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  • DKFZ Publication Database  (1,300)
  • human  (1,300)
  • 1
    Keywords: brain ; CANCER ; human ; PHENOTYPES ; STRESS ; INSIGHTS ; CONSUMPTION ; GLUTAMATE ; DRINKING ; DEPENDENCE ; WIDE ASSOCIATION ; Alcoholism ; drug addiction ; genome-wide association study (GWAS) ; GLUTAMATERGIC NEUROTRANSMISSION ; imaging genetics ; NALTREXONE ; QTL analysis ; TRANSPORTER GENE
    Abstract: Alcohol drinking is highly prevalent in many cultures and contributes to the global burden of disease. In fact, it was shown that alcohol constitutes 3.2% of all worldwide deaths in the year 2006 and is linked to more than 60 diseases, including cancers, cardiovascular diseases, liver cirrhosis, neuropsychiatric disorders, injuries and foetal alcohol syndrome. Alcoholism, which has been proven to have a high genetic load, is one potentially fatal consequence of chronic heavy alcohol consumption, and may be regarded as one of the most prevalent neuropsychiatric diseases afflicting our society today. The aim of the integrated genome research network 'Genetics of Alcohol Addiction'-which is a German inter-/trans-disciplinary life science consortium consisting of molecular biologists, behavioural pharmacologists, system biologists with mathematicians, human geneticists and clinicians-is to better understand the genetics of alcohol addiction by identifying and validating candidate genes and molecular networks involved in the aetiology of this pathology. For comparison, addictive behaviour to other drugs of abuse (e.g. cocaine) is studied as well. Here, we present an overview of our research consortium, the current state of the art on genetic research in the alcohol field, and list finally several of our recently published research highlights. As a result of our scientific efforts, better insights into the molecular and physiological processes underlying addictive behaviour will be obtained, new targets and target networks in the addicted brain will be defined, and subsequently, novel and individualized treatment strategies for our patients will be delivered
    Type of Publication: Journal article published
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  • 2
    Keywords: CANCER ; human ; CLASSIFICATION ; LUNG-CANCER ; EPIDEMIOLOGY ; POPULATION ; MECHANISM ; CARCINOGENESIS ; BREAST-CANCER ; HUMANS ; OXIDATIVE STRESS ; NESTED CASE-CONTROL ; OCCUPATIONAL-EXPOSURE ; CARCINOGEN ; RISK-ASSESSMENT ; animal ; occupational ; IARC ; mechanisms of carcinogenicity ; PARTICLE SURFACE-AREA ; POLYCHLORINATED-BIPHENYLS PCBS ; REFRACTORY CERAMIC FIBER ; TITANIUM-DIOXIDE
    Abstract: OBJECTIVES: There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. DATA SOURCES: For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent. DATA EXTRACTION: Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. DATA SYNTHESIS: Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation. CONCLUSIONS: Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes
    Type of Publication: Journal article published
    PubMed ID: 20562050
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  • 3
    Keywords: CELLS ; EXPRESSION ; GROWTH-FACTOR ; proliferation ; human ; MECHANISM ; cytokines ; IDENTIFICATION ; p53 ; STEM-CELLS ; SQUAMOUS-CELL CARCINOMA ; GM-CSF ; p73 ; P53 HOMOLOG ; DELTA-NP63-ALPHA ; FGF10 ; HAY-WELLS-SYNDROME ; KGF ; TRANSCRIPTIONAL REGULATOR
    Abstract: The transcription factor p63 is required for proper epidermal barrier formation and maintenance. Herein, we used chromatin immunoprecipitation coupled with DNA sequencing to identify novel p63 target genes involved in normal human epidermal keratinocyte (NHEKs) growth and differentiation. We identified over 2000 genomic sites bound by p63, of which 82 were also transcriptionally regulated by p63 in NHEKs. Through the discovery of interleukin-1-alpha as a p63 target gene, we identified that p63 is a regulator of epithelial-mesenchymal crosstalk. Further, three-dimensional organotypic co-cultures revealed TCF7L1, another novel p63 target gene, as a regulator of epidermal proliferation and differentiation, providing a mechanism by which p63 maintains the proliferative potential of basal epidermal cells. The discovery of new target genes links p63 to diverse signaling pathways required for epidermal development, including regulation of paracrine signaling to proliferative potential. Further mechanistic insight into p63 regulation of epidermal cell growth and differentiation is provided by the identification of a number of novel p63 target genes in this study. Cell Death and Disease (2010) 1, e74; doi:10.1038/cddis.2010.49; published online 9 September 2010
    Type of Publication: Journal article published
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  • 4
    Keywords: PHASE ; SODIUM ; MOBILITY ; HEAD ; sensitivity ; MAGNETIC-RESONANCE ; MRI ; SIGNAL ; FIELD ; IONS ; imaging ; IMAGES ; CANCER ; human ; cancer research ; PHASES
    Abstract: For diagnostic purposes, in sodium (23Na) MRI, the discrimination between free sodium ions and sodium ions restricted in their mobility is desirable. One method to isolate the signal from such ions is triple-quantum filtered sodium MRI. However, a problem connected with this method is the pronounced sensitivity to inhomogeneities in the B0 field. To reduce the influence of the latter, pulse phases must be chosen carefully. We propose a fast method to find optimal values for the pulse phases before measurement and acquire triple-quantum filtered sodium images of the human head.
    Type of Publication: Proceeding
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  • 5
    Keywords: Relaxation time ; cancer research ; PHANTOMS ; phantom ; 3 ; TIMES ; human ; CANCER ; OPTIMIZATION ; brain ; TIME ; FIELD ; SEQUENCE ; MAGNETIC-RESONANCE ; DEGRADATION ; PARAMETERS ; DESIGN ; RELAXATION ; PROTOCOL ; human brain
    Abstract: The purpose of this study is to provide parameters for the optimization of 23Na-MRI protocols at 7 T. Therefore, T1 and T2* relaxation times of the human brain and different phantoms were measured. SNR and image quality was investigated at three field strengths (1.5 T, 3 T, 7T). The theoretically expected approximately linear increase in SNR with field strength could be confirmed, with minor deviations that can be attributed to relaxation effects. Furthermore, it was shown that appropriate sequence designs, such as a density adapted radial sequence can reduce degradations of image quality due to B0-inhomogeneities even at 7 T.
