Updated on 2022/03/30

写真a

 
HIROSE Haruka
 
Organization
Graduate School of Medicine Center for Research of Laboratory Animals and Medical Research Engineering Division for Advanced Medical Research Assistant Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine Department of Medicine
Title
Assistant Professor

Degree 1

  1. 博士(医学) ( 2016.3   大阪大学 ) 

Research Areas 2

  1. Life Science / Molecular biology

  2. Life Science / System genome science

 

Papers 34

  1. Functional assessment of miR‑1291 in colon cancer cells. International journal

    Jiaqi Wang, Yuhki Yokoyama, Haruka Hirose, Yuki Shimomura, Saki Bonkobara, Hiroaki Itakura, Shihori Kouda, Yoshihiro Morimoto, Kazumasa Minami, Hidekazu Takahashi, Satoshi Shibata, Shogo Kobayashi, Mamoru Uemura, Susumu Tanaka, Xin Wu, Shinji Tanaka, Masaki Mori, Hirofumi Yamamoto

    International journal of oncology   Vol. 60 ( 2 )   2022.2

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

    miR‑1291 exerts an anti‑tumor effect in a subset of human carcinomas, including pancreatic cancer. However, its role in colorectal cancer (CRC) is largely unknown. In the present study, the expression and effect of miR‑1291 in CRC cells was investigated. It was identified that miR‑1291 significantly suppressed the proliferation, invasion, cell mobility and colony formation of CRC cells. Additionally, miR‑1291 induced cell apoptosis. A luciferase reporter assay revealed that miR‑1291 directly bound the 3'‑untranslated region sequence of doublecortin‑like kinase 1 (DCLK1). miR‑1291 also suppressed DCLK1 mRNA and protein expression in HCT116 cells that expressed DCLK1. Furthermore, miR‑1291 suppressed cancer stem cell markers BMI1 and CD133, and inhibited sphere formation. The inhibitory effects on sphere formation, invasion and mobility in HCT116 cells were also explored and verified using DCLK1 siRNAs. Furthermore, miR‑1291 induced CDK inhibitors p21WAF1/CIP1 and p27KIP1 in three CRC cell lines, and the overexpression of DCLK1 in HCT116 cells led to a decrease of p21WAF1/CIP1 and p27KIP1. Intravenous administration of miR‑1291 loaded on the super carbonate apatite delivery system significantly inhibited tumor growth in the DLD‑1 xenograft mouse model. Additionally, the resultant tumors exhibited significant upregulation of the p21WAF1/CIP1 and p27KIP1 protein with treatment of miR‑1291. Taken together, the results indicated that miR‑1291 served an anti‑tumor effect by modulating multiple functions, including cancer stemness and cell cycle regulation. The current data suggested that miR‑1291 may be a promising nucleic acid medicine against CRC.

    DOI: 10.3892/ijo.2022.5303

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  2. MiR-1291 may inhibit cancer stemness in colon cancer cells

    Wang Jiaqi, Hirose Haruka, Yokoyama Yuhki, Hata Tsuyoshi, Inoue Akira, Hiraki Masayuki, Ohtsuka Masahisa, Takahashi Hidekazu, Mizushima Tsunekazu, Mori Masaki, Yamamoto Hirofumi

    CANCER SCIENCE   Vol. 112   page: 931 - 931   2021.2

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  3. Long noncoding RNA LNC01534 regulates cancer stem cells in colorectal cancer

    Ohtsuka Masahisa, Xin Wu, Ichihara Momoko, Hirose Haruka, Takahashi Hidekazu, Matsuda Chu, Akamatsu Hiroki, Mizushima Tsunekazu, Doki Yuichiro, Yamamoto Hirofumi

    CANCER RESEARCH   Vol. 80 ( 16 )   2020.8

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  4. miR-4711-5p regulates cancer stemness and cell cycle progression via KLF5, MDM2 and TFDP1 in colon cancer cells. International journal

