start-ver=1.4
cd-journal=joma
no-vol=75
cd-vols=
no-issue=3
article-no=
start-page=243
end-page=253
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230401
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=GSK-3α/β and MEK inhibitors assist the microenvironment of tumor initiation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Induced pluripotent stem cells (iPSCs) are useful tools for modeling diseases and developing personalized medicine. We have been developing cancer stem cells (CSCs) from iPSCs with conditioned medium (CM) of cancer-derived cells as the mimicry of the microenvironment of tumor initiation. However, the conversion of human iPSCs has not always been efficient with only CM. In this study, human iPSCs reprogrammed from monocytes of healthy volunteers were cultured in a media containing 50% of the CM from human pancreatic cancer derived BxPC3 cells supplemented with a MEK inhibitor (AZD6244) and a GSK-3α/β inhibitor (CHIR99021). The survived cells were assessed for the characteristics of CSCs in vitro and in vivo. As a result, they exhibited CSC phenotypes of self-renewal, differentiation, and malignant tumorigenicity. Primary culture of the malignant tumors of the converted cells exhibited the elevated expression of CSC related genes CD44, CD24 and EPCAM maintaining the expression of stemness genes. In conclusion, the inhibition of GSK-3α/β and MEK and the microenvironment of tumor initiation mimicked by the CM can convert human normal stem cells into CSCs. This study could provide insights into establishing potentially novel personalized cancer models which could help investigate the tumor initiation and screening of personalized therapies on CSCs.
en-copyright=
kn-copyright=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NawaraHend M.
en-aut-sei=Nawara
en-aut-mei=Hend M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KumonKazuki
en-aut-sei=Kumon
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=IwasakiYoshiaki
en-aut-sei=Iwasaki
en-aut-mei=Yoshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SalomonDavid S.
en-aut-sei=Salomon
en-aut-mei=David S.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
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=9
ORCID=

affil-num=1
en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
kn-affil=

affil-num=6
en-affil=Health Service Center, Okayama University
kn-affil=

affil-num=7
en-affil=Center for Cancer Research, National Cancer Institute
kn-affil=

affil-num=8
en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Cancer Stem Cell Engineering, Faculty of Interdisciplinary Science and Engineering in Health Systems, Institute of Academic and Research, Okayama University
kn-affil=
en-keyword=Cancer stem cells
kn-keyword=Cancer stem cells
en-keyword=Human iPSCs
kn-keyword=Human iPSCs
en-keyword=Signal pathway inhibitors
kn-keyword=Signal pathway inhibitors
en-keyword=Tumor initiation
kn-keyword=Tumor initiation
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=15628
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220917
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cancer stem cells induced by chronic stimulation with prostaglandin E2 exhibited constitutively activated PI3K axis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Previously, our group has demonstrated establishment of Cancer Stem Cell (CSC) models from stem cells in the presence of conditioned medium of cancer cell lines. In this study, we tried to identify the factors responsible for the induction of CSCs. Since we found the lipid composition could be traced to arachidonic acid cascade in the CSC model, we assessed prostaglandin E2 (PGE2) as a candidate for the ability to induce CSCs from induced pluripotent stem cells (iPSCs). Mouse iPSCs acquired the characteristics of CSCs in the presence of 10 ng/mL of PGE2 after 4 weeks. Since constitutive Akt activation and pik3cg overexpression were found in the resultant CSCs, of which growth was found independent of PGE2, chronic stimulation of the receptors EP-2/4 by PGE2 was supposed to induce CSCs from iPSCs through epigenetic effect. The bioinformatics analysis of the next generation sequence data of the obtained CSCs proposed not only receptor tyrosine kinase activation by growth factors but also extracellular matrix and focal adhesion enhanced PI3K pathway. Collectively, chronic stimulation of stem cells with PGE2 was implied responsible for cancer initiation enhancing PI3K/Akt axis.
en-copyright=
kn-copyright=

en-aut-name=MinematsuHideki
en-aut-sei=Minematsu
en-aut-mei=Hideki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SugiharaYuki
en-aut-sei=Sugihara
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=AdachiMasaki
en-aut-sei=Adachi
en-aut-mei=Masaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=

affil-num=1
en-affil=Laboratory of Nao?Biotechnology, Division of Medical Bioengineering, Graduate School of Natural Science and  Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Division of Biochemistry, Chemistry Department, Faculty of Science, Menoufa  University
kn-affil=

affil-num=3
en-affil=R&D Center, Katayama Chemicals Ind., Co. Ltd, Ina,  Minoh
kn-affil=

affil-num=4
en-affil=Department of Biotechnology and Drug Discovery, Graduate School  of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Biotechnology and Drug Discovery, Graduate School  of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Biotechnology and Drug Discovery, Graduate School  of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=7
en-affil=R&D Center, Katayama Chemicals Ind., Co. Ltd, Ina,  Minoh
kn-affil=

affil-num=8
en-affil=Department of Biotechnology and Drug Discovery, Graduate School  of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=2
cd-vols=
no-issue=
article-no=
start-page=15
end-page=29
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220331
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=The 13th International Symposium for Future Technology Creating Better Human Health and Society : The key to innovation that solves complex problems
kn-title=第13 回 高度医療都市を創出する未来技術国際シンポジウム : 複雑な課題を解決する イノベーションを生む鍵
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=SenoMasaharu
en-aut-sei=Seno
en-aut-mei=Masaharu
kn-aut-name=妹尾昌治
kn-aut-sei=妹尾
kn-aut-mei=昌治
aut-affil-num=1
ORCID=

affil-num=1
en-affil=Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=岡山大学学術研究院ヘルスシステム統合科学学域
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=2711
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220217
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The significance of ErbB2/3 in the conversion of induced pluripotent stem cells into cancer stem cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer stem cells (CSCs) are suggested to be responsible for drug resistance and aggressive phenotypes of tumors. Mechanisms of CSC induction are still under investigation. Our lab has established a novel method to generate CSCs from iPSCs under a cancerous microenvironment mimicked by the conditioned medium (CM) of cancer-derived cells. Here, we analyzed the transcriptome of CSCs, which were converted from iPSCs with CM from pancreatic ductal adenocarcinoma cells. The differentially expressed genes were identified and used to explore pathway enrichment. From the comparison of the CSCs with iPSCs, genes with elevated expression were related to the ErbB2/3 signaling pathway. Inhibition of either ErbB2 with lapatinib as a tyrosine kinase inhibitor or ErbB3 with TX1-85-1 or siRNAs arrested cell proliferation, inhibited the in vitro tumorigenicity, and lead to loss of stemness in the converting cells. The self-renewal and tube formation abilities of cells were also abolished while CD24 and Oct3/4 levels were reduced, and the MAPK pathway was overactivated. This study shows a potential involvement of the ErbB2/ErbB3 pathway in CSC generation and could lead to new insight into the mechanism of tumorigenesis and the way of cancer prevention.
en-copyright=
kn-copyright=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

