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News Article | November 28, 2016

Topics range from medical imaging to analysis of authority and trust in US politics and society; €87 million in funding for an initial 4.5 years The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) is establishing 20 new Research Training Groups (RTGs) to further support early career researchers in Germany. They include three International Research Training Groups (IRTGs) with partners in the UK, New Zealand and Austria. This was decided by the responsible Grants Committee during its autumn session in Bonn. The Research Training Groups will receive funding of around 87 million euros for an initial period of four and a half years. In addition to the 20 new collaborations, the Grants Committee approved the extension of seven Research Training Groups for another four and a half years. This funding instrument enables doctoral researchers to complete their theses in a structured research and qualification programme at a high academic level. In total the DFG is currently funding 206 Research Training Groups, including 41 International Research Training Groups; the 20 new groups will commence their work in 2017. The new Research Training Groups in detail (in alphabetical order by their host universities, including the name of the applicant universities): Sketches, abstracts, notes, records, excerpts, essays, articles and glosses: all these 'small forms' of writing are an essential part of the practice of research, teaching, art and the media. The Research Training Group "The Literary and Epistemic History of Small Forms" intends to study their emergence and development, with which they are also involved in the success of prose, from antiquity to the present day. The group will also seek to understand how processes of understanding are controlled, reflected and channelled in specific media using these small forms. (Host university: Humboldt University of Berlin, Spokesperson: Professor Dr. Joseph Vogl) Imaging techniques such as ultrasound, X-rays and CT scans are well known. Medical findings are established on the basis of the image data produced in technically and mathematically complex processes. However, physicians' diagnoses are normally made on the basis of qualitative arguments, which do not make full use of the information content of image data and in particular the potential of imaging methods. The "BIOQIC - BIOphysical Quantitative Imaging Towards Clinical Diagnosis" Research Training Group will therefore study biophysical quantitative medical imaging to further develop these quantitative methods and apply them in clinical pilot studies to obtain more information from the imaging process. (Host universities: Humboldt University of Berlin and Free University of Berlin / Charité - University Hospital Berlin, Spokesperson: Professor Dr. Ingolf Sack) The Research Training Group "World Politics: The Emergence of Political Arenas and Modes of Observation in World Society" is concerned with the emergence of world politics as a type of politics in its own right. From the perspective of the theory of global society, the group aims to investigate the extent to which the emergence of world politics represents both a consequence and a precondition of the constitution of modern states. Researchers specialising in political science, sociology, history and law will collaborate to address this question. (Host university: University of Bielefeld, Spokesperson: Professor Dr. Mathias Albert) Perception, the authorship of action, emotions, and social and linguistic understanding are central cognitive phenomena. The Research Training Group "Situated Cognition - New Concepts in Investigating Core Mental Phenomena" will combine the philosophy of the mind and cognition with cognition sciences, which closely interact with cognitive neurosciences. The main aim of the group is to identify deficits in existing concepts of the human mind and further develop these concepts such as to give more attention to more recent developments in cognition sciences that are not yet adequately reflected in philosophical theory formation. (Host university: University of Bochum, Spokesperson: Professor Dr. Albert Newen; Additional applicant university: University of Osnabrück) Short-term dynamic loads such as impacts, detonations or earthquakes can cause structures to collapse. The aim of the Research Training Group "Mineral-Bonded Composites for Enhanced Structural Impact Safety" is to make existing buildings and structures more resilient through the addition of thin-layer reinforcements. With the help of new mineral-bonded materials known as composites, the researchers aim to improve the safety of people and the infrastructure essential to their lives. (Host university: Technical University of Dresden, Spokesperson: Professor Dr.