Development of 3D histopathological vascular imaging

• Project/Area Number: 19K16557
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Osaka University
• Principal Investigator: Satoshi Nojima 大阪大学, 医学系研究科, 准教授 (40528791)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2020: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2019: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
• Keywords: イメージング / 組織透明化 / 3次元イメージング / 人工知能 / 機械学習 / 人口知能 / 人体病理学 / 臨床病理学

Outline of Research at the Start

組織透明化/３次元イメージング技術CUBICを応用し、本研究では、患者由来の腫瘍組織における血管の３次元構築を研究対象とする。腫瘍の中では特に、その随伴血管の不整さの組織病理診断的価値が高いとされる神経膠腫（グリオーマ）を第一の題材疾患とする。

Outline of Final Research Achievements

We could perform imaging of vasculature in brain tumor using tissue-clearing method by CUBIC-L, CUBIC-R+ reagents and fluorescent dye-conjugated Tomato-lectin. We were also able to observe irregular arrangement of myocardial fibers in a tissue from a patient of dilated cardiomyopathy.

Academic Significance and Societal Importance of the Research Achievements

透明化試薬、蛍光プローブを用いることで、腫瘍内部を走行する血管構造を明瞭にイメージングする手法を確立することができた。今後これらの技術が標準化されることで、従来では難しかった診断が可能になることや、自動診断の発展に寄与することが期待できる。