    Yoshihiro Morimoto, Tsunekazu Mizushima, Xin Wu, Daisuke Okuzaki, Yuhki Yokoyama, Akira Inoue, Tsuyoshi Hata, Haruka Hirose, Yamin Qian, Jiaqi Wang, Norikatsu Miyoshi, Hidekazu Takahashi, Naotsugu Haraguchi, Chu Matsuda, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto

    British journal of cancer   Vol. 122 ( 7 ) page: 1037 - 1049   2020.3

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    BACKGROUND: It is important to establish cancer stem cell (CSC)-targeted therapies to eradicate cancer. As it is a CSC marker, we focused on Kruppel-like factor 5 (KLF5) in this study. METHODS: We searched for candidate microRNAs (miRNAs) that inhibited KLF5 expression by in silico analyses and screened them in colon cancer cell lines. RESULTS: We identified one promising miRNA, miR-4711-5p, that downregulated KLF5 expression by direct binding. This miRNA suppressed cell proliferation, migration and invasion ability, as well as stemness, including decreased stem cell marker expression, reactive oxygen species activity and sphere formation ability. MiR-4711-5p inhibited the growth of DLD-1 xenografts in nude mice with no adverse effects. We found that miR-4711-5p provoked G1 arrest, which could be attributed to direct binding of miR-4711-5p to TFDP1 (a heterodimeric partner of the E2F family). Our findings also suggested that direct binding of miR-4711-5p to MDM2 could upregulate wild-type p53, leading to strong induction of apoptosis. Finally, we found that miR-4711-5p had a potent tumour-suppressive effect compared with a putative anti-oncomiR, miR-34a, in tumour cell cultures derived from five patients with colorectal cancer. CONCLUSIONS: Our data suggest that miR-4711-5p could be a promising target for CSC therapy.

    DOI: 10.1038/s41416-020-0758-1

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  5. miR-1291の大腸癌細胞に対する抗腫瘍効果の検討

    王 佳き, 廣瀬 遥香, 森本 祥悠, 横山 雄起, 山本 浩文

    日本分子腫瘍マーカー研究会誌   Vol. 35   page: 31 - 33   2019.12

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    大腸癌に対するmiR-1291の抗腫瘍効果について検討した。ヒト大腸癌細胞株においてmiR-1291の発現量をqRT-PCRにより検討し、正常細胞よりmiR-1291の発現が低かったDLD1、HT29を用いて、miR-1291導入後の細胞増殖能、浸潤能、運動能、コロニー形成能を評価した。ヒト大腸癌細胞株DLD-1、HT29でのmiR-1291発現は非癌細胞であるHEK293と比較して低いことが分かり、これらの細胞株を用いてmiR-1291の細胞効果について検討した。DLD-1、HT29細胞にmiR-negative control(NC)およびmiR-1291を導入し、48時間、72時間後WST assayによって細胞増殖能について検討すると、miR-NC群と比較してmiR-1291投与群での細胞増殖が有意に抑制されていることが分かった。また、DLD-1、HT29細胞にmiR-1291を導入し、0、24、48、72時間後に細胞の移動面積を計測してmiR-NC群と比較した。その結果、miR-1291群では細胞移動が小さく、72時間後には有意な差がみられた。また、miR-1291の導入による細胞周期の変化について検討した結果、DLD-1においてmiR-1291投与群ではmiR-NC投与群に比べて、12時間においてG1期からS期への移行が抑制されて遅延していた。

  6. E-cadherin-Fc chimera protein matrix enhances cancer stem-like properties and induces mesenchymal features in colon cancer cells. International journal

    Yamin Qian, Xin Wu, Yuhki Yokoyama, Daisuke Okuzaki, Mai Taguchi, Haruka Hirose, Jiaqi Wang, Tsuyoshi Hata, Akira Inoue, Masayuki Hiraki, Masahisa Ohtsuka, Hidekazu Takahashi, Naotsugu Haraguchi, Tsunekazu Mizushima, Shinji Tanaka, Masaki Mori, Hirofumi Yamamoto