    Type of Publication: Proceeding
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  • 6
    Keywords: EXPRESSION ; human ; SKIN ; IN-SITU ; USA
    Type of Publication: Meeting abstract published
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  • 7
    Keywords: USA ; ELEVATED EXPRESSION ; GLIOMA ; DISPLAY ; pathology ; DEMENTIA ; GLIOMAS ; PROTEIN ; human ; EXPRESSION
    Type of Publication: Meeting abstract published
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  • 8
    Keywords: PATIENT ; human ; brain ; CNS ; MULTIPLE-SCLEROSIS ; LESIONS ; multiple sclerosis
    Type of Publication: Meeting abstract published
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  • 9
    Keywords: CELL ; human ; TRANSPLANTATION ; HUMANS ; STEM-CELL
    Type of Publication: Meeting abstract published
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  • 10
    Keywords: cell lines ; CHEMISTRY ; HUMAN CANCER ; CELL-LINE ; CELL-LINES ; LINES ; Germany ; human ; CELL ; CANCER ; APOPTOSIS ; pharmacology ; CANCER-CELL-LINES
    Type of Publication: Meeting abstract published
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  • 11
    Keywords: USA ; molecular biology ; MOLECULAR-BIOLOGY ; BIOLOGY ; CELL-LINE ; CELL ; human ; carcinoma
    Type of Publication: Meeting abstract published
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  • 12
    Keywords: PROPORTION ; HPV genotype ; PARTICLE VACCINE ; QUADRIVALENT VACCINE ; HPV vaccine ; TYPE-18 ; immunology ; CANCERS ; EXTRACTION ; GENOTYPE ; CANCER ; human ; PATIENT ; INFECTION ; DNA ; SAMPLES ; SAMPLE ; POPULATION ; DISEASE ; PREVALENCE ; vaccination ; VACCINE ; IV ; WORLDWIDE ; SINGLE ; WOMEN ; AGE ; ASSAY ; CERVICAL-CANCER ; EFFICACY ; RATES ; cervical cancer ; GENOTYPES ; REGION ; human papillomavirus ; HIGH-RISK ; HPV ; HUMAN-PAPILLOMAVIRUS ; LESIONS ; TRIAL ; STAGE ; ASSOCIATION ; papillomavirus
    Abstract: Despite worldwide human papillomavirus (HPV) types distribution showed constant rates of HPV 16/18 in cervical cancers, regional variations have been consistently documented. Very little data is available on HPV genotype prevalence among Italian women with invasive cervical cancer. This study aims to determine the HPV type distribution in cervical specimens obtained from Italian women diagnosed with invasive cervical cancer and referred to the European Institute of Oncology (IEO). Two hundred-sixty eight cervical specimens were obtained from patients diagnosed with invasive cervical cancer referred to the European Institute of Oncology between 1996 and 2006. Following preparation, all cervical samples were sent to laboratories at the International Agency for Research on Cancer (IARC, Lyon, France) for DNA extraction and HPV typing by the multiplex PCR/APEX assay. The Study population was divided into four groups from different macro regions: (i) Milan and surrounding area (n = 57, 21.3%), (ii) northern Italy (n = 81, 30.2%), (iii) central Italy (n = 64, 23.9%) and (iv) southern Italy (n = 66, 24.6%). The present study is the first at our knowledge that examines a fair number of Italian cervical cancers, about one tenth of all estimated cervical cancer cases occurring yearly, distributed across the whole country. Two-hundred and fifty-one patients (93.7%) resulted HPV DNA positive: of these 201 patients (80.1%) presented a single infection, whereas 50 women (19.9%) presented multiple infection. One hundred and eighty-nine specimens (75.3%) tested positive for either HPV 16 or HPV 18, whereas 62 (24.7%) resulted positive for other high-risk HPV genotypes only. The proportion of HPV 16/18 positive invasive cervical cancers was similar for all the four geographical Italian areas considered. A statistically significant association with younger age and earlier stage was observed for HPV 16/18 related invasive cervical cancers. The results demonstrate that the proportion of HPV 16/18 cervical cancers is fairly constant in all the areas and covers more than 70% of Italian cervical cancer cases. This observation strengthens the decision to start the vaccination programme in all the Italian regions. In addition, the present study provides new and original data on the genotype related differences of the disease that are worth of further investigation. (C) 2009 Elsevier Ltd. All rights reserved
    Type of Publication: Meeting abstract published
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  • 13
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    FEBS Journal 276 (), 19-19 
    Keywords: BIOLOGY ; MOLECULAR-BIOLOGY ; ACID ; aristolochic acid ; molecular biology ; DRUG ; human ; USA
    Type of Publication: Meeting abstract published
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  • 14
    Keywords: PATHOGENESIS ; PROGNOSTIC-FACTORS ; PLASMA ; affymetrix ; CELL-LINE ; chemotherapy ; CELL-LINES ; multiple myeloma ; HIGH-DOSE CHEMOTHERAPY ; CANCER PATIENTS ; RECEPTORS ; PROGNOSTIC FACTORS ; CANCER-PATIENTS ; cell lines ; MULTIPLE-MYELOMA ; CELL ; human ; VITRO ; DIAGNOSIS ; INHIBITION ; IN-VITRO ; proliferation ; SURVIVAL ; CANCER ; CELLS ; EXPRESSION ; RECEPTOR ; ANGIOGENESIS ; APOPTOSIS ; PATIENT ; LINES ; TRANSPLANTATION ; INDUCTION ; IMPACT ; PROTEINS ; PROTEIN ; SAMPLE ; SAMPLES ; cell line ; BONE ; RELEVANCE ; STEM-CELL ; methods ; PROGNOSTIC-FACTOR ; PLASMA-CELLS ; CANDIDATES ; A ; D ; Plasma cells ; autologous ; WELL
