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  • DKFZ Publication Database  (14)
  • DISEASE  (14)
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  • DKFZ Publication Database  (14)
  • 1
    Keywords: EXPRESSION ; COMBINATION ; Germany ; MODEL ; DIAGNOSIS ; DISEASE ; DISTINCT ; PROTEIN ; PROTEINS ; SAMPLE ; SAMPLES ; PATIENT ; SERA ; MARKER ; BIOMARKERS ; FORM ; IDENTIFICATION ; PROGRESSION ; PATTERNS ; DIFFERENCE ; ARRAYS ; mass spectrometry ; MASS-SPECTROMETRY ; EXCHANGE ; MULTIVARIATE ; adenocarcinoma ; sensitivity ; specificity ; REVEALS ; expression profiling ; AFFINITY ; chronic pancreatitis ; protein expression ; PROTEOMICS ; MASSES ; SERUM ; pancreas ; PATTERN ; ARRAY ; PANCREATITIS ; HEALTHY-VOLUNTEERS ; pancreolauryl test ; biomarker ; analysis ; methods ; USA ; SELDI-TOF-MS ; SET ; diagnostic marker ; NOV ; LASER-DESORPTION ; serum proteomics ; STAGE OVARIAN-CANCER ; TUMOR-MARKERS
    Abstract: Objective: Testing of serum for protein patterns to monitor progression of suspected to definite chronic pancreatitis (CP). Methods: Serum samples of CP patients and healthy volunteers were fractionated on anion exchange columns and analyzed by surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry to elucidate CP-related protein alterations and to identify biomarkers for this disease. Potential biomarkers were purified and identified by mass spectrometry. Results: In total, 258 protein peaks were found that discriminated between the 2 groups. Analysis revealed 28 most prominent peaks on immobilized metal affinity capture coupled with Cu and CM10 protein chips, covering the m/z range between 3.3 and 33.3 kd. Performing multivariate pattern analysis, the best pattern model was obtained using fraction 6 on immobilized metal affinity capture coupled with Cu arrays with a sensitivity of 96% and a specificity of 84%. Using a combination of matrix-assisted laser desorption-ionization-time-of- flight mass spectrometry and immunodepletion, we identified 14-m/z peaks. The proteins were found to be significantly decreased in CP serum and were identified as retinol-binding protein, serum amyloid-alpha, apolipoprotein A-II (Apo A-II), Apo C-I, Apo C-II, Apo C-III, and transthyretin and truncated forms thereof. Conclusions: Distinct protein profile differences exist between normal and CP serum and reflect the metabolic and inflammatory condition in CP patients. The identified protein panel may eventually serve as a diagnostic marker set for CP
    Type of Publication: Journal article published
    PubMed ID: 18090239
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  • 2
    Keywords: CANCER ; SURVIVAL ; tumor ; Germany ; DEATH ; DISEASE ; MORTALITY ; NEW-YORK ; PROTEIN ; SURGERY ; TIME ; PATIENT ; IMPACT ; prognosis ; NO ; PERFORMANCE ; PROGRESSION ; DIFFERENCE ; COUNTRIES ; RATES ; DATABASE ; RESECTION ; adenocarcinoma ; PREVALENCE ; pancreatic cancer ; MULTICENTER ; pancreas ; PANCREATIC-CANCER ; WEIGHT ; LEVEL ; methods ; GASTROINTESTINAL CANCER ; USA ; CURATIVE RESECTION ; ANOREXIA ; cachexia ; ENERGY-EXPENDITURE ; HEMOGLOBIN ; DEATHS ; HEAD RESECTION ; nutritional status ; UBIQUITIN-DEPENDENT PROTEOLYSIS
    Abstract: Introduction Pancreatic cancer is the fourth leading cause of cancer-related death in Western countries with a poor prognosis (5-year survival rates, 25% in patients after tumor resection with adjuvant treatment; overall, the 5-year survival rate is about 4%; Jemal et al., CA Cancer J Clin, 55:10-30, 2005). Many patients develop a cachectic status during the progression of the disease, and this syndrome accounts for up to 80% of deaths in patients with advanced pancreatic cancer. Remarkably, there are only a few data available on the impact of cachexia in patients with pancreatic cancer scheduled for tumor resection. Material and Methods Therefore, in this study, 227 consecutive patients with ductal