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Dive into the research topics where Bernd Kost is active.

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Featured researches published by Bernd Kost.


Cardiovascular Toxicology | 2016

Efavirenz Causes Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Endothelial Cells

Marlene Weiß; Bernd Kost; Ingrid Renner-Müller; Eckhard Wolf; Ioannis Mylonas; Ansgar Brüning

The non-nucleoside reverse transcriptase inhibitor efavirenz is a widely prescribed antiretroviral drug used in combined antiretroviral therapy. Despite being an essential and life-saving medication, the required lifelong use of HIV drugs has been associated with a variety of adverse effects, including disturbances in lipid metabolism and increased cardiovascular risk. Efavirenz belongs to those HIV drugs for which cardiovascular and endothelial dysfunctions have been reported. It is here shown that elevated concentrations of efavirenz can inhibit endothelial meshwork formation on extracellular matrix gels by normal and immortalized human umbilical vein cells. This inhibition was associated with an increase in oxidative stress markers, endoplasmic reticulum (ER) stress markers, and autophagy. Induction of ER stress occurred at pharmacologically relevant concentrations of efavirenz and resulted in reduced proliferation and cell viability of endothelial cells, which worsened in the presence of elevated efavirenz concentrations. In combination with the HIV protease inhibitor nelfinavir, both oxidative stress and ER stress became elevated in endothelial cells. These data indicate that pharmacologically relevant concentrations of efavirenz can impair cell viability of endothelial cells and that these effects may be aggravated by either elevated concentrations of efavirenz or by a combined use of efavirenz with other oxidative stress-inducing medications.


Breast Cancer Research and Treatment | 2014

Pooled analysis of the prognostic relevance of progesterone receptor status in five German cohort studies

Jessica Salmen; Julia Neugebauer; Pa Fasching; Lothar Haeberle; Jens Huober; Achim Wöckel; Claudia Rauh; Florian Schuetz; Tobias Weissenbacher; Bernd Kost; Elmar Stickeler; Maximilian Klar; Marzenna Orlowska-Volk; Marisa Windfuhr-Blum; Joerg Heil; Joachim Rom; Christof Sohn; Tanja Fehm; Svjetlana Mohrmann; Christian R. Loehberg; Alexander Hein; R. Schulz-Wendtland; Andreas D. Hartkopf; Sara Y. Brucker; Diethelm Wallwiener; Klaus Friese; Arndt Hartmann; Matthias W. Beckmann; Wolfgang Janni; Brigitte Rack

The progesterone receptor (PR) has been increasingly well described as an important mediator of the pathogenesis and progression of breast cancer. The aim of this study was to assess the role of PR status as a prognostic factor in addition to other well-established prognostic factors. Data from five independent German breast cancer centers were pooled. A total of 7,965 breast cancer patients were included for whom information about their PR status was known, as well as other patient and tumor characteristics commonly used as prognostic factors. Cox proportional hazards models were built to compare the predictive value of PR status in addition to age at diagnosis, tumor size, nodal status, grading, and estrogen receptor (ER) status. PR status significantly increased the accuracy of prognostic predictions with regard to overall survival, distant disease-free survival, and local recurrence-free survival. There were differences with regard to its prognostic value relative to subgroups such as nodal status, ER status, and grading. The prognostic value of PR status was greatest in patients with a positive nodal status, negative ER status, and low grading. The PR-status adds prognostic value in addition to ER status and should not be omitted from clinical routine testing. The significantly greater prognostic value in node-positive and high-grade tumors suggests a greater role in the progression of advanced and aggressive tumors.


Journal of Perinatal Medicine | 2012

High-fidelity simulation increases obstetric self-assurance and skills in undergraduate medical students

Christoph Scholz; Corinna Mann; Veronika Kopp; Bernd Kost; Franz Kainer; Martin R. Fischer

Abstract Objective: Teaching intrapartum care is one of the most challenging tasks in undergraduate medical education. High-fidelity obstetric simulators might support students’ learning experience. The specific educational impact of these simulators compared with traditional methods of model-based obstetric teaching has not yet been determined. Study design: We randomly assigned 46 undergraduate medical students to be taught using either a high-fidelity simulator or a scale wood-and-leather phantom. Their self-assessments were evaluated using a validated questionnaire. We assessed obstetric skills and asked students to solve obstetric paper cases. Main outcome measures: Assessment of fidelity-specific teaching impact on procedural knowledge, motivation, and interest in obstetrics as well as obstetric skills using high- and low-fidelity training models. Results: High-fidelity simulation specifically improved students’ feeling that they understood both the physiology of parturition and the obstetric procedures. Students in the simulation group also felt better prepared for obstetric house jobs and performed better in obstetric skills evaluations. However, the two groups made equivalent obstetric decisions. Conclusion: This study provides first data on the impact of high-fidelity simulation in an undergraduate setting.


