Novel strategy to target glioblastoma-initiating cells using a braintropic adeno-associated virus carrying a miR-dependent genome-editing system
Zhe Wang, Peilin Zou, Zhenzhong Chen, Jiahui Hou, You Lee Son, Daisuke Yamashita, Toru Kondo
British Journal of Cancer, Springer Science and Business Media LLC, 12 Apr. 2025, [Peer-reviewed], [Last author, Corresponding author]
Scientific journal

Eva1 deficiency prevents obesity-induced metabolic disorders by reducing visceral adipose dysfunction
You Lee Son, Jiahui Hou, Mira Kato-Suzuki, Yuko Okamatsu-Ogura, Megumi Watase, Hiroshi Kiyonari, Toru Kondo
Metabolism, 156235, 156235, Elsevier BV, Mar. 2025, [Peer-reviewed], [Last author, Corresponding author]
Scientific journal

EVA1-antibody drug conjugate is a new therapeutic strategy for eliminating glioblastoma-initiating cells
Jiahui Hou, Tamami Uejima, Miho Tanaka, You Lee Son, Kazuharu Hanada, Mutsuko Kukimoto-Niino, Shigeru Yamaguchi, Shigeru Hashimoto, Shigeyuki Yokoyama, Toshitada Takemori, Takashi Saito, Mikako Shirouzu, Toru Kondo
Neuro-Oncology, 27, 3, 682, 694, Oxford University Press (OUP), 29 Oct. 2024, [Peer-reviewed], [Last author, Corresponding author]
Scientific journal, Abstract

Background

The discovery of glioblastoma (GBM)-initiating cells (GICs) has impacted GBM research. These cells are not only tumorigenic but also exhibit resistance to radiotherapy and chemotherapy. Therefore, it is crucial to characterize GICs thoroughly and identify new therapeutic targets. In a previous study, we successfully identified epithelial-V–like antigen 1 (EVA1) as a novel functional factor specific to GICs.

Methods

Hybridoma cells were generated by immunizing BALB/c mice with EVA1-Fc fusion protein. The reactivity of the supernatant from these hybridoma cells was examined using EVA1-overexpressing cells and GICs. Candidate antibodies were further selected using Biacore surface plasmon resonance analysis and 2 cytotoxicity assays—antibody-dependent cell cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Among the antibodies, the cytotoxicity of the B2E5-antibody drug conjugate (B2E5-ADC) was evaluated by both adding it to cultured GICs and injecting it into GIC tumor-bearing brains.

Results

B2E5 demonstrated a high affinity for human EVA1 and effectively killed both EVA1-expressing cell lines and GICs in culture through ADCC and CDC. B2E5-ADC also exhibited strong cytotoxicity to GICs in culture and prevented their tumorigenesis in the brain when administered intracranially to the tumor-bearing brain.

Conclusion

Our data indicate that B2E5-ADC is a new and promising therapeutic strategy for GBM.

Developing a novel therapeutic strategy against cancer stem cell heterogeneity and plasticity
Toru Kondo
Cancer Heterogeneity and Plasticity, 1, 19, Pivot Science Publications Corporation, 27 Sep. 2024, [Peer-reviewed], [Lead author, Last author, Corresponding author]
Scientific journal, Cancer consists of heterogeneous cells, including cancer stem cells (CSCs), cancer cells, and tumor-associated cells, such as immune cells and vascular cells. Considering that these diverse cell types influence one another directly and indirectly through membrane proteins and secretion factors, such as exosomes and growth factors, the overall heterogeneity affects tumorigenicity and resistance to therapy. This review explores cancer heterogeneity, focusing on CSC heterogeneity, and discussed how the heterogeneity emerges by the intrinsic mechanism and the external factors and affects response to therapy. Additionally, as a potential therapeutic strategy to address this heterogeneity, I propose new Adeno-associated virus carrying a miRNA-dependent CSC eradication system that targets all types of CSCs with minimizing side effects.

Combination of blockade of endothelin signalling and compensation of IGF1 expression protects the retina from degeneration
Naoya Shigesada, Naoya Shikada, Manabu Shirai, Michinori Toriyama, Fumiaki Higashijima, Kazuhiro Kimura, Toru Kondo, Yasumasa Bessho, Takuma Shinozuka, Noriaki Sasai
Cellular and Molecular Life Sciences, 81, 1, Springer Science and Business Media LLC, 22 Jan. 2024
Scientific journal, Abstract

Retinitis pigmentosa (RP) and macular dystrophy (MD) cause severe retinal dysfunction, affecting 1 in 4000 people worldwide. This disease is currently assumed to be intractable, because effective therapeutic methods have not been established, regardless of genetic or sporadic traits. Here, we examined a RP mouse model in which the Prominin-1 (Prom1) gene was deficient and investigated the molecular events occurring at the outset of retinal dysfunction. We extracted the Prom1-deficient retina subjected to light exposure for a short time, conducted single-cell expression profiling, and compared the gene expression with and without stimuli. We identified the cells and genes whose expression levels change directly in response to light stimuli. Among the genes altered by light stimulation, Igf1 was decreased in rod photoreceptor cells and astrocytes under the light-stimulated condition. Consistently, the insulin-like growth factor (IGF) signal was weakened in light-stimulated photoreceptor cells. The recovery of Igf1 expression with the adeno-associated virus (AAV) prevented photoreceptor cell death, and its treatment in combination with the endothelin receptor antagonist led to the blockade of abnormal glial activation and the promotion of glycolysis, thereby resulting in the improvement of retinal functions, as assayed by electroretinography. We additionally demonstrated that the attenuation of mammalian/mechanistic target of rapamycin (mTOR), which mediates IGF signalling, leads to complications in maintaining retinal homeostasis. Together, we propose that combinatorial manipulation of distinct mechanisms is useful for the maintenance of the retinal condition.

Tumor cell-induced macrophage senescence plays a pivotal role in tumor initiation followed by stable growth in immunocompetent condition
Haruka Wada, Ryo Otsuka, Wilfred T V Germeraad, Tomoki Murata, Toru Kondo, Ken-ichiro Seino
Journal for ImmunoTherapy of Cancer, 11, 11, e006677, e006677, BMJ, 13 Nov. 2023
Scientific journal, Background

The cancer stem cell theory proposes that tumor formation in vivo is driven only by specific tumor-initiating cells having stemness; however, clinical trials conducted to test drugs that target the tumor stemness provided unsatisfactory results thus far. Recent studies showed clear involvement of immunity in tumors; however, the requirements of tumor-initiation followed by stable growth in immunocompetent individuals remain largely unknown.

Methods

To clarify this, we used two similarly induced glioblastoma lines, 8B and 9G. They were both established by overexpression of an oncogenic H-RasL61 in p53-deficient neural stem cells. In immunocompromised animals in an orthotopic transplantation model using 1000 cells, both show tumor-forming potential. On the other hand, although in immunocompetent animals, 8B shows similar tumor-forming potential but that of 9G’s are very poor. This suggests that 8B cells are tumor-initiating cells in immunocompetent animals. Therefore, we hypothesized that the differences in the interaction properties of 8B and 9G with immune cells could be used to identify the factors responsible for its tumor forming potential in immunocompetent animals and performed analysis.

Results

Different from 9G, 8B cells induced senescence-like state of macrophages around tumors. We investigated the senescence-inducing factor of macrophages by 8B cells and found that it was interleukin 6. Such senescence-like macrophages produced Arginase-1, an immunosuppressive molecule known to contribute to T-cell hyporesponsiveness. The senescence-like macrophages highly expressed CD38, a nicotinamide adenine dinucleotide (NAD) glycohydrolase associated with NAD shortage in senescent cells. The addition of nicotinamide mononucleotide (NMN), an NAD precursor, in vitro inhibited to the induction of macrophage senescence-like phenotype and inhibited Arginase-1 expression resulting in retaining T-cell function. Moreover, exogenous in vivo administration of NMN after tumor inoculation inhibited tumor-initiation followed by stable growth in the immunocompetent mouse tumor model.

Conclusions

We identified one of the requirements for tumor-initiating cells in immunocompetent animals. In addition, we have shown that tumor growth can be inhibited by externally administered NMN against macrophage senescence-like state that occurs in the very early stages of tumor-initiating cell development. This therapy targeting the immunosuppressive environment formed by macrophage senescence-like state is expected to be a novel promising cancer therapeutic strategy.

Selective vulnerability of human-induced pluripotent stem cells to dihydroorotate dehydrogenase inhibition during mesenchymal stem/stromal cell purification
Ziadoon Al-Akashi, Denise Zujur, Daisuke Kamiya, Tomohisa Kato, Toru Kondo, Makoto Ikeya
Frontiers in Cell and Developmental Biology, 11, Frontiers Media SA, 06 Feb. 2023, [Peer-reviewed]
English, Scientific journal, The use of induced mesenchymal stem/stromal cells (iMSCs) derived from human induced pluripotent stem cells (hiPSCs) in regenerative medicine involves the risk of teratoma formation due to hiPSCs contamination in iMSCs. Therefore, eradicating the remaining undifferentiated hiPSCs is crucial for the effectiveness of the strategy. The present study demonstrates the Brequinar (BRQ)-induced inhibition of dihydroorotate dehydrogenase (DHODH), a key enzyme in de novo pyrimidine biosynthesis, selectively induces apoptosis, cell cycle arrest, and differentiation; furthermore, it promotes transcriptional changes and prevents the growth of 3-dimensional hiPSC aggregates. Contrastingly, BRQ-treated iMSCs showed no changes in survival, differentiation potential, or gene expression. The results suggest that BRQ is a potential agent for the effective purification of iMSCs from a mixed population of iMSCs and hiPSCs, which is a crucial step in successful iMSC-based therapy.

