Tagungsbericht: "Den Holocaust erzählen? Historiographie zwischen wissenschaftlicher Empirie und narrativer Kreativität." : Symposium auf dem Alten Schloss Dornburg bei Jena, 9. bis 11. Juni 2011

Im Jahr 2006 brachte Saul Friedländer seine weithin beachtete Gesamtdarstellung „Nazi Germany and the Jews“ mit dem zweiten Band „The Years of Extermination“ zum Abschluss. Das Buch lese sich wie ein Roman, so und ähnlich urteilten Rezensenten über dessen literarische Qualitäten. Auf erzählerische Stärken verweisen auch Kommentare zu Christopher Brownings jüngster Studie „Remembering Survival“ (2010). Das Erzählen in der Geschichtswissenschaft ist seit längerem wieder Gegenstand der Diskussion: Forscherinnen und Forscher auf einem Symposium auf dem Alten Schloss Dornburg bei Jena gingen im Juni 2011 dieser Frage speziell für den Bereich der Holocaust-Historiographie nach

Prediction of regulatory targets of alternative isoforms of the epidermal growth factor receptor in a glioblastoma cell line.

BackgroundThe epidermal growth factor receptor (EGFR) is a major regulator of proliferation in tumor cells. Elevated expression levels of EGFR are associated with prognosis and clinical outcomes of patients in a variety of tumor types. There are at least four splice variants of the mRNA encoding four protein isoforms of EGFR in humans, named I through IV. EGFR isoform I is the full-length protein, whereas isoforms II-IV are shorter protein isoforms. Nevertheless, all EGFR isoforms bind the epidermal growth factor (EGF). Although EGFR is an essential target of long-established and successful tumor therapeutics, the exact function and biomarker potential of alternative EGFR isoforms II-IV are unclear, motivating more in-depth analyses. Hence, we analyzed transcriptome data from glioblastoma cell line SF767 to predict target genes regulated by EGFR isoforms II-IV, but not by EGFR isoform I nor other receptors such as HER2, HER3, or HER4.ResultsWe analyzed the differential expression of potential target genes in a glioblastoma cell line in two nested RNAi experimental conditions and one negative control, contrasting expression with EGF stimulation against expression without EGF stimulation. In one RNAi experiment, we selectively knocked down EGFR splice variant I, while in the other we knocked down all four EGFR splice variants, so the associated effects of EGFR II-IV knock-down can only be inferred indirectly. For this type of nested experimental design, we developed a two-step bioinformatics approach based on the Bayesian Information Criterion for predicting putative target genes of EGFR isoforms II-IV. Finally, we experimentally validated a set of six putative target genes, and we found that qPCR validations confirmed the predictions in all cases.ConclusionsBy performing RNAi experiments for three poorly investigated EGFR isoforms, we were able to successfully predict 1140 putative target genes specifically regulated by EGFR isoforms II-IV using the developed Bayesian Gene Selection Criterion (BGSC) approach. This approach is easily utilizable for the analysis of data of other nested experimental designs, and we provide an implementation in R that is easily adaptable to similar data or experimental designs together with all raw datasets used in this study in the BGSC repository, https://github.com/GrosseLab/BGSC

Patient information in radiation oncology: a cross-sectional pilot study using the EORTC QLQ-INFO26 module

<p>Abstract</p> <p>Background</p> <p>The availability of alternative sources of information, e. g. the internet, may influence the quantity and quality of information cancer patients receive regarding their disease and treatment. The purpose of the present study was to assess perception of information in cancer patients during radiotherapy as well as media preferences and specifically the utilization of the internet.</p> <p>Methods</p> <p>In a cross-sectional, single-centre study 94 patients currently undergoing radiotherapy were asked to complete two questionnaires. The EORTC QLQ-INFO26 module was used to assess the quality and quantity of information received by patients in the areas disease, medical tests, treatment, other services, different places of care and how to help themselves, as well as qualitative aspects as helpfulness of and satisfaction with this information. The importance of different media, in particular the internet, was investigated by a nine-item questionnaire.</p> <p>Results</p> <p>The response rate was n = 72 patients (77%). Patients felt best informed concerning medical tests (mean ± SD score 79 ± 22, scale 0-100) followed by disease (68 ± 21). Treatment (52 ± 24) and different places of care and other services (30 ± 36 and 30 ± 30, respectively) ranked last. 37% of patients were very satisfied and 37% moderately satisfied with the amount of information received, 61% wished more information. Among eight media, brochures, television and internet were ranked as most important. 41% used the internet themselves or via friends or family, mostly for research of classic and alternative treatment options. Unavailability and the necessity of computer skills were most mentioned obstacles.</p> <p>Conclusion</p> <p>In a single-center pilot study, radiotherapy patients indicated having received most information about medical tests and their disease. Patients very satisfied with their information had received the largest amount of information. Brochures, television and internet were the most important media. Individual patient needs should be considered in the development of novel information strategies.</p

