IGF-IR-mediated signaling promotes survival, anchorage-independent growth, and oncogenic transformation, as well as tumor growth and metastasis formation in vivo. NVP-AEW541 is a pyrrolo2,3-
...dpyrimidine derivative small molecular weight kinase inhibitor of the IGF-IR, capable of distinguishing between the IGF-IR (IC
50 = 0.086 μM) and the closely related InsR (IC
50 = 2.3 μM) in cells. As expected for a specific IGF-IR kinase inhibitor, NVP-AEW541 abrogates IGF-I-mediated survival and colony formation in soft agar at concentrations that are consistent with inhibition of IGF-IR autophosphorylation. In vivo, this orally bioavailable compound inhibits IGF-IR signaling in tumor xenografts and significantly reduces the growth of IGF-IR-driven fibrosarcomas. Thus, NVP-AEW541 represents a class of selective, small molecule IGF-IR kinase inhibitors with proven in vivo antitumor activity and potential therapeutic application.
Congregational singing was introduced in German-speaking Switzerland from the beginning of the Reformation, although at different rates depending on the place. The mixed repertoire based on the model ...of the Constance hymnal of about 1534 was replaced from the 17th century by the Lobwasser Psalter, this in turn was replaced in the 19th century by the strongly divergent cantonal hymnals. The Reformed received a common hymnal in 1952, the Catholic dioceses in 1966. The Second Vatican Council and the social upheavals after 1968 shaped the work on the new hymnals and favored the close cooperation of the Reformed and the Catholic leaders. The hymnals introduced in 1998 are both the result and the motor of the good interconfessional relationship in Switzerland.
Summary Background Transcarotid access is an alternative route for transcutaneous aortic valve implantation (TAVI) in patients with impossible transfemoral access. Aims We evaluated the safety, ...effectiveness and early and late clinical outcomes of CoreValve® implantation via the common carotid artery. Methods Eighteen patients (10 men, 8 women; mean age 84 ± 5 years) at high surgical risk (mean EuroSCORE II 16 ± 13%) with significant peripheral artery disease underwent TAVI via common carotid artery access under general anaesthesia. Mean aortic valve area was 0.64 ± 0.13 cm2 (0.36 ± 0.07 cm2 /m2 ). Results At a mean follow-up of 605 ± 352 days, two patients (11%) had died in hospital, on days 6 and 20, as a result of sepsis with multiorgan failure ( n = 1) or pneumonia ( n = 1). There were no perioperative deaths, myocardial infarctions or strokes. Perioperative prosthesis embolization occurred in one patient (6%), requiring implantation of a second valve. In-hospital complications occurred in four patients (23%): blood transfusion for transient significant bleeding at the access site in one patient (6%); permanent pacemaker implantation in two patients (11%); and pericardial drainage in one patient (6%). The rate of event-free in-hospital stay was 66%. Post-procedural echocardiography showed very good haemodynamic performance, with a mean gradient of 8 ± 3 mmHg. Moderate paravalvular leak was present in one patient (6%). Mean intensive care unit stay was 48 ± 31 h; mean in-hospital stay was 7 ± 3 days. Conclusion TAVI performed by transcarotid access in this small series of severely ill patients was associated with a low incidence of complications, which were associated with the procedure itself rather than the access route.
This chapter aims to describe and summarize the regulation of gene and cell therapy products in Switzerland and its legal basis. Product types are briefly described, as are Swiss-specific ...terminologies such as the term "transplant product," which means products manufactured from cells, tissues, or even whole organs. Although some parts of this chapter may show a guideline character, they are not legally binding, but represent the current thinking of Swissmedic, the Swiss Agency for Therapeutic Products. As so far the experience with marketing approval of gene therapy and cell therapy products in Switzerland is limited, this chapter focuses on the regulation of clinical trials conducted with these products. Quality, nonclinical, and clinical aspects are summarized separately for gene therapy products and transplant products.
OBJECTIVEComparison between a Less Invasive Stabilization System (LISS) using monocortical screws with angular stability and two conventional plate systems Condylar Buttress Plate (CBP) and Dynamic ...Condylar Screw (DCS) for the treatment of distal femoral fractures with respect to biomechanical properties.
DESIGNBiomechanical study using paired cadaver femurs. In Test Configuration 1 (distal test), a ten-millimeter gap at the diaphysis–metaphysis junction simulates a supracondylar femoral fracture. Test Configuration 2 (proximal test) has the same configuration, but the gap was cut in the isthmic region. Proximal and distal plate ends were fixed to corresponding cortical bone fragments in both tests. Optical displacement transducers served to quantify the system's ability to withstand a stepwise increased load. Reversible (deflection) and irreversible deformation (subsidence) of the bone–plate construct was investigated.
RESULTSIn Test Configuration 1, LISS showed less irreversible deformation in 72 percent of the left–right comparisons. No correlation between bone mineral density, cross-section area of bones and the measured response of the construct under load was found between pairs. In Test Configuration 2, 83 percent of the left–right comparisons showed less permanent deformation but a higher elastic deformation for LISS.
CONCLUSIONSThese results suggest an enhanced ability to withstand high loads when using the monocortical screw fixation technique with angular stability. A higher elastic deformation of LISS compared with conventional plating systems in distal femoral fractures can be explained by the lower bending stiffness caused by different design and material properties.
Apoptotic cell death in the retina was recently demonstrated in animal models of the hereditary human retinal dystrophy known as retinitis pigmentosa. Although recent evidence indicates that the ...proto-oncogene c-fos is a mediator of apoptosis, its precise role is unclear. In fact, under some conditions, c-fos may even protect against apoptotic cell death. In the retina, c-fos is physiologically expressed in a diurnal manner and is inducible by light. We previously observed a light-elicited, dose-dependent apoptotic response in rat photoreceptors. To determine whether c-fos is involved in the light-induced apoptotic pathway we have used control mice and mice lacking c-fos. We found that following dark adaptation and two hours of light exposure both groups of animals exhibited only a few apoptotic cells. However, at 12 and 24 additional hours after light exposure, apoptosis increased dramatically in controls but was virtually absent in those mice lacking c-fos. Therefore, c-fos is essential for light-induced apoptosis of photoreceptors. Notably, c-fos is continuously upregulated concomitant with apoptotic photoreceptor death in our system and in animal models of retinitis pigmentosa (Agarwal, N. et al., Invest. Ophthalmol. Vis.Sci. Suppl. 36, S638 and Rich, K.A. et al., Invest. Ophthalmol. Vis. Sci. Suppl. 35, 1833). Inhibition of c-fos expression might therefore represent a novel therapeutic strategy to retard the time course of retinal dystrophies and light-induced retinal degeneration.
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