut-mei=Ema
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OkuraTomohiro
en-aut-sei=Okura
en-aut-mei=Tomohiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=UneYuta
en-aut-sei=Une
en-aut-mei=Yuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NishiwakiNoriyuki
en-aut-sei=Nishiwaki
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=OhtsukaJunko
en-aut-sei=Ohtsuka
en-aut-mei=Junko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=OhkiRieko
en-aut-sei=Ohki
en-aut-mei=Rieko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute
kn-affil=
affil-num=12
en-affil=Laboratory of Fundamental Oncology, National Cancer Center Research Institute
kn-affil=
affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Peritoneal metastasis
kn-keyword=Peritoneal metastasis
en-keyword=Gastric cancer
kn-keyword=Gastric cancer
en-keyword=Interleukin-6
kn-keyword=Interleukin-6
en-keyword=Cancer-associated fibroblasts
kn-keyword=Cancer-associated fibroblasts
en-keyword=Interleukin-6 receptor antibody
kn-keyword=Interleukin-6 receptor antibody
END
start-ver=1.4
cd-journal=joma
no-vol=44
cd-vols=
no-issue=6
article-no=
start-page=2497
end-page=2509
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240531
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Senescent Fibroblasts Potentiate Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells via IL-8–mediated Crosstalk
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background/Aim: Diffuse-type gastric cancer (DGC) often forms peritoneal metastases, leading to poor prognosis. However, the underlying mechanism of DGC-mediated peritoneal metastasis is poorly understood. DGC is characterized by desmoplastic stroma, in which heterogeneous cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs) and senescent CAFs (sCAFs), play a crucial role during tumor progression. This study investigated the CAF subtypes induced by GC cells and the role of sCAFs in peritoneal metastasis of DGC cells. Materials and Methods: Conditioned medium of human DGC cells (KATOIII, NUGC-4) and human intestinal-type GC (IGC) cells (MKN-7, N87) was used to induce CAFs. CAF subtypes were evaluated by analyzing the expression of α–smooth muscle actin (α-SMA), senescence-associated β-galactosidase (SA-β-gal), and p16 in human normal fibroblasts (GF, FEF-3). A cytokine array was used to explore the underlying mechanism of GC-induced CAF subtype development. The role of sCAFs in peritoneal metastasis of DGC cells was analyzed using a peritoneally metastatic DGC tumor model. The relationships between GC subtypes and CAF-related markers were evaluated using publicly available datasets. Results: IGC cells significantly induced α-SMA+ myCAFs by secreting transforming growth factor–β, whereas DGC cells induced SA-β-gal+/p16+ sCAFs by secreting interleukin (IL)-8. sCAFs further secreted IL-8 to promote DGC cell migration. In vivo experiments demonstrated that co-inoculation of sCAFs significantly enhanced peritoneal metastasis of NUGC-4 cells, which was attenuated by administration of the IL-8 receptor antagonist navarixin. p16 and IL-8 expression was significantly associated with poor prognosis of DGC patients. Conclusion: sCAFs promote peritoneal metastasis of DGC via IL-8–mediated crosstalk.
