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Comprehensive analysis of cancer cachexia signaling pathway for identifying a new therapeutic strategy in colorectal cancer.

Research Project

Project/Area Number 17K10640
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Digestive surgery
Research InstitutionKumamoto University

Principal Investigator

Miyamoto Yuji  熊本大学, 病院, 講師 (80551259)

Co-Investigator(Kenkyū-buntansha) 坂本 快郎  熊本大学, 病院, 非常勤診療医師 (00452897)
石本 崇胤  熊本大学, 病院, 特任准教授 (00594889)
馬場 祥史  熊本大学, 病院, 非常勤診療医師 (20599708)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords大腸癌 / カヘキシア / サルコペニア / Activin/Myostatin経路 / 骨格筋量 / 腫瘍免疫 / Activin A / 腫瘍局所免疫 / MSI status / アクチビン/ミオスタチン経路 / アクチビン / RAS 遺伝子変異
Outline of Final Research Achievements

We investigated the association between cachexia status and poor prognosis in patients with colorectal cancer. (1) We found that tumor expression of Activin A was associated with tumor malignancy and poor prognosis in colorectal cancer but no association with skeletal muscle mass. (2) A significant correlation was observed between the amount of skeletal muscle mass and tumor-infiltrating lymphocytes in colorectal cancer patients who underwent primary tumor resection. The results suggest that cachexia may contribute to the poor prognosis of colorectal cancer by affecting local tumor immunity.

Academic Significance and Societal Importance of the Research Achievements

カヘキシアは癌などの慢性疾患に関連した多因性の代謝異常をきたした病態であり、不可逆的な骨格筋の減少を特徴とする。今回、我々は大腸癌症例における低骨格筋量が腫瘍局所免疫に影響を与えることで、大腸癌の予後不良に寄与している可能性について明らかにした。今後の高齢化社会に伴い、低骨格筋量のがん患者が増加することが予想され、骨格筋量を維持しながらがん治療を継続していく重要性が明らかになった。このことはがん治療中の生活の質の維持向上にも役立ち、新たに骨格筋分解シグナル分子をターゲットとした治療法開発にもつながる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (30 results)

All 2020 2019 2018 2017

All Journal Article (20 results) (of which Peer Reviewed: 17 results,  Open Access: 2 results) Presentation (10 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] 12-chemokine signature, a predictor of tumor recurrence in colorectal cancer2020

    • Author(s)
      Tokunaga Ryuma、Nakagawa Shigeki、Sakamoto Yasuo、Nakamura Kenichi、Naseem Madiha、Izumi Daisuke、Kosumi Keisuke、Taki Katsunobu、Higashi Takaaki、Miyata Tatsunori、Miyamoto Yuji、Yoshida Naoya、Baba Hideo、Lenz Heinz-Josef
    • Journal Title

      International Journal of Cancer

      Volume: 147(2) Issue: 2 Pages: 532-541

    • DOI

      10.1002/ijc.32982

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Naples Prognostic Score Is a Useful Prognostic Marker in Patients With Metastatic Colorectal Cancer2019

    • Author(s)
      Miyamoto Yuji、Hiyoshi Yukiharu、Daitoku Nobuya、Okadome Kazuo、Sakamoto Yuki、Yamashita Kohei、Kuroda Daisuke、Sawayama Hiroshi、Iwatsuki Masaaki、Baba Yoshifumi、Yoshida Naoya、Baba Hideo
    • Journal Title

      Diseases of the Colon & Rectum

      Volume: 62 Issue: 12 Pages: 1485-1493

    • DOI

      10.1097/dcr.0000000000001484

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Sarcopenia Affects Systemic and Local Immune System and Impacts Postoperative Outcome in Patients with Extrahepatic Cholangiocarcinoma2019

    • Author(s)
      Kitano Yuki、Yamashita Yo-ichi、Saito Yoichi、Nakagawa Shigeki、Okabe Hirohisa、Imai Katsunori、Komohara Yoshihiro、Miyamoto Yuji、Chikamoto Akira、Ishiko Takatoshi、Baba Hideo
    • Journal Title

      World Journal of Surgery

      Volume: 43 Issue: 9 Pages: 2271-2280

    • DOI

      10.1007/s00268-019-05013-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low Skeletal Muscle Mass before Salvage-Line Chemotherapy Is a Poor Prognostic Factor in Patients with Refractory Metastatic Colorectal Cancer2019

    • Author(s)
      Miyamoto Yuji、Hiyoshi Yukiharu、Akiyama Takahiko、Kiyozumi Yuki、Eto Kojiro、Yohei Nagai、Iwagami Shiro、Baba Yoshifumi、Yoshida Naoya、Baba Hideo
    • Journal Title

