Molecular approach of characterize of uterine leiomyosarcoma:development of novel therapy against uterine mesenchymal tumours

• Project/Area Number: 24592510
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Shinshu University
• Principal Investigator: HAYASHI Takuma 信州大学, 学術研究院医学系, 准教授 (60359726)
• Co-Investigator(Renkei-kenkyūsha): YAEGASHI Nobuo 東北大学, 医学系研究科, 教授 (00241597) ; KONISHI Ikuo 京都大学, 医学系研究科, 教授 (90192062)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 子宮間葉系腫瘍 / 子宮平滑筋肉腫 / 子宮平滑筋種 / LMP2 / CAVEOLIN1 / 子宮肉腫 / 血行性転移

Outline of Final Research Achievements

Although most smooth muscle neoplasms detected in the uterus are benign, uterine leiomyosarcoma (Ut-LMS) is extremely malignant with high rates of recurrence and metastasis. CAVEOLIN1 (CAV1) levels in the epithelial cells of some carcinomas have been reported to increase during tumor progression. We herein evaluated the relationship between CAV1 expression and the pathological features of patients diagnosed with uterine mesenchymal tumors. No clinical link was observed between CAV1 expression and the malignancy of uterine mesenchymal tumors. CAV1 expression was decreased in the normal myometrium, whereas it was strongly expressed in uterine mesenchymal tumors. However, CAV1 was not a potential biomarker to distinguish Ut-LMS from other uterine mesenchymal tumors. The perivascular expression of CAV1 was observed in all types of uterine mesenchymal tumors and myometria. The present study suggest that CAV1 may not act as a potential biomarker of uterine malignant mesenchymal tumors.

Research Products

• [Journal Article] Molecular approach of tumorigenesis of human uterine leiomyosarcoma: Structure modeling of JAK1 molecule with somatic mutation (2015)
  • Author(s): Hayashi T, Horiuchi A. Sano K. Ichimura T. Hiraoka N. Sudo T. Nishimura R. Ishiko O. Kanai Y. Yaegashi N. Aburatani H. Shiozawa T. Tonegawa S. Konishi.I
  • Journal Title: Jokull Journal Volume: 65(3) Pages: 1-21
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Somatic mutations in Interferon-ｇ; signal molecules in human uterine leiomyosarcoma (2015)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Konishi I
  • Journal Title: International Journal of Medical Science And Clinical Inventions Volume: 2(4) Pages: 846-850
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mouse models of sarcoma for understanding of the tumourigenesis (2015)
  • Author(s): Hayashi T
  • Journal Title: PARIPEX-Indian Journal of Research Volume: 4(4) Pages: 4-5
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Potential diagnostic biomarkers: LMP2/ｂ1i and Cyclin B1 differential expression in human uterine mesenchymal tumors (2014)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Sudo T, Ishiko O, Yaegashi N, Aburatani H, Konishi I
  • Journal Title: TUMORI Volume: 100 Pages: 509-516
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The identification of somatic mutations in Interferon-ｇ; signaling molecules in human uterine leiomyosarcoma (2014)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Ishiko O, Kanai Y, Yaegashi N, Shiozawa T, Aburatani H, Ikuo Konishi I
  • Journal Title: Jokull Journal Volume: 64 Pages: 1-20
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Preoperative Diagnosis of Usual Leiomyoma, Atypical Leiomyoma, and Leiomyosarcoma (2014)
  • Author(s): Matsuda M, Ichimura T, Kasai M, Murakami M, Kawamura N, Hayashi T, and Sumi T
  • Journal Title: Sarcoma Volume: 2014 Pages: 34-38
  • DOI: 10.1155/2014/498682
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of novel biomarker for human uterine leiomyosarcoma (2014)
  • Author(s): Hayashi T, Horiuchi A, Aburatani H, Ishiko O, Yaegashi N, Kanai Y, Zharhary D, Tonegawa S, Konishi I
  • Journal Title: J Hematology and Oncology Volume: 1 Pages: 1-6
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Potential biomarker for human uterine leiomyosarcoma (2014)
  • Author(s): Hayashi T, Horiuchi A, Aburatani H, Ishiko O, Yaegashi N, Kanai Y, Zharhary D, Shiozawa T, Tonegawa S, Konishi I
  • Journal Title: Journal of Clinical Medicine Research Volume: 6 Pages: 392-394
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Differential expression of LMP2/β1i: as a potential biomarkeral of human uterine mesenchymal tumors. (2013)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Gur G, Aburatani H, Ishiko O, Yaegashi N, Kanai Y, Zharhary D, Tonegawa S, Konishi I.
