Design, synthesis and biological evaluation of pyrazole derivatives as potential multi-kinase inhibitors in hepatocellular carcinoma.

We described the optimization, by molecular modelling, of small pyrazole derivatives, as kinase inhibitors, obtained through a 1,3-dipolar cycloaddition between nitrile imines and functionalized acetylenes. The two compounds, selected as potential agents active against hepatocellular carcinoma (HCC) were then evaluated in vitro for their biological activity on HCC-derived cell lines. The compounds show a promising inhibitory growth efficacy (IC(50) 50-100 μM) in SNU449 cell line, as well as block of cell cycle progression and induction of apoptosis, and can be considered as lead compounds for further SAR developments.

Serum albumin-bound proteomic signature for early detection and staging of hepatocarcinoma: sample variability and data classification.

Background: Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) proteomic signature might be of interest for the early detection and staging of hepatocellular carcinoma (HCC). However, published procedures have been criticized for the lack of data about analytical reproducibility, and the use of inadequate data processing.

Methods: MALDI-TOF profiling of peptides bound to serum albumin ("albuminome") was performed using 90 μL of serum from 45 study subjects (HCV-related cirrhosis, small, unifocal HCCs and advanced HCCs).

Design and synthesis of novel 3,4-disubstituted pyrazoles for nanomedicine applications against malignant gliomas.

A series of novel 3,4-disubstituted pyrazoles were synthesized. The cytotoxicity against U87MG glioma cell line have been investigated in vitro and three of these compounds showed promising inhibitory activity on cell growth with an IC50 lower than 90 microM. AutoDock molecular docking into type I TGF-beta receptor (TGF-beta-RI; PDB: 1py5) has been done for lead optimization of the mentioned compounds as potential TGF-beta-RI1 inhibitors.

High-dose idarubicin in combination with Ara-C in patients with relapsed or refractory acute lymphoblastic leukemia: a pharmacokinetic and clinical study.

Objective: High dose (HD) Ara-C combined with a single HD idarubicin dose (IDA) is an efficient and safe salvage regimen for patients with refractory or relapsed acute lymphoblastic leukemia as indicated by phase II studies. No data are available on the pharmacokinetics of IDA after a rapid HD intravenous infusion. An open phase II pharmacokinetic and clinical study was performed to evaluate antileukemic efficacy, IDA pharmacokinetics and to investigate the presence of IDA and its reduced metabolite idarubicinol (IDAol) in cerebrospinal fluid (CSF) of patients treated with HD-IDA.