Cornelia Sax

Five Genes from Chromosomal Band 8p22 Are Significantly Down-Regulated in Ovarian Carcinoma N33 and EFA6R Have a Potential Impact on Overall Survival

Loss of heterozygosity on chromosomal band 8p22 is a common event in several epithelial tumors including ovarian carcinoma. So far, no clear evidence for a tumor suppressor gene (TSG) in this region has been found.

Perturbation of the Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Cascade in Ovarian Cancer: Overexpression of FLIPL and Deregulation of the Functional Receptors DR4 and DR5

Purpose: Epithelial ovarian cancer is the most common cause of mortality from gynecologic malignancies. Due to advanced stage at diagnosis, most patients need systemic treatment in addition to surgery. Tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) is a member of the TNF family with a promising toxicity profile and synergistic activity with chemotherapeutic agents. Experimental Design: We used an arrayed panel of epithelial ovarian cancer tissue to assess the protein expression of TRAIL and the clinically most relevant members of its pathway death receptors 4 and 5 (DR4 and DR5) and the long form of FLICE inhibitory protein (FLIPL). Results: We could show that a majority (66.2%) of the tumor tissues displayed either reduced DR4/DR5 expression (20.6%), increased FLIPL expression (39.7%), or both (5.9%) as determined by immunohistochemistry. Furthermore, higher TRAIL expression in the surrounding connective tissue but not in the tumor cells is significantly (P < 0.05) linked with favorable overall survival in advanced-stage patients. Conclusions: Mechanisms to escape the immune surveillance mediated by TRAIL are developed by ovarian cancer cells in a high percentage. TRAIL expression in the ovarian cancer microenvironment has an effect on overall survival. These findings enhance our understanding of ovarian cancer pathology and might be helpful in guiding TRAIL-based therapy in future.

Linking the ovarian cancer transcriptome and immunome

BackgroundAutoantigens have been reported in a variety of tumors, providing insight into the interplay between malignancies and the immune response, and also giving rise to novel diagnostic and therapeutic concepts. Why certain tumor-associated proteins induce an immune response remains largely elusive.ResultsThis paper analyzes the proposed link between increased abundance of a protein in cancerous tissue and the increased potential of the protein for induction of a humoral immune response, using ovarian cancer as an example. Public domain data sources on differential gene expression and on autoantigens associated with this malignancy were extracted and compared, using bioinformatics analysis, on the levels of individual genes and proteins, transcriptional coregulation, joint functional pathways, and shared protein-protein interaction networks. Finally, a selected list of ovarian cancer-associated, differentially regulated proteins was tested experimentally for reactivity with antibodies prevalent in sera of ovarian cancer patients.Genes reported as showing differential expression in ovarian cancer exhibited only minor overlap with the public domain list of ovarian cancer autoantigens. However, experimental screening for antibodies directed against antigenic determinants from ovarian cancer-associated proteins yielded clear reactions with sera.ConclusionA link between tumor protein abundance and the likelihood of induction of a humoral immune response in ovarian cancer appears evident.

Alleviation of brain edema and restoration of functional independence by bevacizumab in brain-metastatic breast cancer: a case report.

Background: Brain metastases (BM) are an increasing challenge in modern oncology, as treatment options especially after exhaustion of local treatment approaches are very limited. Patient and Methods: A long-term surviving patient with brain-only metastatic breast cancer, who presented at our department with massive corticosteroid-refractory brain edema with serious neurological symptoms after exhaustion of all local therapy options, was started on bevacizumab. Results: Initiation of bevacizumab monotherapy led to rapid decrease of contrast-enhancing lesions and alleviation of brain edema, and allowed tapering and termination of corticosteroid administration. Neurological and neurocognitive function was restored and marked improvement in quality of life was observed. Conclusion: Our case highlights that bevacizumab may represent a feasible and effective salvage treatment option in selected patients with BM.

Sorafenib for patients with pretreated recurrent or progressive high-grade glioma: a retrospective, single-institution study.