Research Products

• [Journal Article] The expression of trefoil factor 3 is related to histologic subtypes and invasiveness in lung adenocarcinoma. (2021)
  • Author(s): Luo W, Tahara S, Kawasaki K, Kobayashi A, Nojima S, Morii E.
  • Journal Title: Oncol Lett. Volume: 63 Issue: 1 Pages: 63-63
  • DOI: 10.3892/ol.2020.12325
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Detection of fucosylated haptoglobin using the 10-7G antibody as a biomarker for evaluating endoscopic remission in ulcerative colitis (2021)
  • Author(s): Motooka Kei、Morishita Koichi、Ito Nami、Shinzaki Shinichiro、Tashiro Taku、Nojima Satoshi、Shimizu Kayoko、Date Mutsuhiro、Sakata Natsumi、Yamada Momoko、Takamatsu Shinji、Kamada Yoshihiro、Iijima Hideki、Mizushima Tsunekazu、Morii Eiichi、Takehara Tetsuo、Miyoshi Eiji
  • Journal Title: World Journal of Gastroenterology Volume: 27 Issue: 2 Pages: 162-175
  • DOI: 10.3748/wjg.v27.i2.162
  • Peer Reviewed / Open Access
• [Journal Article] Identification of fucosylated haptoglobin‐producing cells in pancreatic cancer tissue and its molecular mechanism (2021)
  • Author(s): Ito Nami、Yamada Momoko、Morishita Koichi、Nojima Satoshi、Motooka Kei、Sakata Natsumi、Asuka Tatsuya、Otsu Ryoji、Takamatsu Shinji、Kamada Yoshihiro、Mori Soichiro、Akita Hirofumi、Eguchi Hidetoshi、Morii Eiichi、Miyoshi Eiji
  • Journal Title: Glycoconjugate Journal Volume: 38 Issue: 1 Pages: 45-54
  • DOI: 10.1007/s10719-020-09970-8
  • Peer Reviewed
• [Journal Article] An immature inhibin‐α‐expressing subpopulation of ovarian clear cell carcinoma cells is related to an unfavorable prognosis (2021)
  • Author(s): Kusumoto Shinya、Kurashige Masako、Ohshima Kenji、Tahara Shinichiro、Matsui Takahiro、Nojima Satoshi、Hattori Satoshi、Morii Eiichi
  • Journal Title: Cancer Medicine Volume: 10 Issue: 5 Pages: 1485-1500
  • DOI: 10.1002/cam4.3801
  • Peer Reviewed / Open Access
• [Journal Article] Proteomics of serum extracellular vesicles identifies a novel COPD biomarker, fibulin-3 from elastic fibres. (2021)
  • Author(s): Koba, Takeda, Narumi, Shiromizu, Nojima, Ito, Kuroyama, Futami, Takimoto, Matsuki, Edahiro, Nojima, Hayama, Fukushima, Hirata, Koyama, Iwahori, Nagatomo, Suzuki, Shirai, Murakami, Nakanishi, Nakatani, Suga, Miyake, Shiroyama, Kida, Sasaki, Ueda, Mizuguchi, Adachi, Tomonaga, Kumanogoh
  • Journal Title: ERJ open research. Volume: 7(1) Issue: 1 Pages: 00658-2020
  • DOI: 10.1183/23120541.00658-2020
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tumour Grade Significantly Correlates With Total Dysfunction of Tumour Tissue-Infiltrating Lymphocytes in Renal Cell Carcinoma (2020)
  • Author(s): Kawashima A, Kanazawa T, Kidani Y, Yoshida T, Hirata M, Nishida K, Nojima S, Yamamoto Y, Kato T, Hatano K, Ujike T, Nagahara A, Fujita K, Morimoto-Okazawa A, Iwahori K, Uemura M, Imamura R, Ohkura N, Morii E, Sakaguchi S, Wada H, Nonomura N.
  • Journal Title: Sci Rep . Volume: 10 Issue: 1 Pages: 6220-6220
  • DOI: 10.1038/s41598-020-63060-1
  • Peer Reviewed / Open Access
• [Journal Article] FAM111B enhances proliferation of KRAS ‐driven lung adenocarcinoma by degrading p16 (2020)
  • Author(s): Kawasaki Keisuke、Nojima Satoshi、Hijiki Sachiko、Tahara Shinichiro、Ohshima Kenji、Matsui Takahiro、Hori Yumiko、Kurashige Masako、Umeda Daisuke、Kiyokawa Hiroki、Kido Kansuke、Okuzaki Daisuke、Morii Eiichi
  • Journal Title: Cancer Science Volume: 111 Issue: 7 Pages: 2635-2646
  • DOI: 10.1111/cas.14483
  • Peer Reviewed / Open Access
• [Journal Article] TERT C228T mutation in non‐malignant bladder urothelium is associated with intravesical recurrence for patients with non‐muscle invasive bladder cancer (2020)
  • Author(s): Hayashi Yujiro、Fujita Kazutoshi、Nojima Satoshi、Tomiyama Eisuke、Matsushita Makoto、Koh Yoko、Nakano Kosuke、Wang Cong、Ishizuya Yu、Kato Taigo、Hatano Koji、Kawashima Atsunari、Ujike Takeshi、Uemura Motohide、Imamura Ryoichi、Morii Eiichi、Nonomura Norio
  • Journal Title: Molecular Oncology Volume: 14 Issue: 10 Pages: 2375-2383
  • DOI: 10.1002/1878-0261.12746
  • Peer Reviewed / Open Access
• [Journal Article] Serine racemase enhances growth of colorectal cancer by producing pyruvate from serine (2020)
  • Author(s): Kenji Ohshima, Satoshi Nojima, Shinichiro Tahara, Masako Kurashige, Keisuke Kawasaki, Yumiko Hori, Moyu Taniguchi, Yutaka Umakoshi, Daisuke Okuzaki, Naoki Wada, Jun-ichiro Ikeda, Eiichiro Fukusaki & Eiichi Morii
  • Journal Title: Nature Metabolism volume Volume: 2 Issue: 1 Pages: 81-96
  • DOI: 10.1038/s42255-019-0156-2
  • Peer Reviewed
• [Journal Article] HTR3A is correlated with unfavorable histology and promotes proliferation through ERK phosphorylation in lung adenocarcinoma (2020)
  • Author(s): Tone Mitsuyo、Tahara Shinichiro、Nojima Satoshi、Motooka Daisuke、Okuzaki Daisuke、Morii Eiichi
  • Journal Title: Cancer Science Volume: 111 Issue: 10 Pages: 3953-3961
  • DOI: 10.1111/cas.14592
  • Peer Reviewed / Open Access
• [Journal Article] Severe myocarditis with slight lymphocytic infiltration after nivolumab treatment (2020)
  • Author(s): Edahiro Ryuya、Shiroyama Takayuki、Hijiki Sachiko、Nojima Satoshi、Shirai Yuya、Koyama Shohei、Kumanogoh Atsushi
  • Journal Title: Lung Cancer Volume: 140 Pages: 116-117
  • DOI: 10.1016/j.lungcan.2019.12.004
  • Peer Reviewed
• [Journal Article] Pathological and therapeutic implications of eosinophil-derived semaphorin 4D in eosinophilic chronic rhinosinusitis (2020)
  • Author(s): Tsuda T、Nishide M、Maeda Y、Hayama Y、Koyama S、Nojima S、Takamatsu H、Okuzaki D、Morita T、Nakatani T、Kato Y、Nakanishi Y、Futami Y、Suga Y、Naito Y、Konaka H、Satoh S、Naito M、Izumi M、Obata S、Nakatani A、Shikina T、Takeda K、Hayama M、Inohara H、Kumanogoh A
  • Journal Title: Journal of Allergy and Clinical Immunology Volume: 145 Issue: 3 Pages: 843-854
  • DOI: 10.1016/j.jaci.2019.12.893
  • Peer Reviewed / Open Access
• [Journal Article] Dysregulated Expression of the Nuclear Exosome Targeting Complex Component Rbm7 in Nonhematopoietic Cells Licenses the Development of Fibrosis (2020)
  • Author(s): Fukushima Kiyoharu、Satoh Takashi、Sugihara Fuminori、Sato Yuki、Okamoto Toru、Mitsui Yuichi、Yoshio Sachiyo、Li Songling、Nojima Satoshi、Motooka Daisuke、Nakamura Shota、Kida Hiroshi、Standley Daron M.、Morii Eiichi、Kanto Tatsuya、Yanagita Motoko、Matsuura Yoshiharu、Nagasawa Takashi、Kumanogoh Atsushi、Akira Shizuo
  • Journal Title: Immunity Volume: 52 Issue: 3 Pages: 542-556
  • DOI: 10.1016/j.immuni.2020.02.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] GREB1 induced by Wnt signaling promotes development of hepatoblastoma by suppressing TGFβ signaling. (2019)
  • Author(s): Matsumoto S, Yamamichi T, Shinzawa K, Kasahara Y, Nojima S, Kodama T, Obika S, Takehara T, Morii E, Okuyama H, Kikuchi A.
  • Journal Title: Nature Communications Volume: 28 Issue: 1 Pages: 3882-3882
  • DOI: 10.1038/s41467-019-11533-x
  • Peer Reviewed / Open Access
• [Presentation] 病理組織標本の透明化と3次元イメージング (2020)
  • Author(s): 野島聡
  • Organizer: 第108回 日本病理学会総会 シンポジウム4