Effects of microwave ablation on serum Golgi protein 73 in patients with primary liver cancer.

BACKGROUND: Microwave ablation (MWA) is an effective treatment option for patients with primary liver cancer. However, it has been reported that the MWA procedure induces a hepatic inflammatory response and injury, which may negatively affect the efficacy of MWA. As such, the discovery of reliable markers to monitor the patient's response to MWA is needed. Golgi protein 73 (GP73) has been shown to be associated with chronic liver disease. To date, the potential value of serum GP73 in the dynamic monitoring during MWA of liver cancer remains unclear. AIM: To examine the effects of MWA on the serum levels of GP73 in patients with primary liver cancer. METHODS: A total of 150 primary liver cancer patients with a single small lesion (≤ 3 cm in diameter) were retrospectively enrolled spanning the period between January 2016 and October 2018. All of the patients received MWA for the treatment of primary liver cancer. Serum GP73, alpha-fetoprotein (AFP), and widely used liver biochemical indicators [serum albumin, total bilirubin (TBIL), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] were compared before MWA and at different time points, including 1, 2, and 4 wk following the ablation procedure. RESULTS: Complete tumor ablation was achieved in 95.33% of the patients at 1 mo after MWA. The 1-, 2-, and 3-year disease-free survival rates were 74.67%, 59.33%, and 54.00%, respectively. The serum AFP levels were significantly decreased at 1, 2, and 4 wk after MWA; they returned to the normal range at 12 wk after MWA; and they remained stable thereafter during follow-up in those cases without recurrence. In contrast, the serum GP73 levels were significantly increased at 1 and 2 wk after MWA. The serum GP73 levels reached the peak at 2 wk after MWA, started to decline after hepatoprotective treatment with glycyrrhizin and reduced glutathione, and returned to the pretreatment levels at 12 and 24 wk after MWA. Notably, the changes of serum GP73 in response to MWA were similar to those of TBIL, ALT, and AST. CONCLUSION: Serum GP73 is markedly increased in response to MWA of liver cancer. Thus, serum GP73 holds potential as a marker to monitor MWA-induced inflammatory liver injury in need of amelioration.

Dyella solisilvae sp. nov., isolated from mixed pine and broad-leaved forest soil.

A Gram-stain-negative, aerobic, motile, yellow-pigmented, rod-shaped with a single polar flagellum bacterial strain, designated strain DHG54T, was isolated from a forest soil sample of Dinghushan Biosphere Reserve, Guangdong Province, China. Strain DHG54T grew at 12-37 °C (optimum, 28 °C), pH 4.5-8.0 (optimum, pH 6.0-7.0) and in the presence of 0-3.0 % (w/v) NaCl (optimum, 0-1.5 %, w/v). Based on 16S rRNA gene sequence analysis, strain DHG54T formed a clade with the members of the genus Dyella and showed highest sequence similarities of 98.2 % to Dyella japonica DSM 16301T and Dyella terrae KACC 12748T. This was also supported by phylogenetic analysis based on the concatenated partial gyrB, lepA and recA housekeeping gene sequences. DNA-DNA hybridization results between strain DHG54T and closely related Dyella species were all lower than 70 %. Ubiquinone-8 was the only respiratory quinone, and iso-C15 : 0, iso-C17 : 0 and iso-C17 : 1 ω9c were major fatty acids. The DNA G+C content of strain DHG54T was 65.4 mol%. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. On the basis of the polyphasic characterization results presented here, strain DHG54T represents a novel species of the genus Dyella, for which the name Dyellasolisilvae sp. nov. (type strain DHG54T=GDMCC 1.1187T = LMG 30091T) is proposed.

Apoptosis induced by ursodeoxycholic acid in human melanoma cells through the mitochondrial pathway.

