Friederike Göke's research while affiliated with University of Bonn and other places

Encephalitis is often caused by viral infections and can affect various brain regions. The clinical symptoms are highly variable. Oligosymptomatic cerebral infections may remain undetected but there are also cases with very severe symptoms (e.g. paralysis, convulsions). This article presents the case of an 8-year-old girl who suffered from headaches and vomiting for several days following a harmless fall with impact on the back of the head. The health condition decreased rapidly and 7 days after the fall the girl was presented to a children's hospital. After a further foudroyant course of the disease the girl was hospitalized 2 days later. Resuscitation became necessary due to convulsions and pulmonary obstruction. Cranial computed tomography (cCT) revealed temporal hypodense areas and local edema. Cardiac echocardiography revealed a decreased left ventricular pump function so that encephalitis and myocarditis were suspected. Despite antiviral and antibiotic therapy the girl died 4 days after admission due to intravital brain death and multiorgan failure. This cause of death was confirmed by forensic autopsy. The fall had not led to any intracranial injury and predisposing diseases were not found. Histological examination revealed necrotizing brainstem encephalitis. © Springer-Verlag 2012.

Background: We previously identified amplification of the fibroblast growth factor receptor 1 gene (FGFR1) as a potential therapeutic target for small-molecule inhibitor therapy in squamous cell lung cancer (L-SCC). Currently, clinical phase I trials are underway to examine whether patients with FGFR1-amplified L-SCC benefit from a targeted therapy approach using small-molecule inhibitors. Because most patients with lung cancer present with metastatic disease, we investigated whether lymph node metastases in L-SCC share the FGFR1 amplification status of their corresponding primary tumor. Methods: The study cohort consisted of 72 patients with L-SCC, 39 with regional lymph node metastases. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tissue of the primary tumors and, where present, of the corresponding lymph node metastasis. A biotin-labeled target probe spanning the FGFR1 locus (8p11.22-23) was used to determine the FGFR1 amplification status by fluorescence in situ hybridization. Results: FGFR1 amplification was detected in 16% (12 of 72) of all primary L-SCCs. In metastatic tumors, 18% (seven of 39) of the lymph node metastases displayed FGFR1 amplification with an exact correlation of FGFR1 amplification status between tumor and metastatic tissue. Conclusions: FGFR1 amplification is a common genetic event occurring at a frequency of 16% in L-SCCs. Moreover, lymph node metastases derived from FGFR1-amplified L-SCCs also exhibit FGFR1 amplification. Therefore, we suggest that the FGFR1 amplification is a clonal event in tumor progression. Beyond this biologically relevant observation, the findings carry potential therapeutic implications in that small-molecule inhibitors may be applicable to the treatment of a subset of patients with metastatic L-SCC.

The tumor suppressor Pdcd4 is involved in multiple pathways. Considering its biological action conflicting data in the literature exist and, consequently, our own studies point to a cell type specific action of Pdcd4. In the present study, using several Pdcd4 knock down cell lines we succeeded to identify angiopoietin-2 (Ang-2) as a gene up-regulated on the mRNA and protein level. The subsequent enhanced peptide secretion forced wild type Bon-1 cells in a neoplastic direction demonstrated by increased proliferation and colony formation while cell adhesion was decreased. Most likely, the stimulation of Ang-2 is in part mediated by increased activation of AP-1 but different signal transduction pathways may also be involved since we found opposite activation of PI3K/Akt/mTOR and MAPK7ERK pathways (both known to regulate in Ang-2 expression). Ang-2 is a modulator of vascular remodeling. Therefore, we analyzed the effect of supernatants from Pdcd4 knock-down cell lines on endothelial cells. Again, we detected reduced cell adhesion and increased colony formation. Probably, the most impressive effect was described on tube formation in a model for angiogenesis. Tube length and junctions of endothelial cells treated with conditioned medium from Pdcd4 knock-down cells were considerably increased. Both, up-regulation of Ang-2 and down-regulation of Pdcd4 are described for many tumors. However, this is the first study showing a direct impact of Pdcd4 on Ang-2 levels and, thereby, angiogenesis. Our data suggest a completely new mechanism for Pdcd4 to act as a tumor suppressor rendering Pdcd4 an attractive target for new therapeutic strategies in cancer treatment.

We investigated the role of the programmed cell death 4 (PDCD4) tumor suppressor gene in specimens of transitional cell carcinoma and of healthy individuals. PDCD4 immunohistochemical expression was investigated in 294 cases in histologically proven transitional cell carcinoma in different tumorous stages (28 controls, 122 non-muscle invasive urothelial carcinoma, stages Tis-T1, 119 invasive transitional cell carcinoma stages T2-T4 and 25 metastases). MiR-21 expression, an important PDCD4 regulator, was assessed with real-time PCR analysis and showed inverse correlation to tissue PDCD4 expression. Nuclear and cytoplasmatic PDCD4 immunostaining decreased significantly with histopathological progression of the tumor (p<0001). Controls showed strong nuclear and cytoplasmatic immunohistochemical staining. MiR-21 up regulation in tissue corresponded to PDCD4 suppression. These data support a decisive role for PDCD4 down regulation in transitional cell carcinoma and confirm miR-21 as a negative regulator for PDCD4. Additionally, PDCD4 immunohistochemical staining turns out to be a possible diagnostic marker for transitional cell carcinoma.

In Germany tuberculosis has a decreasing incidence. The lung is the most common focus, whereas head and neck manifestation occurs rarely. Between 1997 and 2010 all patients with initial diagnosis of tuberculosis of the head and neck region were retrospectively reviewed at the University Hospital of Bonn, Germany. 38 patients (24 female, 14 male, median age 43.5±19.7 years) were analysed. More than 60%  were of foreign nationality. The majority of patients (87% ) presented with an unspecific cervical lymph node swelling. Extranodular manifestations (maxillary sinus, middle ear, larynx, tonsil) leading to organ specific symptoms rarely occurred. In only 3 cases a mycobacterial infection was suspected before surgery. Only the knowledge of different manifestation patterns as well as an accurate anamnesis of infectious diseases can lead to the tentative diagnosis of tuberculosis prior to surgery.