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C-reactive protein is a prognostic indicator in patients with perihilar cholangiocarcinoma

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World Journal of Gastroenterology 2006年第34期12卷 5495-5500页

作者： Thomas Gerhardt Sabine Milz Michael Schepke Georg Feldmann Martin Wolff tilman sauerbruch Franz Ludwig Dumoulin Department of Internal Medicine I University Hospital Bonn Germany Department of Surgery University Hospital Bonn Germany

AIM： To evaluate prognostic indicators for the outcome of patients with perihilar extrahepatic cholangiocarcinoma in an unselected cohort. METHODS： We retrospectively analyzed 98 patients with perihilar cholangiocarcinoma. Twenty-three patients （23.5%） underwent tumor resection. Patients with non-resectable tumors underwent either transpapillary or percutaneous transhepatic biliary drainage. Additionally, 32 patients （32.7%） received photodynamic therapy （PDT） and 18 patients （18.4%） systemic chemotherapy. Predefined variables at the time of diagnosis and characteristics considering the mode of treatment were entered into a Cox＇s proportional hazards model. Included in the analysis were age, tumor stage following the modified Bismuth-Corlette classification, bilirubin, prothrombin time （PT）, C-reactive protein （CRP）, carbohydrate antigen 19-9 （CA19-9）, history of weight loss, surgical resection, chemotherapy and PDT. RESULTS： The Kaplan-Meier estimate of overall median survival was 10.5 （95%CI： 8.4-12.6） mo. In the univariate analysis, low Bismuth stage, low CRP and surgical resection correlated significantly with better survival. In the multivariate analysis, only CRP （P = 0.005） and surgical resection （P = 0.029） were found to be independently predictive of survival in the cohort. Receiver operating characteristic （ROC） analysis identified a CRP level of 11.75 mg/L as the value associated with the highest sensitivity and specificity predicting a survival 〉 5 too. Applying Kaplan-Meier analysis, patients with a CRP 〈 12 mg/L at the time of diagnosis had a significantly longer median survival than patients with higher values （16.2 vs 7.6 mo; P = 0.009）.CONCLUSION： This retrospective analysis identified CRP level at the time of diagnosis as a novel indicator for the prognosis of patients with perihilar cholangiocarcinoma. It should be evaluated in future prospective trials on this entity.

关键词： Perihilar cholangiocarcinoma Prognosticfactors C-reactive protein Resection Outcome

A common variant in the precursor miR-146a sequence does not predispose to cholangiocarcinoma in a large European cohort

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Hepatobiliary & Pancreatic Diseases International 2012年第4期11卷 412-417页

作者： Florentina Mihalache Aksana Hblinger Monica Acalovschi tilman sauerbruch Frank Lammert Vincent Zimmer Department of Medicine Ⅱ Saarland University Hospital66421 HomburgGermany Department of Medicine Ⅲ University Iuliu Hatieganu Department of Internal Medicine Ⅰ University Hospital Bonn

BACKGROUND:Micro-RNAs(miRNAs) are small,non-coding RNA species considered to fine-tune basic cellular functions by modulating target gene translation and/or mRNA stability.A common G/C polymorphism(rs2910164) in the precursor(pre-) miR-146a gene engaged in NF-κB signaling and apoptosis pathways has been reported to modulate the genetic risk of hepatocellular carcinoma by increased G-allelic production of mature *** investigated rs2910164 in a large Europeanbased cholangiocarcinoma(CCA) ***:We recruited 182 CCA patients and 350 controls in three academic medical *** for rs2910164 was performed by PCR-based assays with 5’-nuclease and fluorescence *** frequencies were tested for consistency with the Hardy-Weinberg equilibrium using an exact test;allelic and genotypic differences between the patients and controls were assessed by the Chi-square test and Armitage’s trend *** subgroup analyses included gender,tumor localization(extra-versus intrahepatic CCA) and early-onset ***:Genotype distributions were consistent with the Hardy-Weinberg *** significant differences in either allele or genotype distributions were detected between the CCA and control groups or the respective subgroups ***,there was a trend for a protective effect of the heterozygous single-nucleotide polymorphism state GC,as indicated by an underrepresentation in the CCA group in general(29% vs 35%;P=0.18) and,in particular,for extrahepatic tumor sites(26% vs 35%;OR=0.67;95% CI,0.43-1.02;P=0.065).CONCLUSIONS:Our data do not support a prominent contribution of the pre-miR-146a sequence variant in the genetic predisposition to ***,current studies functionally characterizing rs2910164 have proposed that distinct repertoires of target genes are addressed by genotype-specific mature miR146a *** the detected trend towards a potentially protective role of GC heterozygosity,a subtle modulation of g

