Kafka auf der Bühne - "Der Prozess" und seine Inszenierung durch Gernot Plass (Wien, TAG, 2011)

Im 21. Jahrhundert lässt sich ein regelrechter Trend hin zu Romandramatisierungen erkennen. Die Autoren und Regisseure scheinen fasziniert von der Arbeit, einen Roman für die Bühne zu bearbeiten und zu adaptieren und testen in diesem Vorgang die Grenzen und Möglichkeiten des zeitgenössischen Theaters. Vor allem die Werke Franz Kafkas beeindrucken durch ihre komplizierte Beziehung zur Bühne die Theaterwelt seit Jahren. In dieser Arbeit wurde ein Überblick über die Methoden der Romandramatisierungen gegeben und unter anderem die Elemente der Theatralität, Komik und Groteske in „Der Prozess“ untersucht und deren Bedeutung für eine szenische Umsetzung des Fragments evaluiert. Anhand der Analyse der Inszenierung von Gernot Plass am TAG - Theater an der Gumpendorferstraße konnte gezeigt werden, wie ein zeitgenössischer Regisseur mit dem Material des Romans umgeht, nach welchen Regeln er dramatisiert, wie der entstandene Theatertext seine gesamte Faszination erst durch den Körper des Schauspielers gänzlich entwickeln kann und welche besondere Art der Rollenarbeit nötig ist, um die Figuren Kafkas fassbar zu machen

KRAS mutation analysis in ovarian samples using a high sensitivity biochip assay

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>KRAS </it>gene are one of the most frequent genetic abnormalities in ovarian carcinoma. They are of renewed interest as new epidermal growth factor receptor (EGFR)-targeted therapies are being investigated for use in ovarian carcinoma. As <it>KRAS </it>mutations are associated with poor response and resistance to EGFR-targeting drugs, this study was conducted to obtain more information on the spectrum of <it>KRAS </it>mutations in ovarian carcinoma.</p> <p>Methods</p> <p>The presence of <it>KRAS </it>mutations in codon 12 and 13 was analyzed in frozen and formalin-fixed paraffin-embedded (FFPE) tissue with a low density biochip platform. 381 malignant (29 borderline malignancy, 270 primary carcinomas, and 82 recurrent carcinomas) and 22 benign tissue samples from a total of 394 patients were examined. <it>KRAS </it>mutational status of each sample was correlated with dignity, FIGO stage, grade, histology, and survival.</p> <p>Results</p> <p><it>KRAS </it>mutations were found in 60 (15%) samples with 58 samples deriving from malignant tissue and 2 samples deriving from benign tissue. In 55 (92%) samples codon 12 was found to be mutated. Frozen and FFPE samples concurred with respect to <it>KRAS </it>mutation status.</p> <p>Conclusion</p> <p><it>KRAS </it>mutation is a common event in ovarian cancer primarily in carcinomas of lower grade, lower FIGO stage, and mucinous histotype. The <it>KRAS </it>mutational status is no prognostic factor for patients treated with standard therapy. However, in line with experience from colorectal cancer and non-small-cell-lung cancer (NSCLC), it may be important for prediction of response to EGFR-targeted therapies.</p

Tumor Growth Rate Estimates Are Independently Predictive of Therapy Response and Survival in Recurrent High-Grade Serous Ovarian Cancer Patients