Glioblastoma-initiating cell heterogeneity generated by the cell-of-origin, genetic/epigenetic mutation and microenvironment.　　　　　　　　　　　　　　　
Kondo T
Semin Cancer Biol., 2021, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
English

Tumor edge-to-core transition promotes malignancy in primary-to-recurrent glioblastoma progression in a PLAGL1/CD109-mediated mechanism
Chaoxi Li, Hee Jin Cho, Daisuke Yamashita, Moaaz Abdelrashid, Qin Chen, Soniya Bastola, Gustavo Chagoya, Galal A Elsayed, Svetlana Komarova, Saya Ozaki, Yoshihiro Ohtsuka, Takeharu Kunieda, Harley I Kornblum, Toru Kondo, Do-Hyun Nam, Ichiro Nakano
Neuro-Oncology Advances, 2, 1, Oxford University Press (OUP), 27 Nov. 2020, [Peer-reviewed]
English, Scientific journal,


Glioblastoma remains highly lethal due to its inevitable recurrence. Most of this recurrence is found locally, indicating that postsurgical tumor-initiating cells (TICs) accumulate at the tumor edge. These edge-TICs then generate local recurrence harboring new core lesions. Here, we investigated the clinical significance of the edge-to-core (E-to-C) signature generating glioblastoma recurrence and sought to identify its central mediators.





First, we examined the association of E-to-C-related expression changes to patient outcome in matched primary and recurrent samples (n = 37). Specifically, we tested whether the combined decrease of the edge-TIC marker PROM1 (CD133) with the increase of the core-TIC marker CD109, representing E-to-C transition during the primary-to-recurrence progression, indicates poorer patient outcome. We then investigated the specific molecular mediators that trigger tumor recurrence driven by the E-to-C progression. Subsequently, the functional and translational significance of the identified molecule was validated with our patient-derived edge-TIC models in vitro and in vivo.





Patients exhibiting the CD133low/CD109high signature upon recurrence representing E-to-C transition displayed a strong association with poorer progression-free survival and overall survival among all tested patients. Differential gene expression identified that PLAGL1 was tightly correlated with the core TIC marker CD109 and was linked to shorter patient survival. Experimentally, forced PLAGL1 overexpression enhanced, while its knockdown reduced, glioblastoma edge-derived tumor growth in vivo and subsequent mouse survival, suggesting its essential role in the E-to-C-mediated glioblastoma progression.





E-to-C axis represents an ongoing lethal process in primary glioblastoma contributing to its recurrence, partly in a PLAGL1/CD109-mediated mechanism.

Selective eradication of pluripotent stem cells by inhibiting DHODH activity
Toru Kondo
STEM CELLS, 39, 33, 42, Wiley, 12 Oct. 2020, [Peer-reviewed], [Lead author, Last author, Corresponding author]
English, Scientific journal

Discovery of a new pyrimidine synthesis inhibitor eradicating glioblastoma-initiating cells.
Smile Echizenya, Yukiko Ishii, Satoshi Kitazawa, Tadashi Tanaka, Shun Matsuda, Eriko Watanabe, Masao Umekawa, Shunsuke Terasaka, Kiyohiro Houkin, Tomohisa Hatta, Tohru Natsume, Yoshimasa Maeda, Shin-Ichi Watanabe, Shinji Hagiwara, Toru Kondo
Neuro-oncology, 22, 2, 229, 239, 20 Feb. 2020, [Peer-reviewed], [Last author, Corresponding author], [International Magazine]
English, Scientific journal, BACKGROUND: Glioblastoma-initiating cells (GICs) comprise a tumorigenic subpopulation of cells that are resistant to radio- and chemotherapies and are responsible for cancer recurrence. The aim of this study was to identify novel compounds that specifically eradicate GICs using a high throughput drug screening approach. METHODS: We performed a cell proliferation/death-based drug screening using 10 560 independent compounds. We identified dihydroorotate dehydrogenase (DHODH) as a target protein of hit compound 10580 using ligand-fishing and mass spectrometry analysis. The medical efficacy of 10580 was investigated by in vitro cell proliferation/death and differentiation and in vivo tumorigenic assays. RESULTS: Among the effective compounds, we identified 10580, which induced cell cycle arrest, decreased the expression of stem cell factors in GICs, and prevented tumorigenesis upon oral administration without any visible side effects. Mechanistic studies revealed that 10580 decreased pyrimidine nucleotide levels and enhanced sex determining region Y-box 2 nuclear export by antagonizing the enzyme activity of DHODH, an essential enzyme for the de novo pyrimidine synthesis. CONCLUSION: In this study, we identified 10580 as a promising new drug against GICs. Given that normal tissue cells, in particular brain cells, tend to use the alternative salvage pathway for pyrimidine synthesis, our findings suggest that 10580 can be used for glioblastoma therapy without side effects.Key Points1.  Chemical screening identified 10580 as a novel GIC-eliminating drug that targets DHODH, an essential enzyme for the de novo pyrimidine synthesis pathway. 2. Compound 10580 induced cell cycle arrest, apoptosis, and differentiation in GICs.

Ecrg4 deficiency results in extended replicative capacity of neural stem cells in a Foxg1-dependent manner
Yuka Nakatani, Hiroshi Kiyonari, Toru Kondo
Development, 146, 4, The Company of Biologists, 18 Feb. 2019, [Peer-reviewed], [Last author, Corresponding author]
Scientific journal, The self-renewal activity of neural stem cells (NSCs) has been suggested to decrease with aging, resulting in age-dependent declines in brain function such as presbyopia and memory loss. The molecular mechanisms underlying decreases in NSC proliferation with age need to be elucidated in more detail to develop treatments that promote brain function. We previously reported that the expression of esophageal cancer-related gene 4 (Ecrg4) was up-regulated in aged NSCs, while its overexpression decreased NSC proliferation, suggesting a functional relationship between Ecrg4 and NSC aging. Using Ecrg4-deficient mice replaced the ecrg4 locus with the lacZ gene, we herein show that Ecrg4 deficiency recovered the age-dependent decline in NSC proliferation and enhanced spatial learning and memory in the Morris water-maze paradigm. We demonstrate that the proliferation of Ecrg4-deficient NSCs was partly maintained by the increased expression of Foxg1. Collectively, these results determine Ecrg4 as a NSC aging factor.

Hedgehog Signal and Genetic Disorders.
Noriaki Sasai, Michinori Toriyama, Toru Kondo
Frontiers in genetics, 10, 1103, 1103, 2019, [Peer-reviewed], [Last author], [International Magazine]
English, Scientific journal, The hedgehog (Hh) family comprises sonic hedgehog (Shh), Indian hedgehog (Ihh), and desert hedgehog (Dhh), which are versatile signaling molecules involved in a wide spectrum of biological events including cell differentiation, proliferation, and survival; establishment of the vertebrate body plan; and aging. These molecules play critical roles from embryogenesis to adult stages; therefore, alterations such as abnormal expression or mutations of the genes involved and their downstream factors cause a variety of genetic disorders at different stages. The Hh family involves many signaling mediators and functions through complex mechanisms, and achieving a comprehensive understanding of the entire signaling system is challenging. This review discusses the signaling mediators of the Hh pathway and their functions at the cellular and organismal levels. We first focus on the roles of Hh signaling mediators in signal transduction at the cellular level and the networks formed by these factors. Then, we analyze the spatiotemporal pattern of expression of Hh pathway molecules in tissues and organs, and describe the phenotypes of mutant mice. Finally, we discuss the genetic disorders caused by malfunction of Hh signaling-related molecules in humans.

Prominin-1 modulates Rho/ROCK-mediated membrane morphology and calcium-dependent intracellular chloride fulx.　　　　　　　　　　　　　　　
Hori, A., Nishide, K., Yasukuni, Y., Haga, K., Kakuta, W., Ishikawa, Y., Hayes, M.J., Ohnuma, S.I., Kiyonari, H., Kimura, K., Kondo, T., & Sasai, N.
Sci. Rep., 9, 15911, 2019, [Peer-reviewed]
English, Scientific journal

GPR17 is an essential regulator for the temporal adaptation of Sonic hedgehog signalling in neural tube development
Atsuki Yatsuzuka, Akiko Hori, Minori Kadoya, Mami Matsuo-Takasaki, Toru Kondo, Noriaki Sasai
Development, 146, The Company of Biologists, 01 Jan. 2019, [Peer-reviewed]
English, Scientific journal, Dorsal-ventral pattern formation of the neural tube is regulated by temporal and spatial activities of extracellular signalling molecules. Sonic hedgehog (Shh) assigns ventral neural subtypes via activation of the Gli transcription factors. Shh activity in the neural progenitor cells changes dynamically during differentiation, but the mechanisms regulating this dynamicity are not fully understood.


Here we show that temporal change of the intracellular cAMP level confers the temporal Shh signal, and the purinergic-type G-protein coupled receptor GPR17 plays an essential role for this regulation. GPR17 is highly expressed in the ventral progenitor regions of the neural tube and acts as a negative regulator of the Shh signal in chick embryos. While the activation of the GPR17-related signal inhibits ventral identity, perturbation of GPR17 expression leads to aberrant expansion of ventral neural domains. Notably, perturbation of GPR17 expression partially inhibits the negative feedback of Gli activity. Moreover, GPR17 increases cAMP activity, suggesting that it exerts its function by inhibiting the processing of Gli3 protein. GPR17 also negatively regulates Shh signalling in neural cells differentiated from mouse embryonic stem cells, suggesting that GPR17 function is conserved among different organisms. Our results demonstrate that GPR17 is a novel negative regulator of Shh signalling in a wide range of cellular contexts.

