The effect of HSP 90 inhibition for angiosarcoma

• Project/Area Number: 16K19728
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Kumamoto University
• Principal Investigator: Kajihara Ikko 熊本大学, 医学部附属病院 皮膚科, 助教 (90433036)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 血管肉腫 / heat shock protein 90 / Heat shock protein 90 / 抗腫瘍効果 / HSP90

Outline of Final Research Achievements

New therapy for angiosarcoma is urgent because there are few effective treatments. Heat shock protein 90 (HSP90) regulates cancer-associated proteins and many clinical trials of HSP90 inhibitors are on-going in several cancers. In this study, we investigated the anti-tumor effect of HSP90 inhibition. HSP90 protein are overexpressed in angiosarcoma patient’s tissues and cell lines. Knockdown of HSP90 inhibited the proliferation/migration/invasion of angiosarcoma cells. These anti-tumor effect were based on the suppression of several downstream targets of VEGF signaling. Taken together, HSP90 is a novel therapeutic target against angiosarcoma.

Academic Significance and Societal Importance of the Research Achievements

血管肉腫は、非常に希少且つ悪性度が高い肉腫である。進行例では、化学療法が主体となるが、現在でも有効性の高い治療法は未確立である。そのため、血管肉腫に対する新規治療の開発は急務である。今回、HSP90阻害剤の血管肉腫に対する抗腫瘍効果を検討した。HSP90阻害効果により血管肉腫細胞株の増殖能・浸潤能・遊走能が抑制された。またその抗腫瘍効果に関する分子メカニズムを解明した。

