An important role for Myb-MuvB and its target gene KIF23 in a mouse model of lung adenocarcinoma.

The conserved Myb-MuvB (MMB) multiprotein complex has an important role in transcriptional activation of mitotic genes. MMB target genes are overexpressed in several different cancer types and their elevated expression is associated with an advanced tumor state and a poor prognosis. This suggests that MMB could contribute to tumorigenesis by mediating overexpression of mitotic genes. However, although MMB has been extensively characterized biochemically, the requirement for MMB in tumorigenesis in vivo has not been investigated. Here we demonstrate that MMB is required for tumor formation in a mouse model of lung cancer driven by oncogenic K-RAS. We also identify a requirement for the mitotic kinesin KIF23, a key target gene of MMB, in tumorigenesis. RNA interference-mediated depletion of KIF23 inhibited lung tumor formation in vivo and induced apoptosis in lung cancer cell lines. Our results suggest that inhibition of KIF23 could be a strategy for treatment of lung cancer.

[Integration of the functional signal of intraoperative EMG of the facial nerve in to navigation model for surgery of the petrous bone]. / Integration des intraoperativen EMG-Signals des N. facialis in das Navigationsmodell der Felsenbeinchirurgie.

UNLABELLED: PROBLEM DEFINITION: The goal of this work is the integration of the information of the intraoperative EMG monitoring of the facial nerve into the radiological data of the petrous bone. The following hypotheses are to be examined: (I) the N. VII can be determined intraoperatively with a high reliability by the stimulation-probe. A computer program is able to discriminate true-positive EMG signals from false-positive artifacts. (II) The course of the facial nerve can be registered in a three-dimensional area by EMG signals at a nerve model in the lab test. The individual items of the nerve can be combined into a route model. The route model can be integrated into the data of digital volume tomography (DVT). MATERIAL AND METHODS: (I) Intraoperative EMG signals of the facial nerve were classified at 128 measurements by an automatic software. The results were correlated with the actual intraoperative situation. (II) The nerve phantom was designed and a DVT data set was provided. Phantom was registered with a navigation system (Karl Storz NPU, Tuttlingen, Germany). The stimulation probe of the EMG-system was tracked by the navigation system. The navigation system was extended by a processing unit (MiMed, Technische Universität München, Germany). Thus the classified EMG parameters of the facial route can be received, processed and be generated to a model of the facial nerve route. The operability was examined at 120 (10 x 12) measuring points. RESULTS: The evaluation of the examined algorithm for classification EMG-signals of the facial nerve resulted as correct in all measuring events. In all 10 attempts it succeeded to visualize the nerve route as three-dimensional model. The different sizes of the individual measuring points reflect the appropriate values of Istim and UEMG correctly. DISCUSSION: This work proves the feasibility of an automatic classification of an intraoperative EMG signal of the facial nerve by a processing unit. Furthermore the work shows the feasibility of tracking of the position of the stimulation probe and its integration into amodel of the route of the facial nerve (e. g. DVT). The rediability, with which the position of the nerve can be seized by the stimulation probe, is also included into the resulting route model.

[Improvement of registration accuracy for navigated-control drill in mastoidectomy (autopilot)]. / Der Einfluss von unterschiedlichen Registrierverfahren auf die Genauigkeit der navigiert-kontrollierten Fräse (Safety Assistance-Funktion) für die Mastoidektomie.

BACKGROUND: The goal of this study is the improvement of the surgical accuracy of a navigate-controlled drill for mastoidectomy in a lab test. METHODS: For lab tests an artificial model of the temporal bone with color-coded injury identification of the facial nerve (solution of 0.5 mm) was used. Two different registration methods were examined: (group 1) navigation bow with 4 integrated markers at the upper jaw; (group 2) landmark registration with 4 titanium micro screws. An optical navigation system was used. The targets were illustrated by 3 titanium screws within the range of the planum mastoideum. The accuracy of the navigate-controlled drill in drilling the planned cavity were evaluated at 20 temporal bone models. The measurement of the registration accuracy was evaluated by deviation between the target screw and the calculated position in the navigation system. The evaluation of the resulted cavities was done by 5 senior surgeons with the help of the microscope. RESULTS: The registration accuracy shows a maximum deviation between the real position and the calculated position of 1,73 MM in group of 1 and 0.93 MM in group 2. In group 1 the nerve was hurt in 5/20 cases and a maximum deviation of - 1.5 mm (Std 0.25 mm) (drilled beyond the nerve) was measured. In group 2 the nerve was not hurt, a maximum deviation of 0.5 mm (too early stopped before the nerve) was measured. CONCLUSIONS: Significantly better results of the registration and drilling accuracy show up in group group 2. Thus the preconditions for clinical use are fulfilled.

[Improved accuracy and precision of the automated shaver (navigated control) in functional endoscopic sinus surgery]. / Verbesserte Umsetzung der Resektionsgrenzen in der Nasennebenhöhlenchirurgie mit dem navigiert-kontrollierten Shaver.

BACKGROUND: The feasibility of a navigate-controlled Shaver for the paranasal sinus surgery was proven in an initial study. Deficits showed up in the conversion of the planed cavity. Goal of this study is (1) the development and evaluation of a FESS demonstrator for the investigations to the surgical accuracy and (2) the evaluation of the resulting surgical accuracy for registration and conversion of the work space with an improved rigidity of the Shaver and a completely revised study design. METHODS: As a demonstrator for the navigate-controlled resection of a volume through the Shaver a two-piece plastic head with an anatomical head and soft tissue model was designed. The investigation of the surgical accuracy takes place with 417 measurements to 4 different fiducial markers on the demonstrator head. The measurements for the deviation of the resulting cavity from the planned volume was realised with a work space by 24 x 24 x 30 mm. The 5 walls of the cavity were seized with 80 measuring points for each level and thus altogether 2000 measured values (5 models x 5 levels x 200 points). RESULTS: The described demonstrator showed itself suitable for the close-to-application attempts to the surgical accuracy. The maximum deviation A (max) indicated position of the Shaver from the reference value amounted to 1,93 mm. The maximum average value of the exceeding of a planned cavity amounts to 1,62 mm. CONCLUSIONS: Based on these results a virtual safety passage of 2.00 mm is sufficient. The study refers the clinical serviceability of the navigate-controlled Shaver in paranasal sinus surgery.

Establishing navigated control in head surgery.

Navigated Control (NC) describes an additional control for a tracked power driven instrument within a preoperatively segmented work space. In head surgery the authors first implemented NC in functional endoscopic sinus surgery (FESS). Recently the feasibility of NC for surgery on the petrosal bone is evaluated. NC in FESS and in petrosal bone surgery may reduce the risk of comorbidity and the time effort compared to the conventional surgical interventions.