affil-num=1
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=347
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220110
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The efficacy of PI3K gamma and EGFR inhibitors on the suppression of the characteristics of cancer stem cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer stem cells (CSCs) are capable of continuous proliferation, self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. We have established a model of CSCs that was originally developed from mouse induced pluripotent stem cells (miPSCs) by proposing miPSCs to the conditioned medium (CM) of cancer derived cells, which is a mimic of carcinoma microenvironment. Further research found that not only PI3K-Akt but also EGFR signaling pathway was activated during converting miPSCs into CSCs. In this study, we tried to observe both of PI3K gamma inhibitor Eganelisib and EGFR inhibitor Gefitinib antitumor effects on the models of CSCs derived from miPSCs (miPS-CSC) in vitro and in vivo. As the results, targeting these two pathways exhibited significant inhibition of cell proliferation, self-renewal, migration and invasion abilities in vitro. Both Eganelisib and Gefitinib showed antitumor effects in vivo while Eganelisib displayed more significant therapeutic efficacy and less side effects than Gefitinib on all miPS-CSC models. Thus, these data suggest that the inhibitiors of PI3K and EGFR, especially PI3K gamma, might be a promising therapeutic strategy against CSCs defeating cancer in the near future.
en-copyright=
kn-copyright=

en-aut-name=XuYanning
en-aut-sei=Xu
en-aut-mei=Yanning
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=DuJuan
en-aut-sei=Du
en-aut-mei=Juan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=LiuBingbing
en-aut-sei=Liu
en-aut-mei=Bingbing
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=WangQing
en-aut-sei=Wang
en-aut-mei=Qing
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=LiHanbo
en-aut-sei=Li
en-aut-mei=Hanbo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=LiuYixin
en-aut-sei=Liu
en-aut-mei=Yixin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=FuXiaoying
en-aut-sei=Fu
en-aut-mei=Xiaoying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=ZhuZhengmao
en-aut-sei=Zhu
en-aut-mei=Zhengmao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ChenLing
en-aut-sei=Chen
en-aut-mei=Ling
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
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=12
ORCID=

affil-num=1
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Etiology, Shanxi Provincial Cancer Hospital
kn-affil=

affil-num=4
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Maternity Hospital, Tianjin Key Laboratory of Human Development and Reproductive Regulation
kn-affil=

affil-num=5
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Genetics and Cell Biology, College of Life Sciences, Nankai University
kn-affil=

affil-num=7
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Maternity Hospital, Tianjin Key Laboratory of Human Development and Reproductive Regulation
kn-affil=

affil-num=8
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Maternity Hospital, Tianjin Key Laboratory of Human Development and Reproductive Regulation
kn-affil=

affil-num=9
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Genetics and Cell Biology, College of Life Sciences, Nankai University
kn-affil=

affil-num=11
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Maternity Hospital, Tianjin Key Laboratory of Human Development and Reproductive Regulation
kn-affil=

affil-num=12
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=41
cd-vols=
no-issue=1
article-no=
start-page=29
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220121
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Different pancreatic cancer microenvironments convert iPSCs into cancer stem cells exhibiting distinct plasticity with altered gene expression of metabolic pathways
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background<br>
Cancer stem cells (CSCs) are generated under irregular microenvironment in vivo, of which mimic is quite difficult due to the lack of enough information of the factors responsible for cancer initiation. Here, we demonstrated that mouse induced pluripotent cells (miPSCs) reprogrammed from normal embryonic fibroblasts were susceptible to the microenvironment affected by cancer cells to convert into CSCs in vivo. <br>
Methods Three different pancreatic cancer line cells, BxPC3, PANC1, and PK8 cells were mixed with miPSCs and subcutaneously injected into immunodeficient mice. Tumors were evaluated by histological analysis and cells derived from iPSCs were isolated and selected from tumors. The isolated cells were characterized for cancer stem cell characters in vitro and in vivo as well as their responses to anticancer drugs. The impact of co-injection of iPSCs with cancer cells on transcriptome and signaling pathways of iPSCs was investigated. <br>
Results The injection of miPSCs mixed with human pancreatic cancer cells into immunodeficient mice maintained the stemness of miPSCs and changed their phenotype. The miPSCs acquired CSC characteristics of tumorigenicity and self-renewal. The drug responses and the metastatic ability of CSCs converted from miPSCs varied depending on the microenvironment of cancer cells. Interestingly, transcriptome profiles of these cells indicated that the pathways related with aggressiveness and energy production were upregulated from the levels of miPSCs.<br>
Conclusions<br>
Our result suggests that cancer-inducing microenvironment in vivo could rewire the cell signaling and metabolic pathways to convert normal stem cells into CSCs.
en-copyright=
kn-copyright=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
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=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KumonKazuki
en-aut-sei=Kumon
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=FuXiaoying
en-aut-sei=Fu
en-aut-mei=Xiaoying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=Al KadiMohamad
en-aut-sei=Al Kadi
en-aut-mei=Mohamad
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=SalomonDavid S.
en-aut-sei=Salomon
en-aut-mei=David S.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
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=10
ORCID=

affil-num=1
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Pathology and Experimental Medicine, Medical School, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University
kn-affil=

affil-num=8
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=9
en-affil=Mouse genetics program, Center for Cancer Research, National Cancer Institute
kn-affil=

affil-num=10
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=Cancer stem cells
kn-keyword=Cancer stem cells
en-keyword=iPSCs
kn-keyword=iPSCs
en-keyword=Conversion
kn-keyword=Conversion
en-keyword=Plasticity
kn-keyword=Plasticity
en-keyword=Tumorigenesis
kn-keyword=Tumorigenesis
en-keyword=Pancreatic cancer microenvironments
kn-keyword=Pancreatic cancer microenvironments
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=1
article-no=
start-page=23977
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20211214
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Differentiation of cancer stem cells into erythroblasts in the presence of CoCl2
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer stem cells (CSCs) are subpopulations in the malignant tumors that show self-renewal and multilineage differentiation into tumor microenvironment components that drive tumor growth and heterogeneity. In previous studies, our group succeeded in producing a CSC model by treating mouse induced pluripotent stem cells. In the current study, we investigated the potential of CSC differentiation into blood cells under chemical hypoxic conditions using CoCl2. CSCs and miPS-LLCcm cells were cultured for 1 to 7 days in the presence of CoCl2, and the expression of VEGFR1/2, Runx1, c-kit, CD31, CD34, and TER-119 was assessed by RT-qPCR, Western blotting and flow cytometry together with Wright-Giemsa staining and immunocytochemistry. CoCl2 induced significant accumulation of HIF-1 alpha changing the morphology of miPS-LLCcm cells while the morphological change was apparently not related to differentiation. The expression of VEGFR2 and CD31 was suppressed while Runx1 expression was upregulated. The population with hematopoietic markers CD34(+) and c-kit(+) was immunologically detected in the presence of CoCl2. Additionally, high expression of CD34 and, a marker for erythroblasts, TER-119, was observed. Therefore, CSCs were suggested to differentiate into erythroblasts and erythrocytes under hypoxia. This differentiation potential of CSCs could provide new insight into the tumor microenvironment elucidating tumor heterogenicity.
en-copyright=
kn-copyright=

en-aut-name=KumonKazuki
en-aut-sei=Kumon
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=UenoShunsuke
en-aut-sei=Ueno
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MonzurSadia
en-aut-sei=Monzur
en-aut-mei=Sadia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=NawaraHend M.
en-aut-sei=Nawara
en-aut-mei=Hend M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=Abu QuoraHagar A.
en-aut-sei=Abu Quora
en-aut-mei=Hagar A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ShetaMona
en-aut-sei=Sheta
en-aut-mei=Mona
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=XuYanning
en-aut-sei=Xu
en-aut-mei=Yanning
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FuXiaoying
en-aut-sei=Fu
en-aut-mei=Xiaoying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
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=13
ORCID=

affil-num=1
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics, Nankai University Affiliated Maternity Hospital, Tianjin Key Laboratory of Human Development and Reproductive Regulation
kn-affil=

