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Background: The purpose of this study was to explore the efficacy and safety of high intensity focused ultrasound (HIFU) in gastric cancer with liver metastasis (GCLM) patients who were contraindicated for either hepatectomy or radiofrequency ablation (RFA).Methods: This is a prospective, observational study on GCLM patients with 1-3 liver metastases. The primary gastric lesions were thoroughly resected and any case that exhibited extra-hepatic metastasis was excluded. A 1:2:2 propensity score-matching analysis was performed using a logistic regression model on the HIFU group, best supportive care (BSC) group, and palliative chemotherapy (PC) group. The primary endpoints include progression-free survival (PFS) and overall survival (OS).Results: Forty patients were finally included, there were 8 cases in HIFU group, 16 cases in BSC group, and 16 cases in PC group. The median follow-up time for the entire cohort was 10 months. The median PFS was 16.5 months in HIFU group, 2 months in BSC group, and 5 months in PC group. The median OS was 27.5 months in the HIFU group, 7 months in the BSC group, and 11.5 months in the PC group. Additionally, no grade 3 or higher adverse events occurred in the HIFU group.Conclusion: The results of this study showed that HIFU treatment could improve the long-term prognosis of GCLM patients without a significant increase in the occurrence of adverse events. Compared with PC and BSC, HIFU is the preferred treatment option when GCLM patients without extra-hepatic metastasis are unable to undergo either surgery or RFA. [ABSTRACT FROM AUTHOR]

Backgroud: It has been shown that aberrant expression of microRNAs (miRNAs) and transcriptional factors (TFs) is tightly associated with the development of HCC. Therefore, in order to further understand the pathogenesis of HCC, it is necessary to systematically study the relationship between the expression of miRNAs, TF and genes. In this study, we aim to identify the potential transcriptomic markers of HCC through analyzing common microarray datasets, and further establish the differential co-expression network of miRNAs–TF–mRNA to screen for key miRNAs as candidate diagnostic markers for HCC. Method: We first downloaded the mRNA and miRNA expression profiles of liver cancer from the GEO database. After pretreatment, we used a linear model to screen for differentially expressed genes (DEGs) and miRNAs. Further, we used weighed gene co-expression network analysis (WGCNA) to construct the differential gene co-expression network for these DEGs. Next, we identified mRNA modules significantly related to tumorigenesis in this network, and evaluated the relationship between mRNAs and TFs by TFBtools. Finally, the key miRNA was screened out in the mRNA–TF–miRNA ternary network constructed based on the target TF of differentially expressed miRNAs, and was further verified with external data set. Results: A total of 465 DEGs and 215 differentially expressed miRNAs were identified through differential genes expression analysis, and WGCNA was used to establish a co-expression network of DEGs. One module that closely related to tumorigenesis was obtained, including 33 genes. Next, a ternary network was constructed by selecting 256 pairs of mRNA–TF pairs and 100 pairs of miRNA–TF pairs. Network mining revealed that there were significant interactions between 18 mRNAs and 25 miRNAs. Finally, we used another independent data set to verify that miRNA hsa-mir-106b and hsa-mir-195 are good classifiers of HCC and might play key roles in the progression of HCC. Conclusion: Our data indicated that two miRNAs—hsa-mir-106b and hsa-mir-195— are identified as good classifiers of HCC. [ABSTRACT FROM AUTHOR]

