| Project/Area Number |
14370177
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Kanazawa University |
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Principal Investigator |
SAWABU Norio Kanazawa University, Cancer Research Institute, Professor of Internal Medicine and medical oncology, がん研究所, 教授 (90019969)
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| Co-Investigator(Kenkyū-buntansha) |
MOTOO Yoshiharu Kanazawa University, Cancer Research Institute, Associate Professor of Internal Medicine and Medical Oncology, がん研究所, 助教授 (80210095)
WATANABE Hiroyuki Kanazawa University, University Hospital, Lecturer of Internal Medicine, 医学部附属病院, 講師 (30242564)
YAMAGUCHI Yasushi Kanazawa University, Cancer Research Institute, Research Associate of Internal Medicine and Medical Oncology, がん研究所, 助手 (20303315)
岡井 高 金沢大学, がん研究所, 助教授 (60160660)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥6,100,000 (Direct Cost: ¥6,100,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | pancreatic juice / pancreatic cancer / intraductal papillary mucinous neoplasm (IPMN) / p53 / hypermethylation / mesothelin / h-TERT / SARP-2 / 膵管内乳頭腫瘍 / ppENK / SARP2 / CLDN5 / NPTX2 / 慢性膵炎 / ppENK(proproenkephalin) / 膵管内乳頭状粘液性腫瘍 / hTERT(human telomerase reverse transcriptase) / 膵管内乳頭状腫瘍 / K-ras / 膵液細胞診 |
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| Research Abstract |
We analyzed mutations of p53 in DNA extract not only from the sediment(Sed) but also from the supernatant(sup) of aspirated pancreatic juice(PJ) by ERCP and bile obtained by PTC or ERBD. The incidence of p53 mutations was 43%(9 of 21) and 29%(6 of 21) in the Sup and the Sed of PJ from patients with pancreatic cancer(PCa), respectively, and nurse to 52%(11 of 21) in the combination assay with Sup and Sed. Moreover, p53 mutations were detected in 47%(7 of 15) of PCa cases in which the cyto logic diagnosis was negative. Among 25 patients with chronic pancreatitis(CP), none harbored mutant p53. In bile abtained from patients with biliary tract cancer, the positive rate of p53 mutations was 50%(15 of 30) in the Sup and 33%(10 of 30) in the Sed. On the other hand, there were no pantients with cholelithiasis harboring mutant p53. These results could indicate that the incidence of p53 mutation was higher in the Sup than in the Sed, and the specificity of p53 mutation was higher in the Sup than
… More
in the Sed, and the specificity of p53 mutation for cancer was very high. Mesothlin mRNA expression in the PJ was discovered in 11(52%) of 21 patients with PCa,5(45%) of 11 with intraductal papillary mucinous neoplasm(IPMN) and 3(14%) of 22 with CP. There was significant difference between PCa and CP for mesothelin mRNA. We developed an highly sensitive quantitative analysis for h-TERT mRNA using real-time RT-PCR and measured the amount of h-TERT mRNA in serum and PJ. The levels of h-TERT mRNA were elevated in almost all cases with PCa but also in considerable cases with benign lesions, suggesting low specificity of h-TERT mRNA for cancer. h-TERT mRNA in body fluids from benign lesions originates from lymphocyte.
Using methylation-specific PCR, we nextly analyzed the methylation status of 3 CpG islands of ppENK, SARP2 and NPTX2 in PJ samples. Aberrant methylation of ppENK in the PJ was detected in 14(50%) of 28 patients with PCa, 4(27%) of 15 with IPMN and 1(15%) of 20 with CP, and that of NPTX2 was detected in 24(77%) of 35 patients with PCa, 10(63%) of 16 with IPMN and 6(43%) of 13 with CP. The incidence of aberrant methylation of ppENK or NPTX2 was significantly higher in PCa than in CP. Furthermore, we found aberrant methylation of SARP2 in PJ in 24(74%) of 35 patients with PCa, 15(94%) of 16 with IPMN and 2(11%) of 19 with CP. The incidence of aberrant methylation of SARP2 was significantly higher in PCa or IPMN than in CP. Although the prevalence of aberrant methylation of the tumor-related genes in PJ from PCa was strikingly high, its specificity for cancer was not sufficient. There was no significant difference between benign and malignant groups of IPMN, suggesting that aberrant menthylation of these genes is a early event in PCa development, and quantitative detection of aberrant methylation in PJ may have potential diagnostic implication for PCa. Less
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