There is little evidence that adjuvant therapy after radical surgical resection of hepatocellular carcinoma (HCC) improves recurrence-free survival (RFS) or overall survival (OS). We conducted a ...multicentre, randomised, controlled, phase IV trial evaluating the benefit of an aqueous extract of
Murr (Huaier granule) to address this unmet need.
A total of 1044 patients were randomised in 2:1 ratio to receive either Huaier or no further treatment (controls) for a maximum of 96 weeks. The primary endpoint was RFS. Secondary endpoints included OS and tumour extrahepatic recurrence rate (ERR). The Huaier (n=686) and control groups (n=316) had a mean RFS of 75.5 weeks and 68.5 weeks, respectively (HR 0.67; 95% CI 0.55 to 0.81). The difference in the RFS rate between Huaier and control groups was 62.39% and 49.05% (95% CI 6.74 to 19.94; p=0.0001); this led to an OS rate in the Huaier and control groups of 95.19% and 91.46%, respectively (95% CI 0.26 to 7.21; p=0.0207). The tumour ERR between Huaier and control groups was 8.60% and 13.61% (95% CI -12.59 to -2.50; p=0.0018), respectively.
This is the first nationwide multicentre study, involving 39 centres and 1044 patients, to prove the effectiveness of Huaier granule as adjuvant therapy for HCC after curative liver resection. It demonstrated a significant prolongation of RFS and reduced extrahepatic recurrence in Huaier group.
NCT01770431; Post-results.
Long noncoding RNA UCA1 has emerged as a novel regulator in cancer initiation and progression of various cancers. However, function and underlying mechanism of UCA1 in the progression of gastric ...cancer (GC) remain unclear. In the present study, we report that UCA1 expressed highly in GC tissues and GC cells, which was partly induced by SP1. UCA1 promoted GC cell proliferation and G1/S transition in vitro and in vivo. Moreover, UCA1 exerted its function through interacting with EZH2, promoting direct interaction with cyclin D1 promoter to activate the translation of cyclin D1. Furthermore, AKT/GSK-3B/cyclin D1 axis was activated to upregulate cyclin D1 due to overexpression of UCA1. In addition, EZH2 and phosphorylated AKT induced by UCA1 could impact each other to form a positive feedback to promote cyclin D1 expression. This study demonstrated that UCA1 as a critical regulator involved in GC proliferation and cell cycle progression by promoting cyclin D1 expression, which indicates that it may be clinically a potential therapeutic target in GC.
Background and Objectives
To identify the optimal range and the minimum number of lymph nodes (LNs) to be examined to maximize survival time of patients with curatively resected gallbladder ...adenocarcinoma (GBAC).
Methods
Data were collected from the surveillance, epidemiology, and end results database on patients with GBAC who underwent curative resection between 2004 and 2015. A Bayesian network (BN) model was constructed to identify the optimal range of harvested LNs. Model accuracy was evaluated using the confusion matrix and receiver operating characteristic (ROC) curve.
Results
A total of 1268 patients were enrolled in this study. Accuracy of the BN model was 72.82%, and the area under the curve of the ROC for the testing dataset was 78.49%. We found that at least seven LNs should be harvested to maximize survival time, and that the optimal count of harvested LNs was in the range of 7 to 10 overall, with an optimal range of 10 to 11 for N+ patients, 7 to 10 for stage T1‐T2 patients, and 7 to 11 for stage T3‐T4 patients.
Conclusions
According to a BN model, at least seven LNs should be retrieved for GBAC with curative resection, with an overall optimal range of 7 to 10 harvested LNs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The factors underlying prognosis for gallbladder cancer (GBC) remain unclear. This study combines the Bayesian network (BN) with importance measures to identify the key factors that influence GBC ...patient survival time. A dataset of 366 patients who underwent surgical treatment for GBC was employed to establish and test a BN model using BayesiaLab software. A tree-augmented naïve Bayes method was also used to mine relationships between factors. Composite importance measures were applied to rank the influence of factors on survival time. The accuracy of BN model was 81.15%. For patients with long survival time (>6 months), the true-positive rate of the model was 77.78% and the false-positive rate was 15.25%. According to the built BN model, the sex, age, and pathological type were independent factors for survival of GBC patients. The N stage, liver infiltration, T stage, M stage, and surgical type were dependent variables for survival time prediction. Surgical type and TNM stages were identified as the most significant factors for the prognosis of GBC based on the analysis results of importance measures.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Aim
The prognostic value of the newly raised objective liver function assessment tool, the albumin–bilirubin (ALBI) grade, in patients with hepatocellular carcinoma has not been fully validated. We ...aimed to compare the performance of ALBI grade with the specific Child–Pugh (C‐P) score in predicting prognosis in this study.
Methods
The clinical data of 491 C‐P class A patients who underwent liver resection as initial therapy from January 2000 to December 2007 in Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China) were retrospectively analyzed. The prognostic performances of ALBI and C‐P score in predicting the short‐ and long‐term clinical outcomes were compared.
Results
The ALBI score gained a significantly larger area under the receiver operating characteristic curve for predicting the occurrence of severe postoperative complications than that of C‐P score. With a median follow‐up of 57 months, the 1‐year, 3‐year, and 5‐year overall survival rates of the patients were 92.1%, 65.8%, and 45.2%, respectively. Tumor number, tumor size, and ALBI grade were proved to be the independent prognostic factors for overall survival in the multivariate analysis. Prognostic performance was shown to be better for ALBI grade when it was compared to C‐P score in terms of both the Akaike information criterion value and χ2 value of likelihood ratio test.