-Ing. Viktor Mechtcherine) According to the World Health Organization, more than 422 million people worldwide suffer from diabetes, with approximately 3.7 million mortalities per year. In Germany, experts estimate the number of sufferers at 8 to 10 million. The German-British Research Training Group "Immunological and Cellular Strategies in Metabolic Disease (ICSMD)" aims to achieve a better understanding of the pathophysiology of type 1 and type 2 diabetes and develop strategies to halt the progress of the disease or even discover a cure. (Host university: Technical University of Dresden, Spokesperson: Professor Dr. Stefan R. Bornstein, Cooperation partner: King's College London, Great Britain) The German-Austrian Research Training Group "Resonant Self-World Relations in Ancient and Modern Socio-Religious Practices" will investigate ritual practices which generate, determine or express meaningful relations between people and the world - to other people, things, nature, self, heaven and God or the gods. The nature of these world relations, in turn, says much about a given culture and the social or gender positions which characterise it. The establishment of the group has been approved by the DFG's Grants Committee on Research Training Groups. The Austrian Science Fund (FWF) will reach a decision on co-funding at its next meeting. (Host university: University of Erfurt, Spokesperson: Professor Dr. Jörg Rüpke, Cooperation partner: University of Graz, Austria) The Research Training Group "Configurations of Cinema" understands film as a medium in constant transformation. In three working areas, 'formations', 'usages' and 'localisations', the group intends to analyse the genealogy and transformation of a wide variety of configurations of film, also in regard to the shift from cinemas to portable digital devices. The researchers will thus explore new modes of writing the history of a medium that is subject to constant change and examine film's defining features. (Host university: Goethe University of Frankfurt am Main, Spokesperson: Professor Dr. Vinzenz Hediger) How are authority and trust formed in US politics? How does this happen in American society, in religion and culture? The Research Training Group "Authority and Trust in American Culture, Society, History and Politics" intends to answer these questions. The chosen object of analysis is the USA because, due to its early democratization, egalitarian-libertarian political culture, ethnocultural heterogeneity and international hegemony, the country offers particularly fundamental insights into the problems of authority and trust in the modern age. (Host university: University of Heidelberg, Spokesperson: Professor Dr. Manfred Berg) The Research Training Group "Tip- and Laser-Based 3D-Nanofabrication in Extended Macroscopic Working Areas" will develop manufacturing methods for two-dimensional and three-dimensional structures on a nanometre scale using tip-based and laser-based techniques. The research work will primarily be based on nanopositioning and nanomeasuring machines, allowing structuring and measuring to take place on the same machine. With the aid of this equipment the researchers intend to give particular attention to larger and uneven surfaces, such as optical lenses. (Host university: Technical University of Ilmenau, Spokesperson: Professor Dr.-Ing. Eberhard Manske) Batteries are seen as key components of future technologies such as electric vehicles and energy supplies. The Research Training Group "SIMET - Simulation Mechano-Electro-Thermal Processes in Lithium-Ion Batteries" will work on numerical simulation methods for lithium-ion batteries. The researchers will address the problem in a multi-scale approach in several different orders of magnitude. As well as individual particles, they will simulate the electrode pair and the complete cell. (Host university: Karlsruhe Institute of Technology (KIT), Spokesperson: Professor Dr.-Ing. Thomas Wetzel) Patients with chronic diseases of the brain are normally treated with medication, but this is frequently associated with side effects. Neuroimplants, on the other hand, allow localised therapy, but must satisfy many requirements. The Research Training Group "Materials for Brain (M4B): Thin Film Functional Materials for Minimally Invasive Therapy of Brain Diseases" intends to study the use of nanoscale, therapeutically active coatings for implants of this type. Its aim is to achieve the controlled release of substances into the brain by means of the coating. (Host university: University of Kiel, Spokesperson: Professor Dr. Christine Selhuber-Unkel) We do not know enough about the reaction of lake ecosystems to environmental changes to be able to predict reliably whether they actually return to their original state following renaturation measures. Taking the example of Lake Constance, the Research Training Group "R3 - Responses to Biotic and