Tumor-suppressing effect of miR-4458 on human hepatocellular carcinoma.

BACKGROUND: Besides multiple genetic and epigenetic changes of protein coding genes in hepatocellular carcinoma (HCC), growing evidence indicate that deregulation of miRNAs contribute to HCC development by influencing cell growth, apoptosis, migration, or invasion. IKBKE is amplified and over-expressed in a large percentage of human breast tumors and identified as an oncogene of human breast tumor. Microarray analysis showed that miR-4458 was down-regulated in HCC tissues. METHODS: The level of miR-4458 was up-regulated by miR-4458 mimics transfection, or down-regulated by miR-4458 ASO transfection. Cell proliferation was assayed by MTT analysis. MiRNAs and mRNA expression were assayed by qRT-PCR. These potential targeted genes of miR-4458 were predicted by bioinformatic algorithms. Dual luciferase reporter assay system was used to analyze the interaction between miR-4458 and IKBKE. IKBKE protein level was assayed by Western blot. The role of miR-4458 or IKBKE in the survival of HCC patients were revealed by Kaplan-Meier plot of overall survival. RESULTS: Lower miR-4458 expression level or higher IKBKE level in HCC tissues correlated with worse prognosis of HCC patients. Overexpression of miR-4458 inhibited the HCC cells growth and vice versa. MiR-4458 played its role via targeting 3'UTR of IKBKE. CONCLUSIONS: MiR-4458 or IKBKE may be potential predictors of HCC prognosis. Restoration of miR-4458 or inhibition of IKBKE could be a prospective therapeutic approach for HCC.

Monophosphoryl lipid A induces bone marrow precursor cells to differentiate into myeloid-derived suppressor cells.

Myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs) are important in the immune response. In vitro, DCs are derived from myeloid precursors by stimulation with granulocyte macrophage colony­stimulating factor and interleukin­4. Previous studies demonstrated that lipopolysaccharide (LPS) in combination with interferon­Î³ inhibited DC development but enhanced MDSC functions. Monophosphoryl lipid A (MPL), derived from LPS, is a unique immunomodulatory Toll­like receptor 4 agonist. In the present study, MPL was used to disturb DC differentiation from myeloid precursors and it was observed that prolonged stimulation with MPL led to the accumulation of MDSCs in vitro and in vivo. In conclusion, it was demonstrated that stimulation by MPL from the beginning of cell differentiation disturbed the development of DCs and led to the accumulation of MDSCs.

Serum N-glycome biomarker for monitoring development of DENA-induced hepatocellular carcinoma in rat.

BACKGROUND: There is a demand for serum markers for the routine assessment of the progression of liver cancer. We previously found that serum N-linked sugar chains are altered in hepatocellular carcinoma (HCC). Here, we studied glycomic alterations during development of HCC in a rat model. RESULTS: Rat HCC was induced by the hepatocarcinogen, diethylnitrosamine (DENA). N-glycans were profiled using the DSA-FACE technique developed in our laboratory.In comparison with control rats, DENA rats showed a gradual but significant increase in two glycans (R5a and R5b) in serum total N-glycans during progression of liver cirrhosis and cancer, and a decrease in a biantennary glycan (P5). The log of the ratio of R5a to P1 (NGA2F) and R5b to P1 [log(R5a/P1) and log(R5b/P1)] were significantly (p < 0.0001) elevated in HCC rats, but not in rats with cirrhosis or fibrosis or in control rats. We thus propose a GlycoTest model using the above-mentioned serum glycan markers to monitor the progression of cirrhosis and HCC in the DENA-treated rat model. When DENA-treated rats were subsequently treated with farnesylthiosalicyclic acid, an anticancer drug, progression to HCC was prevented and GlycoTest markers (P5, R5a and R5b) reverted towards non-DENA levels, and the HCC-specific markers, log(R5a/P1) and log(R5b/P1), normalized completely. CONCLUSIONS: We found an increase in core-alpha-1,6-fucosylated glycoproteins in serum and liver of rats with HCC, which demonstrates that fucosylation is altered during progression of HCC. Our GlycoTest model can be used to monitor progression of HCC and to follow up treatment of liver tumors in the DENA rat. This GlycoTest model is particularly important because a rapid non-invasive diagnostic procedure for tumour progression in this rat model would greatly facilitate the search for anticancer drugs.

Acupuncture versus metoclopramide in treatment of postoperative gastroparesis syndrome in abdominal surgical patients: a randomized controlled trial.

BACKGROUND: Postoperative gastroparesis syndrome (PGS) is a common complication after abdominal surgery in patients with primary liver cancer. However, surgeons usually do not have effective treatment for them. OBJECTIVE: To explore the effects of acupuncture applied to Zusanli and other acupoints on PGS in patients after abdominal surgery. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Sixty-three PGS patients of abdominal surgery, from Eastern Hepatobiliary Surgical Hospital, were randomized into acupuncture group (32 cases) and metoclopramide group (31 cases). The patients in acupuncture group were treated with acupuncture applied to Zusanli and other acupoints once a day, while the patients in metoclopramide group were intramuscularly injected 20 mg metoclopramide three times a day. MAIN OUTCOME MEASURES: Volume of gastric drainage, number of treatment and cure rate in the two groups were measured and evaluated. RESULTS: Acupuncture and metoclopramide could significantly reduce gastric drainage volume. In acupuncture group, the cure rate was 90.6% and the number of treatment was 6.58+/-4.26, while in metoclopramide group, the cure rate and the number of treatment were 32.3% and 10.13+/-3.60 respectively. There were significant differences in gastric drainage volume, cure rate and number of treatment between the two groups (P<0.05, P<0.01). CONCLUSION: Acupuncture is a good treatment for PGS, with fewer treatments, high cure rate and rapid effect.

Clinical studies of laser ablation in treatment of primary liver carcinoma-associated portal vein tumor thrombus.

OBJECTIVE: To explore the clinical values of laser ablation as a new treatment for portal vein tumor thrombus (PVTT). METHODS: A total of 43 male patients with primary liver carcinoma (PLC)-associated PVTT were randomized into a laser ablation group and a radiotherapy group. The laser ablation group of 21 cases received direct percutaneous laser ablation under ultrasonographic guide, followed by direct injection into the portal vein with chemotherapy drugs including mitomycin C (MMC) and fluorouracil (5-Fu). The radiotherapy group of 22 cases was treated with X-ray in three-dimensional conformal radiotherapy (3D CRT) once a day for a total of 10 days course. After the treatment, all patients were followed for postoperative adverse reactions, changes of tumor thrombus, and survival time. RESULTS: In comparison with the radiotherapy, laser ablation resulted in decreased postoperative complications such as limb fatigue, ascites, upper gastrointestinal ulcer, and bleeding. The overall remission rates (complete remission [CR] + partial remission [PR]) were 61.9% (13/21) and 31.8% (7/22) in the laser ablation and radiotherapy group, respectively, with a significant difference (P < .05). All cases in the laser group showed clinical improvement and the average survival time prolonged to greater than 19.5 months (P < .002). CONCLUSION: Percutaneous laser ablation to PVTT is an effective, safe, and simply procedure and has proven to offer significant clinical outcomes in the treatment of PLC-associated PVTT.