Regulatory mechanisms of macrophage polarization in adipose tissue.

In adipose tissue, macrophages are the most abundant immune cells with high heterogeneity and plasticity. Depending on environmental cues and molecular mediators, adipose tissue macrophages (ATMs) can be polarized into pro- or anti-inflammatory cells. In the state of obesity, ATMs switch from the M2 polarized state to the M1 state, which contributes to chronic inflammation, thereby promoting the pathogenic progression of obesity and other metabolic diseases. Recent studies show that multiple ATM subpopulations cluster separately from the M1 or M2 polarized state. Various factors are related to ATM polarization, including cytokines, hormones, metabolites and transcription factors. Here, we discuss our current understanding of the potential regulatory mechanisms underlying ATM polarization induced by autocrine and paracrine factors. A better understanding of how ATMs polarize may provide new therapeutic strategies for obesity-related diseases.

miR-500a-3p is a Potential Prognostic Biomarker in Hepatocellular Carcinoma.

PURPOSE: miR-500a-3p has been extensively reported to be implicated in the development and progression in several human cancer types. This study aimed to investigate the diagnostic and prognostic significance of miR-500a-3p as a biomarker in hepatocellular carcinoma (HCC). METHODS: miR-500a-3p expression was evaluated by in situ hybridization (ISH) and real-time PCR in 10 adjacent normal tissues (ANT), 21 liver fibrosis tissues, and 110 HCC tissues. Statistical analysis was used to investigate the correlation of miR-500a-3p expression with clinicopathological features in HCC patients. Kaplan-Meier survival analysis was performed to evaluate the prognostic significance of miR-500a-3p in overall survival and recurrence-free survival in HCC patients. RESULTS: In this study, we found that expression levels of miR-500a-3p were enhanced in HCC tissues. High miR-500a-3p levels were positively correlated with multiple clinicopathological features, including advanced clinical stage, distant metastatic status, increased AFP levels and poor tumor differentiation degree. More importantly, high miR-500a-3p levels predicted poor overall survival and early recurrence in HCC patients. Finally, a strong and positive correlation of miR-500a-3p mRNA expression with ISH staining scores was observed in clinical HCC tissues. CONCLUSION: Our findings suggest that miR-500a-3p might be used as a novel biomarker to facilitate early diagnosis and predict prognosis in HCC patients.

Mechanism underlying long non­coding RNA ILF3­AS1­mediated inhibition of cervical cancer cell proliferation, invasion and migration, and promotion of apoptosis.

Long non­coding RNA ILF3 divergent transcript (ILF3­AS1) displays a tumor­suppressing effect. StarBase predicted that the potential target microRNA (miR) of ILF3­AS1 was miR­454­3p; therefore, the present study investigated the effect of ILF3­AS1 and its target miR­454­3p on cervical cancer (CC). Gene Expression Profiling Interactive Analysis was used to predict the expression of ILF3­AS1 in CC and the overall survival rate of patients. The present study demonstrated that ILF3­AS1 expression was significantly downregulated in human CC tissues and cells compared with adjacent tissues (ANTs) and normal cervical epithelial cells (NCEs), respectively. Patients with CC with high ILF3­AS1 expression displayed higher survival rates compared with patients with low ILF3­AS1 expression. Cell viability, apoptosis, migration and invasion were detected by performing Cell Counting Kit­8, flow cytometry, wound healing and Transwell assays, respectively. Compared with the negative control (NC) group, ILF3­AS1 overexpression significantly inhibited CC cell viability and migration, but significantly increased CC cell apoptosis. Moreover, ILF3­AS1 overexpression significantly upregulated E­Cadherin expression levels, but significantly downregulated N­Cadherin and snail family transcriptional repressor 1 expression levels compared with the NC group. miR­454­3p expression was negatively correlated with ILF3­AS1, and highly expressed in CC tissues and cells compared with ANTs and NCEs, respectively. PTEN, which was predicted and verified as the target gene for miR­454­3p, was significantly downregulated in CC tissues and cells compared with ANTs and NCEs, respectively. ILF3­AS1 expression was positively correlated with PTEN expression, and ILF3­AS1 overexpression partially reversed the inhibitory effect of miR­454­3p on PTEN expression. In conclusion, the present study indicated that ILF3­AS1 inhibited CC cell proliferation and migration, and promoted CC cell apoptosis by inhibiting epithelial­mesenchymal transition, and ILF3­AS1 overexpression partially reversed the inhibitory effect of miR­454­3p on PTEN expression.