affil-num=10
en-affil=Department of Pathology, Tianjin University of Traditional Chinese Medicine
kn-affil=

affil-num=11
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=12
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
END

start-ver=1.4
cd-journal=joma
no-vol=3
cd-vols=
no-issue=3
article-no=
start-page=60
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200821
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Metastasis Model of Cancer Stem Cell-Derived Tumors
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Metastasis includes the dissemination of cancer cells from a malignant tumor and seed in distant sites inside the body forming secondary tumors. Metastatic cells from the primary tumor can move even before the cancer is detected. Therefore, metastases are responsible for more than 90% of cancer-related deaths. Over recent decades there has been adequate evidence suggesting the existence of CSCs with self-renewing and drug-resistant potency within heterogeneous tumors. Cancer stem cells (CSCs) act as a tumor initiating cells and have roles in tumor retrieve and metastasis. Our group recently developed a unique CSC model from mouse induced pluripotent stem cells cultured in the presence of cancer cell-conditioned medium that mimics tumors microenvironment. Using this model, we demonstrated a new method for studying metastasis by intraperitoneal transplantation of tumors and investigate the metastasis ability of cells from these segments. First of all, CSCs were injected subcutaneously in nude mice. The developed malignant tumors were minimized then transplanted into the peritoneal cavity. Following this, the developed tumor in addition to lung, pancreas and liver were then excised and analyzed. Our method showed the metastatic potential of CSCs with the ability of disseminated and moving to blood circulation and seeding in distant organs such as lung and pancreas. This method could provide a good model to study the mechanisms of metastasis according to CSC theory.
en-copyright=
kn-copyright=

en-aut-name=MansourHager
en-aut-sei=Mansour
en-aut-mei=Hager
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YanTing
en-aut-sei=Yan
en-aut-mei=Ting
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

affil-num=1
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Pathology, Shanxi Key Laboratory of Carcinogenesis and Translational Research on Esophageal Cancer, Shanxi Medical University
kn-affil=

affil-num=5
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
en-keyword=metastasis
kn-keyword=metastasis
en-keyword=cancer stem cells
kn-keyword=cancer stem cells
en-keyword=transplantation
kn-keyword=transplantation
en-keyword=surgery
kn-keyword=surgery
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=7
article-no=
start-page=3475
end-page=3495
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=2021
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Microenvironment of mammary fat pads affected the characteristics of the tumors derived from the induced cancer stem cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Breast cancer is the first common cause of cancer-related death in women worldwide. Since the malignancy and aggressiveness of breast cancer have been correlated with the presence of breast cancer stem cells, the establishment of a disease model with cancer stem cells is required for the development of a novel therapeutic strategy. Here, we aimed to evaluate the availability of cancer stem cell models developed from mouse induced pluripotent stem cells with the conditioned medium of different subtypes of breast cancer cell lines, the hormonal-responsive T47D cell line and the triple-negative breast cancer BT549 cell line, to generate in vivo tumor models. When transplanted into the mammary fat pads of BALB/c nude mice, these two model cells formed malignant tumors exhibiting pronounced histopathological characteristics similar to breast cancers. Serial transplantation of the primary cultured cells into mammary fat pads evoked the same features of breast cancer, while this result was perturbed following subcutaneous transplantation. The tumors formed in the mammary fat pads exhibited immune reactivities to prolactin receptor, progesterone receptor, green florescent protein, Ki67, CD44, estrogen receptor alpha/beta and cytokeratin 8, while all of the tumors and their derived primary cells exhibited immunoreactivity to estrogen receptor alpha/beta and cytokeratin 8. Cancer stem cells can be developed from pluripotent stem cells via the secretory factors of cancer-derived cells with the capacity to inherit tissue specificity. However, cancer stem cells should be plastic enough to be affected by the microenvironment of specific tissues. In summary, we successfully established a breast cancer tumor model using mouse induced pluripotent stem cells developed from normal fibroblasts without genetic manipulation.
en-copyright=
kn-copyright=

en-aut-name=Abu QuoraHagar A.
en-aut-sei=Abu Quora
en-aut-mei=Hagar A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=El-GhlbanSamah
en-aut-sei=El-Ghlban
en-aut-mei=Samah
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=NairNeha
en-aut-sei=Nair
en-aut-mei=Neha
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=NawaraHend M.
en-aut-sei=Nawara
en-aut-mei=Hend M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=ShetaMona
en-aut-sei=Sheta
en-aut-mei=Mona
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MonzurSadia
en-aut-sei=Monzur
en-aut-mei=Sadia
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=FuXiaoying
en-aut-sei=Fu
en-aut-mei=Xiaoying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=OsmanAmira
en-aut-sei=Osman
en-aut-mei=Amira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
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=13
ORCID=

affil-num=1
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Division of Biochemistry, Faculty of Science, Menoufia University
kn-affil=

affil-num=4
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=11
en-affil=Department of Histology, Faculty of Medicine, Kafr Elsheikh University
kn-affil=

affil-num=12
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=Mammary fat pad
kn-keyword=Mammary fat pad
en-keyword=microenvironment
kn-keyword=microenvironment
en-keyword=iPSCs
kn-keyword=iPSCs
en-keyword=CSCs
kn-keyword=CSCs
en-keyword=breast cancer
kn-keyword=breast cancer
END

start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=10
article-no=
start-page=2491
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210520
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cripto-1 as a Potential Target of Cancer Stem Cells for Immunotherapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Simple Summary Cancer immunotherapy is gaining attention as a potential fourth treatment following surgery, chemotherapy, and radiation therapy. Cancer stem cells have recently been recognized and validated as a key target for cancer treatment. Cripto-1, which is a GPI-anchored membrane-bound protein that functions as a co-receptor of Nodal, is a marker of cancer stem cells. Since Nodal is a member of the TGF-beta family, which performs an important role in stem cells and cancer stem cells, the inhibition of Cripto-1 could be a strategy by which to block Nodal signaling and thereby suppress cancer stem cells. We propose that Cripto-1 may be a novel target for cancer immunotherapy. The immune system has been found to be suppressed in cancer patients. Cancer cells are extremely resistant to chemotherapeutic drugs, conventional immunotherapy, or cancer antigen vaccine therapy. Cancer immunotherapy, which is mainly based on immune checkpoint inhibitors, such as those for PD-1, PD-L1, and CTLA4, is an effective treatment method. However, no immunotherapeutic target has been found that retains validity in the face of tumor diversity. The transforming growth factor (TGF)-beta cytokine family possesses broad biological activity and is involved in the induction and/or transdifferentiation of helper T cells, which are important in immunotherapy. Nodal is a member of the TGF-beta family playing important roles in tissue stem cells and cancer stem cells (CSCs), interacting with the co-receptor Cripto-1, as well as with Activin type IB (Alk4) and Activin typeIIreceptors, and maintaining stemness and Notch and Wnt/beta-catenin signaling in CSCs. In recent years, it has been reported that Cripto-1 could be a potential therapeutic target in CSCs. Here, we review the accumulated literature on the molecular mechanisms by which Cripto-1 functions in CSCs and discuss the potential of Cripto-1 as an immunotherapeutic target in CSCs.
en-copyright=
kn-copyright=

en-aut-name=IshiiHiroko
en-aut-sei=Ishii
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SalomonDavid S.
en-aut-sei=Salomon
en-aut-mei=David S.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
ORCID=

