Comparison of microarray-based RNA expression with ELISA-based protein determination of HER2, uPA and PAI-1 in tumour tissue of patients with breast cancer and relation to outcome

Purpose  

Prognostic and predictive markers in breast cancer are currently determined by single analysis of protein amounts. If RNA-based multi-gene analyses enter clinical practice, simultaneous determination of currently established markers like human epidermal growth factor receptor 2 (HER2), urokinase plasminogen activator (uPA) and its inhibitor (PAI-1) would represent an elegant simplification. To investigate the correlation between RNA and protein levels, we assessed HER2, uPA and PAI-1 in patients with breast cancer. In addition, we evaluated the influence of these factors on patient outcome.     

From Serendipity to Mitochondria-Targeted Nanocarriers

This review illustrates how a random observation at the laboratory bench has helped pave the way towards the development of organelle-targeted pharmaceutical nanocarriers. A fortuitous discovery in the mid 1990s involving the self-assembly of a molecule, known to accumulate inside mitochondria, has lead to the development of subcellular nanocarriers suited for the selective delivery of biologically active molecules to mitochondria inside living mammalian cells. Applications for mitochondria-specific drug and DNA delivery are described, the current state-of-the-art of mitochondrial drug targeting technology is reviewed, and its future perspectives are discussed.     

Spinophilin is required for normal morphology, Ca2+ homeostasis and contraction but dispensable for ��-adrenergic stimulation of adult cardiomyocytes

Spinophilin (SPN) is a ubiquitously expressed scaffolding protein that interacts through several binding modules with a variety of target proteins. Thus, SPN bundles F-actin, targets protein phosphatase 1 to the ryanodine receptor, and targets regulators of G-protein signaling to G-protein coupled receptors in cardiomyocytes. In this work we studied the role of SPN on cardiomyocyte morphology, function, and β-adrenergic responsiveness using a homozygous SPN knock-out mouse model (SPN-/-). We show that spinophilin deficiency significantly (1) reduced cardiomyocyte length, (2) increases both Ca(2+) amplitude and maximal rate of Ca(2+) rise during systole, and (3) decreased shortening amplitude and maximal rate of shortening, while (4) β-adrenergic stimulation remained intact. Our data suggest that spinophilin is an upstream regulator required for normal growth and excitation-contraction coupling, but is dispensable for β-adrenergic stimulation of adult cardiomyocytes.     

Spinophilin regulates central angiotensin II-mediated effect on blood pressure

Central angiotensin II (AngII) plays an important role in the regulation of the sympathetic nervous system. The underlining molecular mechanisms are largely unknown. Spinophilin (SPL) is a regulator of G protein-coupled receptor signaling. Deletion of SPL induces sympathetically mediated arterial hypertension in mice. We tested the hypothesis that SPL restrains blood pressure (BP) by regulating AngII activity. We equipped SPL(-/-) and SPL(+/+) mice with telemetric devices and applied AngII (1.0?mg?kg(-1)?day(-1), minipumps) or the AngII subtype 1 receptor (AT1-R) blocker valsartan (50?mg?kg(-1)?day(-1), gavage). We assessed autonomic nervous system activity through intraperitoneal application of trimethaphan, metoprolol, and atropine. We also tested the effect of intracerebroventricular (icv) AngII on blood pressure in SPL(-/-) and in SPL(+/+) mice. Chronic infusion of AngII upregulates SPL expression in the hypothalamus of SPL(+/+) mice. Compared with SPL(+/+) mice, SPL(-/-) mice showed a greater increase in daytime BP with AngII (19.2?±?0.8 vs. 13.5?±?1.6?mmHg, p?相似文献   

Stress fractures presenting as tumours: a retrospective analysis of 22 cases

Frequently, the imaging features of stress fractures may be misinterpreted as tumour-like lesions. The aim of this study was to analyse the quality of different examinations in detecting stress fractures mimicking tumour-like lesions in magnetic resonance imaging (MRI). We evaluated 22 cases which were referred to our department with the suspected diagnosis of bone tumours turning out to be stress fractures. Whenever the MRI did not lead to a diagnosis after a second review, computed tomography (CT) scans and, if still required, additional examinations were performed until the fracture was detected. A stress fracture was diagnosed in 15 cases after the additional CT scan, in five cases with the review of the MRI and in two cases with a combination of several examinations. Especially in stress fractures of the tibia and the femur, CT scanning was essential for making a diagnosis by detecting the fracture line. Bone scans and biopsies, in contrast, were not helpful in making a correct diagnosis.     

Comparison of outcomes of minimally invasive mitral valve surgery for posterior, anterior and bileaflet prolapse

Objective: We sought to compare the outcomes of minimally invasive mitral valve (MV) surgery for anterior (anterior mitral leaflet, AML), posterior (posterior mitral leaflet, PML) or bileaflet (BL) MV prolapse. Methods: Between August 1999 and December 2007, 1230 patients who presented with isolated AML (n = 156, 12.7%), isolated PML (n = 672, 54.6%) or BL (n = 402, 32.7%) MV prolapse underwent minimally invasive MV surgery. The preoperative mitral regurgitation (MR) grade was 3.3 ± 0.8, left ventricular ejection fraction (LVEF) was 62 ± 12% and mean age was 58.9 ± 13.0 years; 836 patients (68.0%) were male. Mean follow-up time was 2.7 ± 2.1 years, and the follow-up was 100% complete. Results: Overall, the MV repair rate was 94.0% (1156 patients). Seventy-four patients (6.0%) received MV replacement. MV repair for PML prolapse was accomplished in 651 patients (96.9%), for AML in 142 patients (91%) and for BL in 363 patients (90.3%). Repair techniques consisted predominantly of leaflet resection and/or implantation of neochordae, combined with ring annuloplasty. Concomitant procedures were tricuspid valve surgery (n = 56), atrial fibrillation ablation (n = 286) and closure of an atrial septal defect or patent foramen ovale (PFO) (n = 89). The overall duration of cardiopulmonary bypass was 127 ± 40 min and aortic cross-clamp time was 78 ± 33 min. The mean postoperative hospital stay was 11.6 ± 9.7 days for the overall group. Early echocardiographic follow-up revealed excellent valve function in the vast majority of patients, regardless of the repair technique, with a mean MR grade of 0.3 ± 0.5. For the overall group, 5-year survival rate was 87.3% (95% CI: 83.9–90.1) and 5-year freedom from cardiac reoperation rate was 95.6% (95% CI: 94.1–96.7). The log-rank test revealed no significant difference between the three groups regarding long-term survival or freedom from reoperation. Conclusions: Minimally invasive MV repair can be achieved with excellent results. Long-term outcomes and reoperation rates for AML prolapse are not significantly different from PML or BL prolapse.