Therapeutic options for patients with pretreated advanced high-grade glioma (HGG) are limited. Sorafenib, a small molecule with multiple potential beneficial actions, appears particularly promising. We reviewed the outcomes of 30 patients with recurrent or progressive HGG treated with sorafenib within a named patient program. Overall, 16 patients suffered from recurrent or progressive glioblastoma multiforme and 14 patients had grade 3 gliomas. All but four patients had previously undergone surgical debulking; all but one patient had received previous standard multimodal treatment; and 18 patients (60%) had received more than one line of chemotherapy, in median three. Progression-free survival (PFS), defined as the time from initiation of sorafenib to treatment discontinuation because of tumor progression or death, was selected as the endpoint. The use of sorafenib resulted in a median PFS of 3 months [95% confidence interval (CI) 1.9–4.1 months] in patients with glioblastoma and of 3.1 months (95% CI 1.4–4.8 months) in patients with other HGG. The PFS-6 for the whole cohort was 23%. Sixteen patients reported adverse events, mostly moderate, with hypertension as the most frequently reported toxicity (seven patients). One patient died of cerebral bleeding (grade 5 toxicity). The overall survival after initiation of sorafenib was 6 months (95% CI 3.9–8.0 months) for patients with glioblastoma multiforme and 10 months (95% CI 3.1–16.9 months) for patients with HGG. In this retrospective analysis of heavily pretreated patients with HGG, sorafenib monotherapy was associated with tumor stabilization in a small subset of patients. The risk–benefit ratio was acceptable in the context of an apparent clinical benefit in patients with a fatal disease.

Editorial Board / Contents / Guidelines

Rupert Bartsch, Wien Ute Berndt, Halle Serban-Dan Costa, Magdeburg Peter Dall, Lüneburg Peter Dubsky, Wien Florian Fitzal, Wien Alexander Gaiger, Wien Oleg Gluz, Mönchengladbach Volker Hanf, Fürth Kerstin Hermelink, München Reinhard Horvat, Wien Jens Huober, Ulm Wolfgang Janni, Ulm Walter Jonat, Kiel Michael Knauer, St. Gallen Rolf Kreienberg, Ulm Christiane Kuhl, Bonn Annette Lebeau, Hamburg Cornelia Liedtke, Lübeck Sibylle Loibl, Neu-Isenburg Helmut Madjar, Wiesbaden Christian Marth, Innsbruck Volker Möbus, Frankfurt/M. Ulrike Nitz, Mönchengladbach Angelo Paradiso, Bari Richard Pötter, Wien Kurt Possinger, Berlin Rita Schmutzler, Köln Andreas Schneeweiss, Heidelberg Christian Singer, Wien Isabell Witzel, Hamburg Rachel Würstlein, München Christoph Zielinski, Wien Editors-in-Chief

Clinical outcome of GBM long-term survivors.

e12507 Background: An increasing number of patients with Glioblastoma mulitforme (GBM) are alive up to three years after diagnosis (long-term survivors). Hence there is an urgent need for data about their clinical outcome and quality of life to optimize the medical management and function of patients. METHODS In this cross sectional study we studied 16 GBM long-term survivors treated at the outpatient clinic of the Medical University Hospital Vienna. The patients have been treated there since their diagnosis. We assessed patients clinical outcome to get global information about the circumstances under which they live. RESULTS We assessed 8 female and 8 male GBM long-term survivors with a median age of 52 years (71-30). 14 of them lived together with their partner (and children) while two lived single. The mean of the summary-score of the Neuro Cog-Fx, a computerized instrument for neurocognitive assessment of patients with neurological diseases, was 88 and ranged from 70 to 111, whereas results from 61-79 are defined conspicuous, 80-89 borderline and results up to 90 normal. The global health score ranged from 17% to 100% with a mean of 68%. Drowsiness, weakness in both legs and a headache were the most stated physical problems. The Independent Activities of Daily Living - Score ranged from 0-8 points; mean was 7 points and Barthel Index resulted in 35-100 with a mean of 92 points. Six patients showed impairment in their manual dexterity, one patient in their mobility. Three patients showed conspicuous depression scores, two had conspicuous anxiety results. Furthermore, future uncertainty was stated in 12 patients. CONCLUSIONS GBM long-term survivors show moderate impairment in their cognitive functions and often suffer from physical problems. However, the majority of the GBM long-term survivors is able to manage their activities of daily living independently. Nevertheless, global health and future prospects remain poor.