Medical University of Berlin

Berlin, Germany

Medical University of Berlin

Berlin, Germany
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Mungenast F.,Medical University of Vienna | Aust S.,Medical University of Vienna | Vergote I.,Catholic University of Leuven | Vanderstichele A.,Catholic University of Leuven | And 6 more authors.
Oncology Letters | Year: 2017

17β-estradiol (E2) can contribute to the progression of epithelial ovarian cancer (EOC). Although the majority of patients with EOC are postmenopausal woman, when de novo estrogen production in the ovary has ceased, ovarian cancer cells remain exposed to estrogens synthesized locally in the cancer cells from inactive sulfonated steroid hormone precursors-such as estrone sulfate taken up from the circulation via the sulfatase pathway. An abundance of the estrogen-modifying enzymes, including estrogen-activating steroid sulfatase (STS) and estrogen-inactivating estrogen-sulfotransferase (SULT1E1), is important for providing active estrogen to EOC cells. Therefore, the present study determined the levels of SULT1E1, STS and estrogen receptor α (ERα) protein in paraffin-embedded specimens from 206 patients with Federation of Gynecology and Obstetrics stage II-IV EOC treated with debulking surgery and standard platinum-based adjuvant chemotherapy. The levels of STS, SULT1E1 and ERα were assessed by automated quantitative microscopy-based image analysis subsequent to immunohistochemical staining. Significantly higher SULT1E1 levels were observed in better differentiated EOC tumors compared to grade 3 EOC tumors (P=0.001). STS and SULT1E1 levels were positively associated with ERα abundance (P<0.001 and P=0.001, respectively). In advanced stage high-grade serous EOC (HGSOC; n=132), the most frequent and lethal type of ovarian cancer, SULT1E1 expression was significantly associated with a better overall survival rate (hazard ratio 0.66, 95% confidence interval, 0.45-0.94; P=0.005). These results highlight the importance of SULT1E1-mediated estrogen inactivation in EOC, particularly HGSOC. Therefore, targeting the sulfatase pathway is a potential endocrine therapeutic intervention for certain patients with estrogen-responsive EOC. © 2017, Spandidos Publications. All rights reserved.

Woopen H.,Medical University of Berlin | Pietzner K.,Medical University of Berlin | Darb-Esfahani S.,Charité - Medical University of Berlin | Oskay-Oezcelik G.,Medical University of Berlin | Sehouli J.,Medical University of Berlin
Medical Oncology | Year: 2012

Cutaneous metastasation is a very rare manifestation of ovarian cancer. We present the case of a 64-year-old woman with recurrent platinum-refractory ovarian cancer and skin metastasis. The patient was treated with intraperitoneal catumaxomab due to massive refractory malignant ascites. Clinical response of the skin metastasis was observed during the intraperitoneal treatment with catumaxomab. Even though response of extraperitoneal tumor sites can be explained with intravascular uptake and a possible vaccination effect, this phenomenon has not been reported up to this point to the best of our knowledge. © 2012 Springer Science+Business Media, LLC.

Bechtold S.,Ludwig Maximilians University of Munich | Blaschek A.,Ludwig Maximilians University of Munich | Raile K.,Medical University of Berlin | Dost A.,University Hospital Jena | And 5 more authors.
Diabetes Care | Year: 2014

Objective Type 1 diabetes and multiple sclerosis (MS) are typical autoimmune diseases in children and young adults. We assessed the co-occurrence of type 1 diabetes and MS by estimating the relative risk (RR) for MS in a pediatric and adolescent diabetic population and looked for possible influencing factors. Research Design And Methods Within the Diabetes Patienten Verlaufsdokumentation (DPV)-Wiss Project, from January 1995 to October 2012, data from 56,653 patients with type 1 diabetes were collected in 248 centers in Germany and Austria. Published data on German and Mid-European MS prevalence were taken for comparison. Multivariable regression analysis was used to identify confounders for co-occurrence of type 1 diabetes and MS. Results The RR forMS in patients with type 1 diabetes was estimated at 3.35-4.79 (95% CI 1.56-7.21 and 2.01-11.39, respectively). Immigration status in all patients (P 0.05) and the presence of thyroid antibodies in male patients only (P = 0.05) were identified as influencing factors on MS incidence within the DPV database. The month-of-birth pattern revealed that risk was higher during the spring and summermonths in the populationwith type 1 diabetes and MS in comparisonwith the population with type 1 diabetes. Conclusions The present cohort study demonstrates a higher risk of co-occurrence of MS in a pediatric and adolescent diabetic population. Immigration status and thyroid antibodies in male patients were independent risk indicators for the incidental rate ofMS. Diabetic patients born during spring and summer had a higher risk for the development of MS. We suggest that environmental factors modulate the individual's risk for the co-occurrence of both diseases. © 2014 by the American Diabetes Association.

Frede J.,Imperial College London | Frede J.,University of Heidelberg | Fraser S.P.,Imperial College London | Oskay-Ozcelik G.,Medical University of Berlin | And 7 more authors.
European Journal of Cancer | Year: 2013

Ovarian cancer is associated with limited overall survival, due to problems in early detection and therapy. Membrane ion channels have been proposed to play a significant, concerted role in the cancer process, from initial proliferation to metastasis, and promise to be early, functional biomarkers. We review the evidence for ion channel and aquaporin expression and functioning in human ovarian cancer cells and tissues. In vitro, K+ channels, mainly voltage-gated, including Ca2+-activated channels, have been found to control the cell cycle, as in other cancers. Voltage-gated, volume-regulated and intracellular Cl- channels have been detected in vitro and in vivo and shown to be involved in proliferation, adhesion and invasion. Evidence for 'transient receptor potential', voltage-gated sodium and calcium channels, which have been shown to contribute to pathogenesis of other carcinomas, is also emerging in ovarian cancer. Aquaporins may be involved in cell growth, migration and formation of ascites via increased water permeability of micro-vessels. It is concluded that functional expression of ion channels and their regulation by steroid hormones and growth factors are an integral part of ovarian cancer development and progression. Furthermore, ion channels may be involved in multidrug resistance, commonly associated with treatment of ovarian cancer. We propose that ion channel studies can facilitate our understanding of the pathobiology of ovarian cancer and, ultimately, can serve as viable novel targets for its clinical management. © 2013 Elsevier Ltd. All rights reserved.

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