en-copyright=
kn-copyright=
en-aut-name=LIYUNCHENG
en-aut-sei=LI
en-aut-mei=YUNCHENG
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=TAZAWAHIROSHI
en-aut-sei=TAZAWA
en-aut-mei=HIROSHI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=NAGAIYASUO
en-aut-sei=NAGAI
en-aut-mei=YASUO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=FUJITASHUTO
en-aut-sei=FUJITA
en-aut-mei=SHUTO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=OKURATOMOHIRO
en-aut-sei=OKURA
en-aut-mei=TOMOHIRO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SHOJIRYOHEI
en-aut-sei=SHOJI
en-aut-mei=RYOHEI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=YAMADAMOTOHIKO
en-aut-sei=YAMADA
en-aut-mei=MOTOHIKO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KIKUCHISATORU
en-aut-sei=KIKUCHI
en-aut-mei=SATORU
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KURODASHINJI
en-aut-sei=KURODA
en-aut-mei=SHINJI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OHARATOSHIAKI
en-aut-sei=OHARA
en-aut-mei=TOSHIAKI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NOMAKAZUHIRO
en-aut-sei=NOMA
en-aut-mei=KAZUHIRO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=NISHIZAKIMASAHIKO
en-aut-sei=NISHIZAKI
en-aut-mei=MASAHIKO
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KAGAWASHUNSUKE
en-aut-sei=KAGAWA
en-aut-mei=SHUNSUKE
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=FUJIWARATOSHIYOSHI
en-aut-sei=FUJIWARA
en-aut-mei=TOSHIYOSHI
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Departments of Gastroenterological Surgery and Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Gastric cancer
kn-keyword=Gastric cancer
en-keyword=peritoneal metastasis
kn-keyword=peritoneal metastasis
en-keyword=senescent fibroblast
kn-keyword=senescent fibroblast
en-keyword=IL-8
kn-keyword=IL-8
en-keyword=CXCR1/2
kn-keyword=CXCR1/2
END
start-ver=1.4
cd-journal=joma
no-vol=72
cd-vols=
no-issue=11
article-no=
start-page=3787
end-page=3802
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230905
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity.
en-copyright=
kn-copyright=
en-aut-name=KawasakiKento
en-aut-sei=Kawasaki
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TanabeShunsuke
en-aut-sei=Tanabe
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TakedaYasushige
en-aut-sei=Takeda
en-aut-mei=Yasushige
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MatsumotoHijiri
en-aut-sei=Matsumoto
en-aut-mei=Hijiri
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NishimuraSeitaro
en-aut-sei=Nishimura
en-aut-mei=Seitaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KunitomoTomoyoshi
en-aut-sei=Kunitomo
en-aut-mei=Tomoyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=AkaiMasaaki
en-aut-sei=Akai
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KobayashiTeruki
en-aut-sei=Kobayashi
en-aut-mei=Teruki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=NishiwakiNoriyuki
en-aut-sei=Nishiwaki
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=MaedaNaoaki
en-aut-sei=Maeda
en-aut-mei=Naoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=17
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=18
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Esophageal cancer
kn-keyword=Esophageal cancer
en-keyword=Cancer-associated fibroblasts
kn-keyword=Cancer-associated fibroblasts
en-keyword=Programmed cell death 1
kn-keyword=Programmed cell death 1
en-keyword=Program cell death ligand 1
kn-keyword=Program cell death ligand 1
en-keyword=Immune checkpoint inhibitors
kn-keyword=Immune checkpoint inhibitors
END
start-ver=1.4
cd-journal=joma
no-vol=26
cd-vols=
no-issue=6
article-no=
start-page=1213
end-page=1223
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220208
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Diagnostic Utility of the PD-L1 Immunostaining in Biopsy Specimens of Patients with Biliary Tract Neoplasms
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Anti-programmed death 1/programmed death ligand 1 (PD1/PD-L1) antibodies have been successfully used as treatment agents for several solid tumors; however, it is difficult to predict their effectiveness. We evaluated whether biopsy specimens could predict the positive status of PD-L1 in surgically resected tissue.
Methods Among 91 patients who underwent tissue sampling with endoscopic or liver biopsy before surgery for biliary tract neoplasms in an academic center, 45 (49%) patients were selected for retrospective analysis because the quality and quantity of their biopsy specimens were adequate for histologic evaluation. We performed immunohistochemical staining to investigate the PD-L1 expression in both resected and biopsy specimens. The percentage of the positively stained cells was calculated for subsequent use in the correlation investigation.
