Chitosan-derived nanoparticles impede signal transduction in T790M lung cancer therapy.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treated patients ultimately develop disease progression, about 50% of which are involved in the emergence of a p.Thr790Met (T790M) mutation acquiring drug resistance. In order to solve the aforementioned problem, a therapeutic nanoparticles DGA is developed to overcome EGFR-T790M resistance via downstream anti-apoptotic signal transduction blocking by a combination with persuading mitochondrial dysfunction and inhibiting miRNA expression. As the concept of design, chitosan-derived nanocarrier DCAFP, capable of persuading mitochondrial dysfunction, is demonstrated to convey gefitinib (GFT) and miR21 inhibitor (anti-miR21) to form DGA nanoparticles. The superior accumulation of antitumor therapeutics and synergistic blocking of downstream signal transduction by mitochondrial dysfunction and miRNA regulation lead to high sensitivity of DGA nanoparticles to EGFR-T790M mutated non-small cell lung cancer (NSCLC) cells with significant inhibition of tumor cell growth. The in vivo study demonstrates superior safety and antitumor efficacy of EGFRT790M mutated lung cancer mouse models. These results highlight the promise of DGA nanoparticles for enhancing GFT sensitivity to EGFRT790M NSCLC.

Evaluating the Ability of the New Subclassification to Prognosticate Outcomes Following Hepatectomy for Patients with HBV-Related HCC.

BACKGROUND: Recently, experts proposed subclassification for BCLC B patients. In this study, we aimed to evaluate the efficient of subclassification of patients with hepatitis B virus-related hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) staging system. METHODS: Seven hundred twenty-nine consecutive hepatitis B virus-related HCC patients with BCLC stage B classification who underwent hepatectomy in the period 2006-2012 were retrospectively analyzed. Patients were reclassified based on the new proposed subclassification of the BCLC B stage from B1 to B4. The prognosis of subclassification was tested using Kaplan-Meier statistics analysis. RESULTS: There were 145 (19.9%), 480 (65.8%), 62 (8.5%), and 42 (5.8%) patients in B1, B2, B3, and B4, respectively. The result suggested that overall and tumor-free survival rates among the B1, B2, and B3 subclassification in the Bolondi system had significant difference (P < 0.05). However, no significant difference was found between B3 and B4 subclassifications. Cox regression showed that BCLC B subclassification, largest/smallest diameter, and anatomic liver resection were independent predictors of tumor-free survival. BCLC B subclassification and anatomic liver resection were independent predictors of overall survival. CONCLUSIONS: The subclassification of BCLC stage B can be used in patients with HBV-related HCC who underwent curative intent hepatectomy. Patients in BCLC B1 and B2 subgroups should be treated more aggressively than patients in B3 and B4 subgroups. B3 and B4 groups should be merged for patients with HBV-related HCC who underwent curative intent hepatectomy.

CDCA5 overexpression is an Indicator of poor prognosis in patients with hepatocellular carcinoma (HCC).

BACKGROUND: Accurate and early prognosis of disease is essential to clinical decision making, particularly in diseases, such as HCC, that are typically diagnosed at a late stage in the course of disease and therefore carry a poor prognosis. CDCA5 is a cell cycle regulatory protein that has shown prognostic value in several cancers. METHODS: We retrospectively evaluated 178 patients with HCC treated with curative liver resection between September 2009 and September 2012 at Nanchong Central Hospital in Nanchong, Sichuan Province, China. Patients were screened for their CDCA5 expression levels and assigned to either the high or low expression group. Patient demographics, comorbidities, clinicopathologic data, such as tumor microvascular invasion status and size, and long-term outcomes were compared between the two groups. The effect of CDCA5 on the proliferation of liver cancer cells was analyzed using in vitro and in vivo assays. RESULTS: The present study found that increased CDCA5 expression was associated with increased tumor diameter and microvascular invasion in HCC. It was also found that CDCA5 overexpression may be associated with liver cancer cells. Additionally, this study confirmed that CDCA5 expression was increased in HCC tissue versus normal liver tissue, that CDCA5 expression was associated with decreased survival and that CDCA5 knockdown using shRNA led to cell cycle arrest in the G2/M phase. CONCLUSIONS: These findings suggest that CDCA5 expression is associated with poor prognosis in patients with hepatocellular carcinoma.

Enhanced Peroxidase-Like Activity of MoS2 Quantum Dots Functionalized g-C3N4 Nanosheets towards Colorimetric Detection of H2O2.