Conclusions
The ALBI grade, which was featured by simplicity and objectivity, gained a superior prognostic value than that of C‐P grade in patients with hepatocellular carcinoma who underwent liver resection. Future well‐designed studies with larger sample sizes are warranted.
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In this article, a nonconformal and nonoverlapping domain decomposition method (DDM) based on surface integral equation (SIE) is proposed for the electromagnetic (EM) scattering or radiation of ...multiscale metallic targets. To reduce the unknown amount of the conventional SIE for multiscale EM simulation, we apply curved triangular elements and higher order hierarchical vector (HOHV) basis functions to the SIE. Next, to increase the flexibility of geometrical modeling and accelerate the convergence of the presented SIE system for electrically large and multiscale metallic targets, a DDM scheme is further developed to employ a discontinuous Galerkin (DG) approach to glue conformal/nonconformal surface grids between adjacent subdomains. In addition, an interior penalty term is introduced to stabilize the DDM solution, and half edge-based HOHV basis functions are introduced to model the current associated with nonconformal surface elements. Meanwhile, the basis expansion and recombination (BER) technique is introduced to significantly accelerate the matrix-filling and improve the efficiency. The flexibility of basis order selection is further enhanced by the hierarchical characteristic of HOHV bases. Finally, several numerical results are provided to demonstrate the accuracy, efficiency, and flexibility of the proposed HO-DG-DDM.
A series of 4-aminoquinazoline derivatives were designed and synthesized as epidermal growth factor receptor (EGFR) inhibitors in our group. The bioassay results showed all the target compounds ...possessed potential anti-tumor activities against on A549 and H1975 cell lines. The IC50 values of 8.35 (for A549) and 19.18 μM (for H1975) exhibited remarkable inhibitory activity of compound 7d, which were better compared to the positive control Afatinib (IC50 = 10.41 μM for A549, IC50 = 24.96 μM for H1975). In addition, the molecular docking and ADME prediction of compound 7d was carried out. The experimental results show the compound 7d is worth to further research and discuss.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This article presents a novel optimization algorithm to design a probability density taper for large array thinning. This novel algorithm is based on the iterative Fourier technique (IFT) integrated ...with an innovative adaptive learning mechanism and denoted as the probability learning IFT (PLIFT) here. With successive forward and backward Fourier transforms, the traditional IFT can be capable of thinning large arrays with high convergence rates, but easily get trapped in local optima. The proposed PLIFT utilizes the probability estimation to describe the elements with possible states of "ON" and "OFF" in a thinned array. A probability model is then adopted to determine the locations of elements in the thinned array featuring minimum sidelobe level. In this PLIFT, on the one hand, the probability model of density taper is learned in optimization process and gradually trained to approach the global optima. With the previous information being honored, the probability model taper proves to be reliable and effective in generating diverse competitive seeds, which, in turn, helps training an optimal probability distribution to best-fit the design goal. Several representative examples of large planar arrays thinning are provided to demonstrate the validity, highlighted global searching ability and increased robustness of the PLIFT.
A series of novel 6-substituted quinazoline derivatives were synthesised as epidermal growth factor receptor(EGFR) and Human epidermal growth factor receptor 2 (HER2)inhibitors in our lab. The novel ...compounds were measured for their dual enzyme inhibition as well as their cytotoxic activity on MCF7 cell line. The results revealed that all the compounds showed inhibition of both enzymes. Compound 5c showed the best inhibitory activity against both enzymes and IC50 of its was 2.6 nM against EGFR kinases and 4.3 nM against HER2 kinases, respectively. Most of the measured compounds showed to antitumor activity on MCF7.
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Pulmonary edema associated with increased vascular permeability is a severe complication of Pseudomonas (P.) aeruginosa‐induced acute lung injury. The mechanisms underlying P aeruginosa‐induced ...vascular permeability are not well understood. In the present study, we investigated the role of neuronal Wiskott Aldrich syndrome protein (N‐WASP) in modulating P aeruginosa‐induced vascular permeability. Using lung microvascular endothelial and alveolar epithelial cells, we demonstrated that N‐WASP downregulation attenuated P aeruginosa‐induced actin stress fiber formation and prevented paracellular permeability. P aeruginosa‐induced dissociation between VE‐cadherin and β‐catenin, but increased association between N‐WASP and VE‐cadherin, suggesting a role for N‐WASP in promoting P aeruginosa‐induced adherens junction rupture. P aeruginosa increased N‐WASP‐Y256 phosphorylation, which required the activation of Rho GTPase and focal adhesion kinase. Increased N‐WASP‐Y256 phosphorylation promotes N‐WASP and integrin αVβ6 association as well as TGF‐β‐mediated permeability across alveolar epithelial cells. Inhibition of N‐WASP‐Y256 phosphorylation by N‐WASP‐Y256F overexpression blocked N‐WASP effects in P aeruginosa‐induced actin stress fiber formation and increased paracellular permeability. In vivo, N‐WASP knockdown attenuated the development of pulmonary edema and improved survival in a mouse model of P aeruginosa pneumonia. Together, our data demonstrate that N‐WASP plays an essential role in P aeruginosa‐induced vascular permeability and pulmonary edema through the modulation of actin cytoskeleton dynamics.
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