Liver cancer is one of the top six leading causes of cancer-related death. Radiofrequency ablation (RFA) is an important means of treating liver cancer. Residual cancer after RFA is the most frequent cause of recurrence in cases of liver cancer. The main difference between residual cancer cells and ordinary liver cancer cells is that residual cancer cells experience heat shock. The secretable form of trimeric human tumor necrosis factor-related apoptosis-inducing ligand (stTRAIL) induces apoptosis in a variety of human cancers but not in normal tissues. It has shown potent cancer-selective killing activity and has drawn considerable attention as a possible cancer therapy. In the present work, the therapeutic potential of this stTRAIL-based gene therapy was evaluated in hepatocellular carcinoma subjected to RFA. Rat bone marrow mesenchymal stem cells (BM-MSCs) were isolated and transduced with a lentiviral vector encoding stTRAIL (stTRAIL-MSCs, T-MSCs). Cells treated with heat treatment at 43 °C for 45 min served as simulated residual cancer cells. After treatment with T-MSCs, apoptosis in heat-shock-treated liver cancer cells increased significantly, and caspase-3 was upregulated. When T-MSCs were subcutaneously injected into nude mice, they localized to the tumors and inhibited tumor growth, significantly increasing survival. Collectively, the results of the present study indicate that BM-MSC can provide a steady source of stTRAIL and may be suitable for use in the prevention of the recurrence of hepatocellular carcinoma after RFA with secretable trimeric TRAIL.

BackgroundSub-lethal heat treatment characterizes a transition zone of radiofrequency ablation (RFA) which explains hepatocellular carcinoma (HCC) residual cancer occurrence in this area after RFA treatment. The biochemistry of residual cancer cell recurrence is poorly understood, but long noncoding RNAs (lncRNAs) may have aberrant expression that is associated with diverse cancers. Thus, we measured lncRNA gene expression in sub-lethally heat-treated HCC cells using microarray.MethodDifferentially expressed lncRNA and mRNA were measured with an Agilent Human lncRNA + mRNA Array V4.0 (4 × 180 K format) containing 41,000 lncRNAs and 34,000 mRNAs. Bioinformatics analysis was used to assess differentially expressed lncRNA and mRNA. Seven lncRNA and seven mRNA were validated by qRT-PCR analysis in HCC cells.ResultsGenome-wide lncRNA and mRNA expression data in sub-lethal heat-treated SMMC-7721 HCC cells 558 lncRNA and 250 mRNA were significantly up-regulated and 224 lncRNA and 1031 mRNA down-regulated compared to normal cultured SMMC-7721 cells. We demonstrated for the first time that ENST00000570843.1, ENST00000567668.1, ENST00000582249.1, ENST00000450304.1, TCONS_00015544, ENST00000602478.1, TCONS_00001266 and ARC, IL12RB1, HSPA6 were upregulated, whereas STAT3, PRPSAP1, MCU, URB2 were down-regulated in sub-lethally heat-treated HCC cells.ConclusionslncRNA expression data in sub-lethally heat-treated HCC cells will provide important insights about lncRNAs’ contribution to HCC recurrence after RFA treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12957-017-1194-4) contains supplementary material, which is available to authorized users.

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Abstract. Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal tract, and typically metastasize to the liver. In patients with recurrent metastatic GISTs, no single treatment is effective. The current study reports a case of GIST with 27 metastases in the liver, which was successfully treated using radiofrequency ablation (RFA) combined with surgical resection and imatinib therapy. The patient remains tumor-free 36 months after the first RFA treatment. This case suggests that comprehensive therapy including surgical resection, RFA and imatinib, may be an effective strategy for the treatment of GIST with multiple liver metastases.