Liver X receptor agonists exert antitumor effects against hepatocellular carcinoma via inducing REPS2 expression.

Recent studies show that liver X receptor (LXR) agonists exert significant antitumor effects in a variety of tumor cell lines including hepatocellular carcinoma (HCC). But the molecular mechanisms underlying LXR antitumor activity are not fully understood. In this study we investigated the effect of LXR agonist T0901317 (T317) on HCC development and its relationship with RalA binding protein 1 (RALBP1)-associated EPS domain containing 2 (REPS2)/epidermal growth factor receptor (EGFR) signaling axis. We showed that T317 (0.1-0.5 µM) dose-dependently increased REPS2 expression in normal hepatocytes (BNLCL.2 and LO2) and HCC cells (HepG2 and Huh-7). Using promoter activity assay and chromatin immunoprecipitation (CHIP) assay we demonstrated that T317 enhanced REPS2 expression at the transcriptional level via promoting the binding of LXR protein to the LXR-response element (LXRE) in the REPS2 promoter region. We showed that the inhibitory effect of T317 on the proliferation and migration of HCC cells was closely related to REPS2. Moreover, we revealed that T317 (400 nM) increased expression of REPS2 in HepG2 cells, thus inhibiting epidermal growth factor (EGF)-mediated endocytosis of EGFR as well as the downstream activation of AKT/NF-κB, p38MAPK, and ERK1/2 signaling pathways. Clinical data analysis revealed that REPS2 expression levels were inversely correlated with the development of HCC and reduced REPS2 expression associated with poor prognosis, suggesting that REPS2 might be involved in the development of HCC. In conclusion, this study provides new insights into the potential mechanisms of LXR agonist-inhibited HCC.

Prognostic factors in hepatocellular carcinoma patients with Child-Pugh A liver function after hepatectomy: Not related to the surgical approach.

INTRODUCTION AND OBJECTIVES: Improving the prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is critical. This article aims to investigate the risk factors affecting the prognosis of HCC patients with Child-Pugh A (CPA) liver function after hepatectomy and to compare the prognosis of patients with anatomical resection (AR) and nonanatomical resection (NAR). METHODS: In total, 186 patients diagnosed with HCC between 2013 and 2019 were retrospectively enrolled. Univariate and multivariate analyses were performed using a Cox proportional hazard regression model to explore the factors related to prognosis. Overall survival (OS) and progression-free survival (PFS) were analyzed by log-rank tests and are shown by Kaplan-Meier curves. Chi-square tests and Mann-Whitney U tests were used to compare the difference in clinical characteristics between AR and NAR patients. RESULTS: Among the 186 enrolled patients, only 73 were followed over 60 months. The 1-, 3-, and 5-year survival rates were 74.5%, 46.7% and 26.0%, respectively. Multivariate analyses demonstrated that portal vein invasion (PVI) and tumor size were independent risk factors for OS and PFS. Preoperative hepatitis B surface antigen (HBsAg) and a-fetoprotein (AFP) levels were identified as independent risk factors only for PFS. In univariate analysis, the NAR group had a better OS rate than the AR group (1-year: 80.4% vs. 63.6%, 3-year: 55.9% vs. 30.3%, 5-year: 34.8% vs. 11.1%), but this was not confirmed by multivariate analysis. CONCLUSIONS: PVI and tumor size > 5 cm are risk factors for the prognosis of CPA HCC patients after hepatectomy, but the surgical type is not.

eIF4E-eIF4G complex inhibition synergistically enhances the effect of sorafenib in hepatocellular carcinoma.

