Institute for Experimental Endocrinology

Berlin, Germany

Institute for Experimental Endocrinology

Berlin, Germany
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Muecke R.,Lippe Hospital | Schomburg L.,Institute for Experimental Endocrinology | Glatzel M.,Central Hospital | Berndt-Skorka R.,Municipal Hospital | And 12 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: We assessed whether adjuvant supplementation with selenium improves the selenium status and reduces side effects of patients treated by radiotherapy (RT) for cervical and uterine cancer. Methods and Materials: Whole-blood selenium concentrations were measured in patients with cervical cancer (n = 11) and uterine cancer (n = 70) after surgical treatment, during RT, at the end of RT, and 6 weeks after RT. Patients with initial selenium concentrations of less than 84μg/L were randomized before RT either to receive 500 μg of selenium (in the form of sodium selenite [selenase®, biosyn Arzneimittel GmbH, Fellbach, Germany]) by mouth on the days of RT and 300 μg of selenium on the days without RT or to receive no supplement during RT. The primary endpoint of this multicenter Phase 3 study was to assess the efficiency of selenium supplementation during RT; the secondary endpoint was to decrease radiation-induced diarrhea and other RT-dependent side effects. Results: A total of 81 patients were randomized. We enrolled 39 in the selenium group (SG) and 42 in the control group (CG). Selenium levels did not differ between the SG and CG upon study initiation but were significantly higher in the SG at the end of RT. The actuarial incidence of diarrhea of Grade 2 or higher according to Common Toxicity Criteria (version 2) in the SG was 20.5% compared with 44.5% in the CG (p = 0.04). Other blood parameters, Eastern Cooperative Oncology Group performance status, and self-reported quality of life were not different between the groups. Conclusions: Selenium supplementation during RT is effective in improving blood selenium status in selenium-deficient cervical and uterine cancer patients and reduces the number of episodes and severity of RT-induced diarrhea. © 2010 Elsevier Inc. All rights reserved.


Springer J.,Applied Cachexia Research | Springer J.,Center for Cardiovascular Research | Springer J.,University of East Anglia | Tschirner A.,Applied Cachexia Research | And 18 more authors.
International Journal of Cancer | Year: 2012

Cachexia is a common co-morbidity in cancer occurring in up to 80% of patients depending on the type of cancer. Uric acid (UA), the end-product of the purine metabolism, is elevated in cachexia due to tissue wasting and upregulated xanthine oxidase (XO) activity. High serum UA levels indicate increased XO-dependent production of oxygen free radicals (reactive oxygen species; ROS) and correlate with metabolic illness and poor survival. We hypothesized that XO-inhibition might reduce inflammatory signals accounting for tissue wasting and improve survival in experimental cancer cachexia. Animals were inoculated intraperitoneally with AH-130 hepatoma cells and treated with two XO-inhibitors: allopurinol [Allo, low (LD) and high dose (HD) 4 and 40 mg/kg/d] and its more effective active metabolite oxypurinol (Oxy, 4 and 40 mg/kg/d) or placebo for 15 days. Weight loss and tissue wasting of both fat and lean tissue (assessed by NMR-scanning) was reduced by both LD and HD Allo and LD-Oxy, but not by HD-Oxy. A robust induction of XO-activity for generation of reactive oxygen species was seen in the placebo group (assessed by electron paramagnetic spectroscopy), which was reduced by XO-inhibition. Increased ROS induced cytokine signaling, proteolytic activity and tissue degradation were all attenuated by XO inhibition. Survival was significantly and dose dependently improved. Food intake and spontaneous locomotor activity were higher, indicating a higher quality of life. Inhibition of XO can reduce tissue wasting and improve survival in cancer cachexia and clearly clinical studies are needed. Copyright © 2012 UICC.


Ebner N.,University of Medicine Goettingen | Foldes G.,Imperial College London | Schomburg L.,Institute for Experimental Endocrinology | Renko K.,Institute for Experimental Endocrinology | And 7 more authors.
Journal of Molecular and Cellular Cardiology | Year: 2015