    Cancer science   Vol. 110 ( 11 ) page: 3520 - 3532   2019.11

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    Cancer stem cells (CSC) are a subpopulation of tumor cells with properties of high tumorigenicity and drug resistance, which lead to recurrence and poor prognosis. Although a better understanding of CSC is essential for developing cancer therapies, scarcity of the CSC population has hindered such analyses. The aim of the present study was to elucidate whether the E-cadherin-Fc chimera protein (E-cad-Fc) enhances cancer stem-like properties because studies show that soluble E-cadherin stimulates human epithelial growth factor receptor (EGFR) and downstream signaling pathways that are reported to play a crucial role in CSC. For this purpose, we used ornithine decarboxylase (ODC)-degron-transduced (Degron(+)) KM12SM cells as a CSC model that retains relatively low CSC properties. Compared to cultures without E-cad-Fc treatment, we found that E-cad-Fc treatment further suppressed proteasome activity and largely enhanced cancer stem-like properties of ODC-degron-transduced KM12SM cells. These results include increased expression of stem cell markers Lgr5, Bmi-1, SOX9, CD44, and CD44v9, aldehyde dehydrogenase (ALDH), and enhancement of robust spheroid formation, and chemoresistance to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP). These effects could be attributed to activation of the EGFR pathway as identified by extensive phosphorylation of EGFR, ERK, PI3K, AKT, and mTOR. In SW480 cells, E-cad-Fc matrix induced some CSC markers such as CD44v9 and ALDH. We also found that E-cad-Fc matrix showed high efficiency of inducing mesenchymal changes in colon cancer cells. Our data suggest that the E-cad-Fc matrix may enhance CSC properties such as enhancement of chemoresistance and sphere formation.

    DOI: 10.1111/cas.14193

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  7. miR-1291の大腸癌細胞に対する抗腫瘍効果の検討

    王 佳き, 廣瀬 遥香, 森本 祥悠, 横山 雄起, 山本 浩文

    日本分子腫瘍マーカー研究会プログラム・講演抄録   Vol. 39回   page: 70 - 72   2019.9

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  8. 分子温熱療法の可能性

    安田 知世, 久保田 結衣, 横山 雄起, 廣瀬 遥香, 柴田 理志, 長谷川 武夫, 武田 力, 山本 浩文

    Thermal Medicine   Vol. 35 ( 3 ) page: 75 - 76   2019.9

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    Language:Japanese   Publisher:(一社)日本ハイパーサーミア学会  

  9. C4.4A染色による大腸癌再発予測に関するvalidation study(C4.4A expression at the invasion front may predict disease recurrence of colorectal cancer: A validation study)

    岩崎 真衣, 武田 和, 外山 愛, 大塚 正久, 横山 雄起, 廣瀬 遥香, 大西 直, 村田 幸平, 加藤 健志, 水島 恒和, 土岐 祐一郎, 山本 浩文

    日本癌学会総会記事   Vol. 78回   page: P - 3062   2019.9

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  10. 難治性癌に対する核酸医薬MIRTXの抗腫瘍効果の検討(Anti-tumor effect of MIRTX in refractory tumor cells)

    五島 碧, 横山 雄起, 入江 侑馬, 廣瀬 遥香, 木島 貴志, 三好 康雄, 柴田 理志, 山本 浩文

    日本癌学会総会記事   Vol. 78回   page: P - 1242   2019.9

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  11. 結腸癌細胞においてE-cadherin-Fcは上皮間葉転換を誘導し癌幹様特性を増強する(E-cadherin-Fc Induces Epithelial Mesenchymal Transition and Enhance Cancer Stem-Like Properties in Colon Cancer Cells)