Abiotic Changes, Resilience and Reversibility of Lake Ecosystems" aims to better understand the reactions of lake ecosystems to environmental changes, their resilience - the resistance of an ecosystem to disturbances - and their reversibility, in other words the ability to return to an original state following disturbance. (Host university: University of Constance, Spokesperson: Professor Dr. Frank Peeters) For many mathematical questions, approximation and dimension reduction are the most important tools for achieving simplified representation and therefore saving computing time. The Research Training Group "Mathematical Complexity Reduction (CoRe)" will approach complexity reduction in a more general sense and will also investigate when problems can be made easier to solve through embedding in higher dimensional spaces ('liftings'). The group also intends to systematically examine the influence of the costs of data collection. (Host university: University of Magdeburg, Spokesperson: Professor Dr. Sebastian Sager) One of the basic requirements for the economic success of a business is the efficient use of resources. In an increasingly networked world, several decision-makers are often involved in resource management and the amount of data available is growing. The Research Training Group "Advanced Optimization in a Networked Economy (AdONE)", based in the fields of operations research and management science, aims to develop models and processes and transfer these into software solutions designed to enable efficient use of resources through intelligent planning and control. (Host university: Technical University of Munich, Spokesperson: Professor Dr. Stefan Minner) Rapidly increasing antibiotic resistance and the growth of so-called lifestyle diseases confront humanity with enormous challenges. In the Research Training Group "Evolutionary Processes in Adaptation and Disease (RTG EvoPAD)", doctoral researchers in biology, medicine and the philosophy of science will therefore investigate adaptations and diseases by drawing on modern evolutionary research and approaches in the philosophy of science, in order to better understand them. (Host university: University of Münster, Spokesperson: Professor Dr. Joachim Kurtz) The development of metropolises prior to the age of industrialisation and globalisation has not, so far, been the subject of sufficient research. The "Pre-Modern Metropolitanism" Research Training Group intends to close this gap by investigating the establishment, impact and evolution of major urban centres from Ancient Greece and Rome to the dawn of the industrial age. (Host university: University of Regensburg, Spokesperson: Professor Dr. Jörg Oberste) Until now there have been few if any approaches to the improvement of robots that work with easily modifiable materials or handle soft tissue. In a German-New Zealand Research Training Group, doctoral researchers will investigate "Soft Tissue Robotics - Simulation-Driven Concepts and Design for Control and Automation for Robotic Devices Interacting with Soft Tissues". The aim is to further develop simulation techniques and sensors in order to enable new regulation and control technology for robots that interact with soft materials. (Host university: University of Stuttgart, Spokesperson: Professor Oliver Röhrle, Ph.D., Cooperation partner: University of Auckland, New Zealand) For many tumours there are no means of prevention, which is why they are usually diagnosed in advanced stages. It is also difficult to develop efficient therapies for tumours because there are genomic differences not only between different tumours (intertumoral) but also within a single tumour (intratumoral), which contributes to therapy resistance. The Research Training Group "Heterogeneity and Evolution in Solid Tumors (HEIST): Molecular Characterization and Therapeutic Consequences" aims to understand intra- and intertumoral heterogeneity, the evolutionary history of a tumour and the genes responsible for it in order to improve the treatment of tumours even in advanced stages. (Host university: University of Ulm, Spokesperson: Professor Dr. Thomas Seufferlein) Aberrations in what is known as the ubiquitin system in the body contribute to the development of a wide range of diseases such as cancer, neurodegenerative diseases and infectious diseases. The aim of the Research Training Group "Understanding Ubiquitylation: From Molecular Mechanisms To Disease" is therefore to understand the biochemical and pathogenic mechanisms which underlie diseases associated with the ubiquitin system. (Host university: University of Würzburg, Spokesperson: Professor Dr. Alexander Buchberger) Further information will also be provided by the spokespersons of the Research Training Groups. More details about the funding programme and the funded Research Training Groups is available at: http://www.