Background: The origin of pro-inflammatory activation in chronic heart failure (HF) remains a matter of debate. Lipopolysaccharide (LPS) may enter the blood stream through the morphologically altered and leaky gut barrier. We hypothesized that lower LPS reactivity would be associated with worse survival as compared to normal or higher LPS reactivity. Methods: LPS responsiveness was studied in 122 patients with chronic HF (mean. ±. SD: age 67.3. ±. 10.3. years, 24 female, New York Heart Association class [NYHA] class: 2.5. ±. 0.8, left ventricular ejection fraction [LVEF]: 33.5. ±. 12.5%) and 27 control subjects of similar age (63.7. ±. 7.7. years, p. >. 0.05). Reference LPS was added at increasing doses to ex vivo whole blood samples and necrosis factor-α (TNFα) was measured. Patients were subgrouped into good- and poor-responder status according to their potential to react to increasing doses of LPS (delta TNFα secretion). The optimal cut-off value was calculated by receiver-operator characteristic curve (ROC) analysis. Results: A total of 56 patients with chronic HF died from any cause during follow-up. At 24. months, cumulative mortality was 16.4% (95% confidence interval 16.0-16.7%). The delta TNFα value representing the optimal cut-off for the prediction of mortality was 1522. pg/mL (24. months) with a sensitivity of 49.3% (95% confidence interval 37.2-61.4%) and specificity of 81.5% (95% confidence interval 61.9-93.6%). LPS responder status remained an independent predictor of death after multivariable adjustment (hazard ratio 0.09 for good- vs. poor-responders, 95% confidence interval 0.01-0.67, p. <. 0.05). Conclusions: LPS responsiveness in patients with chronic HF is an independent predictor of death. © 2015 Elsevier Ltd.


PubMed | Institute for Experimental Endocrinology, Imperial College London, University of Medicine Goettingen, Charité - Medical University of Berlin and 2 more.
Type: | Journal: Journal of molecular and cellular cardiology | Year: 2015

The origin of pro-inflammatory activation in chronic heart failure (HF) remains a matter of debate. Lipopolysaccharide (LPS) may enter the blood stream through the morphologically altered and leaky gut barrier. We hypothesized that lower LPS reactivity would be associated with worse survival as compared to normal or higher LPS reactivity.LPS responsiveness was studied in 122 patients with chronic HF (meanSD: age 67.310.3 years, 24 female, New York Heart Association class [NYHA] class: 2.50.8, left ventricular ejection fraction [LVEF]: 33.512.5%) and 27 control subjects of similar age (63.77.7 years, p>0.05). Reference LPS was added at increasing doses to ex vivo whole blood samples and necrosis factor- (TNF) was measured. Patients were subgrouped into good- and poor-responder status according to their potential to react to increasing doses of LPS (delta TNF secretion). The optimal cut-off value was calculated by receiver-operator characteristic curve (ROC) analysis.A total of 56 patients with chronic HF died from any cause during follow-up. At 24 months, cumulative mortality was 16.4% (95% confidence interval 16.0-16.7%). The delta TNF value representing the optimal cut-off for the prediction of mortality was 1522 pg/mL (24 months) with a sensitivity of 49.3% (95% confidence interval 37.2-61.4%) and specificity of 81.5% (95% confidence interval 61.9-93.6%). LPS responder status remained an independent predictor of death after multivariable adjustment (hazard ratio 0.09 for good- vs. poor-responders, 95% confidence interval 0.01-0.67, p<0.05).LPS responsiveness in patients with chronic HF is an independent predictor of death.


Muecke R.,Lippe Hospital Lemgo | Micke O.,Franziskus Hospital | Schomburg L.,Institute for Experimental Endocrinology | Buentzel J.,Sudharz Hospital Nordhausen | And 2 more authors.
Trace Elements and Electrolytes | Year: 2011