adenocarcinoma of the pancreas were documented over an 18-month period regarding the prevalence of cachexia and its influence on perioperative morbidity and mortality with a special interest to postoperative weight gain and survival in a prospectively designed database and followed up. Results In 40.5% of the patients, cachexia was already present at the time of operation. The cachectic patients did present in a worse nutritional status, represented by lower protein, albumins, and hemoglobin levels. Despite no significant differences in tumor size, lymph node status, and CA19-9 levels, the resection rate in patients with cachexia was reduced (77.8% vs. 48.9%) due to a higher rate of metastatic disease in patients with cachexia. The morbidity and in-hospital mortality revealed no significant difference. However, patients with and without cachexia lost weight after operation, and the weight gain started not until 6 months after operation. The survival in patients with cachexia was significantly reduced in patients undergoing tumor resection as well as in palliative treated patients. Conclusion Cachexia has a significant impact on survival and performance status in palliative patients as well as in patients operated for pancreatic cancer. But tumor-related cachexia is not necessarily dependent on tumor size or load and that metastatic dedifferentiation of the tumor might be a critical step in the development of tumor-associated cachexia
    Type of Publication: Journal article published
    PubMed ID: 18347879
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  • 3
    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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  • 4
    Keywords: APOPTOSIS ; CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; GROWTH ; INVASION ; proliferation ; SURVIVAL ; tumor ; carcinoma ; CELL-PROLIFERATION ; Germany ; human ; FOLLOW-UP ; DISEASE ; liver ; PROTEIN ; MOLECULES ; TISSUE ; TUMORS ; TIME ; PATIENT ; MARKER ; DONOR ; prognosis ; TISSUES ; MOLECULE ; BREAST-CANCER ; GLYCOPROTEIN ; IDENTIFICATION ; MALIGNANCIES ; METASTASIS ; metastases ; PCR ; CANCER-CELLS ; ADHESION ; MIGRATION ; CANCER-PATIENTS ; adenocarcinoma ; LIVER METASTASES ; CANCER PATIENTS ; HEALTHY ; pancreatic cancer ; chronic pancreatitis ; SERUM ; ELISA ; MALIGNANCY ; RECOMBINANT ; PANCREATIC-CANCER ; TUMOR-GROWTH ; DUCTAL ADENOCARCINOMA ; INCREASE ; extracellular matrix ; REAL-TIME ; cell adhesion ; cell proliferation ; LEVEL ; OSTEOPONTIN ; SERUM-LEVELS ; downregulation ; function ; BLOCKADE ; IMMUNOHISTOCHEMICAL ANALYSIS ; INVASIVENESS ; lymph node ; LYMPH-NODE ; PLASMA OSTEOPONTIN ; restricting ; serum marker
    Abstract: Pancreatic ductal adenocarcinoma ( PDAC) is one of the most aggressive malignancies, with an overall 5-year survival rate of less than 5%. Invasive tumor growth and early metastasis are two important reasons for this dismal prognosis. Osteopontin ( OPN) is a secretory protein with a variety of functions, for example in cell adhesion and migration, inflammatory reaction and apoptosis. In this study the functional role of OPN in human pancreatic cancer and its potential use as a disease marker were analyzed. By real time quantitative PCR, there was a 2.2- fold and 1.6- fold increase of OPN mRNA in pancreatic cancers (n = 23) and chronic pancreatitis samples (n = 22), respectively, compared to normal pancreatic tissues (n = 20). Immunohistochemical analysis demonstrated OPN staining in 60% of the primary pancreatic tumors and in 72% of the lymph node and liver metastases. ELISA analysis of serum samples obtained from pancreatic cancer patients (n = 70), chronic pancreatitis patients (n = 12), and healthy donors (n = 20) showed a 1.6-fold increase in OPN serum levels in patients with tumors and a 1.9-fold increase in patients with chronic pancreatitis. Recombinant human OPN significantly increased the invasiveness of pancreatic cancer cells, without having any impact on cell proliferation. In addition, downregulation of OPN by specific siRNA molecules decreased pancreatic cancer cell invasion. In conclusion, OPN serum levels in pancreatic cancer and chronic pancreatitis patients are not significantly different, thereby restricting its role as a prognostic or follow-up marker. Our results do suggest, however, that blockade of OPN might be useful as a therapeutic approach to inhibit invasion and metastasis of pancreatic cancer cells
