Comprehensive analysis of cancer cachexia signaling pathway for identifying a new therapeutic strategy in colorectal cancer.
Project/Area Number |
17K10640
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Kumamoto University |
Principal Investigator |
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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)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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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)
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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.
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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。
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Report
(4 results)
Research Products
(30 results)
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[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.
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Journal Title
Anticancer Res.
Volume: 38(1)
Pages: 491-499
Related Report
Peer Reviewed
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[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.
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Journal Title
PLoS One.
Volume: 13(3)
Pages: e0193640
DOI
Related Report
Peer Reviewed
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[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).
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Journal Title
Oncology.
Volume: 94(5)
Pages: 289-296
DOI
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Peer Reviewed
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[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.
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Journal Title
Anticancer Res.
Volume: 38(1)
Pages: 491-499
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Clin Cancer Res.
Volume: 24(4)
Pages: 784-793
DOI
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Peer Reviewed
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[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.
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Journal Title
Ann Oncol.
Volume: 28(11)
Pages: 2780-2785
DOI
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Peer Reviewed
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[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.
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Journal Title
Eur J Cancer.
Volume: 86
Pages: 197-206
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Cancer.
Volume: 123(22)
Pages: 4506-4514
DOI
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Peer Reviewed
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[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.
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Journal Title
Int J Cancer.
Volume: 141(6)
Pages: 1222-1230
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Ann Oncol.
Volume: 28(5)
Pages: 1015-1022
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Int J Cancer.
Volume: 141(2)
Pages: 383-392
DOI
Related Report
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[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.
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Journal Title
Eur J Cancer.
Volume: 77
Pages: 13-20
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Int J Clin Oncol.
Volume: 22(4)
Pages: 740-748
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
Pharmacogenomics J.
Volume: 18(1)
Pages: 29-34
DOI
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Peer Reviewed
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[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
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