Faculty Profiles - KASAI Tomonari

写真a

KASAI Tomonari

Organization

Graduate School of Engineering Applied Energy 2 Designated Associate Professor

Degree 1

博士（農学）（ 2007.3 岡山大学）

To the head of Degree.▲

Research Areas 1

Life Science / Biomedical engineering

To the head of Research Areas.▲

Research History 1

Nagoya University Graduate School of Engineering Designated Associate Professor

2024.9

To the head of Research History.▲

Papers 50

The current status and novel advances of boron neutron capture therapy clinical trials. Reviewed International journal Open Access

Tianyun Zhou, Kazuyo Igawa, Tomonari Kasai, Takuya Sadahira, Wei Wang, Tomofumi Watanabe, Kensuke Bekku, Satoshi Katayama, Takehiro Iwata, Tadashi Hanafusa, Abai Xu, Motoo Araki, Hiroyuki Michiue, Peng Huang

American journal of cancer research Vol. 14 ( 2 ) page： 429 - 447 2024

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Language：English Publishing type：Research paper (scientific journal)

Boron neutron capture therapy (BNCT) is a treatment method that focuses on improving the cure rate of patients with cancer who are difficult to treat using traditional clinical methods. By utilizing the high neutron absorption cross-section of boron, material rich in boron inside tumor cells can absorb neutrons and release high-energy ions, thereby destroying tumor cells. Owing to the short range of alpha particles, this method can precisely target tumor cells while minimizing the inflicted damage to the surrounding normal tissues, making it a potentially advantageous method for treating tumors. Globally, institutions have progressed in registered clinical trials of BNCT for multiple body parts. This review summarized the current achievements in registered clinical trials, Investigator-initiated clinical trials, aimed to integrate the latest clinical research literature on BNCT and to shed light on future study directions.

Open Access

PubMed
Particle and Heavy Ion Transport Code System‐Based Microdosimetry for the Development of Boron Agents for Boron Neutron Capture Therapy Reviewed

Takafumi Shigehira, Tadashi Hanafusa, Kazuyo Igawa, Tomonari Kasai, Shuichi Furuya, Hisakazu Nishimori, Yoshinobu Maeda, Hiroyuki Michiue, Atsushi Fujimura

Advanced Theory and Simulations 2023.4

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Publishing type：Research paper (scientific journal)

DOI： 10.1002/adts.202300163
Deep Learning of Phase-Contrast Images of Cancer Stem Cells Using a Selected Dataset of High Accuracy Value Using Conditional Generative Adversarial Networks. Reviewed International journal Open Access

Zaijun Zhang, Hiroaki Ishihata, Ryuto Maruyama, Tomonari Kasai, Hiroyuki Kameda, Tomoyasu Sugiyama

International journal of molecular sciences Vol. 24 ( 6 ) 2023.3

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Artificial intelligence (AI) technology for image recognition has the potential to identify cancer stem cells (CSCs) in cultures and tissues. CSCs play an important role in the development and relapse of tumors. Although the characteristics of CSCs have been extensively studied, their morphological features remain elusive. The attempt to obtain an AI model identifying CSCs in culture showed the importance of images from spatially and temporally grown cultures of CSCs for deep learning to improve accuracy, but was insufficient. This study aimed to identify a process that is significantly efficient in increasing the accuracy values of the AI model output for predicting CSCs from phase-contrast images. An AI model of conditional generative adversarial network (CGAN) image translation for CSC identification predicted CSCs with various accuracy levels, and convolutional neural network classification of CSC phase-contrast images showed variation in the images. The accuracy of the AI model of CGAN image translation was increased by the AI model built by deep learning of selected CSC images with high accuracy previously calculated by another AI model. The workflow of building an AI model based on CGAN image translation could be useful for the AI prediction of CSCs.

DOI： 10.3390/ijms24065323

Open Access

PubMed
Temporal and Locational Values of Images Affecting the Deep Learning of Cancer Stem Cell Morphology Reviewed Open Access

Yumi Hanai, Hiroaki Ishihata, Zaijun Zhang, Ryuto Maruyama, Tomonari Kasai, Hiroyuki Kameda, Tomoyasu Sugiyama

Biomedicines Vol. 10 ( 5 ) page： 941 - 941 2022.4

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Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Deep learning is being increasingly applied for obtaining digital microscopy image data of cells. Well-defined annotated cell images have contributed to the development of the technology. Cell morphology is an inherent characteristic of each cell type. Moreover, the morphology of a cell changes during its lifetime because of cellular activity. Artificial intelligence (AI) capable of recognizing a mouse-induced pluripotent stem (miPS) cell cultured in a medium containing Lewis lung cancer (LLC) cell culture-conditioned medium (cm), miPS-LLCcm cell, which is a cancer stem cell (CSC) derived from miPS cell, would be suitable for basic and applied science. This study aims to clarify the limitation of AI models constructed using different datasets and the versatility improvement of AI models. The trained AI was used to segment CSC in phase-contrast images using conditional generative adversarial networks (CGAN). The dataset included blank cell images that were used for training the AI but they did not affect the quality of predicting CSC in phase contrast images compared with the dataset without the blank cell images. AI models trained using images of 1-day culture could predict CSC in images of 2-day culture; however, the quality of the CSC prediction was reduced. Convolutional neural network (CNN) classification indicated that miPS-LLCcm cell image classification was done based on cultivation day. By using a dataset that included images of each cell culture day, the prediction of CSC remains to be improved. This is useful because cells do not change the characteristics of stem cells owing to stem cell marker expression, even if the cell morphology changes during culture.

DOI： 10.3390/biomedicines10050941

Open Access
Self-assembling A6K peptide nanotubes as a mercaptoundecahydrododecaborate (BSH) delivery system for boron neutron capture t (BNCT). Reviewed International journal Open Access

Hiroyuki Michiue, Mizuki Kitamatsu, Asami Fukunaga, Nobushige Tsuboi, Atsushi Fujimura, Hiroaki Matsushita, Kazuyo Igawa, Tomonari Kasai, Natsuko Kondo, Hideki Matsui, Shuichi Furuya

Journal of controlled release : official journal of the Controlled Release Society Vol. 330 page： 788 - 796 2020.11

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Boron neutron capture therapy (BNCT) is a tumor selective therapy, the effectiveness of which depends on sufficient 10B delivery to and accumulation in tumors. In this study, we used self-assembling A6K peptide nanotubes as boron carriers and prepared new boron agents by simple mixing of A6K and BSH. BSH has been used to treat malignant glioma patients in clinical trials and its drug safety and availability have been confirmed; however, its contribution to BNCT efficacy is low. A6K nanotube delivery improved two major limitations of BSH, including absence of intracellular transduction and non-specific drug delivery to tumor tissue. Varying the A6K peptide and BSH mixture ratio produced materials with different morphologies-determined by electron microscopy-and intracellular transduction efficiencies. We investigated the A6K/BSH 1:10 mixture ratio and found high intracellular boron uptake with no toxicity. Microscopy observation showed intracellular localization of A6K/BSH in the perinuclear region and endosome in human glioma cells. The intracellular boron concentration using A6K/BSH was almost 10 times higher than that of BSH. The systematic administration of A6K/BSH via mouse tail vein showed tumor specific accumulation in a mouse brain tumor model with immunohistochemistry and pharmacokinetic study. Neutron irradiation of glioma cells treated with A6K/BSH showed the inhibition of cell proliferation in a colony formation assay. Boron delivery using A6K peptide provides a unique and simple strategy for next generation BNCT drugs.