The clinical efficacy of sorafenib in hepatocellular carcinoma (HCC) is disappointing due to its low response rate and high rates of adverse effects. The eukaryotic translation initiation factor 4F (eIF4F) complex, mainly consisting of eIF4E-eukaryotic translation initiation factor 4G (eIF4G) interaction, is involved in the induction of drug resistance. Herein, we aimed to demonstrate that eIF4E-eIF4G complex inhibition enhanced the effect of sorafenib. The antiproliferation effect of combined treatment was evaluated by MTT assay and colony formation assay. Flow cytometry was used to detect the early cell apoptosis and cell cycle. The specific mechanism was demonstrated using western blot and lentivirus transfection. The combination of sorafenib with eIF4E-eIF4G inhibitors 4E1RCat (structural) or 4EGI-1 (competitive) synergistically inhibited the cell viability and colony formation ability of HCC cells. Moreover, the combined treatment induced more early apoptosis than sorafenib alone through downregulating the Bcl-2 expression. Besides, the coadministration of sorafenib and 4E1RCat or 4EGI-1 synergistically inhibited the expressions of eIF4E, eIF4G and phospho-4E-BP1 in HCC cells while blocking the phosphorylation of 4E-BP1 with lentiviral transfection failed to increase the sensitivity of HCC cells to sorafenib treatment. PI3K-AKT-mTOR signaling was also inhibited by the combined treatment. In a word, eIF4E-eIF4G complex inhibition synergistically enhances the effect of sorafenib in HCC treatment.

BiClamp® vessel-sealing device for open hepatic resection of malignant and benign liver tumours: a single-institution experience.

BACKGROUND: Intraoperative blood loss during hepatectomy worsens prognosis, and various tools have been used to improve perioperative safety and feasibility. We aimed to retrospectively evaluate the feasibility and safety of the BiClamp® device for open liver resection. METHODS: We included 84 patients undergoing liver resection from a single centre, with all patients operated by the same surgical group. All hepatectomies were performed using BiClamp® (Erbe Elektromedizin GmbH, Tubingen, Germany), an electrosurgical device that simultaneously transects liver parenchyma and seals vessels <7 mm in diameter. We collected data on intraoperative blood loss, resection time, and perioperative complications, comparing cirrhotic and non-cirrhotic patients. RESULTS: The 84 patients enrolled in this study included 56 cirrhotic and 28 non-cirrhotic patients. All patients underwent hepatectomy (30 major and 54 minor hepatectomies) using the BiClamp®, exclusively, and 54 patients required inflow occlusion (Pringle manoeuvre). Overall intraoperative blood loss (mean ± standard deviation) was 523.5 ± 558.6 ml, liver parenchymal transection time was 36.3 ± 16.5 min (range, 13-80 min), and the mean parenchymal transection speed was 3.0 ± 1.9 cm2/min. Twelve patients received perioperative blood transfusion. The cost of BiClamp® for each patient was 800 RMB (approximately 109€). There were no deaths, and the morbidity rate was 25%. The mean (standard deviation) hospital stay was 9.3 (2.3) days. Comparisons between cirrhotic and non-cirrhotic patients revealed no difference in blood loss (491.0 ± 535.7 ml vs 588.8 ± 617.5 ml, P = 0.598), liver parenchymal transection time (34.1 ± 14.8 min vs 40.9 ± 19.2 min, P = 0.208), mean parenchymal transection speed (3.3 ± 2.1 cm2/min vs 2.5 ± 1.3 cm2/min, P = 0.217), and operative morbidity (28.6% vs 14.3%, P = 0.147). CONCLUSIONS: The reusable BiClamp® vessel-sealing device allows for safe and feasible major and minor hepatectomy, even in patients with cirrhotic liver. TRIAL REGISTRATION: This trial was retrospectively registered and the detail information was as followed. Registration number: ChiCTR-ORC-17011873 (Chinese Clinical Trial Registry). Registration Date: 2017-07-05.

High-efficiency inverted polymer solar cells controlled by the thickness of polyethylenimine ethoxylated (PEIE) interfacial layers.