Ecrg4 peptide is the ligand of multiple scavenger receptors
Tetsuo Moriguchi, Shuji Takeda, Shinzo Iwashita, Kei Enomoto, Tatsuya Sawamura, Uichi Koshimizu, Toru Kondo
Scientific Reports, 8, 1, Springer Science and Business Media LLC, 06 Mar. 2018, [Peer-reviewed], [Last author, Corresponding author]
Scientific journal, Abstract

Esophageal cancer-related gene 4 (Ecrg4) encodes a hormone-like peptide that is believed to be involved in a variety of physiological phenomena, including tumour suppression. Recent progress in the study of Ecrg4 has shown that Ecrg4 is a proinflammatory factor and induces the expression of several cytokines and chemokines in macrophages/microglia. However, the detailed molecular mechanisms of Ecrg4 signalling, especially the Ecrg4 receptors, remain poorly understood. Here, using retrovirus-mediated expression cloning, we identified lectin-like oxidised low-density lipoprotein receptor-1 (LOX-1) as a membrane protein that binds amino acid residues 71–132 of Ecrg4 (Ecrg4(71–132)). Moreover, in addition to LOX-1, several scavenger receptors, such as Scarf1, Cd36 and Stabilin-1, facilitated the efficient internalisation of Ecrg4(71–132) into cells. A broad competitive inhibitor of scavenger receptors, polyinosinic acid, reduced both the binding of Ecrg4(71–132) and the activation of NF-κB in microglia. This activation was dependent on MyD88, an adaptor protein that recruits signalling proteins to Toll-like receptors (TLRs), with the consequent induction of various immune responses. These data suggest that multiple scavenger receptors recognise Ecrg4(71–132) and transduce its signals, together with TLRs, in microglia.

Cellular stress induces cancer stem-like cells through expression of DNAJB8 by activation of heat shock factor 1
Hiroki Kusumoto, Yoshihiko Hirohashi, Satoshi Nishizawa, Masamichi Yamashita, Kazuyo Yasuda, Aiko Murai, Akari Takaya, Takashi Mori, Terufumi Kubo, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Toru Kondo, Noriyuki Sato, Isao Hara, Toshihiko Torigoe
Cancer Science, 109, 3, 741, 750, Blackwell Publishing Ltd, 01 Mar. 2018, [Peer-reviewed]
English, Scientific journal

Metabolomics-based discovery of a metabolite that enhances oligodendrocyte maturation
Brittney A. Beyer, Mingliang Fang, Benjamin Sadrian, J. Rafael Montenegro-Burke, Warren C. Plaisted, Bernard P. C. Kok, Enrique Saez, Toru Kondo, Gary Siuzdak, Luke L. Lairson
Nature Chemical Biology, 14, 1, 22, 28, Nature Publishing Group, 01 Jan. 2018, [Peer-reviewed]
English, Scientific journal

iPSC-based drug repositioning identifies Src/c-Abl as a therapeutic target for ALS motor neurons.
Imamura K, Izumi Y, Watanabe A, Tsukita K, Woltjen K, Yamamoto T, Hotta A, Kondo T, Kitaoka S, Ohta A, Tanaka A, Watanabe D, Morita M, Kaji R, Takuma H, Tamaoka A, Kunath T, Wray S, Furuya H, Era T, Fujisawa T, Nishotoh H, Kengo H, Ichijo H, Julien J-P, Obata N, Hosokawa M, Akiyama H, Ayaki T, Ito H, Takahashi R, Yamanaka S, Inoue H
Science Translational Medicine, 9, 391, May 2017, [Peer-reviewed]
English, Scientific journal

Molecular mechanisms involved in gliomagenesis
Toru Kondo
BRAIN TUMOR PATHOLOGY, 34, 1, 1, 7, Jan. 2017, [Peer-reviewed], [Lead author, Last author, Corresponding author]
English

Ecrg4 contributes to the anti-glioma immunosurveillance through type-I interferon signaling
Tetsuo Moriguchi, Shun Kaneumi, Shuji Takeda, Kei Enomoto, Shyam Kumar Mishra, Tetsuro Miki, Uichi Koshimizu, Hidemitsu Kitamura, Toru Kondo
OncoImmunology, 5, 12, e1242547, 01 Dec. 2016, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Local convection-enhanced delivery of an anti-CD40 agonistic monoclonal antibody induces antitumor effects in mouse glioma models
Takuhiro Shoji, Ryuta Saito, Masashi Chonan, Ichiyo Shibahara, Aya Sato, Masayuki Kanamori, Yukihiko Sonoda, Toru Kondo, Naoto Ishii, Teiji Tominaga
NEURO-ONCOLOGY, 18, 8, 1120, 1128, Aug. 2016, [Peer-reviewed]
English, Scientific journal

Chemical Screening Identifies EUrd as a Novel Inhibitor Against Temozolomide-Resistant Glioblastoma-Initiating Cells
Yoshihiro Tsukamoto, Naoki Ohtsu, Smile Echizenya, Satoko Otsuguro, Ryosuke Ogura, Manabu Natsumeda, Mizuho Isogawa, Hiroshi Aoki, Satoshi Ichikawa, Masahiro Sakaitani, Akira Matsuda, Katsumi Maenaka, Yukihiko Fujii, Toru Kondo
STEM CELLS, 34, 8, 2016, 2025, Aug. 2016, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Plasticity of lung cancer stem-like cells is regulated by the transcription factor HOXA5 that is induced by oxidative stress
Hiroshi Saijo, Yoshihiko Hirohashi, Toshihiko Torigoe, Ryota Horibe, Akari Takaya, Aiko Murai, Terufumi Kubo, Toshimitsu Kajiwara, Tsutomu Tanaka, Yosuke Shionoya, Eri Yamamoto, Reo Maruyama, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Yasuaki Tamura, Yasushi Sasaki, Takashi Tokino, Hiromu Suzuki, Toru Kondo, Hiroki Takahashi, Noriyuki Sato
ONCOTARGET, 7, 31, 50043, 50056, Aug. 2016, [Peer-reviewed]
English, Scientific journal

Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy
Rena Morita, Yoshihiko Hirohashi, Toshihiko Torigoe, Satoko Ito-Inoda, Akari Takahashi, Tasuku Mariya, Hiroko Asanuma, Yasuaki Tamura, Tomohide Tsukahara, Takayuki Kanaseki, Terufumi Kubo, Goro Kutomi, Toru Mizuguchi, Takeshi Terui, Kunihiko Ishitani, Satoshi Hashino, Toru Kondo, Nozomi Minagawa, Norihiko Takahashi, Akinobu Taketomi, Satoru Todo, Masahiro Asaka, Noriyuki Sato
CLINICAL CANCER RESEARCH, 22, 13, 3298, 3309, Jul. 2016, [Peer-reviewed]
English, Scientific journal

Establishment and Analysis of Cancer Stem-Like and Non-Cancer Stem-Like Clone Cells from the Human Colon Cancer Cell Line SW480
Akari Takaya, Yoshihiko Hirohashi, Aiko Murai, Rena Morita, Hiroshi Saijo, Eri Yamamoto, Terufumi Kubo, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Yasuaki Tamura, Ichiro Takemasa, Toru Kondo, Noriyuki Sato, Toshihiko Torigoe
PLOS ONE, 11, 7, e0158903, Jul. 2016, [Peer-reviewed]
English, Scientific journal

A Powerful CRISPR/Cas9-Based Method for Targeted Transcriptional Activation
Shota Katayama, Tetsuo Moriguchi, Naoki Ohtsu, Toru Kondo
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 55, 22, 6452, 6456, May 2016, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Targeting the glioblastoma-initiating cell-associated antigens.　　　　　　　　　　　　　　　
Toru Kondo
Cancer Cell and Metastasis., 3, 1, 5, 2016, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
English, Scientific journal

Eva1 Maintains the Stem-like Character of Glioblastoma-Initiating Cells by Activating the Noncanonical NF-kappa B Signaling Pathway
Naoki Ohtsu, Yuka Nakatani, Daisuke Yamashita, Shiro Ohue, Takanori Ohnishi, Toru Kondo
CANCER RESEARCH, 76, 1, 171, 181, Jan. 2016, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Ceacam1L Modulates STAT3 Signaling to Control the Proliferation of Glioblastoma-Initiating Cells
Sadahiro Kaneko, Yuka Nakatani, Tatsuya Takezaki, Takuichiro Hide, Daisuke Yamashita, Naoki Ohtsu, Takanori Ohnishi, Shunsuke Terasaka, Kiyohiro Houkin, Toru Kondo
CANCER RESEARCH, 75, 19, 4224, 4234, Oct. 2015, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

miR340 Suppresses the Stem-like Cell Function of Glioma-Initiating Cells by Targeting Tissue Plasminogen Activator
Daisuke Yamashita, Toru Kondo, Shiro Ohue, Hisaaki Takahashi, Madoka Ishikawa, Ryo Matoba, Satoshi Suehiro, Shohei Kohno, Hironobu Harada, Junya Tanaka, Takanori Ohnishi
CANCER RESEARCH, 75, 6, 1123, 1133, Mar. 2015, [Peer-reviewed]
English, Scientific journal