    Abstract: Introduction:Pathogenesis of multiple myeloma is associated with an aberrant expression of pro-proliferative-, pro-angiogenic and bone-metabolism modifying factors by malignant plasma cells. Given the timespan from diagnosis of early-stage plasma cell dyscrasias to overt myeloma and the low proliferation rate of malignant plasma cells, we hypothesize these likewise to express a novel class of inhibitory factors of potential prognostic relevance. Bone morphogenic proteins (BMPs) represent possible candidates as they inhibit proliferation, stimulate bone formation, and have impact on the survival of cancer patients.Methods.We assessed expression of BMPs and their receptors by Affymetrix DNA-microarrays (n=434) including CD138-purified primary myeloma cell samples (n=233) of previously untreated patients treated with high-dose chemotherapy and autologous stem cell transplantation. Inhibition of proliferation of human myeloma cell lines (n=10) and apoptosis induction in primary myeloma cell samples (n=5) is assessed. The inhibition of vitro tubule formation by BMP6 is investigated using the AngioKit-assay.Results.BMP6 is the only BMP expressed by malignant or normal plasma cells. Its expression is significantly lower in proliferating myeloma cells, myeloma cell lines, or plasmablasts. BMP6 significantly inhibits proliferation of myeloma cell lines, survival of primary myeloma cells, and in vitro angiogenesis. High BMP6-expression in primary myeloma cell samples delineates significantly superior overall survival for patients undergoing high-dose chemotherapy independent of conventional prognostic factors (ISS-stage, serum-ß2-microglobulin).Conclusion.BMP6 exemplifies a novel class of factors independently prognostic for overall survival expressed by normal as well as malignant plasma cells that inhibits proliferation of myeloma cells and induction of angiogenesis.Gemeinsame Jahrestagung der Deutschen, Österreichischen und Schweizerischen Gesellschaften für Hämatologie und Onkologie, 2.-6. Oktober 2009, Heidelberg/Mannheim
    Type of Publication: Meeting abstract published
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  • 15
    Keywords: brain ; ANGIOGENESIS ; CELLS ; EXPRESSION ; GROWTH ; IN-VITRO ; INHIBITOR ; tumor ; CELL ; human ; IN-VIVO ; MODEL ; VITRO ; VIVO ; COMMON ; GENE ; TUMORS ; MICE ; LIGAND ; NEOPLASIA ; NUDE-MICE ; CELL-LINE ; MELANOMA ; SUBUNITS ; ARCHITECTURE ; INHIBITORS ; mRNA ; USA ; angiopoietin ; angiopoietin-2 ; TIE2 ; CHRONIC GRANULOMATOUS-DISEASE ; gene array ; HEMANGIOMAS ; MIDDLE-T-ONCOGENE ; NEUTROPHIL CYTOCHROME-B
    Abstract: Hemangiomas are the most common type of tumor in infants. As they are endothelial cell-derived neoplasias, their growth can be regulated by the autocrine-acting Tie2 ligand angiopoietin 2 (Ang2). Using an experimental model of human hemangiomas, in which polyoma middle T-transformed brain endothelial (bEnd) cells are grafted subcutaneously into nude mice, we compared hemangioma growth originating from bEnd cells derived from wild-type, Ang2(+/-), and Ang2(-/-) mice. Surprisingly, Ang2-deficient bEnd cells formed endothelial tumors that grew rapidly and were devoid of the typical cavernous architecture of slow-growing Ang2-expressing hemangiomas, while Ang2(+/-) cells were greatly impaired in their in vivo growth. Gene array analysis identified a strong downregulation of NADPH oxidase 4 (Nox4) in Ang2(+/-) cells. Correspondingly, lentiviral silencing of Nox4 in an Ang2-sufficient bEnd cell line decreased Ang2 mRNA levels and greatly impaired hemangioma growth in vivo. Using a structure-based approach, we identified fulvenes as what we believe to be a novel class of Nox inhibitors. We therefore produced and began the initial characterization of fulvenes as potential Nox inhibitors, finding that fulvene-5 efficiently inhibited Nox activity in vitro and potently inhibited hemangioma growth in vivo. In conclusion, the present study establishes Nox4 as a critical regulator of hemangioma growth and identifies fulvenes as a potential class of candidate inhibitor to therapeutically interfere with Nox function
    Type of Publication: Journal article published
    PubMed ID: 19620773
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  • 16
    Keywords: CELLS ; INHIBITOR ; CELL ; human ; INHIBITION ; SUPPORT ; DISEASE ; DISEASES ; PATIENT ; COMPLEXES ; hepatocytes ; BIOLOGY ; MOLECULAR-BIOLOGY ; E6 ; bilirubin ; INHIBITORS ; POTENT ; molecular biology ; FEATURES ; interaction ; EXCRETION ; SUBSTRATE ; pharmacology ; USA ; PRAVASTATIN ; HEME ; NOV ; POSITION ; ACUTE INTERMITTENT PORPHYRIA ; FETAL BILIRUBIN ; MATERNAL LIVER TANDEM ; OATP1B1 inhibitor ; Porphyna ; Porphyrin ; PROTOPORPHYRIA ; REDUCTASE INHIBITORS
    Abstract: The existence of a porphyrin uptake transporter in hepatocytes has been hypothesized in recent years, but to date it has not been identified. While the linear tetrapyrrole bilirubin has been shown to be a substrate for the organic anion transporting polypeptide 1B1 (OATP1B1). similar studies have not been conducted for the cyclic tetrapyrroles (porphyrins). The aim of this study was to determine the structural features of linear and cyclic tetrapyroles necessary for interaction with OATP1B1. The interaction was quantified using HEK cells stably expressing OATP1BI and measuring the inhibition of OATP1B1-mediated uptake of estrachol 170-D-glucuronide in the presence or absence of various linear and cyclic tetrapyrroles. Ditaurine-conjugated bilirubin was the most potent inhibitor of uptake, with an IC50 of 5 nM, while the Substitution of the taurine side chains with methyl ester eliminated the inhibition of estradiol 17 beta-D-glucuronide uptake. Hematoporphyrin. a cyclic tetrapyrrole with carboxyalcohol side chains at positions C-3 and C-8 and carboxyethyl side chains at positions 13 and 17 had an IC50 of 60 nM, while porphyrins lacking charged side chains such as etioporphyrin 1 and phthalocyanine did not inhibit OATP1B1. Chlorin e6 and hematoporphyrin were shown to be competitive inhibitors of OATP1BI-mediated uptake of bromosulfophthalein with Kis of 5.8 +/- 0.3 and 1.6 +/- 0.3 mu M. respectively. While these studies do not provide direct evidence, they do support the assumption that tetrapyrroles are transported by OATP1B1. Adchtionally, these findings offer a possible explanation for the clinical observation that patients suffering from certain porphyrietic diseases have a reduced ability to excrete organic anions. (C) 2009 Elsevier Ireland Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19560444
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  • 17
