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Article ; Online: Publisher Correction: Hypoblast from human pluripotent stem cells regulates epiblast development.

Okubo, Takumi / Rivron, Nicolas / Kabata, Mio / Masaki, Hideki / Kishimoto, Keiko / Semi, Katsunori / Nakajima-Koyama, May / Kunitomi, Haruko / Kaswandy, Belinda / Sato, Hideyuki / Nakauchi, Hiromitsu / Woltjen, Knut / Saitou, Mitinori / Sasaki, Erika / Yamamoto, Takuya / Takashima, Yasuhiro

Nature

2024 Volume 626, Issue 8001, Page(s) E21

Language	English
Publishing date	2024-02-10
Publishing country	England
Document type	Published Erratum
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-024-07166-w
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Article ; Online: Current state and outlook for drug repositioning anticipated in the field of ovarian cancer.

Kobayashi, Yusuke / Banno, Kouji / Kunitomi, Haruko / Tominaga, Eiichiro / Aoki, Daisuke

Journal of gynecologic oncology

2018 Volume 30, Issue 1, Page(s) e10

Abstract: Ovarian cancer is the seventh most common cancer and the eighth most common cause of cancer mortality in women. Although standard chemotherapy is the established treatment for ovarian cancer, the prognosis remains poor, and it is highly anticipated that ... ...

Abstract	Ovarian cancer is the seventh most common cancer and the eighth most common cause of cancer mortality in women. Although standard chemotherapy is the established treatment for ovarian cancer, the prognosis remains poor, and it is highly anticipated that new drugs will be developed. New drugs, such as humanized anti-vascular endothelial growth factor monoclonal antibodies and poly ADP-ribose polymerase inhibitors, are expected to improve clinical outcomes of ovarian cancer. However, long-term, costly research is required to develop such new drugs, and soaring national healthcare costs are becoming a concern worldwide. In this social context, drug repositioning, wherein existing drugs are used to develop drugs with new indications for other diseases, has recently gained attention. Because trials have already confirmed the safety in humans and the pharmacokinetics of such drugs, the development period is shorter than the conventional development of a new drug, thereby reducing costs. This review discusses the available basic experimental and clinical data on drugs used for other types of cancer for which drug repositioning is anticipated to repurpose the drug for the treatment of ovarian cancer. These include statins, which are used to treat dyslipidemia; bisphosphonate, which is used to treat osteoporosis; metformin, which is used to treat diabetes; non-steroidal anti-inflammatory drugs; ivermectin, an antiparasitic agent; and itraconazole, an anti-fungal agent. These drugs will play an important role in future drug repositioning strategies for ovarian cancer. Furthermore, drug repositioning is anticipated to extend not only to ovarian cancer treatment but also to ovarian cancer prevention.
MeSH term(s)	Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Antifungal Agents/pharmacology ; Antiparasitic Agents/pharmacology ; Carcinoma, Ovarian Epithelial/drug therapy ; Diphosphonates/pharmacology ; Drug Repositioning/economics ; Drug Repositioning/trends ; Female ; Health Care Costs ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Itraconazole/pharmacology ; Ivermectin/pharmacology ; Metformin/pharmacology ; Ovarian Neoplasms/drug therapy
Chemical Substances	Anti-Inflammatory Agents, Non-Steroidal ; Antifungal Agents ; Antiparasitic Agents ; Diphosphonates ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Itraconazole (304NUG5GF4) ; Ivermectin (70288-86-7) ; Metformin (9100L32L2N)
Language	English
Publishing date	2018-10-10
Publishing country	Korea (South)
Document type	Journal Article ; Review
ZDB-ID	2478405-9
ISSN	2005-0399 ; 2005-0380
ISSN (online)	2005-0399
ISSN	2005-0380
DOI	10.3802/jgo.2019.30.e10
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Article ; Online: Profiling of the Causative Bacteria in Infected Lymphocysts after Lymphadenectomy for Gynecologic Cancer by Pyrosequencing the 16S Ribosomal RNA Gene Using Next-Generation Sequencing Technology.

Nogami, Yuya / Banno, Kouji / Adachi, Masataka / Kunitomi, Haruko / Kobayashi, Yusuke / Tominaga, Eiichiro / Aoki, Daisuke

Infectious diseases in obstetrics and gynecology

2019 Volume 2019, Page(s) 9326285

Abstract: Background: Surgery for gynecologic cancer with lymphadenectomy and pelvic radiotherapy can produce lymphoceles that sometimes complicate with infection, resulting in abscesses. The true pathogenic bacteria of abscesses are not always found because of ... ...

