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  • 1
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    Pancreatology 4 (2), 67-75 
    Keywords: EXPRESSION ; CELL ; Germany ; DISEASE ; HISTORY ; GENE-EXPRESSION ; PROTEIN ; PROTEINS ; RNA ; DNA ; FIELD ; EXPERIENCE ; AGE ; electrospray ionization ; SPECTROMETRY ; MASS-SPECTROMETRY ; STRATEGIES ; pancreatic carcinoma ; physiology ; PROTEOMICS ; 2-DIMENSIONAL GEL-ELECTROPHORESIS ; IMMOBILIZED PH GRADIENTS ; PROTEIN IDENTIFICATION ; GEL-ELECTROPHORESIS ; MASSES ; 2D ; BINDING-PROTEIN ; pancreas ; review ; genomics ; proteome ; PANCREATITIS ; TISSUE MICROARRAYS ; LASER CAPTURE MICRODISSECTION ; MASS-SPECTROMETRY DATA ; pancreatology ; PROTEIN-ANALYSIS ; SULFATE-POLYACRYLAMIDE GELS
    Abstract: Proteomics represents a novel methodological approach to investigate the expression of all proteins by a cell or organism in its entireness, similar to global strategies for DNA (genomics) and RNA (transcriptomics). This review focuses on the history of protein analysis, which made up the golden age of pancreatic physiology, the current methodology for proteomics (2D gel electrophoresis, mass spectrometry) and the few published experiences with proteomics in the field of pancreatology until now. Finally, potential applications of proteomics for the pancreas, in concert with other techniques, are cited. Copyright (C) 2004 S. Karger AG, Basel and IAP
    Type of Publication: Journal article published
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  • 2
    Keywords: CANCER ; INVASION ; tumor ; carcinoma ; evaluation ; Germany ; CT ; DIAGNOSIS ; FOLLOW-UP ; SPIRAL CT ; TOOL ; DISEASE ; TUMORS ; computed tomography ; RESOLUTION ; PATIENT ; primary ; NO ; METASTASIS ; adenocarcinoma ; COMPUTED-TOMOGRAPHY ; sensitivity ; specificity ; VESSELS ; QUESTIONNAIRE ; pancreatic carcinoma ; HELICAL CT ; HYDRO-CT ; methods ; ROW CT ; CURVED PLANAR REFORMATIONS ; invasion score ; MULTISLICE SPIRAL CT ; resectability ; VASCULAR INVASION
    Abstract: Objective: It was the aim of this study to evaluate a new infiltration score to determine the resectability of pancreatic carcinomas in preoperative planning. Materials and Methods: Eighty patients with suspected pancreatic tumor were examined prospectively using 16-row spiral CT. The scans were evaluated for the presence of pancreatic carcinoma, peripancreatic tumor extension and vascular invasion using a standardized questionnaire. Invasion of the surgically relevant vessels was evaluated using a new invasion score. The operative and histological findings and the clinical follow-up served as the gold standard. Results: Forty patients had a pancreatic carcinoma, 5 had metastasis of a different primary tumor, and in 35 patients, there was no malignant pancreatic disease. The sensitivity for tumor detection was 100%, with a specificity of 88% for differentiating between malignant and benign pancreatic tumors. Invasion of the surrounding vessels was evaluated correctly using the invasion score, with a sensitivity of 89% and a specificity of 99%. In evaluation of resectability, a sensitivity of 94% and a specificity of 89% were achieved. Conclusion: Using 16-row spiral CT, the invasion score is a valid tool for correctly assessing invasion in relevant vessels in cases of pancreatic carcinoma and for determining resectability. Copyright (C) 2008 S. Karger AG, Basel and IAP
    Type of Publication: Journal article published
    PubMed ID: 18434758
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  • 3