DOI： 10.1016/j.jconrel.2020.11.001

Open Access

PubMed
Deep Learning of Cancer Stem Cell Morphology Using Conditional Generative Adversarial Networks Reviewed Open Access

Saori Aida, Junpei Okugawa, Serena Fujisaka, Tomonari Kasai, Hiroyuki Kameda, Tomoyasu Sugiyama

Biomolecules Vol. 10 ( 6 ) page： 931 - 931 2020.6

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Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Deep-learning workflows of microscopic image analysis are sufficient for handling the contextual variations because they employ biological samples and have numerous tasks. The use of well-defined annotated images is important for the workflow. Cancer stem cells (CSCs) are identified by specific cell markers. These CSCs were extensively characterized by the stem cell (SC)-like gene expression and proliferation mechanisms for the development of tumors. In contrast, the morphological characterization remains elusive. This study aims to investigate the segmentation of CSCs in phase contrast imaging using conditional generative adversarial networks (CGAN). Artificial intelligence (AI) was trained using fluorescence images of the Nanog-Green fluorescence protein, the expression of which was maintained in CSCs, and the phase contrast images. The AI model segmented the CSC region in the phase contrast image of the CSC cultures and tumor model. By selecting images for training, several values for measuring segmentation quality increased. Moreover, nucleus fluorescence overlaid-phase contrast was effective for increasing the values. We show the possibility of mapping CSC morphology to the condition of undifferentiation using deep-learning CGAN workflows.

DOI： 10.3390/biom10060931

Open Access
Conditional Generative Adversarial Networks to Model iPSC-Derived Cancer Stem Cells Reviewed International journal

Saori Aida, Hiroyuki Kameda, Sakae Nishisako, Tomonari Kasai, Atsushi Sato, Tomoyasu Sugiyama

Journal of Advanced Computational Intelligence and Intelligent Informatics Vol. 24 ( 1 ) page： 134 - 141 2020.1

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Language：English Publishing type：Research paper (scientific journal) Publisher：FUJI TECHNOLOGY PRESS LTD.

DOI： 10.20965/jaciii.2020.p0134
A Novel Combination Cancer Therapy with Iron Chelator Targeting Cancer Stem Cells via Suppressing Stemness. Reviewed International journal Open Access

Yuki Katsura, Toshiaki Ohara, Kazuhiro Noma, Takayuki Ninomiya, Hajime Kashima, Takuya Kato, Hiroaki Sato, Satoshi Komoto, Toru Narusaka, Yasuko Tomono, Boyi Xing, Yuehua Chen, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Tomonari Kasai, Masaharu Seno, Akihiro Matsukawa, Toshiyoshi Fujiwara

Cancers Vol. 11 ( 2 ) 2019.2

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Language：English Publishing type：Research paper (scientific journal)

Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy.

DOI： 10.3390/cancers11020177

Open Access

PubMed
Use of DNA-generated gold nanoparticles to radiosensitize and eradicate radioresistant glioma stem cells. Reviewed International journal

Kunoh T, Shimura T, Kasai T, Matsumoto S, Mahmud H, Khayrani AC, Seno M, Kunoh H, Takada J

Nanotechnology Vol. 30 ( 5 ) page： 055101 - 055101 2019.2

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The surface reactivity of gold nanoparticles (AuNPs) is receiving attention as a radiosensitizer of cancer cells for radiation therapy and/or as a drug carrier to target cells. This study demonstrates the potential of DNA-AuNPs (prepared by mixing calf thymus DNA with HAuCl4 solution) as a radiosensitizer of human glioma cells that have cancer stem cell (CSC)-like properties, to reduce their survival. CSC-like U251MG-P1 cells and their parental glioblastoma U251MG cells are treated with a prepared DNA-AuNP colloid. The radiosensitivity of the resultant AuNP-associated cells are significantly enhanced. To reveal the mechanism by which survival is reduced, the generation of reactive oxygen species (ROS), apoptosis induction, or DNA damage in the cells is assayed using the fluorescent dye DCFDA, annexin V-FITC/PI, and foci formation of γ-H2AX, respectively. X-ray irradiation with administration of AuNPs overcomes the radioresistance of U251MG-P1 cells. It does not induce ROS generation or apoptosis in the cells but enhances the number of abnormal nuclei with abundant γ-H2AX foci, which is judged as cell death by mitotic catastrophe. The AuNP association with the cells effectively induces mitotic catastrophe in x-ray-irradiated CSC-like cells, implicating that DNA-AuNPs might be a promising tool to develop an efficient radiosensitizer against CSC.

DOI： 10.1088/1361-6528/aaedd5

PubMed
Application of Conditional Generative Adversarial Nets to iPSC-Derived Cancer Stem Cell Modeling Reviewed

Hiroyuki Kameda, Saori Aida, Sakae Nishisako, Tomonari Kasai, Atsushi Sato, Tomoyasu Sugiyama

ISCIIA & ITCA 2018 2018.11

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Language：English Publishing type：Research paper (international conference proceedings)
Suppression effect on IFN-γ of adipose tissue-derived mesenchymal stem cells isolated from β2-microglobulin-deficient mice. Reviewed International journal Open Access

Junko Masuda, Eiji Takayama, Tatsuo Ichinohe, Warren Strober, Masako Mizuno-Kamiya, Tomokatsu Ikawa, Atsushi Kitani, Harumi Kawaki, Ivan Fuss, Hiroshi Kawamoto, Akimasa Seno, Arun Vaidyanath, Naoki Umemura, Akifumi Mizutani, Tomonari Kasai, Yasuko Honjo, Ayano Satoh, Hiroshi Murakami, Yoshimoto Katsura, Nobuo Kondoh, Masaharu Seno

Experimental and therapeutic medicine Vol. 16 ( 5 ) page： 4277 - 4282 2018.11

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Administration of bone marrow-derived mesenchymal stem cells (MSCs) is a possible treatment for graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation and other inflammatory conditions. To address the mechanism of immunosuppression by MSCs, in particular those derived from adipose tissue (AMSCs), AMSCs were isolated from three different mouse strains, and the suppressive capacity of the AMSCs thus obtained to suppress interferon (IFN)-γ generation in mixed lymphocyte reaction cultures serving as an in vitro model of GVHD were assessed. It was revealed that the AMSCs had a potent capacity to suppress IFN-γ production regardless of their strain of origin and that such suppression was not associated with production of interleukin-10. In addition, the results demonstrated that β2-microglobulin (β2m)-deficient AMSCs from β2m-/- mice were also potent suppressor cells, verifying the fact that the mechanism underlying the suppression by AMSCs is independent of major histocompatibility complex (MHC) class I expression or MHC compatibility. As AMSCs appear to have immunosuppressive properties, AMSCs may be a useful source of biological suppressor cells for the control of GVHD in humans.