      Digestion

      Volume: 99 Issue: 1 Pages: 79-85

    • DOI

      10.1159/000494417

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
  • [Journal Article] Low Visceral Fat Content Is a Negative Predictive Marker for Bevacizumab in Metastatic Colorectal Cancer2018

    • Author(s)
      Miyamoto Y, Oki E, Emi Y, Tokunaga S, Shimokawa M, Ogata Y, Akagi Y, Sakamoto Y, Tanaka T, Saeki H, Maehara Y, Baba H.
    • Journal Title

      Anticancer Res.

      Volume: 38(1) Pages: 491-499

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] NOS2 polymorphisms in prediction of benefit from first-line chemotherapy in metastatic colorectal cancer patients.2018

    • Author(s)
      Schirripa M, Zhang W, Yang D, Cao S, Okazaki S, Loupakis F, Berger MD, Ning Y, Miyamoto Y, Suenaga M, Alberti G, West JD, Lonardi S, Khoukaz T, Bergamo F, Battaglin F, Antoniotti C, Falcone A, Stintzing S, Heinemann V, Lenz HJ.
    • Journal Title

      PLoS One.

      Volume: 13(3) Issue: 3 Pages: e0193640-e0193640

    • DOI

      10.1371/journal.pone.0193640

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prophylactic Effect of Dexamethasone on Regorafenib-Related Fatigue and/or Malaise: A Randomized, Placebo-Controlled, Double-Blind Clinical Study in Patients with Unresectable Metastatic Colorectal Cancer (KSCC1402/HGCSG1402).2018

    • Author(s)
      Tanioka H, Miyamoto Y, Tsuji A, Asayama M, Shiraishi T, Yuki S, Kotaka M, Makiyama A, Shimokawa M, Shimose T, Masuda S, Yamaguchi T, Komatsu Y, Saeki H, Emi Y, Baba H, Oki E, Maehara Y; Kyushu Study Group of Clinical Cancer (KSCC).
    • Journal Title

      Oncology.

      Volume: 94(5) Issue: 5 Pages: 289-296

    • DOI

      10.1159/000486624

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low Visceral Fat Content Is a Negative Predictive Marker for Bevacizumab in Metastatic Colorectal Cancer.2018

    • Author(s)
      Miyamoto Y, Oki E, Emi Y, Tokunaga S, Shimokawa M, Ogata Y, Akagi Y, Sakamoto Y, Tanaka T, Saeki H, Maehara Y, Baba H.
    • Journal Title

      Anticancer Res.

      Volume: 38(1) Issue: 1 Pages: 491-499

    • DOI

      10.21873/anticanres.12249

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A Polymorphism within the Vitamin D Transporter Gene Predicts Outcome in Metastatic Colorectal Cancer Patients Treated with FOLFIRI/Bevacizumab or FOLFIRI/Cetuximab.2018

    • Author(s)
      Berger MD, Stintzing S, Heinemann V, Cao S, Yang D, Sunakawa Y, Matsusaka S, Ning Y, Okazaki S, Miyamoto Y, Suenaga M, Schirripa M, Hanna DL, Soni S, Puccini A, Zhang W, Cremolini C, Falcone A, Loupakis F, Lenz HJ.
    • Journal Title

      Clin Cancer Res.

      Volume: 24(4) Issue: 4 Pages: 784-793

    • DOI

      10.1158/1078-0432.ccr-17-1663

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Molecular Landscape and Treatment Options for Patients with Metastatic Colorectal Cancer.2017

    • Author(s)
      Miyamoto Y, Zhang W, Lenz HJ.
    • Journal Title

      Indian J Surg Oncol.

      Volume: 8(4) Issue: 4 Pages: 580-590

    • DOI

      10.1007/s13193-016-0543-z

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of genetic variations in the MAPK signaling pathway on outcome in metastatic colorectal cancer patients treated with first-line FOLFIRI and bevacizumab: data from FIRE-3 and TRIBE trials.2017

    • Author(s)
      Berger MD, Stintzing S, Heinemann V, Yang D, Cao S, Sunakawa Y, Ning Y, Matsusaka S, Okazaki S, Miyamoto Y, Suenaga M, Schirripa M, Soni S, Zhang W, Falcone A, Loupakis F, Lenz HJ.
    • Journal Title

      Ann Oncol.