    Type of Publication: Journal article published
    PubMed ID: 15970685
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  • 5
    Keywords: CELLS ; tumor ; CELL ; Germany ; neoplasms ; imaging ; TOOL ; DISEASE ; DISEASES ; RESOLUTION ; SURGERY ; MECHANISM ; MARKER ; prognosis ; AUTOIMMUNE-DISEASE ; mechanisms ; T cell ; T cells ; T-CELL ; T-CELLS ; treatment ; MARKERS ; RESECTION ; LOCALIZATION ; HEAD ; ATROPHY ; FUTURE ; DIABETES-MELLITUS ; AUTOANTIBODIES ; autoimmune pancreatitis ; PRIMARY SCLEROSING CHOLANGITIS ; SJOGRENS-SYNDROME ; INFLAMMATORY-BOWEL-DISEASE ; FEATURES ; fibrosis ; INFILTRATION ; inflammatory bowel disease ; AUTOIMMUNE-DISEASES ; STENOSIS ; LEVEL ; pancreatic ; MASS ; autoimmune disease ; TOOLS ; DUCT ; serological ; Diabetes Mellitus ; surgical resection ; BOWEL ; EFFECTIVE STEROID-THERAPY ; ENTITY ; IgG4 ; pancreatic neoplasms ; pancreatic tumor ; PSEUDOTUMOROUS PANCREATITIS ; SERUM IGG4 ; steroids ; URSODEOXYCHOLIC ACID
    Abstract: The term autoimmune pancreatitis (AIP) describes a nonalcoholic, chronic lymphoplasmocytic pancreatitis. The lymphoplasmocytic infiltration is characterized by periductal localization of predominantly CD4-positive T cells, fibrosis, and acinar atrophy, frequently resulting in stenosis of the main pancreatic and distal common bile ducts. Imaging studies often reveal a diffuse narrowing of the pancreatic main duct and swelling of the pancreatic head wrongly suggesting the presence of a malignant tumor. Clinical signs include mild abdominal pain,jaundice, recurrent episodes of acute pancreatitis, and even new-onset diabetes mellitus. Additionally, AIP can be associated with other autoimmune diseases such as Sjogren's syndrome, primary sclerosing cholangitis, chronic inflammatory bowel diseases, and retroperitoneal fibrosis. Serological markers include autoantibodies and increased levels of gamma globulin and especially IgG4. Steroids seem to be effective in improving clinical symptoms as well as in the resolution of pancreatic and bile duct narrowing. This distinguishes AIP from other forms of pancreatitis and from pancreatic neoplasms. Further studies of the underlying pathophysiologic mechanisms, prognosis, and new diagnostic tools are needed to provide adequate and effective treatment in the future. In this article, we summarize the current knowledge about AIP and present 17 cases that underwent surgical resection at our institution from 2003 to 2004
    Type of Publication: Journal article published
    PubMed ID: 17007063
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  • 6
    Keywords: INHIBITOR ; Germany ; DISEASE ; RISK ; SITE ; GENE ; GENES ; PROTEIN ; ACTIVATION ; CLEAVAGE ; MUTATION ; genetics ; MUTATIONS ; Jun ; INDIVIDUALS ; heredity ; chronic pancreatitis ; RECOMBINANT ; pancreas ; VARIANT ; ENZYME ; pancreatic ; LOSSES ; odds ratio ; PROTECTS ; HEREDITARY PANCREATITIS ; HUMAN CATIONIC TRYPSINOGEN
    Abstract: Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) 1 and the pancreatic secretory trypsin inhibitor (SPINK1) 2 are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis
    Type of Publication: Journal article published
    PubMed ID: 16699518
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  • 7