Genetic Background and Light-Dependent Progression of Photoreceptor Cell Degeneration in Prominin-1 Knockout Mice
Margaret Dellett, Noriaki Sasai, Kenji Nishide, Silke Becker, Vasiliki Papadaki, G. Astrid Limb, Anthony T. Moore, Toru Kondo, Shin-ichi Ohnuma
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 56, 1, 164, 176, Jan. 2015, [Peer-reviewed]
English, Scientific journal

Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells
Rena Morita, Satoshi Nishizawa, Toshihiko Torigoe, Akari Takahashi, Yasuaki Tamura, Tomohide Tsukahara, Takayuki Kanaseki, Alice Sokolovskaya, Vitaly Kochin, Toru Kondo, Satoshi Hashino, Masahiro Asaka, Isao Hara, Yoshihiko Hirohashi, Noriyuki Sato
CANCER SCIENCE, 105, 4, 389, 395, Apr. 2014, [Peer-reviewed]
English, Scientific journal

Heat shock protein DNAJB8 is a novel target for immunotherapy of colon cancer-initiating cells
Rena Morita, Satoshi Nishizawa, Toshihiko Torigoe, Akari Takahashi, Yasuaki Tamura, Tomohide Tsukahara, Takayuki Kanaseki, Alice Sokolovskaya, Vitaly Kochin, Toru Kondo, Satoshi Hashino, Masahiro Asaka, Isao Hara, Yoshihiko Hirohashi, Noriyuki Sato
Cancer Science, 105, 4, 389, 395, Blackwell Publishing Ltd, 2014, [Peer-reviewed]
English, Scientific journal

Ectopically Expressed Variant Form of Sperm Mitochondria-Associated Cysteine-Rich Protein Augments Tumorigenicity of the Stem Cell Population of Lung Adenocarcinoma Cells
Akari Takahashi, Yoshihiko Hirohashi, Toshihiko Torigoe, Yasuaki Tamura, Tomohide Tsukahara, Takayuki Kanaseki, Vitaly Kochin, Hiroshi Saijo, Terufumi Kubo, Munehide Nakatsugawa, Hiroko Asanuma, Tadashi Hasegawa, Toru Kondo, Noriyuki Sato
PLOS ONE, 8, 11, e69095, Nov. 2013, [Peer-reviewed]
English, Scientific journal

A regenerative approach to the treatment of multiple sclerosis
Vishal A. Deshmukh, Virginie Tardif, Costas A. Lyssiotis, Chelsea C. Green, Bilal Kerman, Hyung Joon Kim, Krishnan Padmanabhan, Jonathan G. Swoboda, Insha Ahmad, Toru Kondo, Fred H. Gage, Argyrios N. Theofilopoulos, Brian R. Lawson, Peter G. Schultz, Luke L. Lairson
NATURE, 502, 7471, 327, +, Oct. 2013, [Peer-reviewed]
English, Scientific journal

Preferential expression of cancer/testis genes in cancer stem-like cells: proposal of a novel sub-category, cancer/testis/stem gene
R. Yamada, A. Takahashi, T. Torigoe, R. Morita, Y. Tamura, T. Tsukahara, T. Kanaseki, T. Kubo, K. Watarai, T. Kondo, Y. Hirohashi, N. Sato
TISSUE ANTIGENS, 81, 6, 428, 434, Jun. 2013, [Peer-reviewed]
English, Scientific journal

DNA methyltransferase 1 is essential for initiation of the colon cancers
Rena Morita, Yoshihiko Hirohashi, Hiromu Suzuki, Akari Takahashi, Yasuaki Tamura, Takayuki Kanaseki, Hiroko Asanuma, Satoko Inoda, Toru Kondo, Satoshi Hashino, Tadashi Hasegawa, Takashi Tokino, Minoru Toyota, Masahiro Asaka, Toshihiko Torigoe, Noriyuki Sato
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 94, 2, 322, 329, Apr. 2013, [Peer-reviewed]
English, Scientific journal

Molecular markers of glioma initiating cells.
Kondo, T
Inflamation and Regeneration, 33, 181, 189, 2013, [Peer-reviewed], [Lead author, Last author, Corresponding author]
English, Symposium

HSP DNAJB8 Controls Tumor-Initiating Ability in Renal Cancer Stem-like Cells
Satoshi Nishizawa, Yoshihiko Hirohashi, Toshihiko Torigoe, Akari Takahashi, Yasuaki Tamura, Takashi Mori, Takayuki Kanaseki, Kenjiro Kamiguchi, Hiroko Asanuma, Rena Morita, Alice Sokolovskaya, Junichi Matsuzaki, Ren Yamada, Reona Fujii, Harm H. Kampinga, Toru Kondo, Tadashi Hasegawa, Isao Hara, Noriyuki Sato
CANCER RESEARCH, 72, 11, 2844, 2854, Jun. 2012, [Peer-reviewed]
English, Scientific journal

Efficiency of G2/M-related tumor-associated antigen-targeting cancer immunotherapy depends on antigen expression in the cancer stem-like population
Takashi Mori, Satoshi Nishizawa, Yoshihiko Hirohashi, Toshihiko Torigoe, Yasuaki Tamura, Akari Takahashi, Vitaly Kochin, Reona Fujii, Toru Kondo, Mark I. Greene, Isao Hara, Noriyuki Sato
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 92, 1, 27, 32, Feb. 2012, [Peer-reviewed]
English, Scientific journal

SOX2 is overexpressed in stem-like cells of human lung adenocarcinoma and augments the tumorigenicity
Munehide Nakatsugawa, Akari Takahashi, Yoshihiko Hirohashi, Toshihiko Torigoe, Satoko Inoda, Masaki Murase, Hiroko Asanuma, Yasuaki Tamura, Rena Morita, Yoshitaka Michifuri, Toru Kondo, Tadashi Hasegawa, Hiroki Takahashi, Noriyuki Sato
LABORATORY INVESTIGATION, 91, 12, 1796, 1804, Dec. 2011, [Peer-reviewed]
English, Scientific journal

CD133(+) Cancer Stem Cell-like Cells Derived from Uterine Carcinosarcoma (Malignant Mixed Mullerian Tumor)
Batsuren Choijamts, Shiro Jimi, Toru Kondo, Yasuko Naganuma, Taichi Matsumoto, Masahide Kuroki, Hiroshi Iwasaki, Makoto Emoto
STEM CELLS, 29, 10, 1485, 1495, Oct. 2011, [Peer-reviewed]
English, Scientific journal

Essential role of the Hedgehog signaling pathway in human glioma-initiating cells
Tatsuya Takezaki, Takuichiro Hide, Hiromi Takanaga, Hideo Nakamura, Jun-ichi Kuratsu, Toru Kondo
CANCER SCIENCE, 102, 7, 1306, 1312, Jul. 2011, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Combination of a Ptgs2 inhibitor and an epidermal growth factor receptor-signaling inhibitor prevents tumorigenesis of oligodendrocyte lineage-derived glioma-initiating cells
Takuichiro Hide, Tatsuya Takezaki, Yuka Nakatani, Hideo Nakamura, Jun-Ichi Kuratsu, Toru Kondo
Stem Cells, 29, 4, 590, 599, 4, Apr. 2011, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Cytotoxic T Lymphocytes Efficiently Recognize Human Colon Cancer Stem-Like Cells
Satoko Inoda, Yoshihiko Hirohashi, Toshihiko Torigoe, Rena Morita, Akari Takahashi, Hiroko Asanuma, Munehide Nakatsugawa, Satoshi Nishizawa, Yasuaki Tamura, Tetsuhiro Tsuruma, Takeshi Terui, Toru Kondo, Kunihiko Ishitani, Tadashi Hasegawa, Koichi Hirata, Noriyuki Sato
AMERICAN JOURNAL OF PATHOLOGY, 178, 4, 1805, 1813, Apr. 2011, [Peer-reviewed]
English, Scientific journal

Tumorigenesis of glioma-initiating cells: Role of Sox11.　　　　　　　　　　　　　　　
Toru Kondo
Stem Cells and Cancer Stem Cells, 1, 93, 98, 2011, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
English, Scientific journal

The Transcriptional Mediator Subunit MED1/TRAP220 in Stromal Cells Is Involved in Hematopoietic Stem/Progenitor Cell Support through Osteopontin Expression
Akiko Sumitomo, Ruri Ishino, Norinaga Urahama, Kana Inoue, Kenji Yonezawa, Natsumi Hasegawa, Osamu Horie, Hiroshi Matsuoka, Toru Kondo, Robert G. Roeder, Mitsuhiro Ito
MOLECULAR AND CELLULAR BIOLOGY, 30, 20, 4818, 4827, Oct. 2010, [Peer-reviewed]
English, Scientific journal

Mouse Induced Glioma-Initiating Cell Models and Therapeutic Targets
Toru Kondo
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 10, 6, 471, 480, Jul. 2010, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
English, Scientific journal

[Cancer stem cells and molecular targeting medicine].
Kondo T
Nihon rinsho. Japanese journal of clinical medicine, 68, 6, 986, 989, 6, Jun. 2010, [Peer-reviewed], [Lead author, Last author, Corresponding author]

Esophageal cancer-related gene 4 is a secreted inducer of cell senescence expressed by aged CNS precursor cells
Yuki Kujuro, Norihiro Suzuki, Toru Kondo
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 107, 18, 8259, 8264, May 2010, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation
Takuichiro Hide, Tatsuya Takezaki, Yuka Nakatani, Hideo Nakamura, Jun-Ichi Kuratsu, Toru Kondo
Cancer Research, 69, 20, 7953, 7959, 20, 15 Oct. 2009, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Side population cells have the characteristics of cancer stem-like cells/cancer-initiating cells in bone sarcomas
M. Murase, M. Kano, T. Tsukahara, A. Takahashi, T. Torigoe, S. Kawaguchi, S. Kimura, T. Wada, Y. Uchihashi, T. Kondo, T. Yamashita, N. Sato
BRITISH JOURNAL OF CANCER, 101, 8, 1425, 1432, Oct. 2009, [Peer-reviewed]
English, Scientific journal