This study aimed to assess the predictive value of tumor growth rate estimates based on serial cancer antigen-125 (CA-125) levels on therapy response and survival of patients with recurrent high-grade serous ovarian cancer (HGSOC). In total, 301 consecutive patients with advanced HGSOC (exploratory cohort: n = 155, treated at the Medical University of Vienna; external validation cohort: n = 146, from the Ovarian Cancer Therapy–Innovative Models Prolong Survival (OCTIPS) consortium) were enrolled. Tumor growth estimates were obtained using a validated two-phase equation model involving serial CA-125 levels, and their predictive value with respect to treatment response to the next chemotherapy and the prognostic value with respect to disease-specific survival and overall survival were assessed. Tumor growth estimates were an independent predictor for response to second-line chemotherapy and an independent prognostic factor for second-line chemotherapy use in both univariate and multivariable analyses, outperforming both the predictive (second line: p = 0.003, HR 5.19 [1.73–15.58] vs. p = 0.453, HR 1.95 [0.34–11.17]) and prognostic values (second line: p = 0.042, HR 1.53 [1.02–2.31] vs. p = 0.331, HR 1.39 [0.71–2.27]) of a therapy-free interval (TFI) &lt; 6 months. Tumor growth estimates were a predictive factor for response to third- and fourth-line chemotherapy and a prognostic factor for third- and fourth-line chemotherapy use in the univariate analysis. The CA-125-derived tumor growth rate estimate may be a quantifiable and easily assessable surrogate to TFI in treatment decision making for patients with recurrent HGSOC

Safety and dose modification for patients receiving niraparib

Background: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved in the United States and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to TEAE was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was performed to identify clinical parameters that predict dose reductions. Patients and methods: All analyses were performed on the safety population, comprising all patients who received at least one dose of study drug. Patients were analyzed according to the study drug consumed (ie, as treated). A predictive modeling method (decision trees) was used to identify important variables for predicting the likelihood of developing grade ≥3 thrombocytopenia within 30 days after the first dose of niraparib and determine cutoff points for chosen variables. Results: Following dose modification, 200 mg was the most commonly administered dose in the ENGOT-OV16/NOVA trial. Baseline platelet count and baseline body weight were identified as risk factors for increased incidence of grade ≥3 thrombocytopenia. Patients with a baseline body weight <77 kg or a baseline platelet count <150,000/μL in effect received an average daily dose approximating 200 mg (median = 207 mg) due to dose interruption and reduction. Progression-free survival in patients who were dose reduced to either 200 mg or 100 mg was consistent with that of patients who remained at the 300 mg starting dose. Conclusions: The analysis presented suggests that patients with baseline body weight of < 77 kg or baseline platelets of < 150,000/μL may benefit from a starting dose of 200 mg per day. (ClinicalTrials.gov ID: NCT01847274)

The prognostic value of estrogen receptor beta and proline-, glutamic acid- and leucine-rich protein 1 (PELP1) expression in ovarian cancer

Background: Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), a coregulator of the estrogen receptors (ERs) alpha and beta, is a potential proto-oncogene in hormone dependent gynecological malignancies. To better understand the role of PELP1 in epithelial ovarian cancer (EOC), the protein expression and prognostic significance of PELP1 was evaluated together with ERalpha and ERbeta in EOC tissues. Methods: The expression of PELP1, ERalpha, and ERbeta was characterized in tumor tissues of 63 EOC patients. The prognostic value was calculated performing log-rank tests and multivariate Cox-Regression analysis. In a second step, validation analysis in an independent set of 86 serous EOC patients was performed. Results: Nuclear PELP1 expression was present in 76.2% of the samples. Prevalence of PELP1 expression in mucinous tumors was significantly lower (37.5%) compared to serous (85.7%) and endometrioid tumors (86.7%). A significant association between PELP1 expression and nuclear ERbeta staining was found (p=0.01). Positive PELP1 expression was associated with better disease-free survival (DFS) (p=0.004) and overall survival (OS) (p=0.04). The combined expression of ERbeta+/PELP1+ revealed an independent association with better DFS (HR 0.3 [0.1-0.7], p=0.004) and OS (HR 0.3 [0.1-0.7], p=0.005). In the validation set, the combined expression of ERbeta+/PELP1+ was not associated with DFS (HR 0.7 [0.4-1.3], p=0.3) and OS (HR 0.7 [0.3-1.4], p=0.3). Conclusion: Positive immunohistochemical staining for the ER coregulator PELP1, alone and in combination with ERbeta, might be of prognostic relevance in EOC.Stefanie Aust, Peter Horak, Dietmar Pils, Sophie Pils, Christoph Grimm, Reinhard Horvat, Dan Tong, Bernd Schmid, Paul Speiser, Alexander Reinthaller, and Stephan Polteraue