DOI： 10.3892/etm.2018.6689

Open Access

PubMed
Deep-learning of cancer stem cell morphology for anti-cancer stem cell molecule screening Reviewed

Sakae Nishisako, Saori Aida, Hiroyuki Kameda, Tomonari Kasai, Atsushi Sato, Tomoyasu Sugiyama

Chem-Bio Informatics Society(CBI) Annual Meeting 2018 2018.10

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Language：English
HSP-enriched properties of extracellular vesicles involve survival of metastatic oral cancer cells. Reviewed International journal

Kisho Ono, Takanori Eguchi, Chiharu Sogawa, Stuart K Calderwood, Junya Futagawa, Tomonari Kasai, Masaharu Seno, Kuniaki Okamoto, Akira Sasaki, Ken-Ichi Kozaki

Journal of cellular biochemistry Vol. 119 ( 9 ) page： 7350 - 7362 2018.9

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Cancer cells often secrete extracellular vesicles (EVs) that carry heat shock proteins (HSPs) with roles in tumor progression. Oral squamous cell carcinoma (OSCC) belongs to head and neck cancers (HNC) whose lymph-node-metastases often lead to poor prognosis. We have examined the EV proteome of OSCC cells and found abundant secretion of HSP90-enriched EVs in lymph-node-metastatic OSCC cells. Double knockdown of HSP90α and HSP90β, using small interfering RNA significantly reduced the survival of the metastatic OSCC cells, although single knockdown of each HSP90 was ineffective. Elevated expression of these HSP90 family members was found to correlate with poor prognosis of HNC cases. Thus, elevated HSP90 levels in secreted vesicles are potential prognostic biomarkers and therapeutic targets in metastatic OSCC.

DOI： 10.1002/jcb.27039

PubMed
Up-Regulation of PI 3-Kinases and the Activation of PI3K-Akt Signaling Pathway in Cancer Stem-Like Cells Through DNA Hypomethylation Mediated by the Cancer Microenvironment. Reviewed International journal Open Access

Aung Ko Ko Oo, Anna Sanchez Calle, Neha Nair, Hafizah Mahmud, Arun Vaidyanath, Junya Yamauchi, Aprilliana Cahya Khayrani, Juan Du, Md Jahangir Alam, Akimasa Seno, Akifumi Mizutani, Hiroshi Murakami, Yoshiaki Iwasaki, Ling Chen, Tomonari Kasai, Masaharu Seno

Translational oncology Vol. 11 ( 3 ) page： 653 - 663 2018.6

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Language：English

Previously, we have succeeded in converting induced pluripotent stem cells (iPSCs) into cancer stem cells (CSCs) by treating the iPSCs with conditioned medium of Lewis lung carcinoma (LLC) cells. The converted CSCs, named miPS-LLCcm cells, exhibited the self-renewal, differentiation potential, and potential to form malignant tumors with metastasis. In this study, we further characterized miPS-LLCcm cells both in vivo and in vitro. The tumors formed by subcutaneous injection showed the structures with pathophysiological features consisting of undifferentiated and malignant phenotypes generally found in adenocarcinoma. Metastasis in the lung was also observed as nodule structures. Excising from the tumors, primary cultured cells from the tumor and the nodule showed self-renewal, differentiation potential as well as tumor forming ability, which are the essential characters of CSCs. We then characterized the epigenetic regulation occurring in the CSCs. By comparing the DNA methylation level of CG rich regions, the differentially methylated regions (DMRs) were evaluated in all stages of CSCs when compared with the parental iPSCs. In DMRs, hypomethylation was found superior to hypermethylation in the miPS-LLCcm cells and its derivatives. The hypo- and hypermethylated genes were used to nominate KEGG pathways related with CSC. As a result, several categories were defined in the KEGG pathways from which most related with cancers, significant and high expression of components was PI3K-AKT signaling pathway. Simultaneously, the AKT activation was also confirmed in the CSCs. The PI3K-Akt signaling pathway should be an important pathway for the CSCs established by the treatment with conditioned medium of LLC cells.

DOI： 10.1016/j.tranon.2018.03.001

Open Access

PubMed
Targeting Glioblastoma Cells Expressing CD44 with Liposomes Encapsulating Doxorubicin and Displaying Chlorotoxin-IgG Fc Fusion Protein. Reviewed International journal Open Access

Hafizah Mahmud, Tomonari Kasai, Apriliana Cahya Khayrani, Mami Asakura, Aung Ko Ko Oo, Juan Du, Arun Vaidyanath, Samah El-Ghlban, Akifumi Mizutani, Akimasa Seno, Hiroshi Murakami, Junko Masuda, Masaharu Seno

International journal of molecular sciences Vol. 19 ( 3 ) 2018.2

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We recently have established a successful xenograft model of human glioblastoma cells by enriching hyaluronic acid-dependent spheroid-forming populations termed U251MG-P1 cells from U251MG cells. Since U251MG-P1 cells have been confirmed to express CD44 along with principal stemness marker genes, OCT3/4, SOX2, KLF4 and Nanog, this CD44 expressing population appeared to majorly consist of undifferentiated cells. Evaluating the sensitivity to anti-cancer agents, we found U251MG-P1 cells were sensitive to doxorubicin with IC50 at 200 nM. Although doxorubicin has serious side-effects, establishment of an efficient therapy targeting undifferentiated glioblastoma cell population is necessary. We previously designed a chlorotoxin peptide fused to human IgG Fc region without hinge sequence (M-CTX-Fc), which exhibited a stronger growth inhibitory effect on the glioblastoma cell line A172 than an original chlorotoxin peptide. Combining these results together, we designed M-CTX-Fc conjugated liposomes encapsulating doxorubicin and used U251MG-P1 cells as the target model in this study. The liposome modified with M-CTX-Fc was designed with a diameter of approximately 100-150 nm and showed high encapsulation efficiency, adequate loading capacity of anticancer drug, enhanced antitumor effects demonstrating increasing uptake into the cells in vitro; M-CTX-Fc-L-Dox shows great promise in its ability to suppress tumor growth in vivo and it could serve as a template for targeted delivery of other therapeutics.

DOI： 10.3390/ijms19030659

Open Access

PubMed
Iron depletion is a novel therapeutic strategy to target cancer stem cells. Reviewed International journal Open Access

Takayuki Ninomiya, Toshiaki Ohara, Kazuhiro Noma, Yuki Katsura, Ryoichi Katsube, Hajime Kashima, Takuya Kato, Yasuko Tomono, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Fumiaki Kimura, Ling Chen, Tomonari Kasai, Masaharu Seno, Akihiro Matsukawa, Toshiyoshi Fujiwara

Oncotarget Vol. 8 ( 58 ) page： 98405 - 98416 2017.11

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Adequate iron levels are essential for human health. However, iron overload can act as catalyst for the formation of free radicals, which may cause cancer. Cancer stem cells (CSCs), which maintain the hallmark stem cell characteristics of self-renewal and differentiation capacity, have been proposed as a driving force of tumorigenesis and metastases. In the present study, we investigated the role of iron in the proliferation and stemness of CSCs, using the miPS-LLCcm cell model. Although the anti-cancer agents fluorouracil and cisplatin suppressed the proliferation of miPS-LLCcm cells, these drugs did not alter the expression of stemness markers, including Nanog, SOX2, c-Myc, Oct3/4 and Klf4. In contrast, iron depletion by the iron chelators deferasirox and deferoxamine suppressed the proliferation of miPS-LLCcm cells and the expression of stemness markers. In an allograft model, deferasirox inhibited the growth of miPS-LLCcm implants, which was associated with decreased expression of Nanog and Sox2. Altogether, iron appears to be crucial for the proliferation and maintenance of stemness of CSCs, and iron depletion may be a novel therapeutic strategy to target CSCs.