Glioblastoma Formation from Cell Population Depleted of Prominin1-Expressing Cells
Kenji Nishide, Yuka Nakatani, Hiroshi Kiyonari, Toru Kondo
PLOS ONE, 4, 8, e6869, Aug. 2009, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Common mechanism underlying oligodendrocyte development and oligodendrogliomagenesis
Toru Kondo
Brain and Nerve, 61, 7, 741, 751, 7, Jul. 2009, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
Japanese

Gli2 Is a Novel Regulator of Sox2 Expression in Telencephalic Neuroepithelial Cells
Hiromi Takanaga, Nobuko Tsuchida-Straeten, Kenji Nishide, Akira Watanabe, Hiroyuki Aburatani, Toru Kondo
STEM CELLS, 27, 1, 165, 174, 2009, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Brain tumor stem cells as research and treatment targets
Takuichiro Hide, Tatsuya Takezaki, Hideo Nakamura, Junichi Kuratsu, Toru Kondo
BRAIN TUMOR PATHOLOGY, 25, 2, 67, 72, Nov. 2008, [Peer-reviewed], [Last author]
English

Making of glioma-initiating cells.
Kondo, T
Inflamation and Regeneration, 28, 6, 537, 542, The Japanese Society of Inflammation and Regeneration, 2008, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
English, Scientific journal, There is an increasing body of evidence that suggests that malignant tumors, such as leukemia, breast cancers, and brain cancers, contain cells that maintain the characteristics of tissue-specific stem cells (TSSCs) and are malignant. Malignant gliomas, for example, contain proliferating cells expressing neural stem cell (NSC) markers, such as nestin and CD133, and differentiating cells expressing either neuronal markers or glial markers, raising the possibility that the tumors may contain NSC-like cancer cells. Additional evidence also exists, which indicate that malignant tumors might contain stem cell-like cancer cells, called "cancer stem cells" (CSCs) or "tumor initiating cells". Although a number of anti-cancer drugs and irradiation therapy have been successful in eliminating cancers, occasionally some cancer cells survive and invade other tissues, leading to the recurrence of cancer; this indicates that the surviving cells are not only resistant to such anti-cancer drugs and irradiation but are also malignant. Previous studies have shown that various ATP binding cassette transporters, such as the multi-drug resistant protein encoded by the multi-drug resistant gene, and the breast cancer resistant protein 1 (BCRP1), contribute to drug resistance in cancers. Interestingly, some of these transporters are also expressed in many types of normal stem cells. BCRP1, for example, excludes the fluorescent dye Hoechst 33342, identifying a side population (SP) enriched with TSSCs. Taking advantage of the common characteristics that exist between TSSCs and cancer cells, many groups have demonstrated that CSCs in tumors or cancer cell lines can self-renew, express well-known TSSC markers, form tumors when transplanted in vivo and show resistance to anti-cancer treatments; this suggests that CSCs are important targets for curable therapy. In order to develop an effective therapy against tumors, characterizing and finding ways to kill CSCs is essential. In this review, I have summarized the recent progresses made in glioma CSC research and discuss the perspectives of this field.

Stem cell-like brain cancer cells
Toru Kondo
Current Cancer Therapy Reviews, 4, 3, 201, 205, 2008, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
English, Scientific journal

A potential role for bone morphogenetic protein signalling in glial cell fate determination following adult central nervous system injury in vivo
David W. Hampton, Richard A. Asher, Toru Kondo, John D. Steeves, Matt S. Ramer, James W. Fawcett
EUROPEAN JOURNAL OF NEUROSCIENCE, 26, 11, 3024, 3035, Dec. 2007, [Peer-reviewed]
English, Scientific journal

Inhibition of histone deacetylase activity induces developmental plasticity in oligodendrocyte precursor cells
Costas A. Lyssiotis, John Walker, Chunlei Wu, Toru Kondo, Peter G. Schultz, Xu Wu
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 104, 38, 14982, 14987, Sep. 2007, [Peer-reviewed]
English, Scientific journal

Stem cell-like cancer cells in cancer cell lines
T. Kondo
Cancer Biomarkers, 3, 4-5, 245, 250, IOS Press, 2007, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
English, Scientific journal

Epigenetic alchemy for cell fate conversion
Toru Kondo
CURRENT OPINION IN GENETICS & DEVELOPMENT, 16, 5, 502, 507, Oct. 2006, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
English

Multiple roles of Id4 in developmental myelination: Predicted outcomes and unexpected findings
Mireya Marin-Husstege, Ye He, Jiadong Li, Toru Kondo, Fred Sablitzky, Patrizia Casaccia-Bonnefil
GLIA, 54, 4, 285, 296, Sep. 2006, [Peer-reviewed]
English, Scientific journal

Brain cancer stem-like cells
T Kondo
EUROPEAN JOURNAL OF CANCER, 42, 9, 1237, 1242, Jun. 2006, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
English, Scientific journal

[Cancer stem cells in cancer cell lines].
Setoguchi T, Kondo T, Taga T
Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme, 50, 15, 1995, 2000, 15, Dec. 2005, [Peer-reviewed]

Id4 is required for the correct timing of neural differentiation
L Bedford, R Walker, T Kondo, van Cruchten, I, ER King, F Sablitzky
DEVELOPMENTAL BIOLOGY, 280, 2, 386, 395, Apr. 2005, [Peer-reviewed]
English, Scientific journal

Chromatin remodeling and histone modification in the conversion of oligodendrocyte precursors to neural stem cells
T Kondo, M Raff
GENES & DEVELOPMENT, 18, 23, 2963, 2972, Dec. 2004, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

Nuclear export of OLIG2 in neural stem cells is essential for ciliary neurotrophic factor-induced astrocyte differentiation
T Setoguchi, T Kondo
JOURNAL OF CELL BIOLOGY, 166, 7, 963, 968, Sep. 2004, [Peer-reviewed], [Last author, Corresponding author]
English, Scientific journal

Cancer stem cells persist in many cancer cell lines
T Setoguchi, T Taga, T Kondo
CELL CYCLE, 3, 4, 414, 415, Apr. 2004, [Peer-reviewed], [Invited], [Last author, Corresponding author]
English, Scientific journal

A role for Noggin in the development of oligodendrocyte precursor cells
T Kondo, MC Raff
DEVELOPMENTAL BIOLOGY, 267, 1, 242, 251, Mar. 2004, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

Negative regulatory effect of an oligodendrocytic bHLH factor OLIG2 on the astrocytic differentiation pathway
S Fukuda, T Kondo, H Takebayashi, T Taga
CELL DEATH AND DIFFERENTIATION, 11, 2, 196, 202, Feb. 2004, [Peer-reviewed], [Corresponding author]
English, Scientific journal

Persistence of a small subpopulation of cancer stem-like cells in the C6 glioma cell line
T Kondo, T Setoguchi, T Taga
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 101, 3, 781, 786, Jan. 2004, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

Reversion of oligodendrocyte precursor cells to multipotent neural stem cells.　　　　　　　　　　　　　　　
Toru Kondo
Biotech Medicine, 20, 4, 6, 2001, [Peer-reviewed], [Invited], [Lead author, Last author, Corresponding author]
English, Scientific journal

Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells
T Kondo, M Raff
SCIENCE, 289, 5485, 1754, 1757, Sep. 2000, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

Basic helix-loop-helix proteins and the timing of oligodendrocyte differentiation
T Kondo, M Raff
DEVELOPMENT, 127, 14, 2989, 2998, Jul. 2000, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

Identification and characterization of cell lines with a defect in a post-adsorption stage of Sendai virus-mediated membrane fusion
A Eguchi, T Kondoh, H Kosaka, T Suzuki, H Momota, A Masago, T Yoshida, H Taira, A Ishii-Watabe, J Okabe, JH Hu, N Miura, S Ueda, Y Suzuki, T Taki, T Hayakawa, M Nakanishi
JOURNAL OF BIOLOGICAL CHEMISTRY, 275, 23, 17549, 17555, Jun. 2000, [Peer-reviewed]
English, Scientific journal

The Id4 HLH protein and the timing of oligodendrocyte differentiation
T Kondo, M Raff
EMBO JOURNAL, 19, 9, 1998, 2007, May 2000, [Peer-reviewed], [Lead author, Corresponding author]
English, Scientific journal

Activation of distinct caspase-like proteases by Fas and reaper in Drosophila cells
T Kondo, T Yokokura, S Nagata
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 94, 22, 11951, 11956, Oct. 1997, [Peer-reviewed], [Lead author]
English, Scientific journal

Cytoplasmic gene expression system enhances the efficiency of cationic liposome-mediated in vivo gene transfer into mouse brain
H Mizuguchi, T Nakagawa, Y Morioka, S Imazu, M Nakanishi, T Kondo, T Hayakawa, T Mayumi
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 234, 1, 15, 18, May 1997, [Peer-reviewed]
English, Scientific journal

Essential roles of the Fas ligand in the development of hepatitis
T Kondo, T Suda, H Fukuyama, M Adachi, S Nagata
NATURE MEDICINE, 3, 4, 409, 413, Apr. 1997, [Peer-reviewed], [Lead author]
English, Scientific journal