Absence of GAPDH regulation in tumor-cells of different origin under hypoxic conditions in – vitro

<p>Abstract</p> <p>Background</p> <p>Gene expression studies related to cancer diagnosis and treatment are important. In order to conduct such experiment accurately, absolutely reliable housekeeping genes are essential to normalize cancer related gene expression. The most important characteristics of such genes are their presence in all cells and their expression levels remain relatively constant under different experimental conditions. However, no single gene of this group of genes manifests always stable expression levels under all experimental conditions. Incorrect choice of housekeeping genes leads to interpretation errors of experimental results including evaluation and quantification of pathological gene expression. Here, we examined (a) the degree of GAPDH expression regulation in Hep-1-6 mouse hepatoma and Hep-3-B and HepG2 human hepatocellular carcinoma cell lines as well as in human lung adenocarcinoma epithelial cell line (A-549) in addition to both HT-29, and HCT-116 colon cancer cell lines, under hypoxic conditions <it>in vitro </it>in comparison to other housekeeping genes like β-actin, serving as experimental loading controls, (b) the potential use of GAPDH as a target for tumor therapeutic approaches was comparatively examined <it>in vitro </it>on both protein and mRNA level, by western blot and semi quantitative RT-PCR, respectively.</p> <p>Findings</p> <p>No hypoxia-induced regulatory effect on GAPDH expression was observed in the cell lines studied <it>in vitro </it>that were; Hep-1-6 mouse hepatoma and Hep-3-B and HepG2 human hepatocellular carcinoma cell lines, Human lung adenocarcinoma epithelial cell line (A-549), both colon cancer cell lines HT-29, and HCT-116.</p> <p>Conclusion</p> <p>As it is the case for human hepatocellular carcinoma, mouse hepatoma, human colon cancer, and human lung adenocarcinoma, GAPDH represents an optimal choice of a housekeeping gene and/(or) loading control to determine the expression of hypoxia induced genes in tumors of different origin. The results confirm our previous findings in human glioblastoma that this gene is not an attractive target for tumor therapeutic approaches because of the lack of GAPDH regulation under hypoxia.</p

Influence of hypoxia and irradiation on osteopontin expression in head and neck cancer and glioblastoma cell lines

Background Tumor hypoxia is a known risk factor for reduced response to radiotherapy. The evaluation of noninvasive methods for the detection of hypoxia is therefore of interest. Osteopontin (OPN) has been discussed as an endogenous hypoxia biomarker. It is overexpressed in many cancers and is involved in tumor progression and metastasis. Methods To examine the influence of hypoxia and irradiation on osteopontin expression we used different cell lines (head and neck cancer (Cal27 and FaDu) and glioblastoma multiforme (U251 and U87)). Cells were treated with hypoxia for 24 h and were then irradiated with doses of 2 and 8 Gy. Osteopontin expression was analyzed on mRNA level by quantitative real-time RT-PCR (qPCR) and on protein level by western blot. Cell culture supernatants were evaluated for secreted OPN by ELISA. Results Hypoxia caused an increase in osteopontin protein expression in all cell lines. In Cal27 a corresponding increase in OPN mRNA expression was observed. In contrast the other cell lines showed a reduced mRNA expression under hypoxic conditions. After irradiation OPN mRNA expression raised slightly in FaDu and U87 cells while it was reduced in U251 and stable in Cal27 cells under normoxia. The combined treatment (hypoxia and irradiation) led to a slight increase of OPN mRNA after 2 Gy in U251 (24 h) and in U87 (24 and 48 h) cell lines falling back to base line after 8 Gy. This effect was not seen in Cal27 or in FaDu cells. Secreted OPN was detected only in the two glioblastoma cell lines with reduced protein levels under hypoxic conditions. Again the combined treatment resulted in a minor increase in OPN secretion 48 hours after irradiation with 8 Gy. Conclusion Osteopontin expression is strongly modulated by hypoxia and only to a minor extent by irradiation. Intracellular OPN homeostasis seems to vary considerably between cell lines. This may explain the partly conflicting results concerning response prediction and prognosis in the clinical setting

3-D reconstruction of anterior mantle-field techniques in Hodgkin's disease survivors: doses to cardiac structures