Background: Hepatectomy generally offers the best chance of long-term survival for patients with hepatocellular carcinoma (HCC). Many studies have shown that hepatectomy accelerates tumor metastasis, but the mechanism remains unclear. Methods: An orthotopic nude mice model with palliative HCC hepatectomy was performed in this study. Metastasis-related genes in tumor following resection were screened; HCC invasion, metastasis, and some molecular alterations were examined in vivo and in vitro. Clinical significance of key gene mRNA expression was also analyzed. Results: Metastasis suppressor 1 (MTSS1) located in the central position of gene function net of residual HCC. MTSS1 was up-regulated in residual tumor after palliative resection. In hepatitis B-related HCC patients undergone palliative hepatectomy, those with higher MTSS1 mRNA expression accompanied by activation of matrix metalloproteinase 2 (MMP2) in residual HCC, had earlier residual HCC detection after hepatectomy and poorer survival when compared to those with lower MTSS1. In different cell lines, the levels of MTSS1 mRNA increased in parallel with metastatic potential. MTSS1 down regulation via siRNA decreased MMP2 activity, reduced invasive potentials of HCC by 28.9 % in vitro, and averted the deteriorated lung metastatic extent in vivo. Conclusions: The poor prognosis of hepatitis B-related HCC patients following palliative hepatectomy associates with elevated MTSS1 mRNA expression; therefore, MTSS1 may provide a new research field for HCC diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The present study aimed to quantitatively determine the aberrant methylation signal of the adenomatous polyposis coli (APC) gene in hepatocellular carcinoma (HCC), and to evaluate whether hypermethylation of the APC promoter could be a prognostic biomarker for HCC. Taqman probe-based quantitative methylation-specific polymerase chain reaction was performed to identify the APC promoter methylation levels in 57 HCC and corresponding non-tumorous liver tissues. In the present study, the methylation level of the APC promoter was upregulated by 4.51-fold in the HCC tissues compared with the non-cancerous tissues (P=0.0003). With regard to the clinicopathological data, the methylation level of the APC promoter in the HCC samples was higher in the patients with larger tumors when the cut-off was set at 4 cm (P=0.0008), and in the older patients when the cut-off was set at 60 years old (P=0.0438). However, the methylation status in the HCC samples appeared not to affect the overall patient survival rate (P=0.1684). The findings of the present study showed that APC promoter hypermethylation accumulates during the development of HCC, but that it may not be a promising prognostic biomarker for HCC. [ABSTRACT FROM AUTHOR]

To examine the expressions of focal adhesion kinase (FAK) and its clinical significance in hepatocellular carcinoma (HCC). We determined the expression levels of FAK on both steady-state mRNA and protein levels in 50 HCC samples by quantitative real-time PCR and immunohistochemistry, respectively. The correlations between FAK expression and various clinicopathological parameters were analyzed. The expression of FAK on the mRNA level was consistent with that on the protein level. FAK mRNA levels in tumor tissues were significantly higher than in the paratumor tissues (0.229 ± 0.027 vs. 0.163 ± 0.019; P < 0.001), but lower than in the macroscopic cancer emboli (0.506 ± 0.155 vs. 0.377 ± 0.176; P < 0.05). Compared within the tumor tissues, FAK expressions were significantly higher in those with cancer emboli than those without (0.343 ± 0.05 vs. 0.165 ± 0.025; P = 0.003). Univariate and multivariate analyses revealed that FAK expression was an independent prognostic factor for disease-free survival and overall survival. Both 3-year disease-free survival rates and overall survival rates in FAK-negative group were significantly higher than in positive group (52 vs. 20% and 72 vs. 29%, P < 0.001). Our results suggest that FAK expression is up-regulated in HCC and its expression is an independent prognostic factor for HCC. [ABSTRACT FROM AUTHOR]

