PRMT3-mediated arginine methylation of IGF2BP1 promotes oxaliplatin resistance in liver cancer.

Although oxaliplatin-based chemotherapy has been effective in the treatment of hepatocellular carcinoma (HCC), primary or acquired resistance to oxaliplatin remains a major challenge in the clinic. Through functional screening using CRISPR/Cas9 activation library, transcriptomic profiling of clinical samples, and functional validation in vitro and in vivo, we identify PRMT3 as a key driver of oxaliplatin resistance. Mechanistically, PRMT3-mediated oxaliplatin-resistance is in part dependent on the methylation of IGF2BP1 at R452, which is critical for the function of IGF2BP1 in stabilizing the mRNA of HEG1, an effector of PRMT3-IGF2BP1 axis.

S100A9 Derived from Chemoembolization-Induced Hypoxia Governs Mitochondrial Function in Hepatocellular Carcinoma Progression.

Transarterial chemoembolization (TACE) is the major treatment for advanced hepatocellular carcinoma (HCC), but it may cause hypoxic environment, leading to rapid progression after treatment. Here, using high-throughput sequencing on different models, S100 calcium binding protein A9 (S100A9) is identified as a key oncogene involved in post-TACE progression. Depletion or pharmacologic inhibition of S100A9 significantly dampens the growth and metastatic ability of HCC.

Elafin promotes tumour metastasis and attenuates the anti-metastatic effects of erlotinib via binding to EGFR in hepatocellular carcinoma.

Background: Elafin is a serine protease inhibitor critical for host defence. We previously reported that Elafin was associated with the recurrence of early-stage hepatocellular carcinoma (HCC) after surgery. However, the exact role of Elafin in HCC remains obscure.

Surgical Resection versus Re-Ablation for Intrahepatic Recurrent Hepatocellular Carcinoma after Initial Ablation Therapy.

Background And Aims: Whether surgical resection or repeated ablation should be recommended for intrahepatic recurrent hepatocellular carcinoma (HCC) conforming to the Milan criteria after initial ablation remains unclear. In this study, we compared the outcomes of patients who underwent surgical resection with those who underwent re-ablation for recurrent HCC after initial curative-intent ablation.

Methods: The data of 28 and 98 patients who underwent surgical resection and re-ablation, respectively, for recurrent HCC after initial ablation between January 2003 and 2017 were analyzed using propensity score matching.

Apatinib versus sorafenib in patients with advanced hepatocellular carcinoma: a preliminary study.

Background: Apatinib, a selective inhibitor of vascular endothelial growth factor receptor 2 (VEGFR 2), has exhibited modest antitumor efficacy in hepatocellular carcinoma (HCC). We aimed to evaluate the effectiveness and tolerability of apatinib versus sorafenib in patients with advanced HCC.

Methods: All patients with advanced HCC who underwent sorafenib or apatinib between January 2016 to December 2017 were retrospectively reviewed.

Transcatheter arterial chemoembolization alone or combined with ablation for recurrent intermediate-stage hepatocellular carcinoma: a propensity score matching study.

Purpose: The recurrence after curative hepatectomy is common. Limited data have investigated the effect of transcatheter arterial chemoembolization (TACE) combined with ablation in treating recurrent intermediate-stage hepatocellular carcinoma (HCC) after hepatectomy. We aim to compare the efficacy of TACE combined with ablation versus TACE alone in treating recurrent intermediate-stage HCC after hepatectomy.

Dysregulated Sp1/miR-130b-3p/HOXA5 axis contributes to tumor angiogenesis and progression of hepatocellular carcinoma.

Angiogenesis, one of the hallmarks of cancer, is essential for both tumor growth and metastasis. However, its molecular mechanisms in hepatocellular carcinoma (HCC) are largely unknown. Here, we report the role of HOXA5 in tumor angiogenesis of HCC.

Comparison of the prognostic value of inflammation-based scores in early recurrent hepatocellular carcinoma after hepatectomy.

Background & Aims: Inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), Prognostic Nutritional Index (PNI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and systemic immune-inflammation index (SII), are correlated with the survival of hepatocellular carcinoma (HCC) patients, while remain unclear for recurrent HCC. This study aimed to compare the prognostic value of inflammation-based prognostic scores for post-recurrence survival (PRS) in patients with early recurrent HCC (ErHCC, within 2 years after hepatectomy).