关键词： miR-146a miR-SNP biliary tract cancer cholangiocarcinoma genetic risk

Clinical characteristics and outcome of a cohort of 101 patients with hepatocellular carcinoma

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World Journal of Gastroenterology 2001年第2期7卷 208-215页

作者： Christian Rabe Tillmann Pilz Christoph Klostermann Marc Berna Hans H.Schild tilman sauerbruch Wolfgang H.Caselmann Department of Medicine I Department of RadiologyUniversity of BonnGermany

AIM: To conduct a cohort study of 101 patients with hepatocellular carcinoma (HCC) presenting to a tertiary care medical referral center in Germany between 1997 and 1999. METHODS AND RESULTS: Data were retrospectively analyzed by chart review. In 95 cases (72 males and 23 females) sufficient data were available for analysis. Twenty five (29%) of 85 patients were HBsAg or anti HBc positive, 21/85 (25%) were anti HCV positive, and 6/85 (7%) were positive for both HBV and HCV-markers. Age was significantly lower in HBV positive patients than in the other two groups. Thirty one (34%) of 90 patients had histories of alcohol abuse. In 79/94 (84%) patients, cirrhosis was diagnosed. Of these cirrhotic patients, 29/79 (37%) belonged to Child Pugh's group (CHILD) A, 32/79 (40%) to CHILD B, and 18/79 (23%) to CHILD C. AFP was elevated in 61/91 (67%) patients. A single tumor nodule was found in 38/94 (40%), more than one nodule in 31/94 (34%), and 25/94 (26%) had a diffusely infiltrating tumor, i.e. the tumor margins could not be seen on imaging procedures. Portal vein thrombosis was present in 19/94 (20%). Imaging data consistent with lymph node metastases were found in 10/92 (11%), while distant metastases were found in 8/93 (9%). According to Okuda 28/94 (30%) were grouped to stage I, 53/94 (56%) were grouped to stage II, and 13/94 (14%) were grouped to stage II. Survival data were available for 83 patients. The Kaplan-Meier estimate for median survival was 8 4 months. Factors influencing survival were the Okuda score, the presence of portal vein thrombosis, and the presence of ascites. The presence of non complicated liver cirrhosis by itself, distant metastases, or infection with hepatitis viruses did not influence survival. AFP positivity by itself did not influence survival, though patients with an AFP value greater than 100 microg/L did experience shortened survival. Treatment besides tamoxifen or supportive care was associated with prolonged survival. The influence of

关键词： Adult Aged Aged, 80 and over Carcinoma, Hepatocellular Cohort Studies Female Germany Hepatitis B Hepatitis C Humans Liver Cirrhosis, Alcoholic Liver Neoplasms Male Middle Aged Research Support, Non-U.S. Gov't Retrospective Studies Risk Factors Survival Analysis

HCV-specific cytokine induction in monocytes of patients with different outcomes of hepatitis C

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World Journal of Gastroenterology 2002年第3期8卷 562-566页

作者： Rainer P.Woitas Uwe Petersen Dirk Moshage Hans H.Brackmann Bertfried Matz tilman sauerbruch Ulrich Spengler Department of Intemal Medicine I University of Bonn53105 BonnGermany Institute of Experimental Hematology University of Bonn53105 BonnGermany Institute of Medical Microbiology and Immunology University of Bonn53105 BonnGermany