DOI： 10.18632/oncotarget.21846

Open Access

PubMed
Practical Liposomal Formulation for Taxanes with Polyethoxylated Castor Oil and Ethanol with Complete Encapsulation Efficiency and High Loading Efficiency Reviewed Open Access

Tsukasa Shigehiro, Junko Masuda, Shoki Saito, Apriliana C. Khayrani, Kazumasa Jinno, Akimasa Seno, Arun Vaidyanath, Akifumi Mizutani, Tomonari Kasai, Hiroshi Murakami, Ayano Satoh, Tetsuya Ito, Hiroki Hamada, Yuhki Seno, Tadakatsu Mandai, Masaharu Seno

NANOMATERIALS Vol. 7 ( 10 ) 2017.10

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.3390/nano7100290

Open Access

Web of Science

PubMed
A cancer stem cell model as the point of origin of cancerassociated fibroblasts in tumor microenvironment Reviewed Open Access

Neha Nair, Anna Sanchez Calle, Maram Hussein Zahra, Marta Prieto-Vila, Aung Ko Ko Oo, Laura Hurley, Arun Vaidyanath, Akimasa Seno, Junko Masuda, Yoshiaki Iwasaki, Hiromi Tanaka, Tomonari Kasai, Masaharu Seno

SCIENTIFIC REPORTS Vol. 7 ( 1 ) page： 6838 2017.7

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1038/s41598-017-07144-5

Open Access

Web of Science

PubMed
Anticancer effects of novel thalidomide analogs in A549 cells through inhibition of vascular endothelial growth factor and matrix metalloproteinase-2 Reviewed

Bishoy El-Aarag, Tomonari Kasai, Junko Masuda, Hussein Agwa, Magdy Zahran, Masaharu Seno

BIOMEDICINE & PHARMACOTHERAPY Vol. 85 page： 549 - 555 2017.1

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DOI： 10.1016/j.biopha.2016.11.063

Web of Science

PubMed
Hyaluronic Acid Mediated Enrichment of CD44 Expressing Glioblastoma Stem Cells in U251MG Xenograft Mouse Model Reviewed

Arun Vaidyanath, Hafizah Binti Mahmud, Apriliana Cahya Khayrani, Aung KoKo Oo, Akimasa Seno, Mami Asakura, Tomonari Kasai, Masaharu Seno

Journal of Stem Cell Research & Therapy Vol. 07 ( 04 ) 2017

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Publisher：{OMICS} Publishing Group

DOI： 10.4172/2157-7633.1000384
Transient Tcf3 Gene Repression by TALE-Transcription Factor Targeting Reviewed

Junko Masuda, Hiroshi Kawamoto, Warren Strober, Eiji Takayama, Akifumi Mizutani, Hiroshi Murakami, Tomokatsu Ikawa, Atsushi Kitani, Narumi Maeno, Tsukasa Shigehiro, Ayano Satoh, Akimasa Seno, Vaidyanath Arun, Tomonari Kasai, Ivan J. Fuss, Yoshimoto Katsura, Masaharu Seno

APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY Vol. 180 ( 8 ) page： 1559 - 1573 2016.12

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1007/s12010-016-2187-4

Web of Science

PubMed
Characterization of gene expression patterns among artificially developed cancer stem cells using spherical self-organizing map Reviewed

Akimasa Seno, Tomonari Kasai, Masashi Ikeda, Arun Vaidyanath, Junko Masuda, Akifumi Mizutani, Hiroshi Murakami, Tetsuya Ishikawa, Masaharu Seno

Cancer Informatics Vol. 15 page： 163 - 178 2016.8

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Language：English Publishing type：Research paper (scientific journal) Publisher：Libertas Academica Ltd.

DOI： 10.4137/CIN.S39839

Scopus

PubMed
Evaluation of glycosylated docetaxel-encapsulated liposomes prepared by remote loading under solubility gradient Reviewed

Tsukasa Shigehiro, Wenjia Zhai, Arun Vaidyanath, Junko Masuda, Akifumi Mizutani, Tomonari Kasai, Hiroshi Murakami, Hiroki Hamada, David S. Salomon, Katsuhiko Mikuni, Yuhki Seno, Tadakatsu Mandai, Masaharu Seno

JOURNAL OF MICROENCAPSULATION Vol. 33 ( 2 ) page： 172 - 182 2016.2

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Language：English Publishing type：Research paper (scientific journal)

DOI： 10.3109/02652048.2016.1144815

Web of Science

PubMed
Synthesis and in vitro cancer cell growth inhibition evaluation of 11-amino-modified 5-Me-indolo[2,3-b]quinolines and their COMPARE analyses. Reviewed

Okada M, Mei ZW, Hossain MI, Tominaga T, Takebayashi T, Murakami M, Yasuda M, Shigehiro T, Kasai T, Mizutani A, Murakami H, El Sayed, Iel T, Dan S, Yamori T, Seno M, Inokuchi T

Med Chem Res Vol. 25 ( 5 ) page： 879 - 892 2016.2

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Publishing type：Research paper (scientific journal)

DOI： 10.1007/s00044-016-1508-z

Scopus
A new PDAC mouse model originated from iPSCs-converted pancreatic cancer stem cells (CSCcm) Reviewed Open Access

Anna Sanchez Calle, Neha Nair, Aung KoKo Oo, Marta Prieto-Vila, Megumi Koga, Apriliana Cahya Khayrani, Maram Hussein, Laura Hurley, Arun Vaidyanath, Akimasa Seno, Yoshiaki Iwasaki, Malu Calle, Tomonari Kasai, Masaharu Seno

AMERICAN JOURNAL OF CANCER RESEARCH Vol. 6 ( 12 ) page： 2799 - 2815 2016

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Language：English Publishing type：Research paper (scientific journal)

Open Access

Web of Science

PubMed
A Unique Procedure to Identify Cell Surface Markers Through a Spherical Self-Organizing Map Applied to DNA Microarray Analysis. Reviewed

Sugii Y, Kasai T, Ikeda M, Vaidyanath A, Kumon K, Mizutani A, Seno A, Tokutaka H, Kudoh T, Seno M

Biomarkers in cancer Vol. 8 page： 17 - 23 2016

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DOI： 10.4137/BIC.S33542

PubMed
iPSC-derived cancer stem cells provide a model of tumor vasculature Reviewed Open Access

Marta Prieto-Vila, Ting Yan, Anna Sanchez Calle, Neha Nair, Laura Hurley, Tomonari Kasai, Hiroki Kakuta, Junko Masuda, Hiroshi Murakami, Akifumi Mizutani, Masaharu Seno

AMERICAN JOURNAL OF CANCER RESEARCH Vol. 6 ( 9 ) page： 1906 - 1921 2016

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Language：English Publishing type：Research paper (scientific journal)

Open Access

Web of Science

PubMed
Spherical Self-Organizing Map Detects MYBL 1 As Candidate Gene for Triple-Negative Breast Cancer. Reviewed

Ikeda M, Kumon K, Omoto K, Sugii Y, Mizutani A, Vaidyanath A, Kudoh T, Kasai T, Masuda S, Seno M

Neurosci Biomed Eng Vol. 3 ( 2 ) page： 94 - 101 2015
Bacteria: Prospective Savior in Battle against Cancer Reviewed