Chantraine F.,CHR Citadelle | Chantraine F.,University of Liège | Braun T.,University Hospital Berlin | Gonser M.,Horst Schmidt Kliniken | And 3 more authors.
Acta Obstetricia et Gynecologica Scandinavica | Year: 2013

Objective Abnormally invasive placenta (AIP) poses diagnostic and therapeutic challenges. We analyzed clinical cases with confirmed placenta increta or percreta. Design Retrospective case series. Setting Multicenter study. Population Pregnant women with AIP. Methods Chart review. Main outcome measures Prenatal detection rates, treatment choices, morbidity, mortality and short-term outcome. Results Sixty-six cases were analyzed. All women and all but three fetuses survived; 57/64 women (89%) had previous uterine surgery. In 26 women (39%) the diagnosis was not known before delivery (Group 1), in the remaining 40 (61%) diagnosis had been made between 14 and 37 weeks of gestation (Group 2). Placenta previa was present in 36 women (54%). In Groups 1 and 2, 50% (13/26) and 62% (25/40) of the women required hysterectomy, respectively. In Group 1 (unknown at the time of delivery) 69% (9/13) required (emergency) hysterectomy for severe hemorrhage in the immediate peripartum period compared with only 12% (3/25) in Group 2 (p = 0.0004). Mass transfusions were more frequently required in Group 1 (46%, 12/26 vs. 20%, 8/40; p = 0.025). In 18/40 women (45%) from Group 2 the placenta was intentionally left in situ; secondary hysterectomies and infections were equally frequent (18%) among these differently treated women. Overall, postpartum infections occurred in 11% and 20% of women in Groups 1 and 2, respectively. Conclusions AIP was known before delivery in more than half of the cases. Unknown AIP led to significantly more emergency hysterectomies and mass transfusions during or immediately after delivery. Prenatal diagnosis of AIP reduces morbidity. Future studies should also address the selection criteria for cases appropriate for leaving the placenta in situ. © 2013 The Authors Acta Obstetricia et Gynecologica Scandinavica © 2013 Nordic Federation of Societies of Obstetrics and Gynecology.

Badakhshi H.,University Hospital Berlin | Kaul D.,University Hospital Berlin | Nadobny J.,Charité - Medical University of Berlin | Wille B.,University Hospital Berlin | And 2 more authors.
British Journal of Radiology | Year: 2013

Objective: To test the feasibility of volumetric modulated arc therapy (VMAT) in breast cancer and to compare it with three-dimensional conformal radiotherapy (3D-CRT) as conventional tangential field radiotheraphy ( conTFRT). Methods: 12 patients (Stage 1, 8: 6 left breast cancer and 2 right breast cancer; Stage 2, 4: 2 on each side). Three plans were calculated for each case after breast-conserving surgery. Breast was treated with 50Gy in four patients with supraclavicular lymph node inclusion, and in eight patients without the node inclusion. Multiple indices and dose parameters were measured. Results: V95% was not achieved by any modality. Heterogeneity index: 0.16 (VMAT), 0.13 [intensity-modulated radiotherapy (IMRT)] and 0.14 ( conTFRT). Conformity index: 1.06 (VMAT), 1.15 (IMRT) and 1.69 ( conTFRT). For both indices, IMRT was more effective than VMAT (p=0.009, p=0.002). Dmean and V20 for ipsilateral lung were lower for IMRT than VMAT (p>0.0001, p=0.003). Dmean, V2 and V5 of contralateral lung were lower for IMRT than VMAT (p.0.0001, p50.005). Mean dose and V5 to the heart were lower for IMRT than for VMAT (p=0.015, p=0.002). Conclusion: The hypothesis of equivalence of VMAT to IMRT was not confirmed for planning target volume parameter or dose distribution to organs at risk. VMAT was inferior to IMRT and 3D-CRTwith regard to dose distribution to organs at risk, especially at the low dose level. Advances in knowledge: New technology VMAT is not superior to IMRT or conventional radiotherapy in breast cancer in any aspect. © 2013 The Authors. Published by the British Institute of Radiology.

Matziolis G.,University Hospital Berlin | Hube R.,OCM | Perka C.,University Hospital Berlin | Matziolis D.,University Hospital Berlin
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2012