CFDA-SE Combined with MACSiBeads™ Particles to Evaluate the Inhibitory Effect of Treg Cells in vitro.

OBJECTIVE: To explore the application of carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) and MACSiBeads™ Particles within in vitro suppression assays of regulatory T (Treg) cells. METHODS: CD4+CD25+ Treg cells and CD8+ T cells were sorted using magnetically activated cell sorting. CD8+ T cells were subjected to CFDA-SE staining to determine their optimal staining concentration. MACSi-Beads™ Particles, a component of the Treg expansion kit, were used as stimulators in suppression assays. Five experimental groups were set based on the condition of MACSiBeads™ Particles, CFDA-SE staining and cell composition of co-culture system, which were stimulated CD8+ cells without CFDA-SE staining, unstimulated CD8+ cells with CFDA-SE staining, stimulated CD8+ cells with CFDA-SE staining, co-cultured with Treg cells at a ratio of 1:0.25, 1:0.125 and 1:0, respectively. Flow cytometry was performed using the BD FACS Canto™ and flow data was analyzed using FCS Express 4 Plus software. RESULTS: CFSE fluorescence intensity correlated with cell type and culture time. The final CFDA-SE staining concentration was 0.5µM. Within in vitro suppression assays, Treg cells showed a significant inhibitory effect on the proliferation of CD8+ T cells increasing as its concentration increased. CONCLUSION: CFDA-SE combined with MACSiBeads™ Particles can be used to evaluate the in vitro inhibition effect of Treg cells.

Predictive factors of treatment outcomes after percutaneous ablation of hepatocellular carcinoma in the caudate lobe: a retrospective study.

BACKGROUND: Hepatocellular carcinomas (HCC) arising in the caudate lobe is rare and the treatment is difficult. The aim of this study is to summarize the experience of ultrasound-guided percutaneous ablation therapy for HCC located in the caudate lobe and to investigate the predictive factors of the treatment outcomes. METHODS: From August 2006 to June 2017, 73 patients (63 males and 10 females; mean age, 54.9 ± 11.6 years; age range, 25-79 years) with 73 caudate lobe HCCs (mean size, 2.6 ± 1.1 cm; size range, 1.0-5.0 cm) were treated with percutaneous ablation, including 33 patients with radiofrequency ablation (RFA), 23 patients with ethanol ablation (EA), and 17 patients with combination of RFA and EA. The treatment outcome and survival after ablation for caudate lobe HCC were assessed and the predictive factors were calculated by univariate and multivariate analyses. RESULTS: A total of 72 patients achieved complete ablation after the first or second session of ablation. The treatment effectiveness was 98.6% (72/73). During the follow-up, 16 tumors developed local tumor progression (LTP) and a total of 61 patients (61/73, 83.6%) were detected distant recurrence (DR). According to univariate and multivariate analyses, tumor size > 2 cm (hazard ratio[HR] = 3.667; 95% confidence interval[CI], 1.043-12.889; P = 0.043) was a significant prognostic factor of LTP after ablation for HCC in the caudate lobe, while tumor number (HR = 2.245; 95%CI, 1.168-4.317; P = 0.015) was a significant prognostic factor of DR. The mean overall survival time after ablation was 28.7 ± 2.8 months, without independent predictive factors detected. Four patients (4/73, 5.5%) were detected treatment-related major complications, without independent predictive factor detected. CONCLUSION: Ultrasound-guided percutaneous ablation is a feasible treatment for a selected case with HCC in the caudate lobe. Tumor size > 2 cm increases the risk of LTP and intrahepatic tumor number is associated with DR after ablation.

Combined transcatheter arterial chemoembolization and radiofrequency ablation versus hepatectomy for recurrent hepatocellular carcinoma after initial surgery: a propensity score matching study.