      Volume: 28(11) Issue: 11 Pages: 2780-2785

    • DOI

      10.1093/annonc/mdx412

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Potential role of polymorphisms in the transporter genes ENT1 and MATE1/OCT2 in predicting TAS-102 efficacy and toxicity in patients with refractory metastatic colorectal cancer.2017

    • Author(s)
      Suenaga M, Schirripa M, Cao S, Zhang W, Yang D, Dadduzio V, Salvatore L, Borelli B, Pietrantonio F, Ning Y, Okazaki S, Berger MD, Miyamoto Y, Gopez R Jr, Barzi A, Yamaguchi T, Loupakis F, Lenz HJ.
    • Journal Title

      Eur J Cancer.

      Volume: 86 Pages: 197-206

    • DOI

      10.1016/j.ejca.2017.08.033

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tandem repeat variation near the HIC1 (hypermethylated in cancer 1) promoter predicts outcome of oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer.2017

    • Author(s)
      Okazaki S, Schirripa M, Loupakis F, Cao S, Zhang W, Yang D, Ning Y, Berger MD, Miyamoto Y, Suenaga M, Iqubal S, Barzi A, Cremolini C, Falcone A, Battaglin F, Salvatore L, Borelli B, Helentjaris TG, Lenz HJ.
    • Journal Title

      Cancer.

      Volume: 123(22) Issue: 22 Pages: 4506-4514

    • DOI

      10.1002/cncr.30880

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Predictive value of TLR7 polymorphism for cetuximab-based chemotherapy in patients with metastatic colorectal cancer.2017

    • Author(s)
      Okazaki S, Stintzing S, Sunakawa Y, Cao S, Zhang W, Yang D, Ning Y, Matsusaka S, Berger MD, Miyamoto Y, Suenaga M, Schirripa M, West JD, Gopez R, Akihito T, Ichikawa W, Heinemann V, DePaolo RW, Lenz HJ.
    • Journal Title

      Int J Cancer.

      Volume: 141(6) Issue: 6 Pages: 1222-1230

    • DOI

      10.1002/ijc.30810

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Genetic variants of DNA repair-related genes predict efficacy of TAS-102 in patients with refractory metastatic colorectal cancer.2017

    • Author(s)
      Suenaga M, Schirripa M, Cao S, Zhang W, Yang D, Murgioni S, Rossini D, Marmorino F, Mennitto A, Ning Y, Okazaki S, Berger MD, Miyamoto Y, Gopez R Jr, Barzi A, Yamaguchi T, Loupakis F, Lenz HJ.
    • Journal Title

      Ann Oncol.

      Volume: 28(5) Issue: 5 Pages: 1015-1022

    • DOI

      10.1093/annonc/mdx035

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Single nucleotide polymorphisms in the IGF-IRS pathway are associated with outcome in mCRC patients enrolled in the FIRE-3 trial.2017

    • Author(s)
      Schirripa M, Zhang W, Heinemann V, Cao S, Okazaki S, Yang D, Loupakis F, Berger MD, Ning Y, Miyamoto Y, Suenaga M, Gopez RF, West JD, Hanna D, Barzi A, Falcone A, Stintzing S, Lenz HJ.
    • Journal Title

      Int J Cancer.

      Volume: 141(2) Issue: 2 Pages: 383-392

    • DOI

      10.1002/ijc.30715

    • Related Report
      2017 Research-status Report
  • [Journal Article] Recent Advances in Targeting the EGFR Signaling Pathway for the Treatment of Metastatic Colorectal Cancer.2017

    • Author(s)
      Miyamoto Y, Suyama K, Baba H.
    • Journal Title

      Int J Mol Sci

      Volume: 18(4) Issue: 4 Pages: 752-752

    • DOI

      10.3390/ijms18040752

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autophagy-related polymorphisms predict hypertension in patients with metastatic colorectal cancer treated with FOLFIRI and bevacizumab: Results from TRIBE and FIRE-3 trials.2017

    • Author(s)
      Berger MD, Yamauchi S, Cao S, Hanna DL, Sunakawa Y, Schirripa M, Matsusaka S, Yang D, Groshen S, Zhang W, Ning Y, Okazaki S, Miyamoto Y, Suenaga M, Lonardi S, Cremolini C, Falcone A, Heinemann V, Loupakis F, Stintzing S, Lenz HJ.
    • Journal Title

      Eur J Cancer.

