Fabian A.-K.,Max Planck Institute of Psychiatry |
Marz A.,Max Planck Institute of Psychiatry |
Neimanis S.,Universitaetsklinikum Frankfurt |
Biondi R.M.,Universitaetsklinikum Frankfurt |
And 2 more authors.
PLoS ONE | Year: 2013
The FK506-binding protein 51 (FKBP51) is an Hsp90-associated co-chaperone which regulates steroid receptors and kinases. In pancreatic cancer cell lines, FKBP51 was shown to recruit the phosphatase PHLPP to facilitate dephosphorylation of the kinase Akt, which was associated with reduced chemoresistance. Here we show that in addition to FKBP51 several other members of the FKBP family bind directly to Akt. FKBP51 can also form complexes with other AGC kinases and mapping studies revealed that FKBP51 interacts with Akt via multiple domains independent of their activation or phosphorylation status. The FKBP51-Akt1 interaction was not affected by FK506 analogs or Akt active site inhibitors, but was abolished by the allosteric Akt inhibitor VIII. None of the FKBP51 inhibitors affected AktS473 phosphorylation or downstream targets of Akt. In summary, we show that FKBP51 binds to Akt directly as well as via Hsp90. The FKBP51-Akt interaction is sensitive to the conformation of Akt1, but does not depend on the FK506-binding pocket of FKBP51. Therefore, FKBP inhibitors are unlikely to inhibit the Akt-FKBP-PHLPP network. © 2013 Fabian et al.
Vogl T.J.,Universitaetsklinikum Frankfurt |
Pflugmacher R.,Charite - Medical University of Berlin |
Hierholzer J.,Klinikum Ernst von Bergmann GmbH |
Stender G.,Paracelsus Klinik |
And 4 more authors.
Spine | Year: 2013
STUDY DESIGN.: A novel randomized, controlled, unblinded clinical trial comparing 2 procedural interventions for painful osteoporotic vertebral compression fractures. OBJECTIVE.: The primary study objective was to evaluate cement leakage for a cement directed kyphoplasty system (CDKS) with anteriorly biased cement flow and vertebroplasty. The secondary study objective was to compare adjacent level fracture rates and vertebral body height for these 2 intervention methods. SUMMARY OF BACKGROUND DATA.: Cement leakage remains a significant clinical problem associated with vertebroplasty and kyphoplasty procedures. Uncontrolled cement flow in the posterior direction can result in leakage into the vertebral veins or spinal canal, leading to potentially serious clinical complications. METHODS.: Seventy-seven patients with painful osteoporotic vertebral compression fractures were enrolled. Patients were randomized 2:1 for treatment with CDKS (49 patients, 65 levels) or vertebroplasty (28 patients, 39 levels). Cement leakage was evaluated from radiographs and computed tomographic scans. Three- and 12-month follow-ups included additional radiographs and computed tomographic scans to assess changes in vertebral body height and the incidence of new fractures. RESULTS.: Treatment with CDKS significantly reduced the number of levels with leaks and the total number of leaks per level, as compared with vertebroplasty (P = 0.0132 and P = 0.0012, respectively). Significantly, fewer lateral cortical and spinal canal leaks (posterior leaks) occurred in the CDKS group (P = 0.0050, P = 0.02260, respectively). Three adjacent level fractures occurred in the vertebroplasty group, as compared with 2 in the CDKS group. Vertebral body height maintenance was equivalent. CONCLUSION.: Cement directed kyphoplasty effectively reduces posterior cement leakage, reducing the risk of leakage related complications. Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Ramm U.,Universitaetsklinikum Frankfurt |
Kohn J.,Universitaetsklinikum Frankfurt |
Rodriguez Dominguez R.,Universitaetsklinikum Frankfurt |
Rodriguez Dominguez R.,Wiesbaden University of Applied Sciences |
And 6 more authors.
Physica Medica | Year: 2014
The purpose of this study is to demonstrate the feasibility of verification and documentation in electron beam radiotherapy using the photon contamination detected with an electronic portal imaging device. For investigation of electron beam verification with an EPID, the portal images are acquired irradiating two different tissue equivalent phantoms at different electron energies. Measurements were performed on an Elekta SL 25 linear accelerator with an amorphous-Si electronic portal imaging device (EPID: iViewGT™, Elekta Oncology Systems, Crawley, UK). As a measure of EPID image quality contrast (CR) and signal-to-noise ratio (SNR) are determined. For characterisation of the imaging of the EPID RW3 slabs and a Gammex 467 phantom with different material inserts are used. With increasing electron energy the intensity of photon contamination increases, yielding an increasing signal-to-noise ratio, but images are showing a decreasing contrast. As the signal-to-noise ratio saturates with increasing dose a minimum of 50MUs is recommended. Even image quality depends on electron energy and diameter of the patient, the acquired results are mostly sufficient to assess the accuracy of beam positioning. In general, the online EPID acquisition has been demonstrated to be an effective electron beam verification and documentation method. The results are showing that this procedure can be recommended to be routinely and reliably done in patient treatment with electron beams. © 2013 Associazione Italiana di Fisica Medica.