Stefan Gattenlöhner

Justus-Liebig-Universität Gießen, Gieben, Hesse, Germany

Are you Stefan Gattenlöhner?

Claim your profile

Publications (102)419.16 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The prevalence of systemic atherosclerosis and overactive bladder (OAB)/detrusor overactivity (DO) increases almost simultaneously with age, but an association between these diseases is not yet proven. We aimed to evaluate changes in bladder function and morphology, including vascularization, in apoE(-/-)LDLR(-/-) double knockout mice suffering from systemic atherosclerosis, but without involvement of the central nervous system.
    The Journal of urology. 08/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: A possible approach to objectively classify complex patterns in tumor tissue is a mathematical and statistical investigation of the distribution of cell nuclei as a geometric representation of cancer cells by fractal dimensions. Both the existence and changes in the fractal structure of tumor tissue have important consequences for the objective system of tumor grading. In addition, the complexity of growth in different carcinomas or their intercellular interactions can be compared to each other.
    Der Urologe. Ausg. A. 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Significant intra- and interobserver variability ranging between 40 and 80% is observed in tumor grading of prostate carcinoma. By combining geometric and statistical methods, an objective system of grading can be designed.
    Der Urologe. Ausg. A. 07/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The treatment of rhabdomyosarcoma (RMS) remains challenging, with metastatic and alveolar RMS offering a particularly poor prognosis. Therefore, the identification and evaluation of novel antigens, which are suitable targets for immunotherapy, is one attractive possibility to improve the treatment of this disease. Here we show that chondroitin sulfate proteoglycan 4 (CSPG4) is expressed on RMS cell lines and RMS patient material. We evaluated the immunotoxin (IT) αMCSP-ETA', which specifically recognizes CSPG4 on the RMS cell lines RD, FL-OH1, TE-671 and Rh30. It is internalized rapidly, induces apoptosis and thus kills RMS cells selectively. We also demonstrate the specific binding of this IT to RMS primary tumor material from three different patients.
    Cancer letters. 07/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Myelodysplastic syndromes (MDS) are hematopoietic disorders characterized by ineffective hematopoiesis and progression to acute leukemia. In patients ineligible for hematopoietic stem cell transplantation, azacitidine is the only treatment shown to prolong survival. However, with the availability of a growing compendium of cancer biomarkers and related drugs, analysis of relevant genetic alterations for individual MDS patients might become part of routine evaluation. Therefore and in order to cover the entire bone marrow microenvironment involved in the pathogenesis of MDS, SNP array analysis and targeted next generation sequencing (tNGS) for the mostly therapy relevant 46 onco- and tumor-suppressor genes were performed on bone marrow biopsies from 29 MDS patients. In addition to the detection of mutations known to be associated with MDS in NRAS, KRAS, MPL, NPM1, IDH1, PTPN11, APC and MET, single nucleotide variants so far unrelated to MDS in STK11 (n = 1), KDR (n = 3), ATM (n = 1) and JAK3 (n = 2) were identified. Moreover, a recurrent microdeletion was detected in Xq26.3 (n = 2), causing loss of PHF6 expression, a potential tumor suppressor gene, and the miR-424, which is involved in the development of acute myeloid leukemia. Finally, combined genetic aberrations affecting the VEGF/VEGFR pathway were found in the majority of cases demonstrating the diversity of mutations affecting different nodes of a particular signaling network as an intrinsic feature in MDS patients. We conclude that combined SNP array analyses and tNGS can identify established and novel therapy relevant genomic aberrations in MDS patients and track them in a clinical setting for individual therapy selection.