    Keywords: CANCER ; tumor ; carcinoma ; CELL ; Germany ; CT ; imaging ; DISEASE ; DIFFERENTIATION ; TISSUE ; computed tomography ; SURGERY ; PATIENT ; primary ; MRI ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; NO ; DIFFERENCE ; NUMBER ; METASTASIS ; metastases ; REGION ; REGIONS ; DISSEMINATED TUMOR-CELLS ; adenocarcinoma ; COMPUTED-TOMOGRAPHY ; CELL CARCINOMA ; renal cell carcinoma ; pancreas ; ENHANCEMENT ; methods ; multidetector CT ; RENAL-CELL
    Abstract: Aims: To investigate the characteristics of metastasis to the pancreas using computed tomography (CT) and magnetic resonance imaging (MRI). Methods: Twenty-two patients with metastases to the pancreas were examined preoperatively by MRI (7/22) and/or multidetector CT (15/22). Pre- and post-contrast images were acquired and morphology, size, and contrast enhancement of the tumor analyzed. Subsequently, all patients underwent surgery, and the histopathologic findings were compared with the imaging results. Results: In 22 patients, a total of 29 metastases were found on CT and MRI. These metastases originated from renal cell carcinomas (RCC; 22/29), colorectal carcinoma (3/29), and other malignancies (4/29). The metastases differed not in size or location, but in their contrast enhancement characteristics. RCC metastases had either intense homogeneous enhancement (in small lesions) or rim enhancement (in large lesions). Outer regions of colorectal metastases showed no difference from normal pancreatic tissue, whereas the inner area showed hypo-enhancement due to central necrosis. Conclusion: Imaging features of metastases from RCC point to their primary origin. While they can be distinguished from primary adenocarcinoma of the pancreas, differentiation from endocrine carcinoma might be difficult. Differentiation of colorectal carcinoma remains to be investigated on larger numbers of cases. Copyright (C) 2008 S. Karger AG, Basel and IAP
    Type of Publication: Journal article published
    PubMed ID: 18434757
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  • 4
    Keywords: CANCER ; SURVIVAL ; TOXICITY ; TRIALS ; CRITERIA ; COOPERATIVE-ONCOLOGY-GROUP ; OLDER ; 1ST-LINE THERAPY ; COMPREHENSIVE GERIATRIC ASSESSMENT ; PLUS GEMCITABINE
    Type of Publication: Journal article published
    PubMed ID: 24854617
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  • 5
    Abstract: BACKGROUND/OBJECTIVES: Solid pseudopapillary neoplasms of the pancreas (SPN) are rare tumors. For patients with unresectable liver metastases of SPN, no standard treatment has been defined so far. Here we report a case of a 40-year-old woman with SPN and metastases confirmed to the liver, and disease progression in the liver after primary tumor resection and chemotherapy with gemcitabine and cisplatin. METHODS: Chemosaturation with percutaneous hepatic perfusions is a minimally invasive, repeatable regional therapy which delivers chemotherapy directly to the liver while limiting systemic toxicity. As an individual treatment approach, the patient was treated with chemosaturation with percutaneous hepatic perfusions of melphalan. RESULTS: The procedure was performed twice within 8 weeks after which the liver metastases showed a marked reduction in size and vascularization (partial response). Grade 3 leukopenia after the second procedure was managed effectively with granulocyte colony-stimulating factor. No other toxicities were observed. Ten months after initiating treatment, the patient had a good performance status and remained stable. CONCLUSIONS: For SPN with unresectable liver metastases and progression despite systemic treatment, repeat chemosaturation with high-dose melphalan may also offer an effective regional treatment option.