In this work, we investigate the effect of the thickness of the polyethylenimine ethoxylated (PEIE) interface layer on the performance of two types of polymer solar cells based on inverted poly(3-hexylthiophene) (P3HT):phenyl C61-butryric acid methyl ester (PCBM) and thieno[3,4-b]thiophene/benzodithiophene (PTB7):[6,6]-phenyl C71-butyric acid methyl ester (PC71BM). Maximum power conversion efficiencies of 4.18% and 7.40% were achieved at a 5.02 nm thick PEIE interface layer, for the above-mentioned solar cell types, respectively. The optimized PEIE layer provides a strong enough dipole for the best charge collection while maintaining charge tunneling ability. Optical transmittance and atomic force microscopy measurements indicate that all PEIE films have the same high transmittance and smooth surface morphology, ruling out the influence of the PEIE layer on these two parameters. The measured external quantum efficiencies for the devices with thick PEIE layers are quite similar to those of the optimized devices, indicating the poor charge collection ability of thick PEIE layers. The relatively low performance of devices with a PEIE layer of thickness less than 5 nm is the result of a weak dipole and partial coverage of the PEIE layer on ITO.

[Retracted] Sulforaphane sensitizes human cholangiocarcinoma to cisplatin via the downregulation of anti­apoptotic proteins.

Following the publication of the above article and a corrigendum that was published in October 2023 to address the issue of misplaced control ß­actin western blots comparing between Figs. 3 and 4A (doi: 10.3892/or.2023.8646), an attentive reader drew to the authors' attention that the first author had apparently made additional unreported corrections to the revised version of Fig. 4 presented in the corrigendum. Although these image discrepancies did not alter the study's primary conclusions, they were such that they did cast doubt on the data's integrity. Consequently, the authors have decided to retract the paper and the Editor of Oncology Reports has agreed to the authors' request. The authors deeply regret any confusion or inconvenience this retraction may cause, and offer their sincere apologies to the Editor of Oncology Reports and the readership. [Oncology Reports 37: 3660­3666, 2017; DOI: 10.3892/or.2017.5622].

Total laparoscopic partial hepatectomy versus open partial hepatectomy for primary left-sided hepatolithiasis: study protocol for a randomized controlled trial.

BACKGROUND: The advantages of laparoscopic left-sided hepatectomy (LLH) for treating hepatolithiasis in terms of the time to postoperative length of hospital stay (LOS), morbidity, long-term abdominal wall hernias, hospital costs, residual stone rate, and recurrence of calculus have not been confirmed by a randomized controlled trial. The aim of this trial is to compare the safety and effectiveness of LLH with open left-sided hepatectomy (OLH) for the treatment of hepatolithiasis. METHODS: Patients with hepatolithiasis eligible for left-sided hepatectomy will be recruited. The experimental design will produce two randomized arms (laparoscopic and open hepatectomy) at a 1:1 ratio and a prospective registry. All patients will undergo surgery in the setting of an enhanced recovery after surgery (ERAS) programme. The prospective registry will be based on patients who cannot be randomized because of the explicit treatment preference of the patient or surgeon or because of ineligibility (not meeting the inclusion and exclusion criteria) for randomization in this trial. The primary outcome is the LOS. The secondary outcomes are percentage readmission, morbidity, mortality, hospital costs, long-term incidence of incisional hernias, residual stone rate, and recurrence of calculus. It will be assumed that, in patients undergoing LLH, the length of hospital stay will be reduced by 1 day. A sample size of 86 patients in each randomization arm has been calculated as sufficient to detect a 1-day reduction in LOS [90% power and α = 0.05 (two-tailed)]. The trial is a randomized controlled trial that will provide evidence for the merits of laparoscopic surgery in patients undergoing liver resection within an ERAS programme. CONCLUSIONS: Although the outcomes of LLH have been proven to be comparable to those of OLH in retrospective studies, the use of LLH remains restricted, partly due to the lack of short- and long-term informative RCTs pertaining to patients with hepatolithiasis in ERAS programmes. To evaluate the surgical and long-term outcomes of LLH, we will perform a prospective RCT to compare LLH with OLH for hepatolithiasis within an ERAS programme. TRIAL REGISTRATION: ClinicalTrials.gov NCT03958825. Registered on 21 May 2019.