affil-num=1
en-affil=GSP Enterprise, Inc.
kn-affil=

affil-num=2
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute
kn-affil=

affil-num=5
en-affil=
kn-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
en-keyword=Cripto-1
kn-keyword=Cripto-1
en-keyword=TGF-beta
kn-keyword=TGF-beta
en-keyword=cancer stem cells
kn-keyword=cancer stem cells
en-keyword=immunotherapy
kn-keyword=immunotherapy
en-keyword=antibody
kn-keyword=antibody
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=5
article-no=
start-page=500
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210502
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Paclitaxel-Based Chemotherapy Targeting Cancer Stem Cells from Mono- to Combination Therapy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Paclitaxel (PTX) is a chemotherapeutical agent commonly used to treat several kinds of cancer. PTX is known as a microtubule-targeting agent with a primary molecular mechanism that disrupts the dynamics of microtubules and induces mitotic arrest and cell death. Simultaneously, other mechanisms have been evaluated in many studies. Since the anticancer activity of PTX was discovered, it has been used to treat many cancer patients and has become one of the most extensively used anticancer drugs. Regrettably, the resistance of cancer to PTX is considered an extensive obstacle in clinical applications and is one of the major causes of death correlated with treatment failure. Therefore, the combination of PTX with other drugs could lead to efficient therapeutic strategies. Here, we summarize the mechanisms of PTX, and the current studies focusing on PTX and review promising combinations.
en-copyright=
kn-copyright=

en-aut-name=NawaraHend M.
en-aut-sei=Nawara
en-aut-mei=Hend M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

affil-num=1
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=paclitaxel
kn-keyword=paclitaxel
en-keyword=microtubule targeting agent
kn-keyword=microtubule targeting agent
en-keyword=anticancer
kn-keyword=anticancer
en-keyword=cancer stem cells
kn-keyword=cancer stem cells
en-keyword=combination therapy
kn-keyword=combination therapy
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=2
article-no=
start-page=441
end-page=457
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=2021
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Isolation and characterization of cancer stem cells derived from human glioblastoma
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer stem cell (CSC) is considered as a cause of cancer recurrence and metastasis. Simultaneously CSCs are responsible for the heterogeneous population in tumor tissues due to their differentiation potential. However, the characterizations of CSCs are still not enough and cancer stem cell lines widely available is desired to be established for the advancement of cancer research. In this study, we tried to isolate and characterize stem like cells from human glioblastoma cell line U-251MG cells. U-251MG P1 cells, which was previously condensed in the presence of hyaluronic acid as CD44 positive population were subjected to single cell isolation procedure. Although 5 clones were isolated, only one clone exhibited high expression of CD44, Nanog, OCT3/4 and SOX2, and named U-251MGSC1. The sphere forming ability of U-251MGSC1 cell was significantly higher than the parental U-251MG cells. Tumorigenicity of U-251MG-SC1 cells were higher than that of U-251MG cells. U-251MGSC1 cells exhibited higher expression of CD44, SOX2, Nestin and A2B5 than U-251MG cells in vitro and in vivo. The expression of GFAP and NF-M was enhanced when the cells were treated with the conditioned medium of U-251MG cells indicating the potential of differentiation. Sphere forming ability was more efficient than that of U-251MG cells and was enhanced in the presence of hyaluronic acid, which enhanced the cell growth as well. U-251MGSC1 cells exhibited rapid growth tumor in nude mice and efficient metastatic ability in transmembrane assay when compared with U-251MG cells. As the result, we concluded U-251MGSC1 cell was a glioblastoma CSC line derived from the parental U-251MG cells. U-251MGSC1 cells will be a good tool to develop effective therapeutic agents against CSCs and to elucidate the properties of glioma derived CSCs and the mechanism of tumor development in brain.
en-copyright=
kn-copyright=

en-aut-name=IshiiHiroko
en-aut-sei=Ishii
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MimuraYuki
en-aut-sei=Mimura
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KatayamaShota
en-aut-sei=Katayama
en-aut-mei=Shota
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=7
ORCID=

affil-num=1
en-affil=GSP Enterprise, Inc.
kn-affil=

affil-num=2
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=6
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=7
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=Cancer stem cell
kn-keyword=Cancer stem cell
en-keyword=glioblastoma
kn-keyword=glioblastoma
en-keyword=sphere formation
kn-keyword=sphere formation
en-keyword=CD44
kn-keyword=CD44
en-keyword=SOX2
kn-keyword=SOX2
en-keyword=GFAP
kn-keyword=GFAP
END

start-ver=1.4
cd-journal=joma
no-vol=22
cd-vols=
no-issue=4
article-no=
start-page=1709
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210208
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Novel Artificially Humanized Anti-Cripto-1 Antibody Suppressing Cancer Cell Growth
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cripto-1 is a member of the EGF-CFC/FRL1/Cryptic family and is involved in embryonic development and carcinogenesis. We designed a novel anti-Cripto-1 artificial antibody and assessed the recognition to the antigen and the potential to suppress the growth of cancer stem cells. First, single chain antibody clones were isolated by bio-panning with the affinity to recombinant Cripto-1 protein from our original phage-display library. Then, the variable regions of heavy chain VH and light chain VL in each clone were fused to constant regions of heavy chain CH and light chain CL regions respectively. These fused genes were expressed in ExpiCHO-S cells to produce artificial humanized antibodies against Cripto-1. After evaluation of the expression levels, one clone was selected and the anti-Cripto-1 antibody was produced and purified. The purified antibody showed affinity to recombinant Cripto-1 at 1.1 pmol and immunoreactivity to cancer tissues and cell lines. The antibody was available to detect the immunoreactivity in tissue microarrays of malignant tumors as well as in Cripto-1 overexpressing cells. Simultaneously, the antibody exhibited the potential to suppress the growth of human colon cancer derived GEO cells overexpressing Cripto-1 with IC50 at approximately 110 nM. The artificially humanized antibody is proposed to be a good candidate to target cancer cells overexpressing Cripto-1.
en-copyright=
kn-copyright=

en-aut-name=IshiiHiroko
en-aut-sei=Ishii
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=TakayanagiAtushi
en-aut-sei=Takayanagi
en-aut-mei=Atushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
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=4
ORCID=

affil-num=1
en-affil=GSP Enterprise, Inc.
kn-affil=

affil-num=2
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=GSP Enterprise, Inc.
kn-affil=

affil-num=4
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=phage display library
kn-keyword=phage display library
en-keyword=artificial humanized antibody
kn-keyword=artificial humanized antibody
en-keyword=Cripto-1
kn-keyword=Cripto-1
en-keyword=anti-Cripto-1 antibody
kn-keyword=anti-Cripto-1 antibody
en-keyword=tissue-micro array
kn-keyword=tissue-micro array
en-keyword=cell growth inhibition
kn-keyword=cell growth inhibition
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=1
article-no=
start-page=45
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20201228
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cancer Stem Cell Microenvironment Models with Biomaterial Scaffolds In Vitro
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Defined by its potential for self-renewal, differentiation and tumorigenicity, cancer stem cells (CSCs) are considered responsible for drug resistance and relapse. To understand the behavior of CSC, the effects of the microenvironment in each tissue are a matter of great concerns for scientists in cancer biology. However, there are many complicated obstacles in the mimicking the microenvironment of CSCs even with current advanced technology. In this context, novel biomaterials have widely been assessed as in vitro platforms for their ability to mimic cancer microenvironment. These efforts should be successful to identify and characterize various CSCs specific in each type of cancer. Therefore, extracellular matrix scaffolds made of biomaterial will modulate the interactions and facilitate the investigation of CSC associated with biological phenomena simplifying the complexity of the microenvironment. In this review, we summarize latest advances in biomaterial scaffolds, which are exploited to mimic CSC microenvironment, and their chemical and biological requirements with discussion. The discussion includes the possible effects on both cells in tumors and microenvironment to propose what the critical factors are in controlling the CSC microenvironment focusing the future investigation. Our insights on their availability in drug screening will also follow the discussion.
en-copyright=
kn-copyright=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=KitanoShiro
en-aut-sei=Kitano
en-aut-mei=Shiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=IshiiHiroko
en-aut-sei=Ishii
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ShangYucheng
en-aut-sei=Shang
en-aut-mei=Yucheng
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MatsusakiMichiya
en-aut-sei=Matsusaki
en-aut-mei=Michiya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
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=8
ORCID=