Results The biopsy methods were endoscopic retrograde cholangiopancreatography (ERCP) in 28 cases, percutaneous liver biopsy in 10 cases, and endoscopic ultrasound fine-needle aspiration in 7 cases. Among the 45 patients, when patients with > 10% positive tumor cells in surgically resected tissues were regarded as truly positive PD-L1, the positive and negative concordance rates between surgically resected tissues and biopsy samples were 56% (5/9) and 100% (36/36), respectively. With regard to the use of preoperative biopsy as a diagnostic tool, all (5/5) PD-L1-positive patients had a positive resected specimen. The accuracy of each biopsy method was as follows: ERCP, 89% (25/28); fine-needle aspiration, 86% (6/7); and liver biopsy, 100% (10/10).
Conclusions Biopsy samples could be a surrogate material for the assessment of the PD-L1 expression with substantial positive and high negative concordance rates.
en-copyright=
kn-copyright=
en-aut-name=MatsumotoKazuyuki
en-aut-sei=Matsumoto
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TakakiAkinobu
en-aut-sei=Takaki
en-aut-mei=Akinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TakaharaMasahiro
en-aut-sei=Takahara
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoHironari
en-aut-sei=Kato
en-aut-mei=Hironari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=YagiTakahito
en-aut-sei=Yagi
en-aut-mei=Takahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MatsukawaAkihiro
en-aut-sei=Matsukawa
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=OkadaHiroyuki
en-aut-sei=Okada
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
affil-num=1
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Programmed death ligand 1
kn-keyword=Programmed death ligand 1
en-keyword=Bile tract neoplasm
kn-keyword=Bile tract neoplasm
en-keyword=Biopsy specimen
kn-keyword=Biopsy specimen
en-keyword=Immunohistochemistry
kn-keyword=Immunohistochemistry
END
start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=11
article-no=
start-page=2971
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230530
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Conventional Cancer Therapies Can Accelerate Malignant Potential of Cancer Cells by Activating Cancer-Associated Fibroblasts in Esophageal Cancer Models
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Esophageal cancer is one of the most aggressive tumors, and the outcome remains poor. One contributing factor is the presence of tumors that are less responsive or have increased malignancy when treated with conventional chemotherapy, radiotherapy, or a combination of these. Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Focusing on conventional cancer therapies, we investigated how CAFs acquire therapeutic resistance and how they affect tumor malignancy. In this study, low-dose chemotherapy or radiotherapy-induced normal fibroblasts showed enhanced activation of CAFs markers, fibroblast activation protein, and α-smooth muscle actin, indicating the acquisition of malignancy in fibroblasts. Furthermore, CAFs activated by radiotherapy induce phenotypic changes in cancer cells, increasing their proliferation, migration, and invasion abilities. In in vivo peritoneal dissemination models, the total number of tumor nodules in the abdominal cavity was significantly increased in the co-inoculation group of cancer cells and resistant fibroblasts compared to that in the co-inoculation group of cancer cells and normal fibroblasts. In conclusion, we demonstrated that conventional cancer therapy causes anti-therapeutic effects via the activation of fibroblasts, resulting in CAFs. It is important to select or combine modalities of esophageal cancer treatment, recognizing that inappropriate radiotherapy and chemotherapy can lead to resistance in CAF-rich tumors.