[Endoscopic papillary balloon dilatation vs. endoscopic sphincteropapillotomy for common bile duct stones: a meta analysis].

OBJECTIVE: To evaluate the safety and efficacy between endoscopic papillary balloon dilatation (EPBD) and endoscopic sphincteropapillotomy ( EST) for common bile duct stones using meta-analysis method. METHODS: Randomizd controlled trials comparing EPBD with EST for common bile duct stones and published from January 1990 to July 2012 were recruited. This meta-analysis was conducted to estimate short-term and long-term complications. Fixed random effect model or random effect model was established to analyze the data. RESULTS: Twelve randomizd controlled trials were included in this analysis. These studies included 1865 patients, 925 of them were treated with EPBD and 940 were treated with EST. The analysis of basic characteristics of these included studies showed that: compared to EST, patients in the EPBD group were younger (OR = -1.16, 95% CI: -1.49 to -0.84, P = 0.00), while in two groups, there were no significant difference (P > 0.05) in gender proportion, average size of stones, number of gallstones, previous cholecystectomy, the number of merged duodenal diverticulum, common bile duct diameter, the total follow-up time. Also, compared to EST, the overall stone clearance in the EPBD group was lower (OR = 0.64, 95% CI: 0.42 to 0.96, P = 0.03), pancreatitis incidence was higher (OR = 2.67, 95% CI: 1.61 to 4.43, P = 0.00), incidence of bleeding (OR = 0.12, 95% CI: 0.04 to 0.34, P = 0.00), acute cholecystitis (OR= 0.39, 95% CI: 0.18 to 0.84, P = 0.02), total long-term complication rate (OR = 0.53, 95% CI: 0.36 to 0.77, P = 0.01), stone recurrence rate more than a year were lower (OR= 0.48, 95% CI: 0.26 to 0.90, P = 0.02). While in two groups, there were no significant difference (P > 0.05) in the stone removal on 1 '' attempt, the total near-term complications and acute cholangitis. CONCLUSIONS: On the basis of lower rates of bleeding, EPBD seems to be preferred strategy over EST for endoscopic remove of common bile duct stones in patients who have coagulopathy. Although stone recurrence rate more than a year of EPBD is lower, but the overall stone clearance rate is lower and the risk of pancreatitis is higher than that of EST.

[Corrigendum] Sulforaphane sensitizes human cholangiocarcinoma to cisplatin via the downregulation of anti­apoptotic proteins.

Following the publication of this article, an interested reader drew to the authors' attention that, in Figs. 3 and 4A on p. 3664, the respective ß­actin controls for the cell lines TFK­1 and HuCCT­1 appeared to have mixed up, comparing the western blots between the two figures. After re­examining their data, the authors have realized that the control blots in Fig. 4A were inadvertently presented the wrong way around. The corrected version of Fig. 4, showing the correctly presented western blotting data in Fig. 4A, is shown on the next page. Note that this error did not grossly affect the results or the conclusions reported in this paper. The authors sincerely apologize for the error that was introduced during the preparation of this figure, and thank the Editor of Oncology Reports for allowing them the opportunity to publish a corrigendum. Furthermore, they regret any inconvenience caused to the readership. [Oncology Reports 37: 3660­3666, 2017; DOI: 10.3892/or.2017.5622].

Blocking the CXCL1-CXCR2 axis enhances the effects of doxorubicin in HCC by remodelling the tumour microenvironment via the NF-κB/IL-1ß/CXCL1 signalling pathway.