Abstract	Background: Surgery for gynecologic cancer with lymphadenectomy and pelvic radiotherapy can produce lymphoceles that sometimes complicate with infection, resulting in abscesses. The true pathogenic bacteria of abscesses are not always found because of false-negative results due to administered antibiotics and difficulty with detection, including for anaerobic bacteria. Analyzing bacteria flora by next-generation sequencing (NGS) using 16S ribosomal DNA may reveal the true pathogenic bacteria in abscesses. This is the first report on causative pathogens for infectious lymphocele using this technology. Methods: The subjects were patients who developed infectious lymphocele after surgery for gynecologic cancer at our hospital from July 2015 to September 2016. NGS analyses of bacterial flora were performed using specimens preserved at -80°C. Two steps of PCR were performed for purified DNA samples to obtain sequence libraries. Processing of sequence data, including operational taxonomic unit (OTU) definition, taxonomy assignment, and an OTU BLAST search were performed. All patients gave written informed consent and the study was approved by the institutional research ethics committee. Results: Six patients underwent puncture and drainage. The result in most cases indicated a single causative pathogen, including
MeSH term(s)	DNA, Bacterial ; DNA, Ribosomal ; Female ; Genital Neoplasms, Female/complications ; Genital Neoplasms, Female/surgery ; High-Throughput Nucleotide Sequencing ; Humans ; Lymph Node Excision/adverse effects ; Lymphocele/etiology ; Lymphocele/microbiology
Chemical Substances	DNA, Bacterial ; DNA, Ribosomal
Language	English
Publishing date	2019-02-21
Publishing country	Egypt
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1176776-5
ISSN	1098-0997 ; 1064-7449
ISSN (online)	1098-0997
ISSN	1064-7449
DOI	10.1155/2019/9326285
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Article ; Online: H1FOO-DD promotes efficiency and uniformity in reprogramming to naive pluripotency.

Stem cell reports

2024 Volume 19, Issue 5, Page(s) 710–728

Abstract: Heterogeneity among both primed and naive pluripotent stem cell lines remains a major unresolved problem. Here we show that expressing the maternal-specific linker histone H1FOO fused to a destabilizing domain (H1FOO-DD), together with OCT4, SOX2, KLF4, ... ...

Abstract	Heterogeneity among both primed and naive pluripotent stem cell lines remains a major unresolved problem. Here we show that expressing the maternal-specific linker histone H1FOO fused to a destabilizing domain (H1FOO-DD), together with OCT4, SOX2, KLF4, and LMYC, in human somatic cells improves the quality of reprogramming to both primed and naive pluripotency. H1FOO-DD expression was associated with altered chromatin accessibility around pluripotency genes and with suppression of the innate immune response. Notably, H1FOO-DD generates naive induced pluripotent stem cells with lower variation in transcriptome and methylome among clones and a more uniform and superior differentiation potency. Furthermore, we elucidated that upregulation of FKBP1A, driven by these five factors, plays a key role in H1FOO-DD-mediated reprogramming.
MeSH term(s)	Kruppel-Like Factor 4 ; Cellular Reprogramming/genetics ; Humans ; Induced Pluripotent Stem Cells/cytology ; Induced Pluripotent Stem Cells/metabolism ; Histones/metabolism ; Cell Differentiation/genetics ; Kruppel-Like Transcription Factors/metabolism ; Kruppel-Like Transcription Factors/genetics ; SOXB1 Transcription Factors/metabolism ; SOXB1 Transcription Factors/genetics ; Chromatin/metabolism ; Pluripotent Stem Cells/metabolism ; Pluripotent Stem Cells/cytology ; Transcription Factors/metabolism ; Transcription Factors/genetics ; Transcriptome
Language	English
Publishing date	2024-05-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2024.04.005
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Article ; Online: Hypoblast from human pluripotent stem cells regulates epiblast development.

Nature

2023 Volume 626, Issue 7998, Page(s) 357–366

Abstract: Recently, several studies using cultures of human embryos together with single-cell RNA-seq analyses have revealed differences between humans and mice, necessitating the study of human ... ...