en-copyright=
kn-copyright=
en-aut-name=KomotoSatoshi
en-aut-sei=Komoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KobayashiTeruki
en-aut-sei=Kobayashi
en-aut-mei=Teruki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NishiwakiNoriyuki
en-aut-sei=Nishiwaki
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NarusakaToru
en-aut-sei=Narusaka
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SatoHiroaki
en-aut-sei=Sato
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KatsuraYuki
en-aut-sei=Katsura
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=cancer-associated fibroblast
kn-keyword=cancer-associated fibroblast
en-keyword=chemotherapy
kn-keyword=chemotherapy
en-keyword=radiotherapy
kn-keyword=radiotherapy
en-keyword=esophageal cancer
kn-keyword=esophageal cancer
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
END
start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=20152
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221123
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Dual-targeted near-infrared photoimmunotherapy for esophageal cancer and cancer-associated fibroblasts in the tumor microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer-associated fibroblasts (CAFs) play a significant role in tumor progression within the tumor microenvironment. Previously, we used near-infrared photoimmunotherapy (NIR-PIT), a next-generation cancer cell-targeted phototherapy, to establish CAF-targeted NIR-PIT. In this study, we investigated whether dual-targeted NIR-PIT, targeting cancer cells and CAFs, could be a therapeutic strategy. A total of 132 cases of esophageal cancer were analyzed for epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and fibroblast activation protein (FAP) expression using immunohistochemistry. Human esophageal cancer cells and CAFs were co-cultured and treated with single- or dual-targeted NIR-PIT in vitro. These cells were co-inoculated into BALB/c-nu/nu mice and the tumors were treated with single-targeted NIR-PIT or dual-targeted NIR-PIT in vivo. Survival analysis showed FAP- or EGFR-high patients had worse survival than patients with low expression of FAP or EGFR (log-rank, P < 0.001 and P = 0.074, respectively), while no difference was observed in HER2 status. In vitro, dual (EGFR/FAP)-targeted NIR-PIT induced specific therapeutic effects in cancer cells and CAFs along with suppressing tumor growth in vivo, whereas single-targeted NIR-PIT did not show any significance. Moreover, these experiments demonstrated that dual-targeted NIR-PIT could treat cancer cells and CAFs simultaneously with a single NIR light irradiation. We demonstrated the relationship between EGFR/FAP expression and prognosis of patients with esophageal cancer and the stronger therapeutic effect of dual-targeted NIR-PIT than single-targeted NIR-PIT in experimental models. Thus, dual-targeted NIR-PIT might be a promising therapeutic strategy for cancer treatment.
en-copyright=
kn-copyright=
en-aut-name=SatoHiroaki
en-aut-sei=Sato
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KawasakiKento
en-aut-sei=Kawasaki
en-aut-mei=Kento
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=AkaiMasaaki
en-aut-sei=Akai
en-aut-mei=Masaaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KobayashiTeruki
en-aut-sei=Kobayashi
en-aut-mei=Teruki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NishiwakiNoriyuki
en-aut-sei=Nishiwaki
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NarusakaToru
en-aut-sei=Narusaka
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KomotoSatoshi
en-aut-sei=Komoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KatsuraYuki
en-aut-sei=Katsura
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=KobayashiHisataka
en-aut-sei=Kobayashi
en-aut-mei=Hisataka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=17
en-affil=Molecular Imaging Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda
kn-affil=
affil-num=18
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=11
article-no=
start-page=673
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20221110
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Functional Blockage of S100A8/A9 Ameliorates Ischemia-Reperfusion Injury in the Lung
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=(1) Background: Lung ischemia-reperfusion (IR) injury increases the mortality and morbidity of patients undergoing lung transplantation. The objective of this study was to identify the key initiator of lung IR injury and to evaluate pharmacological therapeutic approaches using a functional inhibitor against the identified molecule. (2) Methods: Using a mouse hilar clamp model, the combination of RNA sequencing and histological investigations revealed that neutrophil-derived S100A8/A9 plays a central role in inflammatory reactions during lung IR injury. Mice were assigned to sham and IR groups with or without the injection of anti-S100A8/A9 neutralizing monoclonal antibody (mAb). (3) Results: Anti-S100A8/A9 mAb treatment significantly attenuated plasma S100A8/A9 levels compared with control IgG. As evaluated by oxygenation capacity and neutrophil infiltration, the antibody treatment dramatically ameliorated the IR injury. The gene expression levels of cytokines and chemokines induced by IR injury were significantly reduced by the neutralizing antibody. Furthermore, the antibody treatment significantly reduced TUNEL-positive cells, indicating the presence of apoptotic cells. (4) Conclusions: We identified S100A8/A9 as a novel therapeutic target against lung IR injury.
