Novel hepatocellular carcinoma molecules with prognostic and therapeutic potentials

Hepatocellular carcinoma(HCC), the predominant form of primary liver cancer, is the sixth most common cancer worldwide and the third leading cause of cancerrelated death. The difficulty to diagnose early cancer stages, the aggressive behaviors of HCC, and the poor effectiveness of therapeutic treatments, represent the reasons for the quite similar deaths per year and incidence number. Considering the fact that the diagnosis of HCC typically occurs in the advanced stages of the disease when the therapeutic options have only modest efficacy, the possibility to identify early diagnostic markers could be of significant benefit. So far, a large number of biomarkers have been associated to HCC progression and aggressiveness, but many of them turned out not to be of practical utility. This is the reason why active investigations are ongoing in this field. Given the huge amount of published works aimed at the identification of HCC biomarkers, in this review we mainly focused on the data published in the last year, with particular attention to the role of(1) molecular and biochemical cellular markers;(2) micro-interfering RNAs;(3) epigenetic variations; and(4) tumor stroma. It is worth mentioning that a significant number of the HCC markers described in the present review may be utilized also as targets for novel therapeutic approaches, indicating the tight relation between diagnosis and therapy. In conclusion, we believe that integrated researches among the different lines of investigation indicated above should represent the winning strategies to identify effective HCC markers and therapeutic targets.

Therapeutic potential of small interfering RNAs/micro interfering RNA in hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the predominant form of primary liver cancer and represents the third leading cause of cancer-related death worldwide. Current available therapeutic approaches are poorly effective,especially for the advanced forms of the disease. In the last year,short double stranded RNA molecules termed small interfering RNAs(si RNAs) and micro interfering RNAs(mi RNA),emerged as interesting molecules with potential therapeutic value for HCC. The practical use of these molecules is however limited by the identification of optimal molecular targets and especially by the lack of effective and targeted HCC delivery systems. Here we focus our discussion on the most recent advances in the identification of si RNAs/mi RNAs molecular targets and on the development of suitable si RNA/mi RNAs delivery systems.

Dual stimuli-responsive polyurethane-based hydrogels as smart drug delivery carriers for the advanced treatment of chronic skin wounds

The design of multi-stimuli-responsive vehicles for the controlled and localized release of drugs is a challenging issue increasingly catching the attention of many research groups working on the advanced treatment of hard-to-close wounds.In this work,a thermo-and pH-responsive hydrogel(P-CHP407)was prepared from an ad hoc synthesized amphiphilic poly(ether urethane)(CHP407)exposing a significant amount of-COOH groups(8.8±0.9 nmol/g_(polymer)).The exposure of acid moieties in P-CHP407 hydrogel led to slightly lower initial gelation temperature(12.1◦C vs.14.6◦C,respectively)and gelation rate than CHP407 hydrogel,as rheologically assessed.Nanoscale hydrogel characterization by Low Field NMR(LF-NMR)spectroscopy suggested that the presence of carboxylic groups in P-CHP407 caused the formation of bigger micelles with a thicker hydrated shell than CHP407 hydrogels,as further proved by Dynamic Light Scattering analyses.In addition,P-CHP407 hydrogel showed improved capability to change its internal pH compared to CHP407 one when incubated with an alkaline buffer(pH 8)(e.g.,pH_(change_5min)=3.76 and 1.32,respectively).Moreover,LF-NMR characterization suggested a stronger alkaline-pH-induced interaction of water molecules with micelles exposing-COOH groups.Lastly,the hydrogels were found biocompatible according to ISO 10993 and able to load and release Ibuprofen:delivery kinetics of Ibuprofen was enhanced by P-CHP407 hydrogels at alkaline pH,suggesting their potential use as smart delivery systems in the treatment of chronic infected wounds.