OBJECTIVES: To compare retrospectively the efficacy of transcatheter arterial chemoembolization (TACE) plus radiofrequency ablation (RFA) (TACE-RFA) with that of repeat hepatectomy in the treatment of initial recurrent hepatocellular carcinoma (HCC) after hepatectomy by propensity score matching (PSM). METHODS: From September 2006 to June 2015, 186 patients who underwent TACE-RFA (n=107) or repeat hepatectomy (n=79) for recurrent HCC ≤ 5.0 cm were included. The overall survival (OS) and disease-free survival (DFS) were compared. PSM was used to correct potential confounding factors between these two groups. RESULTS: 1-, 3-, and 5-year OS rates after TACE-RFA and repeat hepatectomy were 84.6%, 66.9%, 49.1%, and 84.8%, 60.2%, 51.9%, respectively (p=.871). The corresponding DFS rates were 58.2%, 35.2%, 29.6% and 64.8%, 41.6%, 38.3% (p=.258). TACE-RFA has lower major complication rates (p=.009) and shorter hospital stay (p<.001). After PSM, 1-, 3-, 5- year OS rates after TACE-RFA (n=51) and repeat hepatectomy (n=51) were 84.3%, 60.4%, 46.4% and 84.3%, 64.5%, 49.8% (p=.951), the corresponding DFS rates were 54.9%, 35.0%, 30.6% and 58.7%, 35.8%, and 33.6% (p=.733). AFP and micro-vessel invasion of initial tumour were significant prognostic factors for OS and DFS, respectively. CONCLUSIONS: TACE-RFA provides comparable OS and DFS to repeat hepatectomy, fewer major complications and shorter hospital stay. KEY POINTS: • TACE-RFA achieved similar OS and DFS with repeat hepatectomy for recurrent HCC • Major complication rate was lower in the TACE-RFA group • The hospital stay was shorter in the TACE-RFA group • AFP was a predictor for OS, MVI was a predictor for DFS • The treatment strategies were not significant prognostic factor for OS or DFS.

Safety margin after radiofrequency ablation of hepatocellular carcinoma: precise assessment with a three-dimensional reconstruction technique using CT imaging.

PURPOSE: To analyse the precise ablative margin (AM) after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) and the correlation between AM and local tumour progression (LTP) with a three-dimension (3D) reconstruction technique. METHODS: From March 2011 to May 2013, 134 patients who underwent RFA for 159 primary or recurrent HCCs within Milan criteria were enrolled. Contrast-enhanced computed tomography (CECT) scans were performed 1 week before and 1 month after treatment. The AM was measured in various directions using a 3D reconstruction technique that shows the index tumour and ablated zone on the same image. The average of all obtained AMs (average AM) and the smallest AM (min-AM) were calculated. RESULTS: The min-AM after RFA ranged from 1 to 9.3 mm (median ± standard deviation, 4.8 ± 1.8 mm). LTP was observed in 19 tumours from 19 patients. The median min-AM was 3.1 ± 1.6 mm for patients with LTP, while the median min-AM of patients without LTP was 5.1 ± 1.8 mm (p = 0.023). After RFA, the 1-, 2- and 3-year LTP rates were 10.9, 25.9 and 35.1%, respectively, for patients with min-AM <5 mm, and 4.1, 4.1 and 4.1%, respectively, for patients with min-AM ≥5 mm (p = 0.016). Multivariate analysis showed that only min-AM <5 mm was an independent risk factor for LTP after RFA (p = 0.044, hazard ratio =4.587, 95% confidence interval, 1.045-22.296). CONCLUSIONS: The 3D reconstruction technique is a precise method for evaluating the post-ablation margin. Patients with min-AM less than 5 mm had a higher probability of developing LTP.

Advanced Recurrent Hepatocellular Carcinoma: Treatment with Sorafenib Alone or in Combination with Transarterial Chemoembolization and Radiofrequency Ablation.