AIM:Cytokine release by macrophages critically determines the type of immune response to an ***,we studied hepatitis C virus(HCV)-specific induction of interleukins-1β,-10,-12(IL-1β,IL-10,IL-12),and tumor necrosis factor-α(TNF-α)in monocytes. METHODS:Intracallular cytokine expression was studied by flow cytometry in 23 patients with chronic hepatitis C,14 anti-HCV seropositives without viremia and 11 controls after stimulation of peripheral blood mononuclear calls with recombinant core,NS3,NS4,NSSa and NSSb proteins. RESULTS:Patients with HCV viremia revealed greater spontaneous expression of IL-1β,TNF-α,and IL-10. Furthermore,greater than twofold higher IL-10 expression was induced by the HCV antigens in chronic hepatitis C than in the other two groups(P<0.05).In contrast,neither IL- 12 nor TNF-α was induced preferentially. CONCLUSION:In chronic hepatitis C antigen-specific cytokine induction in monocytes is apparently shifted towards predominant IL-10 induction-not counterbalanced by antiviral type 1 *** may contribute to persistent viral replication.

关键词： Adult Cytokines Female Hepacivirus Hepatitis C, Chronic Humans In Vitro Interleukin-1 Interleukin-10 Interleukin-12 Male Middle Aged Monocytes Research Support, Non-U.S. Gov't Tumor Necrosis Factor-alpha Viremia

Treatment of metastatic colorectal carcinomas by systemic inhibition of vascular endothelial growth factor signaling in mice

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World Journal of Gastroenterology 2005年第28期11卷 4332-4336页

作者： Volker Schmitz Miroslaw Kornek Tobias Hilbert Christian Dzienisowicz Esbher Raskopf Christian Rabe tilman sauerbruch Cheng Qian Wolfgang H Caselmann Medizinische Klinik und Poliklinik I Universitatsklinikum BonnGermany Universidad de Navarra Clinica Universitaria Pamplona Spain Bavarian State Ministry of the Environment Public Health and Consumer Protection Munich 81901 Germany

AIM： Tumor angiogenesis has been shown to be promoted by vascular endothelial growth factor （VEGF） via stimulating endothelial cell proliferation, migration, and survival. Blockade of VEGF signaling by different means has been demonstrated to result in reduced tumor growth and suppression of tumor angiogenesis in distinct tumor entities. Here, we tested a recombinant adenovirus, AdsFItl-3, that encodes an antagonistically acting fragment of the VEGF receptor 1 （Fit-l）, for systemic antitumor effects in pre-established subcutaneous CRC tumors in mice.METHODS： Murine colorectal carcinoma cells （CT26） were inoculated subcutaneously into Balb/c mice for in vivo studies. Tumor size and survival were determined. 293 cell line was used for propagation of the adenoviral vectors. Human lung cancer line A549 and human umbilical vein endothelial cells were transfected for in vitro experiments.RESULTS： Infection of tumor cells with AdsFlt1-3 resulted in protein secretion into cell supernatant, demonstrating correct vector function. As expected, the secreted sFlt1-3 protein had no direct effect on CT26 tumor cell proliferation in vitro, but endothelial cell function was inhibited by about 46% as compared to the AdLacZ control in a tube formation assay. When AdsFlt1-3 （5×10^9 PFU/animal） was applied to tumor bearing mice, we found a tumor inhibition by 72% at d 12 after treatment initiation, in spite of these antitumoral effects, the survival time was not improved. According to reduced intratumoral microvessel density in AdsFlt1-3-treated mice, the antitumor mechanism can be attributed to angiostatic vector effects. We did not detect increased systemic VEGF levels after AdsFlt1-3 treatment and liver toxicity was low as judged by serum alanine aminotransferase determination.CONCLUSION： In this study we confirmed the value of a systemic administration of AdsFItl-3 to block VEGF signaling as antitumor therapy in an experimental metastatic colorectal carcinoma model in mice.

