Proposal of new diagnosis, treatment, prevention approach for endometrial cancer targeting estrogen-mediated pathway

2022 Fiscal Year Research-status Report

• Project/Area Number: 21K09523
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: 森 泰輔 京都府立医科大学, 医学(系)研究科(研究院), 教授 (00569824)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 子宮体癌

Outline of Annual Research Achievements

わが国において子宮体癌は著しく増加している。特に手術不能な進行例や再発例が増加しており、このような場合には化学療法が施行されるものの予後はきわめて不良である。一方、初期例は比較的予後良好のものが多いが、子宮全摘および付属器摘出術を治療の原則とするため将来的な妊娠を断念せざるを得ない。子宮内膜に限局する病変に対して妊孕能温存療法としてプロゲスチン療法が行われているが、その再発率は高い。このように子宮体癌に対する新たな治療法の開発が切望されている。
子宮体癌に対してこれまで多くの分子標的薬が試行されてきたが、いずれも満足な結果は得られていない。網羅的遺伝子解析から子宮体癌は単一の強いがん遺伝子の変異では癌化しにくいことが示されており、腫瘍の生物学的特性に基づいた治療戦略が求められている。研究代表者はこれまで一貫して「エストロゲン依存性増殖機構」に着目し研究を展開してきた中で、エストロゲン関連受容体aが子宮体癌における細胞増殖、浸潤・転移、血管新生、アポトーシス誘導を制御し、これを標的とする化合物が in vitro および in vivo において抗腫瘍効果をもたらすことを実証してきた。本研究では、① エストロゲン関連受容体がエストロゲン応答や薬剤感受性に及ぼす影響、② エストロゲン関連受容体とがんの代謝異常との関連性、について明らかにすることで、個別化医療実現に向けての新規診断バイオマーカー開発や新たな治療・疾患予防アプローチを提唱する。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

がん代謝に関連する因子を同定することができている。

Strategy for Future Research Activity

今後、がん代謝との関連をin vitroおよびin vivoの系を用いて検証していく。

Causes of Carryover

メタボローム解析などの費用がかからなかったこと、webでの学会出席となり出張費が生じなかったこと、より次年度使用額が生じた。次年度に物品費および出張費として使用予定である。