Neha Nair, Tomonari Kasai, Masaharu Seno

ANTICANCER RESEARCH Vol. 34 ( 11 ) page： 6289 - 6296 2014.11

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Language：English

Web of Science

PubMed
Characterization of cancer stem-like cells derived from mouse induced pluripotent stem cells transformed by tumor-derived exosomes/microvesicles Reviewed

Ting Yan, Masuda Junko, Mizutani Akifumi, Chen Ling, Shigehiro Tsukasa, Matsuda Shuichi, Kasai Tomonari, Kudoh Takayuki, Murakami Hiroshi, Hendrix Mary J. C, Strizzi Luigi, Salomon David S, Fu Li, Seno Masaharu

CANCER RESEARCH Vol. 74 ( 19 ) 2014.10

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DOI： 10.1158/1538-7445.AM2014-3016

Web of Science
Cancer stem cells maintain a hierarchy of differentiation by creating their niche Reviewed

Akifumi Mizutani, Shuichi Matsuda, Ting Yan, Marta Prieto-Vila, Ling Chen, Ayano Satoh, Tomonari Kasai, Junko Masuda, Takyuki Kudoh, Hiroshi Murakami, Li Fu, David S. Salomon, Masaharu Seno

CANCER RESEARCH Vol. 74 ( 19 ) 2014.10

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DOI： 10.1158/1538-7445.AM2014-3026

Web of Science
Mutual dependence between cancer stem cells and their progenies: the niche created by the progenies is sustaining cancer stem cells Invited Reviewed

Ting Yan, Akifumi Mizutani, Shuichi Matsuda, Hiroshi Murakami, Tomonari Kasai, Masaharu Seno

Cancer Cell & Microenvironment Vol. 1 page： e236 2014.9

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DOI： 10.14800/ccm.236
Efficient Drug Delivery of Paclitaxel Glycoside: A Novel Solubility Gradient Encapsulation into Liposomes Coupled with Immunoliposomes Preparation Reviewed Open Access

Tsukasa Shigehiro, Tomonari Kasai, Masaharu Murakami, Sreeja C. Sekhar, Yuki Tominaga, Masashi Okada, Takayuki Kudoh, Akifumi Mizutani, Hiroshi Murakami, David S. Salomon, Katsuhiko Mikuni, Tadakatsu Mandai, Hiroki Hamada, Masaharu Seno

PLOS ONE Vol. 9 ( 9 ) page： e107976 2014.9

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DOI： 10.1371/journal.pone.0107976

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Web of Science

PubMed
In vitro anti-proliferative and anti-angiogenic activities of thalidomide dithiocarbamate analogs Reviewed

Bishoy Y. A. El-Aarag, Tomonari Kasai, Magdy A. H. Zahran, Nadia I. Zakhary, Tsukasa Shigehiro, Sreeja C. Sekhar, Hussein S. Agwa, Akifumi Mizutani, Hiroshi Murakami, Hiroki Kakuta, Masaharu Seno

INTERNATIONAL IMMUNOPHARMACOLOGY Vol. 21 ( 2 ) page： 283 - 292 2014.8

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DOI： 10.1016/j.intimp2014.05.007

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PubMed
Cancer stem cells maintain a hierarchy of differentiation by creating their niche Reviewed Open Access

Shuichi Matsuda, Ting Yan, Akifumi Mizutani, Tatsuyuki Sota, Yuki Hiramoto, Marta Prieto-Vila, Ling Chen, Ayano Satoh, Takayuki Kudoh, Tomonari Kasai, Hiroshi Murakami, Li Fu, David S. Salomon, Masaharu Seno

INTERNATIONAL JOURNAL OF CANCER Vol. 135 ( 1 ) page： 27 - 36 2014.7

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DOI： 10.1002/ijc.28648

Open Access

Web of Science

PubMed
Characterization of Cancer Stem-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Transformed by Tumor-Derived Extracellular Vesicles Reviewed Open Access

Ting Yan, Akifumi Mizutani, Ling Chen, Mai Takaki, Yuki Hiramoto, Shuichi Matsuda, Tsukasa Shigehiro, Tomonari Kasai, Takayuki Kudoh, Hiroshi Murakami, Junko Masuda, Mary J. C. Hendrix, Luigi Strizzi, David S. Salomon, Li Fu, Masaharu Seno

JOURNAL OF CANCER Vol. 5 ( 7 ) page： 572 - 584 2014

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DOI： 10.7150/jca.8865

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Web of Science

PubMed
Chlorotoxin-Fc Fusion Inhibits Release of MMP-2 from Pancreatic Cancer Cells Reviewed Open Access

Samah El-Ghlban, Tomonari Kasai, Tsukasa Shigehiro, Hong Xia Yin, Sreeja Sekhar, Mikiko Ida, Anna Sanchez, Akifumi Mizutani, Takayuki Kudoh, Hiroshi Murakami, Masaharu Seno

BIOMED RESEARCH INTERNATIONAL Vol. 2014 page： 152659 2014

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DOI： 10.1155/2014/152659

Open Access

Web of Science

PubMed
Mouse induced pluripotent stem cell microenvironment generates epithelial-mesenchymal transition in mouse Lewis lung cancer cells Reviewed Open Access

Ling Chen, Akifumi Mizutani, Tomonari Kasai, Ting Yan, Guoliang Jin, Arun Vaidyanath, Bishoy Y. A. El-Aarag, Yixin Liu, Takayuki Kudoh, David S. Salomon, Li Fu, Masaharu Seno

AMERICAN JOURNAL OF CANCER RESEARCH Vol. 4 ( 1 ) page： 80 - U92 2014

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PubMed
Eosinophil cationic protein enhances stabilization of beta-catenin during cardiomyocyte differentiation in P19CL6 embryonal carcinoma cells Reviewed

Guoliang Jin, Akifumi Mizutani, Takayuki Fukuda, Takayuki Otani, Ting Yan, Marta Prieto Vila, Hiroshi Murakami, Takayuki Kudoh, Satoshi Hirohata, Tomonari Kasai, David S. Salomon, Masaharu Seno

MOLECULAR BIOLOGY REPORTS Vol. 40 ( 4 ) page： 3165 - 3171 2013.4

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DOI： 10.1007/s11033-012-2390-5

Web of Science

PubMed
Identification of Caveolin-1 as a Potential Causative Factor in the Generation of Trastuzumab Resistance in Breast Cancer Cells Reviewed Open Access

Sreeja C. Sekhar, Tomonari Kasai, Ayano Satoh, Tsukasa Shigehiro, Akifumi Mizutani, Hiroshi Murakami, Bishoy Y. A. El-Aarag, David S. Salomon, Anna Massaguer, Rafael de Llorens, Masaharu Seno

JOURNAL OF CANCER Vol. 4 ( 5 ) page： 391 - 401 2013

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DOI： 10.7150/jca.6470

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Web of Science

PubMed
Eosinophil cationic protein enhances cardiomyocyte differentiation of P19CL6 embryonal carcinoma cells by stimulating the FGF receptor signaling pathway Reviewed

Guoliang Jin, Akifumi Mizutani, Takayuki Fukuda, Ling Chen, Keisuke Nakanishi, Ting Yan, Takayuki Kudoh, Satoshi Hirohata, Tomonari Kasai, Hiroshi Murakami, David S. Salomon, Masaharu Seno

