2010 Fiscal Year Final Research Report
The personalized therapy using Annexin II as a gemcitabine-resistant factor for pancreatic cancer patients after surgery.
| Project/Area Number |
20591622
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Chiba University |
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Principal Investigator |
TAKANO Shigetsugu Chiba University, 医学部附属病院, 助教 (20436380)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHITOMI Hideyuki 千葉大学, 医学部附属病院, 助教 (60375631)
FURUKAWA Katsunori 千葉大学, 医学部附属病院, 助教 (00400987)
KATO Atsushi 千葉大学, 大学院・医学研究院, 助教 (70344984)
SHIMIZU Hiroaki 千葉大学, 大学院・医学研究院, 講師 (80272318)
MIYAZAKI Masaru 千葉大学, 大学院・医学研究院, 教授 (70166156)
SHIDA Takashi 千葉大学, 医学部附属病院, 医員 (60456019)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 膵臓外科学 |
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| Research Abstract |
Background : Although gemcitabine has been widely used as a first-line chemo reagent for patients with pancreatic cancer, the response rate still remains low. We previously identified Annexin II as a factor involved in gemcitabine resistance against pancreatic cancer. The aim of this study was to elucidate the signaling mechanism by which Annexin II induces gemcitabine resistance and to develop a new therapy which overcomes the resistance against gemcitabine.
Materials and methods : We comprehensively investigated and compared the specific profiles of 12 targeted phosphorylated signaling proteins in gemcitabine-resistant (GEM-MIA PaCa-2) and wild-type (WT-MIA PaCa-2) pancreatic cancer cell lines by the Bio-Plex phosphorylation protein assay system. We also evaluated the expression levels of Annexin II and two phosphoproteins, which showed different expression in these two cell lines, by immunohistochemistry of pancreatic cancer tissues.
Results : Annexin II overexpression in cancer cells was significantly associated with rapid recurrence after gemcitabine-adjuvant chemotherapy in patients with resected pancreatic cancer (P=0.0118). Bio-Plex analysis showed upregulation of p-Akt in GEM-MIA PaCa-2 cells in which Annexin II is highly expressed. On immunohistochemistry, the expression level of p-Akt was significantly correlated with that of p-mTOR in pancreatic cancer tissues. Inhibition of mTOR phosphorylation canceled gemcitabine resistance in GEM-MIA PaCa-2 cells.
Conclusion : The Akt/mTOR pathway is involved in the mechanisms of gemcitabine resistance induced by Annexin II in pancreatic cancer cells. Annexin II as an indicator for selection of gemcitabine resistance could thus be applied to the development of novel tailor-made approaches for pancreatic cancer treatment.
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Research Products
(12 results)
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[Journal Article] Increased circulating cell signalling phosphoproteins in sera are useful for the detect ion of pancreatic cancer.2010
Author(s)
Takano S, Sogawa K, Yoshitomi H, Shida T, Mogushi K, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Kato A, Ishihara T, Tanaka H, Yokosuka O, Nomura F, Miyazaki M.
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Journal Title
Br J Cancer. 103(2)
Pages: 223-31
Peer Reviewed
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[Journal Article] One hundred seven consecutive surgical resections for hilar cholangiocarcinoma of Bismuth types II, III, IV between 2001 and 2008.2010
Author(s)
Miyazaki M, Kimura F, Shimizu H, Yoshidome H, Otuka M, Kato A, Yoshitomi H, Furukawa K, Takeuchi D, Takayashiki T, Suda K, Takano S.
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Journal Title
J Hepatobiliary Pancreat Sci. 17(4)
Pages: 470-475
Peer Reviewed
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[Journal Article] Expression of an activated mammalian target of rapamycin (mTOR) in gastroenteropancreatic neuroendocrine tumors.2010
Author(s)
Shida T, Kishimoto T, Furuya M, Nikaido T, Koda K, Takano S, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Tanizawa T, Nakatani Y, Miyazaki M.
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Journal Title
Cance rChemo ther Pharmacol. 65(5)
Pages: 889-893
Peer Reviewed
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[Journal Article] Annexin II overexpression predicts rapid recurrence after surgery in pancreatic cancer patients undergoing gemcitabine-adjuvant chemotherapy.2008
Author(s)
Takano S, Togawa A, Yoshitomi H, Shida T, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Kato A, Tomonaga T, Nomura F, Miyazaki M.
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Journal Title
Ann Surg Oncol. 15(11)
Pages: 3157-3168
Peer Reviewed
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[Journal Article] FGF10/FGFR2 signal induces cell migration and invasion in pancreatic cancer.2008
Author(s)
Nomura S, Yoshitomi H, Takano S, Shida T, Kobayashi S, Ohtsuka M, Kimura F, Shimizu H, Yoshidome H, Kato A, Miyazaki M.
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Journal Title
Br J Cancer. 99(2)
Pages: 305-313
Peer Reviewed
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[Journal Article] The expression of NeuroD and mASH1 in the gastroentero-pancreatic neuroendocrine tumors.2008
Author(s)
Shida T, Furuya M, Kishimoto T, Nikaido T, Tanizawa T, Koda K, Oda K, Takano S, Kimura F, Shimizu H, Yoshidome H, Ohtsuka M, Nakatani Y, Miyazaki M.
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Journal Title
Mod Pathol. 21(11)
Pages: 1363-1370
Peer Reviewed
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[Journal Article] Identification of novel immunohisto- chemical tumor markers for primary hepatocellular carcinoma ; clathrin heavy chain and formiminotransferase cyclodeaminase.2008
Author(s)
Seimiya M, Tomonaga T, Matsushita K, Sunaga M, Oh-Ishi M, Kodera Y, Maeda T, Takano S, Togawa A, Yoshitomi H, Otsuka M, Yamamoto M, Nakano M, Miyazaki M, Nomura F.
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Journal Title
Hepatology. 48(2)
Pages: 519-530
Peer Reviewed
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