BACKGROUND: The long-term dose-effect relationship for specific cardiac structures in mediastinal radiotherapy has rarely been investigated. As part of an interdisciplinary project, the 3-D dose distribution within the heart was reconstructed in all long-term Hodgkin's disease survivors (n = 55) treated with mediastinal radiotherapy between 1978 and 1985. For dose reconstruction, original techniques were transferred to the CT data sets of appropriate test patients, in whom left (LV) and right ventricle (RV), left (LA) and right atrium (RA) as well as right (RCA), left anterior descending (LAD) and left circumflex (LCX) coronary arteries were contoured. Dose-volume histograms (DVHs) were generated for these heart structures and results compared between techniques. RESULTS: Predominant technique was an anterior mantle field (cobalt-60). 26 patients (47%) were treated with anterior mantle field alone (MF), 18 (33%) with anterior mantle field and monoaxial, bisegmental rotation boost (MF+ROT), 7 (13%) with anterior mantle field and dorsal boost (MF+DORS) and 4 (7%) with other techniques. Mean ± SD total mediastinal doses for MF+ROT (41.7 ± 3.5 Gy) and for MF+DORS (42.7 ± 7.4) were significantly higher than for MF (36.7 ± 5.2 Gy). DVH analysis documented relative overdosage to right heart structures with MF (median maximal dose to RV 129%, to RCA 127%) which was siginificantly reduced to 117% and 112%, respectively, in MF+ROT. Absolute doses in right heart structures, however, did not differ between techniques. Absolute LA doses were significantly higher in MF+ROT patients than in MF patients where large parts of LA were blocked. Median maximal doses for all techniques ranged between 48 and 52 Gy (RV), 44 and 46 Gy (LV), 47 and 49 Gy (RA), 38 and 45 Gy (LA), 46 and 50 Gy (RCA), 39 and 44 Gy (LAD) and 34 and 42 Gy (LCX). CONCLUSION: In patients irradiated with anterior mantle-field techniques, high doses to anterior heart portions were partly compensated by boost treatment from non-anterior angles. As the threshold doses for coronary artery disease, cardiomyopathy, pericarditis and valvular changes are assumed to be 30 to 40 Gy, cardiac toxicity must be anticipated in these patients. Thus, dose distributions in individual subjects should be correlated to the corresponding cardiovascular findings in these long-term survivors, e. g. by cardiovascular magnetic resonance imaging

Glioblastoma multiforme with oligodendroglial component (GBMO): favorable outcome after post-operative radiotherapy and chemotherapy with nimustine (ACNU) and teniposide (VM26)

BACKGROUND: The presence of an oligodendroglial component within a glioblastoma multiforme (GBM) is considered a prognostically favorable factor, but the clinical outcome of patients with glioblastoma multiforme with oligodendroglial component (GBMO) after combined post-operative radiotherapy and chemotherapy has rarely been reported. METHODS: We analyzed overall and progression-free survival in a group of ten consecutive patients initially diagnosed with GBMO between 1996 and 2004 (4.2% of all GBM patients). Median (range) age was 54 (34–73) years, 90% were resected and median radiotherapy dose was 54 (45–60.6) Gy. 80% of patients received post-operative chemotherapy with nimustine (ACNU) and VM26 (teniposide) for a median of 3.5 (1–6) cycles, the remainder were treated with post-operative radiotherapy alone. All specimens were reviewed by an experienced neuropathologist. RESULTS: Neuropathological re-evaluation revealed GBM with an oligodendroglial component of 30% or less in five cases, predominant oligoastrocytic tumors with focal areas of GBM in four patients and WHO grade III oligoastrocytoma with questionable transition to GBM in one patient. Four of ten patients were alive at at 40, 41, 41 and 82 months. The median overall survival (Kaplan-Meier) was 26 months, the 2-year survival rate was 60% (progression-free survival: 9.8 months and 40%, respectively). CONCLUSION: In conclusion, patients with GBMO treated with post-operative radiotherapy and chemotherapy with ACNU/VM26 had a better prognosis than reported for GBM in modern chemoradiation series

TFE3 Translocation-Associated Renal Cell Carcinoma Presenting as Avascular Necrosis of the Femur in a 19-Year-Old Patient: Case Report and Review of the Literature

In the United States, renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 90–95% of all neoplasms arising from the kidney. According to the National Cancer Institute, 58 240 new cases and 13 040 deaths from renal cancer will occur in 2010. RCC usually occurs in older adults between the ages of 50 and 70 and is rare in young adults and children. We describe a case of a TFE3 translocation-associated RCC in a 19-year-old patient presenting as avascular necrosis of the femur. Due to the rarity of this malignancy, we present this case including a review of the existing literature relative to diagnosis and treatment