| Project/Area Number |
18591501
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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 |
NOZAWA Satoshi Chiba University, Chiba Univrersiy Hospital, Assistant Professor (30345582)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAZAKI Masaru Chiba University, Graduate School of Medicine, Professor (70166156)
SHIMIZU Hiroaki Chiba University, Graduate Schcol of Medicine, Assistant Professor (80272318)
YOSHITOMI Hideyuki Chiba University, Chiba University Hospital, Research Associate (60375631)
TAKEUCHI Dan Chiba University, Chiba University Hospital, Research Associate (20400822)
TAKANO Shigetsugu Chiba University, Chiba University Hospital, Research Associate (20436380)
川本 潤 千葉大学, 医学部附属病院, 医員 (90400910)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,950,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2007: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | proteome / cancer / protein / knockdown / pancreatic cancer / 発現制御 |
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| Research Abstract |
We compared pre- and postoperative serum protein profiling obtained from pancreatic cancer patients who had curative pancreatectomy using surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS). The peak intensity levels of both 6630 and 6420 Da were significantly higher in the preoperative serum than in the postoperative serum (p<0. 002). Sequential amino acid analysis identified these proteins to be apolipoprotein C-1 (ApoC-1). Furthermore, ApoC-1 was abundantly expressed in pancreas neoplastic epithelium, and was detected in the culture medium of the pancreatic cancer cell line in vitro, which suggests that cancer cells secrete ApoC-1. The high level of ApoC-1 in preoperative serum significantly correlated with poor prognosis in the preoperative serum samples from an independent group of 69 pancreatic cancer patients who had surgical resection of cancer. We also performed the receiver-operator-characteristics (ROC) analysis between patients with survival time more and less than two years. The respective area under the ROC curve (AUC) was 0. 66 for ApoC-1 peak intensity and 0. 60 for CA19-9 level. These results indicated that serum ApoC-1 peak intensity had the better ability as a prognostic marker than serum CA19-9 level.
Inhibition of ApoC-1 expression by siRNA suppressed cell proliferation and induced apoptosis of pancreatic cancer cells. The specific expression of ApoC-1 and its rote in preventing from spontaneous apoptosis in pancreatic cancer cells suggest that ApoC-1 contributes to the aggressiveness of pancreatic cancer and will be useful as a new therapeutic target.
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