Background: Selenium (Se) has been shown to possess cancer-preventive and cytoprotective activities in both animal models and humans. Recent clinical trials showed the importance of Se for clinical oncology. With this review we want to outline the main results of the scientific activities of the German Working Group Trace Elements and Electrolytes in Oncology concerning adjuvant Se supplementation in radiation oncology. Moreover, we highlight strategies for identifying those tumor patients who might benefit most from Se supplementation, and we discuss the potential benefits and risks of Se supplementation. Material and methods: We compared our results and experiences with the current literature on selenium and radiation oncology as published in PubMed. Results: Blood and tissue Se levels: In the majority of tumor patients with different diagnoses (carcinomas of the uterus, head and neck cancer, lung cancer, rectal cancer and prostate cancer) we identified a relative Se deficiency in whole blood and serum in comparison to the published normal reference range. In patients with prostate cancer, tissue Se levels are reduced in the compartment surrounding the carcinoma in comparison to patients with benign prostatic hyperplasia, and circulating Se and selenoprotein P (Se-PP) concentrations are lower compared to controls. Experimental Study: The recent experimental study of our group showed a radiosensitizing effect of Se in irradiated rat glioma cells particularly at radiation doses > 2 Gy. Clinical studies on radioprotection by Se: We conducted two randomized Phase III clinical studies in order to examine the radioprotective properties of Se in radiation oncology. We observed a significant benefit of Se supplementation with regard to Se deficiency and radiotherapy-induced diarrhea in the first of these studies concerning postoperative pelvic radiotherapy of patients with carcinomas of the uterus. Survival data imply that supplementation with Se does not interfere with radiation treatment. The second of these randomized trials in head and neck tumor patients undergoing radiation therapy showed limited effects of Se in the prevention of ageusia (loss of taste) and dysphagia due to radiotherapy. A clinical relevant radioprotection was not observed, and side-effects were not reported by the patients. Se use in patients with lymphedemas: Our clinical study indicated a positive effect of Se supplementation on radiation-associated secondary lymphedema in patients with limb edemas as well as in the head and neck region, including endolaryngeal edema. Conclusion: In tumor patients with different diagnoses we observed a Se deficiency in whole blood or serum and in tissue surrounding the carcinoma. Supplementation of Se yielded promising results concerning radioprotection and edema prevention in tumor patients. Nevertheless, a better understanding of Se biology is needed in order to justify Se supplementation as an adjuvant treatment in radiation oncology. Unfortunately, the field of Se research and adjuvant supplementation of cancer patients has suffered a serious drawback recently, when data were published indicating no chemopreventive effects against prostate cancer but an increased risk of developing diabetes mellitus with constant high Se intake. These studies point again to the relatively narrow therapeutic width of Se intake in humans and the potential risk associated with exaggerated Se supplementation. Nevertheless, given the relative Se deficiency of most Europeans, the benefit-risk ratio of our patients is clearly on the positive side, for they are insufficiently supplied with this essential trace element and the disease appears to cause a further decline in Se status which seems to aggravate the disease and hampers fast and uncomplicated recovery. ©2011 Dustri-Verlag Dr. K. Feistle.


Muecke R.,Lippe Hospital Lemgo | Muecke R.,Ruhr University Bochum | Micke O.,Franziskus Hospital | Schomburg L.,Institute for Experimental Endocrinology | And 4 more authors.
Radiation Oncology | Year: 2014

Considering the review by Puspitasari and colleagues, an additional discussion of the endpoints of the Se supplementation studies described would be helpful. In our view, selenium can safely be given to selenium-deficient cancer patients prior to and during radiotherapy. Therefore, in order to help the radiation oncologist in decision making, we strongly advocate to determine the selenium status prior to and during a potential adjuvant selenium supplementation, e.g. when trying to ease the side-effects of radiation treatment or in the aftercare situation when the selenium status may become insufficient.. © Muecke et al.; licensee BioMed Central Ltd.


Micke O.,Franziskus Hospital | Schomburg L.,Institute for Experimental Endocrinology | Buentzel J.,Sudharz Hospital Nordhausen | Kisters K.,St Anna Hospital | Muecke R.,Lippe Hospital Lemgo
Trace Elements and Electrolytes | Year: 2010

Selenium has been shown to possess cancer-preventive and cytoprotective activities in both animal models and human. Recent clinical trials showed the importance of selenium for clinical oncology. Our own clinical study involving 48 patients suggest that selenium has a positive effect on radiation-associated secondary lymphedema in patients with limb edemas as well as in the head and neck region, including endolaryngeal edema. Another randomized Phase III study of our group was performed to examine the cytoprotective properties of selenium in radiation oncology. From this study, for the first time, the significant benefit of selenium supplementation with regard to selenium deficiency and radiotherapy induced diarrhea has been shown in a prospective randomized trial. Survival data implies that supplementation with selenium does not interfere with radiation treatment. More recently there were emerging concerns coming up from two large clinical prevention trials, that selenium increases the possible risk of developing diabetes. Despite obvious flaws of both studies and good counterarguments, a controversial debate remains on the possible advantages and risks of selenium in cancer prevention. However, in light of the recent clinical trials the potential benefits of selenium supplementation in tumor patients are undeniable, although further research is needed. ©2010 Dustri-Verlag Dr. K. Feistle.


PubMed | Institute for Experimental Endocrinology, Sudharz Hospital, Lippe Hospital Lemgo, St Anna Hospital and 3 more.
Type: | Journal: Radiation oncology (London, England) | Year: 2015

Considering the review by Puspitasari and colleagues, an additional discussion of the endpoints of the Se supplementation studies described would be helpful. In our view, selenium can safely be given to selenium-deficient cancer patients prior to and during radiotherapy. Therefore, in order to help the radiation oncologist in decision making, we strongly advocate to determine the selenium status prior to and during a potential adjuvant selenium supplementation, e.g. when trying to ease the side-effects of radiation treatment or in the aftercare situation when the selenium status may become insufficient.

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