Inflammation is a core mechanism for oncogenesis. Chemokines act as important mediators of chronic inflammation and the tumour inflammatory response. However, there is limited information on chemokines in hepatocellular carcinoma (HCC), a disease for which almost all cases are derived from chronic liver inflammation. Here, we explored the protumor effects of CXCL1, a commonly elevated inflammatory chemokine in cirrhosis, in HCC. The protumor role was confirmed in clinical samples from HCC patients. CXCL1 enhanced tumorigenesis in the hepatic inflammatory microenvironment directly by acting on tumour cells and indirectly through promoting the recruitment of macrophages. The increase in the number of macrophages in the tumour microenvironment (TME) promoted tumour cell epithelial-mesenchymal transition (EMT) and significantly increased CXCL1 levels in the TME partly through NF-κB/IL-1ß activation. To investigate the potential therapeutic value of CXCL1 in HCC with an inflammatory background, an antibody blocking CXCL1 was used alone or combined with the chemotherapy agent doxorubicin (DOX), with the goal of reshaping the TME. It has been shown that blocking CXCL1-CXCR2 inhibits tumour progression and reduces macrophage recruitment in the TME. The combination regimen has been shown to synergistically reduce the number of pro-tumour macrophages in the TME and suppress tumour progression. This provides insight into therapeutic strategies for treating HCC patients with high CXCL1 expression.

The hilar plane compared with the Rouviere's sulcus plane during laparoscopic cholecystectomy.

Introduction: Rouviere's sulcus (RS) has been widely used as an important landmark during laparoscopic cholecystectomy; however, some shortcomings remain unaddressed. Aim: To evaluate the safety and application values of the hilar plane in laparoscopic cholecystectomy (LC) by comparing it with the plane of Rouviere's sulcus (RS plane). Material and methods: A retrospective study of 155 consecutive patients undergoing LC used the hilar plane as a guide for surgical procedures was performed. Intraoperative images were used to evaluate and analyze the value of using the hilar plane vs. the RS plane in preventing bile duct and vascular injuries. Meanwhile, anatomical data, including the types and orientations of Rouviere's sulci, were also recorded for further analysis. Results: Rouviere's sulci failed to be identified clearly in 9 cases due to severe adhesions. The prevalence of RS was 83.6% (122/146). The hilar plane was a constant landmark. The hilar plane can also form a "security dissection triangle" in the posterior triangle of the gallbladder. The hilar plane and the RS plane formed a similar triangle in 59.8% (73/122) of cases, while in other cases, the hilar plane formed a smaller dissection triangle than the RS plane due to a higher spatial position. The hilar plane had a better protective effect for avoiding ectopic hepatic ducts or ectopic right hepatic arteries injury. Conclusions: The hilar plane has the features of constant location, large coverage area, and higher location, hence being further away from the critical structures. The hilar plane on its own can provide a safe anatomic plane in some case when RS was difficult to observe or identify.

Factors Influencing Suture Difficulty of T-tube Fixation and Closure in Laparoscopic Common Bile Duct Exploration.

BACKGROUND: Suture under the laparoscopy was considered as one of the most difficult and time-consuming tasks in laparoscopic common bile duct (CBD) exploration. Difficult suturing can lead to prolonged suturing time and decreased suturing quality. The aim of this study was to identify preoperative factors associated with the difficulty of T-tube suture following laparoscopic bile duct exploration. MATERIALS AND METHODS: Retrospective analysis of consecutive patients who experienced successful laparoscopic CBD exploration with T-tube drainage were collected. Perioperative outcomes and short-term and long-term complications were recorded. Associations of the average suture time per stitch with preoperative demographic data and laboratory tests in patients were analyzed. RESULTS: A total of 106 cases (46 males and 60 females) were included in this study. The average suture time per stitch was between 3 and 7.5 minutes with a median of 4.5 minutes (4, 5). There were no biliary leakage and other T-tube-related complications in all patients during follow-up. Spearman correlation analysis revealed that biliary tract reoperation (r=0.384, P<0.0001) and a higher body mass index (r=0.486, P<0.0001) were positively correlated with the average suture time per stitch, while there was no association between the average suture time per stitch and other preoperative demographic data and preoperative blood parameters, including CBD diameter, age, sex, operative time, preoperative white cell count, alanine transaminase, total bilirubin, and gamma-glutamyl transpeptidase. CONCLUSIONS: We have identified 2 preoperative variables (biliary tract reoperation and a higher body mass index) that were positively associated with the suture difficulty under laparoscopy. An adequately powered prospective multicentre study is needed to validate our findings.

