Now showing 1 - 5 of 5
  • 2012Journal Article
    [["dc.bibliographiccitation.firstpage","218"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Digestion"],["dc.bibliographiccitation.lastpage","227"],["dc.bibliographiccitation.volume","86"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Goralczyk, Armin Dietmar"],["dc.contributor.author","Schneider, S."],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Lindhorst, Alexander"],["dc.contributor.author","Mihm, Sabine"],["dc.contributor.author","van Thiel, D. H."],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T09:14:47Z"],["dc.date.available","2018-11-07T09:14:47Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Chronic hepatitis C virus genotype 1 (HCV-G1) infection is treated with pegylated interferon-a and ribavirin. Predictive factors for treatment success are even more important now as direct-acting antiviral agents are available. Methods: Clinical and laboratory parameters were analyzed by uni- and multivariate statistical means in 264 patients with HCV-G1 infections with regard to treatment outcome. Results:The overall sustained virological response (SVR) rate was 44%. Univariate analyses revealed SVRs to be associated with age, high alanine aminotransferase (ALT) and low gamma-glutamyltransferase (gamma-GT) serum activities, a low pretreatment gamma-GT/ALT ratio, rapid virological response (RVR), and absence of steatosis. Multivariate analyses unveiled IL28B rs12979860 genotype (CC vs. CT: OR = 2.8, CI: 1.5-4.9, p = 0.001; CC vs. TT: OR = 7.1, CI: 3.1-16.7, p < 0.001), low pretreatment gamma-GT/ALT ratio (OR = 2.5, CI: 1.7-3.3, p <0.001), age (OR = 0.96, CI: 0.94-0.98, p = 0.001) and RVR (OR = 4.18, CI: 2.85-8.65, p <0.001) to be significantly related to treatment outcome. Patients with the IL28B rs12979860 CC genotype and a low pretreatment gamma-GT/ALT ratio achieved the highest rate of a SVR with the highest predictive values (OR = 26.7, 95% CI: 10-71.1, p<0.0001). Conclusion: The pretreatment gamma-GT/ALT ratio significantly enhances the predictability of the IL28B genotype. Employing this combination will help to identify patients who will most likely benefit from an interferon-alpha-based combination therapy in a nontriaged ordinary setting. Copyright (C) 2012 S. Karger AG, Basel"],["dc.identifier.doi","10.1159/000339879"],["dc.identifier.isi","000310717600007"],["dc.identifier.pmid","22964578"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9079"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27501"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","S. Karger AG"],["dc.relation.eissn","1421-9867"],["dc.relation.issn","0012-2823"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","High Predictability of a Sustained Virological Response (87%) in Chronic Hepatitis C Virus Genotype 1 Infection Treatment by Combined IL28B Genotype Analysis and gamma-Glutamyltransferase/Alanine Aminotransferase Ratio: A Retrospective Single-Center Study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2014Journal Article
    [["dc.bibliographiccitation.artnumber","503"],["dc.bibliographiccitation.journal","BMC Infectious Diseases"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Goralczyk, Armin Dietmar"],["dc.contributor.author","Reinhardt, Lars"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Mihm, Sabine"],["dc.date.accessioned","2018-11-07T09:35:10Z"],["dc.date.available","2018-11-07T09:35:10Z"],["dc.date.issued","2014"],["dc.description.abstract","Background: A decline in hemoglobin (Hb) concentration during antiviral therapy in chronic hepatitis C (CHC) is a serious side effect. It may compel to dose reduction or even termination of antiviral treatment. The activation of erythropoietin (EPO) synthesis as a physiological response to anemia and its relation to a genetic variation within the EPO gene has not been evaluated yet. Methods: Data of 348 CHC patients were reviewed retrospectively. Samples were genotyped for EPO rs1617640 and inosine triphosphatase (ITPA) rs1127354. Serum EPO concentrations were determined before and during therapy. Primary endpoints were set as Hb decline > 3 g/dl at weeks 4 and 12. Results: EPO rs1617640 G homozygotes showed a significantly lower rise of serum EPO level over time than T allele carriers (p < 0.001). The cumulative frequency of a significant Hb reduction added up to 40%. Multivariate analysis revealed that besides age, ribavirin starting dose and baseline Hb also EPO rs1617640 G homozygosity associates with Hb reduction at week 4 (p = 0.025) and 12 (p = 0.029), while ITPA C homozygotes are at risk for Hb decline particularly early during treatment. Furthermore, EPO rs1617640 G homozygotes were more frequently in need for blood transfusion, epoetin-a supplementation, or ribavirin dose reduction (p < 0.001). Conclusions: Our data suggest that EPO rs1617640 genotype, the rise of serum EPO concentration as well as ITPA rs1127354 genotype are promising parameters to evaluate the Hb decline during antiviral therapy. A rational adjustment of therapy with epoetin-a supplementation might prevent serious adverse events or the need to terminate treatment."],["dc.identifier.doi","10.1186/1471-2334-14-503"],["dc.identifier.isi","000341954900001"],["dc.identifier.pmid","25227310"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32330"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2334"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Erythropoietin rs1617640 G allele associates with an attenuated rise of serum erythropoietin and a marked decline of hemoglobin in hepatitis C patients undergoing antiviral therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2011Journal Article