affil-num=1
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Technical Research Institute, Toppan Printing Co., Ltd.
kn-affil=

affil-num=4
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=GSP Enterprise, Inc.
kn-affil=

affil-num=6
en-affil=Department of Applied Chemistry, Graduate School of Engineering, Osaka University
kn-affil=

affil-num=7
en-affil=Department of Applied Chemistry, Graduate School of Engineering, Osaka University
kn-affil=

affil-num=8
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=cancer stem cells
kn-keyword=cancer stem cells
en-keyword=biomaterial scaffolds
kn-keyword=biomaterial scaffolds
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
en-keyword=drug screening
kn-keyword=drug screening
END

start-ver=1.4
cd-journal=joma
no-vol=122
cd-vols=
no-issue=9
article-no=
start-page=1378
end-page=1390
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200317
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A novel model of liver cancer stem cells developed from induced pluripotent stem cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background</br>
Liver cancer is the second most common cause of cancer-related death. Every type of tumours including liver cancer contains cancer stem cells (CSCs). To date, the molecular mechanism regulating the development of liver CSCs remains unknown.</br>
Methods</br>
In this study, we tried to generate a new model of liver CSCs by converting mouse induced pluripotent stem cells (miPSCs) with hepatocellular carcinoma (HCC) cell line Huh7 cells conditioned medium (CM). miPSCs treated with CM were injected into the liver of BALB/c nude mice. The developed tumours were then excised and analysed.</br>
Results</br>
The primary cultured cells from the malignant tumour possessed self-renewal capacity, differentiation potential and tumorigenicity in vivo, which were found rich in liver cancer-associated markers as well as CSC markers.</br>
Conclusions</br>
We established a model of liver CSCs converting from miPS and showed different stages of stemness during conversion process. Our CSC model will be important to assess the molecular mechanisms necessary to develop liver CSCs and could help in defeating liver cancer.
en-copyright=
kn-copyright=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=CalleAnna Sanchez
en-aut-sei=Calle
en-aut-mei=Anna Sanchez
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KumonKazuki
en-aut-sei=Kumon
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=NawaraHend M.
en-aut-sei=Nawara
en-aut-mei=Hend M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MansourHager M.
en-aut-sei=Mansour
en-aut-mei=Hager M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KhayraniApriliana Cahya
en-aut-sei=Khayrani
en-aut-mei=Apriliana Cahya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=AlamMd Jahangir
en-aut-sei=Alam
en-aut-mei=Md Jahangir
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=DuJuan
en-aut-sei=Du
en-aut-mei=Juan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=IwasakiYoshiaki
en-aut-sei=Iwasaki
en-aut-mei=Yoshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
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=13
ORCID=

affil-num=1
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Division of Molecular and Cellular Medicine, National Cancer Center Research Institute
kn-affil=

affil-num=3
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=6
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=7
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=9
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=10
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=11
en-affil=Okayama University Research Laboratory of Stem Cell Engineering in Detroit, IBio, Wayne State University
kn-affil=

affil-num=12
en-affil=Department of Gastroenterology and Hepatology, Graduate School of Medicine, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
en-keyword=Cancer models
kn-keyword=Cancer models
en-keyword=Cancer stem cells
kn-keyword=Cancer stem cells
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=6
article-no=
start-page=1360
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200526
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Paclitaxel and Sorafenib: The Effective Combination of Suppressing the Self-Renewal of Cancer Stem Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Combination therapy, which is a treatment modality combining two or more therapeutic agents, is considered a cornerstone of cancer therapy. The combination of anticancer drugs, of which functions are different from the other, enhances the efficiency compared to the monotherapy because it targets cancer cells in a synergistic or an additive manner. In this study, the combination of paclitaxel and sorafenib in low concentration was evaluated to target cancer stem cells, miPS-BT549cmP and miPS-Huh7cmP cells, developed from mouse induced pluripotent stem cells. The synergistic effect of paclitaxel and sorafenib on cancer stem cells was assessed by the inhibition of proliferation, self-renewal, colony formation, and differentiation. While the IC(50)values of paclitaxel and sorafenib were approximately ranging between 250 and 300 nM and between 6.5 and 8 mu M, respectively, IC(50)of paclitaxel reduced to 20 and 25 nM, which was not toxic in a single dose, in the presence of 1 mu M sorafenib, which was not toxic to the cells. Then, the synergistic effect was further assessed for the potential of self-renewal of cancer stem cells by sphere formation ability. As a result, 1 mu M of sorafenib significantly enhanced the effect of paclitaxel to suppress the number of spheres. Simultaneously, paclitaxel ranging in 1 to 4 nM significantly suppressed not only the colony formation but also the tube formation of the cancer stem cells in the presence of 1 mu M sorafenib. These results suggest the combination therapy of paclitaxel and sorafenib in low doses should be an attractive approach to target cancer stem cells with fewer side effects.
en-copyright=
kn-copyright=

en-aut-name=NawaraHend M.
en-aut-sei=Nawara
en-aut-mei=Hend M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=AtallahMarwa N.
en-aut-sei=Atallah
en-aut-mei=Marwa N.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=MansourHager
en-aut-sei=Mansour
en-aut-mei=Hager
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=Abu QuoraHagar A.
en-aut-sei=Abu Quora
en-aut-mei=Hagar A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AlamMd Jahangir
en-aut-sei=Alam
en-aut-mei=Md Jahangir
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=OsmanAmira
en-aut-sei=Osman
en-aut-mei=Amira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KakutaHiroki
en-aut-sei=Kakuta
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=HamadaHiroki
en-aut-sei=Hamada
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=妹尾彬正
kn-aut-sei=妹尾
kn-aut-mei=彬正
aut-affil-num=12
ORCID=

en-aut-name=SenoMasaharu
en-aut-sei=Seno
en-aut-mei=Masaharu
kn-aut-name=妹尾昌治
kn-aut-sei=妹尾
kn-aut-mei=昌治
aut-affil-num=13
ORCID=

affil-num=1
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=Vertebrates Embryology and Comparative Anatomy, Zoology Department, Faculty of Science, Menoufia University
kn-affil=

affil-num=6
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=7
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=8
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=9
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=10
en-affil=Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=

affil-num=11
en-affil=Department of Life Science, Faculty of Science, Okayama University of Science
kn-affil=