MoS2 quantum dots (QDs) functionalized g-C3N4 nanosheets (MoS2@CNNS) were prepared through a protonation-assisted ion exchange method, which were developed as a highly efficient biomimetic catalyst. Structural analysis revealed that uniformly-dispersed MoS2 QDs with controllable size and different loading amount grew in-situ on the surface of CNNS, forming close-contact MoS2@CNNS nanostructures and exhibiting distinct surface properties. Compared to MoS2 QDs and CNNS, the MoS2@CNNS nanocomposites exhibited a more than four times stronger peroxidase-like catalytic activity, which could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of H2O2 to generate a blue oxide. Among the MoS2@CNNS nanocomposites, MoS2@CNNS(30) was verified to present the best intrinsic peroxidase-like performance, which could be attributed to the more negative potential and larger specific surface area. A simple, rapid and ultrasensitive system for colorimetric detection of H2O2 was thus successfully established based on MoS2@CNNS, displaying nice selectivity, reusability, and stability. The detection limit of H2O2 could reach as low as 0.02 µM. Furthermore, the kinetic and active species trapping experiments indicated the peroxidase-like catalytic mechanism of MoS2@CNNS. This work develops a novel, rapid, and ultrasensitive approach for visual assay of H2O2, which has a potential application prospect on clinical diagnosis and biomedical analysis.

Lipids as integral components in mussel adhesion.

Lipids are fundamental components of cells in organisms. Recent studies reveal that lipids are also present in cell-free bioadhesives. Examples include barnacle cement, sea star footprints, hairy and smooth pads of insects and gecko setae. Whether reliance on lipids is universal in bioadhesion is not known. In the present study, we demonstrated, for the first time, the involvement of lipids in mussel adhesion. We extracted, identified and localized lipids in the byssal threads. The lipids were confirmed as fatty acids by gas chromatograpy mass spectrometry. δ13C measurements of the fatty acids in the byssus were also conducted. Results show that byssal fatty acids, with concentrations ranging from 1.10-2.51 mg g-1 by thread dry weight depending on the mussel species, are localized both on the surface of and inside the byssal thread and plaque. Over half of the fatty acids were loosely attached to the surface while a small portion were tightly bound to the byssus. Most of the surface fatty acids disappear within a week of thread deposition. δ13C values of byssal fatty acids show isotope fractionation suggesting that thread fatty acids are derived from the foot. It is possible that fatty acids are key players in expelling water and preparing the substrate surface for adhesion. Using lipids in the adhesion process might be a common strategy for organisms in need of temporary or permanent attachment. The process of lipid participation may be as important as adhesive components for developing more efficient man-made glues.

Comparison of Hepatectomy for Patients with Metabolic Syndrome-Related HCC and HBV-Related HCC.

BACKGROUND: Metabolic syndrome (MetS) is a group of clinicopathological manifestations. The outcome of liver surgery in metabolic syndrome-related hepatocellular carcinoma (MetS-HCC) still needs to be evaluated. We aim to clarify the outcomes following liver resection in patients with MetS-HCC compared those with hepatitis B virus-related HCC (HBV-HCC). METHODS: All the consecutive patients undergoing hepatectomy for HCC between January 2009 and December 2012 were retrospectively considered. Patients were divided into three groups: MetS-HCC, MetS-HBV-HCC, and HBV-HCC. Data on clinical characteristics, postoperative complications, and long-term outcome were collected and analyzed. RESULTS: A total of 1352 patients were included in this study. In MetS-HCC group, the severe morbidity rate was 33.33%, which was higher than that of HBV-HCC group (15.68%). In subgroup analysis, patients with MetS-HCC in American Joint Committee on Cancer (AJCC) stage I had superior DFS and OS when compared with those of the other two groups. CONCLUSIONS: We should pay more attention to patients with MetS-HCC perioperatively due to the high rate of surgical complications. Nevertheless, curative treatment should be provided to patients with MetS.

Optic Perineuritis in Behçet Disease.

BACKGROUND: Optic perineuritis (OPN), an uncommon optic neuropathy, has previously not been described in patients with Behçet disease (BD). We conducted this study to describe the clinical features, response to treatment, and outcome of OPN due to BD, with particular emphasis on those features that might distinguish this from the idiopathic variety. METHODS: This is a retrospective, case series review of all patients with a diagnosis of OPN seen in a hospital-based neurology department from 2008 to 2014 who also met the international criteria for the diagnosis of BD. RESULTS: Twenty-one patients with OPN were identified, of whom 10 (12 eyes) met the criteria for BD. OPN developed 2-10 years (mean, 4 years) after onset of BD, but the diagnosis of BD was made only after onset of OPN in 6. Nine of 12 eyes (75%) had severe visual loss (≤20/200), and 80% of patients progressed over several days from onset. After high-dose corticosteroid treatment, all patients experienced relief of pain, and 5 patients (50%) showed improved visual acuity. At last follow-up (mean, 25 months) 7 of 11 (64%) of affected eyes had good visual outcome (≥14/20), and no patient experienced a subsequent neurological event. CONCLUSIONS: OPN may occur as a manifestation of BD and, in non-Western countries, this may be more common than the idiopathic variety. In contrast to idiopathic cases, OPN in BD is more likely to demonstrate initial rapid progression of visual loss and more severe loss at presentation. Patients show less recovery of vision in response to corticosteroids but carry a lower rate of subsequent relapse. Patients with OPN should be specifically questioned regarding symptoms of BD.