Single irradiation of the pituitary with a narrow beam of protons having 200 MeV of energy in generalized breast cancer

Eighteen patients with congestive cardiomyopathy were studied by echocardiography and cardiac catheterization. Patients with coronary disease on angiography or primary valvular disease were excluded. Six patients showed mild or no mitral regurgitation; in 12 others the degree of mitral regurgitation was moderate or severe. The echocardiographic features in these patients were: (1) a dilated left ventricle (LV), (2) normal LV wall thickness, (3) reduced LV posterior wall motion, and (4) reduced or absent systolic thickening of the interventricular septum (IVS). IVS motion was reduced in 10 patients, and appeared "normal" or increased in another eight, all of whom showed moderate or severe mitral regurgitation on angiography. It is concluded that an apparent normal or increased motion of the IVS with reduced or absent systolic thickening in congestive cardiomyopathy is evidence for coexistence of significant mitral regurgitation. Reduced or absent systolic thickening can distinguish these patients from those with segmental myocardial disease and normal septa or dilated LV's due to volume overload.     

Soluble CD146 as a Potential Target for Preventing Triple Negative Breast Cancer MDA-MB-231 Cell Growth and Dissemination

Background: Triple Negative Breast Cancers (TNBC) are the most aggressive breast cancers and lead to poor prognoses. This is due to a high resistance to therapies, mainly because of the presence of Cancer Stem Cells (CSCs). Plasticity, a feature of CSCs, is acquired through the Epithelial to Mesenchymal Transition (EMT), a process that has been recently shown to be regulated by a key molecule, CD146. Of interest, CD146 is over-expressed in TNBC. Methods: The MDA-MB-231 TNBC cell line was used as a model to study the role of CD146 and its secreted soluble form (sCD146) in the development and dissemination of TNBC using in vitro and in vivo studies. Results: High expression of CD146 in a majority of MDA-MB-231 cells leads to an increased secretion of sCD146 that up-regulates the expression of EMT and CSC markers on the cells. These effects can be blocked with a specific anti-sCD146 antibody, M2J-1 mAb. M2J-1 mAb was able to reduce tumour development and dissemination in a model of cells xenografted in nude mice and an experimental model of metastasis, respectively, in part through its effects on CSC. Conclusion: We propose that M2J-1 mAb could be used as an additional therapeutic approach to fight TNBC.     

Interpretation of simulation studies for efficient estimation of population pharmacokinetic parameters

OBJECTIVE: To develop new approaches for evaluating results obtained from simulation studies used to determine sampling strategies for efficient estimation of population pharmacokinetic parameters. METHODS: One-compartment kinetics with intravenous bolus injection was assumed and the simulated data (one observation made on each experimental unit [human subject or animal]), were analyzed using NONMEM. Several approaches were used to judge the efficiency of parameter estimation. These included: (1) individual and joint confidence intervals (CIs) coverage for parameter estimates that were computed in a manner that would reveal the influence of bias and standard error (SE) on interval estimates; (2) percent prediction error (%PE) approach; (3) the incidence of high pair-wise correlations; and (4) a design number approach. The design number (phi) is a new statistic that provides a composite measure of accuracy and precision (using SE). RESULTS: The %PE approach is useful only in examining the efficiency of estimation of a parameter considered independently. The joint CI coverage approach permitted assessment of the accuracy and reliability of all model parameter estimates. The phi approach is an efficient method of achieving an accurate estimate of parameter(s) with good precision. Both the phi for individual parameter estimation and the overall phi for the estimation of model parameters led to optimal experimental design. CONCLUSIONS: Application of these approaches to the analyses of the results of the study was found useful in determining the best sampling design (from a series of two sampling times designs within a study) for efficient estimation of population pharmacokinetic parameters.     

Rapid molecular diagnosis of erythropoietic protoporphyria among Swiss patients

Erythropoietic protoporphyria (EPP) is an autosomal dominant inherited disorder with incomplete penetrance. It is caused by partial deficiency of ferrochelatase, the last enzyme in the heme biosynthetic pathway. Measurement of protoporphyrin concentrations in red cells and feces, although sufficient for diagnosis of symptomatic EPP patients, fails to detect asymptomatic gene carriers. We have developed a molecular diagnostic procedure for rapid and reliable screening of five known mutations in the ferrochelatase gene among Swiss EPP patients in a single denaturing gradient gel electrophoresis (DGGE) gel.