Clinical Infectious Diseases | 2010

Protease Inhibitor–Based Antiretroviral Prophylaxis during Pregnancy and the Development of Drug Resistance

Andrea Gingelmaier; Josef Eberle; Bernd Kost; Johannes R. Bogner; Joerg Hofmann; Tobias Weissenbacher; Ralph Köstner; Klaus Friese; Katharina Weizsaecker

BACKGROUND The aim of this study was to determine the development of drug resistance among pregnant women receiving a protease inhibitor-based antiretroviral prophylaxis for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV). METHODS HIV-infected pregnant women without maternal indication for antiretroviral therapy were enrolled prospectively. Genotypic resistance testing was performed prior to initiation of antiretroviral prophylaxis and was repeated 4-8 weeks after cessation of antiretroviral therapy at the time of delivery. RESULTS Forty pregnant women with HIV infection (Centers for Disease Control and Prevention stage A1 or A2) were included. All women received an antiretroviral regimen including either fixed-dose lopinavir/ritonavir (n = 33) or ritonavir-boosted saquinavir (n = 7) and a backbone consisting of 2 nucleoside reverse-transcriptase inhibitors. The mean duration of antiretroviral treatment was 8.4 weeks (range, 5-22 weeks). Primary resistance mutations were found in 2 patients (nonnucleoside reverse-transcriptase inhibitor resistance, K103N; protease inhibitor resistance, G48V). Postpartum genotypic resistance revealed no new relevant resistance mutations. CONCLUSIONS In our study no clinically significant resistance mutations developed in pregnant women receiving a short-term protease inhibitor-based antiretroviral regimen for prophylaxis of mother-to-child transmission of HIV. Future therapeutic options are therefore preserved.


Oncology Letters | 2017

Prevalence of human papillomavirus infection of the anal canal in women: A prospective analysis of high-risk populations

Bernd Kost; Jörg Hofmann; Susanne Stoellnberger; Florian Bergauer; Thomas Blankenstein; Irene Alba‑Alejandre; Angela Stein; Claudia Stuckart; Katharina Weizsäcker; Ioannis Mylonas; Sven Mahner; Andrea Gingelmaier

Infection with certain types of human papillomavirus (HPV) has been associated with the development of cervical and anal cancer. Worldwide, the incidence of anal cancer has increased markedly. The present study aimed to evaluate the prevalence of HPV infection of the uterine cervix and anal canal in human immunodeficiency virus (HIV)- and non-HIV-infected risk populations. Cervical and anal HPV swabs and cytology samples were collected from 287 patients at the University Hospital of Munich, Germany between 2011 and 2013. Patients were divided into HIV-negative controls (G1) and two risk groups, including HIV-negative patients with cytological abnormalities of the cervix (G2) and HIV-infected patients (G3). Data, including clinical parameters, were analysed. The risk groups had significantly more positive results for HPV in the anus (71.03 and 83.15% for G2 and G3, respectively), as compared with G1. The predominant HPV genotypes found in the anus were high-risk HPV genotypes, which were significantly correlated with concomittant cervical HPV findings. In the risk groups, a significant association between the cytological findings and HPV detection in the cervix was found, while the results of the anus revealed no significance. The results of the present study suggested that the prevalence of HPV infection in the anal canal of risk populations is high. Furthermore, patients with abnormal cervical cytology results and HIV-infected women, irrespective of their individual cervical findings, may have a risk of concomittant anal high-risk HPV infection. Based on the predominant HPV genotypes found in the study, HPV vaccination could reduce the incidence of anal cancer. Nevertheless, high-risk patients should be intensively screened for anal squamous intraepithelial abnormalities to avoid invasive cancer stages.