    Pathology - Research and Practice 01/2014; · 1.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ewing sarcoma, the second most common bone tumor in children and young adults, is an aggressive malignancy with a strong potential to metastasize. Ewing sarcoma is characterised by translocations encoding fusion transcription factors with an EWSR1 transactivation domain fused to an ETS family DNA binding domain. microRNAs are post-transcriptional regulators of gene expression and aberrantly expressed microRNAs have been identified as tumor suppressors or oncogenes in most cancer types. To identify potential oncogenic and tumor suppressor microRNAs in Ewing sarcoma, we determined and compared the expression of 377 microRNAs in 40 Ewing sarcoma biopsies, 6 Ewing sarcoma cell lines and mesenchymal stem cells, the putative cellular origin of Ewing sarcoma, from 6 healthy donors. Of the 35 differentially expressed microRNAs identified (fold change >4 and q<0.05), 19 were higher and 16 lower expressed in Ewing sarcoma. In comparisons between Ewing sarcoma samples with EWS-FLI or EWS-ERG translocations, with differing dissemination characteristics and of primary samples and metastases no significantly differential expressed microRNAs were detected using various stringency criteria. For miR-31, the microRNA with lowest expression in comparison to mesenchymal stem cells, functional analyses were performed to determine its potential as a tumor suppressor in Ewing sarcoma. Two of four miR-31 transfected Ewing sarcoma cell lines showed a significantly reduced proliferation (19% and 33% reduction) due to increased apoptosis in one and increased length of G1-phase in the other cell line. All three tested miR-31 transfected Ewing sarcoma cell lines showed significantly reduced invasiveness (56% to 71% reduction). In summary, we identified 35 microRNAs differentially expressed in Ewing sarcoma and demonstrate that miR-31 affects proliferation and invasion of Ewing sarcoma cell lines in ex vivo assays.
    PLoS ONE 01/2014; 9(3):e93067. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report the case of a 67 year old female patient with a multifocal colonic adenocarcinoma (pT3 N0 L0 V0 G2 R0 and pT1 N0 L0 V0 G2 R0) (Figure 1a) with classical histological morphology and immunohistochemical phenotype (CK7-, CK20+, CDX2+ TTF1-). During staging two lesions in the right and the left lung each suspicious of beeing primary/metastatic carcinomas were detected and after right-sided upper lobectomy an additional bronchopulmonary adenocarcinoma (pT1a N1a L1 V0 G2 R0) (Figure 1a) with expression of "lung-specific" immunomarkers (CK7+, CK20-, CDX2-, TTF1+) was identified. By contrast histological examination of the left-sided lung tumor revealed a biphenotypic adenocarcinoma with tubular and mucinous differentiation (Figures 1b-d), a "lung-specific" immunoprofile in tubular areas (CK7+, CK20-, CDX2-, TTF1+) (Figure 1e), and a pattern compatible with bronchopulmonary mucinous adenocarcinoma (CK7+, CK20+, TTF1-) in the mucinous tumor parts (Figure 1f), suggesting an intrapulmonal metastasis of the right-sided bronchopulmonary adenocarcoinoma. This article is protected by copyright. All rights reserved.
    Histopathology 12/2013; · 2.86 Impact Factor
  • Journal of Clinical Oncology 04/2013; · 18.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cellular immunotherapy may provide a strategy to overcome the poor prognosis of metastatic and recurrent rhabdomyosarcoma (RMS) under the current regimen of polychemotherapy. Because little is known about resistance mechanisms of RMS to cytotoxic T cells, we investigated RMS cell lines and biopsy specimens for expression and function of immune costimulatory receptors and anti-apoptotic molecules by RT-PCR, Western blot analysis, IHC, and cytotoxicity assays using siRNA or transfection-modified RMS cell lines, together with engineered RMS-directed cytotoxic T cells specific for the fetal acetylcholine receptor. We found that costimulatory CD80 and CD86 were consistently absent from all RMSs tested, whereas ICOS-L was expressed by a subset of RMSs and was inducible by tumor necrosis factor α in two of five RMS cell lines. Anti-apoptotic survivin, along with other inhibitor of apoptosis (IAP) family members (cIAP1, cIAP2, and X-linked inhibitor of apoptosis protein), was overexpressed by RMS cell lines and biopsy specimens. Down-regulation of survivin by siRNA or pharmacologically in RMS cells increased their susceptibility toward a T-cell attack, whereas induction of ICOS-L did not. Treatment of RMS-bearing Rag(-/-) mice with fetal acetylcholine receptor-specific chimeric T cells delayed xenograft growth; however, this happened without definitive tumor eradication. Combined blockade of survivin and application of chimeric T cells in vivo suppressed tumor proliferation during survivin inhibition. In conclusion, survivin blockade provides a strategy to sensitize RMS cells for T-cell-based therapy.
