A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world: 2010-2016

Many guidelines for hepatocellular carcinoma (HCC) have been published and updated globally. In contrast to other cancers, there is a range of treatment options for HCC involving several multidisciplinary care of the patient. Consequently, enormous heterogeneity in management trends has been observed. To support standard care for HCC, we systematically appraised 8 current guidelines for HCC around the world, including 3 guidelines from Asia, 2 from Europe, and 3 from the United States according to the selection criteria of credibility influence and multi-faceted. After a systematic appraisal, we found that these guidelines have both similarities and dissimilarities in terms of surveillance and treatment allocation recommendations due to regional differences in disease and other variables (diagnosis, staging systems) secondary to the lack of a solid, high level of evidence. In contrast to other tumors, the geographic differences in tumor biology (i.e., areas of increased hepatitis B prevalence) and available resources (organ availability for transplantation, medical technology, accessibility to treatment, health systems, and health resources) make it impractical to have an internationally universal guideline for all patients with HCC. Although Barcelona-Clinic Liver Cancer (BCLC) has long been dominant system for treatment-guiding staging of HCC, many Asia-pacific experts do not fully agree with its principle. The concepts of BCLC, for surgical resection or other locoregional therapy, are considered too conservative. Asian guidelines represent consensus about surgical resection and TACE indication for more advanced tumor

Point Defects and Localized Excitons in 2D WSe2

Identifying the point defects in 2D materials is important for many applications. Recent studies have proposed that W vacancies are the predominant point defect in 2D WSe2, in contrast to theoretical studies, which predict that chalcogen vacancies are the most likely intrinsic point defects in transition metal dichalcogenide semiconductors. We show using first principles calculations, scanning tunneling microscopy (STM) and scanning transmission electron microscopy experiments, that W vacancies are not present in our CVD-grown 2D WSe2. We predict that O-passivated Se vacancies (O_Se) and O interstitials (Oins) are present in 2D WSe2, because of facile O2 dissociation at Se vacancies, or due to the presence of WO3 precursors in CVD growth. These defects give STM images in good agreement with experiment. The optical properties of point defects in 2D WSe2 are important because single photon emission (SPE) from 2D WSe2 has been observed experimentally. While strain gradients funnel the exciton in real space, point defects are necessary for the localization of the exciton at length scales that enable photons to be emitted one at a time. Using state-of-the-art GW-Bethe-Salpeter-equation calculations, we predict that only Oins defects give localized excitons within the energy range of SPE in previous experiments, making them a likely source of previously observed SPE. No other point defects (O_Se, Se vacancies, W vacancies and Se_W antisites) give localized excitons in the same energy range. Our predictions suggest ways to realize SPE in related 2D materials and point experimentalists toward other energy ranges for SPE in 2D WSe2

Reduction of Monocyte Chemoattractant Protein-1 and Interleukin-8 Levels by Ticlopidine in TNF-α Stimulated Human Umbilical Vein Endothelial Cells

Atherosclerosis and its associated complications represent major causes of morbidity and mortality in the industrialized or Western countries. Monocyte chemoattractant protein-1 (MCP-1) is critical for the initiating and developing of atherosclerotic lesions. Interleukin-8 (IL-8), a CXC chemokine, stimulates neutrophil chemotaxis. Ticlopidine is one of the antiplatelet drugs used to prevent thrombus formation relevant to the pathophysiology of atherothrombosis. In this study, we found that ticlopidine dose-dependently decreased the mRNA and protein levels of TNF-α-stimulated MCP-1, IL-8, and vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Ticlopidine declined U937 cells adhesion and chemotaxis as compared to TNF-α stimulated alone. Furthermore, the inhibitory effects were neither due to decreased HUVEC viability, nor through NF-kB inhibition. These results suggest that ticlopidine decreased TNF-α induced MCP-1, IL-8, and VCAM-1 levels in HUVECs, and monocyte adhesion. Therefore, the data provide additional therapeutic machinery of ticlopidine in treatment and prevention of atherosclerosis

Ellagic Acid, the Active Compound of Phyllanthus urinaria, Exerts In Vivo Anti-Angiogenic Effect and Inhibits MMP-2 Activity