  • Journal Title: J Interdisciplinary Histopathology Volume: 1 Issue: 3 Pages: 153-159
  • DOI: 10.5455/jihp.20130210114005
  • Peer Reviewed
• [Journal Article] A novel diagnostic marker: Proteasome LMP2/b1i-differential expression in human uterus mesenchymal tumors. (2013)
  • Author(s): Hayashi T, Horiuchi. A, Yaegashi. N, Shiozawa.T, Tonegawa.S, Konishi I
  • Journal Title: Cancer Research Journal Volume: 1(1) Issue: 1 Pages: 1-6
  • DOI: 10.11648/j.crj.20130101.11
  • Peer Reviewed
• [Journal Article] The proteasome subunit LMP2/β1i in the female genital system. (2013)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Gur G, Aburatani H, Ichimura T, Yaegashi N, Kanai Y, Zharhary D, Tonegawa S, Konishi I.
  • Journal Title: Journal Gynecology Obstetrics Volume: 1 Issue: 1 Pages: 1-6
  • DOI: 10.11648/j.jgo.20130101.11
  • Peer Reviewed
• [Journal Article] Proteasome Subunit LMP2/ b1i As a Biomarker for Human Uterine Mesenchymal Tumors. (2013)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Gur G, Aburatani H, Ishiko O, Yaegashi N, Shiozawa T, Kanai Y, Zharhary D, Tonegawa S, Konishi I
  • Journal Title: J Oncobiomarkers Volume: 1(2) Pages: 1-6
  • Peer Reviewed
• [Journal Article] 子宮平滑筋肉腫の新規診断法：LMP2とCalponin h1のバイオマーカーとしての信頼性 (2013)
  • Author(s): 林 琢磨, 堀内 晶子, 利根川 進, 小西 郁生
  • Journal Title: 末病と抗老化 Volume: 22 Pages: 50-56
  • Peer Reviewed
• [Journal Article] Biological Significance of the Proteasome Subunit LMP2/β1i as a Tumor Suppresso in Human Uterine Leiomyosarcoma. (2012)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Gur G, Aburatani H, Ishiko O, Yaegashi N, Shiozawa T, Kanai Y, Zharhary D, Tonegawa S, Konishi I.
  • Journal Title: J Cancer Res. Updates Volume: 1 Issue: 2 Pages: 181-188
  • DOI: 10.6000/1929-2279.2012.01.02.4
  • Peer Reviewed
• [Journal Article] Proteasome LMP2/b1i-differential expression in human uterine mesenchymal tumor. (2012)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Gur G, Aburatani H, Ishiko O, Yaegashi N, Shiozawa T, Kanai Y, Zharhary D, Tonegawa S, Konishi I.
  • Journal Title: Current Res. Cancer Volume: 1 Pages: 17-25
  • Peer Reviewed
• [Journal Article] Tumor immunoediting: T cell-mediated immune surveillance to uterine leiomyosarcoma. (2012)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Kasai M, Ichimura T, Nagase S, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I.
  • Journal Title: Current Res. Immunol Volume: 1 Pages: 9-19
  • Peer Reviewed
• [Journal Article] A POTENTIAL DIAGNOSTIC BIOMARKER FOR HUMAN UTERINE MESENCHYMAL TUMOR: PROTEASOME LMP2/b 1i SUBUNIT-DIFFERENTIAL EXPRESSION (2012)
  • Author(s): Hayashi T, Horiuchi A, Gur G, Aburatani H, Ishiko O, Yaegashi N, Shiozawa T, Zharhary D, Tonegawa S, Konishi I
  • Journal Title: Advance Laboratory Medicine International Volume: 2 Pages: 78-86
  • Peer Reviewed
• [Journal Article] Potential role of LMP2 as an anti-oncogenic factor in human uterine leiomyosarcoma: morphological significance of calponin h1 (2012)
  • Author(s): Hayashi T,Horiuchi A,Sano K,Hiraoka N,Kasai M,Ichimura T,Sudo T,Nishimura R,Ishiko O,Shiozawa T,Kanai Y,Yaegashi N,Aburatani H,Konishi I.