    田口 真衣, 山本 浩文, 横山 雄起, 銭 雅敏, 廣瀬 遥香, 呉 しん

    日本癌学会総会記事   Vol. 78回   page: P - 3063   2019.9

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  12. 大腸癌細胞株におけるKLF5エンハンサー領域の同定(Identification of the KLF5 enhancer region in colon cancer cell lines)

    武田 和, 横山 雄起, 藤田 敏次, 北川 公望, 廣瀬 遥香, 高橋 秀和, 植村 守, 松田 宙, 水島 恒和, 森 正樹, 土岐 祐一郎, 藤井 穂高, 山本 浩文

    日本癌学会総会記事   Vol. 78回   page: P - 3056   2019.9

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  13. Nucleic acid medicine for KRAS mutant colon cancer.

    Ishikawa Sho, Takahashi Hidekazu, Yokoyama Yuhki, Qian Yamin, Hirose Haruka, Miyoshi Norikatsu, Haraguchi Naotsugu, Hata Taishi, Matsuda Chu, Mizushima Tsunekazu, Doki Yuichiro, Mori Masaki, Yamamoto Hirofumi

    Japan Journal of Molecular Tumor Marker Research   Vol. 34 ( 0 ) page: 61 - 63   2019

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    DOI: 10.11241/jsmtmr.34.61

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  14. Anti-tumor effect of miR-1291 in colon cancer cells

    Wang Jiaqi, Hirose Haruka, Morimoto Yoshihiro, Yokoyama Yuhki, Yamamoto Hirofumi

    Japan Journal of Molecular Tumor Marker Research   Vol. 35 ( 0 ) page: 31 - 33   2019

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    DOI: 10.11241/jsmtmr.35.31

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  15. Sox2 is associated with cancer stem-like properties in colorectal cancer. International journal

    Koki Takeda, Tsunekazu Mizushima, Yuhki Yokoyama, Haruka Hirose, Xin Wu, Yamin Qian, Katsuya Ikehata, Norikatsu Miyoshi, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto

    Scientific reports   Vol. 8 ( 1 ) page: 17639 - 17639   2018.12

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    Sox2 is known as the undifferentiated cell marker. Recent studies have shown that Sox2 may also be involved in the maintenance of cancer stem cells (CSCs) in skin and bladder cancers. In this study, we aimed to clarify the role of Sox2 in colorectal CSCs. Sox2 expression was measured in colon cancer cells and colorectal clinical samples by qRT-PCR and western blot analysis. To visualize the active Sox2 mRNA production, we generated a Sox2 promoter-dependent DsRed fluorescence emission system. Colon cancer cell lines and colorectal tumor tissues generally expressed the Sox2 protein. Knockdown of Sox2 by siRNA led to increased proliferative activity in Caco2 cells. Kaplan-Meier survival curves showed that the group with high Sox2 mRNA expression had a worse prognosis for relapse-free survival (RFS) than the low expression group (P = 0.045, median follow-up 60.0 months). Time-lapse image analysis revealed that most DsRed+ cells exhibited typical asymmetric cell division and had higher CSC marker expressions. The DsRed+ cells exhibited chemoresistance and they grew slower in vitro, yet they established rather larger tumors in vivo. Our data suggest that Sox2 may be a potential biomarker for colorectal CSCs.

    DOI: 10.1038/s41598-018-36251-0

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  16. A model of quiescent cancer stem cell through condensation of ODC degron plus cells

    Ikeshima Ryo, Yokoyama Yuhki, Hirose Haruka, Takahashi Hidekazu, Haraguchi Naotsugu, Miyoshi Norikatsu, Nishida Naohiro, Hata Taishi, Matsuda Chu, Mizushima Tsunekazu, Doki Yuichiro, Mori Masaki, Yamamoto Hirofumi

    CANCER SCIENCE   Vol. 109   page: 704 - 704   2018.12

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  17. E-cadherin-coating enhances cancer stem-like properties and induces mesenchymal features in colon cancer cells