en-copyright=
kn-copyright=
en-aut-name=NakataKentaro
en-aut-sei=Nakata
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OkazakiMikio
en-aut-sei=Okazaki
en-aut-mei=Mikio
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=SakaueTomohisa
en-aut-sei=Sakaue
en-aut-mei=Tomohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KinoshitaRie
en-aut-sei=Kinoshita
en-aut-mei=Rie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KomodaYuhei
en-aut-sei=Komoda
en-aut-mei=Yuhei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=ShimizuDai
en-aut-sei=Shimizu
en-aut-mei=Dai
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=YamamotoHaruchika
en-aut-sei=Yamamoto
en-aut-mei=Haruchika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TanakaShin
en-aut-sei=Tanaka
en-aut-mei=Shin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=SuzawaKen
en-aut-sei=Suzawa
en-aut-mei=Ken
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=ShienKazuhiko
en-aut-sei=Shien
en-aut-mei=Kazuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=MiyoshiKentaroh
en-aut-sei=Miyoshi
en-aut-mei=Kentaroh
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
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=14
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=15
ORCID=
en-aut-name=MatsukawaAkihiro
en-aut-sei=Matsukawa
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=SakaguchiMasakiyo
en-aut-sei=Sakaguchi
en-aut-mei=Masakiyo
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=
affil-num=1
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine
kn-affil=
affil-num=4
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Cardiovascular and Thoracic Surgery, Ehime University Graduate School of Medicine
kn-affil=
affil-num=6
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network
kn-affil=
affil-num=8
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=17
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=18
en-affil=Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=ischemia reperfusion injury
kn-keyword=ischemia reperfusion injury
en-keyword= S100A8/A9
kn-keyword= S100A8/A9
en-keyword=lung transplantation
kn-keyword=lung transplantation
en-keyword=damage-associated molecule patterns
kn-keyword=damage-associated molecule patterns
END
start-ver=1.4
cd-journal=joma
no-vol=25
cd-vols=
no-issue=
article-no=
start-page=249
end-page=261
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220616
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Modulation of p53 expression in cancer-associated fibroblasts prevents peritoneal metastasis of cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are associated with the establishment and progression of peritoneal metastasis. This study investigated the efficacy of replicative oncolytic adenovirus-mediated p53 gene therapy (OBP-702) against CAFs and peritoneal metastasis of gastric cancer (GC). Higher CAF expression in the primary tumor was associated with poor prognosis of GC, and higher CAF expression was also observed with peritoneal metastasis in immunohistochemical analysis of clinical samples. And, we found transcriptional alteration of p53 in CAFs relative to normal gastric fibroblasts (NGFs). CAFs increased the secretion of cancer-promoting cytokines, including interleukin-6, and gained resistance to chemotherapy relative to NGFs. OBP-702 showed cytotoxicity to both GC cells and CAFs but not to NGFs. Overexpression of wild-type p53 by OBP-702 infection caused apoptosis and autophagy of CAFs and decreased the secretion of cancer-promoting cytokines by CAFs. Combination therapy using intraperitoneal administration of OBP-702 and paclitaxel synergistically inhibited the tumor growth of peritoneal metastases and decreased CAFs in peritoneal metastases. OBP-702, a replicative oncolytic adenovirus-mediated p53 gene therapy, offers a promising biological therapeutic strategy for peritoneal metastasis, modulating CAFs in addition to achieving tumor lysis.
en-copyright=
kn-copyright=
en-aut-name=OgawaToshihiro
en-aut-sei=Ogawa
en-aut-mei=Toshihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TabuchiMotoyasu
en-aut-sei=Tabuchi
en-aut-mei=Motoyasu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MitsuiEma
en-aut-sei=Mitsui
en-aut-mei=Ema
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=UneYuta
en-aut-sei=Une
en-aut-mei=Yuta
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=UrataYasuo
en-aut-sei=Urata
en-aut-mei=Yasuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Oncolys BioPharma
kn-affil=
affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=1
article-no=
start-page=1693
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210118
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Fibroblast activation protein targeted near infrared photoimmunotherapy (NIR PIT) overcomes therapeutic resistance in human esophageal cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.
