Functional analysis and development of novel treatment targeting for Nrf2 in hapatobiliary pancreatic cancer
Project/Area Number |
18K16370
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Kumamoto University |
Principal Investigator |
Kitano Yuki 熊本大学, 病院, 非常勤診療医師 (40814760)
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Project Period (FY) |
2018-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | がん代謝 / 腫瘍免疫 / 免疫チェックポイント / バイオマーカー / 肝胆膵領域癌 / Nrf2 / PD-L1 / CD8+ T細胞 / 膵癌 / CD8 T細胞 |
Outline of Final Research Achievements |
In this study, we analyzed the effect of Nrf2 on the progression of hepatobiliary-pancreatic cancer through tumor immunity. In vitro experiments using pancreatic cancer cell lines showed that Nrf2 could affect tumor growth. We found that there was a correlation between Nrf2 and PD-L1 expression in pancreatic cancer from the TCGA database. Immunohistochemistry using resected pancreatic cancer showed a poor prognosis in the PD-L1 high expression group and the CD8 low expression group. In cholangiocarcinoma, although there was no correlation between Nrf2 and PD-L1 expression, there was a negative correlation between Nrf2 and CD8 expression. Immunohistochemistry using resected cholangiocarcinoma showed a poor prognosis in the PD-L1 high expression group and CD8 low expression group. We might show that Nrf2 promotes tumor progression in association with tumor immunity in hepato-biliary-pancreatic cancer and causes poor patient prognosis.
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Academic Significance and Societal Importance of the Research Achievements |
肝胆膵領域癌は有効な抗癌剤や分子標的治療薬が限られており、その予後は未だに不良である。基礎研究及び臨床研究により分子標的治療薬に代表される革新的な治療法を開発することが喫緊の課題である。“がん代謝”は、がん細胞の発育・進展において非常に重要な役割を担っており、近年がん研究において注目されている。Nrf2はがん代謝の主要な制御遺伝子であると報告され、さらに腫瘍免疫と複雑に関連していると言われている。本研究により、肝胆膵領域癌においてNrf2が腫瘍免疫と関連して腫瘍進展を促し、患者予後に与える影響について検討した。
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Report
(3 results)
Research Products
(21 results)
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[Journal Article] Conophylline suppresses pancreatic cancer desmoplasia and cancer-promoting cytokines produced by cancer-associated fibroblasts2019
Author(s)
N. Ishii, K. Araki, T. Yokobori, K. Hagiwara, G. Dolgormaa, T. Yamanaka, T. Handa, M. Tsukagoshi, T. Igarashi, A. Watanabe, N. Kubo, N. Harimoto, A. Masamune, K. Umezawa, H. Kuwano, K. Shirabe
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Journal Title
Cancer Science
Volume: 10
Issue: 1
Pages: 334-434
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A case of acute perforated cholecystitis with intracystic tumor thrombus of hepatocellular carcinoma.2019
Author(s)
Nakao Y, Okabe H, Yamashita Y, Itoyama R, Yusa T, Kitano Y, Arima K, Miyata T, Nakagawa S, Imai K, Chikamoto A, Baba H
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Journal Title
Int Canc Conf J
Volume: 8(1)
Pages: 43-45
Related Report
Peer Reviewed
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[Journal Article] Clinical role of fludeoxyglucose (18F) positron emission tomography/computed tomography ((18)F-FDG PET/CT) in patients with pancreatic neuroendocrine tumors.2019
Author(s)
Matsumoto T, Okabe H, Yamashita Y, Yusa T, Itoyama R, Nakao Y, Yamao T, Umzaki N, Tsukamoto M, Kitano Y, Miyata T, Arima K, Nitta H, Hayashi H, Imai K, Chikamoto A, Baba H
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Journal Title
Surg Today
Volume: 49(1)
Issue: 1
Pages: 21-26
DOI
Related Report
Peer Reviewed
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[Journal Article] Clinical significance of preoperative hepatocellular carcinoma with high lens culinaris agglutinin-reactive fraction of alpha-fetoprotein, but low alpha-fetoprotein.2019
Author(s)
Yamao T, Yamashita Y, Imai K, Umezaki N, Tsukamoto M, Kitano Y, Arima K, Miyata T, Nakagawa S, Okabe H, Hayashi H, Chikamoto A, Ishiko T, Baba H
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Journal Title
Anticancer Res
Volume: 39(2)
Issue: 2
Pages: 883-889
DOI
Related Report
Peer Reviewed
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[Journal Article] Nrf2 promotes oesophageal cancer cell proliferation via metabolic reprogramming and detoxification of reactive oxygen species.2018
Author(s)
Kitano Y, Baba Y, Nakagawa S, Miyake K, Iwatsuki M, Ishimoto T, Yamashita YI, Yoshida N, Watanabe M, Nakao M, Baba H.