Methods: A total of 580 patients with ErHCC were enrolled retrospectively.

Microwave ablation resection for hepatocellular carcinoma within the Milan criteria: a propensity-score analysis.

Background: Whether the efficient heat-generating mechanism of microwave ablation (MWA) is comparable with resection (RES) in treating hepatocellular carcinoma (HCC) remains unclear.

Methods: This retrospective cohort study comprised 126 and 1183 patients with HCC meeting the Milan criteria who received MWA or RES between 2002 and 2017. We compared 5-year overall survival (OS) and recurrence-free survival (RFS) using both propensity-score matching (PSM) and inverse-probability-of-treatment-weighting (IPW) analysis and investigated the prognostic factors with multivariate Cox analysis.

KCNK levels are prognostic and diagnostic markers for hepatocellular carcinoma.

Two-pore-domain (KCNK, K2P) K channels are transmembrane protein complexes that control the flow of ions across biofilms, which underlie many essential cellular functions. Because KCNK family members are known to contribute to tumorigenesis in various types of cancer, we hypothesized that they might be differentially expressed in hepatocellular carcinoma (HCC) cells as compared to healthy tissue and serve as diagnostic or prognostic biomarkers. We tested this hypothesis through bioinformatic analyses of publicly available data for the expression of various KCNK subunits in HCC.

Resection vs Ablation for Multifocal Hepatocellular Carcinomas meeting the Barcelona-Clinic Liver Cancer A Classification: A Propensity Score Matching Study.

With development of surgical technology, we aimed to investigate whether resection could challenge the standard treatment, ablation, in treating multifocal hepatocellular carcinomas meeting the Barcelona-Clinic Liver Cancer A stage. From January 2005 to January 2017, the oncological outcomes of patients undergoing resection (n = 72) or ablation (n = 63) were retrospectively analysed using propensity score matching. At baseline, patients in the ablation group had more tri-focal lesions (30.

Lipiodol deposition in portal vein tumour thrombus predicts treatment outcome in HCC patients after transarterial chemoembolisation.

Objective: To study lipiodol deposition in portal vein tumour thrombus (PVTT) in predicting the treatment outcome of hepatocellular carcinoma (HCC) patients after transarterial chemoembolisation (TACE).

Methods: We retrospectively reviewed data from 379 HCC patients with PVTT who underwent TACE as the initial treatment at Sun Yat-Sen University Cancer Center from January 2008 to December 2015. Patients were grouped by positive and negative lipiodol deposition based on the extent of lipiodol deposition in PVTT.

Tyrosine kinase SYK is a potential therapeutic target for liver fibrosis.

Spleen tyrosine kinase (SYK) plays a critical role in immune cell signaling pathways and has been reported as a biomarker for human hepatocellular carcinoma (HCC). We sought to investigate the mechanism by which SYK promotes liver fibrosis and to evaluate SYK as a therapeutic target for liver fibrosis. We evaluated the cellular localization of SYK and the association between SYK expression and liver fibrogenesis in normal, hepatitis B virus (HBV)-infected, hepatitis C virus (HCV)-infected and non-alcoholic steatohepatitis (NASH) liver tissue (n=36, 127, 22 and 30, respectively).

Optimized construction of MUC1-VNTR DNA vaccine and its anti-pancreatic cancer efficacy.

Considering mucin 1-variable number tandem repeat (MUC1-VNTR) as a novel target for pancreatic cancer immunotherapy, the present study aimed to screen and identify the pVAX1-MUC1-VNTR DNA vaccine with the strongest immunogenicity. Following construction of a pVAX1-MUC1-VNTR plasmid, immature dendritic cells (DCs) were subjected to transfection, and mature DCs were then co-cultured with autologous T-cells. The numbers of cytotoxic T lymphocytes (CTLs) secreting interferon (IFN)-γ were determined using an enzyme-linked immunospot assay, and CytoTox was also used to examine the MUC1-VNTR-specific Lethal effect of CTLs on Capan2 cells.

Serum Insulin-Like Growth Factor Axis and the Risk of Pancreatic Cancer: Systematic Review and Meta-Analysis.

Objective: To investigate the association between serum concentration of insulin-like growth factor (IGF) and the risk of pancreatic cancer (PaC).