Purpose To retrospectively investigate the safety and efficacy of sorafenib combined with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, TACE-RFA) in the treatment of recurrent hepatocellular carcinoma (rHCC) with portal vein tumor thrombosis, extrahepatic metastases (advanced hepatocellular carcinoma), or both after initial hepatectomy. Materials and Methods The study was centrally approved by the ethics committee of three tertiary medical centers in China. From January 2010 to January 2015, 207 consecutive patients with advanced rHCC after initial hepatectomy received sorafenib combined with TACE-RFA (combination group, n = 106) or sorafenib alone (sorafenib group, n = 101) at the three medical centers. Overall survival (OS) and time to progression (TTP) were compared between the two groups. Complications were assessed. Survival curves were constructed with the Kaplan-Meier method and were compared with the log-rank test. Results Baseline characteristics were balanced between the two groups. No treatment-related death occurred in either group. The toxicity profile in the combination group was similar to that in the sorafenib group. After treatment, median OS (14.0 vs 9.0 months, respectively; P < .001) and TTP (7.0 vs 4.0 months, respectively; P < .001) were significantly longer in the combination group than in the sorafenib group. Multivariate analysis showed that treatment allocation was a significant predictor of OS and TTP, while the number of intrahepatic tumors was another prognostic factor of OS. Conclusion Sorafenib combined with TACE-RFA was well tolerated and safe and was superior to sorafenib alone in improving survival outcomes in patients with advanced rHCC after initial hepatectomy. © RSNA, 2018 Online supplemental material is available for this article.

Multipronged ethanol ablation combined with TACE for intermediate hepatocellular carcinoma.

PURPOSE: To retrospectively investigate the efficacy of multipronged ethanol ablation with or without transarterial chemoembolization (TACE) in the treatment of intermediate hepatocellular carcinoma (HCC) (3.1-5.0 cm in diameter) at high-risk locations . MATERIAL AND METHODS: From March 2009 to April 2014, 25 consecutive patients with intermediate HCC who underwent multipronged ethanol ablation combined with TACE were included in the combination treatment group, while 50 patients who underwent multipronged ethanol ablation alone were included in the control group. RESULTS: Primary technique effectiveness was achieved in 70 patients (25/25, 100% in the combination treatment group; 45/50, 90% in the control group; p = .162). The local tumor progression (LTP) rates at 1, 3, 5, and 7 years were 8.0%, 24.0%, 24.0%, and 24.0% in the combination treatment group, respectively, which were significantly lower than those in the control group (24.4%, 44.1%, 66.5% and 66.5%, respectively; p = .043). However, no significant differences of overall survival and disease-free survival were found between the two groups (p = .996 and .974, respectively). CONCLUSION: Multipronged ethanol ablation combined with TACE could improve local tumor control for patients with intermediate HCC at high-risk locations when compared with multipronged ethanol ablation alone, although the survival outcomes were comparable.

Maintenance of stemness by miR-589-5p in hepatocellular carcinoma cells promotes chemoresistance via STAT3 signaling.

The strength and duration of STAT3 signaling are tightly controlled by multiple negative feedback mechanisms under physical conditions. However, how these serial feedback loops are simultaneously disrupted in cancers, leading to constitutive activation of STAT3 signaling in hepatocellular carcinoma (HCC), remains obscure. Here we report that miR-589-5p is elevated in HCC tissues, which is caused by recurrent gains. Overexpression of miR-589-5p correlates with poor overall and relapse-free survival in HCC patients. Upregulating miR-589-5p enhances spheroid formation ability, fraction of CD133 positive and side population cells, expression of cancer stem cell factors and the mitochondrial potential, and represses the apoptosis induced by doxorubicin in vitro and tumorigenicity in vivo in HCC cells; conversely, silencing miR-589-5p yields an opposite effect. Our findings further demonstrate miR-589-5p promotes the cancer stem cell characteristics and chemoresistance via targeting multiple negative regulators of STAT3 signaling pathway, including SOCS2, SOCS5, PTPN1 and PTPN11, leading to constitutive activation of STAT3 signaling. Collectively, our results unravel a novel mechanism by which miR-589-5p promotes the maintenance of stemness and chemoresistance in HCC, providing a potential rational registry of anti-miR-589-5p combining with conventional chemotherapy against HCC.

Combined radiofrequency ablation and ethanol injection versus repeat hepatectomy for elderly patients with recurrent hepatocellular carcinoma after initial hepatic surgery.