    Qian Yamin, Wu Xin, Yokoyama Yuhki, Taguchi Mai, Wang Jiaqi, Hirose Haruka, Mori Seiji, Matsuura Nariaki, Yamamoto Hirofumi

    CANCER SCIENCE   Vol. 109   page: 262 - 262   2018.12

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  18. Sox2 gene endows colon cancer cells with cancer stem like property

    Takeda Koki, Hata Taishi, Yokoyama Yuhki, Hirose Haruka, Miyoshi Norikatsu, Takahashi Hidekazu, Haraguchi Naotsugu, Nishida Naohiro, Matsuda Chu, Mizushima Tsunekazu, Doki Yuichiro, Mori Masaki, Yamamoto Hirofumi

    CANCER SCIENCE   Vol. 109   page: 676 - 676   2018.12

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  19. Promoter-dependent visualization of cancer cells

    Hirose Haruka, Yokoyama Yuhki, Takeda Koki, Ikehata Katsuya, Ikeshima Ryo, Mizushima Tsunekazu, Koizumi Masahiko, Mori Masaki, Yamamoto Hirofumi

    CANCER SCIENCE   Vol. 109   page: 1315 - 1315   2018.12

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  20. Nucleic acid medicine for KRAS mutant colon cancer

    Ishikawa Sho, Takahashi Hidekazu, Yokoyama Yuhki, Qian Yamin, Hirose Haruka, Miyoshi Norikatsu, Haraguchi Naotsugu, Hata Taishi, Matsuda Chu, Mizushima Tsunekazu, Doki Yuichiro, Mori Masaki, Yamamoto Hirofumi

    CANCER SCIENCE   Vol. 109   page: 1084 - 1084   2018.12

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  21. MicroRNA-29 may suppress colon carcinogenesis by inhibiting DSS-induced colitis

    Tsujimura Naoto, Yokoyama Yuhki, Inoue Akira, Hirose Haruka, Miyoshi Norikatsu, Takahashi Hidekazu, Haraguchi Naotsugu, Hata Taishi, Matsuda Chu, Mizushima Tsunekazu, Doki Yuichiro, Mori Masaki, Yamamoto Hirofumi

    CANCER SCIENCE   Vol. 109   page: 808 - 808   2018.12

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  22. Mesothelial cells facilitate cancer stem-like properties in spheroids of ovarian cancer cells

    Shishido Akemi, Mori Seiji, Yokoyama Yuhki, Hamada Yoshinosuke, Minami Kazumasa, Qian Yamin, Wang Jiaqi, Hirose Haruka, Wu Xin, Kawaguchi Naomasa, Nagumo Sachiko, Matsuura Nariaki, Yamamoto Hirofumi

    CANCER SCIENCE   Vol. 109   page: 1256 - 1256   2018.12

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  23. Mesothelial cells facilitate cancer stem‑like properties in spheroids of ovarian cancer cells. International journal

    Akemi Shishido, Seiji Mori, Yuhki Yokoyama, Yoshinosuke Hamada, Kazumasa Minami, Yamin Qian, Jiaqi Wang, Haruka Hirose, Xin Wu, Naomasa Kawaguchi, Sachiko Nagumo, Nariaki Matsuura, Hirofumi Yamamoto

