University Medical Center Duesseldorf

Düsseldorf, Germany

University Medical Center Duesseldorf

Düsseldorf, Germany

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Ottaviano L.,University Medical Center Duesseldorf | Schaefer K.-L.,University Medical Center Duesseldorf | Gajewski M.,University Medical Center Duesseldorf | Huckenbeck W.,University Medical Center Duesseldorf | And 14 more authors.
Genes Chromosomes and Cancer | Year: 2010

Usage of cancer cell lines has repeatedly generated conflicting results provoked by differences among subclones or contamination with mycoplasm or other immortal mammalian cells. To overcome these limitations, we decided within the EuroBoNeT consortium to characterize a common set of cell lines including osteosarcomas (OS), Ewing sarcomas (ES), and chondrosarcomas (CS). DNA fingerprinting was used to guarantee the identity of all of the cell lines and to distinguish subclones of osteosarcoma cell line HOS. Screening for homozygous loss of 38 tumor suppressor genes by MLPA revealed deletion of CDKN2A as the most common event (15/36), strictly associated with absence of the CDKN2A (p16) protein. Ten cell lines showed missense mutations of the TP53 gene while another set of nine cell lines showed mutations resulting in truncation of the TP53 protein. Cells harboring missense mutations expressed high levels of nuclear TP53, while cell lines with nonsense mutations showed weak/absent staining for TP53. TP53wt cell lines usually expressed the protein in 2-10% of the cells. However, seven TP53wt osteosarcomas were negative for both mRNA and protein expression. Our analyses shed light on the correlation between immunohistochemical and genetic data for CDKN2A and TP53, and confirm the importance of these signaling pathways. The characterization of a substantial number of cell lines represents an important step to supply research groups with proven models for further advanced studies on tumor biology and may help to make results from different laboratories more comparable. © 2009 Wiley-Liss, Inc.

Mao X.-G.,Johns Hopkins University | Mao X.-G.,PLA Fourth Military Medical University | Hutt-Cabezas M.,Johns Hopkins University | Orr B.A.,Johns Hopkins University | And 12 more authors.
Oncotarget | Year: 2013

The cellular reprogramming factor LIN28A promotes tumorigenicity in cancers arising outside the central nervous system, but its role in brain tumors is unknown. We detected LIN28A protein in a subset of human gliomas observed higher expression in glioblastoma (GBM) than in lower grade tumors. Knockdown of LIN28A using lentiviral shRNA in GBM cell lines inhibited their invasion, growth and clonogenicity. Expression of LIN28A in GBM cell lines increased the number and size of orthotopic xenograft tumors. LIN28A expression also enhanced the invasiveness of GBM cells in vitro and in vivo. Increasing LIN28A was associated with down-regulation of tumor suppressing microRNAs let-7b and let-7g and up-regulation of the chromatin modifying protein HMGA2. The increase in tumor cell aggressiveness in vivo and in vitro was accompanied by an upregulation of pro-invasive gene expression, including SNAI1. To further investigate the oncogenic potential of LIN28A, we infected hNSC with lentiviruses encoding LIN28A together with dominant negative R248W-TP53, constitutively active KRAS and hTERT. Resulting subclones proliferated at an increased rate and formed invasive GBM-like tumors in orthotopic xenografts in immunodeficient mice. Similar to LIN28A-transduced GBM neurosphere lines, hNSC-derived tumor cells showed increased expression of HMGA2. Taken together, these data suggest a role for LIN28A in high grade gliomas and illustrate an HMGA2-associated, pro-invasive program that can be activated in GBM by LIN28A-mediated suppression of let-7 microRNAs.

PubMed | University Medical Center Duesseldorf, Johns Hopkins Hospital, Albert Ludwigs University of Freiburg, University Medical Center Erlangen and Bahcesehir University
Type: | Journal: Experimental & translational stroke medicine | Year: 2014

Although there are many experimental studies describing the methodology of the middle cerebral artery occlusion (MCAO) in the literature, only limited data on these distinct anatomical structures and the details of the surgical procedure in a step by step manner. The aim of the present study simply is to examine the surgical anatomy of MCAO model and its modifications in the rat.Forty Sprague-Dawley rats were used; 20 during the training phase and 20 for the main study. The monofilament sutures were prepared as described in the literature. All surgical steps of the study were performed under the operating microscope, including insertion of monofilament into middle cerebral artery through the internal carotid artery.After an extensive training period, we lost two rats in four weeks. The effects of MCAO were confirmed by the evidence of severe motor deficit during the recovery period, and histopathological findings of infarction were proved in all 18 surviving rats.In this study, a microsurgical guideline of the MCAO model in the rat is provided with the detailed description of all steps of the intraluminal monofilament insertion method with related figures.