    [["dc.bibliographiccitation.firstpage","3296"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Digestive Diseases and Sciences"],["dc.bibliographiccitation.lastpage","3304"],["dc.bibliographiccitation.volume","56"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Goralczyk, Armin"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Schaefer, Inga-Marie"],["dc.contributor.author","van Thiel, David H."],["dc.contributor.author","Mihm, Sabine"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T08:50:09Z"],["dc.date.available","2018-11-07T08:50:09Z"],["dc.date.issued","2011"],["dc.description.abstract","Background and Aims The standard treatment regimen for chronic HCV genotype 3 (HCV-G3) hepatitis consists of PEGylated interferon-alpha (IFN-alpha) and ribavirin at varying doses ranging from 400 to 1,200 mg and results in response rates of 80%. However, this therapy has substantial side-effects including anemia, is teratogenic, and costly. To reduce the side-effects of therapy, the role of monotherapy consisting of only IFN-alpha was investigated. Methods A retrospective analysis of individual therapy courses of HCV-G3-infected patients who were treated with IFN-alpha(2a) monotherapy or a combination therapy with attention to the treatment outcome and the presence of IL28B rs12979860 and IL28B rs8099917 single-nucleotide polymorphism genotypes was performed. Conventional prognostic features in each case were assessed as well. Results In the study, 15/30 (50%) of patients treated with IFN-alpha(2a) monotherapy and 32/36 (89%) treated with combination therapy achieved a sustained virological response (SVR). In addition, 7/11 (64%) of those treated initially with monotherapy and subsequently with combination therapy achieved an SVR. An \"ultra-rapid\" virological response occurring within 2 weeks of initiation of therapy (p = 0.005), young age (< 40; p < 0.001) and low initial gamma-GT/ALT-ratio (p = 0.03) were associated with a SVR to IFN-alpha(2a) monotherapy. An SVR in those treated with combination therapy was found to be associated with a rapid virological response (RVR) (p = 0.03). The absence of histologic steatosis was associated with SVR in all patient groups (p = 0.01). Therapy duration (24 vs. 48 weeks) did not affect the SVR in either group. As expected, combination therapy resulted in more hematological side-effects than did monotherapy. Conclusions An \"ultra-rapid\" virological response, young age, low initial gamma-GT/ALT-ratio and absence of steatosis were each associated with an SVR in those receiving IFN-alpha(2a) monotherapy. Therefore, monotherapy in these patients should still be discussed independently of the existence of the IL28B polymorphisms."],["dc.identifier.doi","10.1007/s10620-011-1933-2"],["dc.identifier.isi","000296643400027"],["dc.identifier.pmid","21994136"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7154"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21634"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0163-2116"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Ultra-Rapid Virological Response, Young Age, Low gamma-GT/ALT-Ratio, and Absence of Steatosis Identify a Subgroup of HCV Genotype 3 Patients Who Achieve SVR with IFN-alpha(2a) Monotherapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2014Journal Article
    [["dc.bibliographiccitation.firstpage","2979"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","World Journal of Gastroenterology"],["dc.bibliographiccitation.lastpage","2994"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Khan, Sajjad"],["dc.contributor.author","Cameron, Silke"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Naz, Naila"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Ramadori, Giuliano"],["dc.contributor.author","Malik, Ihtzaz Ahmed"],["dc.date.accessioned","2018-11-07T09:42:27Z"],["dc.date.available","2018-11-07T09:42:27Z"],["dc.date.issued","2014"],["dc.description.abstract","AIM: To study KRAS/BRAF mutations in colorectalcancer (CRC) that influences the efficacy of treatment. To develop strategies for overcoming combination of treatment. METHODS: Five colonic cell-lines were investigated: DLD-1 with KRAS (G13D) mutation, HT 29 and Colo 205 with BRAF (V600E) mutation as well as the wild type (Wt) cell-lines Caco2 and Colo-320. DLD-1 (KRAS), HT-29 (BRAF) and Caco2 (Wt) cell lines were treated with cytokines (TNF alpha 50 ng, IL-1 beta 1 ng and IFN. 50 ng) and harvested at different time points (1-24 h). KRAS inhibition was performed by the siRNA-approach. Two colorectal cancer cells DLD-1 and Caco2 were used for KRAS inhibition. About 70% confluency were confirmed before transfection with small interferring RNA (siRNA) oligonucleotides. All the synthetic siRNA sequences were designed in our laboratory. Total RNA and protein was isolated from the cells for RT-PCR and