Prediction of therapeutic effect in preoperative chemotherapy for rectal cancer based on clock genes and its application to novel therapeutic agents

• Project/Area Number: 20K09095
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Hirosaki University
• Principal Investigator: Morohashi Satoko 弘前大学, 医学研究科, 客員研究員 (90569592)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 直腸癌 / 時計遺伝子 / 術前化学療法 / 治療効果予測 / 大腸癌 / 治療効果

Outline of Research at the Start

従来の直腸癌の治療は外科治療が中心であった。しかし, 術前化学療法は, 根治切除・機能温存という視点から, 腫瘍縮小効果が著明に得られ, 直腸癌治療において注目されつつある。直腸癌術前化学療法の治療効果予測を推測するにあたり, 時計遺伝子が癌微小環境において様々な側面から癌細胞の浸潤や増殖に関与しているという, これまでの我々の研究成果から, 直腸癌の化学療法にも時計遺伝子が関与している可能性を導き出した。 時計遺伝子DECを基盤とした直腸癌術前化学療法治療効果予測を解明するため, 我々は病理組織標本や細胞培養実験を用いた従来の病理学的研究手法に加え, 今回新たに放射線画像の導入を検討する。

Outline of Final Research Achievements

Fifty cases of preoperative chemotherapy for rectal cancer and pre- and post-chemotherapy were divided into a group showing a high reduction rate and a group showing a low reduction rate (23% cut off value) by computed tomography (CT) or magnetic resonance imaging (MRI). A comparison was made with clinicopathological factors.
In order to understand the invasion and progression of colorectal cancer, we used tissue clearing techniques and used cytokeratin (an antibody that stains tumor cells) and CD34 (an antibody that stains blood vessels) to detect fluorescence. Multiple staining was performed to observe the three-dimensional structure in detail.

Academic Significance and Societal Importance of the Research Achievements

大腸癌は、食習慣の変化等により日本人の罹患数が増えている疾患の一つである。術前に化学療法を行い、適切な時期に手術を行うことで、患者のQOLを高く保ち、さらに手術の根治性を上げることが期待される。化学療法効果を予測することは、治療ストラテジーを構築する上で、非常に有用な情報となる。個々の腫瘍の治療効果予測が立てられれば、手術優先か化学療法優先かの選択が適切に決められ、病期進行を制御した状態をなるべく維持し、時期を逸しない根治治療が可能になるものと考える。
術前化学療法でより腫瘍縮小効果を認めた症例群における病理組織学因子を解析することにより、化学療法効果良好症例の特徴を理解することができた。

Research Products

• [Journal Article] 18F-fluorodeoxyglucose positron emission tomography predicts recurrence and histological grade of extrahepatic bile duct cancer. (2023)
  • Author(s): Yachi T, Yoshizawa T, Kimura N, Seino H, Morohashi M, Goto S, Ishido K, Kijima H, Hakamada K.
  • Journal Title: Oncol Lett. Volume: 25 Issue: 3 Pages: 125-125
  • DOI: 10.3892/ol.2023.13711
  • Peer Reviewed / Open Access
• [Journal Article] Use of time density curves of dynamic contrast enhanced computed tomography for determination of the histological therapeutic effects of neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma (2023)
  • Author(s): Goto S, Yoshizawa T, Ishido K, Seino H, Morohashi S, Ogasawara H, Kubota S, Ogasawara K, Nakamura A, Hakamada K, Kijima H.
  • Journal Title: Oncol Rep Volume: 49 Issue: 3 Pages: 61-61
  • DOI: 10.3892/or.2023.8498
  • Peer Reviewed / Open Access
• [Journal Article] Usefulness of Fractal Analysis of Kirsch Edge Images for the Tissue Fragment Inner Structure in Breast FNAB (2022)
  • Author(s): Yoshioka Haruhiko、Shimoda Tsubasa、Oikawa Sota、Morohashi Satoko、Hasegawa Yoshie、Horie Kayo、Watanabe Jun
  • Journal Title: Acta Cytologica Volume: 66 Issue: 2 Pages: 149-158
  • DOI: 10.1159/000519490
  • Peer Reviewed / Open Access
• [Journal Article] Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer (2021)
  • Author(s): Wakiya Taiichi、Ishido Keinosuke、Kimura Norihisa、Nagase Hayato、Yoshizawa Tadashi、Morohashi Satoko、Fujita Hiroaki、Kanda Taishu、Tatara Yota、Saruwatari Junji、Kijima Hiroshi、Hakamada Kenichi
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 21197-21197
  • DOI: 10.1038/s41598-021-00727-3
  • Peer Reviewed / Open Access
• [Journal Article] Time density curve of dynamic contrast enhanced computed tomography correlates with histological characteristics of pancreatic cancer (2021)
  • Author(s): Shintaro Goto, Hiroko Seino, Tadashi Yoshizawa, Satoko Morohashi, Keinosuke Ishido, Kenichi Hakamada, Hiroshi Kijima.
  • Journal Title: Oncology Letters Volume: 21 Issue: 4 Pages: 276-276
  • DOI: 10.3892/ol.2021.12537
  • Peer Reviewed / Open Access
• [Journal Article] Fractal Analysis Method for the Complexity of Cell Cluster Staining on Breast FNAB (2020)
  • Author(s): Haruhiko Yoshioka, Anna Herai, Sota Oikawa, Satoko Morohashi, Yoshie Hasegawa, Kayo Horie, Jun Watanabe.
  • Journal Title: Acta Cytologica Volume: 65 Issue: 1 Pages: 4-12
  • DOI: 10.1159/000509668
  • Peer Reviewed