Background: The symmetry and equality of the flexion and extension gap are essential for successful endoprosthetic knee arthroplasty. Cruciate ligament sparing endoprosthetic designs are implanted with a measured resection technique, so that the posterior bone resection corresponds to the posterior condyle thickness. However, this correlation only applies if the sagittal alignment is set at 0°. The aim of the present study was therefore to investigate the extent to which the flexion gap is influenced by a flexed implantation of the femoral component. Methods: The implant geometry of all available sizes of the knee systems Columbus, e. motion (Aesculap), PFC Sigma (DePuy), Natural Knee II, Innex, Nexgen LPS Flex and Gender (Zimmer), and TC Plus (Smith & Nephew) was recorded. Based on this data, a virtual implantation of the femoral component with a sagittal alignment between 0° and 5° of flexion was simulated. The resulting flexion gaps were calculated depending on the component alignment. The relationships between component alignment (in degrees) and flexion gap (in mm) were documented for every implant. Results: The narrowing of the flexion gap with increasing flexion was more or less linear in the range investigated and was dependent on the system used and the implant size. A narrowing of the flexion gap by 1 mm resulted from 2° (1. 9°-2. 3°) flexion in the e. motion prosthesis, 1. 9° (1. 6°-2. 4°) in the Columbus, 1. 6° (1. 5°-1. 8°) in the PFC Sigma, 2. 0° (1. 7°-2. 4°) in the Nexgen LPS Flex and Gender, 1. 7° (1. 6°-1. 8°) in the Innex, 2. 2° (1. 5°-2. 6°) in the TC Plus and 2. 0° (2. 0°-2. 1°) in the Natural Knee. Conclusions: Even a small flexion of the femoral component leads to a reduction of the flexion gap and thus potentially to limited mobility in the measured resection technique. On the other hand, in navigation-assisted implantation, slight flexion of the component can possibly be used to adjust the flexion gap smoothly. Level of evidence: II. © 2011 Springer-Verlag.

Arsenic R.,University Hospital Berlin | Lehmann A.,University Hospital Berlin | Budczies J.,University Hospital Berlin | Koch I.,University Hospital Berlin | And 6 more authors.
Applied Immunohistochemistry and Molecular Morphology | Year: 2014

Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit a (PIK3CA) is a central element of a signaling pathway involved in cell proliferation, survival, and growth. Certain mutations in this pathway result in enhanced PI3K signaling, which is associated with oncogenic cellular transformation and cancer. The aims of this study were to characterize different types of PIK3CA mutations in exons 9 and 20 in a series of primary breast carcinomas and to correlate the results with clinicopathologic parameters and survival. We used frozen tissue samples and sequenced exons 9 and 20 for a series of 241 patients with a diagnosis of breast carcinoma. We found that 15.8% of the primary breast carcinomas possessed PIK3CA mutations in either exon 9 or exon 20. The rate of PIK3CA mutations was increased in HR+/HER2- tumors (18.6%), but this difference did not reach a statistical significance. The lowest rate of mutations was observed in HR+/HER2+ tumors (5.3%). No statistically significant association was found betweenthe presence of PIK3CA mutations and the prognostic/clinical features of breast cancer, including histologic subtype, Her2 status, axillary lymph node involvement, tumor grade, and tumor stage. However, the presence of the H1047R mutation in 10 samples was associated with a statistically significantly worse overall survival. PIK3CA mutation was found to be a frequent genetic change in all breast cancer subtypes but occurred with the highest rate in HR +/HER2- tumors. Further studies are needed to validate the prognostic impact of different PIK3CA mutations. © 2013 by Lippincott Williams and Wilkins.

Hartwig I.R.V.,University of Hamburg | Pincus M.K.,University Hospital Berlin | Diemert A.,University of Hamburg | Hecher K.,University of Hamburg | Arck P.C.,University of Hamburg
Human Reproduction | Year: 2013