    Type of Publication: Journal article published
    PubMed ID: 25280592
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  • 6
    Keywords: CANCER ; EXPRESSION ; TUMOR-CELLS ; ACTIVATION ; T-CELLS ; B-CELLS ; DUCTAL ADENOCARCINOMA ; AMYLASE RELEASE ; MARKER FOXP3 ; ACINAR-CELLS
    Abstract: BACKGROUND/OBJECTIVES: Meaningful profiling of pancreatic cancer samples is particularly challenging due to their complex cellular composition. Beyond tumor cells, surgical biopsies contain desmoplastic stroma with infiltrating inflammatory cells, adjacent normal parenchyma, and "non-pancreatic tissues". The risk of misinterpretation rises when the heterogeneous cancer tissues are sub-divided into smaller fragments for multiple analytic procedures. Pre-analytic histological evaluation is the best option to characterize pancreatic tissue samples. Our aim was to develop a complement or alternative procedure to determine the cellular composition of pancreatic cancerous biopsies, basing on intra-analytic molecular annotation. A standard process for sample stratification at a molecular level does not yet exist. Particularly in the case of retrospective or data depository-based studies, when hematoxylin-eosin stained sections are not available, it supports the correct interpretation of expression profiles. METHODS: A five-gene transcriptional signature (RNACellStrat) was defined that allows cell type-specific stratification of pancreatic tissues. Testing biopsy material from biobanks with this procedure demonstrated high correspondence of molecular (qRT-PCR and microarray) and histologic (hematoxylin-eosin stain) evaluations. RESULTS: Notably, about a quarter of randomly selected samples (tissue fragments) were exposed as inappropriate for subsequent clinico-pathological interpretation. CONCLUSIONS: Via immediate intra-analytical procedure, our RNA-based stratification RNACellStrat increases the accuracy and reliability of the conclusions drawn from diagnostic and prognostic molecular information.
    Type of Publication: Journal article published
    PubMed ID: 26118650
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  • 7
    Keywords: CELLS ; IN-VITRO ; BLOOD ; carcinoma ; CELL ; COMBINATION ; Germany ; human ; IN-VIVO ; MODEL ; PERFUSION ; THERAPY ; VITRO ; VIVO ; BLOOD-FLOW ; pig ; TRANSPLANTATION ; animals ; blood flow ; FLOW ; EFFICACY ; chemotherapy ; DAMAGE ; arteries ; THERAPEUTIC EFFICACY ; CARCINOMAS ; ARTERY ; BODY ; pancreatic carcinoma ; FEASIBILITY ; DUCTAL CARCINOMA ; 2-DECHLOROETHYLIFOSFAMIDE ; 3-DECHLOROETHYLIFOSFAMIDE ; 4-HYDROXYIFOSFAMIDE ; angiographical targeting ; CARDIOPULMONARY BYPASS ; CYP2B1 ; FRACTIONATED INTRAVENOUS IFOSFAMIDE ; ifosfamide ; intra-arterial application ; pig pancreas
    Abstract: Background: The therapeutic efficacy of intratumoral instillation of genetically engineered, CYP2B1-expressing, microencapsulated cells in combination with ifosfamide had been previously demonstrated in xeno-grafted human pancreatic ductal carcinomas [Gene Ther 1998;5:1070-1078]. Prior to a clinical study, the feasibility of an intra-arterial application of microencapsulated cells to the pancreas and its consequences to the organ had to be evaluated. Material and Methods: Microencapsulated, CYP2B1-producing cells were instilled both in vivo (transfemoral angiographical access) and in vitro (perfusion model) in the splenic lobe of the pig pancreas. In vivo, animals were monitored clinically for 7 days, then treated with ifosfamide and sacrificed. In vitro, ifosfamide was administered intra-arterially. Results: In all animals, 100 microcapsules could be instilled safely via the femoral route without clinical, biochemical or histological signs of pancreatitis. Histological examination revealed partial obstruction of small arteries by the capsules, without causing any parenchymal damage. In vitro, instillation reduced blood flow by half. Ifosfamide, also in combination with the capsules, did not add any damage to the pancreas. Conclusion: Intra-arterial instillation of microencapsulated cells to the pig pancreas is feasible and safe. Neither pancreatitis, foreign body reactions nor circulatory disturbances were observed. Clinical application of this genetically enhanced chemotherapeutic method seems possible. Copyright (C) 2003 S. Karger AG, Basel and IAP