affil-num=12
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=13
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
en-keyword=cancer stem cells
kn-keyword=cancer stem cells
en-keyword=combination therapy
kn-keyword=combination therapy
en-keyword=paclitaxel
kn-keyword=paclitaxel
en-keyword=sorafenib
kn-keyword=sorafenib
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=1
article-no=
start-page=200
end-page=207
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=2020
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Upregulated CCL20 and CCR6 in Cancer Stem Cells Converted from Mouse iPS Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Cancer stem cells (CSCs) as a class of malignant cancer cells play an important role in tumor progression. Previous studies by our group have demonstrated the establishment of the model of CSCs converting mouse iPS cells (miPSCs) into CSCs by treating the miPSCs with a conditioned medium (CM) of Lewis Lung Carcinoma (LLC) cells with or without the nonmutagenic chemical compounds. CSCs converted from miPSCs developed highly malignant adenocarcinoma when subcutaneously transplanted into the nude mice.</br>
Methods: The miPSCs were treated with each compound for 1 week in the presence of a CM of LLC cells. We evaluated the gene expression in the resultant CSCs comparing that in miPSCs by microarray analysis. And the expression of chemokine (C-C motif) ligand 20 (CCL20) and C-C chemokine receptor type 6 (CCR6) in converted cells were evaluated by rt-qPCR. The CCR6 expression in converted cells and primary cells were determined by flow cytometry.</br>
Results: As the result, the expression of CCL20 was found upregulated in the presence of CM supplemented with PD0325901. Then we assessed the expression of CCR6, which was considered to be stimulated by CCL20. Then the expression of CCR6 was also found up-regulated. Interestingly, IL17A expression was also observed only in the CSCs from the primary tumor implying the effect of tumor microenvironment. Moreover, significantly high level of CCR6 was showed in flow cytometric analysis.</br>
Conclusion: These results suggest that a model of CSCs with CCL20-CCR6 autocrine loop was obtained as the result of the conversion of iPSCs. This CSC should be a good model to study targeting CCR6 as a G protein-coupled receptor (GPCR).
en-copyright=
kn-copyright=

en-aut-name=DuJuan
en-aut-sei=Du
en-aut-mei=Juan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=SasadaSaki
en-aut-sei=Sasada
en-aut-mei=Saki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=XuYanning
en-aut-sei=Xu
en-aut-mei=Yanning
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OoAung Ko Ko
en-aut-sei=Oo
en-aut-mei=Aung Ko Ko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=UenoShunsuke
en-aut-sei=Ueno
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ZahraMaram H
en-aut-sei=Zahra
en-aut-mei=Maram H
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=OkadaNobuhiro
en-aut-sei=Okada
en-aut-mei=Nobuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ChenLing
en-aut-sei=Chen
en-aut-mei=Ling
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=FuXiaoying
en-aut-sei=Fu
en-aut-mei=Xiaoying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=TokutakaHeizo
en-aut-sei=Tokutaka
en-aut-mei=Heizo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=YanTing
en-aut-sei=Yan
en-aut-mei=Ting
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
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=15
ORCID=

affil-num=1
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama Universityalth Systems
kn-affil=

affil-num=3
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics
kn-affil=

affil-num=5
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=6
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=7
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=8
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=9
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=10
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=11
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics
kn-affil=

affil-num=12
en-affil=School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine
kn-affil=

affil-num=13
en-affil=SOM Japan
kn-affil=

affil-num=14
en-affil=The Hong Kong University of Science and Technology Medical Center, Shenzhen Peking University
kn-affil=

affil-num=15
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=
en-keyword=miPSCs
kn-keyword=miPSCs
en-keyword=CSCs
kn-keyword=CSCs
en-keyword=CCR6
kn-keyword=CCR6
en-keyword=CCL20
kn-keyword=CCL20
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=4
article-no=
start-page=879
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200404
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Revisiting Cancer Stem Cells as the Origin of Cancer-Associated Cells in the Tumor Microenvironment: A Hypothetical View from the Potential of iPSCs
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The tumor microenvironment (TME) has an essential role in tumor initiation and development. Tumor cells are considered to actively create their microenvironment during tumorigenesis and tumor development. The TME contains multiple types of stromal cells, cancer-associated fibroblasts (CAFs), Tumor endothelial cells (TECs), tumor-associated adipocytes (TAAs), tumor-associated macrophages (TAMs) and others. These cells work together and with the extracellular matrix (ECM) and many other factors to coordinately contribute to tumor growth and maintenance. Although the types and functions of TME cells are well understood, the origin of these cells is still obscure. Many scientists have tried to demonstrate the origin of these cells. Some researchers postulated that TME cells originated from surrounding normal tissues, and others demonstrated that the origin is cancer cells. Recent evidence demonstrates that cancer stem cells (CSCs) have differentiation abilities to generate the original lineage cells for promoting tumor growth and metastasis. The differentiation of CSCs into tumor stromal cells provides a new dimension that explains tumor heterogeneity. Using induced pluripotent stem cells (iPSCs), our group postulates that CSCs could be one of the key sources of CAFs, TECs, TAAs, and TAMs as well as the descendants, which support the self-renewal potential of the cells and exhibit heterogeneity. In this review, we summarize TME components, their interactions within the TME and their insight into cancer therapy. Especially, we focus on the TME cells and their possible origin and also discuss the multi-lineage differentiation potentials of CSCs exploiting iPSCs to create a society of cells in cancer tissues including TME.
en-copyright=
kn-copyright=

en-aut-name=OsmanAmira
en-aut-sei=Osman
en-aut-mei=Amira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=FuXiaoying
en-aut-sei=Fu
en-aut-mei=Xiaoying
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

affil-num=1
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=5
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=6
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=CAFs
kn-keyword=CAFs
en-keyword=TECs
kn-keyword=TECs
en-keyword=TAAs
kn-keyword=TAAs
en-keyword=TAMs
kn-keyword=TAMs
en-keyword=CSCs
kn-keyword=CSCs
END

start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=1
article-no=
start-page=82
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20191229
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Hematopoietic Cells Derived from Cancer Stem Cells Generated from Mouse Induced Pluripotent Stem Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer stem cells (CSCs) represent the subpopulation of cancer cells with the ability to differentiate into other cell phenotypes and initiated tumorigenesis. Previously, we reported generating CSCs from mouse induced pluripotent stem cells (miPSCs). Here, we investigated the ability of the CSCs to differentiate into hematopoietic cells. First, the primary cells were isolated from malignant tumors that were formed by the CSCs. Non-adherent cells (NACs) that arose from adherent cells were collected and their viability, as well as the morphology and expression of hematopoietic cell markers, were analyzed. Moreover, NACs were injected into the tail vein of busulfan conditioned Balb/c nude mice. Finally, CSCs were induced to differentiate to macrophages while using IL3 and SCF. The round nucleated NACs were found to be viable, positive for hematopoietic lineage markers and CD34, and expressed hematopoietic markers, just like homing to the bone marrow. When NACs were injected into mice, Wright-Giemsa staining showed that the number of white blood cells got higher than those in the control mice after four weeks. CSCs also showed the ability to differentiate toward macrophages. CSCs were demonstrated to have the potential to provide progenies with hematopoietic markers, morphology, and homing ability to the bone marrow, which could give new insight into the tumor microenvironment according to the plasticity of CSCs.
en-copyright=
kn-copyright=