关键词： Colorectal carcinomas Vascular endothelial growth factor Systemic inhibition

Distribution and effects of polymorphic RANTES gene alleles in HIV/HCV coinfection - A prospective cross-sectional study

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World Journal of Gastroenterology 2005年第48期11卷 7631-7638页

作者： Golo Ahlenstiel Agathe Iwan Jacob Nattermann Karin Bueren Jürgen K Rockstroh Hans H Brackmann Bernd Kupfer Olfert Landt Amnon Peled tilman sauerbruch Ulrich Spengler Rainer P Woitas Department of Internal Medicine 1 Institute of Experimental Hematology Institute of Medical Microbiology and Immunology TIB MOLBIOL Synthesis Laboratory Goldyne Savad Institute of Gene Therapy

AIM: Chemokines and their receptors are crucial for immune responses in HCV and HIV infection. RANTES gene polymorphisms lead to altered gene expression and influence the natural course of HIV infection. Therefore,these mutations may also affect the course of HIV/HCV ***: We determined allele frequencies of RANTES-403 (G→A), RANTES-28 (C→G) and RANTESIN1.1 (T→C) polymorphisms using real-time PCR and hybridization probes in patients with HIV (n = 85), HCV (n= 112), HIV/HCV coinfection (n = 121), and 109 healthy controls. Furthermore, HIV and HCV loads as well as CD4+ and CD8+ cell counts were compared between different RANTES ***: Frequencies of RANTES-403 A, RANTES-28 G and RANTES-IN1.1 C alleles were higher in HIV infected patients than in healthy controls (-403: 28.2% vs 15.1%,P = 0.002; -28: 5.4% vs 2.8%, not significant; IN1.1:19.0% vs 11.0%, P = 0.038). In HIV/HCV coinfected patients, these RANTES alleles were less frequent than in patients with HIV infection alone (15.4% P = 0.002;1.7%; P = 0.048; 12.0%; not significant). Frequencies of these alleles were not significantly different between HIV/HCV positive patients, HCV positive patients and healthy ***: All three RANTES polymorphisms showed increased frequencies of the variant allele exclusively in patients with HIV monoinfection. The finding that the frequencies of these alleles remained unaltered in HIV/HCV coinfected patients suggests that HCV coinfection interferes with selection processes associated with these alleles in HIV infection.

关键词： RANTES polymorphism HIV/HCV-coinfectJon HCV

Transjugular intrahepatic portosystemic shunt in refractory chylothorax due to liver cirrhosis

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World Journal of Gastroenterology 2013年第7期19卷 1140-1142页

作者： Philipp Lutz Holger Strunk Hans Heinz Schild tilman sauerbruch Department of Internal Medicine I University of Bonn53129 BonnGermany Department of Radiology University of Bonn53129 BonnGermany

A pleural effusion containing chylomicrons is termed chylothorax and results from leakage of lymph fluid into the pleural *** report on the case of a 59-year-old woman with severe dyspnea due to a large *** was known to have liver cirrhosis but no *** was no history of trauma,cardiac function was normal and thorough diagnostic work-up did not reveal any signs of *** summary,no other etiology of the chylothorax than portal hypertension could be *** with diuretics as well as parenteral feeding failed to relieve *** a transjugular intrahepatic portosystemic shunt(TIPS) had successfully been placed,pleural effusion decreased *** months later,TIPS revision had to be performed because of stenosis,resulting in remission from *** case shows that even in the absence of ascites,chylothorax might be caused by portal hypertension and that TIPS can be an effective treatment option.