Abstract	Recently, several studies using cultures of human embryos together with single-cell RNA-seq analyses have revealed differences between humans and mice, necessitating the study of human embryos
MeSH term(s)	Humans ; Cell Differentiation ; Embryo Implantation ; Embryo, Mammalian/cytology ; Embryo, Mammalian/embryology ; Embryo, Mammalian/metabolism ; Embryonic Development/genetics ; Embryonic Development/physiology ; Germ Layers/cytology ; Germ Layers/embryology ; Germ Layers/metabolism ; Pluripotent Stem Cells/cytology ; Interleukin-6/metabolism ; Gastrula/cytology ; Gastrula/embryology ; Amnion/cytology ; Amnion/embryology ; Amnion/metabolism ; Ectoderm/cytology ; Ectoderm/embryology ; Ectoderm/metabolism ; Intercellular Signaling Peptides and Proteins/genetics ; Intercellular Signaling Peptides and Proteins/metabolism ; Otx Transcription Factors/genetics ; Otx Transcription Factors/metabolism
Chemical Substances	Interleukin-6 ; DKK1 protein, human ; OTX2 protein, human ; IL6 protein, human ; Intercellular Signaling Peptides and Proteins ; Otx Transcription Factors
Language	English
Publishing date	2023-12-05
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-023-06871-2
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Article: Response Predictive Markers and Synergistic Agents for Drug Repositioning of Statins in Ovarian Cancer.

Kobayashi, Yusuke / Takeda, Takashi / Kunitomi, Haruko / Chiwaki, Fumiko / Komatsu, Masayuki / Nagai, Shimpei / Nogami, Yuya / Tsuji, Kosuke / Masuda, Kenta / Ogiwara, Hideaki / Sasaki, Hiroki / Banno, Kouji / Aoki, Daisuke

Pharmaceuticals (Basel, Switzerland)

2022 Volume 15, Issue 2

Abstract: In the field of drug repurposing, the use of statins for treating dyslipidemia is considered promising in ovarian cancer treatment based on epidemiological studies and basic research findings. Biomarkers should be established to identify patients who ... ...

Abstract	In the field of drug repurposing, the use of statins for treating dyslipidemia is considered promising in ovarian cancer treatment based on epidemiological studies and basic research findings. Biomarkers should be established to identify patients who will respond to statin treatment to achieve clinical application. In the present study, we demonstrated that statins have a multifaceted mode of action in ovarian cancer and involve pathways other than protein prenylation. To identify biomarkers that predict the response to statins, we subjected ovarian cancer cells to microarray analysis and calculated Pearson's correlation coefficients between gene expression and cell survival after statin treatment. The results showed that
Language	English
Publishing date	2022-01-21
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph15020124
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Article ; Online: The insulin-PI3K-Rac1 axis contributes to terminal adipocyte differentiation through regulation of actin cytoskeleton dynamics.

Kunitomi, Haruko / Oki, Yoshinao / Onishi, Nobuyuki / Kano, Koichiro / Banno, Kouji / Aoki, Daisuke / Saya, Hideyuki / Nobusue, Hiroyuki

Genes to cells : devoted to molecular & cellular mechanisms

2020 Volume 25, Issue 3, Page(s) 165–174

Abstract: Adipocyte differentiation is accompanied by a pronounced change in the actin cytoskeleton characterized by the reorganization of filamentous (F)-actin stress fibers into cortical F-actin structures. We previously showed that depolymerization of F-actin ... ...