Keil T.,Charité - Medical University of Berlin | Bockelbrink A.,Charité - Medical University of Berlin | Reich A.,Charité - Medical University of Berlin | Hoffmann U.,TU Munich | And 6 more authors.
Pediatric Allergy and Immunology | Year: 2010

The distinction between 'seasonal' and 'perennial' allergic rhinitis (AR) is not always adequate. The 'Allergic Rhinitis and its Impact on Asthma' (ARIA) work group suggested a new classification for AR based on severity and duration of symptoms. Our primary aim was to describe the natural history and burden of AR according to the new ARIA criteria in a population-based birth cohort study of children up to 13 yr. We defined symptoms as 'severe' (impairment of daily activities) or 'mild' (no impairment) and 'persistent' (duration > 1 month) or 'intermittent' (≤1 month) using annual questionnaires. Serum immunoglobulin E to five common aero-allergens was determined at six time points. We analyzed complete follow-up data from 467 children (54% boys). The 12-month prevalence of AR quadrupled from 6% (at age 3 yr) to 24% (at age 13 yr) in children with non-allergic parents and more than tripled from 13% (3 yr) to 44% (13 yr) in children with at least one allergic parent. Half or more of the children with AR had 'severe persistent' symptoms. At age 13, these children were significantly more often sensitized than those with 'mild persistent' disease: 91% vs. 70% (p = 0.015). Sensitization to aero-allergens (adjusted OR 18.9; 95%CI 9.3-38.4) and having 2 parents with allergy (3.1; 1.1-9.3) were significantly associated with AR. According to the ARIA criteria, the impact of AR seems to be substantial; the vast majority of affected children suffered persistently for periods of 2 months or more annually, and most of the children with persistent AR were impaired in their daily activities. © 2010 John Wiley & Sons AS.

Mohseny A.B.,Leiden University | MacHado I.,University of Valencia | Cai Y.,Leiden University | Cai Y.,Shandong University | And 5 more authors.
Laboratory Investigation | Year: 2011

Cancer cell lines represent in vitro models for studying malignancies, general cell biology, drug discovery and more. Whether they can be considered as exact representative models of the parental tumors remains uncertain given the acquisition of additional ex vivo changes of the cells and the lack of tissue architecture and stroma. Previously, within the EuroBoNeT consortium, we characterized a collection of bone sarcoma cell lines on genomic and proteomic level. Here, we address the phenotypical and functional characterization of the unique set of osteosarcoma cell lines (n19) in vitro and in vivo. For functional analysis of differentiation capacity, cells were stimulated towards osteoblasts, adipocytes and chondrocytes. Furthermore, all cell lines were injected subcutaneously and intramuscularly into nude mice to assay their in vivo tumor formation capacity as well as for phenotypical analysis of the tumors. All formed tumors were further characterized histologically and immunohistochemically. Out of 19 cell lines, 17 (89%) showed adipogenic differentiation, 13/19 (68%) could differentiate towards osteoblasts and in 6/19 (32%) cell lines chondrogenic differentiation was evident. About half of the cell lines (8/19, 42%) produced tumors in vivo after subcutaneous and intramuscular injections. Several cell lines showed invasion into adjacent tissues and one tumor developed several lung metastases. The use of cell lines, especially in cancer research, is of paramount importance. Here, we identify comprehensively characterized osteosarcoma cell lines, which robustly represent clinical osteosarcoma providing researchers useful in vitro and in vivo models to study the genetics and functional characteristics of this highly malignant neoplasm. © 2011 USCAP, Inc All rights reserved.

Stein J.,University of Leipzig | Luppa M.,University of Leipzig | Maier W.,University of Bonn | Tebarth F.,University of Bonn | And 15 more authors.
Dementia and Geriatric Cognitive Disorders | Year: 2012

Background/Aims: The diagnostic criteria for dementia include reliable evidence of cognitive deterioration over time measured by cognitive tests. The Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, Multi-infarct Dementia and Dementia of other Etiology according to DSM-III-R, DSM-IV and ICD-10 (SIDAM) is a neuropsychological instrument to determine cognitive status in patients with mild cognitive impairment (MCI) and dementia. Normative data for changes in cognitive functioning that normally occur in cognitively healthy individuals are required to interpret changes in SIDAM test scores. Methods: A sample of 1,090 cognitively healthy individuals participating in the German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe) aged 75 years and older was assessed four times at 1.5-year intervals over a period of 4.5 years using the SIDAM. Age- and education-specific reliable change indices (RCIs) accounting for probable measurement error and practice effects were computed for a 90% confidence interval. Results: Across different age and education subgroups, changes from at least 3-5 points indicated significant (i.e. reliable) changes in SIDAM test scores at the 90% confidence level. Conclusion: This study offers age- and education-specific normative data for the SIDAM based upon established RCI methods. The RCI scores provided in this study may help clinicians and researchers to interpret cognitive changes in SIDAM test scores and may contribute to the early detection and diagnosis of MCI and dementia in the elderly. Copyright © 2012 S. Karger AG, Basel.

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