GROWTH FACTORS Vol. 30 ( 5 ) page： 344 - 355 2012.10

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DOI： 10.3109/08977194.2012.709852

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PubMed
A Model of Cancer Stem Cells Derived from Mouse Induced Pluripotent Stem Cells Reviewed Open Access

Ling Chen, Tomonari Kasai, Yueguang Li, Yuh Sugii, Guoliang Jin, Masashi Okada, Arun Vaidyanath, Akifumi Mizutani, Ayano Satoh, Takayuki Kudoh, Mary J. C. Hendrix, David S. Salomon, Li Fu, Masaharu Seno

PLOS ONE Vol. 7 ( 4 ) page： e33544 2012.4

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DOI： 10.1371/journal.pone.0033544

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Web of Science

PubMed
The Conformational Polymorphism of the Green Fluorescent Protein Reviewed

Haidong Tan, Yueguang Li, Ling Chen, Takayuki Kudoh, Tomonari Kasai, Masaharu Seno

MOLECULAR BIOLOGY Vol. 46 ( 1 ) page： 142 - 148 2012.2

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DOI： 10.1134/S0026893311060045

Web of Science
Chlorotoxin Fused to IgG-Fc Inhibits Glioblastoma Cell Motility via Receptor-Mediated Endocytosis. Reviewed

Kasai T, Nakamura K, Vaidyanath A, Chen L, Sekhar S, El-Ghlban S, Okada M, Mizutani A, Kudoh T, Murakami H, Seno M

Journal of drug delivery Vol. 2012 page： 975763 2012

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DOI： 10.1155/2012/975763

PubMed
Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand Reviewed Open Access

Arun Vaidyanath, Toshihiro Hashizume, Tadahiro Nagaoka, Nao Takeyasu, Hitomi Satoh, Ling Chen, Jiyou Wang, Tomonari Kasai, Takayuki Kudoh, Ayano Satoh, Li Fu, Masaharu Seno

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol. 15 ( 11 ) page： 2525 - 2538 2011.11

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DOI： 10.1111/j.1582-4934.2011.01277.x

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Web of Science

PubMed
Structural and Spatial Associations between Fe, O, and C in the Network Structure of the Leptothrix ochracea Sheath Surface Reviewed Open Access

Tomoko Suzuki, Hideki Hashimoto, Hiromichi Ishihara, Tomonari Kasai, Hitoshi Kunoh, Jun Takada

APPLIED AND ENVIRONMENTAL MICROBIOLOGY Vol. 77 ( 21 ) page： 7873 - 7875 2011.11

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DOI： 10.1128/AEM.06003-11

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PubMed
Isolation of a Leptothrix Strain, OUMS1, from Ocherous Deposits in Groundwater Reviewed

Michinori Sawayama, Tomoko Suzuki, Hideki Hashimoto, Tomonari Kasai, Mitsuaki Furutani, Naoyuki Miyata, Hitoshi Kunoh, Jun Takada

CURRENT MICROBIOLOGY Vol. 63 ( 2 ) page： 173 - 180 2011.8

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DOI： 10.1007/s00284-011-9957-6

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Construction of a high-efficiency multi-site-directed mutagenesis Reviewed Open Access

Haidong Tan, Yueguang Li, Ling Chen, Tomonari Kasai, Masaharu Seno

AFRICAN JOURNAL OF BIOTECHNOLOGY Vol. 10 ( 3 ) page： 449 - 452 2011.1

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DOI： 10.5897/AJB10.1408

Open Access

Web of Science
Analysis of endothelium mimicry by the CSC-like cells derived from iPS cells

S-I. Matsuda, A. Mizutani, T. Kasai, A. Satoh, T. Kudoh, L. Chen, M. Seno

MOLECULAR BIOLOGY OF THE CELL Vol. 22 2011

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Generation of Cancer Stem Cell Model from Mouse iPS Cells

A. Mizutani, S-I. Matsuda, T. Kasai, T. Kudoh, L. Chen, M. Seno

MOLECULAR BIOLOGY OF THE CELL Vol. 22 2011

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To the head of Papers.▲

MISC 24

癌の血管走行を深層学習した人工知能の開発

杉山友康, 藤澤真義, 土井晃一郎, 亀田弘之, 笠井智成, 大原利章

日本生物工学会大会講演要旨集 Vol. 2024年 page： 82 - 82 2024.8

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Development of Paclitaxel Glycoside Liposomes Conjugated with Anti-CD44 Antibody Targeting Ovarian Cancer Cells

Apriliana C. Khayrani, Hafizah Mahmud, Tomonari Kasai, Tsukasa Shigehiro, Aung Ko Ko Oo, Juan Du, Md. Jahangir Alam, Koji Hara, Hiroki Hamada, Yuhki Seno, Said M. Afify, Tadakatsu Mandai, Masaharu Seno

CANCER SCIENCE Vol. 109 page： 1097 - 1097 2018.12

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Web of Science
異なる転移能を有する口腔扁平上皮癌細胞由来エクソソームに含まれるプロテオームの特性

小野喜章, 江口傑徳, 十川千春, 村上純, 藤原敏史, 笠井智成, 妹尾昌治, 佐々木朗, 小崎健一, 岡元邦彰

生命科学系学会合同年次大会 Vol. 2017年度 page： [1LBA - 052] 2017.12

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Language：Japanese Publisher：生命科学系学会合同年次大会運営事務局
舌癌細胞株由来エクソソーム解析による頸部リンパ節転移マーカーの探索

小野喜章, 江口傑徳, 十川千春, 村上純, 笠井智成, 妹尾昌治, 佐々木朗, 小崎健一

日本癌学会総会記事 Vol. 76回 page： J - 1062 2017.9

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口腔扁平上皮癌細胞由来エクソソームに含まれる分子シャペロンについての検討

小野喜章, 小野喜章, 江口傑徳, 十川千春, 村上純, 藤原敏史, 藤原敏史, 笠井智成, 妹尾昌治, 佐々木朗, 小崎健一, 岡元邦彰

臨床ストレス応答学会大会抄録集 Vol. 12th 2017

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J-GLOBAL
Cancer stem cells as the novel origin of cancer-associated fibroblast-like cells

Neha Nair, Arun Vaidyanath, Kenta Hoshikawa, Anna Sanchez Calle, Tomonari Kasai, Masaharu Seno

CANCER RESEARCH Vol. 76 2016.7

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Language：English Publishing type：Research paper, summary (international conference)

DOI： 10.1158/1538-7445.AM2016-LB-278

Web of Science
The significance of c-Kit protooncogene in iCSC-derived PDAC model

Anna Sanchez Calle, Kenta Hoshikawa, Neha Nair, Marta Prieto-Vila, Arun Vaidyanath, Tomonari Kasai, Masaharu Seno

CANCER RESEARCH Vol. 76 2016.7

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Language：English Publishing type：Research paper, summary (international conference)

DOI： 10.1158/1538-7445.AM2016-1725

Web of Science
Synthesis, Biological Evaluation, Docking and QSAR Studies of Some Novel Naphthalimide Dithiocarbamate Analogs as Antitumor and Anti-Inflammatory Agents.