PURPOSE: To retrospectively compare the efficacy and safety of combined radiofrequency ablation and percutaneous ethanol injection (RFA-PEI) with repeat hepatectomy for elderly patients with initial recurrent hepatocellular carcinoma (HCC) after hepatic surgery. METHODS: From January 2009 to June 2015, 105 elderly patients (≥70 years) who underwent RFA-PEI (n = 57) or repeated hepatectomy (n = 48) for recurrent HCC ≤ 5.0 cm were included in the study. The overall survival (OS) and recurrence-free survival (RFS) were analysed with the Kaplan-Meier method and compared by the log-rank test. Non-tumour-related death, complications and hospital stays were assessed. Univariate and multivariate analyses were performed to identify the prognostic significance of the variables in predicting the OS and RFS. RESULTS: OS rates were 78.2%, 40.8% and 36.7% at 1, 3 and 5 years after RFA-PEI and 76.3%, 52.5% and 42.6% after repeat hepatectomy, respectively (p = 0.413). Correspondingly, the 1-, 3- and 5-year RFS rates after RFA-PEI and repeat hepatectomy were 69.5%, 37.8%, 33.1% and 73.1%, 49.7%, 40.7%, respectively (p = 0.465). Non-tumour-related deaths in the RFA-PEI group (2/57) were significantly fewer than those in the repeat hepatectomy group (10/48) (p = 0.016). RFA-PEI was superior to repeat hepatectomy regarding the major complication rates and length of in-hospital stay (both p < 0.001). Multivariate analysis showed that the tumour number was the significant prognostic factor for the OS (hazard ratio (HR) = 1.961, 95% CI = 1.043-3.686, p = 0.037) and RFS (HR = 1.866, 95% CI = 1.064-3.274, p = 0.030). CONCLUSION: RFA-PEI provides comparable OS and RFS to repeat hepatectomy for elderly patients with small recurrent HCC after hepatectomy but with fewer non-tumour-related deaths, major complications and shorter hospital stays.

miR-217 targeting DKK1 promotes cancer stem cell properties via activation of the Wnt signaling pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies and exhibits heterogeneity in terms of clinical outcomes and biological activities. Emerging evidence has demonstrated that cancer stem cells (CSCs) play important roles in the tumorigenesis and progression of HCC. However, the molecular mechanisms underlying the stemness maintenance of CSCs remain largely unknown. In the present study, through real-time PCR, western blotting, luciferase assays, RNA immunoprecipitation, and in vitro and in vivo assays, we demonstrated that miR-217 expression was markedly increased in HCC tissues and cells. Overexpression of miR-217 promoted, while silencing miR-217 suppressed, the fraction of the side population and the expression of cancer stem cell factors in vitro and tumorigenicity in vivo in HCC cells. Our findings further demonstrated that miR-217 promoted the CSC-like phenotype via dickkopf-1 (DKK1) targeting, resulting in constitutive activation of Wnt signaling. Moreover, the stimulatory effects of miR-217 on stem cell properties and Wnt signaling were antagonized by the upregulation of DKK1 in miR-217-overexpressing cells. Conversely, the inhibitory effects of silencing miR-217 on stem cell properties and Wnt signaling were reversed by the downregulation of DKK1 in miR-217-downregulated cells. Therefore, our results indicate that miR-217 plays a vital role in the CSC-like phenotypes of HCC cells and may be used as a potential therapeutic target against HCC.

miR-500a-3p promotes cancer stem cells properties via STAT3 pathway in human hepatocellular carcinoma.

BACKGROUND: miR-500a-3p has been demonstrated to be involved in the development, progression and metastasis in several human cancers. Constitutive activation of JAK/STAT3 signaling pathway has been reported to play an important role in the development and progression of hepatocellular carcinoma (HCC).The purpose of this study was to determine the biological roles and clinical significance of miR-500a-3p in HCC and to identify whether miR-500a-3p has an effect on the activity of JAK/STAT3 signaling in HCC. METHODS: miR-500a-3p expression was examined by real-time PCR in 8 paired HCC tissues and individual 120 HCC tissues respectively. Statistical analysis was performed to explore the clinical correlation between miR-500a-3p expression and clinicopathological features and overall and relapse-free survival in HCC patients. In vitro and in vivo assays were performed to investigate the biological roles of miR-500a-3p in HCC. The bioinformatics analysis, real-time PCR, western blot and luciferase reporter assay were performed to discern and examine the relationship between miR-500a-3p and its potential targets. Clinical correlation of miR-500a-3p with its targets was examined in HCC tissues. RESULTS: miR-500a-3p is dramatically elevated in HCC tissues and cells and high expression of miR-500a-3p correlates with poor overall and relapse-free survival in HCC patients. Upregulating miR-500a-3p enhances, while silencing miR-500a-3p suppresses, the spheroid formation ability, fraction of side population and expression of cancer stem cell factors in vitro and tumorigenicity in vivo in HCC cells. Our findings further reveal miR-500a-3p promotes the cancer stem cell characteristics via targeting multiple negative regulators of JAK/STAT3 signaling pathway, including SOCS2, SOCS4 and PTPN11, leading to constitutive activation of STAT3 signaling. Moreover, the inhibitory effects of anti-miR-500a-3p on cancer stem cell phenotypes and activity of STAT3 signaling were reversed by silencing SOCS2, SOCS4 and PTPN11 in miR-500a-3p-downexpressing cells, respectively. Clinical correlation of miR-500a-3p with the targets was examined in human HCC tissues. CONCLUSION: our results uncover a novel mechanism by which miR-500a-3p promotes the stemness maintenance of cancer stem cell in HCC, suggesting that silencing miR-500a-3p may serve as a new therapeutic strategy in the treatment of hepatocellular carcinoma.