[Percutaneous radiofrequency ablation versus hepatic resection for small hepatocellular carcinoma: a meta analysis].

OBJECTIVE: To evaluate the curative effect of percutaneous radiofrequency ablation (RFA) and hepatic resection (RES) for small hepatocarcinoma eligible for Milan criterion using meta analysis method. METHODS: Retrieved clinical trials comparing percutaneous radiofrequency ablation with RES for small hepatocarcinoma published from 1990 to 2010. A meta-analysis was conducted to estimate overall survival and disease free survival. A fixed random effect model or random effect model was established to collect the data. RESULTS: Four randomized controlled trials were included in this analysis. These studies included a total of 539 patients: 252 treated with percutaneous RFA and 287 treated with RES. The differences in overall survival were not statistically significant between RFA and RES (P > 0.05). In the patients treated with RES group, the 2-, 3- and 4-years disease free survival rates were significantly better than that in the patients treated with percutaneous RFA (P < 0.05). The postoperative morbidity rate was significant lower in patients treated with percutaneous RFA (OR: 0.14, 95%CI: 0.09 - 0.22, P = 0.000). But percutaneous RFA had a higher rate of tumor recurrence compared to RES (OR: 2.63, 95%CI: 1.67 - 4.15, P = 0.000). CONCLUSIONS: For small hepatocarcinoma eligible for Milan criterion, percutaneous RFA had a similar overall survival to RES. Percutaneous RFA was the invasive lesser and had a lower postoperative morbidity rate than RES, but RES may had a better prevention of the tumor recurrence than percutaneous RFA. For those patients who don't want to be treated by RES, percutaneous RFA may be a recommendable choice.

The role of miRNA125b in the progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common tumours worldwide, and identifying markers related to HCC is an important area of research. As a microRNA (miRNA), miRNA125b (miR-125b) plays an important role in the prediction and prognosis of HCC. In the past 10 years, with increasing research on miR-125b and HCC, the molecular mechanism of its relationship with the development of HCC has been elucidated. MiR-125b inhibits the development of HCC and is highly accurate in predicting HCC and is therefore a valuable predictive marker of HCC. This article summarizes the clinical application of miR-125b in HCC and the potential mechanism of its involvement in the progression of HCC.

Comparative analysis of vascular bulldog clamps used in laparoscopic liver resection.

ABSTRACT: To compare the clinical effect of Bulldog clamps with traditional Pringle for vascular occlusion during laparoscopic hepatectomy.One hundred ten patients were retrospectively investigated in this research from December 2014 to January 2019 in the second hospital of Anhui Medical University, who underwent laparoscopic liver resection using Bulldog (modified group, n = 54) and cotton tourniquet (traditional group, n = 56) for blocking the liver inflow-blood. Intraoperative blood loss, duration of the operation time, clamping time, postoperative outcomes were analyzed.All the operations were accomplished successfully without conversion to laparotomy, perioperative period clinical date was calculated. Intraoperative operative time, blood loss and resection sections had no statistical significance, but the clamping time (36.2 ±â€Š5.6 vs 277.3 ±â€Š88.4 s, P < .001) was significantly shorter in the bulldog group. Albumin, alanine aminotransferase, aspartate aminotransferase and serum total bilirubin had no statistical differences in postoperative day (POD) 1and 3, but POD 5 alanine aminotransferase (71.0 ±â€Š46.8vs 105.8 ±â€Š61.7IU/L P = .018) and aspartate aminotransferase (72.8 ±â€Š39.7 vs 100.2 ±â€Š16.7 IU/L P = .028). The postoperative hospital stays (7.02 ±â€Š1.56 vs 8.50 ±â€Š2.35 days P = .026) in bulldog group were lower than cotton group and differences had statistical significance. The C-reactive protein levels were significantly higher in the traditional group than in the modified group on POD 3 (46.3 ±â€Š19.2 vs 57.7 ±â€Š23.9 mg/L P = .019), and POD5 (13.3 ±â€Š4.2 vs 17.5 ±â€Š7.3 mg/L P = .001). There were 8 postoperative complications occurred in cotton group, while there was 5 in Bulldog group, all patients with complications were discharged after adequate drainage and symptomatic treatment.Bulldog is an effectively performed approach for vascular occlusion during laparoscopic hepatectomy than traditional Pringle maneuver.