Study Question Are maternal progesterone levels in early pregnancy associated with fetal birthweight? Summary Answer Low levels of first-trimester maternal progesterone are significantly associated with a reduction in birthweight in girls, but not boys. What is Already KnownProgesterone in the third trimester of pregnancy has previously been related to birthweight in humans. Study Design, Size, Duration Pregnant women between gestational weeks 4 and 12 were recruited by 99 obstetricians in private practice and enrolled in a prospective cohort study. A follow-up took place at birth. Women younger than 18 years, who had undergone fertility treatments or were diagnosed with infectious diseases, were excluded from the study. A subgroup of 906 participants in whom progesterone had been measured was then selected retrospectively based on the following criteria: no miscarriages, elective abortions or pregnancy complications, infections or multiple births. Data from the follow-up were available for 623 women, who were included in the analyses. Participants/ Materials, Setting, Methods The study was coordinated at the Charité University Medicine in Berlin, Germany. Anthropometric, medical and psychosocial information were collected and serum progesterone and estradiol levels were measured in women during the first trimester of pregnancy, followed by the documentation of the pregnancy outcome at birth. Univariable and multivariable regression analyses were performed to identify maternal markers, among them progesterone, affecting birthweight and to determine environmental and maternal factors that are associated with maternal progesterone levels during pregnancy. Main Results AND THE ROLE OF CHANCEIn the multivariable regression model, each increase in maternal progesterone by 1 ng/ml during the first trimester increased girls' birthweight by 10.17 g (95% CI: 2.03-18.31 g). If the mother carried a boy, maternal smoking and perceived worries during early pregnancy predicted a reduced birthweight, irrespective of progesterone levels. Maternal body mass index over 25 and maternal age <21 years significantly correlated with the reduced levels of progesterone. Correlations between environmental challenges and maternal progesterone did not reach levels of significance. Since the analyses were exploratory, the likelihood that results may be due to chance is increased. Limitations, Reasons for Caution Due to the exploratory nature of the analyses, results need to be independently confirmed in a larger sample. Furthermore, our findings pertain to pregnant women without pregnancy complications or fertility treatments. Wider Implications of the Findings Maternal progesterone during early pregnancy is an indicator of subsequent fetal development in female children. Future studies should confirm this relationship and determine whether maternal progesterone is a useful tool in predicting pregnancies at risk resulting in the birth of a girl with low birthweight. Detailed identification of environmental factors modulating maternal progesterone levels should be addressed in future studies. Study Funding/Potential Competing InterestsFinancial support was provided by the Alexander von Humboldt Foundation, Excellence Initiative of the Hamburg Foundation for Research and the Association for Prevention and Information for Allergy and Asthma (Pina e.V.). The authors have no conflict of interest. © 2012 The Author.

Matziolis G.,University Hospital Berlin | Mehlhorn S.,University Hospital Berlin | Schattat N.,University Hospital Berlin | Diederichs G.,University Medicine Berlin | And 3 more authors.
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2012

Purpose: There are two different techniques for retaining the posterior cruciate ligament (PCL) in total knee arthroplasty. The attachment of the PCL can be spared during resection of the tibial plateau, so that a small posterior bone block remains. In contrast to this, many surgeons resect the tibial plateau completely and detach a part of the tibial PCL attachment from the resected material. The objective of this study was to determine how big this part is in an anatomical resection of the tibial plateau with 0° and 7° slope and whether it is gender-dependent. Methods: Two hundred consecutive patients who had undergone MRI of a knee joint were included. Patients were excluded if they were younger than 18 years or had dysplasia of the knee joint or injuries of the posterior cruciate ligament. The MRIs of 182 knees that fulfilled the inclusion criteria were analysed. For each knee, an anatomical tibial resection with 0° and 7° posterior slope was simulated, and the parts of the tibial PCL attachment that were resected and retained were determined. Results: Given a measured tibial resection with 0° slope, 45 ± 28% of the tibial PCL attachment was removed in the men, compared with 46 ± 30% in the women (n. s.). Given a resection with 7° slope, 69 ± 24% of the tibial PCL attachment was removed in the men and 67 ± 25% in the women. This corresponded to a complete resection in 19 men (20%) and 16 women (24%). Conclusions: Independently of gender, the anatomical resection of the tibia leads to the removal of a considerable part of the tibial PCL attachment, if this is not spared in the form of a bone block during resection. This becomes increasingly relevant with higher posterior slope of the resection plane. In the case of a cruciate-retaining surgical technique, the retention of the posterior tibial cortical bone in the area of attachment of the PCL is therefore strongly recommended. Level of evidence: II. © 2011 Springer-Verlag.