    American Journal Of Pathology 04/2013; · 4.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although current cancer treatment strategies are highly aggressive, they are often not effective enough to destroy the collectivity of malignant cells. The residual tumor cells that survived the first-line treatment may continue to proliferate or even metastasize. Therefore, the development of novel more effective strategies to specifically eliminate also single cancer cells is urgently needed. In this respect, the development of antibody-based therapeutics, in particular example immunotoxins, has attracted broad interest. Since the internalization of immunotoxins is essential for their cytotoxic effectivity, it is of crucial importance to study their internalization behavior to assess the potential for their therapeutic use. In this study, we determined the internalization behavior of four different single-chain fragments variable (scFv) when binding to the corresponding target antigen as expressed on solid or non-solid tumor cell lines. The scFvs were recombinantly fused to the SNAP-tag, an engineered variant of the human repair enzyme O6-alkylguanine-DNA alkyltransferase that covalently reacts with benzylguanine derivatives. Since a large number of highly sensitive organic fluorescent dyes are already available or can easily be derivatized to react with the self-labeling SNAP-tag, this system provides versatile applications for imaging of intra- and extracellular compartments of living cells. The fusion proteins were coupled to SNAP-surface® Alexa Fluor® 488 or SNAP-surface® Alexa Fluor® 647 and binding as well as internalization was monitored by flow cytometry and confocal microscopy, respectively. Depending on the respective target antigen, we could distinguish between slow and rapid internalization behavior. Moreover, we detected increased internalization rate for bivalent scFv constructs. Our approach allows for rapid and early stage evaluation of the internalization characteristics of new antibodies designated for further therapeutic development.
    Current pharmaceutical design 02/2013; · 4.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite recent advances in understanding the relevance of cell adhesion-related signaling in the pathogenesis of ischemic cardiomyopathy (ICM) in animal models, substantial questions remain unanswered in the human setting. We have previously shown that the neural cell adhesion molecule CD56 [neural cell adhesion molecule (NCAM1)] is specifically overexpressed in ICM; it was the aim of the current study to further elucidate the role of CD56 in the pathogenesis of human ICM. We used quantitative real-time PCR and IHC in human ICM and a rat model of coronary obstruction to demonstrate that CD56140kD, the only extraneuronally expressed NCAM1 isoform with a cytoplasmic protein domain capable of inducing intracellular signaling, is the only up-regulated CD56 isoform in failing cardiomyocytes in human ICM in vivo. In subsequent analyses of the cellular effects of CD56140kD overexpression in the development of ICM using differential whole transcriptome expression analyses and functional in vitro cardiomyocyte cell culture assays, we further show that the up-regulation of CD56140kD is associated with profound gene expression changes, increased apoptosis, and reduced Ca2+ signaling in failing human cardiomyocytes. Because apoptosis and Ca2+-related sarcomeric dysfunction are molecular hallmarks of ICM in humans, our results provide strong evidence that CD56140kD up-regulation plays a pivotal role in the pathogenesis of ICM and may be a target for future immunotherapeutic strategies in the treatment of this common and often fatal disease.
    American Journal Of Pathology 02/2013; · 4.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Influenza viruses (IV) cause pneumonia in humans with progression to lung failure and fatal outcome. Dysregulated release of cytokines including type I interferons (IFNs) has been attributed a crucial role in immune-mediated pulmonary injury during severe IV infection. Using and IV infection models, we demonstrate that alveolar macrophage (AM)-expressed IFN-β significantly contributes to IV-induced alveolar epithelial cell (AEC) injury by autocrine induction of the pro-apoptotic factor TNF-related apoptosis-inducing ligand (TRAIL). Of note, TRAIL was highly upregulated in and released from AM of patients with pandemic H1N1 IV-induced acute lung injury. Elucidating the cell-specific underlying signalling pathways revealed that IV infection induced IFN-β release in AM in a protein kinase R- (PKR-) and NF-κB-dependent way. Bone marrow chimeric mice lacking these signalling mediators in resident and lung-recruited AM and mice subjected to alveolar neutralization of IFN-β and TRAIL displayed reduced alveolar epithelial cell apoptosis and attenuated lung injury during severe IV pneumonia. Together, we demonstrate that macrophage-released type I IFNs, apart from their well-known anti-viral properties, contribute to IV-induced AEC damage and lung injury by autocrine induction of the pro-apoptotic factor TRAIL. Our data suggest that therapeutic targeting of the macrophage IFN-β-TRAIL axis might represent a promising strategy to attenuate IV-induced acute lung injury.