Zahra MH, Osman AMA, Agwa H, Nair N, Calle AS, Hurley L, Farag D, Kasai T, Seno M, Zahran M

Medicinal Chemistry (Los Angeles) Vol. 6 ( 12 ) page： 694 - 703 2016
がんモデル動物を用いた悪性度の違いによる全身免疫能変化の解析

増田潤子, 高山英次, 佐藤あやの, 守本祐司, 本庶仁子, 石塚俊晶, 徳野慎一, 青笹季文, 光吉俊二, 重廣司, 前野成実, 村上宏, 笠井智成, 水谷昭文, Vaidyanath Arun, 妹尾彬正, 川木晴美, 神谷真子, 野, 近藤信夫, 一瀬雅夫, 一戸辰夫, 妹尾昌治

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 Vol. 88回・38回 page： [1P1079] - [1P1079] 2015.12

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肝臓がんへ分化するがん幹細胞モデルの作成

堤愛姫, 竹尻崇人, 水谷昭文, Vaidyanath Arun, 大原利章, 岩崎良章, 笠井智成, 妹尾昌治

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 Vol. 88回・38回 page： [2P1127] - [2P1127] 2015.12

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鉄コントロールによる新規がん幹細胞治療

二宮卓之, 大原利章, 勝部亮一, 賀島肇, 加藤卓也, 野間和広, 田澤大, 香川俊輔, 水谷昭文, 笠井智成, 妹尾昌治, 藤原俊義

日本癌学会総会記事 Vol. 74回 page： IS4 - 6 2015.10

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Derivation of a model of cancer stem cell from human induced pluripotent stem cells

Tomonari Kasai, Kenta Hoshikawa, Shuto Takejiri, Masashi Ikeda, Kazuki Kumon, Anna Sanchez Calle, Arun Vaidyanath, Akifumi Mizutani, Chen Ling, Masaharu Seno

CANCER RESEARCH Vol. 75 2015.8

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DOI： 10.1158/1538-7445.AM2015-LB-144

Web of Science
Iron control is a novel therapeutic target of cancer stem cells

Takayuki Ninomiya, Toshiaki Ohara, Hajime Kashima, Ryoichi Katsube, Kazuhiro Noma, Yasuko Tomono, Akifumi Mizutani, Tomonari Kasai, Masaharu Seno, Shinji Kuroda, Hiroyuki Kishimoto, Hiroshi Tazawa, Yasuhiro Shirakawa, Shunsuke Kagawa, Toshiyoshi Fujiwara

CANCER RESEARCH Vol. 75 2015.8

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DOI： 10.1158/1538-7445.AM2015-4243

Web of Science
Insight into Cancer Stem Cell Niche; Lessons from Cancer Stem Cell Models Generated In Vitro.

MizutaniA, Yan T, Vaidyanath A, Masuda J, Seno A, Kasai T, Murakami H, Seno M

Biology in Stem Cell Niche, Part of the series Stem Cell Biology and Regenerative Medicine 2015

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DOI： 10.1007/978-3-319-21702-4
The application to the gene data of the significance degree analysis by SOM

Tokutaka Heizo, Ohkita Masaaki, Ikeda Masashi, Kasai Tomonari, Seno Masaharu

Proceedings of the Fuzzy System Symposium Vol. 31 page： 476 - 481 2015

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Language：Japanese Publisher：Japan Society for Fuzzy Theory and Intelligent Informatics

The significance degree of each component was calculated only by once SOM learning where the Spherical Self-Organizing-Map (SSOM) was used for the analysis. This method was applied to a great deal of gene data of the breast cancer. Then, the relation between each gene and the breast cancer was examined. Finally, the method succeeded in 22 genetic extraction to be connected with breast cancer carcinogenesis from 831 genes

DOI： 10.14864/fss.31.0_476

CiNii Research
Anti-cancer activity of immunoliposomes encapsulated effective amount of glycosylated paclitaxel with novel loading strategy

Tsukasa Shigehiro, Tomonari Kasai, Akifumi Mizutani, Hiroshi Murakami, Katsuhiko Mikuni, Tadakatsu Mandai, Hiroki Hamada, Masaharu Seno

CANCER RESEARCH Vol. 74 ( 19 ) 2014.10

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DOI： 10.1158/1538-7445.AM2014-4461

Web of Science
鉄コントロールによるがん幹細胞の新規治療法(Iron control is a potent novel therapeutic for cancer stem cells) Reviewed

二宮卓之, 大原利章, 浦野真一, 勝部亮一, 野間和広, 田澤大, 香川俊輔, 水谷昭文, 笠井智成, 妹尾昌治, 藤原俊義

日本癌学会総会記事 Vol. 73回 page： P - 1187 2014.9

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A Cancer Stem Cell Model, an insight into the conversion of induced pluripotent stem cells to cancer stem-like cells.

Mizutani A, Chen L, Kasai T, Kudoh T, Murakami H, Fu L, Seno M

Cancer Stem Cells page： 61 - 77 2014

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DOI： 10.1002/9781118356203.ch6
Cancer stem cells converted from pluripotent stem cells and the cancerous niche.

Kasai T, Chen L, Mizutani A, Kudoh T, Murakami H, Fu L, Seno M

Journal of Stem cells & regenerative medicine Vol. 10 ( 1 ) page： 2 - 7 2014
A novel remote loading method with solubility gradient to encapsulate effevtive amount of taxanes into liposomes.

Tsukasa Shigehiro, Tomonari Kasai, Akifumi Mizutani, Hiroshi Murakami, Katsuhiko Mikuni, Tadakatsu Mandai, Hiroki Hamada, Masaharu Seno

CANCER RESEARCH Vol. 73 ( 8 ) 2013.4

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DOI： 10.1158/1538-7445.AM2013-LB-8

Web of Science
Function of ECP as a Cardiomyocyte Differentiation Enhancing Factor for a Regeneration Medicine

Vol. 64 ( 4 ) page： 249 - 253 2013.4

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CiNii Research
マウスiPS細胞から作るがん幹細胞モデル

笠井智成, 陳凌, 工藤孝幸, 水谷昭文, 妹尾昌治

細胞工学 Vol. 32 ( 3 ) page： 330 - 337 2013
Development and characterization of cancer stem cell model from mouse iPS cells

Ling Chen, Shuichi Matsuda, Tomonari Kasai, Yuh Sugii, Masashi Okada, Koichi Igarashi, Ayano Satoh, Takayuki Kudoh, Takayuki Kudoh, Li Fu, Masaharu Seno

CANCER RESEARCH Vol. 72 2012.4

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DOI： 10.1158/1538-7445.AM2012-418

Web of Science
Preparation and evaluation of glycosylated paclitaxel loaded in tastuzumab-immunoliposome

Masaharu Murakami, Tomonari Kasai, Masashi Okada, Katsuhiko Mikuni, Naoyoshi Egashira, Masaharu Seno, Hiroki Hamada

CANCER RESEARCH Vol. 72 2012.4

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DOI： 10.1158/1538-7445.AM2012-5700

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Research Project for Joint Research, Competitive Funding, etc. 6

Development of new boron-drugs and models for BNCT targeting malignant cells.

