Transarterial chemoembolization (TACE) is the current standard of treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). Brivanib, a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor signaling, may improve the effectiveness of TACE when given as an adjuvant to TACE. In this multinational, randomized, double-blind, placebo-controlled, phase III study, 870 patients with TACE-eligible HCC were planned to be randomly assigned (1:1) after the first TACE to receive either brivanib 800 mg or placebo orally once-daily. The primary endpoint was overall survival (OS). Secondary endpoints included time to disease progression (TTDP; a composite endpoint based on development of extrahepatic spread or vascular invasion, deterioration of liver function or performance status, or death), time to extrahepatic spread or vascular invasion (TTES/VI), rate of TACE, and safety. Time to radiographic progression (TTP) and objective response rate were exploratory endpoints. The trial was terminated after randomization of 502 patients (brivanib, 249; placebo, 253) when two other phase III studies of brivanib in advanced HCC patients failed to meet OS objectives. (brivanib, 18% vs. placebo, 5%) and hypertension (13% vs. 3%). Conclusions: In this study, brivanib as adjuvant therapy to TACE did not improve OS. (HEPATOLOGY 2014;60:1697-1707

The aim of the study was to investigate the value of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the early and short-term responses to chemoradiotherapy (CRT) in patients with nasopharyngeal carcinoma (NPC).Forty-three NPC patients underwent IVIM-DWI and DCE-MRI at baseline (pretreatment) and after the first cycle of induction chemotherapy (posttreatment). Based on whether locoregional lesions were identified, patients were divided into the residual and nonresidual groups at the end of CRT and into the good-responder and poor-responder groups 6 months after the end of CRT. The pretreatment and posttreatment IVIM-DWI parameters (ADC, D, D∗, and f) and DCE-MRI parameters (Ktrans, Kep, and Ve) values and their percentage changes (Δ%) were compared between the residual and nonresidual groups and between the good-responder and poor-responder groups.None of perfusion-related parametric values derived from either DCE-MRI or IVIM-DWI showed significant differences either between the residual and nonresidual groups or between the good-responder and poor-responder groups. The nonresidual group exhibited lower pre-ADC, lower pre-D, and higher Δ%D values than did the residual group (all P <0.05). The good-responder group had lower pre-D and pre-ADC values than did the poor-responder group (both P <0.05). Based on receiver operating characteristic (ROC) curve analysis, pre-D had the highest area under the curve in predicting both the early and short-term responses to CRT for NPC patients (0.817 and 0.854, respectively).IVIM-DWI is more valuable than DCE-MRI in predicting the early and short-term response to CRT for NPC, and furthermore diffusion-related IVIM-DWI parameters (pre-ADC, pre-D, and Δ%D) are more powerful than perfusion-related parameters derived from both IVIM-DWI and DCE-MRI.

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Abstract. microRNAs (miRNAs/miRs) are crucial regulators of gene expression at the post-translational level through promoting mRNA degradation or the repression of translation of target genes. miRs have been confirmed to serve a dominant role in tumor biology. miR-486-5p has been ascertained to be involved in non-small-cell lung cancer, breast cancer and hepatocellular carcinoma; however, the expression and function of miR-486-5p in esophageal squamous cell carcinoma (ESCC) has yet to be elucidated. The present study aimed to analyze the expression levels of miR-486-5p in ESCC tissues and paired normal adjacent tissues, and determine the effects of miR-486-5p on esophageal cancer cells using MTT, wound scratch and apoptosis assays. The current results showed that miR-486-5p was significantly downregulated in ESCC specimens. Ectopic expression of miR-486-5p by synthetic mimics reduced cell proliferation and migration and induced increased cell apoptosis. The results indicated miR-486-5p may function as a tumor suppressor in ESCC. The present study demonstrated that miR-486-5p was downregulated in ESCC and served a anti-oncogene role in ESCC via affecting cellular migration.