Research Products

• [Journal Article] The expression of EpCAM in extramammary Paget's disease (2019)
  • Author(s): Yamada-Kanazawa Saori、Tasaki Yukino、Kajihara Ikko、Sakamoto Ryoko、Maeda-Otsuka Saki、Ihn Hironobu
  • Journal Title: Intractable & Rare Diseases Research Volume: 8 Issue: 1 Pages: 20-23
  • DOI: 10.5582/irdr.2019.01010
  • NAID: 130007612176
  • ISSN: 2186-361X, 2186-3644
  • Year and Date: 2019-02-28
  • Peer Reviewed
• [Journal Article] Overexpression of cyclin-dependent kinase 4 protein in extramammary Paget's disease. (2019)
  • Author(s): YUrata K, Kajihara I, Myangat TM, Tasaki Y, Otsuka-Maeda S, Sawamura S, Kanazawa-Yamada S, Sakamoto R, Makino K, Aoi J, Igata T, Makino T, Masuguchi S, Fukushima S, Jinnin M, Ihn H.
  • Journal Title: J Dermatol. Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] Infliximab improved the refractory cutaneous involvement in a patient with dermatomyositis. (2019)
  • Author(s): Yamada-Kanazawa S, Kajihara I, Kobayashi A, Watanabe C, Ihn H.
  • Journal Title: Dermatol Ther. Volume: 印刷中
• [Journal Article] Serum cell-free DNA levels are a useful marker for extramammary Paget disease. (2019)
  • Author(s): Mijiddorj T, Kajihara I, Tasaki Y, Otsuka-Maeda S, Sakamoto R, Sawamura S, Kanazawa-Yamada S, Egashira S, Inoue K, Makino K, Miyashita A, Aoi J, Igata T, Makino T, Masuguchi S, Fukushima S, Jinnin M, Morinaga J, Ikeda T, Ihn H.
  • Journal Title: Br J Dermatol. Volume: 印刷中
• [Journal Article] Hypoxia accelerates the progression of angiosarcoma through the regulation of angiosarcoma cells and tumor microenvironment. (2019)
  • Author(s): Maeda-Otsuka S, Kajihara I, Tasaki Y, Yamada-Kanazawa S, Sakamoto R, Sawamura S, Masuzawa M, Masuzawa M, Amoh Y, Hoshina D, Abe R, Komohara Y, Ihn H.
  • Journal Title: J Dermatol Sci. Volume: 93 Pages: 123-132
• [Journal Article] Simple and effective modification of the axial frontonasal flap to prevent flap distortion. (2019)
  • Author(s): Aoi J, Kajihara I, Masuguchi S, Fukushima S, Ihn H.
  • Journal Title: J Dermatol. Volume: 46
• [Journal Article] Sweet's syndrome with laryngoparalysis due to laryngitis. (2018)
  • Author(s): Miyamura T, Kajihara I, Makino K, Ihn H.
  • Journal Title: J Dermatol. Volume: 45
• [Journal Article] Expression of aurora kinase A expression in dermatofibrosarcoma protuberans. (2018)
  • Author(s): Kanamori S, Kajihara I, Kanazawa-Yamada S, Otsuka-Maeda S, Ihn H.
  • Journal Title: J Dermatol. Volume: 45 Pages: 507-508
• [Journal Article] Case of pigmented lipofibromatosis in a 27-year-old woman. (2018)
  • Author(s): Sonoda-Shimada K, Kajihara I, Shimada S, Igata T, Jinnin M, Honda Y, Ihn H.
  • Journal Title: J Dermatol. Volume: 45
• [Journal Article] Expression of aurora kinase A expression in dermatofibrosarcoma protuberans (2018)
  • Author(s): Sanayo Kanamori Ikko Kajihara Saori Kanazawa‐Yamada Saki Otsuka‐Maeda Hironobu Ihn
  • Journal Title: J Dermatol. Volume: 45 Issue: 4 Pages: 507-508
  • DOI: 10.1111/1346-8138.14235
  • Peer Reviewed
• [Journal Article] Dyskeratosis congenita associated with congenital hypothyroidism (2017)
  • Author(s): Noda-Yamashita Tomoka、Kajihara Ikko、Kidou Masato、Ihn Hironobu
  • Journal Title: The Journal of Dermatology Volume: 印刷中 Issue: 4
  • DOI: 10.1111/1346-8138.14109
  • Peer Reviewed
• [Journal Article] Secukinumab-induced interstitial pneumonia in a patient with psoriasis vulgaris (2017)
  • Author(s): Kajihara Ikko、Yamada-Kanazawa Saori、Maeda-Otsuka Saki、Jinnin Masatoshi、Akaike Kimitaka、Ihn Hironobu
  • Journal Title: The Journal of Dermatology Volume: 44 Issue: 12
  • DOI: 10.1111/1346-8138.13986
  • Peer Reviewed
• [Journal Article] S100A7 expression levels in coordination with interleukin-8 indicate the clinical response to infliximab for psoriasis patients (2017)
  • Author(s): Sato Yasuhiko、Kajihara Ikko、Yamada-Kanazawa Saori、Jinnin Masatoshi、Ihn Hironobu
  • Journal Title: The Journal of Dermatology Volume: 44 Issue: 7 Pages: 838-839
  • DOI: 10.1111/1346-8138.13631
  • Peer Reviewed
• [Journal Article] Intratumor dihydropyrimidine dehydrogenase mRNA expression levels are decreased in extramammary Paget's disease (2017)
  • Author(s): Nakamura Yuki、Kajihara Ikko、Yamada-Kanazawa Saori、Maeda-Otsuka Saki、Johno Takamitsu、Aoi Jun、Igata Toshikatsu、Masuguchi Shinichi、Fukushima Satoshi、Jinnin Masatoshi、Ihn Hironobu
  • Journal Title: Drug Discoveries & Therapeutics Volume: 11 Issue: 3 Pages: 152-155
  • DOI: 10.5582/ddt.2017.01022
  • NAID: 130005875038
  • ISSN: 1881-7831, 1881-784X
  • Peer Reviewed
• [Journal Article] Inhibition of HSP90 exerts anti-tumor effect on angiosarcoma: Involvement of VEGF signaling pathway. (2017)
  • Author(s): Yamada-Kanazawa S, Kajihara I, Fukushima S, Jinnin M, Masuzawa M, Masuzawa M, Amoh Y, Hoshina D, Abe R, Ihn H.
  • Journal Title: Br J Dermatol. Volume: 印刷中 Issue: 2 Pages: 456-469
  • DOI: 10.1111/bjd.15303
  • Peer Reviewed
• [Journal Article] Cutaneous spindle cell adenolipoma on the nose: A rare variant of lipoma. (2017)
  • Author(s): Sawamura S, Kajihara I, Jinnin M, Honda Y, Ihn H
  • Journal Title: J Dermatol. Volume: 印刷中 Issue: 7
  • DOI: 10.1111/1346-8138.13826
  • Peer Reviewed
• [Journal Article] Achieved good response of S-1 and docetaxel combination chemotherapy in two patients with metastatic extramammary Paget's disease. (2017)
  • Author(s): Egashira S, Kajihara I, Kanemaru H, Uemura-Kiyohara M, Yamada-Kanazawa S, Nakahara S, Nagamoto E, Fukushima S, Jinnin M, Inoue Y, Ihn H.
  • Journal Title: J Dermatol. Volume: 44 Issue: 5
  • DOI: 10.1111/1346-8138.13693
  • Peer Reviewed
• [Journal Article] Bromoderma in a pituitary adenoma patient treated with bromocriptine. (2017)
  • Author(s): Maeda S, Kajihara I, Ogata A, Johno T, Jinnin M, Ihn H.
  • Journal Title: J Dermatol. Volume: 44 Issue: 5 Pages: 95-96
  • DOI: 10.1111/1346-8138.13683
  • Peer Reviewed
• [Journal Article] Systemic lupus erythematosus associated with myasthenia gravis, pemphigus foliaceus and chronic thyroiditis after thymectomy. (2017)
  • Author(s): Sawamura S, Kajihara I, Makino K, Makino T, Fukushima S, Jinnin M, Oyama B, Hashimoto T, Ihn H.
  • Journal Title: Australas J Dermatol. Volume: 印刷中 Issue: 3
  • DOI: 10.1111/ajd.12510
  • Peer Reviewed
• [Journal Article] Enhanced CCR9 expression levels in psoriatic skin are associated with poor clinical outcome to infliximab treatment. (2015)
  • Author(s): Koga A, Kajihara I, Yamada S, Makino K, Ichihara A, Aoi J, Makino T, Fukushima S, Jinnin M, Ihn H.
  • Journal Title: J Dermatol. Volume: 43 Issue: 5 Pages: 522-5
  • DOI: 10.1111/1346-8138.13178
  • Peer Reviewed / Open Access
• [Presentation] 乳房外パジェット病におけるCDK4発現の検討 (2018)
  • Author(s): 梶原一亨
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] Heat shock protein 90は血管肉腫の治療標的になりうる。 (2018)
  • Author(s): 梶原一亨、金澤早織、尹浩信
  • Organizer: 第26回血管生物医学会学術集会