en-copyright=
kn-copyright=
en-aut-name=KatsubeRyoichi
en-aut-sei=Katsube
en-aut-mei=Ryoichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NishiwakiNoriyuki
en-aut-sei=Nishiwaki
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KobayashiTeruki
en-aut-sei=Kobayashi
en-aut-mei=Teruki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KomotoSatoshi
en-aut-sei=Komoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SatoHiroaki
en-aut-sei=Sato
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KobayashiHisataka
en-aut-sei=Kobayashi
en-aut-mei=Hisataka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, US National Institutes of Health
kn-affil=
affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=
article-no=
start-page=16378
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=2019118
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Visualization of epithelial-mesenchymal transition in an inflammatory microenvironment-colorectal cancer network
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Epithelial-mesenchymal transition (EMT) is a biological process by which epithelial cells acquire mesenchymal characteristics. In malignant tumors, EMT is crucial for acquisition of a mesenchymal phenotype with invasive and metastatic properties, leading to tumor progression. An inflammatory microenvironment is thought to be responsible for the development and progression of colorectal cancer (CRC); however, the precise role of inflammatory microenvironments in EMT-related CRC progression remains unclear. Here, we show the spatiotemporal visualization of CRC cells undergoing EMT using a fluorescence-guided EMT imaging system in which the mesenchymal vimentin promoter drives red fluorescent protein (RFP) expression. An inflammatory microenvironment including TNF-alpha, IL-1 beta, and cytokine-secreting inflammatory macrophages induced RFP expression in association with the EMT phenotype in CRC cells. In vivo experiments further demonstrated the distribution of RFP-positive CRC cells in rectal and metastatic tumors. Our data suggest that the EMT imaging system described here is a powerful tool for monitoring EMT in inflammatory microenvironment-CRC networks.
en-copyright=
kn-copyright=
en-aut-name=IedaTakeshi
en-aut-sei=Ieda
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OkabayashiHiroki
en-aut-sei=Okabayashi
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=YanoShuya
en-aut-sei=Yano
en-aut-mei=Shuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=ShigeyasuKunitoshi
en-aut-sei=Shigeyasu
en-aut-mei=Kunitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KishimotoHiroyuki
en-aut-sei=Kishimoto
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=SaitouTakashi
en-aut-sei=Saitou
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=ImamuraTakeshi
en-aut-sei=Imamura
en-aut-mei=Takeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine
kn-affil=
affil-num=14
en-affil=Department of Molecular Medicine for Pathogenesis, Ehime University Graduate School of Medicine
kn-affil=
affil-num=15
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=2
article-no=
start-page=177
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190203
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy.
en-copyright=
kn-copyright=
en-aut-name=KatsuraYuki
en-aut-sei=Katsura
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NinomiyaTakayuki
en-aut-sei=Ninomiya
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatoTakuya
en-aut-sei=Kato
en-aut-mei=Takuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SatoHiroaki
en-aut-sei=Sato
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KomotoSatoshi
en-aut-sei=Komoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=NarusakaToru
en-aut-sei=Narusaka
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=TomonoYasuko
en-aut-sei=Tomono
en-aut-mei=Yasuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=XingBoyi
en-aut-sei=Xing
en-aut-mei=Boyi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=ChenYuehua
en-aut-sei=Chen
en-aut-mei=Yuehua
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=TazawaHiroshi
en-aut-sei=Tazawa
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=Kasai Tomonari
en-aut-sei=Kasai
en-aut-mei=Tomonari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=SenoMasaharu
en-aut-sei=Seno
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=MatsukawaAkihiro
en-aut-sei=Matsukawa
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
affil-num=1
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil= Shigei Medical Research Institute
kn-affil=
affil-num=11
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=15
en-affil= Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=16
en-affil=School of Bioscience and Biotechnology, Tokyo University of Technology
kn-affil=
affil-num=17
en-affil= Laboratory of Nano-Biotechnology, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems
kn-affil=
affil-num=18
en-affil= Department of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=19
en-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=cancer stem cells
kn-keyword=cancer stem cells
en-keyword=combination therapy
kn-keyword=combination therapy
en-keyword=iron
kn-keyword=iron
en-keyword=stemness
kn-keyword=stemness
END
start-ver=1.4
cd-journal=joma
no-vol=54
cd-vols=
no-issue=11
article-no=
start-page=1019
end-page=1028
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190429
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The relationship between the PD-L1 expression of surgically resected and fine-needle aspiration specimens for patients with pancreatic cancer
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=BACKGROUND:
Recently, therapeutic antibodies against programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) have shown promising clinical results for several solid tumors, including pancreatic cancer. In this study, we evaluated the relationship between the PD-L1 expression of surgical resected and fine-needle aspiration (FNA) specimens for patients with pancreatic cancer.