en-aut-name=HassanGhmkin
en-aut-sei=Hassan
en-aut-mei=Ghmkin
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=NairNeha
en-aut-sei=Nair
en-aut-mei=Neha
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=KumonKazuki
en-aut-sei=Kumon
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OsmanAmira
en-aut-sei=Osman
en-aut-mei=Amira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=DuJuan
en-aut-sei=Du
en-aut-mei=Juan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=MansourHager
en-aut-sei=Mansour
en-aut-mei=Hager
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=Abu QuoraHagar A.
en-aut-sei=Abu Quora
en-aut-mei=Hagar A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=NawaraHend M.
en-aut-sei=Nawara
en-aut-mei=Hend M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SatohAyano
en-aut-sei=Satoh
en-aut-mei=Ayano
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=OkadaNobuhiro
en-aut-sei=Okada
en-aut-mei=Nobuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
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=14
ORCID=

affil-num=1
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=3
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=4
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=5
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=6
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=7
en-affil=
kn-affil=Graduate School of Natural Science and Technology, Okayama University

affil-num=8
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=9
en-affil=Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=10
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=11
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=12
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=13
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=14
en-affil=Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=
en-keyword=Induced pluripotent stem cells
kn-keyword=Induced pluripotent stem cells
en-keyword=Cancer stem cells differentiation
kn-keyword=Cancer stem cells differentiation
en-keyword=tumor microenvironment
kn-keyword=tumor microenvironment
en-keyword=hematopoietic cells
kn-keyword=hematopoietic cells
END

start-ver=1.4
cd-journal=joma
no-vol=18
cd-vols=
no-issue=3
article-no=
start-page=2756
end-page=2762
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=201909
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cancer stem cell induction from mouse embryonic stem cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Although cancers are often removed by surgery and treated by chemotherapy and/or radiation therapies, they often reoccur following treatment due to the presence of resistant residual cells such as cancer stem cells (CSCs). CSCs are characterized by their self-renewal, pluripotency, and tumorigenicity properties, and are promising therapeutic targets for the complete therapy of cancers; however, the number of CSCs in cancer tissue is typically too small to investigate fully. We have previously reported that CSCs could be established from induced pluripotent stem cells (iPSCs) using a conditioned medium during cancer cell culture. In the present study, mouse embryonic stem cells (mESCs) were observed to be converted to CSCs (mES-CSCs). This demonstrated that CSC induction does not exclusively occur following gene editing in somatic cells, and that conditioned medium from cancer cells may contain factors that can induce CSCs. Therefore, not only iPSCs but also mESCs, were demonstrated to be able to produce CSCs as one of the potentials of pluripotency of stem cells, suggesting that the conversion to CSCs is not specific to iPSCs. The resultant mES-CSCs would be also useful to generate tissue specific cancers and these naturally occurring cancers can contribute to drug screenings, but also undergo further investigation in order to reveal cancer mechanisms.
en-copyright=
kn-copyright=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MurakamiChikae
en-aut-sei=Murakami
en-aut-mei=Chikae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=El?AaragBishoy
en-aut-sei=El?Aarag
en-aut-mei=Bishoy
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=IwasakiYoshiaki
en-aut-sei=Iwasaki
en-aut-mei=Yoshiaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
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=5
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=6
ORCID=

affil-num=1
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=3
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=4
en-affil=Health Service Center, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Pathology and Experimental MedicineOkayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=

affil-num=6
en-affil=Laboratory of Nano-Biotechnology, Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems
kn-affil=
en-keyword=cancer stem cell
kn-keyword=cancer stem cell
en-keyword=conditioned medium
kn-keyword=conditioned medium
en-keyword=mouse embryonic stem cells
kn-keyword=mouse embryonic stem cells
END

start-ver=1.4
cd-journal=joma
no-vol=20
cd-vols=
no-issue=5
article-no=
start-page=1042
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190227
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15?20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies.
en-copyright=
kn-copyright=

en-aut-name=Apriliana Cahya Khayrani
en-aut-sei=Apriliana Cahya Khayrani
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MahmudHafizah
en-aut-sei=Mahmud
en-aut-mei=Hafizah
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ZahraMaram H.
en-aut-sei=Zahra
en-aut-mei=Maram H.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=Aung Ko Ko Oo
en-aut-sei=Aung Ko Ko Oo
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=OzeMiharu
en-aut-sei=Oze
en-aut-mei=Miharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=DuJuan
en-aut-sei=Du
en-aut-mei=Juan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=AlamMd Jahangir
en-aut-sei=Alam
en-aut-mei=Md Jahangir
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=Hagar A. Abu Quora
en-aut-sei=Hagar A. Abu Quora
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=ShigehiroTsukasa
en-aut-sei=Shigehiro
en-aut-mei=Tsukasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=Anna Sanchez Calle
en-aut-sei=Anna Sanchez Calle
en-aut-mei=
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

en-aut-name=OkadaNobuhiro
en-aut-sei=Okada
en-aut-mei=Nobuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=

en-aut-name=SenoAkimasa
en-aut-sei=Seno
en-aut-mei=Akimasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=

en-aut-name=FujitaKoki
en-aut-sei=Fujita
en-aut-mei=Koki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=

en-aut-name=HamadaHiroki
en-aut-sei=Hamada
en-aut-mei=Hiroki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=

en-aut-name=SenoYuhki
en-aut-sei=Seno
en-aut-mei=Yuhki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=

en-aut-name=MandaiTadakatsu
en-aut-sei=Mandai
en-aut-mei=Tadakatsu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
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=18
ORCID=

affil-num=1
en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=3
en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=4
en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=5
en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=6
en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=7
en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=8
en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=9
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=10
en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=11
en-affil= Division of Molecular and Cellular Medicine, National Cancer Center Research Institute
kn-affil=

affil-num=12
en-affil= Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=13
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=14
en-affil=Ensuiko Sugar Refining Co., Ltd.
kn-affil=

affil-num=15
en-affil=Faculty of Science, Okayama University of Science
kn-affil=

affil-num=16
en-affil= Graduate School of Pharmaceutical Science, Tokushima University
kn-affil=

affil-num=17
en-affil= Faculty of Life Science, Kurashiki University of Science and the Arts
kn-affil=

affil-num=18
en-affil= Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
en-keyword=CD44
kn-keyword=CD44
en-keyword=glycosylated paclitaxel
kn-keyword=glycosylated paclitaxel
en-keyword=liposome
kn-keyword=liposome
en-keyword=modified paclitaxel
kn-keyword=modified paclitaxel
en-keyword=ovarian cancer
kn-keyword=ovarian cancer
en-keyword=specific targeting
kn-keyword=specific targeting
END

start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=3
article-no=
start-page=345
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190311
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Conversion of Stem Cells to Cancer Stem Cells: Undercurrent of Cancer Initiation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Cancer stem cells (CSCs) also known as cancer-initiating cells (CIC), are responsible for the sustained and uncontrolled growth of malignant tumors and are proposed to play significant roles in metastasis and recurrence. Several hypotheses have proposed that the events in either stem and/or differentiated cells, such as genomic instability, inflammatory microenvironment, cell fusion, and lateral gene transfer, should be considered as the possible origin of CSCs. However, until now, the exact origin of CSC has been obscure. The development of induced pluripotent stem cells (iPSCs) in 2007, by Yamanaka's group, has been met with much fervency and hailed as a breakthrough discovery by the scientific and research communities, especially in regeneration therapy. The studies on the development of CSC from iPSCs should also open a new page of cancer research, which will help in designing new therapies applicable to CSCs. Currently most reviews have focused on CSCs and CSC niches. However, the insight into the niche before the CSC niche should also be of keen interest. This review introduces the novel concept of cancer initiation introducing the conversion of iPSCs to CSCs and proposes a relationship between the inflammatory microenvironment and cancer initiation as the key concept of the cancer-inducing niche responsible for the development of CSC.
en-copyright=
kn-copyright=

