Anti-Albumin monoclonal antibody, clone CHO/2439/44

Purpose: To develop a novel model to predict outcomes in patients with previously treated metastatic renal cell carcinoma. Patients and methods: This study included 78 consecutive metastatic renal cell carcinoma patients receiving first- and second-line targeted therapies at our institution. Predictive factors of overall survival (OS) at the second-line setting in these patients were investigated, and a novel prognostic model was developed. Results: Median OS from the initiation of second-line therapy was 21.9 months. A multivariate analysis of several parameters identified the following independent predictors associated with poor OS: albumin (Alb, <= 3.5 g/dl), C-reactive protein (CRP, >0.5 mg/dl), and lactate dehydrogenase (LDH, >1.5 x upper limit of normal). When patients were divided into 3 groups based on the positive numbers of these 3 independent risk factors, named the ACL (Alb, CRP, and LDH) model, median OS durations were 50 months in the favorable risk group without risk factors (n = 26), 25 months in the intermediate-risk group with a single risk factor (n = 24), and 8 months in the poor risk group (n = 28) with multiple risk factors. The superiority of the ACL model as a prognostic tool to the Memorial Sloan Kettering Cancer Center model for previously treated patients and the International Metastatic Renal Cell Carcinoma Database Consortium model was demonstrated by Harrell's concordance index and a decision curve analysis. Conclusions: The ACL model in the second-line targeted therapy setting may predict outcomes more accurately than the Memorial Sloan Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium models. (C) 2019 Elsevier Inc. All rights reserved.

Liver fibrosis is a major pathological feature of chronic liver diseases, and effective therapies are limited at present. Asiatic acid (AA) is a triterpenoid isolated from Centella asiatica, which exhibits efficient anti-inflammatory and anti-oxidative activities. However, AA shows very low plasma levels after oral administration. In this study, AA loading PEGylated nanostructured lipid carriers (P-AA-NLCs) were prepared. P-AA-NLCs were characterized for particle size distribution, polydispersity index, entrapment efficiency, X-ray powder diffraction (XRD) pattern, differential scanning colorimeter (DSC), and transmission electron microscopy (TEM). The intestinal absorption, in vivo distribution, pharmacokinetics, and anti-fibrosis effects of P-AA-NLC were studied compared with that of AA-NLC. In situ single-pass intestinal perfusion model shows that there are significant differences in absorption between the free and NLCs formulation. The P-eff values of P-AA-NLC were significantly enhanced in all four intestinal segments compared to AA-NLC and free AA (p < .05). f(a)% and K-a showed similar trends, suggesting the PEGylated NLC can improve the gastrointestinal absorption of the drug. The pharmacokinetic studies presented that P-AA-NLC prolonged blood circulation times with a 1.5-fold higher relative bioavailability compared with AA-NLC. In vivo distribution experiments demonstrated that the fluorescence concentration in the liver was higher than that in other organs and the fluorescence intensity in the liver of DIR-P-NLC was about 1.3 times that of DIR-NLC. In addition, oral administration of P-AA-NLC can significantly attenuate CCl4-induced liver fibrosis and functional impairment in a dosage-dependent manner, including an increase in the albumin (ALB) and decrease in aspartate aminotransferase (AST) and alanine transaminase (ALT). Moreover, the MDA and HYP in liver tissue were downregulated, while the SOD activity was upregulated. In conclusion, P-AA-NLC can increase gastrointestinal absorption of AA and enhance anti-liver fibrosis effects in SD rats.