METHODS:
Of 121 patients who underwent endoscopic ultrasound-guided (EUS)-FNA before surgery for pancreatic cancer in an academic center, the 94 (78%) with adequate FNA specimens for a histological evaluation were retrospectively analyzed. All the patients had undergone upfront surgery without any chemotherapy or radiotherapy. We performed immunohistochemistry (IHC) staining to investigate the PD-L1 expression in both resected and FNA specimens. The positive-stained cells were counted, and their percentage was used for the investigation.
RESULTS:
Of the 94 patients, 16 (17%) and 11 (10%) were defined as positive on resected cancer specimens using cutoff points of 5% and 10% positively stained cancer cell counts, respectively. The concordance rates for the positive frequency of PD-L1 expression between resected and FNA specimens were 44% (7/16) and 55% (6/11) when the positivity was set to ≥ 5% and ≥ 10%, respectively. The concordance rates for the negative frequency of PD-L1 expression between two specimens were 97% (76/78) and 99% (82/83) when the positivity was set to ≥ 5% and ≥ 10%, respectively.
CONCLUSIONS:
Approximately, half of the patients with PD-L1 expression positive and almost all the patients with PD-L1 expression negative could be diagnosed on FNA specimens.
en-copyright=
kn-copyright=
en-aut-name=MatsumotoKazuyuki
en-aut-sei=Matsumoto
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=FujisawaMasayoshi
en-aut-sei=Fujisawa
en-aut-mei=Masayoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TakakiAkinobu
en-aut-sei=Takaki
en-aut-mei=Akinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TakaharaMasahiro
en-aut-sei=Takahara
en-aut-mei=Masahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TanakaNoriyuki
en-aut-sei=Tanaka
en-aut-mei=Noriyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KatoHironari
en-aut-sei=Kato
en-aut-mei=Hironari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=HoriguchiShigeru
en-aut-sei=Horiguchi
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=YoshidaRyuichi
en-aut-sei=Yoshida
en-aut-mei=Ryuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=UmedaYuzo
en-aut-sei=Umeda
en-aut-mei=Yuzo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=FushimiSoichiro
en-aut-sei=Fushimi
en-aut-mei=Soichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=YagiTakahito
en-aut-sei=Yagi
en-aut-mei=Takahito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=MatsukawaAkihiro
en-aut-sei=Matsukawa
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=OkadaHiroyuki
en-aut-sei=Okada
en-aut-mei=Hiroyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=
kn-affil=
affil-num=6
en-affil=Department of PathologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical OncologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical OncologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of PathologyHimeji Red Cross Hospital
kn-affil=
affil-num=12
en-affil=Department of Gastroenterological Surgery, Transplant and Surgical OncologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Gastroenterology and HepatologyOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
en-keyword=Immunohistochemistry
kn-keyword=Immunohistochemistry
en-keyword=PD-L1
kn-keyword=PD-L1
en-keyword=Pancreatic cancer
kn-keyword=Pancreatic cancer
END
start-ver=1.4
cd-journal=joma
no-vol=70
cd-vols=
no-issue=3
article-no=
start-page=213
end-page=216
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=201606
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Recurrence after Endoscopic Curative Resection of Mucosal Gastric Cancer Associated with an Adjacent Neoplastic Precursor Lesion
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A 69-year-old man underwent endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) at the lesser curvature in the angle of stomach. Histological examination revealed tub1, pM, ly0, v0, pLM(-), pVM(-), and the resection was considered curative. The scar after ESD was followed by esophagogastroduodenoscopy (EGD) and biopsy. Twenty months later, EGD showed an ulcerative lesion in the vicinity of the ESD scar, and histological examination of the biopsy specimen showed adenocarcinoma. A distal gastrectomy with lymph node dissection was then performed. Postoperative pathology showed tub1, pM, pN0, ly0, v0, and Stage 1A. Skip lesions were seen in the specimen resected by ESD, and the histological review confirmed so-called “dysplasia-like atypia” (DLA) between the lesions. It has been reported recently that in DLA, the dysplasia-like change involves only the bases of the pits, without upper pit or surface epithelium involvement, and it is said that the rate of DLA is higher in gastric cancer patients. We speculated that a precancerous lesion close to the resected cancer developed into a local recurrence.