Banning A.,Justus Liebig University | Regenbrecht C.R.A.,University Hospital Berlin | Tikkanen R.,Justus Liebig University
Cellular Signalling | Year: 2014

Flotillins are highly conserved and widely spread proteins that function in receptor tyrosine kinase signaling and membrane trafficking processes. Flotillin-1 and flotillin-2 have been shown to form both homo- and hetero-oligomers, and their cellular localization changes during signaling. Increased expression of flotillins has been detected in several types of cancer and shown to correlate with poor survival. Consistently, flotillin-2 knockout mice show a reduced formation of metastases in a breast cancer animal model. Our recent data have shown that flotillin-1 depletion results in diminished activation of the epidermal growth factor receptor and impairs its downstream signaling towards the mitogen activated protein kinases and the respective transcriptional response. Here we show that genetic ablation of flotillin-2 in a mouse model or its knockdown in cultured cells increases extracellular signal regulated kinase (ERK) activation. Furthermore, the downstream transcriptional targets of ERK and p53 are upregulated at both mRNA and protein levels. These data suggest that opposite effects are obtained upon ablation of one of the two flotillins, with flotillin-2 knockout/knockdown enhancing and flotillin-1 knockdown inhibiting ERK signaling. Due to their overexpression in cancers, flotillins may be considered as cancer therapy targets. However, our findings suggest that care needs to be taken when interfering with flotillin function, as undesired effects such as deregulation of growth-associated genes may emerge in certain cell types. © 2013 Elsevier Inc.

Badakhshi H.,University Hospital Berlin | Graf R.,University Hospital Berlin | Budach V.,University Hospital Berlin | Wust P.,University Hospital Berlin
Strahlentherapie und Onkologie | Year: 2015

Purpose: The biochemical relapse-free survival (bRFS) rate after treatment with permanent iodine-125 seed implantation (PSI) or combined seeds and external beam radiotherapy (COMB) for clinical stage T1–T2 localized prostate cancer is a clinically relevant endpoint. The goal of this work was to evaluate the influence of relevant patient- and treatment-related factors. Materials and methods: The study population comprised 312 consecutive patients treated with permanent seed implantation. All patients were evaluable for analysis of overall survival (OS) and disease-specific survival (DSS), 230 for bRFS, of which 192 were in the PSI group and 38 in the COMB group. The prescribed minimum peripheral dose was 145 Gy for PSI, for COMB 110 Gy implant and external beam radiotherapy of 45 Gy. The median follow-up time was 33 months (range 8–66 months). bRFS was defined as a serum prostate-specific antigen (PSA) level ≤ 0.2 ng/ml at last follow-up. Results: Overall, the actuarial bRFS at 50 months was 88.4 %. The 50-month bRFS rate for PSI and COMB was 90.9 %, and 77.2 %, respectively. In the univariate analysis, age in the categories ≤ 63 and > 63 years (p < 0.00), PSA nadir (≤ 0.5 ng/ml and > 0.5 ng\ml) and PSA bounce (yes/no) were the significant predicting factors for bRFS. None of the other patient and treatment variables (treatment modality, stage, PSA, Gleason score, risk group, number of risk factors, D90 and various other dose parameters) were found to be a statistically significant predictor of 50-month bRFS. Conclusion: The biochemical failure rates were low in this study. As a proof of principle, our large monocenteric analysis shows that low-dose-rate brachytherapy is an effective and safe procedure for patients with early stage prostate cancer. © 2014, Springer-Verlag Berlin Heidelberg.

Arsenic R.,University Hospital Berlin
Diagnostic Pathology | Year: 2014

Background: 3-phosphoinositide-dependent protein kinase-1 (PDK1) functions downstream of phosphoinositide 3-kinase (PIK3) and activates members of the AGC family of protein kinases that are known to play crucial roles in physiological processes associated with cell metabolism, growth, proliferation and survival. Changes in the expression and activity of PDK1 and several AGC kinases have been linked to human disease, including cancer.Methods: We used immunohistochemical analysis to determine PDK1 expression in 241 tumors from patients with breast cancer in which we had previously analyzed PIK3CA mutation status.Results: Moderate or high expression of PDK1 was observed in 213 of the 241 cases (88%). There was no correlation between PIK3CA mutation status and PDK1 overexpression.Conclusion: Our findings indicate that PDK1 is independently activated in breast cancer and not only as part of the PIK3CA pathway, suggesting that PDK1 plays a specific and distinct role from the canonical PIK3/Akt pathway and promotes oncogenesis independently of AKT. Our data implicate PDK-1 and downstream components of the PDK-1 signaling pathway as promising therapeutic targets for the treatment of breast cancer. © 2014 Arsenic; licensee BioMed Central Ltd.

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