  • Journal Title: FEBS Lett Volume: 586 Issue: 13 Pages: 1824-31
  • DOI: 10.1016/j.febslet.2012.05.029
  • NAID: 120007110569
  • Peer Reviewed
• [Journal Article] A potential diagnostic biomarker: Proteasome subunit LMP2/b1i-differential expression in human uterus neoplasm. (2012)
  • Author(s): Hayashi T, Horiuchi A, Aburatani H, Ishiko O, Yaegashi N, Tonegawa S, Konishi I
  • Journal Title: Diagnostic and Therapeutic Study Volume: 1 Pages: 45-51
  • Peer Reviewed
• [Journal Article] Involvement of pelvic inflammation-related mismatch repair abnormalities and microsatellite instability in the malignant transformation of ovarian endometriosis. (2012)
  • Author(s): Fuseya C, Horiuchi A, Hayashi A, Suzuki A, Miyamoto T, Hayashi T, Shiozawa T.
  • Journal Title: Hum Pathol. Volume: 43 Issue: 11 Pages: 1964-72
  • DOI: 10.1016/j.humpath.2012.02.005
  • Peer Reviewed
• [Journal Article] Hypoxia up regulates ovarian cancer invasiveness via the binding of HIF-1αto a hypoxia-induced, methylation-free hypoxia response element of S100A4 gene (2012)
  • Author(s): Horiuchi A, Hayashi T, Kikuchi N, Hayashi A, Fuseya C, Shiozawa T, Konishi I.
  • Journal Title: Int J Cancer Volume: 27 Issue: 8 Pages: 755-67
  • DOI: 10.1002/ijc.27448
  • Peer Reviewed
• [Journal Article] Tumor Immuno editing from T cell-Mediated Immune Surveillance to Tumor-Escape of Uterine Laiomyosarcoma (2012)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N, Ichimura T, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I
  • Journal Title: J Vaccines Vacci Volume: 1 Pages: 1-6
  • Peer Reviewed
• [Presentation] Preventive effect of ascorbic acid against Tat-dependent HIV-1 replication (2015)
  • Author(s): Hayashi T, Young R.A.
  • Organizer: 19th International Conference of FFC and 7th International Symposium of ASFFBC, Functional and Medical Foods, Bioactive Compounds and Biomarkers: Longevity and Quality of Life.
  • Place of Presentation: Kobe University, Kobe, Japan
  • Year and Date: 2015-11-17
  • Int'l Joint Research
• [Presentation] Potential roles of LMP2 and Caveolin 1 define new targets for uterine leiomyosarcoma therapy. (2015)
  • Author(s): Hayashi T, Horiuchi A, Shiozawa T, Ishiko O, Yaegashi N, Tonegawa S, Konishi I
  • Organizer: FACO Internal Workshop, 3rd International Conference of Federation of Asian Clinical Oncology (FACO)
  • Place of Presentation: Kyoto International Hall, Kyoto, Japan
  • Year and Date: 2015-10-29
  • Int'l Joint Research / Invited
• [Presentation] Potential role of LMP2 as negative regulator defines new targets for uterineleiomyosarcoma therapy (2015)
  • Author(s): Hayashi T, Horiuchi A, Shiozawa T, Ishiko O, Yaegashi N, Tonegawa S, Konishi I
  • Organizer: 5th World Congress on Cancer Research
  • Place of Presentation: Atlanta, USA