    PLoS Pathogens 02/2013; 9(2):e1003188. · 8.14 Impact Factor
  • E Roeb, T Dreyer, D Steiner, A Bräuninger, S Gattenlöhner
    [Show abstract] [Hide abstract]
    ABSTRACT: A 75-year-old woman was found to have left-sided pleural effusion and endoscopy revealed the rare entity of adenoid cystic carcinoma metastases in the gastric mucosa. Approximately 20 % of patients with this carcinoma suffer from distant metastases. For the initial staging detection of adenoid cystic carcinoma metastasis with positron emission tomography (PET) or PET computed tomography (CT) is recommended. The recurrent t(6;9)(q22-23;p23-24) translocation that results in a fusion of the two transcription factor genes MYB and NFIB is detectable in half of the cases. As in our case molecular pathology can confirm the correct diagnosis and identification of the localization of the primary tumor.
    Der Internist 12/2012; · 0.33 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The extracardiac juvenile rhabdomyoma is extremely rare in the field of Otorhinolaryngology. The tumour usually arises from the soft tissue of the face or from mucosal sites, especially the oropharynx and the oral cavity but only sporadic endolaryngeal cases have been described in literature so far with predominance of young males. Here, we describe the very rare case of endolaryngeal extracardiac juvenile rhabdomyoma in a 42-year-old male. Clinical examination showed a mass of the right vocal cord, resembling a cystic lesion. Microlaryngoscopy revealed a non-encapsulated lesion and histopathology including immunohistochemistry which consecutively led to the correct diagnosis. This case suggests that the endolaryngeal extracardiac juvenile rhabdomyoma can be easily confused with a vocal cord cyst. Malignant transformations have not been reported but recurrences have been described. When total excision cannot be accomplished, reoperation or narrow follow-up is indicated to prevent advanced revision surgeries.
    Archives of Oto-Rhino-Laryngology 11/2012; · 1.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Influenza viruses (IVs) cause pneumonia in humans with progression to lung failure. Pulmonary DCs are key players in the antiviral immune response, which is crucial to restore alveolar barrier function. The mechanisms of expansion and activation of pulmonary DC populations in lung infection remain widely elusive. Using mouse BM chimeric and cell-specific depletion approaches, we demonstrated that alveolar epithelial cell (AEC) GM-CSF mediates recovery from IV-induced injury by affecting lung DC function. Epithelial GM-CSF induced the recruitment of CD11b+ and monocyte-derived DCs. GM-CSF was also required for the presence of CD103+ DCs in the lung parenchyma at baseline and for their sufficient activation and migration to the draining mediastinal lymph nodes (MLNs) during IV infection. These activated CD103+ DCs were indispensable for sufficient clearance of IVs by CD8+ T cells and for recovery from IV-induced lung injury. Moreover, GM-CSF applied intratracheally activated CD103+ DCs, inducing increased migration to MLNs, enhanced viral clearance, and attenuated lung injury. Together, our data reveal that GM-CSF-dependent cross-talk between IV-infected AECs and CD103+ DCs is crucial for effective viral clearance and recovery from injury, which has potential implications for GM-CSF treatment in severe IV pneumonia.
    The Journal of clinical investigation 09/2012; 122(10):3652-64. · 15.39 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The frozen section procedure for immediate intraoperative pathological diagnosis represents a pivotal method in tumor diagnosis. In laryngeal tumors the most frequent indication for the use of this method is the documentation of the residual tumor status, while intraoperative consultation with the purpose of primary tumor diagnosis is less common. The specimen management employed in each case should be chosen depending on the clinical question: while the collection of a maximum amount of tissue is advisable for the determination of the residual tumor status, sparing a portion of the remaining tissue for possible future examinations is advisable in the case of primary tumor diagnosis. Moreover, intraoperative frozen section diagnosis with no immediate consequences should be avoided.