    Keywords: RECEPTOR ; SPECTRA ; ANGIOGENESIS ; APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; INHIBITOR ; tumor ; CELL ; FACTOR RECEPTOR ; Germany ; IN-VIVO ; INHIBITION ; KINASE ; THERAPY ; TYROSINE KINASE ; VIVO ; QUANTIFICATION ; DEATH ; DISEASE ; GENE ; PROTEIN ; cell line ; LINES ; PATIENT ; LIGAND ; FLOW ; cell cycle ; CELL-CYCLE ; CELL-LINES ; CYCLE ; protein kinase ; PROTEIN-KINASE ; TYROSINE KINASE INHIBITOR ; TARGET ; PROGRESSION ; immunohistochemistry ; ASSAY ; CELL-DEATH ; MUTATION ; CELL-LINE ; LINE ; MUTATIONS ; CANCER-PATIENTS ; POLYMERASE-CHAIN-REACTION ; PROTEIN-KINASE-C ; CHAIN-REACTION ; RECEPTORS ; CANCER PATIENTS ; point mutation ; cell lines ; pancreatic cancer ; RANDOMIZED-TRIAL ; TUMOR ANGIOGENESIS ; MANAGEMENT ; CELL-CYCLE PROGRESSION ; INHIBITORS ; CELL-GROWTH ; CHAIN ; ONCOLOGY ; PANCREATIC-CANCER ; TUMOR-GROWTH ; flow cytometry ; THERAPIES ; ACUTE MYELOID-LEUKEMIA ; polymerase chain reaction ; REAL-TIME ; POINT MUTATIONS ; MURINE MODEL ; TYROSINE KINASES ; analysis ; methods ; pancreatic ; ASSAYS ; cell death ; BIOLOGICAL-ACTIVITY ; USA ; POTENTIAL ROLE ; vascular endothelial growth factor ; COMPOUND ; in vivo ; SPECTRUM ; SPECIMENS ; KINASE INHIBITOR ; GROWTH-FACTOR-RECEPTOR ; receptor tyrosine kinase ; RECEPTOR TYROSINE KINASES ; - ; POINT ; modeling ; quantitative ; block ; ACTIVATING MUTATION ; ENDOTHELIAL GROWTH ; FLT3 ; FLT3 MUTATIONS ; INTERNATIONAL CONSENSUS ; PKC412 ; SOLID HUMAN TUMORS ; VEGF-RII
    Abstract: BACKGROUND. PKC412 is a kinase inhibitor that blocks protein kinase C (PKC), vascular endothelial growth factor receptors, platelet-derived growth factor receptor FLT3, and other class III receptor tyrosine kinases. The enthusiasm for this compound is based on its inhibitory effect even in the case of FLT3 mutations. The aim of this study was to analyze the role of FLT3 in pancreatic cancer and to study the biological activity of combined inhibition of neovascularization and mitogenesis in this disease. METHODS. FLT3 expression was analyzed in 18 pancreatic cancer specimens by real-time quantitative polymerase chain reaction (RTQ-PCR) and immunohistochemistry. Sixteen pancreatic cancer cell lines were screened for ITD and D835 point mutations of the FLT3 gene. MTT assays and anchorage-independent growth assays were used to study cell growth. Flow cytometry was used for cell cycle analysis and apoptosis quantification. In vivo AsPC-1 and HIAF-II cells were used for orthotopic tumor modeling. Immunohistochemistry was used to quantity tumor angiogenesis. RESULTS. FLT3 expression is down-regulated in pancreatic cancer. Activating FLT3 mutations (ITD, D835) were not detectable in any of the pancreatic cancer cell lines. Cell growth was significantly inhibited as cell-cycle progression was reduced and programmed cell death increased. In vivo PKC412 therapy resulted in a significant inhibition of orthotopic tumor growth with abrogation of tumor angiogenesis. CONCLUSIONS. These data highlight that PKC412 may be a new compound in target therapy of inoperable pancreatic cancer patients and suggest a potential role for the combined use of broad spectrum kinase inhibitors in the management of these patients
    Type of Publication: Journal article published
    PubMed ID: 17676584
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  • 8
    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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  • 9
    Keywords: RECEPTOR ; CANCER ; CELLS ; EXPRESSION ; proliferation ; tumor ; carcinoma ; Germany ; human ; MODEL ; neoplasms ; PATHWAY ; PATHWAYS ; DISEASE ; MICE ; ACTIVATION ; CARCINOGENESIS ; treatment ; MOUSE ; TRANSGENIC MICE ; LESIONS ; PROGRESSION ; MOUSE SKIN ; PHENOTYPE ; CARCINOMAS ; adenocarcinoma ; ADENOCARCINOMAS ; intraepithelial neoplasia ; NONSTEROIDAL ANTIINFLAMMATORY DRUGS ; OVEREXPRESSION ; pancreatic cancer ; inflammation ; Ras ; HER-2/neu ; INCREASED EXPRESSION ; pancreas ; PANCREATIC-CANCER ; ENZYME ; pancreatic ; LOSSES ; PROSTAGLANDIN SYNTHESIS ; IMMUNOHISTOCHEMICAL ANALYSIS ; cyclooxygenase ; CANCERS ; ANTICANCER AGENTS ; CELL HYPERPLASIA ; CYSTIC NEOPLASMS ; PAPILLARY-MUCINOUS TUMORS
