Coaction of Spheroid-Derived Stem-Like Cells and Endothelial Progenitor Cells Promotes Development of Colon Cancer

Although some studies described the characteristics of colon cancer stem cells (CSCs) and the role of endothelial progenitor cells (EPCs) in neovascularization, it is still controversial whether an interaction exists or not between CSCs and EPCs. In the present study, HCT116 and HT29 sphere models, which are known to be the cells enriching CSCs, were established to investigate the roles of this interaction in development and metastasis of colon cancer. Compared with their parental counterparts, spheroid cells demonstrated higher capacity of invasion, higher tumorigenic and metastatic potential. Then the in vitro and in vivo relationship between CSCs and EPCs were studied by using capillary tube formation assay and xenograft models. Our results showed that spheroid cells could promote the proliferation, migration and tube formation of EPCs through secretion of vascular endothelial growth factor (VEGF). Meanwhile, the EPCs could increase tumorigenic capacity of spheroid cells through angiogenesis. Furthermore, higher microvessel density was detected in the area enriching cancer stem cells in human colon cancer tissue. Our findings indicate that spheroid cells possess the characteristics of cancer stem cells, and the coaction of CSCs and EPCs may play an important role in the development of colon cancer

Effect of prescribing a high protein diet and increasing the dose of dialysis on nutrition in stable chronic haemodialysis patients:a randomized, controlled trial

Background. Protein requirements in stable, adequately dialysed haemodialysis patients are not known and recommendations vary. It is not known whether increasing the dialysis dose above the accepted adequate level has a favourable effect on nutrition. The aim of this study was to determine whether prescribing a high protein diet and increasing the dose of dialysis would have a favourable effect on dietary protein intake and nutritional status in stable, adequately dialysed haemodialysis patients. Effects on hyperphosphataemia and acidosis were also studied. Methods. Patients were randomized to a high dialysis dose (HDD) group (target Kt/V-eq of 1.4) or a regular dialysis dose (RDD) group (target Kt/V-eq of 1.0). All patients were prescribed a high protein (HP) diet [1.3 g/kg of ideal body weight (IBW)/day] and a regular protein (RP) diet (0.9 g/kg/day), each during 40 weeks in a crossover design. In 50 patients, 23 in the HDD and 27 in the RDD group follow-up was greater than or equal to10 weeks. These patients, aged 56 15 years, were included in the analysis. Nutritional status was assessed by anthropometry, plasma albumin and a nutritional index. Results. Delivered Kt/V-eq in the HDD group (1.26 +/- 0.14) was significantly higher than in the RDD group (1.02 +/- 0.08). Protein intake estimated from total nitrogen appearance (PNA) measurements and food records (DPI) was significantly higher during the HP diet (PNA(IBW), 1.01 +/- 0.18 g/kg/day; DPIIBW, 1.15 +/- 0.18 g/kg/day) than during the RP diet (PNA(IBW), 0.90 +/- 0.14 g/kg/day; DPIIBW, 0.94 +/- 0.11 g/kg/day). Increasing the dialysis dose did not increase protein intake either during the HP or RP diet. Plasma albumin (41.9 +/- 3.0 g/l) lean body mass (107 +/- 15% of normal values) and the nutritional index did not differ between the dialysis dose groups or protein diets and remained stable overtime. Dry body weight (97 +/- 14%) and total fat mass increased over time in the HDD group, but remained stable in the RDD group suggesting an effect of dialysis dose on energy balance. There was no effect of the protein diets on dry body weight or total fat mass. Plasma phosphate levels and oral bicarbonate supplements were lower in the HDD group, but were comparable between the protein diets. Conclusions. Prescribing a HP diet resulted in a modest increase in actual protein intake, but increasing dialysis dose did not have a contributing effect. A HP diet or increasing the dialysis dose did not have a favourable effect on the nutritional status. A dietary protein intake of at least 0.9 g/kg IBW/day appears to be sufficient for adequately dialysed haemodialysis patients without overt malnutrition

Clinical Perspectives on Lacosamide

Despite the advent of new antiepileptic drugs (AEDs) over the past 15 years, the treatment of uncontrolled partial-onset seizures remains a dilemma for clinicians. The most recent AEDs offer new mechanisms of action and more favorable safety profiles than the first generation of AEDs. Lacosamide (LCM) is the latest AED awaiting approval by the FDA for adjunctive use in partial-onset seizures. It differs from all other approved AEDs in that it has two novel mechanisms of action and favorable pharmacokinetic and safety profiles. The purposes of this article are to present the significant parameters for its use in clinical practice, by summarizing the preliminary results of phase II and III clinical trials, and to compare its efficacy data with other second-generation AEDs