    Keywords: RECEPTOR ; IN-VITRO ; Germany ; human ; VITRO ; PROTEIN ; PROTEINS ; COMPLEX ; COMPLEXES ; INFECTION ; RAT ; RATS ; BINDING ; antibody ; NEUTRALIZING ANTIBODIES ; immune response ; IMMUNOGENICITY ; HUMAN-IMMUNODEFICIENCY-VIRUS ; GP120 ; SERUM ; POTENT ; ENVELOPE GLYCOPROTEINS ; ENHANCEMENT ; HIV ; CONFORMATION ; HUMAN MONOCLONAL-ANTIBODY ; DISULFIDE BOND ; HIV-1 vaccine ; Induced Env epitope ; Neutralising antibodies ; RECEPTOR COMPLEXES ; RETROVIRAL PARTICLES ; RHESUS MACAQUES ; TYPE-1 ENV
    Abstract: Immune responses to a pseudovirion-based HIV vaccine enriched in Env conformations, which have been induced to an authentic intermediate fusion stage by interaction with the cellular HIV receptor complex, have been analysed in human CD4/CCR5-transgenic rats. High titre Env-binding antibodies were elicited. However, these immune sera failed to neutralise HIV-1, but rather led to an enhancement of infection in vitro. This enhancing activity appeared to be directed towards contaminating cellular proteins in the vaccine and was able to mask neutralisation of potent, mixed-in neutralising antibodies. The induced Env-specific antibodies, purified on the basis of binding to monomeric Env, retained high-binding activity, but failed to be neutralising. Thus, it remains unclear whether vaccines based on induced HIV Env fusion intermediates can elicit broadly neutralising responses. (C) 2009 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19428834
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  • 18
    Keywords: APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; tumor ; CELL ; human ; MODEL ; DISEASE ; SITES ; GENE ; GENES ; transcription ; MICE ; NF-KAPPA-B ; COMPLEX ; COMPLEXES ; DNA ; MECHANISM ; murine ; TRANSCRIPTION FACTOR ; IMPACT ; animals ; mechanisms ; BINDING ; SEQUENCE ; SEQUENCES ; TARGET ; MOUSE ; STAGE ; TRANSCRIPTION FACTORS ; PROGRESSION ; MALIGNANCIES ; PATTERNS ; PROMOTER ; AGE ; transgenic ; leukemia ; DNA methylation ; TUMOR-SUPPRESSOR GENE ; REGION ; B-CELLS ; RECRUITMENT ; STRATEGIES ; MOUSE MODEL ; TARGETS ; REPRESSION ; METHYLATION ; TRANSCRIPTIONAL REPRESSION ; REGULATOR ; MALIGNANCY ; PROGRAM ; TUMOR-SUPPRESSOR ; CLL ; MURINE MODEL ; development ; BINDING-SITE ; USA ; EPIGENETICS ; ONSET ; CPG-ISLAND METHYLATION ; BINDING-SITES ; OCCURS ; tumor suppressor ; epigenetic ; STATE ; BINDING SITE ; histone modifications ; ABERRANT METHYLATION ; 3 ; therapeutic ; THERAPEUTIC TARGET ; WELL ; STRATEGY ; INVESTIGATE ; RATIONALE ; TRANSCRIPTION-FACTOR ; FOXD3
    Abstract: Epigenetic alterations, including gain or loss of DNA methylation, are a hallmark of nearly every malignancy. Changes in DNA methylation can impact expression of cancer-related genes including apoptosis regulators and tumor suppressors. Because such epigenetic changes are reversible, they are being aggressively investigated as potential therapeutic targets. Here we use the E mu-TCL1 transgenic mouse model of chronic lymphocytic leukemia (CLL) to determine the timing and patterns of aberrant DNA methylation, and to investigate the mechanisms that lead to aberrant DNA methylation. We show that CLL cells from E mu-TCL1 mice at various stages recapitulate epigenetic alterations seen in human CLL. Aberrant methylation of promoter sequences is observed as early as 3 months of age in these animals, well before disease onset. Abnormally methylated promoter regions include binding sites for the transcription factor FOXD3. We show that loss of Foxd3 expression due to an NF-kappa B p50/p50:HDAC1 repressor complex occurs in TCL1-positive B cells before methylation. Therefore, specific transcriptional repression is an early event leading to epigenetic silencing of target genes in murine and human CLL. These results provide strong rationale for the development of strategies to target NF-kappa B components in CLL and potentially other B-cell malignancies
    Type of Publication: Journal article published
    PubMed ID: 19666576
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  • 19
    Keywords: CANCER ; CELLS ; CELL ; Germany ; human ; LINES ; COMPLEX ; LIGAND ; COMPLEXES ; murine ; BIOLOGY ; CELL-LINES ; leukemia ; US ; CRYSTAL-STRUCTURE ; cell lines ; molecular biology ; CARBONIC-ANHYDRASE INHIBITORS ; sulfonamides ; pharmacology ; BIOLOGICAL-ACTIVITY ; ELECTROPORATION ; CISPLATIN-INDUCED APOPTOSIS ; WELL ; ANTICANCER ; Cytostatic Agents ; ELECTROCHEMOTHERAPY ; ISOZYME-II INHIBITORS ; Platinum complexes ; TRANS GEOMETRY
    Abstract: The series of complexes: cis-[Pd(PMSA)(2)X-2], cis-[Pt(PMSA)(2)X-2], trans-[Pt(PMSA)(2)I-2] and [Pt(PMSA)(4)]Cl-2 (PMSA = N-3-pyridinylmethanesulfonamide; X = Cl, Br, I), previously synthesized and characterized by us, as well as the free ligand PMSA, were tested for their cytotoxic activity without electroporation - against murine leukemia F4N and human SKW-3 and MDA-MB-231 tumour cell lines - and with electroporation - against the latter two cell lines. The majority of the complexes exhibited cytotoxic effects (IC50 〈 100 mu mol/l) under the conditions of electroporation. Both cis- and trans-[Pt(PMSA)(2)I-2] had pronounced cytotoxic effects (29-61 mu mol/l against MDA-MB-231 cells)
    Type of Publication: Journal article published
    PubMed ID: 19526709
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  • 20
    Keywords: EXPRESSION ; Germany ; human ; SUPPORT ; DEATH ; DISEASE ; MORTALITY ; POPULATION ; GENE ; GENES ; GENOME ; PATIENT ; FAMILY ; DISORDER ; LINKAGE ; PATHOGENESIS ; REGION ; LINKAGE DISEQUILIBRIUM ; MUSCLE ; PHENOTYPE ; POPULATIONS ; UNITED-STATES ; DILATED CARDIOMYOPATHY ; SINGLE ; FAMILIES ; DETERMINANTS ; REARRANGEMENT ; CARDIOMYOPATHY ; LOCI ; VERTEBRATE GENOMES ; GENOMES ; DYSFUNCTION ; STATE ; Genetic ; FUNCTIONAL ASSESSMENT ; Case-Control Studies Cell Line Chrom