    Type of Publication: Journal article published
    PubMed ID: 12649565
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  • 8
    Keywords: RECEPTOR ; tumor ; carcinoma ; CELL ; Germany ; LUNG ; THERAPY ; CT ; DIAGNOSIS ; LUNG-CANCER ; DISEASE ; HISTORY ; liver ; PATIENT ; primary ; prognosis ; tumour ; LYMPH-NODES ; 5-FLUOROURACIL ; NO ; NEOPLASIA ; MALIGNANCIES ; METASTASIS ; metastases ; chemotherapy ; INVOLVEMENT ; SCINTIGRAPHY ; LIVER METASTASES ; SOMATOSTATIN ; POOR-PROGNOSIS ; pancreatic carcinoma ; ETOPOSIDE ; CELL CARCINOMA ; MALIGNANCY ; ENDOCRINE ; EXTRAPULMONARY ; GEMCITABINE ; NODES ; OF-THE-LITERATURE ; pancreas ; review ; small cell carcinoma ; somatostatin-analogue ; UNDIFFERENTIATED CARCINOMA
    Abstract: Small cell carcinoma (SCC) of the pancreas is a rare malignancy with an extremely poor prognosis. We present the case of a 74-year-old man with a 2-month history of upper abdominal discomfort who was diagnosed with SCC of the pancreas tail, involvement of peripancreatic and mesenteric lymph nodes and multiple liver metastases ( extended disease). A CT scan and a positive somatostatin receptor scintigraphy showed no evidence of a primary lung tumour. The diagnosis of a SCC was confirmed by biopsy. Local tumour control could be achieved by gemcitabine once a week and a long-acting somatostatin analogue once a month, but liver metastasis showed progress. Thus, 5-fluorouracil on a weekly basis was started. The patient died 8 months after diagnosis and had not been hospitalised in the meantime. Copyright (C) 2004 S. Karger AG, Basel and IAP
    Type of Publication: Journal article published
    PubMed ID: 15334003
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  • 9
    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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  • 10
    Keywords: RECEPTOR ; CANCER ; CANCER CELLS ; EXPRESSION ; tumor ; Germany ; DISEASE ; GENE ; GENES ; GENOME ; PROTEIN ; RNA ; TUMORS ; IDENTIFICATION ; LESIONS ; immunohistochemistry ; MICROARRAY DATA ; expression profiling ; pancreatic cancer ; pancreatic carcinoma ; review ; PANCREATIC-CANCER ; DUCTAL ADENOCARCINOMA ; MEDIATED APOPTOSIS ; development ; CYSTIC LESIONS ; pancreatic tumor ; EXPERIMENT ANNOTATIONS ; Fas-activated serine/threonine kinase ; PAPILLARY MUCINOUS NEOPLASMS ; siRNA silencing
    Abstract: Aim: The diversity in the aggressiveness of cystic tumors of the pancreas - ranging from the usually benign serous cystadenoma to lesions of variable degrees of malignancy - was utilized for the identification of molecular factors that are involved in the occurrence of malignancy. Methods: We analyzed the transcript profiles of different cystic tumor types. The results were confirmed at the protein level by immunohistochemistry. Also, functional studies with siRNA silencing were performed. Results: Expression variations at the RNA and protein level were identified that are closely correlated with the degree of malignancy. Besides, all tumors could be classified effectively by this means. Many of the identified factors had not previously been known to be associated with malignant cystic lesions. siRNA silencing of the gene with the most prominent variation - the anti-apoptotic factor FASTK (Fas-activated serine/threonine kinase) - revealed a regulative effect on several genes known to be relevant to the development of tumors. Conclusion: By a molecular analysis of rare types of pancreatic cancer, which are less frequent in terms of disease, variations could be identified that could be critical for the regulation of malignancy and thus relevant to the treatment of also the majority of pancreatic tumors. Copyright (C) 2008 S. Karger AG, Basel and IAP
    Type of Publication: Journal article published
    PubMed ID: 19077453
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