      Volume: 77 Pages: 13-20

    • DOI

      10.1016/j.ejca.2017.02.020

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of systemic inflammatory and nutritional scores in colorectal cancer patients who underwent potentially curative resection.2017

    • Author(s)
      Tokunaga R, Sakamoto Y, Nakagawa S, Izumi D, Kosumi K, Taki K, Higashi T, Miyata T, Miyamoto Y, Yoshida N, Baba H.
    • Journal Title

      Int J Clin Oncol

      Volume: in press Issue: 4 Pages: 740-748

    • DOI

      10.1007/s10147-017-1102-5

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical relevance of EMT and stem-like gene expression in circulating tumor cells of metastatic colorectal cancer patients.2017

    • Author(s)
      Ning Y, Zhang W, Hanna DL, Yang D, Okazaki S, Berger MD, Miyamoto Y, Suenaga M, Schirripa M, El-Khoueiry A, Lenz HJ.
    • Journal Title

      Pharmacogenomics J.

      Volume: 18(1) Issue: 1 Pages: 29-34

    • DOI

      10.1038/tpj.2016.62

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 大腸癌患者におけるカヘキシア関連分子Activin A発現の臨床的意義2019

    • Author(s)
      1.大徳 暢哉、宮本 裕士、坂本 悠樹、江藤 弘二郎、日吉 幸晴、長井 洋平、石本 崇胤、馬場 祥史、岩上 志朗、吉田 直矢、馬場 秀夫
    • Organizer
      第119回日本外科学会定期学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 大腸癌におけるPNIおよび腫瘍内CD8陽性T細胞と予後の関連2019

    • Author(s)
      2.大徳 暢哉、宮本 裕士、坂本 悠樹、日吉 幸晴、石本 崇胤、岩槻 政晃、馬場 祥史、岩上 志朗、吉田 直矢、馬場 秀夫
    • Organizer
      第74回日本消化器外科学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腸癌における腫瘍内CD3、CD8陽性T細胞の臨床的意義2019

    • Author(s)
      3.大徳 暢哉、宮本 裕士、秋山 貴彦、坂本 悠樹、江藤 弘二郎、日吉 幸晴、長井 洋平、岩槻 政晃、馬場 祥史、岩上 志朗、吉田 直矢、馬場 秀夫
    • Organizer
      第74回日本大腸肛門病学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腫瘍におけるアクチビンAの発現は大腸癌患者の予後と関連している2018

    • Author(s)
      Nobuya Daitoku、Yuji Miyamoto, Yuki Sakamoto, Kojiro Eto, Yukiharu Hiyoshi, Masaaki Iwatsuki, Takatsugu Ishimoto, Yoshifumi Baba, Shiro Iwagami, Naoya Yoshida, Hideo Baba
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] アクチビンAは大腸癌患者の予後予測因子となりうる2018

    • Author(s)
      大徳暢哉、宮本裕士、坂本悠樹、江藤弘二郎、日吉幸晴、長井洋平、石本崇胤、馬場祥史、岩上志朗、吉田直矢、馬場秀夫
    • Organizer
      第29回日本消化器癌発生学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Polymorphisms in left-right axis-related genes predict outcome in KRAS-wt mCRC patients received cetuximab chemotherapy.2018

    • Author(s)
      Yuji Miyamoto, Hideo Baba, Heinz-Josef Lenz
    • Organizer
      日本消化器癌発生学会 2018
    • Related Report
      2017 Research-status Report
  • [Presentation] 切除不能大腸癌症例における化学療法時の骨格筋量測定の意義2018

    • Author(s)
      宮本裕士、日吉幸晴、大徳暢哉、澤山 浩、岩槻政晃、馬場祥史、吉田直矢、馬場秀夫
    • Organizer
      日本消化管学会 2018
    • Related Report
      2017 Research-status Report
  • [Presentation] Genetic variations in Semaphorin / Neuropilin signaling predict clinical outcome in patients (pts) with metastatic colorectal cancer (mCRC) receiving bevacizumab-based chemotherapy.2018

    • Author(s)
      Yuji Miyamoto, Fotios Loupakis, Wu Zhang, et al.
    • Organizer
      ASCO annual meeting 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genetic variations in genes implicated in the left-right axis are associated with outcome in patients (pts) with metastatic colorectal cancer (mCRC) treated with cetuximab plus chemotherapy.2018

    • Author(s)
      Yuji Miyamoto, Sebastian Stintzing, Wu Zhang, et al.
    • Organizer
      ASCO annual meeting 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 内臓肥満が大腸癌に与える影響:Leptinは女性の大腸癌予後を悪化させる。2017

    • Author(s)
      宮本裕士、大内繭子、坂本快郎、徳永竜馬、澤山 浩、岩槻政晃、馬場祥史、吉田直矢、馬場秀夫
    • Organizer
      日本消化器外科学会総会 2017
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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