Transarterial Embolization and Percutaneous Ethanol Injection as an Effective Bridge Therapy before Liver Transplantation for Hepatitis C-Related Hepatocellular Carcinoma

Background. Transarterial chemoembolization alone or in association with radiofrequency ablation is an effective bridging strategy for patients with hepatocellular carcinoma awaiting for a liver transplant. However, cost of this therapy may limit its utilization. This study was designed to evaluate the outcomes of a protocol involving transarterial embolization, percutaneous ethanol injection, or both methods for bridging hepatocellular carcinomas prior to liver transplantation. Methods. Retrospective review of all consecutive adult patients who underwent a first liver transplant as a treatment to hepatitis C-related hepatocellular carcinoma at our institution between 2002 and 2012. Primary endpoint was patient survival. Secondary endpoint was complete tumor necrosis. Results. Forty patients were analyzed, age 58 ± 7 years. There were 23 males (57.5%). Thirty-six (90%) out of the total 40 patients were within Milan criteria. Complete necrosis was achieved in 19 patients (47.5%). One-, 3-, and 5-year patient survival were, respectively, 87.5%, 75%, and 69.4%. Univariate analysis did not reveal any variable to impact on overall patient survival. Conclusions. Transarterial embolization, ethanol injection, or the association of both methods followed by liver transplantation comprises effective treatment strategy for hepatitis C-related hepatocellular carcinoma. This strategy should be adopted whenever transarterial chemoembolization and/or radiofrequency ablation are not available options

QSAR-Driven Discovery of Novel Chemical Scaffolds Active against Schistosoma mansoni.

Schistosomiasis is a neglected tropical disease that affects millions of people worldwide. Thioredoxin glutathione reductase of Schistosoma mansoni (SmTGR) is a validated drug target that plays a crucial role in the redox homeostasis of the parasite. We report the discovery of new chemical scaffolds against S. mansoni using a combi-QSAR approach followed by virtual screening of a commercial database and confirmation of top ranking compounds by in vitro experimental evaluation with automated imaging of schistosomula and adult worms. We constructed 2D and 3D quantitative structure-activity relationship (QSAR) models using a series of oxadiazoles-2-oxides reported in the literature as SmTGR inhibitors and combined the best models in a consensus QSAR model. This model was used for a virtual screening of Hit2Lead set of ChemBridge database and allowed the identification of ten new potential SmTGR inhibitors. Further experimental testing on both shistosomula and adult worms showed that 4-nitro-3,5-bis(1-nitro-1H-pyrazol-4-yl)-1H-pyrazole (LabMol-17) and 3-nitro-4-{[(4-nitro-1,2,5-oxadiazol-3-yl)oxy]methyl}-1,2,5-oxadiazole (LabMol-19), two compounds representing new chemical scaffolds, have high activity in both systems. These compounds will be the subjects for additional testing and, if necessary, modification to serve as new schistosomicidal agents

Experimental and Theoretical Study on the One- and Two-Photon Absorption Properties of Novel Organic Molecules Based on Phenylacetylene and Azoaromatic Moieties

This Article reports a combined experimental and theoretical analysis on the one and two-photon absorption properties of a novel class of organic molecules with a pi-conjugated backbone based on phenylacetylene (JCM874, FD43, and FD48) and azoaromatic (YB3p2S) moieties. Linear optical properties show that the phenylacetylene-based compounds exhibit strong molar absorptivity in the UV and high fluorescence quantum yield with lifetimes of approximately 2.0 ns, while the azoaromatic-compound has a strong absorption in the visible region with very low fluorescence quantum yield. The two-photon absorption was investigated employing nonlinear optical techniques and quantum chemical calculations based on the response functions formalism within the density functional theory framework. The experimental data revealed well-defined 2PA spectra with reasonable cross-section values in the visible and IR. Along the nonlinear spectra we observed two 2PA allowed bands, as well as the resonance enhancement effect due to the presence of one intermediate one-photon allowed state. Quantum chemical calculations revealed that the 2PA allowed bands correspond to transitions to states that are also one-photon allowed, indicating the relaxation of the electric-dipole selection rules. Moreover, using the theoretical results, we were able to interpret the experimental trends of the 2PA spectra. Finally, using a few-energy-level diagram, within the sum-over-essential states approach, we observed strong qualitative and quantitative correlation between experimental and theoretical results.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Air Force Office of Scientific ResearchKOLUMB fellowship by the Foundation for Polish Science (FNP