Methods: We identified eligible studies in Medline and EMBASE databases (no reference trials from 2014 to 2016) in addition to the reference lists of original studies and review articles on this topic. A summary of relative risks with 95% confidence intervals (CI) was calculated using a random-effects model.

Sorafenib therapy following resection prolongs disease-free survival in patients with advanced hepatocellular carcinoma at a high risk of recurrence.

Sorafenib is the standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC); however, its therapeutic value in patients with HCC following resection remains controversial. The current retrospective study was undertaken to assess the effects of sorafenib treatment following surgical resection in patients with advanced HCC disease who were at a high risk for recurrence. Between July 2010 and July 2013, a consecutive cohort of 42 patients with advanced HCC and at a high risk of recurrence (i.

Effectiveness of ω-3 Polyunsaturated Fatty Acids Based Lipid Emulsions for Treatment of Patients after Hepatectomy: A Prospective Clinical Trial.

Objective: The present study aimed to investigate the effectiveness of parenteral nutritional support with ω-3 PUFAs-based lipid emulsions in patients after liver resection.

Methods: A total of 119 patients were randomly assigned to the immunonutrition (IM) group (n = 59) and control group (n = 60). The IM group was continuously given Omegaven(®) 10% 100 mL/day rather than regular nutrition for five days postoperatively.

Resection versus ablation in hepatitis B virus-related hepatocellular carcinoma patients with portal hypertension: A propensity score matching study.

Background: With recent improvements in operative techniques, many studies have reported that resection is safe for hepatocellular carcinoma (HCC) patients with portal hypertension (PHT). However, no direct evidence exists to compare resection with ablation in patients with hepatitis B virus (HBV)-related PHT.

Methods: Of 259 HBV-related PHT patients who met the Milan criteria, 123 patients underwent resection and 136 underwent ablation as a primary treatment.

The role of clinically significant portal hypertension in hepatic resection for hepatocellular carcinoma patients: a propensity score matching analysis.

Background: Whether portal hypertension (PHT) is an appropriate contraindication for hepatic resection (HR) in hepatocellular carcinoma (HCC) patient is still under debate.

Aims: Our aim was to assess the impact of clinically significant PHT on postoperative complication and prognosis in HCC patients who undergo HR.

Methods: Two hundred and nine HCC patients who underwent HR as the initial treatment were divided into two groups according to the presence (n = 102) or absence (n = 107) of clinically significant PHT.

Hepatectomy Versus Hepatectomy With Lymphadenectomy in Hepatocellular Carcinoma: A Prospective, Randomized Controlled Clinical Trial.

Goals And Background: The role of preventive lymphadenectomy has not yet been determined for hepatocellular carcinoma (HCC) patients. We designed a study to evaluate the effect of hepatectomy combined with preventive lymphadenectomy on HCC patients.

Study: Patients were randomly divided into group A (treated with hepatectomy alone) and group B (underwent hepatectomy combined with lymphadenectomy).

Upregulation of microRNA-106b is associated with poor prognosis in hepatocellular carcinoma.

Background: MicroRNA-106b (miR-106b) is a member of the miR-106b ~ 25 cluster. It has been reported that miR-106b acts as an oncogene and is upregulated in many human cancers. However, the prognostic value of miR-106b in hepatocellular carcinoma (HCC) remains unclear.

MicroRNA-130a is down-regulated in hepatocellular carcinoma and associates with poor prognosis.

MicroRNA-130a (miR-130a) has recently been found to be implicated in many critical processes in various types of human cancer. However, the prognostic value of miR-130a in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the expression of miR-130a in HCC and analyzed its association with clinical features and prognosis of HCC patients.

Expression of variant isoforms of the tyrosine kinase SYK determines the prognosis of hepatocellular carcinoma.

The spleen tyrosine kinase (SYK) has been reported as a novel biomarker for human hepatocellular carcinoma, but the functional contributions of its two isoforms SYK(L) and SYK(S) are undefined. In this study, we investigated their biologic functions and possible prognostic values in hepatocellular carcinoma. SYK(L) was downregulated in 38% of human specimens of hepatocellular carcinoma examined, whereas SYK(S) was detectable in 40% of these specimens but not in normal liver tissue samples without cirrhosis.