    Abstract: Background & Aims: Basic research aimed at a better understanding of pancreatic carcinogenesis and improving the treatment of this disease is crucial because the majority of pancreatic cancers are highly aggressive and therapeutically nonaccessible. Cyclooxygenase (COX)-2, which is a key enzyme of prostaglandin (PG) biosynthesis, is overexpressed in around 75% of human carcinomas including those of the pancreas. Methods: The pathologic changes of transgenic mouse pancreas with keratin 5-promoter-driven expression and activity of COX-2 were characterized. Results: Aberrant expression of COX-2 in a few ductal cells and COX-2-mediated PG synthesis in the transgenic mice resulted in keratin 19- and mucin-positive intraductal papillary mucinous neoplasm- and pancreatic intraepithelial neoplasia-like structures, characterized by an increased proliferation index and serous cystadenomas. Moreover, Ras activation was enhanced and the HER-2/Neu receptor was overexpressed. Loss of acini, fibrosis, and inflammation were pronounced. Feeding a COX-2-selective inhibitor to the transgenic mice suppressed the accumulation of PG and the phenotype. The changes resemble the human disease in which COX-2 was overexpressed consistently. Conclusions: We present strong evidence for a causal relationship between aberrant COX-2 overexpression and COX-2-mediated PG synthesis and the development of serous cystadenoma, intraductal papillary mucinous, and pancreatic intraepithelial neoplasms. This model offers the unique possibility of identifying molecular pathways leading to the formation and malignant progression of the various types of preinvasive lesions of pancreatic adenocarcinomas that show different dismal outcomes
    Type of Publication: Journal article published
    PubMed ID: 16762637
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  • 10
    Keywords: APOPTOSIS ; CELLS ; IN-VITRO ; AGENTS ; human ; MODEL ; DEATH ; DISEASE ; liver ; SAMPLES ; TISSUE ; TIME ; INFECTION ; SERA ; primary ; INDUCTION ; hepatocytes ; culture ; virus ; VECTORS ; hepatitis B virus ; isolation ; HUMAN-LIVER ; FAS-MEDIATED APOPTOSIS ; ANTICANCER DRUGS ; ADULT HUMAN HEPATOCYTES ; LONG-TERM CULTURE ; X-PROTEIN
    Abstract: Background/Aims: Apoptosis is a key event in the pathophysiology of many liver diseases. Primary human hepatocytes (PHH) provide a useful model to study physiological and pathophysiological processes in the liver. Our aim was to optimize PHH cultures to allow studies on induction of apoptosis and of hepatitis B virus (HBV) infection. Methods: PHH were isolated from human liver tissue by two-step collagenase perfusion. PHH and hepatoma cells were treated with different apoptosis-inducing agents in parallel. PHH cultures were infected with wild type HBV and transduced with HBV genomes using adenoviral vectors. Results: PHH were successfully isolated from 40 different tissue samples with high viability and purity. Perfusion time and seeding density turned out to be critical parameters for optimal cell yield and culture conditions, respectively. Serum addition to the medium reduced viability of PHH. PHH allowed reproducible studies of CD95-dependent and-independent apoptosis. Sensitivity towards CD95-mediated apoptosis was markedly higher than in hepatoma cells. PHH could efficiently be infected with HBV, but infection did neither induce apoptosis nor prevent CD95-induced cell death. Conclusions: Our data show that PHH provide an excellent tool for the investigation of apoptosis induced by agents like death receptor-ligands and hepatotropic viruses. (C) 2003 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 12763365
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