    Abstract: Human dilated cardiomyopathy (DCM), a disorder of the cardiac muscle, causes considerable morbidity and mortality and is one of the major causes of sudden cardiac death. Genetic factors play a role in the etiology and pathogenesis of DCM. Disease-associated genetic variations identified to date have been identified in single families or single sporadic patients and explain a minority of the etiology of DCM. We show that a 600-kb region of linkage disequilibrium (LD) on 5q31.2-3, harboring multiple genes, is associated with cardiomyopathy in three independent Caucasian populations (combined P-value = 0.00087). Functional assessment in zebrafish demonstrates that at least three genes, orthologous to loci in this LD block, HBEGF, IK, and SRA1, result independently in a phenotype of myocardial contractile dysfunction when their expression is reduced with morpholino antisense reagents. Evolutionary analysis across multiple vertebrate genomes suggests that this heart failure-associated LD block emerged by a series of genomic rearrangements across amphibian, avian, and mammalian genomes and is maintained as a cluster in mammals. Taken together, these observations challenge the simple notion that disease phenotypes can be traced to altered function of a single locus within a haplotype and suggest that a more detailed assessment of causality can be necessary
    Type of Publication: Journal article published
    PubMed ID: 19064678
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  • 21
    Keywords: CANCER ; CANCER CELLS ; CELLS ; CELL ; COMBINATION ; Germany ; human ; MODEL ; MODELS ; PATHWAY ; PATHWAYS ; ALGORITHMS ; GENE ; GENES ; microarray ; RNA ; COMPLEX ; COMPLEXES ; DNA ; BIOLOGY ; BREAST ; breast cancer ; BREAST-CANCER ; microarrays ; SIGNALING PATHWAY ; SIGNALING PATHWAYS ; CANCER-CELLS ; signaling ; review ; INTERFERENCE ; SIGNALING NETWORK ; signaling networks ; Nested effects models ; Perturbation data ; Signaling pathway inference
    Abstract: Targeted gene perturbations have become a major tool to gain insight into complex cellular processes. In combination with the measurement of downstream effects via DNA microarrays, this approach can be used to gain insight into signaling pathways. Nested Effects Models were first introduced by Markowetz et al. as a probabilistic method to reverse engineer signaling cascades based on the nested structure of downstream perturbation effects. The basic framework was substantially extended later on by Frohlich et al., Markowetz et al., and Tresch and Markowetz. In this paper, we present a review of the complete methodology with a detailed comparison of so far proposed algorithms on a qualitative and quantitative level. As an application, we present results on estimating the signaling network between 13 genes in the ER-a pathway of human MCF-7 breast cancer cells. Comparison with the literature shows a substantial overlap
    Type of Publication: Journal article published
    PubMed ID: 19358219
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  • 22
    Keywords: RECEPTOR ; APOPTOSIS ; CELLS ; EXPRESSION ; SURVIVAL ; tumor ; TUMOR-CELLS ; CELL ; human ; KINASE ; PATHWAY ; PATHWAYS ; TYROSINE KINASE ; COHORT ; DEATH ; LONG-TERM ; GENE ; DIFFERENTIATION ; TUMORS ; NEUROBLASTOMA-CELLS ; PATIENT ; ACTIVATION ; MECHANISM ; DOMAIN ; BINDING ; CELL-DEATH ; REGION ; LONG-TERM SURVIVAL ; specificity ; DOMAINS ; neuroblastoma ; signaling ; NEURONS ; medulloblastoma ; interaction ; LEVEL ; cell death ; TECHNOLOGY ; USA ; pediatric ; MEDIATOR ; TYROSINE ; 2-HIT MECHANISM ; CEREBRAL CAVERNOUS MALFORMATIONS ; P75 NEUROTROPHIN RECEPTOR
    Abstract: The TrkA receptor tyrosine kinase is crucial for differentiation and survival of nerve-growth-factor-dependent neurons. Paradoxically, TrkA also induces cell death in pediatric tumor cells of neural origin, via an unknown mechanism. Here, we show that CCM2, a gene product associated with cerebral cavernous malformations, interacts with the juxtamembrane region of TrkA via its phosphotyrosine binding (PTB) domain and mediates TrkA-induced death in diverse cell types. Both the PTB and Karet domains of CCM2 are required for TrkA-dependent cell death, such that the PTB domain determines the specificity of the interaction, and the Karet domain links to death pathways. Downregulation of CCM2 in medulloblastoma or neuroblastoma cells attenuates TrkA-dependent death. Combined high expression levels of CCM2 and TrkA are correlated with long-term survival in a large cohort of human neuroblastoma patients. Thus, CCM2 is a key mediator of TrkA-dependent cell death in pediatric neuroblastic tumors
    Type of Publication: Journal article published
    PubMed ID: 19755102
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  • 23
    Keywords: evaluation ; Germany ; human ; MODEL ; MODELS ; ALGORITHM ; ALGORITHMS ; CLASSIFICATION ; COMMON ; CT ; IMAGES ; imaging ; segmentation ; SYSTEM ; SYSTEMS ; liver ; ACCURACY ; validation ; image analysis ; PERFORMANCE ; score ; EFFICIENT ; DATABASE ; REGISTRATION ; VARIABILITY ; DEFORMATION ; radiology ; TECHNOLOGY ; USA ; ERROR ; CLASSIFIERS ; WELL ; Statistical shape model ; DIAGNOSTIC SYSTEM ; FREE-FORM DEFORMATIONS ; IMAGE SEGMENTATION ; SHAPE MODELS
    Abstract: This paper presents a comparison study between 10 automatic and six interactive methods for liver segmentation from contrast-enhanced CT images. It is based on results from the "MICCAI 2007 Grand Challenge" workshop, where 16 teams evaluated their algorithms on a common database. A collection of 20 clinical images with reference segmentations was provided to train and tune algorithms in advance. Participants were also allowed to use additional proprietary training data for that purpose. All teams then had to apply their methods to 10 test datasets and submit the obtained results. Employed algorithms include statistical shape models, atlas registration, level-sets, graph-cuts and rule-based systems. All results were compared to reference segmentations five error measures that highlight different aspects of segmentation accuracy. All measures were combined according to a specific scoring system relating the obtained values to human expert variability. In general, interactive methods reached higher average scores than automatic approaches and featured a better consistency of segmentation quality. However, the best automatic methods (mainly based on statistical shape models with some additional free deformation) could compete well on the majority of test images. The study provides an insight in performance of different segmentation approaches under real-world conditions and highlights achievements and limitations of current image analysis techniques