Initiation of Sendai virus multiplication from transfected cDNA or RNA with negative or positive sense
A Kato, Y Sakai, T Shioda, T Kondo, M Nakanishi, Y Nagai
GENES TO CELLS, 1, 6, 569, 579, Jun. 1996, [Peer-reviewed]
English, Scientific journal

TARGETED MUTATION IN THE FAS GENE CAUSES HYPERPLASIA IN PERIPHERAL LYMPHOID ORGANS AND LIVER
M ADACHI, S SUEMATSU, T KONDO, J OGASAWARA, T TANAKA, N YOSHIDA, S NAGATA
NATURE GENETICS, 11, 3, 294, 300, Nov. 1995, [Peer-reviewed]
English, Scientific journal

A NOVEL GENE-TRANSFER TECHNIQUE MEDIATED BY HVJ (SENDAI VIRUS), NUCLEAR-PROTEIN, AND LIPOSOMES
N TOMITA, J HIGAKI, T OGIHARA, T KONDO, Y KANEDA
CANCER DETECTION AND PREVENTION, 18, 6, 485, 491, 1994, [Peer-reviewed]
English, Scientific journal

TEMPERATURE-SENSITIVE PHENOTYPE OF A MUTANT SENDAI VIRUS-STRAIN IS CAUSED BY ITS INSUFFICIENT ACCUMULATION OF THE M-PROTEIN
T KONDO, T YOSHIDA, N MIURA, M NAKANISHI
JOURNAL OF BIOLOGICAL CHEMISTRY, 268, 29, 21924, 21930, Oct. 1993, [Peer-reviewed], [Lead author]
English, Scientific journal

腫瘍開始細胞は炎症環境を形成し免疫細胞を老化させて抗腫瘍応答の低下を導くことで免疫健常個体における腫瘍発生を許容させる　　　　　　　　　　　　　　　
和田 はるか, 近藤 亨, 清野 研一郎, 日本癌学会総会記事, 79回, OJ12, 8, Oct. 2020
(一社)日本癌学会, English

がん幹細胞はそれ自身が原炎症性細胞であり微小環境に免疫老化及び免疫抑制をもたらすことで健常動物における造腫瘍能を担保する(Tumor-initiating cell induce immuno-hyporesponsiveness following cellular senescence to Mφs guarantee its tumorigenesis)　　　　　　　　　　　　　　　
和田 はるか, バグダーディー・ムハンマド, 近藤 亨, 清野 研一郎, 日本癌学会総会記事, 78回, J, 1042, Sep. 2019
(一社)日本癌学会, English

がん幹細胞はそれ自身が原炎症性細胞であり微小環境に免疫老化及び免疫抑制をもたらすことで健常動物における造腫瘍能を担保する　　　　　　　　　　　　　　　
和田 はるか, 村田 智己, 大塚 亮, 森口 徹夫, バグダーディー・ムハンマド, 近藤 亨, 清野 研一郎, 日本がん免疫学会総会プログラム・抄録集, 23回, 131, 131, Jul. 2019
日本がん免疫学会, Japanese

血漿エクソソーム由来microRNAを用いたグリオブラストーマ診断バイオマーカーの探索
山口 響子, 森口 徹生, 山下 大介, 大西 丘倫, 金子 貞男, 的場 亮, 鄭 漢忠, 近藤 亨, 北海道歯学雑誌, 39, 2, 94, 103, Mar. 2019
北海道歯学会, Japanese

免疫健常個体において造腫瘍能を発揮する腫瘍開始細胞の免疫学的因子の同定(Tumor initiating cell in immunocompetent animal defined by immunological features)　　　　　　　　　　　　　　　
和田 はるか, Baghdadi Muhammad, 森口 徹生, 近藤 亨, 清野 研一郎, 日本癌学会総会記事, 77回, 2327, 2327, Sep. 2018
(一社)日本癌学会, English

Secreted tumor suppressor Ecrg4 acts as a novel immunosurveillance factor
Tetsuo Moriguchi, Shuji Takeda, Uichi Koshimizu, Hidemitsu Kitamura, Toru Kondo, INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 40, S37, S37, 2017
English, Summary international conference

グリオーマ幹細胞に特異的な発現を示すexosomal microRNAの同定　　　　　　　　　　　　　　　
山下 大介, 末廣 諭, 近藤 亨, 大西 丘倫, 日本癌学会総会記事, 75回, P, 3093, Oct. 2016
日本癌学会, English

Glimはマウス及びヒトのグリオーマ形成能を亢進させる　　　　　　　　　　　　　　　
大津 直樹, 中谷 有香, 山下 大介, 大西 丘倫, 近藤 亨, 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, 88回・38回, [4T18, 12(3P1074)], Dec. 2015
(公社)日本生化学会, English

グリオーマ幹細胞の腫瘍形成を抑制するmicroRNA-340および標的分子PLATの同定と機能解析　　　　　　　　　　　　　　　
山下 大介, 近藤 亨, 大西 丘倫, 日本癌学会総会記事, 74回, E, 1086, Oct. 2015
日本癌学会, English

Glim2 regulates the proliferation of glioblastoma-initiating cells through the activation of the STAT3 signaling
Toru Kondo, Sadahiro Kaneko, INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 36, S33, S33, 2015
English, Summary international conference

ヒトグリオーマ幹細胞の腫瘍形成を抑制するmicroRNA-340の同定 機能解析と標的分子の検索　　　　　　　　　　　　　　　
山下 大介, 近藤 亨, 大上 史朗, 高橋 寿明, 末廣 諭, 井上 明宏, 高野 昌平, 大西 丘倫, Brain Tumor Pathology, 31, Suppl., 110, 110, May 2014
日本脳腫瘍病理学会, Japanese

ヒトグリオーマ幹細胞の腫瘍形成を抑制するmicroRNA‐340とその標的分子PLATの機能解析
山下大介, 近藤亨, 末廣諭, 井上明宏, 高野昌平, 大上史朗, 大西丘倫, 日本脳腫瘍学会プログラム・抄録集, 32nd, 84, 2014
Japanese

IDENTIFICATION AND CHARACTERIZATION OF A NOVEL microRNA INVOLVED IN GLIOMAGENESIS
Daisuke Yamashita, Toru Kondo, Hisaaki Takahashi, Akihiro Inoue, Shohei Kohno, Hironobu Harada, Shiro Ohue, Takanori Ohnishi, NEURO-ONCOLOGY, 15, 31, 31, Nov. 2013
English, Summary international conference

グリオーマ形成に関わる新規microRNAの性状解析　　　　　　　　　　　　　　　
山下 大介, 近藤 亨, 高橋 寿明, 井上 明宏, 高野 昌平, 原田 広信, 大上 史朗, 久門 良明, 田中 潤也, 大西 丘倫, Brain Tumor Pathology, 30, Suppl., 124, 124, May 2013
日本脳腫瘍病理学会, Japanese

新規グリオーマ幹細胞膜タンパク質Glimの機能解析
大津直樹, 中谷友香, 山下大介, 大西丘倫, 近藤亨, 日本分子生物学会年会プログラム・要旨集(Web), 36th, 1P-0815 (WEB ONLY), 2013
Japanese

Glioma形成に関わる新規microRNA(miR‐X)の機能解析及びその標的遺伝子の同定
山下大介, 近藤亨, 大上史朗, 高橋寿明, 末廣諭, 井上明宏, 高野昌平, 大西丘倫, 日本脳腫瘍学会プログラム・抄録集, 31st, 190, 2013
Japanese

SOX11 PREVENTS TUMORIGENESIS OF GLIOMA-INITIATING CELLS
Takuichiro Hide, Tatsuya Takezaki, Hideo Nakamura, Keishi Makino, Jun-ichi Kuratsu, Toru Kondo, NEURO-ONCOLOGY, 12, 122, 122, Nov. 2010
English, Summary international conference

Induced glioma-initiating cell models reveal novel therapeutic targets
Toru Kondo, Takuichiro Hide, Tatsuya Takezaki, Yuka Nakatani, Hideo Nakamura, Junichi Kuratsu, INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 26, S36, S36, 2010
English, Summary international conference

ESTABLISHMENT OF ARTIFICIAL GLIOBLASTOMA INITIATING CELLS IN MOUSE
Takuichiro Hide, Tatsuya Takezaki, Hideo Nakamura, Keishi Makino, Jun-ichi Kuratsu, Toru Kondo, NEURO-ONCOLOGY, 11, 6, 932, 932, Dec. 2009
English, Summary international conference

HEDGEHOG PATHWAY AND GLIOMAGENESIS
Tatsuya Takezaki, Hideichiro Taku, Hideo Nakamura, Jun-ichi Kuratsu, Toru Kondo, NEURO-ONCOLOGY, 11, 6, 956, 956, Dec. 2009
English, Summary international conference

Functional analysis of neural stem cell factors in gliomas
Toru Kondo, Tatsuya Takezaki, Hiromi Takanaga, Takuichiro Hide, NEUROSCIENCE RESEARCH, 61, S69, S69, 2008
English, Summary international conference

癌幹細胞の同定とその意義
瀬戸口 啓夫, 近藤 亨, 田賀 哲也, 蛋白質核酸酵素, 50, 15, 1995, 2000, Dec. 2005
共立出版, Japanese

A role for Noggin in the development of oligodendrocyte precursor cells (vol 267, pg 242, 2004)
T Kondo, MC Raff, DEVELOPMENTAL BIOLOGY, 270, 1, 272, 272, Jun. 2004
English, Others