    Oncology reports   Vol. 40 ( 4 ) page: 2105 - 2114   2018.10

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    Ovarian cancer is characterized by widespread peritoneal dissemination with ascites. Spheroids observed in the ascites of ovarian cancer patients are a mixture of cancer cells and mesothelial cells. In the present study, we evaluated whether mesothelial cells exfoliated from the peritoneum facilitate tumor spheroid formation and give rise to cancer stem‑like properties in ovarian cancer cells. Spheroids from the CAOV3 and A2780 ovarian cancer cell lines grew much larger in co‑culture with mesothelial cells than in monoculture under 3D conditions. The spheroids in co‑culture displayed high Ki‑67 expression in the peripheral zone and low expression in the central zone area. The expression of CD133 emerged in the inner portion of spheroids at later time‑points (96 and 168 h), indicating that cancer cells expanded to the inner spheroid and acquired stem cell‑properties. The mRNA levels of cancer stem cell markers Dclk‑1, CD44 and Bmi‑1 significantly increased in co‑cultured CAOV3 and mesothelial cells compared to CAOV3 cells alone. Furthermore, the mesothelial cells promoted the tumorigenesis and growth of the CAOV3 cells in a mouse xenograft model compared to cancer cells alone. In conclusion, mesothelial cells promoted spheroid formation by ovarian cancer cells and facilitated cancer stem‑like properties.

    DOI: 10.3892/or.2018.6605

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  24. The Supercarbonate Apatite-MicroRNA Complex Inhibits Dextran Sodium Sulfate-Induced Colitis. International journal

    Tadafumi Fukata, Tsunekazu Mizushima, Junichi Nishimura, Daisuke Okuzaki, Xin Wu, Haruka Hirose, Yuhki Yokoyama, Yui Kubota, Kazuya Nagata, Naoto Tsujimura, Akira Inoue, Norikatsu Miyoshi, Naotsugu Haraguchi, Hidekazu Takahashi, Taishi Hata, Chu Matsuda, Hisako Kayama, Kiyoshi Takeda, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto

    Molecular therapy. Nucleic acids   Vol. 12   page: 658 - 671   2018.9

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    The incidence of inflammatory bowel disease (IBD) is increasing. Nucleic acid-based medicine has potential as a next-generation treatment, but it is rarely successful with IBD. The aim of this study was to establish a microRNA-based therapy in an IBD model. For this purpose, we used microRNA-29 (miR-29) and a supercarbonate apatite (sCA) nanoparticle as a drug delivery system. Injection of sCA-miR-29a-3p or sCA-miR-29b-3p into mouse tail veins markedly prevented and restored inflammation because of dextran sulfate sodium (DSS)-induced colitis. RNA sequencing analysis revealed that miR-29a and miR-29b could inhibit the interferon-associated inflammatory cascade. Subcutaneous injection of sCA-miR-29b also potently inhibited inflammation, and it efficiently targeted CD11c+ dendritic cells (DCs) among various types of immune cells in the inflamed mucosa. RT-PCR analysis indicated that the miR-29 RNAs in CD11c+ DCs suppressed the production of interleukin-6 (IL-6), transforming growth factor β (TGF-β), and IL-23 subunits in DSS-treated mice. This may inhibit Th17 differentiation and subsequent activation, which is critical in IBD pathogenesis. In vivo experiments using a non-natural artificial microRNA sequence revealed that targeting of DCs in the inflamed colon is an exceptional feature of sCA. This study suggests that sCA-miR-29s may open a new avenue in nucleic acid-based medicine for IBD treatment.

    DOI: 10.1016/j.omtn.2018.07.007

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  25. E-cad-Fcコーティングによる癌幹細胞性質の増強(E-cadherin-coating enhances cancer stem-like properties and induces mesenchymal features in colon cancer cells)

    銭 雅敏, 呉 しん, 横山 雄起, 田口 真衣, 王 かき, 廣瀬 遥香, 森 誠司, 松浦 成昭, 山本 浩文

    日本癌学会総会記事   Vol. 77回   page: 276 - 276   2018.9

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  26. 中皮細胞はスフェロイド中の卵巣癌細胞の幹細胞様形質を促進する(Mesothelial cells facilitate cancer stem-like properties in spheroids of ovarian cancer cells)

    宍戸 明美, 森 誠司, 横山 雄起, 濱田 吉之輔, 皆巳 和賢, 銭 雅敏, 王 かき, 廣瀬 遥香, 呉 しん, 河口 直正, 南雲 サチ子, 松浦 成昭, 山本 浩文