en-aut-name=AfifySaid M.
en-aut-sei=Afify
en-aut-mei=Said M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
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=2
ORCID=

affil-num=1
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=2
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
en-keyword=cancer stem cells
kn-keyword=cancer stem cells
en-keyword=cancer-inducing niche
kn-keyword=cancer-inducing niche
en-keyword=chronic inflammation
kn-keyword=chronic inflammation
en-keyword=induced pluripotent stem cells
kn-keyword=induced pluripotent stem cells
en-keyword=stem cell
kn-keyword=stem cell
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=69
cd-vols=
no-issue=3
article-no=
start-page=145
end-page=153
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=Eosinophil Cationic Protein Shows Survival Effect on H9c2 Cardiac Myoblast Cells with Enhanced Phosphorylation of ERK and Akt/GSK-3β under Oxidative Stress
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Eosinophil cationic protein (ECP) is well known as a cationic protein contained in the basic granules of activated eosinophils. Recent studies have reported that ECP exhibits novel activities on various types of cells, including rat neonatal cardiomyocytes. Here we evaluated the effects of ECP on rat cardiac myoblast H9c2 cells. Our results showed that ECP enhanced the survival of the cells, in part by promoting the ERK and Akt/GSK-3β signaling pathways. ECP attenuated the cytotoxic effects of H2O2 on H9c2 cells as well as the production of reactive oxygen species, the number of apoptotic cells and caspase 3/7 activity in the cells. In conclusion, ECP activated the ERK and Akt/GSK-3β pathways, resulting in anti-oxidative effects on H9c2 cells that attenuated apoptosis.
en-copyright=
kn-copyright=

en-aut-name=IshiiHiroko
en-aut-sei=Ishii
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KamikawaShigeshi
en-aut-sei=Kamikawa
en-aut-mei=Shigeshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=HirohataSatoshi
en-aut-sei=Hirohata
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MizutaniAkifumi
en-aut-sei=Mizutani
en-aut-mei=Akifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=AbeKoji
en-aut-sei=Abe
en-aut-mei=Koji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
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=6
ORCID=

en-aut-name=OohashiToshitaka
en-aut-sei=Oohashi
en-aut-mei=Toshitaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=NinomiyaYoshifumi
en-aut-sei=Ninomiya
en-aut-mei=Yoshifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

affil-num=1
en-affil=
kn-affil=Departments of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine

affil-num=2
en-affil=
kn-affil=Departments of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine

affil-num=3
en-affil=
kn-affil=Departments of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine

affil-num=4
en-affil=
kn-affil=Department of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University

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

affil-num=6
en-affil=
kn-affil=Department of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University

affil-num=7
en-affil=
kn-affil=Departments of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine

affil-num=8
en-affil=
kn-affil=Departments of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine
en-keyword=ECP
kn-keyword=ECP
en-keyword=reactive oxygen species
kn-keyword=reactive oxygen species
en-keyword=Akt
kn-keyword=Akt
en-keyword=ERK
kn-keyword=ERK
END

start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=9
article-no=
start-page=e107976
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20140929
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Efficient Drug Delivery of Paclitaxel Glycoside: A Novel Solubility Gradient Encapsulation into Liposomes Coupled with Immunoliposomes Preparation
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Although the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpressing cancer cells and showed more rapid suppression of cell growth. The immunoliposomes strongly inhibited the tumor growth of HT-29 cells xenografted in nude mice. Notably, mice survived when treated with the immunoliposomes formulation, even when administered at a lethal dose of 7-glucosyloxyacetylpaclitaxel in vivo. This data successfully demonstrates immunoliposomes as a promising candidate for the efficient delivery of paclitaxel glycoside.
en-copyright=
kn-copyright=

en-aut-name=ShigehiroTsukasa
en-aut-sei=Shigehiro
en-aut-mei=Tsukasa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=KasaiTomonari
en-aut-sei=Kasai
en-aut-mei=Tomonari
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MurakamiMasaharu
en-aut-sei=Murakami
en-aut-mei=Masaharu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SekharSreeja C.
en-aut-sei=Sekhar
en-aut-mei=Sreeja C.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=TominagaYuki
en-aut-sei=Tominaga
en-aut-mei=Yuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=OkadaMasashi
en-aut-sei=Okada
en-aut-mei=Masashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KudohTakayuki
en-aut-sei=Kudoh
en-aut-mei=Takayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=MizutaniAkifumi
en-aut-sei=Mizutani
en-aut-mei=Akifumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=MurakamiHiroshi
en-aut-sei=Murakami
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=SalomonDavid S.
en-aut-sei=Salomon
en-aut-mei=David S.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=MikuniKatsuhiko
en-aut-sei=Mikuni
en-aut-mei=Katsuhiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
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kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University

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kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University

affil-num=3
en-affil=
kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University

affil-num=4
en-affil=
kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University

affil-num=5
en-affil=
kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University

affil-num=6
en-affil=
kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University

affil-num=7
en-affil=
kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University

affil-num=8
en-affil=
kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University

affil-num=9
en-affil=
kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University

affil-num=10
en-affil=
kn-affil=Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute

affil-num=11
en-affil=
kn-affil=Ensuiko Sugar Refining Co., Ltd.

affil-num=12
en-affil=
kn-affil=Faculty of Life Science, Kurashiki University of Science and the Arts

affil-num=13
en-affil=
kn-affil=Faculty of Science, Okayama University of Science

affil-num=14
en-affil=
kn-affil=Department of Biotechnology, Graduate School of Natural Science and Technology, Okayama University
END

start-ver=1.4
cd-journal=joma
no-vol=7
cd-vols=
no-issue=4
article-no=
start-page=e33544
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=20120412
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer stem cells (CSCs) are capable of continuous proliferation and self-renewal and are proposed to play significant roles in oncogenesis, tumor growth, metastasis and cancer recurrence. CSCs are considered derived from normal stem cells affected by the tumor microenvironment although the mechanism of development is not clear yet. In 2007, Yamanaka's group succeeded in generating Nanog mouse induced pluripotent stem (miPS) cells, in which green fluorescent protein (GFP) has been inserted into the 5'-untranslated region of the Nanog gene. Usually, iPS cells, just like embryonic stem cells, are considered to be induced into progenitor cells, which differentiate into various normal phenotypes depending on the normal niche. We hypothesized that CSCs could be derived from Nanog miPS cells in the conditioned culture medium of cancer cell lines, which is a mimic of carcinoma microenvironment. As a result, the Nanog miPS cells treated with the conditioned medium of mouse Lewis lung carcinoma acquired characteristics of CSCs, in that they formed spheroids expressing GFP in suspension culture, and had a high tumorigenicity in Balb/c nude mice exhibiting angiogenesis in vivo. In addition, these iPS-derived CSCs had a capacity of self-renewal and expressed the marker genes, Nanog, Rex1, Eras, Esg1 and Cripto, associated with stem cell properties and an undifferentiated state. Thus we concluded that a model of CSCs was originally developed from miPS cells and proposed the conditioned culture medium of cancer cell lines might perform as niche for producing CSCs. The model of CSCs and the procedure of their establishment will help study the genetic alterations and the secreted factors in the tumor microenvironment which convert miPS cells to CSCs. Furthermore, the identification of potentially bona fide markers of CSCs, which will help the development of novel anti-cancer therapies, might be possible though the CSC model.
en-copyright=
kn-copyright=

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END