Research Products

• [Journal Article] he Tpl2-MEK pathway plays a critical role in spheroid-cultured endometriotic stromal cells (2023)
  • Author(s): Minami T, Tsuzuki Y, Tanaka Y, Kitawaki J, Mori T.
  • Journal Title: Am J Reprod Immunol . Volume: 89 Pages: e13689
  • DOI: 10.1111/aji.13689
  • Peer Reviewed
• [Journal Article] Decrease in activated regulatory T cell populations in the endometrium during ovulation in endometriosis (2023)
  • Author(s): Fujii M, Tanaka Y, Okimura H, Maeda E, Hamaguchi M, Fukui M, Kitawaki J, Mori T.
  • Journal Title: J Reprod Immunol. Volume: 156 Pages: 103825
  • DOI: 10.1016/j.jri.2023.103825
  • Peer Reviewed
• [Journal Article] Low-Nutrient Environment-Induced Changes in Inflammation, Cell Proliferation, and PGC-1α Expression in Stromal Cells with Ovarian Endometriosis (2023)
  • Author(s): Shimura K, Tarumi Y, Fujii M, Ogawa K, Maeda E, Tanaka Y, Okimura H, Kataoka H, Takaoka O, Ito F, Koshiba A, Khan KN, Kusuki I, Kitawaki J, Mori T.
  • Journal Title: Reprod Sci. Volume: 30 Pages: 1094-1102
  • DOI: 10.1007/s43032-022-01089-5
  • Peer Reviewed
• [Journal Article] Pathogenesis of Human Adenomyosis: Current Understanding and Its Association with Infertility (2022)
  • Author(s): Khan KN, Fujishita A, Mori T.
  • Journal Title: J Clin Med Volume: 11 Pages: 4057
  • DOI: 10.3390/jcm11144057
  • Peer Reviewed / Open Access
• [Journal Article] Clinical practice guidelines for endometriosis in Japan (The 3rd edition). (2022)
  • Author(s): Harada T, Taniguchi F, Kitajima M, Kitawaki J, Koga K, Momoeda M, Mori T, Murakami T, Narahara H, Osuga Y, Yamaguchi K.
  • Journal Title: J Obstet Gynaecol Res Volume: 48 Pages: 2993-3044
  • DOI: 10.1111/jog.15416.
  • Peer Reviewed / Open Access
• [Journal Article] Reduced innate lymphoid cells in the endometrium of women with endometriosis (2022)
  • Author(s): Sugahara T, Tanaka Y, Hamaguchi M, Fujii M, Shimura K, Ogawa K, Mori T, Kusuki I, Fukui M, Kitawaki J.
  • Journal Title: Am J Reprod Immunol. Volume: 87 Pages: e13502
  • DOI: 10.1111/aji.13502.
  • Peer Reviewed
• [Journal Article] 3D-Image-Guided Multi-Catheter Interstitial Brachytherapy for Bulky and High-Risk Stage IIB-IVB Cervical Cancer (2022)
  • Author(s): Kokabu T, Masui K, Tarumi Y, Noguchi N, Aoyama K, Kataoka H, Matsushima H, Yoriki K, Shimizu D, Yamazaki H, Yamada K, Mori T.
  • Journal Title: Cancers Volume: 14 Pages: 1257
  • DOI: 10.3390/cancers14051257.
  • Peer Reviewed / Open Access
• [Journal Article] Robot-assisted laparoscopic hysterectomy for early-stage endometrial cancer with massive uterine leiomyomas: A case report (2022)
  • Author(s): Kakibuchi A, Ito F, Kokabu T, Okimura H, Takaoka O, Mori T.
  • Journal Title: Int J Surg Case Rep Volume: 97 Pages: 107473
  • DOI: 10.1016/j.ijscr.2022.107473.
  • Peer Reviewed
• [Journal Article] Progesterone Receptor Status of Epithelial Cells as a Predictive Marker for Postoperative Recurrence of Endometriosis (2022)
  • Author(s): Tarumi Y, Mori T, Shimura K, Izumi Y, Okimura H, Kataoka H, Kokabu T, Ito F, Koshiba A, Khan KN, Kusuki I, Kitawaki J.
  • Journal Title: J Clin Endocrinol Metab. Volume: 107 Pages: 1552-1559
  • DOI: 10.1210/clinem/dgac118.
  • Peer Reviewed
• [Journal Article] Changes in the proportion of regulatory T cell subpopulations during menstrual cycle and early pregnancy (2022)
  • Author(s): Okimura H, Tanaka Y, Fujii M, Shimura K, Maeda E, Ito F, Khan KN, Nakamura Y, Mori T, Kitawaki J.
  • Journal Title: Am J Reprod Immunol. Volume: 88 Pages: e13636
  • DOI: 10.1111/aji.13636
  • Peer Reviewed
• [Journal Article] Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan (2022)
  • Author(s): Tanaka T, Yamashita S, Kuroboshi H, Kamibayashi J, Sugiura A, Yoriki K, Mori T, Tanaka K, Nagashima A, et al.
  • Journal Title: Int J Clin Oncol. Volume: 27 Pages: 1084-1092
  • DOI: 10.1007/s10147-022-02152-6
  • Peer Reviewed
• [Journal Article] Successful nedaplatin desensitization therapy in a patient with platinum-sensitive recurrent ovarian cancer: A case report and literature review (2022)
  • Author(s): Kokabu T, Aoyama K, Tarumi Y, Kataoka H, Yoriki K, Mori T.
  • Journal Title: Gynecol Oncol Rep. Volume: 43 Pages: 101065
  • DOI: 10.1016/j.gore.2022.101065
  • Peer Reviewed
• [Journal Article] Genistein induces long-term expression of progesterone receptor regardless of estrogen receptor status and improves the prognosis of endometrial cancer patients (2022)
  • Author(s): Yoriki K, Mori T, Aoyama K, Tarumi Y, Kataoka H, Kokabu T, Kitawaki J.
  • Journal Title: Sci Rep Volume: 12 Pages: 10303
  • DOI: 10.1038/s41598-022-13842-6
  • Peer Reviewed
• [Journal Article] A targeted educational programme improves fundamental knowledge of menstrual pain and endometriosis in young women: The Endometriosis Awareness Promotion Project (2022)
  • Author(s): Khan KN, Ogawa K, Iwasa K, Kuroboshi H, Okimura H, Koshiba A, Manabe E, Izumi M, Akira S, Kashi AM, Allahqoli L, Tahermanesh K, Matloobi M, Ramasauskaite D, Silkunas M, Cerniauskaite M, Tintara H, Klangsin S, Horiguchi G, Teramukai S, Sawa T, Fushiki S, Itoh K, Nakashima M, Fujishita A, Guo SW, Kitawaki J, Mori T.
  • Journal Title: Reprod Biomed Online . Volume: 45 Pages: 1216-1229
  • DOI: 10.1016/j.rbmo.2022.07.009.
  • Peer Reviewed