  • Year and Date: 2015-09-28
  • Int'l Joint Research / Invited
• [Presentation] Potential role of LMP2 as negative regulator defines new targets for uterine leiomyosarcoma therapy (2014)
  • Author(s): Takuma Hayashi, Akiko Horiuchi, Ikuo Konishi
  • Organizer: Cell Symposium: Hallmarks of Cancer
  • Place of Presentation: ラッフルズ北京ホテル、北京、中国
  • Year and Date: 2014-11-09 – 2014-11-11
• [Presentation] Potential role of LMP2 as negative regulator defines new targets for uterine leiomyosarcoma therapy (2014)
  • Author(s): Takuma Hayashi, Akiko Horiuchi, Tanri Shiozawa, Osamu Ishiko, Nobuo Yaegashi, Susumu Tonegawa, Ikuo Konishi
  • Organizer: 第73回日本癌学会
  • Place of Presentation: パシフィコ横浜、横浜、神奈川県
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 子宮平滑筋肉腫：造腫瘍化と老化 (2014)
  • Author(s): 林 琢磨, 堀内 晶子, 塩沢 丹里, 石河 修, 八重樫 伸生, 利根川 進, 小西 郁生
  • Organizer: 第56回日本婦人科腫瘍学会
  • Place of Presentation: 栃木県総合文化センター、宇都宮、栃木県
  • Year and Date: 2014-07-17 – 2014-07-19
  • Invited
• [Presentation] 子宮間葉系腫瘍に対する新規バイオマーカーの探索 (2014)
  • Author(s): 林 琢磨, 堀内 晶子, 塩沢 丹里, 石河 修, 八重樫 伸生, 利根川 進, 小西 郁生
  • Organizer: 第2回 婦人科がんバイオマーカー研究会学術集会
  • Place of Presentation: 東京慈恵医科大学、港区、東京都
  • Year and Date: 2014-07-05
  • Invited
• [Presentation] Potential role of LMP2 as negative regulator defines new targets for uterine leiomyosarcoma therapy (2014)
  • Author(s): Takuma Hayashi, Akiko Horiuchi, Tanri Shiozawa, Osamu Ishiko, Nobuo Yaegashi, Susumu Tonegawa, Ikuo Konishi
  • Organizer: 第13回日本婦人科がん分子標的研究会
  • Place of Presentation: 皆生グランドホテル天水、米子、鳥取県
  • Year and Date: 2014-04-14 – 2014-04-15
• [Presentation] Potential role of LMP2 as negative regulator defines new targets for uterine leiomyosarcoma therapy (2014)
  • Author(s): Hayashi T, Horiuchi A, Shiozawa T, Ishiko O, Yaegashi N, Tonegawa S, Konishi I
  • Organizer: 第13回日本婦人科がん分子標的研究会
  • Place of Presentation: 米子 皆生ホテル
• [Presentation] Potential role of LMP2 as negative regulator defines new targets for uterine leiomyosarcoma therapy (2013)
  • Author(s): Hayashi T, Horiuchi A, Shiozawa T, Ishiko O, Yaegashi N, Tonegawa S, Konishi I.
  • Organizer: 第3回アジア婦人科腫瘍学会
  • Place of Presentation: ウェステイン都ホテル京都
  • Invited
• [Presentation] 子宮平滑筋肉腫の生物学的特徴：血行性転移でのLMP2の関与.子宮肉腫の基礎と臨床 (2013)
  • Author(s): 林 琢磨、堀内 晶子、塩沢 丹里、小西 郁生
  • Organizer: 第54回日本婦人科腫瘍学会
  • Place of Presentation: 東京・お台場 LeDaibaホテル
  • Invited
• [Presentation] 子宮筋腫、異型筋腫および平滑筋肉腫の術前鑑別診断に関する検討 (2013)
  • Author(s): 松田 真希子、市村 友季、村上 誠、笠井 真理、川村 直樹、林 琢磨、堀内 晶子、角 俊幸、石河 修
  • Organizer: 第54回日本婦人科腫瘍学会
  • Place of Presentation: 東京・お台場 LeDaibaホテル
  • Invited
• [Presentation] Candidate molecules and ki-67/MIB1 as novel diagnostic biomarker for human uterine mesenchymal tumors. (2013)
  • Author(s): Hayashi T, Horiuchi A, Tonegawa S, Konishi I.
  • Organizer: International Cession, Japan Cancer Association.