    Type of Publication: Journal article published
    PubMed ID: 19211338
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  • 24
    Keywords: CANCER ; CANCER CELLS ; CELLS ; EXPRESSION ; CELL ; human ; SUPPORT ; PROTEIN ; LINES ; COMPLEX ; COMPLEXES ; BIOLOGY ; FORM ; PROGRESSION ; colorectal cancer ; COLORECTAL-CANCER ; FIBER ; CANCER-CELLS ; MAMMALIAN-CELLS ; MICROTUBULES ; DUPLICATION ; ORGANIZATION ; HUMAN BREAST-TUMORS ; C-ELEGANS ; centrosome ; USA ; BIOGENESIS ; hydroxyurea ; colorectal ; centrosomes ; Plk4 ; 9-FOLD SYMMETRY ; Centrioles ; CENTROSOME REPLICATION ; Cep135 ; gamma-tubulin ; HAMSTER OVARY CELLS ; HCT116 cells ; MICROTUBULE ORGANIZATION ; Nine-triplet microtubules ; PTK2 CELLS ; RING ; SAS6
    Abstract: Cancer cells frequently induce aberrant centrosomes, which have been implicated in cancer initiation and progression. Human colorectal cancer cells, HCT116, contain aberrant centrioles composed of disorganized cylindrical microtubules and displaced appendages. These cells also express unique centrosome-related structures associated with a subset of centrosomal components, including gamma-tubulin, centrin and PCM1. During hydroxyurea treatment, these abnormal structures become more abundant and undergo a change in shape from small dots to elongated fibers. Although gamma-tubulin seems to exist as a ring complex, the abnormal structures do not support microtubule nucleation. Several lines of evidence suggest that the fibers correspond to a disorganized form of centriolar microtubules. Plk4, a mammalian homolog of ZYG-1 essential for initiation of centriole biogenesis, is not associated with the gamma-tubulin-specific abnormal centrosomes. The amount of Plk4 at each centrosome was less in cells with abnormal centrosomes than cells without gamma-tubulin-specific abnormal centrosomes. In addition, the formation of abnormal structures was abolished by expression of exogenous Plk4, but not SAS6 and Cep135/Bld10p, which are downstream regulators required for the organization of nine-triplet microtubules. These results suggest that HCT116 cells fail to organize the ninefold symmetry of centrioles due to insufficient Plk4
    Type of Publication: Journal article published
    PubMed ID: 19454482
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  • 25
    Keywords: RECEPTOR ; CANCER ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; tumor ; CELL ; FACTOR RECEPTOR ; Germany ; human ; GENE ; GENES ; TUMORS ; MECHANISM ; TRANSCRIPTION FACTOR ; prognosis ; mechanisms ; cell cycle ; CELL-CYCLE ; CYCLE ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; FREQUENCIES ; BREAST ; breast cancer ; BREAST-CANCER ; AMPLIFICATION ; mass spectrometry ; cancer risk ; MASS-SPECTROMETRY ; case-control studies ; OVEREXPRESSION ; EPIDERMAL-GROWTH-FACTOR ; CYCLIN D1 ; case-control study ; REGRESSION ; MS ; SINGLE-NUCLEOTIDE POLYMORPHISMS ; GENOTYPE ; ADJUVANT CHEMOTHERAPY ; HER2 ; USA ; LOCI ; TRASTUZUMAB ; CCND1 ; breast tumor ; CCND3 ; E2F2 ; HER2 status
    Abstract: Overexpression of the human epidermal growth factor receptor 2 (HER2) in breast tumors is associated with bad prognosis. Therefore, it is highly relevant to further improve understanding of the regulatory mechanisms of HER2 expression. In addition to gene amplification, transcriptional regulation plays a crucial role in HER2 overexpression. In this study, we analyzed 3 polymorphisms E2F2_-5368-A〉G, CCND1-870-A〉G and CCND3_-677_C〉T located in genes involved in cell cycle regulation in the GENICA population-based and age-matched breast cancer case-control study from Germany. We genotyped 1,021 cases and 1,015 controls by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Statistical analyses were performed by conditional logistic regression. We observed no differences in genotype frequencies between breast cancer cases and controls. Subgroup analysis showed associations between carriers of the E2F2_-5368_G allele (OR: 0.60, 95% CI: 0.42-0.85), carriers of the (C) over bar CND (1) over bar _870 G allele (OR: 0.66, 95% CI: 0.45-0.96) and carriers of the -CC (N) over bar D3_-677_T allele (OR: 1.72, 95% CI: 1.20-2.49) and HER2 expression in breast tumors. This finding points to an association of an increased expression of these cell cycle regulators with lower expression of HER2. An explanation for this observation might be that low expression of E2F2, CCND1 and CCND3 decrease levels of factors down-regulating HER2. We conclude that the analyzed polymorphisms located in E2F2, CCND1 and CCAID3 are potential markers for HER2 status of breast tumors. (C) 2008 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 19142864
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  • 26
    Keywords: PEPTIDE ; CELLS ; IN-VITRO ; CELL ; human ; VITRO ; PROTEIN ; DOMAIN ; BIOLOGY ; SPECTROSCOPY ; FORM ; SUBUNIT ; MUTATION ; CRYSTAL-STRUCTURE ; STABILITY ; INTERMEDIATE-FILAMENTS ; vimentin ; DIMER ; lamin ; DOMAINS ; ATOMIC-STRUCTURE ; intermediate filament ; SINGLE ; molecular biology ; assembly ; REARRANGEMENT ; coiled coil ; COILED-COIL ; nuclear lamins ; TEMPERATURE ; AMINO-ACID SUBSTITUTIONS ; circular dichroism ; POSITION ; STATE ; biophysical analysis ; CONSENSUS MOTIF ; GCN4 LEUCINE-ZIPPER ; HYDROPHOBIC CORE ; Oligomerisation ; OLIGOMERIZATION STATE ; PROTEIN STRUCTURES