Abstract	Adipocyte differentiation is accompanied by a pronounced change in the actin cytoskeleton characterized by the reorganization of filamentous (F)-actin stress fibers into cortical F-actin structures. We previously showed that depolymerization of F-actin stress fibers induced by inactivation of RhoA-ROCK (Rho-associated kinase) signaling acts as a trigger for adipocyte differentiation. The relevance and underlying mechanism of the formation of cortical F-actin structures from depolymerized actin during adipocyte differentiation have remained unclear, however. We have now examined the mechanistic relation between actin dynamics and adipogenic induction. Transient exposure to the actin-depolymerizing agent latrunculin A (LatA) supported the formation of adipocyte-associated cortical actin structures and the completion of terminal adipocyte differentiation in the presence of insulin, whereas long-term exposure to LatA prevented such actin reorganization as well as terminal adipogenesis. Moreover, these effects of insulin were prevented by inhibition of phosphatidylinositol 3-kinase (PI3K)-Rac1 signaling and the actin-related protein 2/3 (Arp2/3) complex which is a critical component of the cortical actin networks. Our findings thus suggest that the insulin-PI3K-Rac1 axis leads to the formation of adipocyte-associated cortical actin structures which is essential for the completion of adipocyte differentiation.
MeSH term(s)	Actin Cytoskeleton/metabolism ; Adipocytes/metabolism ; Animals ; Cell Differentiation ; Cells, Cultured ; Insulin/metabolism ; Mice ; Neuropeptides/metabolism ; Phosphatidylinositol 3-Kinase/metabolism ; rac1 GTP-Binding Protein/metabolism
Chemical Substances	Insulin ; Neuropeptides ; Rac1 protein, mouse ; Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; rac1 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2020-01-29
Publishing country	England
Document type	Journal Article
ZDB-ID	1330000-3
ISSN	1365-2443 ; 1356-9597
ISSN (online)	1365-2443
ISSN	1356-9597
DOI	10.1111/gtc.12747
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Article ; Online: LAMC1 is a prognostic factor and a potential therapeutic target in endometrial cancer.

Kunitomi, Haruko / Kobayashi, Yusuke / Wu, Ren Chin / Takeda, Takashi / Tominaga, Eiichiro / Banno, Kouji / Aoki, Daisuke

Journal of gynecologic oncology

2019 Volume 31, Issue 2, Page(s) e11

Abstract: Objective: With the emerging significance of genetic profiles in the management of endometrial cancer, the identification of tumor-driving genes with prognostic value is a pressing need. The : Methods: We evaluated the immunohistochemical expression ... ...

Abstract	Objective: With the emerging significance of genetic profiles in the management of endometrial cancer, the identification of tumor-driving genes with prognostic value is a pressing need. The Methods: We evaluated the immunohistochemical expression of LAMC1 in atypical endometrial hyperplasia and endometrial cancer. Within the endometrial cancer cases, we analyzed the association of LAMC1 overexpression with clinicopathological factors and prognosis. Furthermore, to indentify genes influenced by LAMC1 overexpression, we transfected HEC50B and SPAC-S cells with siRNA targeting Results: While none of the atypical endometrial hyperplasia specimens exhibited LAMC1 overexpression, endometrial cancer possessed a significantly higher LAMC1 overexpression rate. LAMC1 overexpression was strongly associated with histological type, lymphovascular space invasion, lymph node metastasis, advanced International Federation of Gynecology and Obstetrics stage, and poor overall survival in endometrial cancer. Gene expression microarray analysis identified 8 genes correlated with tumor progression ( Conclusion: LAMC1 overexpression is a potent biomarker for identifying endometrial cancer patients needing aggressive adjuvant therapy. We elucidated 8 candidate genes that may mediate progression of LAMC1 overexpressing cancer. Further investigation of the underlying mechanism should lead to the discovery of new therapeutic targets.
MeSH term(s)	Cell Line, Tumor ; Chemotherapy, Adjuvant ; Endometrial Hyperplasia/genetics ; Endometrial Neoplasms/chemistry ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/pathology ; Endometrium/chemistry ; Endometrium/pathology ; Female ; Gene Expression ; Gene Silencing ; Humans ; Laminin/analysis ; Laminin/genetics ; Lymphatic Metastasis/genetics ; Neoplasm Invasiveness/genetics ; Neoplasm Staging ; Prognosis ; Protein Array Analysis ; RNA, Small Interfering/genetics ; Survival Rate ; Transfection
Chemical Substances	Laminin ; RNA, Small Interfering ; laminin gamma 1
Language	English
Publishing date	2019-08-21
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2478405-9
ISSN	2005-0399 ; 2005-0380
ISSN (online)	2005-0399
ISSN	2005-0380
DOI	10.3802/jgo.2020.31.e11
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Article ; Online: ROCK Inhibition Induces Terminal Adipocyte Differentiation and Suppresses Tumorigenesis in Chemoresistant Osteosarcoma Cells.