Objective: Although signal transducer and activator of transcription 1 (STAT1), a transcription factor, plays a critical role in carcinogenesis and has been implicated as a tumor suppressor, few studies have investigated the associations between polymorphisms of this gene and the risk of cancer development. The aim of this study was to examine whether STAT1 gene polymorphisms are associated with the risk of hepatocellular carcinoma (HCC). Methods: Ten single nucleotide polymorphisms in the STAT1 gene were genotyped by TaqMan assays in 469 HCC cases and 558 age-, sex- and HBsAg-matched controls in a Chinese population. Results: Minor allele homozygous genotypes at rs867637 (9,046 bp 3′ of STP A>G), rs3771300 (IVS24-153T>G), and rs2280235 (IVS20-103G>A), compared with their homozygote genotypes of common alleles, were associated with 1.6- (95% CI 1.1-2.3), 1.6- (95% CI 1.1-2.4), and 1.4-fold (95% CI 0.95-1.9) increased risk of HCC, respectively. The GGA haplotype, comprised of risk alleles at rs867637, rs3771300 and rs2280235, conferred a 1.2-fold (95% CI 1.0-1.5) increased risk of HCC, as compared to the most common haplotype of ATG. Diplotype GGA/GGA conferred a 1.6-fold (95% CI 1.0-2.5) increased risk of HCC compared with diplotype ATG/ATG. Conclusion: Our results demonstrate for the first time that polymorphisms in the STAT1 gene are associated with HCC susceptibility. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Liver resection is a widely accepted treatment for hepatocellular carcinoma (HCC). Our previous clinical study showed that the rate of palliative resection was 34.0% (1958-2008, 2754 of 8107). However, the influence of palliative resection on tumor metastasis remains controversial. The present study was conducted to evaluate the effect of palliative resection on residual HCC and to explore interventional approaches. Methods: Palliative resection was done in an orthotopic nude mice model of HCC (MHCC97H) with high metastatic potential. Tumor growth, invasion, metastasis, lifespan, and some molecular alterations were examined in vivo and in vitro. Mice that underwent palliative resection were treated with the Chinese herbal compound "Songyou Yin," interferon-alfa-1b (IFN-α), or their combination to assess their effects. Results: In the palliative resection group, the number of lung metastatic nodules increased markedly as compared to the sham operation group (14.3 ± 4.7 versus 8.7 ± 3.6, P < 0.05); tumor matrix metalloproteinase 2 (MMP2) activity was elevated by 1.4-fold, with up-regulation of vascular endothelial growth factor (VEGF) and downregulation of tissue inhibitor of metalloproteinase 2 (TIMP2). The sera of mice undergoing palliative resection significantly enhanced cell invasiveness by 1.3-fold. After treatment, tumor volume was 1205.2 ± 581.3 mm3, 724.9 ± 337.6 mm3, 507.6 ± 367.0 mm3, and 245.3 ± 181.2 mm3 in the control, "Songyou Yin," IFN-α, and combination groups, respectively. The combined therapy noticeably decreased the MMP2/TIMP2 ratio and prolonged the lifespan by 42.2%. Moreover, a significant (P < 0.001) reduction of microvessel density was found: 43.6 ± 8.5, 34.5 ± 5.9, 23.5 ± 5.6, and 18.2 ± 8.0 in the control and treatment groups, respectively. Conclusion: Palliative resection-stimulated HCC metastasis may occur, in part, by up-regulation of VEGF and MMP2/TIMP2. "Songyou Yin" reinforced the ability of IFN-α to inhibit the metastasis-enhancing potential induced by palliative resection, which indicated its potential postoperative use in patients with HCC. [ABSTRACT FROM AUTHOR]

Background Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The aim of this study is to evaluate the synergistic anti-tumor effects and underlying mechanism of κ-selenocarrageenan (KSC) in combination with the chemotherapy drug epirubicin (EPI) in H22 tumor-bearing mice. Methods Hepatocellular carcinoma H22 cells were implanted into mice. After the transplants were successfully established, the animals were divided into four groups: namely the control group, the KSC group, the EPI group and the KSC + EPI group. The effects of KSC and EPI on tumor growth, survival time, thymus index, spleen index, white blood cells (WBC), splenocyte proliferation, natural killer (NK) cell activity, serum TNF-α and IL-2 levels, and antioxidant enzymes in the liver cells were determined. Results KSC and/or EPI significantly reduced tumor weight and prolonged the survival time. Furthermore, KSC could attenuate EPI-induced atrophy in the thymus and spleen, as well as other toxicities, which may indicate an additive effect of this combination against organ dysfunction and cellular injury. KSC significantly promoted Con A- and LPS-stimulated splenocyte proliferation, enhanced NK cell activity, and reversed the inhibition of NK activity induced by EPI ( P < 0.01). In addition, KSC could elevate serum TNF-α and IL-2 levels, increase the GSH-Px, SOD, CAT and GSH activity levels in liver tissue, and reduce MDA content. Conclusions These results suggest that KSC can regulate immune function in mice and suppress the growth of tumor in H22 tumor-bearing mice, and its synergistic antitumor activity with epirubicin may be related to its antioxidant and immuno-modulatory effects. [ABSTRACT FROM AUTHOR]