Advances in liver transplantation for unresectable colon cancer liver metastasis.

It is estimated that 50% of patients with colorectal cancer will develop liver metastasis. Surgical resection significantly improves survival and provides a chance of cure for patients with colorectal cancer liver metastasis (CRLM). Increasing the resectability of primary unresectable liver metastasis provides more survival benefit for those patients. Considerable surgical innovations have been made to increase the resection rate and decrease the potential risk of hepatic failure postoperation. Liver transplantation (LT) has been explored as a potential curative treatment for unresectable CRLM. However, candidate selection criteria, chemotherapy strategies, refined immunity regimens and resolution for the shortage of grafts are lacking. This manuscript discusses views on surgical indication, peritransplantation anti-tumor and anti-immunity therapy and updated advances in LT for unresectable CRLM. A literature review of published articles and registered clinical trials in PubMed, Google Scholar, and Clinicaltrials.gov was performed to identify studies related to LT for CRLM. Some research topics were identified, including indications for LT for CRLM, oncological risk, antitumor regimens, graft loss, administration of anti-immunity drugs and solutions for graft deficiency. The main candidate selection criteria are good patient performance, good tumor biological behavior and chemosensitivity. Chemotherapy should be administered before transplantation but is not commonly administered posttransplantation for preventive purposes. Mammalian target of rapamycin regimens are recommended for their potential oncological benefit, although there are limited cases. In addition to extended criterion grafts, living donor grafts and small grafts combined with two-stage hepatectomy are efficient means to resolve organ deficiency. LT has been proven to be an effective treatment for selected patients with liver-only CRLM. Due to limited donor grafts, high cost and poorly clarified oncological risks, LT for unresectable CRLM should be strictly performed under a well-organized study plan in selected patients. Some vital factors, like LT indication and anti-tumor and anti-immune treatment, remain to be confirmed. Ongoing clinical trials are expected to delineate these topics.

Laparoscopic Liver Resection Ameliorates the Postoperative Liver Function Impairment for Hepatocellular Carcinoma Patients.

To study whether laparoscopic liver resection (LLR) is able to alleviate the postoperative liver function impairment for hepatocellular carcinoma patients, the clinical data of 103 patients were retrospectively analyzed, including 42 patients who underwent LLR and 61 patients who underwent open liver resection (OLR), during the period spanning from 2012 to 2017. The postoperative peak aspartate aminotransferase and alanine aminotransferase levels in the LLR group were significantly lower than those of the OLR group (209.76±189.516 vs. 262.55±181.19, P=0.046; 250.56±200.944 vs. 411.01±412.51, P=0.005, for aspartate aminotransferase and alanine aminotransferase, respectively). The recovering of postoperative total protein and albumin in the LLR group was faster than that in the OLR group, and the total protein and albumin levels on the postoperative day-5 were significantly higher in the LLR group than in the OLR group (62.528±9.427 vs. 57.87±6.101, P=0.019; 36.456±4.875 vs. 33.653±4.112, P=0.012, respectively). In conclusion, these data show that LLR alleviates postoperative liver function impairment and increases liver function recovery.