    Abstract: Interestingly, our previously published structure of the coil 1A fragment of the human intermediate filament protein vimentin turned out to be a monomeric alpha-helical coil instead of the expected dimeric coiled coil. However, the 39-amino-acid-long helix had an intrinsic curvature compatible with a coiled coil. We have now designed four mutants of vimentin coil 1A, modifying key a and d positions in the heptad repeat pattern, with the aim of investigating the molecular criteria that are needed to stabilize a dimeric coiled-coil structure. We have analysed the biophysical properties of the mutants by circular dichroism spectroscopy, analytical ultracentrifugation and X-ray crystallography. All four mutants exhibited an increased stability over the wild type as indicated by a rise in the melting temperature (T-m). At a concentration of 0.1 mg/ml, the T-m of the peptide with the single point mutation Y117L increased dramatically by 46 degrees C compared with the wild-type peptide. In general, the introduction of a single stabilizing point mutation at an a or a d position did induce the formation of a stable dimer as demonstrated by sedimentation equilibrium experiments. The dimeric oligomerisation state of the Y117L peptide was furthermore confirmed by Xray crystallography, which yielded a structure with a genuine coiled-coil geometry. Most notably, when this mutation was introduced into full-length vimentin, filament assembly was completely arrested at the unit-length filament (ULF) level, both in vitro and in cDNA-transfected cultured cells. Therefore, the low propensity of the wild-type coil 1A to form a stable two-stranded coiled coil is most likely a prerequisite for the end-to-end annealing of ULFs into filaments. Accordingly, the coil 1A domains might "switch" from a dimeric alpha-helical coiled coil into a more open structure, thus mediating, within the ULFs, the conformational rearrangements of the tetrameric subunits that are needed for the intermediate filament elongation reaction. (C) 2009 Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19422834
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  • 27
    Keywords: CANCER ; CELLS ; EXPRESSION ; GROWTH ; SURVIVAL ; carcinoma ; CELL ; Germany ; human ; MODEL ; PATHWAY ; PATHWAYS ; NETWORK ; SUPPORT ; DEATH ; HEPATOCELLULAR-CARCINOMA ; liver ; GENE ; GENES ; PROTEIN ; PROTEINS ; TISSUE ; NF-KAPPA-B ; ACTIVATION ; murine ; CARCINOGENESIS ; INDUCTION ; SIGNAL ; TARGET ; MOUSE ; hepatocarcinogenesis ; hepatocellular carcinoma ; PROGRESSION ; CELL-DEATH ; CELL-LINE ; SIGNALING PATHWAY ; SIGNALING PATHWAYS ; RAGE ; MOUSE MODEL ; KAPPA-B ; OXIDATIVE STRESS ; expression profiling ; inflammation ; signaling ; MOLECULAR-MECHANISMS ; cell death ; CANCER PROGRESSION ; USA ; GROWTH-CONTROL ; SUPPRESSOR-CELLS ; nuclear factor kappa B ; COEXPRESSION ; COMPENSATORY PROLIFERATION
    Abstract: The nuclear factor-kappaB (NF-kappa B) signaling pathway has been recently shown to participate in inflammation-induced cancer progression. Here, we describe a detailed analysis of the NF-kappa B-dependent gene regulatory network in the well-established Mdr2 knockout mouse model of inflammation-associated liver carcinogenesis. Expression profiling of NF-kappa B-deficient and NF-kappa B-proficient hepatocellular carcinoma (HCC) revealed a comprehensive list of known and novel putative NF-kappa B target genes, including S100a8 and S100a9. We detected increased co-expression of S100A8 and S100A9 proteins in mouse HCC cells, in human HCC tissue, and in the HCC cell line Hep3B on ectopic RelA expression. Finally, we found a synergistic function for S100A8 and S100A9 in Hep3B cells resulting in a significant induction of reactive oxygen species (ROS), accompanied by enhanced cell survival. Conclusion: We identified S100A8 and S100A9 as novel NF-kappa B target genes in HCC cells during inflammation-associated liver carcinogenesis and provide experimental evidence that increased co-expression of both proteins supports malignant progression by activation of ROS-dependent signaling pathways and protection from cell death. (HEPATOLOGY 2009;50: 1251-1262.)
    Type of Publication: Journal article published
    PubMed ID: 19670424
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  • 28
    Keywords: CELLS ; BLOOD ; CELL ; COMBINATION ; Germany ; human ; SITES ; GENE-EXPRESSION ; PROTEIN ; PROTEINS ; DIFFERENTIATION ; COMPLEX ; COMPLEXES ; INFECTION ; BIOLOGY ; FORM ; NUCLEUS ; cytoskeleton ; vimentin ; lamin ; MEMBRANE PROTEIN ; MONOCYTE ; ACTIN CYTOSKELETON ; RETINOIC ACID ; BINDING PROTEIN ; BLOOD-VESSELS ; USA ; macrophage ; adaptation ; MONOCYTES ; STATE ; neutrophil ; HL-60 CELLS ; WELL ; ENVELOPE ARCHITECTURE ; LAMIN-B-RECEPTOR ; Nuclear enveloped ; PROMYELOCYTIC LEUKEMIA-CELLS
    Abstract: The major blood granulocyte (neutrophil) is rapidly recruited to sites of bacterial and fungal infections. It is a highly malleable cell, allowing it to squeeze out of blood vessels and migrate through tight tissue spaces. The human granulocyte nucleus is lobulated and exhibits a paucity of nuclear lamins, increasing its capability for deformation. The present study examined the existence of protein connections between the nuclear envelope and cytoskeletal elements (the LINC complex) in differentiated cell states (i.e. granulocytic, monocytic and macrophage) of the human leukemic cell line HL-60, as well as in human blood leukocytes. HL-60 granulocytes exhibited a deficiency of several LINC complex proteins (i.e. nesprin I giant, nesprin 2 giant, SUN1, plectin and vimentin); whereas, the macrophage state revealed nesprin I giant, plectin and vimentin. Both states possessed SUN2 in the nuclear envelope. Parallel differences were observed with some of the LINC complex proteins in isolated human blood leukocytes, including macrophage cells derived from blood monocytes. The present study documenting the paucity of LINC complex proteins in granulocytic forms, in combination with previous data on granulocyte nuclear shape and nuclear envelope composition, suggest the hypothesis that these adaptations evolved to facilitate granulocyte cellular malleability. (C) 2008 Elsevier GmbH. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19019491