Western blotting. Densitometry of the Western blotting was analyzed with the Image J software (NIH). Results are shown as mean +/- SD. RESULTS: RT-PCR analysis in non-stimulated cells showed a low basal expression of TNFa and IL-1 beta in the DLD-1 KRAS -mutated cell-line, compared to Caco2 wild type. No detection was found for IL-6 and IFN. in any of the studied cell lines. In contrast, pro-angiogenic chemokines (CXCL1, CXCL8) showed a high constitutive expression in the mutated cell-lines DLD-1 (KRAS), HT-29 and Colo205 (BRAF), compared to wild type (Caco2). The anti-angiogenic chemokine (CXCL10) showed a high basal expression in wild-type, compared to mutated cell-lines. KRAS down-regulation by siRNA showed a significant decrease in CXCL1 and CXCL10 gene expression in the DLD-1 (KRAS) cell-line in comparison to wild type (Caco2) at 72 h after KRAS silencing. In contrast, the specific KRAS inhibition resulted in an up-regulation of CXCL1 and CXCL10. The results of our study show a higher expression of pro-angiogenic chemokines at basal level in mutated cell-lines, which was further increased by cytokine treatment. CONCLUSION: To summarize, basal chemokine gene expression for pro-angiogenic chemokines was high in mutated as compared to wild type cell-lines. This reflects the likely existence of a different microenvironment in tumours consistent of wild type or mutated cells. This may help to rationalize the choice of molecular targets for suitable therapeutic investigation in clinical studies. c 2014 Baishideng Publishing Group Co., Limited. All rights reserved."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.3748/wjg.v20.i11.2979"],["dc.identifier.isi","000333667200026"],["dc.identifier.pmid","24659889"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10180"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33957"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Baishideng Publ Grp Co Ltd"],["dc.relation.issn","2219-2840"],["dc.relation.issn","1007-9327"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Differential gene expression of chemokines in KRAS and BRAF mutated colorectal cell lines: Role of cytokines"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2013Journal Article
    [["dc.bibliographiccitation.firstpage","473"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Histochemistry and Cell Biology"],["dc.bibliographiccitation.lastpage","485"],["dc.bibliographiccitation.volume","139"],["dc.contributor.author","Moriconi, Federico"],["dc.contributor.author","Ramadori, Pierluigi"],["dc.contributor.author","Schultze, Frank Christian"],["dc.contributor.author","Blaschke, Martina"],["dc.contributor.author","Amanzada, Ahmad"],["dc.contributor.author","Khan, Sajjad"],["dc.contributor.author","Ramadori, Giuliano"],["dc.date.accessioned","2018-11-07T09:27:52Z"],["dc.date.available","2018-11-07T09:27:52Z"],["dc.date.issued","2013"],["dc.description.abstract","It has been recently shown that the biological effects of erythropoietin (EPO) are not limited to the hematopoietic compartment but, as pleiotropic glycoprotein, this hormone can exert pro-angiogenic and tissue-protective functions also in a wide range of non-hematopoietic organs. The role of EPO and the effective functionality of its receptor in solid tumors are still a controversial point of debate. In the present work we analyzed the gene expression of EPO and its cognate receptor (EpoR) in a rat model of thioacetamide-induced damage and tumor. An analysis of the EPO/EpoR axis was also performed on human cholangiocarcinoma (CC) cell lines. A progressive increase of EPO and EpoR mRNA can already be observed during the fibrotic-cirrhotic development with a peak of expression rising at tumor formation (24.7 +/- A 9.9-fold increase and 15.5 +/- A 1.1-fold increase, respectively, for the two genes). Co-localization studies by immunofluorescence revealed hepatocytes in the regenerative cirrhotic nodules (Hep Par-1(+)) and in the dysplastic bile duct cells (CK19(+)) as the major EPO producers in this specific condition. The same cell populations, together with endothelial cells, exhibited an increased expression of EpoR, although all the non-parenchymal cell populations in the liver exhibited modest basal mRNA levels. Challenging human CC cells, Mz-Cha-2, with a combination of EPO and SCF resulted in a synergistic effect on the gene expression of EPO, CyclinD1 and PCNA. This study suggests that the autocrine and paracrine release of endogenous EPO in the microenvironment may contribute to the development and maintenance of the CC possibly in cooperation with other signaling pathways."],["dc.identifier.doi","10.1007/s00418-012-1037-x"],["dc.identifier.isi","000314972000007"],["dc.identifier.pmid","23052842"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10312"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30639"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prĂĽfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0948-6143"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Characterization of the erythropoietin/erythropoietin receptor axis in a rat model of liver damage and cholangiocarcinoma development"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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