    日本癌学会総会記事   Vol. 77回   page: 2107 - 2107   2018.9

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  27. KRAS変異を有する大腸癌、膵癌に対するmicroRNAによる治療

    石川 翔, 高橋 秀和, 横山 雄起, 銭 雅敏, 廣瀬 遥香, 三吉 範克, 原口 直紹, 畑 泰司, 松田 宙, 水島 恒和, 土岐 祐一郎, 森 正樹, 山本 浩文

    日本分子腫瘍マーカー研究会プログラム・講演抄録   Vol. 38回   page: 78 - 80   2018.9

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  28. プロモーター作動性癌細胞可視化システムの構築(Promoter-dependent visualization of cancer cells)

    廣瀬 遥香, 横山 雄起, 武田 昂樹, 池端 克哉, 池嶋 遼, 水島 恒和, 小泉 雅彦, 森 正樹, 山本 浩文

    日本癌学会総会記事   Vol. 77回   page: 2330 - 2330   2018.9

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  29. Sox2遺伝子は大腸癌細胞に癌幹細胞様性質を賦与する(Sox2 gene endows colon cancer cells with cancer stem like property)

    武田 昂樹, 畑 泰司, 横山 雄起, 廣瀬 遥香, 三吉 範克, 高橋 秀和, 原口 直紹, 西田 尚弘, 松田 宙, 水島 恒和, 土岐 祐一郎, 森 正樹, 山本 浩文

    日本癌学会総会記事   Vol. 77回   page: 991 - 991   2018.9

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  30. ODCデグロン陽性細胞濃縮による静止期大腸癌幹細胞モデルの作製(A model of quiescent cancer stem cell through condensation of ODC degron+ cells)

    池嶋 遼, 横山 雄起, 廣瀬 遥香, 高橋 秀和, 原口 直紹, 三吉 範克, 西田 尚弘, 畑 泰司, 松田 宙, 水島 恒和, 土岐 祐一郎, 森 正樹, 山本 浩文

    日本癌学会総会記事   Vol. 77回   page: 1220 - 1220   2018.9

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    Language:English   Publisher:日本癌学会  

  31. MicroRNA-29はDSS腸炎を抑制することにより発癌を抑える可能性がある(MicroRNA-29 may suppress colon carcinogenesis by inhibiting DSS-induced colitis)

    辻村 直人, 横山 雄起, 井上 彬, 廣瀬 遥香, 三吉 範克, 高橋 秀和, 原口 直紹, 畑 泰司, 松田 宙, 水島 恒和, 土岐 祐一郎, 森 正樹, 山本 浩文

    日本癌学会総会記事   Vol. 77回   page: 1253 - 1253   2018.9

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  32. KRAS変異型大腸癌の核酸治療(Nucleic acid medicine for KRAS mutant colon cancer)

    石川 翔, 高橋 秀和, 横山 雄起, 銭 雅敏, 廣瀬 遥香, 三吉 範克, 原口 直紹, 畑 泰司, 松田 宙, 水島 恒和, 土岐 祐一郎, 森 正樹, 山本 浩文

    日本癌学会総会記事   Vol. 77回   page: 1923 - 1923   2018.9

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  33. A miR-29b Byproduct Sequence Exhibits Potent Tumor-Suppressive Activities via Inhibition of NF-κB Signaling in KRAS-Mutant Colon Cancer Cells. International journal

    Akira Inoue, Tsunekazu Mizushima, Xin Wu, Daisuke Okuzaki, Nanami Kambara, Sho Ishikawa, Jiaqi Wang, Yamin Qian, Haruka Hirose, Yuhki Yokoyama, Ryo Ikeshima, Masayuki Hiraki, Norikatsu Miyoshi, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Yuichiro Doki, Masaki Mori, Hirofumi Yamamoto