    Der Pathologe 08/2012; 33(5):397-401. · 0.62 Impact Factor
  • Elke Roeb, Benjamin Etschmann, Stefan Gattenlöhner
    Gastroenterology 05/2012; 143(1):e7-8. · 12.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ras association domain family (RASSF) comprises several tumor suppressor genes, which are often epigenetically inactivated in human tumors. Here, we aim to analyze the relevance of the recently identified member RASSF10 in prostate carcinogenesis. RASSF10 promoter methylation and mRNA expression were investigated by bisulfite-pyrosequencing and qRT-PCR, respectively, in prostate carcinoma (PCa) cell lines (LNCaP, 22Rv1, DU-145) and in 83 primary PCa and 53 primary benign prostatic hyperplasia (BPH) tissues obtained after radical prostatectomy. Histological localization of RASSF10 was done by in situ hybridization. To prove the epigenetic nature of RASSF10 down regulation, PCa cell lines were treated with 5-aza-2-deoxycytidine and trichostatin A. Potential function of RASSF10 was analyzed in LNCaP by colony formation and apoptosis assays. RASSF10 mRNA was localized to cells of the basal layer of the prostatic gland. Absence (LNCaP) and decrease (22Rv1, DU-145) of RASSF10 expression was associated with promoter methylation and could be restored by demethylating agents. A link between RASSF10 mRNA reduction and promoter methylation was also detected in primary prostate tissues (P = 0.006), where PCa showed more frequently reduced RASSF10 levels when compared with BPH (33.7% vs. 13.2%, P = 0.009). RASSF10 methylation could be further associated with advanced tumor stage and advanced age (P-values < 0.05). Our preliminary functional assays revealed the ability of RASSF10 to inhibit colony formation (P = 0.018) and to increase apoptosis (P = 0.035). This is the first study, which demonstrates the frequent epigenetic inactivation of RASSF10 in PCa and its implication in clinical symptoms of PCa.
    The Prostate 03/2012; 72(14):1550-8. · 3.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The overall prognosis of chordoma is poor, and current treatment options are limited. The insulin-like growth factor 1 receptor (IGF-1R) pathway is important for cell signalling, and attractive for selective inhibition. We investigated the expression of IGF-1R and its ligands, IGF-1 and IGF-2, in a series of 50 chordomas, in order to assess whether IGF-1R-signalling could be a potential target for specific inhibition in chordomas. Fifty chordomas (34 primary tumours, 16 recurrences) from 44 patients were evaluated immunohistochemically for the expression of IGF-1R, IGF-1 and IGF-2. Thirty-eight chordomas (76%) expressed IGF-1R, 46 (92%) expressed IGF-1 and 25 (50%) expressed IGF-2. Semi-quantitative analyses revealed a moderate to strong staining intensity in ≥ 50% of tumour cells for IGF-1R, IGF-1 and IGF-2 in 18 (36%), 32 (64%) and eight (16%) chordomas, respectively. Tumour volume correlated significantly with IGF-1R-staining intensity in primary chordomas (P = 0.042). IGF-1R and IGF-1 are expressed in the majority of chordomas. IGF-1 expression is much stronger than IGF-2 expression. Patients whose chordomas show a moderate to strong staining intensity in ≥ 50% of tumour cells for IGF-1R (36%) might benefit most from IGF-1R targeting, particularly if they suffer from large and surgically non-resectable chordomas.
    Histopathology 02/2012; 60(6):999-1003. · 2.86 Impact Factor
  • U Schedelbeck, S Gattenlöhner, D Hahn, C O Ritter
    [Show abstract] [Hide abstract]
    ABSTRACT: A 53-year-old female patient presented with splenomegaly, uncertain lesions of the spleen, pancytopenia and suspected aortitis. Reduced strength and muscular pain but no B symptoms were also present. Alterations of the spleen had been known for a long time. Blood examination, laboratory tests and magnetic resonance imaging (MRI) confirmed an aortitis. Concerning the splenic changes neither ultrasound nor MRI could provide conclusive or even pathognomonic findings. Because of an existing pancytopenia and diagnostic obscurity, the patient underwent splenectomy. The histological diagnosis was finally concluded as multifocal littoral cell angioma.
    Der Radiologe 02/2012; 52(3):263-6. · 0.47 Impact Factor

Publication Stats

779 Citations
419.16 Total Impact Points

Institutions

  • 2011–2014
    • Justus-Liebig-Universität Gießen
      • • Institut für Parasitologie
      • • Department of Internal Medicine
      Gieben, Hesse, Germany
  • 2013
    • Vitos Gießen-Marburg
      Gieben, Hesse, Germany
  • 2011–2013
    • Universitätsklinikum Gießen und Marburg
      Marburg, Hesse, Germany
  • 2010–2013
    • Universität Heidelberg
      • • Institute of Papyrology
      • • Institute of Pathology (Mannheim)
      Heidelberg, Baden-Wuerttemberg, Germany
    • Medical University of Graz
      • Institut für Pathologie
      Graz, Styria, Austria
  • 1994–2012
    • University of Wuerzburg
      • Institute for Pathology
      Würzburg, Bavaria, Germany