Takahashi, Nobuhiro / Nobusue, Hiroyuki / Shimizu, Takatsune / Sugihara, Eiji / Yamaguchi-Iwai, Sayaka / Onishi, Nobuyuki / Kunitomi, Haruko / Kuroda, Tatsuo / Saya, Hideyuki

Cancer research

2019 Volume 79, Issue 12, Page(s) 3088–3099

Abstract: Tumors comprise heterogeneous cell types including cancer stem cells (CSC), progenitor cells, and differentiated cells. Chemoresistance is a potential cause of relapse and a key characteristic of CSC, but the development of novel therapeutic approaches ... ...

Abstract	Tumors comprise heterogeneous cell types including cancer stem cells (CSC), progenitor cells, and differentiated cells. Chemoresistance is a potential cause of relapse and a key characteristic of CSC, but the development of novel therapeutic approaches for targeting these cells has been limited. We previously established osteosarcoma-initiating (OSi) cells by introducing the gene for c-Myc into bone marrow stromal cells of
MeSH term(s)	Actin Cytoskeleton/drug effects ; Adipocytes/cytology ; Adipocytes/drug effects ; Adipocytes/metabolism ; Animals ; Antineoplastic Agents/pharmacology ; Bone Neoplasms/metabolism ; Bone Neoplasms/pathology ; Bone Neoplasms/prevention & control ; Carcinogenesis/drug effects ; Carcinogenesis/metabolism ; Carcinogenesis/pathology ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Drug Resistance, Neoplasm/drug effects ; Male ; Mesenchymal Stem Cells/cytology ; Mesenchymal Stem Cells/drug effects ; Mesenchymal Stem Cells/metabolism ; Mice ; Mice, Inbred C57BL ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Osteosarcoma/metabolism ; Osteosarcoma/pathology ; Osteosarcoma/prevention & control ; rho-Associated Kinases/antagonists & inhibitors
Chemical Substances	Antineoplastic Agents ; rho-Associated Kinases (EC 2.7.11.1)
Language	English
Publishing date	2019-04-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-18-2693
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Article ; Online: Warburg effect in Gynecologic cancers.

Kobayashi, Yusuke / Banno, Kouji / Kunitomi, Haruko / Takahashi, Takayuki / Takeda, Takashi / Nakamura, Kanako / Tsuji, Kosuke / Tominaga, Eiichiro / Aoki, Daisuke

The journal of obstetrics and gynaecology research

2018 Volume 45, Issue 3, Page(s) 542–548

Abstract: Mammalian cells produce energy by oxidative phosphorylation under aerobic conditions. However, in the 1920s, Otto Warburg reported the so-called "Warburg effect" in which cancer cells produce ATP that is biased toward glycolysis rather than mitochondrial ...

Abstract	Mammalian cells produce energy by oxidative phosphorylation under aerobic conditions. However, in the 1920s, Otto Warburg reported the so-called "Warburg effect" in which cancer cells produce ATP that is biased toward glycolysis rather than mitochondrial oxidative phosphorylation not only in anaerobic environment but also in aerobic environment. Glucose is converted into lactate without going into mitochondria after being metabolized in glycolysis. Compared with oxidative phosphorylation, the glycolysis has a faster ATP production rate but it is very inefficient, resulting in cancer cells consuming a large amount of glucose. Increased glucose metabolism has become a biomarker for cancer cells and has led to the development of positron emission tomography with fluorodeoxyglucose. Till date, the Warburg effect has been an inefficient system for cancer cells with regard to efficient energy production, but since the consumption of oxygen can be suppressed as the tumor grows in mass, it is thought that the Warburg effect is advantageous in this situation wherein the tumor can increase despite the lack of vessels. In addition, an increased lactate by the glycolysis causes acidosis in the microenvironment of tissues, which is thought to damage the surrounding normal tissues and favor the invasion and metastasis of cancer. Thus, Warburg effect is one of the key mechanisms for cancer development and will be the next promising target. In this review, we introduce key players that can be targeted in the Warburg effect and outline the prospects of treatment, targeting the Warburg effect in gynecological cancer.
MeSH term(s)	Female ; Genital Neoplasms, Female/metabolism ; Genital Neoplasms, Female/pathology ; Glycolysis/physiology ; Humans ; Mitochondria/metabolism ; Mitochondria/pathology ; Neoplasms/metabolism ; Neoplasms/pathology ; Oxidative Phosphorylation
Language	English
Publishing date	2018-12-03
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	1327307-3
ISSN	1447-0756 ; 1341-8076
ISSN (online)	1447-0756
ISSN	1341-8076
DOI	10.1111/jog.13867
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