International Journal of Molecular Sciences | 2017

Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer

Susanne Beyer; Junyan Zhu; Doris Mayr; Christina Kuhn; Sandra Schulze; Simone Hofmann; Christian Dannecker; Udo Jeschke; Bernd Kost

Chromatin remodeling alters gene expression in carcinoma tissue. Although cervical cancer is the fourth most common cancer in women worldwide, a systematic study about the prognostic value of specific changes in the chromatin structure, such as histone acetylation or histone methylation, is missing. In this study, the expression of histone H3 acetyl K9, which is known to denote active regions at enhancers and promoters, and histone H3 tri methyl K4, which preferentially identifies active gene promoters, were examined as both show high metastatic potential. A panel of patients with cervical cancer was selected and the importance of the histone modifications concerning survival-time (overall survival and relapse-free survival) was analyzed in 250 cases. Histone H3 acetyl K9 staining was correlated with low grading, low FIGO (TNM classification and the International Federation of Gynecology and Obstetrics) status, negative N-status and low T-status in cervical cancer, showing a higher expression in adenocarcinoma than in squamous cell carcinoma. Cytoplasmic expression of histone H3 tri methyl K4 in a cervical cancer specimen was correlated with advanced T-status and poor prognosis. While cytoplasmic H3K4me3 expression seemed to be a marker of relapse-free survival, nuclear expression showed a correlation to poor prognosis in overall survival. Within this study, we analyzed the chemical modification of two histone proteins that are connected to active gene expression. Histone H3 acetyl K9 was found to be an independent marker of overall survival. Histone H3 tri methyl K4 was correlated with poor prognosis and it was found to be an independent marker of relapse-free survival. Therefore, we could show that chromatin remodeling plays an important role in cervical cancer biology.


Journal of Histochemistry and Cytochemistry | 2015

Expression of Thyroid Hormone Receptors in Villous Trophoblasts and Decidual Tissue at Protein and mRNA Levels Is Downregulated in Spontaneous and Recurrent Miscarriages

Brigitte Ziegelmüller; Aurelia Vattai; Bernd Kost; Christina Kuhn; Simone Hofmann; Birgit Bayer; Bettina Toth; Udo Jeschke; Nina Ditsch

Thyroid hormones are essential for the maintenance of pregnancy, and a deficiency in maternal thyroid hormones has been associated with early pregnancy losses. The expression of THRα1, THRβ1 and THRα2 increases with gestational age. The aim of this study was the investigation of the protein and mRNA-levels of THR isoforms THRα1, THRα2, THRβ1 and THRβ2 in normal, spontaneous and recurrent miscarriages. The identification of THR-expressing cells in the decidua was done with double immunofluorescence. The nuclear expression of THRα1, THRα2, THRβ1 and THRβ2 is downregulated at protein level in spontaneous and recurrent miscarriages in villous trophoblast tissue. In decidual tissue, we found a significant downregulation only for THRα1 in spontaneous miscarriages. For recurrent miscarriages, THRα1 and THRβ1 were both significantly downregulated in decidual tissue. By applying HLA-G as a trophoblast marker, we found a significant co-expression only for THRβ2. The results of our study show that thyroid hormone receptors THRα1, THRα2, THRβ1 and THRβ2 are downregulated in spontaneous and recurrent miscarriages. The majority of cells expressing the thyroid hormone receptors in the decidua are decidual stromal cells.


European Journal of Obstetrics & Gynecology and Reproductive Biology | 2015

The expression of thyroid hormone receptors (THR) is regulated by the progesterone receptor system in first trimester placental tissue and in BeWo cells in vitro.

Aurelia Vattai; Brigitte Ziegelmüller; Bernd Kost; Christina Kuhn; Simone Hofmann; Birgit Bayer; Katja Anslinger; Udo Jeschke; Nina Ditsch

BACKGROUND Thyroid hormones are essential for the maintenance of pregnancy and a deficiency in maternal thyroid hormones has been associated with early pregnancy losses. The aim of this study was a systematic investigation of the influence of mifepristone (RU 486) on the expression of the thyroid hormone receptor (THR) isoforms THRα1, THRα2, THRβ1 and THRβ2 on protein and mRNA-level. METHODS Samples of placental tissue were obtained from patients with mifepristone induced termination of pregnancy (n=13) or mechanical induced termination of normal pregnancy (n=20), each from the 4th to 13th week of pregnancy. Expression of THRα1, THRα2, THRβ1 and THRβ2 was analysed on protein level by immunohistochemistry and on mRNA level by real time RT-PCR (TaqMan). The influence of progesterone on THR gene expression was analysed in the trophoblast tumour cell line BeWo by real time RT-PCR (TaqMan). RESULTS Nuclear expression of THRα1, THRα2 and THRβ1 is downregulated on protein level in mifepristone (RU 486) treated villous trophoblast tissue. In decidual tissue, we found a significant downregulation only for THRα1 in mifepristone treated tissue. On mRNA level, we also found a significantly reduced expression of THRA but no significant downregulation for THRB in placental tissue. The gene THRA encodes the isoform THRα and the gene THRB encodes the isoform THRβ. The majority of cells expressing the thyroid hormone receptors in the decidua are decidual stromal cells. In addition, in vitro experiments with trophoblast tumour cells showed that progesterone significantly induced THRA but not THRB expression. CONCLUSIONS Termination of pregnancy with mifepristone (RU 486) leads to a downregulation of THRα1, THRα2 and THRβ1 in villous trophoblasts and in addition to a decreased expression of THRA in placental tissue. Decreased expression of THRα1 induced by RU486 could also be found in the decidua. Therefore inhibition of the progesterone receptor may be responsible for this downregulation. This assumption is supported by the finding, that stimulation of the progesterone receptor by progesterone itself up-regulated THRA in trophoblast cells in vitro.