    Molecular cancer therapeutics   Vol. 17 ( 5 ) page: 977 - 987   2018.5

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

    We previously demonstrated that miR-29b-3p is a hopeful miRNA-based therapy against colorectal cancer. In this study, we aimed to clarify a value of miR-29b-1-5p as a next-generation treatment, especially for KRAS-mutant colorectal cancer. RT-PCR assay showed that the expression of miR-29b-3p was high, and its partner strand, miR-29b-1-5p, level was only negligible in clinical colorectal cancer samples. Mimic-miR-29b-1-5p significantly inhibited proliferation of KRAS-mutant colorectal cancer cell lines DLD1 and SW480 and KRAS wild-type HT29 cells. Proliferative activity was further examined by either miR-29b-1-5p strand or its opposite complementary sequence because miR-29b-1-5p is a passenger miRNA and may have no physiologic function. We found that completely opposite complementary strand to miR-29b-1-5p, but not miR-29b-1-5p, possessed a potent antitumor effect and named this byproduct miRNA sequence "MIRTX." MIRTX directly targeted the 3'-UTR of CXCR2 and PIK3R1 mRNA and suppressed the NF-κB signaling pathway in KRAS-mutated colorectal cancer cells. MIRTX induced apoptosis in DLD1 with downregulation of antiapoptotic BCL2, BCL-xL, and MCL1 and upregulation of cleaved caspase-3 and cleaved PARP. In mouse xenograft models, systemic administration of MIRTX using a super carbonate apatite as a delivery vehicle significantly inhibited tumor growth of DLD1 and HT29 cells without any particular toxicities. In conclusion, these findings indicate that inhibition of NF-κB signaling by this novel miRNA-based therapeutic could be a promising treatment against refractory KRAS-mutant colorectal cancer and KRAS wild-type colorectal cancer. Mol Cancer Ther; 17(5); 977-87. ©2018 AACR.

    DOI: 10.1158/1535-7163.MCT-17-0850

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    PubMed

  34. Super Carbonate Apatite Nanoparticles Can Adjunctively Reduce Tumor Interstitial Fluid Pressure and Enhance the Uptake of Chemicals into Tumor

    Wu X., Yamamoto H., Hirose H., Yamamoto Y., Ueno H., Mori M.

    ANNALS OF SURGICAL ONCOLOGY   Vol. 23   page: S81 - S81   2016.2

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    Language:Japanese  

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MISC 1

  1. MiR-1291 may inhibit cancer stemness in colon cancer cells

    王佳き, 廣瀬遥香, 横山雄起, 波多豪, 井上彬, 平木将之, 大塚正久, 高橋秀和, 水島恒和, 森正樹, 山本浩文, 山本浩文

    日本癌学会学術総会抄録集(Web)   Vol. 79th   2020

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KAKENHI (Grants-in-Aid for Scientific Research) 1

  1. 乳がんゲノム遺伝子変異の不均一性及び幹細胞階層性の1細胞レベル統合解明

    Grant number:21H02761  2021.4 - 2024.3

    科学研究費助成事業  基盤研究(B)

    後藤 典子, 鈴木 穣, 岡本 康司, 廣瀬 遥香

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    Authorship:Coinvestigator(s) 

    本研究では、研究代表者がこれまでに収集してきたヒト乳がん臨床検体由来patient-derived xenograft (PDX)を活用し、ゲノム遺伝子変異の蓄積によるがん組織の不均一性と、幹細胞性を維持するシグナルを指標とした機能的ヒエラルキーを統合させる研究を行い、がんの病態の本質を理解することを目的とする。具体的には、がん幹細胞を濃縮させた細胞分画を用いて、1細胞ごとのトランスクリプトーム並びにゲノム遺伝子変異解析を行う。さらにPDX組織切片上で、網羅的に遺伝子発現を可視化する。最終的には、真にがんを根治できる全く新しい治療コンセプトの確立を目指す。