Target profiling of an antimetastatic RAPTA agent by chemical proteomics: relevance to the mode of action.

The clinical development of anticancer metallodrugs is often hindered by the elusive nature of their molecular targets. To identify the molecular targets of an antimetastatic ruthenium organometallic complex based on 1,3,5-triaza-7-phosphaadamantane (RAPTA), we employed a chemical proteomic approach. The approach combines the design of an affinity probe featuring the pharmacophore with mass-spectrometry-based analysis of interacting proteins found in cancer cell lysates. The comparison of data sets obtained for cell lysates from cancer cells before and after treatment with a competitive binder suggests that RAPTA interacts with a number of cancer-related proteins, which may be responsible for the antiangiogenic and antimetastatic activity of RAPTA complexes. Notably, the proteins identified include the cytokines midkine, pleiotrophin and fibroblast growth factor-binding protein 3. We also detected guanine nucleotide-binding protein-like 3 and FAM32A, which is in line with the hypothesis that the antiproliferative activity of RAPTA compounds is due to induction of a G2/M arrest and histone proteins identified earlier as potential targets

Monitoring of muscle and bone recovery in spinal cord injury patients treated with electrical stimulation using three-dimensional imaging and segmentation techniques: methodological assessment.

Artif Organs. 2011 Mar;35(3):275-81. doi: 10.1111/j.1525-1594.2011.01214.x. Monitoring of muscle and bone recovery in spinal cord injury patients treated with electrical stimulation using three-dimensional imaging and segmentation techniques: methodological assessment. Gargiulo P, Helgason T, Reynisson PJ, Helgason B, Kern H, Mayr W, Ingvarsson P, Carraro U. Source Department of Development and Consultancy UTS, Landspitali-University Hospital University of Reykjavik, Reykjavik. [email protected] Abstract Muscle tissue composition accounting for the relative content of muscle fibers and intramuscular adipose and loose fibrous tissues can be efficiently analyzed and quantified using images from spiral computed tomography (S-CT) technology and the associated distribution of Hounsfield unit (HU) values. Muscle density distribution, especially when including the whole muscle volume, provides remarkable information on the muscle condition. Different physiological and pathological scenarios can be depicted using the muscle characterization technique based on the HU values and the definition of appropriate intervals and the association of such intervals to different colors. Using this method atrophy, degeneration, and restoration in denervated muscle undergoing electrical stimulation treatments can be clearly displayed and monitored. Moreover, finite element methods are employed to calculate Young's modulus on the patella bone and to analyze correlation between muscle contraction and bone strength changes. The reliability of this tool though depends on S-CT assessment and calibration. To assess imaging quality and the use of HU values to display muscle composition, different S-CT devices are compared using a Quasar body scanner. Density distributions and volumes of various calibration elements such as lung, polyethylene, water equivalent, and trabecular and dense bone are measured with different scanning protocols and at different points of time. The results show that every scanned element undergoes HU variations, which are greater for materials at the extremes of the HU scale, such as dense bone and lung inhale. Moreover, S-CT scanning with low tube voltages (80 KV) produces inaccurate HU values especially in bones. In conclusion, 3-D modeling techniques based on S-CT scanning is a powerful follow-up tool that may provide structural information at the millimeter scale, and thus may drive choice and timing to validate rehabilitation protocols. \ua9 2011, Copyright the Authors. Artificial Organs \ua9 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc. PMID: 21401674 [PubMed - indexed for MEDLINE

A multimodal image guiding system for Navigated Ultrasound Bronchoscopy (EBUS): A human feasibility study

Background Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) is the endoscopic method of choice for confirming lung cancer metastasis to mediastinal lymph nodes. Precision is crucial for correct staging and clinical decision-making. Navigation and multimodal imaging can potentially improve EBUS-TBNA efficiency. Aims To demonstrate the feasibility of a multimodal image guiding system using electromagnetic navigation for ultrasound bronchoschopy in humans. Methods Four patients referred for lung cancer diagnosis and staging with EBUS-TBNA were enrolled in the study. Target lymph nodes were predefined from the preoperative computed tomography (CT) images. A prototype convex probe ultrasound bronchoscope with an attached sensor for position tracking was used for EBUS-TBNA. Electromagnetic tracking of the ultrasound bronchoscope and ultrasound images allowed fusion of preoperative CT and intraoperative ultrasound in the navigation software. Navigated EBUS-TBNA was used to guide target lymph node localization and sampling. Navigation system accuracy was calculated, measured by the deviation between lymph node position in ultrasound and CT in three planes. Procedure time, diagnostic yield and adverse events were recorded. Results Preoperative CT and real-time ultrasound images were successfully fused and displayed in the navigation software during the procedures. Overall navigation accuracy (11 measurements) was 10.0 ± 3.8 mm, maximum 17.6 mm, minimum 4.5 mm. An adequate sample was obtained in 6/6 (100%) of targeted lymph nodes. No adverse events were registered. Conclusions Electromagnetic navigated EBUS-TBNA was feasible, safe and easy in this human pilot study. The clinical usefulness was clearly demonstrated. Fusion of real-time ultrasound, preoperative CT and electromagnetic navigational bronchoscopy provided a controlled guiding to level of target, intraoperative overview and procedure documentation.publishedVersio