Sendai virus vectors: New systems for gene transfer and expression
M Nakanishi, H Mizuguchi, K Ashihara, T Senda, E Nagoshi, T Akuta, T Kondoh, T Mayumi, JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION, 21, 1, 92, 94, Jul. 1996
English

神経膠芽腫幹細胞膜タンパク質Ceacam1LとEva1　　　　　　　　　　　　　　　
近藤亨
細胞, 2016, [Single work]

グリオブラストーマ幹細胞の基礎研究からの新規治療法探索　　　　　　　　　　　　　　　
近藤亨
Bio Express, 2016, [Single work]

神経膠芽腫幹細胞とマイクロRNA　　　　　　　　　　　　　　　
近藤亨
医学のあゆみ、医歯薬出版, 2014, [Single work]

グリオーマ幹細胞特異的因子群を標的とした新規治療法の開発　　　　　　　　　　　　　　　
近藤亨
次世代がん戦略研究update がん基盤生物学ー革新的シーズ育成に向けてー, 2013

癌幹細胞を標的とした治療のこれからーグリオーマ幹細胞をモデルとして　　　　　　　　　　　　　　　
近藤亨
Frontiers in Gastroenterology、メディカルレビュー社, 2013, [Single work]

モデル動物利用マニュアル「疾患モデルの作製と利用－がん」　　　　　　　　　　　　　　　
近藤亨, グリオーマ
エル・アイ・シー社, 2012, [Single work]

オリゴデンドロサイト前駆細胞　　　　　　　　　　　　　　　
近藤亨
細胞工学, 2012, [Single work]

Stem Cells and Cancer Stem Cells　　　　　　　　　　　　　　　
Kondo, T, Tumorigenesis of glioma-initiating cells: Role of Sox11.
Springer, 2011, [Single work]

Advances in Cancer Stem Cell Biology　　　　　　　　　　　　　　　
Kondo, T, Stem cells and cancer stem cells –new insights.
Springer, 2011, [Single work]

脳腫瘍の癌幹細胞治療戦略　　　　　　　　　　　　　　　
近藤亨
医薬ジャーナル, 2011, [Single work]

脳腫瘍のCSC　　　　　　　　　　　　　　　
近藤亨
BIO Clinica, 2011, [Single work]

グリオーマ　　　　　　　　　　　　　　　
近藤亨
臨床検査, 2011, [Single work]

膠芽腫　　　　　　　　　　　　　　　
近藤亨
Clinical Neuroscience、中外医学社, 2010, [Single work]

幹細胞生物学からみた脳腫瘍の発生機序　　　　　　　　　　　　　　　
近藤亨
新時代の脳腫瘍学—診断・治療の最前線— 日本臨床社, 2010, [Single work]

人工グリオーマからの考察　　　　　　　　　　　　　　　
近藤亨
再生医療、メディカルレビュー社, 2010, [Single work]

カラー図説：癌幹細胞と分子標的薬　　　　　　　　　　　　　　　
近藤亨
固形癌の最新治療—癌治療への新たな取り組みー 日本臨床社, 2010, [Single work]

炎症・再生医学事典　　　　　　　　　　　　　　　
近藤亨, 癌幹細胞
朝倉書店, 2009, [Single work]

オリゴデンドロサイトの分化制御機構とオリゴデンドログリオーマの発生　　　　　　　　　　　　　　　
近藤亨
Brain and Nerve, 2009, [Single work]

癌幹細胞マーカー　　　　　　　　　　　　　　　
近藤亨
Surgery Frontier, 2009, [Single work]

脳腫瘍における癌幹細胞　　　　　　　　　　　　　　　
近藤亨
実験医学別冊 癌と微小環境, 2009, [Single work]

シリーズ脳科学4、脳の発生と発達　　　　　　　　　　　　　　　
近藤亨, 神経細胞分化と可塑性
東京大学出版, 2008, [Single work]

脳腫瘍「癌幹細胞」研究の現状　　　　　　　　　　　　　　　
秀拓一郎, 近藤亨
実験医学、羊土社, 2008, [Joint work]

癌幹細胞¬−癌研究のフロンティア　　　　　　　　　　　　　　　
近藤亨
実験医学、羊土社, 2008, [Single work]

グリオーマ幹細胞　　　　　　　　　　　　　　　
近藤亨
細胞, 2008, [Single work]

固形がんにおけるがん幹細胞研究の進展　　　　　　　　　　　　　　　
近藤亨
血液・腫瘍化, 2008

幹細胞様グリオーマ細胞　　　　　　　　　　　　　　　
近藤亨
医学のあゆみ、医歯薬出版, 2008, [Single work]

グリオーマ起源細胞　　　　　　　　　　　　　　　
近藤亨
Clinical neuroscience、中外医学社, 2008, [Single work]

Cancer stem cell marker　　　　　　　　　　　　　　　
Toru Kondo
Cancer Frontier, 2008, [Single work]

腫瘍発生とエピジェネテック　　　　　　　　　　　　　　　
近藤亨
分子細胞治療、先端医学社, 2007, [Single work]

グリオーマ細胞株に存在する幹細胞様細胞　　　　　　　　　　　　　　　
近藤亨
医学のあゆみ、医歯薬出版, 2006, [Single work]

幹細胞様ガン細胞　　　　　　　　　　　　　　　
近藤亨
Cancer Frontier, 2006, [Single work]

脳腫瘍に内在する幹細胞様細胞　　　　　　　　　　　　　　　
近藤亨
再生医療、メディカルレビュー社, 2006, [Single work]

癌幹細胞の単離と制御シグナル〜真の癌幹細胞分離へのアプローチ　　　　　　　　　　　　　　　
近藤亨
実験医学、 羊土社, 2006, [Single work]

オリゴデンドロサイト前駆細胞の脱分化とエピジェネティクス変化　　　　　　　　　　　　　　　
近藤亨
実験医学別冊、 羊土社, 2006, [Single work]

オリゴデンドロサイト前駆細胞の可塑性　　　　　　　　　　　　　　　
近藤亨
実験医学、羊土社, 2004, [Single work]

オリゴデンドロサイトの分化制御とその可塑性　　　　　　　　　　　　　　　
近藤亨
分子細胞治療、先端医学社, 2002, [Single work]

組織幹細胞の可塑性　　　　　　　　　　　　　　　
近藤亨
再生医学・再生医療、現代化学増刊、東京化学同人, 2002

オリゴデンドロサイトの発生を制御する細胞内在時計　　　　　　　　　　　　　　　
近藤亨
医学のあゆみ、医歯薬出版, 2002

グリア前駆細胞の可塑性　　　　　　　　　　　　　　　
近藤亨
Clinical neuroscience、中外医学社, 2002

神経幹細胞の分化制御機構　　　　　　　　　　　　　　　
近藤亨
炎症と免疫、先端医学社, 2002

ラットオリゴデンドロサイト前駆細胞の単離法　　　　　　　　　　　　　　　
近藤亨
実験医学、羊土社, 2001

Timing cell-cycle exit and differentiation in oligodendrocyte development　　　　　　　　　　　　　　　
Raff, M, Apperly, J, Kondo, T, Tokumoto, Y, Tang, D
Novartis Found Symp., 2001, [Joint work]

オリゴデンドロサイトの発生を制御する“細胞時計”　　　　　　　　　　　　　　　
近藤亨
蛋白質核酸酵素、共立出版, 2001, [Single work]

神経発生の逆行；オリゴデンドロサイト前駆細胞から神経幹細胞へ　　　　　　　　　　　　　　　
近藤亨
実験医学、羊土社, 2000, [Single work]

肝炎発症におけるFas/Fasリガンドの働き　　　　　　　　　　　　　　　
近藤亨
免疫 Immunology Frontier、メディカルビュー社, 1998

生物薬科学実験講座 第３巻　　　　　　　　　　　　　　　
中西真人, 芦原賢一, 真弓忠範, 近藤 亨, 米田悦啓, HVJエンベロープタンパク質を用いた細胞内導入法
広川書店, 1995, [Joint work]

Fasリガンド　　　　　　　　　　　　　　　
近藤亨
免疫 Immunology Frontier、メディカルビュー社, 1995

Gene Introduction into animal tissues　　　　　　　　　　　　　　　
Harwood Academic Publishers Gmbh, 1995, [Joint work]

膜融合リポソームを使った細胞への高能率遺伝子導入　　　　　　　　　　　　　　　
中西真人, 芦原賢一, 千田隆夫, 近藤 亨, 真弓忠範
実験医学、羊土社, 1994, [Joint work]

標的臓器への遺伝子導入による治療　　　　　　　　　　　　　　　
中西真人, 近藤 亨, 芦原賢一
nanoGIGA、日本臨床社, 1992, [Joint work]

動物個体臓器への遺伝子導入　　　　　　　　　　　　　　　
中西真人, 加藤啓子, 近藤 亨
代謝別冊 中山書店, 1990, [Joint work]