This study aimed to assess the potential anti-angiogenic mechanism of Phyllanthus urinaria (P. urinaria) and characterize the major compound in P. urinaria that exerts anti-angiogenic effect. The water extract of P. urinaria and Ellagic Acid were used to evaluate the anti-angiogenic effect in chorioallantoic membrane (CAM) in chicken embryo and human vascular endothelial cells (HUVECs). The matrix metalloproteinase-2 (MMP-2) activity was determined by gelatin zymography. The mRNA expressions of MMP-2, MMP-14 and tissue inhibitor of metalloproteinase-2 (TIMP-2) were analyzed by reverse transcription polymerase chain reaction (RT-PCR). Level of MMP-2 proteins in conditioned medium or cytosol was determined by western blot analysis. We confirmed that P. urinaria's in vivo anti-angiogenic effect was associated with a reduction in MMP-2 activity. Ellagic acid, one of the major polyphenolic components as identified in P. urinaria by high performance liquid chromatography mass spectrometry (HPLC/MS), exhibited the same anti-angiogenic effect in vivo. Both P. urinaria and Ellagic Acid inhibited MMP-2 activity in HUVECs with unchanged mRNA level. The mRNA expression levels of MMP-14 and TIMP-2 were not altered either. Results from comparing the change of MMP-2 protein levels in conditioned medium and cytosol of HUVECs after the P. urinaria or Ellagic Acid treatment revealed an inhibitory effect on the secretion of MMP-2 protein. This study concluded that Ellagic Acid is the active compound in P. urinaria to exhibit anti-angiogenic activity and to inhibit the secretion of MMP-2 protein from HUVECs

In Situ NMR Study on the Interaction between LiBH_4–Ca(BH_4)_2 and Mesoporous Scaffolds

We discuss the use of nuclear magnetic resonance (NMR) spectroscopy to investigate the physical state of the eutectic composition of LiBH_(4)–Ca(BH_4)_2 (LC) infiltrated into mesoporous scaffolds and the interface effect of various scaffolds. Eutectic melting and the melt infiltration of mixed borohydrides were observed through in situ NMR. In situ and ex situ NMR results for LC mixed with mesoporous scaffolds indicate that LiBH_4 and Ca(BH_4)_2 exist as an amorphous mixture inside of the pores after infiltration. Surprisingly, the confinement of the eutectic LC mixture within the mesopores is initiated below the melting temperature, which indicates a certain interaction between the borohydrides and the mesoporous scaffolds. The confined borohydrides remain inside of the pores after cooling. These phenomena were not observed in microporous or nonporous materials, and this observation highlights the importance of the pore structure of the scaffolds. Such surface interactions may be associated with a faster dehydrogenation of the nanoconfined borohydrides

Sofosbuvir-based therapy for patients with chronic hepatitis C: Early experience of its efficacy and safety in Korea

Background/AimsThe previous standard treatment for chronic hepatitis C (CHC) patients, comprising a combination of pegylated interferon (IFN) and ribavirin, was associated with suboptimal efficacy and severe adverse reactions. A new era of direct-acting antivirals is now dawning in Korea. Early experience of applying sofosbuvir-based therapy to CHC patients in Korea is reported herein.MethodsData on efficacy and safety were collected for CHC patients treated with a combination of sofosbuvir plus ribavirin or sofosbuvir/ledipasvir with or without ribavirin.ResultsThis retrospective study included 25 consecutive patients who received sofosbuvir-based therapy (19 with genotype 1b and 6 with genotype 2) at Seoul National University Hospital from May 2014 to April 2015. A virologic response was achieved at week 4 by 85.7% and 80% of the patients with genotypes 1b and 2, respectively. The HCV-RNA level decreased more slowly in IFN-experienced than in treatment-naïve patients with genotype 1b. However, the sustained virologic response at week 12 (SVR12) rate did not differ among these patients, and was as high as 100%. The presence of cirrhosis significantly increased the risk of a virologic response failure at week 4 (OR, 11.0; P=0.011) among patients with HCV genotype 1b. Only five patients (20%) experienced minor adverse events, including grade 1 fatigue and headache. The hemoglobin level decreased slightly after sofosbuvir-based therapy, but there was no case of premature discontinuation of this therapy.ConclusionsIn a real clinical practice, sofosbuvir-based therapy for CHC patients in Korea achieved optimal antiviral efficacy with insignificant adverse events. Long-term follow-up data are warranted to ensure the sustained antiviral efficacy and long-term safety of sofosbuvir-based IFN-free therapy

An endoscope with integrated transparent bioelectronics and theranostic nanoparticles for colon cancer treatment

The gastrointestinal tract is a challenging anatomical target for diagnostic and therapeutic procedures for bleeding, polyps and cancerous growths. Advanced endoscopes that combine imaging and therapies within the gastrointestinal tract provide an advantage over stand-alone diagnostic or therapeutic devices. However, current multimodal endoscopes lack the spatial resolution necessary to detect and treat small cancers and other abnormalities. Here we present a multifunctional endoscope-based interventional system that integrates transparent bioelectronics with theranostic nanoparticles, which are photoactivated within highly localized space near tumours or benign growths. These advanced electronics and nanoparticles collectively enable optical fluorescence-based mapping, electrical impedance and pH sensing, contact/temperature monitoring, radio frequency ablation and localized photo/chemotherapy, as the basis of a closed-loop solution for colon cancer treatment. In vitro, ex vivo and in vivo experiments highlight the utility of this technology for accurate detection, delineation and rapid targeted therapy of colon cancer or precancerous lesions.