en-copyright=
kn-copyright=
en-aut-name=KikuchiSatoru
en-aut-sei=Kikuchi
en-aut-mei=Satoru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KubotaTetsushi
en-aut-sei=Kubota
en-aut-mei=Tetsushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KuwadaKazuya
en-aut-sei=Kuwada
en-aut-mei=Kazuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KagawaTetsuya
en-aut-sei=Kagawa
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KurodaShinji
en-aut-sei=Kuroda
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=NishizakiMasahiko
en-aut-sei=Nishizaki
en-aut-mei=Masahiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Departments of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=dysplasia-like atypia
kn-keyword=dysplasia-like atypia
en-keyword=early gastric cancer
kn-keyword=early gastric cancer
en-keyword=endoscopic submucosal dissection
kn-keyword=endoscopic submucosal dissection
en-keyword=local recurrence
kn-keyword=local recurrence
END
start-ver=1.4
cd-journal=joma
no-vol=69
cd-vols=
no-issue=3
article-no=
start-page=173
end-page=176
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=201506
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Prone-Position Thoracoscopic Ligation of the Thoracic Duct for Chyle Leak Following Radical Neck Dissection in a Patient with a Right Aortic Arch
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=A chyle leak can occur as a complication after neck or chest surgery. Such a leak prolongs the hospital stay and is sometimes life-threatening. The treatment options are conservative management, interventional radiologic embolization, and surgery. Thoracoscopic ligation of the thoracic duct has emerged as a promising and definitive treatment. The case of a 65-year-old Japanese male patient with a rare congenital right aortic arch (typeⅢB1 of Edwardʼs classification) and a severe chyle leak that occurred after a total pharyngolaryngo-esophagectomy (TPLE) is described. The chyle leak was successfully managed by thoracoscopic ligation of the thoracic duct via a left-side approach with the patient in the prone position.
en-copyright=
kn-copyright=
en-aut-name=ShirakawaYasuhiro
en-aut-sei=Shirakawa
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NomaKazuhiro
en-aut-sei=Noma
en-aut-mei=Kazuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OharaToshiaki
en-aut-sei=Ohara
en-aut-mei=Toshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KashimaHajime
en-aut-sei=Kashima
en-aut-mei=Hajime
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MaedaNaoaki
en-aut-sei=Maeda
en-aut-mei=Naoaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TanabeShunsuke
en-aut-sei=Tanabe
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=FujiwaraToshiyoshi
en-aut-sei=Fujiwara
en-aut-mei=Toshiyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=2
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=3
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=4
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=5
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=6
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=7
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=8
en-affil=
kn-affil=Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=chyle leak
kn-keyword=chyle leak
en-keyword=thoracic duct
kn-keyword=thoracic duct
en-keyword=thoracoscopy
kn-keyword=thoracoscopy
en-keyword=prone position
kn-keyword=prone position
END