Ultrasound-Guided Percutaneous Radiofrequency Ablation of Liver Metastasis From Ovarian Cancer: A Single-Center Initial Experience.

OBJECTIVE: The aim of this study was to evaluate the feasibility, effectiveness, and safety of ultrasound-guided percutaneous radiofrequency ablation (RFA) for the treatment of liver metastasis from ovarian cancer (OC). METHODS: A retrospective review was performed on 11 patients (mean age, 53.0 ± 10.1 years) with 22 liver metastases (mean diameter, 2.0 ± 0.8 cm) from OC undergone RFA. Radiofrequency ablation was carried out with Starburst XL electrodes (RITA Medical System, Mountain View, CA) or Cool-tip electrodes (Cool-tip Systems; Valleylab, Boulder, CO). The tumor response, time to progression, and survival after RFA were assessed. RESULTS: Complete ablation was achieved for all lesions. The technique effectiveness was 100%. During the follow-up period, local tumor progression was observed in 1 (4.5%) of 22 lesions. The median time to progression was 8.0 months after RFA. Three patients died because of disease progression after 13, 18, and 24 months, respectively. The mean overall survival time after RFA was 53.1 ± 10.0 months, with the 1-, 3-, and 5-year overall survival rates of 100%, 61%, and 61%, respectively. No major complications were encountered. CONCLUSIONS: Radiofrequency ablation as an alternative treatment strategy is feasible and effective for selected patients with liver metastasis from OC, providing a high rate of local tumor control.

MicroRNA-15a-5p suppresses cancer proliferation and division in human hepatocellular carcinoma by targeting BDNF.

We examined the expression pattern and functional roles of microRNA 15a-5p (miR-15a-5p) in human hepatocellular carcinoma (HCC). Possible miR-15a-5p aberrant expression in HCC cell lines or clinical HCC specimens was examined by quantitative real-time PCR (qRT-PCR). In HCC HepG2 and SNU-182 cells, miR-15a-5p was ectopically overexpressed by lentiviral transduction. Its effect on HCC proliferation, cancer division, and in vivo tumor growth were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle assay, and tumorigenicity assay, respectively. The targeting of miR-15a-5p on its downstream gene, brain-derived neurotrophic factor (BDNF), was examined by dual-luciferase assay, qRT-PCR, and Western blot, respectively. BDNF was then overexpressed in HepG2 and SNU-182 cells to evaluate its selective effect on miR-15a-5p in HCC modulation. MiR-15a-5p is aberrantly downregulated in in vitro HCC cell lines and in vivo HCC clinical specimens. Ectopic overexpression of miR-15a-5p suppressed cancer proliferation, induced cell cycle arrest in HepG2 or SNU-182 cells in vitro, and inhibited HCC tumor growth in vivo. MiR-15a-5p selectively and negatively regulated BDNF at both gene and protein levels in HCC cells. Forced overexpression of BDNF effectively reversed the tumor suppressive functions of miR-15a-5p on HCC proliferation and cell division in vitro. Our study demonstrated that miR-15a-5p is a tumor suppressor in HCC and its regulation is through BDNF in HCC.

First Experience of Ultrasound-guided Percutaneous Ablation for Recurrent Hepatoblastoma after Liver Resection in Children.