MicroRNA200a enhances antitumor effects in combination with doxorubicin in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is often treated with doxorubicin. MicroRNAs have been shown to have important regulatory roles in cancer and serve as a target in chemoresistance. In this study, we investigated the effects of specific microRNA-200a (miR-200a) on HCC tumor cell growth and effect of doxorubicin-mediated cytotoxicity. Our results show miR-200a is downregulated in human HCC and HCC tumor cell lines. Increasing miR-200a expression inhibited HCC growth and synergized with the antitumor effects of doxorubicin. Inhibiting endogenous miR-200a promoted tumor growth and chemotherapeutic resistance. Increasing miR-200a expression inhibited tumor metabolism (ATP production, mitochondrial respiration, glycolysis), while inhibition of endogenous miR-200a reversed these effects. MiR-200a expression also increased autophagy and synergized with doxorubicin-mediated cytotoxicity. This study identifies a novel role of miR-200a in potentiating doxorubicin-mediated therapeutic effects in HCC.

Upregulation of eukaryotic translation initiation factor 4E associates with a poor prognosis in gallbladder cancer and promotes cell proliferation in vitro and in vivo.

Eukaryotic translation initiation factor 4 (eIF4E) has been demonstrated to promote tumorigenesis in different types of cancer; however, whether eIF4E is involved in the development of GBC is unclear. The present study aimed to explore the biological function of eIF4E in gallbladder cancer (GBC) and identified that the expression level of eIF4E was significantly increased in GBC tissues compared with that in normal gallbladder tissues. The overall survival (OS) was also shorter in the group of patients with GBC with increased eIF4E expression. Increased eIF4E was correlated with advanced stage and higher histologic grade. Knockdown of eIF4E significantly inhibited cell proliferation, colony formation and cell cycle­associated protein expression levels in 2 GBC cell lines. The weight of the tumors in the eIF4E knockdown group was remarkably decreased compared with the control group. It also was revealed that knockdown of eIF4E is associated with upregulating cyclin­dependent kinase inhibitor 1B and downregulating the expression levels of cyclin E1 and cyclin D1 in vitro and in vivo. These data demonstrated that eIF4E is a novel prognostic marker in GBC and may serve a critical role in the regulation of cell proliferation.

CARMA3/NF-κB signaling contributes to tumorigenesis of hepatocellular carcinoma and is inhibited by sodium aescinate.

BACKGROUND: Primary hepatocellular carcinoma (HCC) is a very malignant tumor in the world. CARMA3 plays an oncogenic role in the pathogenesis of various tumors. However, the function of CARMA3 in HCC has not been fully clarified. AIM: To study the biological function of CAEMA3 in HCC. METHODS: Tissue microarray slides including tissues form 100 HCC patients were applied to access the expression of CARMA3 in HCC and its clinical relevance. Knockdown and overexpression of CARMA3 were conducted with plasmid transfection. MTT, colony formation, and apoptosis assays were performed to check the biological activity of cells. RESULTS: Higher expression of CARMA3 in HCC was relevant to poor prognostic survival (P < 0.05). Down-regulation of CARMA3 inhibited proliferation and colony formation and induced apoptosis in HCC cell lines, while increasing its expression promoted tumorigenesis. We also found that sodium aescinate (SA), a natural herb extract, exerted anti-proliferation effects in HCC cells by suppressing the CARMA3/nuclear factor kappa-B (NF-κB) pathway. CONCLUSION: Overexpression of CARMA3 in HCC tissues correlates with a poor prognosis in HCC patients. CARMA3 acts pro-tumorigenic effects partly through activation of CARMA3/NF-κB. SA inhibits HCC growth by targeting CARMA3/NF-κB.