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Journal Title
J Pathol.
Volume: 244(3)
Issue: 3
Pages: 346-357
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Tumor-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma.2018
Author(s)
Kitano Y, Okabe H, Yamashita YI, Nakagawa S, Saito Y, Umezaki N, Tsukamoto M, Yamao T, Yamamura K, Arima K, Kaida T, Miyata T, Mima K, Imai K, Hashimoto D, Komohara Y, Chikamoto A, Ishiko T, Baba H
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Journal Title
Br J Cancer
Volume: 118(2)
Issue: 2
Pages: 171-180
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Prognostic value of LINE-1 methylation level in 321 patients with primary liver cancer including hepatocellular carcinoma and intrahepatic cholangiocarcinoma.2018
Author(s)
Miyata T, Yamashita Y, Baba Y, Harada K, Yamao T, Umezaki N, Tsukamoto M, Kitano Y, Yamamura K, Arima K, Nakagawa S, Okabe H, Imai K, Hashimoto D, Chikamoto A, Shimokawa M, Baba H
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Journal Title
Oncotarget
Volume: 9
Issue: 29
Pages: 20795-20806
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Controlling Nutritional Status (CONUT) score is a prognostic marker for gastric cancer patients after curative resection. Gastric Cancer.2018
Author(s)
Kuroda D, Sawayama H, Kurashige J, Iwatsuki M, Eto T, Tokunaga R, Kitano Y, Yamamura K, Ouchi M, Nakamura K, Baba Y, Sakamoto Y, Yamashita Y, Yoshida N, Chikamoto A, Baba H
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Journal Title
Gastric Cancer.
Volume: 21(2)
Issue: 2
Pages: 204-212
DOI
Related Report
Peer Reviewed
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[Journal Article] Hepatic resection followed by hepatic arterial infusion chemotherapy for hepatocellular carcinoma with intrahepatic dissemination.2018
Author(s)
Kuramoto K, Beppu T, Nitta H, Imai K, Masuda T, Miyata T, Koga Y, Kitano Y, Kaida T, Nakagawa S, Okabe H, Hayashi H, Hashimoto D, Yamashita Y, Chikamoto A, Kikuchi K, Baba H
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Journal Title
Anticancer Res
Volume: 38(1)
Pages: 525-531
Related Report
Peer Reviewed
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[Journal Article] A case of 15-year recurrence-free survival after microwave coagulation therapy for liver metastasis from gastric cancer.2018
Author(s)
Kinoshita K, Beppu T, Miyata T, Kuramoto K, Yoshida Y, Umesaki N, Kitano Y, Nakagawa S, Okabe H, Nitta H, Imai K, Hayashi H, Yamashita Y, Komori H, Horino K, Misumi A, Baba H
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Journal Title
Anticancer Res
Volume: 38(3)
Pages: 1595-1598
Related Report
Peer Reviewed
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[Journal Article] Multiple primary cancers in patients with pancreatic cancer.2018
Author(s)
Yamamura K, Hashimoto D, Kitano Y, Kuroda D, Eto T, Arima K, Kaida T, Miyata T, Nakagawa S, Imai K, Yamashita Y, Chikamoto A, Matsumura F, Baba H
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Journal Title
Related Report
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[Journal Article] Cystic gastric metastasis from pancreatic cancer.2018
Author(s)
Umezaki N, Hashimoto D, Nakagawa S, Yamao T, Tsukamoto M, Kitano Y, Arima K, Yamamura K, Miyata T, Okabe H, Chikamoto A, Matsumura F, Baba H
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Journal Title
Surg Case Rep
Volume: 4(1)
Issue: 1
Pages: 31-31
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Complete remission of advanced hepatocellular carcinoma following transient chemoembolization and portal vein ligation.2018
Author(s)
Koga Y, Beppu T, Imai K, Kuramoto K, Miyata T, Kitano Y, Nakagawa S, Okabe H, Okabe K, Yamashita Y, Chikamoto A, Baba H
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Journal Title
Surg Case Rep
Volume: 4(1)
Issue: 1
Pages: 102-102
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Clinical usefulness of postoperative C-reactive protein/albumin ratio in pancreatic ductal adenocarcinoma.2017
Author(s)
Arima K, Yamashita YI, Hashimoto D, Nakagawa S, Umezaki N, Yamao T, Tsukamoto M, Kitano Y, Yamamura K, Miyata T, Okabe H, Ishimoto T, Imai K, Chikamoto A, Baba H.
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Journal Title
Am J Surg.
Volume: Aug 26
Issue: 1
Pages: 111-115
DOI
Related Report
Peer Reviewed