This study aimed to summarize the first experience with ultrasound-guided percutaneous ablation treatment (PAT) for recurrent hepatoblastoma (HB) after liver resection in children. From August 2013 to October 2014, PAT was used to treat 5 children with a total of 8 recurrent HB (mean size, 1.4 ± 0.8 cm; size range, 0.7-3.1 cm), including 4 patients with 7 tumors in the liver and 1 patient with 1 tumor in the lung. Technical success was achieved in all patients (5/5, 100%). The complete ablation rate after the first ablation session was 80% (4/5) on a patient-by-patient basis and 87.5% (7/8) on a tumor-by-tumor basis. Only 1 patient developed a fever with temperature >39 °C; it lasted 4 days after radiofrequency ablation (RFA) and was resolved by conservative therapy. During the follow-up period, new intrahepatic recurrences after PAT were detected in two patients. One died due to tumor progression 4 months after ablation. The median overall survival time after PAT was 13.8 months. PAT is a safe and promising therapy for children with recurrent HB after liver resection, and further investigation in large-scale randomized clinical trials is required to determine its role in the treatment of this disease.

Mcl-1 Is a Novel Target of miR-26b That Is Associated with the Apoptosis Induced by TRAIL in HCC Cells.

AIM: To investigate the role of miR-26b and Mcl-1 in TRAIL-inducing cell death in hepatocellular carcinoma. Methods. The expression of miR-26b and Mcl-1 in HCC was detected by RT-qPCR and western blot. The regulation of Mcl-1 by miR-26b was determined by luciferase reporter assay. MTT and flow cytometry were employed to detect the cell viability and apoptosis. RESULTS: miR-26b is commonly downregulated in HCC cell lines compared with the LO2 cell line. In contrast, the Mcl-1 expression is upregulated in HCC cell lines. Bioinformatic analysis identified a putative target site in the Mcl-1 mRNA for miR-26b and luciferase reporter assay showed that miR-26b directly targeted the 3'-UTR (3'-Untranslated Regions) of Mcl-1 mRNA. Transfection of miR-26b mimics suppressed Mcl-1 expression in HCC cells and sensitized the cancer cells to TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) cytotoxicity. In addition, transfection of HCC cells with Mcl-1 expression plasmid abolished the sensitization effect of miR-26b to TRAIL-inducing apoptosis. CONCLUSIONS: Our study showed that miR-26b was a negative regulator of Mcl-1 gene and sensitized TRAIL-inducing apoptosis in HCC cells, suggesting that the miR-26b-Mcl-1 pathway might be a novel target for the treatment of HCC.

Local Recurrence after Radiofrequency Ablation of Hepatocellular Carcinoma: Treatment Choice and Outcome.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) has been proven effective for treating small hepatocellular carcinoma (HCC) nodules. However, post-RFA local recurrence is a major factor limiting prognosis. Up to now, there is no consensus on a standardized treatment strategy for these local recurrences. The aim of this study is to evaluate the outcomes of salvage treatments for RFA-related local recurrence. METHODS: From May 2008 to June 2013, a total of 112 patients with HCC were detected with local recurrence after RFA. Among them, 94 patients received sequential treatments in our hospital, including salvage resection (SR) (n = 24), salvage liver transplantation (n = 2), repeated RFA (n = 62), and transarterial chemoembolization (TACE) (n = 6). We evaluated the treatment outcomes of patients by salvage surgery (SS), RFA, and TACE. RESULTS: The median follow-up time was 32 months. After treatment, local recurrence was eradicated in 82 of 94 patients (87.2%). The complete response (CR) rate in the RFA group was 90.3% (56/62), while it was 100% (26/26) in the SS group (P = 0.175) and 0% (0/6) in the TACE group. When analysis confined to patients with CR, the 1- and 3-year disease-free survival (DFS) rates were 57.7 and 20.2% in the SS group, and 41.7 and 28.6% in the RFA group, respectively (P = 0.640). The 1- and 3-year overall survival (OS) rates were 93.3 and 69.1% in the SS group, and 78.6 and 57.5% in the RFA group, respectively (P = 0.251). CONCLUSION: Repeated RFA is the first treatment choice for patients with post-RFA local recurrence. SS should be considered when RFA failed or is inapplicable.