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  • 1
    Keywords: CANCER ; EXPRESSION ; SURVIVAL ; tumor ; carcinoma ; Germany ; THERAPY ; DISEASE ; PROTEINS ; TISSUE ; TUMORS ; MARKER ; prognosis ; BIOLOGY ; PATTERNS ; mass spectrometry ; MARKERS ; MASS-SPECTROMETRY ; Jun ; adenocarcinoma ; pancreatic cancer ; pancreatic carcinoma ; PROTEOMICS ; 2-DIMENSIONAL GEL-ELECTROPHORESIS ; chemoresistance ; SERUM ; PANCREATIC-CANCER ; DUCTAL ADENOCARCINOMA ; SOLID TUMORS ; analysis ; pancreatic ; PROGNOSTIC MARKER ; TECHNOLOGY ; JUICE ; genomic ; protein profiling
    Abstract: Ductal pancreatic adenocarcinoma is a dismal disease, having the worst prognosis of all solid tumors. While genomics and transcriptomics have provided a wealth of data, no contribution has been made to clinical medicine in terms of diagnostic or prognostic markers. Hope lies in yet another novel technology, proteomics. Conceptually, proteomics bears the advantage of incorporating both posttranslational modifications as well as host factors. This is thought to be important in factors influencing survival such as chemoresistance. This tutorial review discusses the state of the art in pancreatic cancer proteomics in light of technical developments. At this moment, proteomics is still at the beginning in clinical application. First results, however, suggest some hope for the development of a new understanding of the molecular biology in pancreatic cancer yielding into very specific markers of disease or allowing a rational and individualized therapy
    Type of Publication: Journal article published
    PubMed ID: 16773365
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  • 2
    Keywords: CANCER ; CELLS ; EXPRESSION ; carcinoma ; CELL ; human ; PROTEIN ; PROTEINS ; RNA ; LINES ; primary ; CELL-LINES ; 5-FLUOROURACIL ; BREAST ; breast cancer ; BREAST-CANCER ; ASSAY ; resistance ; CARCINOMA CELLS ; CELL-LINE ; chemotherapy ; LINE ; CARCINOMA-CELLS ; sensitivity ; MULTIDRUG-RESISTANCE ; pancreatic cancer ; pancreatic carcinoma ; protein expression ; CYTOTOXICITY ; multidrug resistance ; PANCREATIC-CANCER ; INTERFERENCE ; RNA INTERFERENCE ; P-GLYCOPROTEIN ; TRANSPORTER ; mRNA ; methods ; multidrug resistance protein ; MRP3 ; MRP4 ; MULTIDRUG-RESISTANCE-PROTEIN ; MULTIDRUG ; quantitative ; PROFILE ; CANCER RESISTANCE PROTEIN ; MDR1 P-GLYCOPROTEIN ; expression profile ; ABC
    Abstract: Pancreatic cancer is characterized by high resistance to chemotherapy. Such chemoresistance can be mediated by multidrug resistance proteins (MRPs), breast cancer resistance protein (BCRP), and MDR1 P-glycoprotein. However, the contribution of individual MRP isoforms to chemoresistance in pancreatic carcinoma is unclear. We studied ATP-binding cassette (ABC) transporter expression in human pancreatic carcinoma cell lines as compared to primary pancreatic duct cells, and analyzed the MRP expression profile in 5-fluorouracil-resistant cells. Methods: Transporter expression was analyzed by quantitative and qualitative RT-PCR, by immunoblot, and chemoresistance by cytotoxicity assay. Results: Primary pancreatic duct cells expressed MRP1, MRP3, MRP4, and MRP5, but not MRP2 mRNA. The established carcinoma cell lines expressed MRP1, MRP4, and MRP5, most of them also MRP2, MRP3, MRP7, and BCRP, but none contained detectable amounts of MRP6, MRP8, or MRP9 mRNA. Immunoblot analyses demonstrated presence of MRP1, MRP4, and MRP5 protein in all, but MRP3 and BCRP protein only in some of these cells. Compared to parental Capan-1 cells, Capan-1 cells with acquired chemoresistance towards 5-fluorouracil showed an upregulated mRNA and protein expression of MRP3, MRP4, and MRP5. In addition, silencing of MRP5 by RNA interference resulted in enhanced sensitivity of parental Capan-1 cells towards 5-fluorouracil cytotoxicity. Conclusion: MRP3, MRP4, and MRP5 are upregulated in 5-fluorouracil-resistant cells, and MRP5 contributes to 5-FU resistance in pancreatic carcinoma cells. and IAP
    Type of Publication: Journal article published
    PubMed ID: 19077464
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  • 3
    Keywords: CANCER ; ANTIGEN ; PROGNOSTIC VALUE ; SERUM ; GEMCITABINE ; PANCREATIC-CANCER ; CEA ; BIOLOGICAL VARIATION ; CA19-9 gastrointestinal cancer antigen ; GI Monitor,pancreatic cancer ; IMMUNOASSAYS MARKER CA-19-9 ; method comparison,diagnosis ; TUMOR-ASSOCIATED ANTIGEN ; UTILITY
    Abstract: Background: This study was designed to investigate the clinical performance of the Access GI Monitor (Beckman Coulter) on the UniCel DxI 800, a method for CA19-9 antigen determination, and to compare with CA19-9 assay on the AxSYM system (Abbott). Methods: 1,063 serum samples from unselected patients with different underlying diagnoses were tested with both methods. Passing-Bablok regression analysis and Bland Altman analysis was performed. In addition, using ROC analysis, the distribution of Access Cl Monitor and AxSYM CA19-9 antigen levels was tested in patients with pancreatic cancer (n = 50), acute inflammatory disease (n = 20), and with chronic inflammation of the pancreatic gland (n = 18). Furthermore, four patients with pancreatic cancer were monitored individually in their courses of the disease (before, during, and after therapeutic procedures) to compare their CA19-9 values with regard to inter-method concordance. Results: Passing-Bablok analysis showed a systematic difference with R = 0.93, slope 0.75, and intercept -1.0. Bland Altman analysis showed a wide scatter of relative differences between both methods, especially in the low end measuring range. In the selected group of patients with pancreatic diseases the analysis of concordance revealed 95.5 % agreement between both methods with a comparable area under the ROC curves (0.73 vs. 0.76). A clear concordance was found for all four selected patients. Conclusions: Although we found significant systematic measuring variations in the global analysis, the two different automated methods for the quantitative determination of CA19-9 antigen were comparable with respect to their clinical accuracy and applicability to support decision making in the management of pancreatic cancer.
    Type of Publication: Journal article published
    PubMed ID: 20857896
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