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Idiopathic pulmonary fibrosis (IPF) is a kind of a chronic and fatal lung disease leading to progressive lung function decline. Although several RNA microarray studies on IPF patients have been reported, their results were merely specific to each study with distinct platforms or sample types. In the current study, an integrative transcriptome meta-analysis of IPF was performed to explore regulated pathways, based on four independent expression profiling microarrays of IPF datasets, including 73 samples from IPF tissues or lung fibroblast cells. The results suggested the discoidin domain receptor 1 (DDR1) and downstream c-Jun N-terminal kinases (JNK) pathway may play important roles in the progression of IPF. To our knowledge, discoidin domain receptor 1 (DDR1) is a kind of receptor tyrosine kinase (RTK) with a unique ability to bind both fibrillar and non-fibrillar collagens. Based on the crystallographic structures of DDR1, the combination of molecular dynamics simulation and a hybrid protocol of a virtual screening method, comprised of PBVS (multicomplex-pharmacophore based virtual screening) and DBVS (docking based virtual screening) methods were used for retrieving novel DDR1 inhibitors from the SPECS database. Twelve hit compounds were selected from the hit compounds and shifted to experimental validations, and the most potent compound was evaluated for its anti-IPF capacity on murine IPF models. Thus, these results may provide valuable information for further discovery of potential lead compounds for IPF therapy.

Abstract. MicroRNAs (miRs) are small endogenous non-coding RNAs that play a vital role in carcinogenesis. miR-193a-3p has been described in multiple cancers. However, the function of miR-193a-3p in esophageal squamous cell carcinoma (ESCC) is still unclear. To explore the role of miR-193a-3p in ESCC, reverse transcription-quantitative polymerase chain reaction was used to evaluate the expression of miR-193a-3p in 48 paired ESCC and adjacent normal tissues. In addition, the impact of miR-193a-3p on cell proliferation, migration and apoptosis were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, wound scratch assay and flow cytometry, respectively. The results revealed that miR-193a-3p was upregulated in ESCC, compared with adjacent normal tissues. Downregulation of miR-193a-3p expression using a synthesized inhibitor suppressed cell proliferation and migration, and induced cell apoptosis, indicating that miR-193a-3p could be characterized as an oncogene in ESCC. In summary, the present study demonstrated that miR-193a-3p was upregulated in ESCC, where it plays a significant role by affecting cellular proliferation, migration and apoptosis.

The aim of the study was to investigative the utility of gray-level co-occurrence matrix (GLCM) texture analysis based on intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for predicting the early response to chemoradiotherapy for nasopharyngeal carcinoma (NPC).Baseline IVIM-DWI was performed on 81 patients with NPC receiving chemoradiotherapy in a prospective nested case–control study. The patients were categorized into the residue (n = 11) and nonresidue (n = 70) groups, according to whether there was local residual lesion or not at the end of chemoradiotherapy. The pretreatment tumor volume and the values of IVIM-DWI parameters (apparent diffusion coefficient [ADC], D, D∗, and f) and GLCM features based on IVIM-DWI were compared between the 2 groups. Receiver operating characteristic (ROC) curves in univariate and multivariate logistic regression analysis were generated to determine significant indicator of treatment response.The nonresidue group had lower tumor volume, ADC, D, CorrelatADC, CorrelatD, InvDfMomADC, InvDfMomD and InvDfMomD∗ values, together with higher ContrastD, Contrastf, SumAvergADC, SumAvergD, and SumAvergD∗ values, than the residue group (all P < .05). Based on ROC curve in univariate analysis, the area under the curve (AUC) values for individual GLCM features in the prediction of the treatment response ranged from 0.635 to 0.879, with sensitivities from 54.55% to 100.00% and specificities from 52.86% to 85.71%. Multivariate logistic regression analysis demonstrated D (P = .026), InvDfMomADC (P = .033) and SumAvergD (P = .015) as the independent predictors for identifying NPC without residue, with an AUC value of 0.977, a sensitivity of 90.91% and a specificity of 95.71%.Pretreatment GLCM features based on IVIM-DWI, especially on the diffusion-related maps, may have the potential to predict the early response to chemoradiotherapy for NPC.