Oncology | 2016

Comparison of HER2 Expression in Primary Tumor and Disseminated Tumor Cells in the Bone Marrow of Breast Cancer Patients.

Brigitte Rack; Ewa Zombirt; Elisabeth Trapp; Julia Jückstock; Ulrich Andergassen; Julia Neugebauer; Bernd Kost; Tobias Weissenbacher; Udo Jeschke; Christian Schindlbeck; Wolfgang Janni; Marianna Alunni-Fabbroni

Objective: The aim of this study was to measure the human epidermal growth factor receptor 2 (HER2) status of disseminated tumor cells (DTCs) from bone marrow (BM) aspirates and to assess correspondence or discrepancy with the primary tumor. Methods: DTCs were isolated from the BM of 156 breast cancer patients. Cytokeratin-positive DTCs were further analyzed by the chromogenic in situ hybridization method to detect HER2 gene amplification. Results: A significant correlation (p = 0.021) was found between the HER2 status of DTCs and the primary tumors. Sixty-one (68.5%) patients had a corresponding status. However, a shift of phenotype between primary tumor and DTCs was found in the remaining patients. Conclusion: This study showed a significant grade of discordance of the HER2 status between primary tumors and DTCs in the BM of a relevant subgroup of patients. Detection of HER2 amplification on DTCs could therefore help to better stratify patients for a more tailored therapy, since they would benefit from a HER2-targeted therapy.


Oncology Letters | 2017

The involvement of E6, p53, p16, MDM2 and Gal-3 in the clinical outcome of patients with cervical cancer

Annika Stiasny; Christoph P. Freier; Christina Kuhn; Sandra Schulze; Doris Mayr; Christoph Alexiou; Christina Janko; Irmi Wiest; Christian Dannecker; Udo Jeschke; Bernd Kost

High-risk human papilloma virus (HPV) is the leading cause of cervical cancer. HPV oncogenes are responsible for the development of malignancy, and the E6 oncoprotein that HPV expresses induces the degradation of tumour suppressor protein p53 (p53). This degradation leads to the upregulation of p16; however, unidentified proteins may also serve a role in the development and progression of cervical cancer. Therefore, the aim of the present study was to analyse the expression levels of E6, p53, p16, MDM2 proto-oncogene (MDM2) and galectin-3 (gal-3) in cervical cancer specimens. A total of 250 cervical cancer tissue slides were used. The expression of E6, p53, p16, MDM2 and gal-3 was analysed with immunohistochemical methods and a semi-quantitative scoring. SPSS software was used for the statistical evaluation of staining results and survival analysis of patients with cervical cancer. Cervical cancer specimens demonstrated significantly increased E6 staining with advanced T-status and increased International Federation of Gynecology and Obstetrics classification. E6, p53 and p16 demonstrated significantly different expression levels in squamous epithelial tissue compared with adenocarcinomas. MDM2 and gal-3 demonstrated positively correlated expression levels in cervical cancer. In addition, gal-3 expression was correlated with poor prognosis in p16-negative cases. A negative correlation between the expression of E6 and a mutated form of p53 was also identified in cervical cancer. p53 mutation was demonstrated to be common in cervical cancer, and gal-3 and MDM2 appeared to act in a combined manner in this type of tumour. As gal-3 is overexpressed in the cervical cancer tissue of patients with poor prognosis, the use of gal-3 inhibitors should be investigated in future studies.

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Christoph Alexiou

University of Erlangen-Nuremberg

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Christina Janko

University of Erlangen-Nuremberg

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Matthias W. Beckmann

University of Erlangen-Nuremberg

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Alexander Hein

University of Erlangen-Nuremberg

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