关键词： Chylothorax Cirrhosis Liver Portal hypertension Transjugular intrahepatic portosystemic shunt

Exome sequencing identifies a likely causative variant in 53%of families with ciliopathy-related features on renal ultrasound after excluding NPHP1 deletions

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Genes & Diseases 2024年第5期11卷 40-43页

作者： Konstantin Deutsch Verena Klambt Thomas M.Kitzler tilman Jobst-Schwan Ronen Schneider Florian Buerger Steve Seltzsam Sherif El Desoky Jameela A.Kari Farkhanda Hafeez Maria Szczepanska Loai A.Eid Hazem S.Awad Muna Al-Saffar Neveen A.Soliman Velibor Tasic Camille Nicolas-Frank Kirollos Yousef Luca M.Schierbaum Sophia Schneider Abdul Halawi Izzeldin Elmubarak Katharina Lemberg Shirlee Shril Shrikant M.Mane Nancy Rodig Friedhelm Hildebrandt Division of Nephrology Department of PediatricsBoston Children’s HospitalHarvard Medical SchoolBostonMA 02215USA Department of Pediatric Gastroenterology Nephrology and Metabolic DiseasesCharite Universitatsmedizin BerlinBerlin 13353Germany Berlin Institute of Health at Charitee Universitatsmedizin Berlin BIH Biomedical Innovation AcademyBIH Charite Clinician Scientist ProgramBerlin 10178Germany Department of Nephrology and Hypertension FriedrichAlexander-Universitat Erlangen-NurnbergErlangen 91054Germany Department of Pediatrics Faculty of Medicine King Abdulaziz UniversityPediatric Nephrology Center of ExcellenceKing Abdulaziz University HospitalJeddah 21589Saudi Arabia Department of Pediatric Nephrology The Children’s Hospital and Institute of Child HealthLahore 54000Pakistan Department of Pediatrics Faculty of Medical Sciences in ZabrzeMedical University of Silesia in KatowiceKatowice 40-752Poland Dubai Hospital and Al-Jalila Children’s Specialty Hospital Kidney Center of ExcellenceDubai 4545United Arab Emirates Department of Genetics and Genomics UAE UniversityAbu Dhabi 15551United Arab Emirates Department of Pediatrics Division of Genetics and GenomicsBoston Children’s HospitalHarvard Medical SchoolBostonMA 02215USA Department of Pediatrics Center of Pediatric Nephrology and TransplantationKasr Al Ainy School of MedicineCairo UniversityCairo 11562Egypt Egypt Center for Research and Regenerative Medicine(ECRRM) Cairo 11511Egypt Medical Faculty Skopje University Children’s HospitalSkopje 1000North Macedonia Department of Genetics Yale University School of MedicineNew HavenCT 06520USA

Nephronophthisis-related ciliopathies(NPHP-RC)represent one of the most common causes of chronic kidney disease in the first three decades of life and are characterized by a broad genetic and clinical heterogeneity.1 To date,more than 90 genes have been identified that cause autosomalrecessive NPHP-RC if mutated,accounting for up to 60%of cases.1 Among these,homozygous deletions of NPHP1 are the most common *** genes localize to primary cilia,basal bodies,or the centrosome and lead to a primary ciliary disruption if mutated,thereby causing a broad phenotypical spectrum.1 Patients that suffer from NPHP-RC can either have an isolated renal phenotype,such as polyuria,polydipsia,decreased urinary concentration ability,and secondary enuresis due to loss of tubular function,or present with extrarenal symptoms including retinal degeneration,cerebellar vermis hypoplasia,or hepatic *** are often diagnosed in early adolescence,reaching end-stage renal disease before 25 years of age,but early onset and rapidly progressive forms of NPHP-RC also exist.1 Renal ultrasound indicates kidneys of normal or reduced renal length with increased echogenicity and corticomedullary cysts.

关键词： degeneration urinary likely

Enhancer-promoter communication:unraveling enhancer strength and positioning within a given topologically associating domain(TAD)

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3161-3162页

作者： Benedetto Daniele Giaimo tilman Borggrefe Institute of Biochemistry Justus-Liebig-University GiessenFriedrichstrasse 2435392 GiessenGermany

In a recent study published in Nature,Zuin et *** the molecular mechanisms of how enhancer positioning and strength affect gene expression levels.'Cell-type-specific transcription factors(TFs)and ubiquitously expressed cofactors regulate the complex network of eukar-yotic gene transcription in an exquisitely specific and sensitive *** DNA elements bound by TFs are called enhancers and can be located close to the transcription start site(TSS)or far away.

关键词： al. strength topological