  • Place of Presentation: パシフィコ横浜
• [Presentation] 子宮平滑筋肉腫の生物学的特性：腫瘍能と老化 (2013)
  • Author(s): 林 琢磨
  • Organizer: 東北大学医学部統合産婦人科学研究コアセンターシンポジウム 2013
  • Place of Presentation: 東北大学医学部 仙台
  • Invited
• [Presentation] 子宮間葉系腫瘍の鑑別に対する新規バイオマーカーの検討 (2013)
  • Author(s): 林 琢磨、堀内 晶子、油谷 浩幸、利根川 進、小西 郁生
  • Organizer: 第１回婦人科がんバイオマーカー研究会学術集会
  • Place of Presentation: 東京大学本郷キャンパス
• [Presentation] Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy (2012)
  • Author(s): Hayashi T, Horiuchi A, Shiozawa T, Tonegawa S, Konishi I
  • Organizer: 第26回日本産婦人科学会学術講演会
  • Place of Presentation: 神戸国際展示場
• [Presentation] 子宮平滑筋肉腫の腫瘍細胞浸潤と血行性転移における、LMP2の生物学的重要性の関与 (2012)
  • Author(s): Hayashi T, Horiuchi A, Shiozawa T, Tonegawa S, Konishi I
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市教育文化会館
• [Presentation] 子宮平滑筋肉腫の生物学的特徴：血行性転移でのLMP2の関与 (2012)
  • Author(s): 林 琢磨
  • Organizer: 第21回日本がん転移学会学術集会
  • Place of Presentation: オリエンタルホテル広島
• [Presentation] 子宮平滑筋肉腫の生物学的特徴：血行性転移でのLMP2の関与 (2012)
  • Author(s): 林 琢磨
  • Organizer: 第20回日本血管生物医学学術総会
  • Place of Presentation: 徳島県郷土文化会館
• [Presentation] Tumor invasion and hematogenous metastasis of uterine leiomyosarcoma: involvement of biological significance of LMP2 (2012)
  • Author(s): Hayashi T., Horiuchi A., Aburatani H., Tonegawa S., Konishi
  • Organizer: 12th Korea-Japan Joint Symposium on Vascular Biology
  • Place of Presentation: Tokushima
• [Presentation] Molecular mechanism of hematogenous metastasis of uterine leiomyosarcoma:involvement of biological significance of LMP2 (2012)
  • Author(s): Takuma Hayashi, Akiko Horiuchi, Susumu Tonegawa, Ikuo Konishi
  • Organizer: World Cancer Congress 2012
  • Place of Presentation: Beijing
  • Invited
• [Book] Current Research in Cancer (2014)
  • Author(s): Hayashi T, Horiuchi A, Sano K, Hiraoka N,Kasai M, Ichimura T, Nagase S, Ishiko O, Kanai Y, Yaegashi N, Aburatani H, Shiozawa T, Tonegawa S, Konishi I
  • Total Pages: 24
  • Publisher: Research Media
• [Remarks] http://www.shinshu-u.ac.jp/faculty/medicine/topics
• [Remarks] 財団法人博慈会平成25年優秀研究ダ・ヴィンチ賞を受賞しました。
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/topics/2013/04/1652609.php
• [Remarks] 神澤医学研究振興財団より平成24年度 神澤医学賞を授与されました。
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/topics/2013/03/550984.php
• [Remarks] 癌抑制因子LMP2 とCalponin h1 とのコミュニケーションリンク
  • URL: http://www.shinshu-u.ac.jp/graduate/medicine/i-topics
• [Remarks] 林 琢磨 准教授らの研究グループが財団法人博慈会平成25年優秀研究ダ・ヴィンチ賞を受賞しました。
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/topics/2013/04/1652609.php
• [Remarks] 林 琢磨 准教授らの研究グループが神澤医学研究振興財団より平成24年度 神澤医学賞を授与されました。
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/topics/2013/03/550984.php
• [Remarks] 医学部医学科 林 琢磨 准教授らの研究グループが平成24年度神澤医学賞を授与されました。
  • URL: http://www.shinshu-u.ac.jp/faculty/medicine/topics/2013/03/550984.html
• [Remarks] 子宮間葉系腫瘍に対する新規治療法・診断法の確立にむけて
  • URL: http://www.shinshu-u.ac.jp/graduate/medicine/i-topics/#47929