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  • 29
    Keywords: APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; INHIBITOR ; proliferation ; SURVIVAL ; tumor ; carcinoma ; CELL ; CELL-PROLIFERATION ; Germany ; human ; MODEL ; HEPATOCELLULAR-CARCINOMA ; GENE ; GENES ; PROTEIN ; PROTEINS ; transcription ; TUMOR-NECROSIS-FACTOR ; LIGAND ; DNA ; MECHANISM ; TRANSPLANTATION ; BINDING ; cell cycle ; CELL-CYCLE ; CYCLE ; TARGET ; virus ; ELEMENT ; MOUSE ; hepatocellular carcinoma ; YEAST ; CELL-DEATH ; RESECTION ; sensitivity ; TARGETS ; C-MYC ; OVEREXPRESSION ; REPRESSION ; APOPTOSIS-INDUCING LIGAND ; BINDING PROTEIN ; INHIBITORS ; TUMOR-GROWTH ; regulation ; cell proliferation ; LEVEL ; SCREEN ; USA ; NECROSIS ; C-MYC EXPRESSION ; TFIIH
    Abstract: We identified the far upstream element binding protein 1 (FBP1), an activator of transcription of the proto-oncogene c-myc, in a functional yeast survival screen for tumor-related antiapoptotic proteins and demonstrated strong overexpression of FBP1 in human hepatocellular carcinoma (HCC). Knockdown of the protein in HCC cells resulted in increased sensitivity to apoptotic stimuli, reduced cell proliferation, and impaired tumor formation in a mouse xenograft transplantation model. Interestingly, analysis of gene regulation in these cells revealed that c-myc levels were not influenced by FBP1 in HCC cells. Instead, we identified the cell cycle inhibitor p21 as a direct target gene repressed by FBP1, and in addition, expression levels of the proapoptotic genes tumor necrosis factor a, tumor necrosis factor-related apoptosis-inducing ligand, Noxa, and Bik were elevated in the absence of FBP1. Conclusion: Our data establish FBP1 as an important oncoprotein overexpressed in HCC that induces tumor propagation through direct or indirect repression of cell cycle inhibitors and proapoptotic target genes. (HEPATOLOGY 2009;50:1121-1129.)
    Type of Publication: Journal article published
    PubMed ID: 19637194
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  • 30
    Keywords: CELLS ; EXPRESSION ; CELL ; Germany ; human ; MICROSCOPY ; PROTEIN ; PROTEINS ; FAMILY ; MARKER ; KERATINOCYTES ; SKIN ; antibodies ; antibody ; IN-SITU ; immunohistochemistry ; MELANOMA ; EPITHELIAL-CELLS ; MALIGNANT-MELANOMA ; melanoma cells ; human hair follicle ; CYTOKERATIN EXPRESSION ; intermediate filament ; FAMILIES ; keratinocyte ; keratins ; MELANOMA-CELLS ; hair ; MELANOCYTES ; USA ; PIGMENTATION ; LIGHT-MICROSCOPY ; reporting ; Melanocyte
    Abstract: Background Keratin family proteins are generally accepted as being restricted to epithelial cells. However, several studies have challenged this paradigm by reporting, for example, that melanoma cells can express keratins and that normal human epidermal melanocytes, which derive from the neural crest, express keratin 16 (K16) in situ. Objectives We wished to confirm or refute that K16 and/or its intermediate filament partner, keratin 6 (K6), are expressed in normal human epidermal and/or hair follicle melanocytes in situ. Methods Cryosections of normal human scalp skin were subjected to highly sensitive double immunohistochemistry with specific antibodies against K16 or K6 and against the melanocyte-specific marker NKI/beteb (gp100). Immunoreactivity (IR) was visualized by conventional light microscopy and confocal fluorescence microscopy. Results Despite the use of different, high-sensitivity immunostaining methods, stringent positive and negative controls, and monospecific, well-characterized antikeratin antibodies, we could detect neither K16 nor K6 IR within intraepidermal or intrafollicular pigment cells of normal human scalp skin. Instead, NKI/beteb+ cells were found to be intimately embedded in foci of K16+ and/or K6+ keratinocytes, which might create the illusion of keratin expression by these cells. Conclusions Human epidermal or hair follicle melanocytes do not express K16 and/or K6 while residing in their natural habitat
    Type of Publication: Journal article published
    PubMed ID: 19519832
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  • 31
    Keywords: CANCER ; CANCER CELLS ; CELLS ; SURVIVAL ; tumor ; carcinoma ; CELL ; Germany ; human ; THERAPY ; SURGERY ; LINES ; INFECTION ; CELL-LINES ; chemotherapy ; CANCER-CELLS ; cell lines ; pancreatic cancer ; pancreatic carcinoma ; PANCREATIC-CANCER ; RESVERATROL ; THERAPIES ; parvovirus ; therapeutic ; additive ; norfloxacin
    Abstract: Standard therapies such as surgery and chemotherapy offer only minimal improvement in pancreatic cancer. However, the viruses killing cancer cells and substances like some antibiotics and phytoalexins with anticancer potential may represent a candidate non-conventional mean of cancer treatment in the future. In this study, the effect of infection with oncolytic H-1 parvovirus (H-1PV) combined with antibiotic norfloxacin (NFX) or phytoalexin resveratrol oil the survival of cell lines Panc-1 and BxPC3 derived from human pancreatic carcinoma was tested. Whereas H-1PV with NFX exerted a synergistic effect, H-1PV with resveratrol resulted in an additive effect only. All the effects were partial, but they were more pronounced in Panc-1 compared to BxPC3 cells
    Type of Publication: Journal article published
    PubMed ID: 19301953
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  • 32
    Keywords: CANCER ; CELLS ; IN-VITRO ; tumor ; TUMOR-CELLS ; CELL ; Germany ; human ; IN-VIVO ; MICROSCOPY ; THERAPY ; VITRO ; SYSTEM ; DISEASE ; PROTEIN ; TUMORS ; TIME ; ACTIVATION ; T cells ; T-CELL ; T-CELLS ; MEMORY ; virus ; ASSAY ; VECTOR ; EFFICACY ; metastases ; PCR ; LYMPHOCYTES ; REPLICATION ; T-LYMPHOCYTES ; FLOW-CYTOMETRY ; CANCER-THERAPY ; tumor vaccine ; APOPTOSIS-INDUCING LIGAND ; THERAPIES ; cancer therapy ; cancer vaccine ; VIRULENCE ; Newcastle disease virus ; tumor targeting ; WELL ; IMMUNE CELL ; co-culture