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=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=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=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=10
cd-vols=
no-issue=1
article-no=
start-page=9955
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200622
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Signaling Inhibitors Accelerate the Conversion of mouse iPS Cells into Cancer Stem Cells in the Tumor Microenvironment
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Cancer stem cells (CSCs) are a class of cancer cells characterized by self-renewal, differentiation and tumorigenic potential. We previously established a model of CSCs by culturing mouse induced pluripotent stem cells (miPSCs) for four weeks in the presence of a conditioned medium (CM) of cancer cell lines, which functioned as the tumor microenvironment. Based on this methodology of developing CSCs from miPSCs, we assessed the risk of 110 non-mutagenic chemical compounds, most of which are known as inhibitors of cytoplasmic signaling pathways, as potential carcinogens. We treated miPSCs with each compound for one week in the presence of a CM of Lewis lung carcinoma (LLC) cells. However, one-week period was too short for the CM to convert miPSCs into CSCs. Consequently, PDO325901 (MEK inhibitor), CHIR99021 (GSK-3 beta inhibitor) and Dasatinib (Abl, Src and c-Kit inhibitor) were found to confer miPSCs with the CSC phenotype in one week. The tumor cells that survived exhibited stemness markers, spheroid formation and tumorigenesis in Balb/c nude mice. Hence, we concluded that the three signal inhibitors accelerated the conversion of miPSCs into CSCs. Similarly to our previous study, we found that the PI3K-Akt signaling pathway was upregulated in the CSCs. Herein, we focused on the expression of relative genes after the treatment with these three inhibitors. Our results demonstrated an increased expression of pik3ca, pik3cb, pik3r5 and pik3r1 genes indicating class IA PI3K as the responsible signaling pathway. Hence, AKT phosphorylation was found to be up-regulated in the obtained CSCs. Inhibition of Erk1/2, tyrosine kinase, and/or GSK-3 beta was implied to be involved in the enhancement of the PI3K-AKT signaling pathway in the undifferentiated cells, resulting in the sustained stemness, and subsequent conversion of miPSCs into CSCs in the tumor microenvironment.	
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=XuYanning
en-aut-sei=Xu
en-aut-mei=Yanning
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=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=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=MahmudHafizah
en-aut-sei=Mahmud
en-aut-mei=Hafizah
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
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=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=KumonKazuki
en-aut-sei=Kumon
en-aut-mei=Kazuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=UesakiRyo
en-aut-sei=Uesaki
en-aut-mei=Ryo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
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=11
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=12
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=13
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=14
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=15
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=16
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=17
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=18
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=19
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=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, 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=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=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

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

affil-num=13
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

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

affil-num=15
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=

affil-num=16
en-affil=Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
kn-affil=

affil-num=17
en-affil=Department of Pathology, Tianjin Central Hospital of Gynecology Obstetrics
kn-affil=

affil-num=18
en-affil=Department of Pathology, Shanxi Key Laboratory of Carcinogenesis and Translational Research on Esophageal Cancer, Shanxi Medical University
kn-affil=

affil-num=19
en-affil=Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University
kn-affil=
en-keyword=2020-06-22
kn-keyword=2020-06-22
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=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=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=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210403
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Cooperation between NRF2-mediated transcription and MDIG-dependent epigenetic modifications in arsenic-induced carcinogenesis and cancer stem cells
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Environmental exposure to arsenic, a well-established carcinogen linked to a number of human cancers, is a public health concern in many areas of the world. Despite extensive studies on the molecular mechanisms of arsenic-induced carcinogenesis, how initial cellular responses, such as activation of stress kinases and the generation of reactive oxygen species, converge to affect the transcriptional and/or epigenetic reprogramming required for the malignant transformation of normal cells or normal stem cells remains to be elucidated. In this review, we discuss some recent discoveries showing how the transcription factor NRF2 and an epigenetic regulator, MDIG, contribute to the arsenic-induced generation of cancer stem-like cells (CSCs) as determined by applying CRISPR-Cas9 gene editing and chromosome immunoprecipitation followed by DNA sequencing (ChIP-seq).
en-copyright=
kn-copyright=

en-aut-name=BiZhuoyue
en-aut-sei=Bi
en-aut-mei=Zhuoyue
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=ZhangQian
en-aut-sei=Zhang
en-aut-mei=Qian
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=FuYao
en-aut-sei=Fu
en-aut-mei=Yao
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=WadgaonkarPriya
en-aut-sei=Wadgaonkar
en-aut-mei=Priya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=QiuYiran
en-aut-sei=Qiu
en-aut-mei=Yiran
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=AlmutairyBandar
en-aut-sei=Almutairy
en-aut-mei=Bandar
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=XuLiping
en-aut-sei=Xu
en-aut-mei=Liping
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=ZhangWenxuan
en-aut-sei=Zhang
en-aut-mei=Wenxuan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=ThakurChitra
en-aut-sei=Thakur
en-aut-mei=Chitra
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

en-aut-name=ChenFei
en-aut-sei=Chen
en-aut-mei=Fei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=

affil-num=1
en-affil=Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University
kn-affil=

affil-num=2
en-affil=Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University
kn-affil=

affil-num=3
en-affil=Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University
kn-affil=

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

affil-num=5
en-affil=Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University
kn-affil=

affil-num=6
en-affil=Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University
kn-affil=

affil-num=7
en-affil=Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University
kn-affil=

affil-num=8
en-affil=Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University
kn-affil=

affil-num=9
en-affil=Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University
kn-affil=

affil-num=10
en-affil=Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University
kn-affil=

affil-num=11
en-affil=Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University
kn-affil=
en-keyword=Arsenic
kn-keyword=Arsenic
en-keyword=NRF2
kn-keyword=NRF2
en-keyword=MDIG
kn-keyword=MDIG
en-keyword=Cancer stem cells
kn-keyword=Cancer stem cells
en-keyword=Carcinogenesis
kn-keyword=Carcinogenesis
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=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=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=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=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=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=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=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