[Show abstract][Hide abstract] ABSTRACT: A disintegrin and metalloproteases (ADAMs) comprise a multifunctional family of membrane-anchored proteins. ADAM 9 and ADAM 15 are involved in cell migration and invasion. Expression of ADAM 9 and ADAM 15 was reported to be altered in several types of cancer.
Quantitative real-time reverse transcription-polymerase chain reaction was performed to measure the expression of ADAM 9 mRNA in bulk pancreatic tissues. Results showed no significant difference in the expression of ADAM 9 mRNA between pancreatic cancer and non-neoplastic pancreas. Primary cultured pancreatic fibroblasts also expressed ADAM 9 mRNA. Therefore, a laser microdissection and pressure catapulting technique was employed to isolate cancer cells from tumor tissues. The expression of ADAM 9 and ADAM 15 mRNA was measured in microdissected samples (cancer cells, n = 11; normal epithelial cells, n = 13 for ADAM 9; cancer cells, n = 9; normal epithelial cells, n = 9 for ADAM 15).
Pancreatic cancer cells expressed significantly higher levels of ADAM 9 and ADAM 15 mRNA than did normal pancreatic epithelial cells (p = 0.016 for ADAM 9; p = 0.004 for ADAM 15).
ADAM 9 and ADAM 15 are involved in pancreatic cancer. Microdissection-based analysis appears to be indispensable for the accurate analysis of the expression of certain ADAM family members in pancreatic cancer.
Anticancer research 01/2007; 27(2):793-9. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate c-met expression during early pancreatic carcinogenesis.
We used 46 bulk tissues and 36 micro-dissected samples, including normal pancreas, chronic pancreatitis, and pancreatic cancer, for quantitative real-time reverse transcription-polymerase chain reaction.
In bulk tissue analyses, pancreatic cancer tissues expressed significantly higher levels of c-met than did chronic pancreatitis and normal pancreas tissues. c-met levels did not differ between chronic pancreatitis and normal pancreas tissues. In microdissection-based analyses, c-met was expressed at higher levels in microdissected pancreatic cancer cells and pancreatitis-affected epithelial cells than in normal ductal epithelial cells (both, P < 0.01). Interestingly, pancreatitis-affected epithelial cells expressed levels of c-met similar to those of pancreatic cancer cells.
Overexpression of c-met occurs during the early stage of pancreatic carcinogenesis, and a single alteration of c-met expression is not sufficient for progression of chronic pancreatitis-affected epithelial cells to pancreatic cancer cells.
World Journal of Gastroenterology 07/2006; 12(24):3878-82. · 2.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pancreatic cancer frequently recurs after operative treatment, resulting in a poor prognosis. Inhibition of proliferation of residual cancer cells is important for improved survival of patients with pancreatic cancer. Fibrin glue (FG) is a biocompatible, adherent hemostat that can deliver high concentrations of anticancer drugs to residual cancer cells. The aim of this study was to evaluate the local antitumor effect of a mixture of gemcitabine (GEM) and FG on pancreatic cancer cells implanted orthotopically in nude mice.
SUIT-2 human pancreatic cells were injected into the tail of the pancreas of nude mice. Seven days later, groups of mice were treated with 80 mg/kg GEM mixed with 0.5 mL fibrin glue (GEM + FG), 0.5 mL FG alone (FG), single intraperitoneal (i.p.) injection of 80 mg/kg GEM (GEM1), i.p. injection of 80 mg/kg GEM weekly for 3 weeks (GEM1,2,3), GEM + FG followed by weekly GEM injections for 2 weeks (GEM + FG + GEM2,3), or i.p. injection of PBS weekly for 3 weeks (controls).
Twenty-eight days after cell injections, tumor volumes of groups treated with GEM + FG + GEM2,3, GEM1,2,3, GEM + FG, GEM1, and FG were decreased by 84%, 70%, 62%, 37%, and 10%, respectively, compared to that of control mice. GEM + FG + GEM2,3 had the strongest anticancer effect compared to all other groups (P < .05). Additionally, GEM + FG showed a more potent antitumor effect compared to GEM1 (P < .05). Survival of mice treated with GEM + FG + GEM2,3 was longer than that of mice in all other groups (P < .05).
A mixture of GEM and FG was effective in inhibiting the growth of orthotopically implanted pancreatic neoplasms in nude mice. This procedure may be useful clinically to prevent the local recurrence of pancreatic cancer after pancreatectomy.
Surgery 07/2006; 140(1):66-71. · 3.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although telomerase activity is a promising diagnostic marker, clinical introduction of this marker for cancer diagnosis is still problematic due to the lack of means of evaluating sample quality. Human telomerase reverse transcriptase (hTERT), one of the subunits of telomerase, is also a promising diagnostic marker. In the present study, we did large-scale analysis of 88 pancreatic juice samples to determine the feasibility of quantitative analysis of hTERT mRNA for diagnosis of pancreatic cancer. We found significant differences in hTERT expression among carcinoma-derived, intraductal papillary mucinous neoplasm (IPMN)-derived, and chronic pancreatitis-derived juice samples. Results showed that quantitative analyses of hTERT mRNAs are more useful in discriminating carcinoma from IPMN than from chronic pancreatitis. When the specificity was set at 100%, the sensitivity for differentiation between carcinoma and IPMN was 43.5%, whereas the sensitivity of cytologic examination was 22.0%. There were significant differences in hTERT expression among carcinoma cells, IPMN cells, and normal ductal cells isolated from pancreatic tissues by microdissection. Lymphocytes and hyperplastic epithelial cells isolated from tissues with the histologic appearance of pancreatitis showed various expression levels of hTERT. Our results suggest that quantitative analysis of hTERT mRNA in pancreatic juice is advantageous over cytologic analysis for differentiation between carcinoma and IPMN but probably not for differentiation between carcinoma and chronic pancreatitis.
Clinical Cancer Research 05/2006; 12(7 Pt 1):2066-9. · 7.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pancreatic juice is a promising type of diagnostic sample for pancreatic cancer, and members of the mucin (MUC) family are diagnostic candidates. To evaluate the utility of MUC family members as diagnostic markers, we measured MUC mRNA expression in pancreatic tissues and pancreatic juice obtained from patients with different pancreatic diseases as well as in pancreatic cancer cell lines by real-time PCR. Furthermore, to support the possibility of early diagnosis by quantification of MUC1 and MUC5AC, immunohistochemistry and microdissection-based quantitative analysis of mRNA were carried out. There was no significant correlation between MUC1 and MUC5AC expression in cell lines. When beta-actin was used as a reference gene, median MUC1 and MUC5AC mRNA expression levels were remarkably greater in tumoral tissues than in non-tumoral tissues, but median MUC4 and MUC6 mRNA expression levels were not. Receiver operating characteristic curve analysis showed that quantitative analysis of MUC1 and MUC5AC mRNA in pancreatic juice is better diagnostic modality than that of MUC4 and MUC6 mRNA. Immunohistochemistry showed that MUC1 and MUC5AC were highly expressed in invasive ductal carcinomas (IDC) and moderately expressed in high-grade pancreatic intraepithelial neoplasia (PanIN); no staining was observed in normal ducts. Analysis of cells isolated by microdissection showed stepwise upregulation of MUC1 and MUC5AC in the development of high-grade PanIN to IDC. Our results suggest that MUC1 and MUC5AC are upregulated stepwise in pancreatic carcinogenesis and that quantitative assessment of MUC1 and MUC5AC mRNA in pancreatic juice has high potential for preoperative diagnosis of pancreatic cancer.
International Journal of Cancer 02/2006; 118(2):405-11. · 6.20 Impact Factor