Grant number：21K04790 2021.4 - 2024.3

Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Kasai Tomonari

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Authorship：Principal investigator

Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

The new boron-drug uptake and gene expression level were confirmed by using the liver cancer stem cell model derived from mouse iPS cells and human cancer cell lines. We developed a model for boron uptake from gene expression levels and measured the boron uptake of cancer cell lines. As a result, 70% of cancer cell lines were matched with the prediction. It was found that the concentration of a new boron agent taken into the cell was greatly influenced by not only cell surface markers, but the factors thought to be involved in intracellular retention, The novel boron drug has a high possibility of cancer cell elimination by boron neutron capture reaction, since it was observed that the drugs accumulate in the nucleus and in intracellular organelles involved in metabolism.
Preparation of and drug discovery studies by hepatobiliary pancreatic cancer stem cell models derived from organoid and induced pluripotent stem cells

Grant number：19K06457 2019.4 - 2022.3

Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Iwasaki Yoshiaki

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Authorship：Coinvestigator(s)

Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

We induced differentiation of mouse induced pluripotent stem cells into liver and bile duct progenitors and pancreatic progenitors via embryonic endoderm, and induced tumorigenesis of cells at each stage using a method to generate cancer stem cell models. Organoids at each stage of differentiation were also generated and induced to become cancerous in the same manner. These cells and organoids were transplanted subcutaneously and into the liver of mice to form masses. The efficiency of organoid and tumor formation was higher in undifferentiated cells, but the efficiency of tumor formation was still low, requiring further investigation of conditions for induction of differentiation and tumorigenesis. On the other hand, organoids of mouse liver and bile duct progenitor cells were induced to become cancerous and transplanted into mouse liver, but the conditions at each step need to be improved for stable tumor formation.
Establishment and application of animal model of liver cancer stem cell using induced pluripotent stem cells

Grant number：16K07116 2016.4 - 2019.3

Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

IWASAKI Yoshiaki

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Authorship：Coinvestigator(s)

Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

Cancer stem cells were induced from mouse iPS cells by culturing in the presence of conditioned medium prepared from human hepatoma cell lines using a method that we have established. The cancer stem cells exhibited high tumorigenicity with rapid growth in immunodeficient mice. Primary cultured cells derived from this tumor were induced to differentiate into hepatocytes by a series of growth factors to produce liver cancer stem cell-like cells. Tumors formed by directly transplanting these cells into the livers of immunodeficient mice showed markers specific to liver cancer cells and also expression of factors related to stemness. However, only a part of tumors show differentiation to hepatocyte lineage, and it is necessary to establish more efficient animal models of liver cancer stem cells for detailed analysis of these cells.
Analysis of molecular mechanisms involved in the conversion of iPSs into cancer stem cells

Grant number：26640079 2014.4 - 2017.3

Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Seno Masaharu

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Authorship：Coinvestigator(s)

Grant amount：\3900000 （ Direct Cost: \3000000 、 Indirect Cost：\900000 ）

During the process of cancer stem cells (CSC) generation from induced pluripotent stem cells (iPS), we investigated which signaling pathways were involved in the CSC generation. By screening from various signal inhibitors, we found that the GSK3beta and MEK inhibition promoted CSC generation. In addition, we performed the comprehensive gene expression and epigenetic analysis to find out the intracellular change(s), and nominated candidate genes that might be contributing to the CSC generation.
Development of the strategy for fundamental therapy of cancer using iPS derived Cancer Stem cell models

Grant number：25242045 2013.10 - 2017.3

Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

Seno Masaharu

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Grant amount：\32890000 （ Direct Cost: \25300000 、 Indirect Cost：\7590000 ）

For the purpose of the development of the fundamental therapeutic strategies to target cancer stem cells (CSCs), we have been taking advantage of iPS-derived CSCs (iPS-CSCs). In this project, we have proven the direct contribution of CSCs to tumor vasculature development, and have established a new model of pancreatic CSCs. In addition, we performed gene expression profiling of CSCs. These results should be valuable to identify new therapeutic target molecule(s) in CSCs and cancer niche. We also performed drug screening, tried to design new drug. Among the several approved anticancer drugs, we found a drug showing highly effective to iPS-CSCs.
An analysis of bacteria, which produce 'Biotech-materials'

Grant number：24510151 2012.4 - 2015.3

Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

KASAI Tomonari, SENO Masaharu, HASHIMOTO Hideki

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Authorship：Principal investigator

Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

We developed an application for 3D cell culture substrate using amorphous iron oxide (L-BIOX). This culture system should be a promising the production of proteins. On the other hand, to develop the application for drug delivery system, we studied protein ligands and anti-cancer drugs for targeting the cancer cells.

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Industrial property rights 9

タキサン化合物を内包するリポソーム

濱田博喜, 妹尾昌治, 笠井智成, 重廣司, 原浩司, 伊藤哲也, 藤原一郎

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Applicant：塩水港精糖株式会社, 濱田博喜, 清水芳雄, 国立大学法人岡山大学

Application no：JP2016079837 Date applied：2016.10

Announcement no：WO2017-061562 Date announced：2017.4

J-GLOBAL
がんの非ヒトモデル動物及びその作製方法、がん幹細胞及びその製造方法

妹尾昌治, 笠井智成, 岩▲崎▼ 良章, 大原利章, 廣畑聡, 加来田博貴

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Applicant：国立大学法人岡山大学

Application no：JP2016060309 Date applied：2016.3

Announcement no：WO2016-170938 Date announced：2016.10

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被検物質のがん幹細胞誘導性評価技術

妹尾昌治, 笠井智成, 古矢修一

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Applicant：国立大学法人岡山大学

Application no：特願2015-082409 Date applied：2015.4

Announcement no：特開2016-106617 Date announced：2016.6

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がん幹細胞を含む細胞集団を得る方法

妹尾昌治, 水谷昭文, 笠井智成

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Applicant：国立大学法人岡山大学, LSIPファンド運営合同会社

Application no：JP2014057572 Date applied：2014.3

Announcement no：WO2014-148562 Date announced：2014.9

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不均一ながん幹細胞及びその用途

妹尾昌治, 水谷昭文, 笠井智成

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Applicant：国立大学法人岡山大学

Application no：特願2014-042544 Date applied：2014.3

Announcement no：特開2014-207889 Date announced：2014.11

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がん幹細胞及びその用途

妹尾昌治, 水谷昭文, 笠井智成

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Applicant：国立大学法人岡山大学

Application no：特願2014-014778 Date applied：2014.1

Announcement no：特開2014-207883 Date announced：2014.11

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細胞を培養する担体及び培養細胞を用いたタンパク質又はペプチドの生産方法

笠井智成, 妹尾昌治, 高田潤, 橋本英樹, 鈴木智子

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Applicant：国立大学法人岡山大学

Application no：JP2013072178 Date applied：2013.8

Announcement no：WO2014-030641 Date announced：2014.2

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ヒアルロン酸を利用したスフェロイド培養法

妹尾昌治, 笠井智成

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Applicant：国立大学法人岡山大学

Application no：特願2013-082671 Date applied：2013.4

Announcement no：特開2014-204674 Date announced：2014.10

Patent/Registration no：特許第6226545号 Date issued：2017.10

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パクリタキセルモノグリコシド及び/又はドセタキセルモノグリコシドを内包するリポソームの製造方法

濱田博喜, 妹尾昌治, 笠井智成, 重廣司, 村上雅春, 三國克彦, 藤原一郎

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Applicant：塩水港精糖株式会社, 濱田博喜, 藤原一郎, 国立大学法人岡山大学

Application no：JP2013058242 Date applied：2013.3

Announcement no：WO2013-141346 Date announced：2013.9

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