2012 - Present
北海道癌談話会　　　　　　　　　　　　　　　

Positional and quantitative regulation of the central nervous cells by interaction of pattern formation, proliferation and differentiation timing
Grants-in-Aid for Scientific Research
01 Apr. 2020 - 31 Mar. 2023
笹井 紀明, 磯谷 綾子, 近藤 亨, 別所 康全, 白井 学
生物の各器官には、様々な機能を持つ細胞が位置的だけでなく量的（細胞数）にも正確に配置されており、それらが相互作用し合うことによって全体として特有の機能を発揮している。本研究の目的は、発生途上にある中枢神経系をモデルにして、シグナルの経時的な変化、時空間特異的な増殖と細胞の分化を司る分子を同定して機能解析し、組織内での多様な細胞分化・パターン形成の分子メカニズムを明らかにすることである。
2020年度は、神経前駆細胞を分化方向にスイッチする遺伝子の１つをスクリーニングにより同定し、主にニワトリ胚を用いてその機能を明らかにした。ニワトリ胚から単離した神経前駆細胞に経時的に遺伝子発現解析を行い、分化と同時に発現が惹起される遺伝子を網羅的に探索した結果、いくつかの分化制御因子が単離された。このうちの１つの転写因子Sox14は神経管が形成された直後から前駆細胞に発現し、神経前駆細胞の分化を一定段階まで促進することが明らかになった。さらに、同時期に同細胞で発現する別の転写因子Chx10との機能的差異を解析したところ、Sox14は神経分化を促進する役割を持つ一方、Chx10は細胞運命（分化方向）を決める因子であることが示唆された。このように２つの転写因子が相互的に働くことにより、分化が進行するメカニズムの一端が明らかになった。
同時に、Sox14のノックアウト細胞をマウスES細胞において作成し、マウスの神経分化でSox14が必須の役割を果たすことを証明した。
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Nara Institute of Science and Technology, 20H03263

Development of Innovative Gene-Virus Therapy for Tumor Lysis, Immunity Induction, and Cancer Stem Cell Suppression in Bone and Soft Tissue Sarcoma.
Grants-in-Aid for Scientific Research
01 Apr. 2017 - 31 Mar. 2020
Kosai Ken-ichiro
We generated novel Surv.m-CRA expressing various therapeutic genes and analyzed their in vitro expression and various functions (tumor lysis, systemic anti-tumor immunity induction, etc.). These experiments first confirmed the expression and function of the therapeutic genes in each of the novel Surv. m-CRA and then largely confirmed their therapeutic properties. In addition, we conducted treatment experiments on several novel Surv. m-CRA in in vivo animal models to confirm their therapeutic efficacy. Thus, therapeutic properties of each new Surv. m-CRA-1 as well as experimental data on its usefulness, have been obtained from time to time.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Kagoshima University, 17H04315

miRNA制御Crispr/Cas9発現依存的にがん幹細胞機能因子群をゲノム編集する新規がん治療用ベクターの開発　　　　　　　　　　　　　　　
革新的がん医療実現化研究事業
Nov. 2016 - Mar. 2017
近藤亨
日本医療研究開発機構, Principal investigator, Competitive research funding

グリオーマ幹細胞特異的因子群を標的とした新規治療法の開発　　　　　　　　　　　　　　　
次世代がん研究戦略推進プロジェクト
2011 - 2016
近藤亨
文部科学省, Principal investigator, Competitive research funding

癌幹細胞を標的とした癌根絶療法の創出　　　　　　　　　　　　　　　
分子イメージング研究戦略推進プログラム
Apr. 2010 - Mar. 2015
近藤亨
文部科学省, Principal investigator, Competitive research funding

人工グリオーマ幹細胞エキソソームを利用した診断・治療標的検索マイクロアレイの開発　　　　　　　　　　　　　　　
研究成果最適展開支援プログラム
2011 - 2012
近藤亨
科学技術振興機構, Principal investigator, Competitive research funding

癌幹細胞―正常細胞間コミュニーケーション分子の同定と性状解析
科学研究費補助金(新学術領域研究(研究領域提案型))
2011 - 2012
近藤 亨
１、Ecrg4下流因子の同定とその機能解析
H23年度にEcrg4+/+グリオーマ幹細胞（GIC）の野生型マウス脳における腫瘍形成能が、Ecrg4-/-GICに比べ著しく弱い事が発見した。両GICはヌードマウス脳に腫瘍を形成する事から、Ecrg4は免疫細胞を活性化する新規癌抗原であると考えられた。H24年度は、Ecrg4がT・B細胞のどちらに働いているのかの検討を進めた。始めに、抗Ecrg4抗体がEcrg4+/+GICを移植した野生型マウス末梢血中に 存在するかについて検討した結果、検出感度以下であった。この結果は、液性免疫によるEcrg4+/+GICの腫瘍形成抑制の可能性は低いことを示唆している。T細胞／NK細胞による細胞傷害実験系の確立と癌抗原としてのEcrg4の働きについて検討する予定である。同時に、Ecrg4+/+、+/-と-/-神経幹細胞（NSC）とこれら細胞から誘導したGICの遺伝子発現プロファイルを調べ、NSCとGICのEcrg4下流因子群を抽出した。これら因子の働きについて今後検討を進める予定である。
２、Ecrg4受容体の同定
Ecrg4-Fc融合タンパク質とcDNA発現ライブラリーを用いたスクリーニングにより抽出したEcrg4受容体（Ecrg4R）候補因子群からEcrg4Rを同定した。Ecrg4Rは様々な生物学的機能（疾患、細胞老化を含む）を有する細胞膜タンパク質である。様々なEcrg4とその受容体の欠損タンパク質を作製し、Ecrg4のカルボキシル末端とEcrg4Rの細胞外領域が結合領域であることを同定した。今後はEcrg4Rシグナル伝達について検討を進める予定である。
３、グリオーマ幹細胞由来細胞老化誘導因子の同定
マウスGICとヒトGIC群の遺伝子発現プロファイル解析から、発現上昇している分泌タンパク質群を抽出した。それらの機能は今後検討を進める予定である。
文部科学省, 新学術領域研究(研究領域提案型), 愛媛大学, Principal investigator, Competitive research funding, 23112512

The development of conditionally replicating adenovirus targeting cancer stem cell for innovative treatment for pediatric cancer
Grants-in-Aid for Scientific Research
2010 - 2012
KOSAI Kenichiro, MITSUI Kaoru, IRIE Rie, KONDO Toru
Although pediatric carcinomas have differentclinical and biological features from those of adult carcinomas, gene therapy for pediatric carcinoma has not been well developed. The present study aims to develop m-CRAs (conditionally replicating adenovirus targeting with multiple tumor-specific factors) that specifically treat cancer stem cells, leading to innovative therapy against pediatric carcinoma.
First, we have established the methods to enrich and purify cancer stem cells in soft tissue sarcoma, giloblastoma, hepatoblastoma et al.
Second, we revealed that our original m-CRAs efficiently treat cancer stem cells in such pediatric carcinoma.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Kagoshima University, 22390210

Functional analysis of Sox11 and Plagl1 in glioma stem cells.
Grants-in-Aid for Scientific Research
2010 - 2012
KONDO Toru, OHNISHI Takanori, KOMATSU Kenshi
We have examined about the expression of Sox11 and Plagl1 and their functions in glioma stem cells (GSC) and neural stem cells (NSC) and found the following results. (1) Expression of Sox11 in GSC is not regulated by either NeuroD or Neurogenin, both of which induce Sox11 expression in neural differentiation. We have identified the DNA domain (200bp) that regulates Sox11 expression in GSC. (2) Plagl1 is involved in both the maintenance of stemness in NSC and their DNA repair. (3) We have established efficient methods for human GSC preparation and their maintenance and examined their expression profiles.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), 愛媛大学, Principal investigator, Competitive research funding, 22390278

ヒトグリオーマ細胞株に存在する幹細胞様細胞の精製および新規マーカー遺伝子の単離　　　　　　　　　　　　　　　
科学研究費補助金（特定領域研究）
Apr. 2006 - Mar. 2008
近藤亨
文部科学省, Principal investigator, Competitive research funding

中枢神経系発生における分化抑制転写因子Id4の機能解析　　　　　　　　　　　　　　　
科学研究費補助金（特定領域研究）
Apr. 2002 - Mar. 2003
近藤亨
文部科学省, Principal investigator, Competitive research funding

アポト-シスの分子機構とその生理作用
科学研究費補助金(重点領域研究, 特定領域研究(A))
1994 - 1999
長田 重一, 近藤 亨, 渡辺 大介, 須田 貴司, 江成 政人, 田中 正人, 福永 理己郎, 福山 英啓
アポトーシスは動物の発生過程で産生される不要な細胞,害となる細胞を取り除く細胞死の過程であり、細胞・核の凝縮、断片化、染色体DNAのヌクレオソームの単位への切断をともなっている。私達は、昨年、カスパーゼ(システンプロテアーゼ)によって活性化されるDNase(CAD,caspase-activated DNase)とその阻害たんぱく質(ICAD,inhibitor of CAD)を精製、その遺伝子を単離し、アポトーシスにおけるDNA断片化の分子機構を明らかとした。すなわちCADは増殖している細胞中ではICADと複合体を形成しており、アポトーシスの刺激によりカスパーゼが活性化されると、カスパーゼはICADを切断、不活化し自由になったCADが染色体DNAを切断する。本年度、CAD,ICADの組換えたんぱく質を大腸菌や蚕細胞で合成し,CADは高い比活性を持つDNaseであること,ICADはCADの阻害たんぱく質としてばかりでなく、CADが合成される際,シャペロンとして作用することを示した。すなわち、無細胞系や動物細胞でCADはそれ単独では活性を持つたんぱく質としては合成されず,機能的なたんぱく質が合成されるにはICADの存在が必須であった。また、ICADは塩酸グアニヂンによってdenatureしたCADのrefolding過程を促進した。一方,カスパーゼによって切断される部位に変異を...
文部科学省, 重点領域研究, 特定領域研究(A), (財)大阪バイオサイエンス研究所->大阪大学, Coinvestigator not use grants, Competitive research funding, 06283229