Ursodeoxycholic acid (UDCA) is a type of hydrophilic bile acid extracted from animal bile with a wide range of biological functions. The present results demonstrated that UDCA could effectively inhibit the proliferation of two human melanoma cell line (M14 and A375) with time­ and concentration­dependence. Following exposure to various concentrations of UDCA, M14 cells exhibited typical morphological changes and weaker ability of colony forming. Flow cytometry analysis demonstrated that UDCA could induce a decrease of mitochondrial membrane potential and an increase in reactive oxygen species (ROS) levels in M14 cells. The cell cycle was arrested in the G2/M phase, which was confirmed by the decrease of cyclin­dependent kinase 1 and cyclinB1 at the protein level. However, when M14 cells were treated with UDCA and Z­VAD­FMK (caspase inhibitor) synchronously, the apoptosis rate of the cells was reduced significantly. In addition, it was demonstrated that UDCA induced apoptosis of human melanoma M14 cells through the ROS­triggered mitochondrial­associated pathway, which was indicated by the increased expression of cleaved­caspase­3, cleaved­caspase­9, apoptotic protease activating factor­1, cleaved­poly (ADP­ribose) polymerase 1 and the elevation of B cell lymphoma­2 (Bcl­2) associated X protein/Bcl­2 ratio associated with apoptosis. Therefore, UDCA may be a potential drug for the treatment of human melanoma.

miR-601 is a prognostic marker and suppresses cell growth and invasion by targeting PTP4A1 in breast cancer.

MicroRNAs (miRNA) play important roles in the initiation and progression of breast cancer. Here, we investigated the role of miR-601 in breast cancer and found that its expression was significantly down-regulated in breast cancer tissues compared with matched adjacent non-cancerous breast tissues. Moreover, we found that down-regulation of miR-601 was closely associated with distant metastasis and poor distant metastasis-free survival in breast cancer. In addition, miR-601 levels were inversely correlated with metastatic potential of human breast cancer cell lines. Further experiments showed that ectopic overexpression of miR-601 suppressed breast cancer cell proliferation, migration and invasion, whereas miR-601 knockdown promoted breast cancer cell proliferation, migration and invasion. Furthermore, protein tyrosine phosphatase type IVA 1 (PTP4A1) was identified as a direct target of miR-601. Overexpression of miR-601 repressed PTP4A1 mRNA and protein expression. Conversely, inhibition of miR-601 increased PTP4A1 mRNA and protein expression. Taken together, our data suggest that miR-601 inhibits growth and invasion of breast cancer cells by targeting PTP4A1 and that miR-601 is a potential biomarker for prognosis and therapeutic target in breast cancer.

MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma.

Some microRNAs (miRNAs) have been implicated in hepatocellular carcinoma (HCC) development and progression. However, the roles and mechanisms of several miRNAs in HCC remain poorly understood. Here, we report that miR-379-5p, which is down-regulated in HCC tissues and cell lines, is associated with advanced TNM stage and metastasis in HCC. The ectopic overexpression of miR-379-5p inhibited HCC cell migration, invasion, epithelial-to-mesenchymal transition (EMT) and metastasis both in vitro and in vivo. Conversely, miR-379 knockdown increased migration, invasion and EMT in HCC cells. Moreover, miR-379-5p exerted this function by directly targeting focal adhesion kinase (FAK) 3'-UTR and repressing FAK expression, thus leading to suppression of AKT signaling. Furthermore, the tumor suppressive effects of miR-379-5p in HCC cells were reversed by activating AKT signaling or restoring FAK expression. In clinical samples of HCC, miR-379-5p negatively correlated with FAK, which was up-regulated in HCC. Taken together, our findings highlight the important role of miR-379-5p in regulating the EMT and metastasis of HCC by targeting FAK/AKT signaling, suggesting that miR-379-5p may represent a novel potential therapeutic target and prognostic marker for HCC.

Aberrant DNA methylation of P16, MGMT, and hMLH1 genes in combination with MTHFR C677T genetic polymorphism and folate intake in esophageal squamous cell carcinoma.

AIM: The present case-control study was conducted to explore the association of MTHFR gene polymorphism and relations of P16, MGMT and HMLH1 to MTHFR and folate intake. METHODS: A total of 257 cases of esophageal squamous cell carcinoma confirmed by histopathological examination were collected. Genotyping of P16, MGMT and HMLH1 was accomplished by methylation-specific polymerase chain reaction (PCR) after sodium bisulfate modification of DNA and the MTHFR C677T genetic polymorphism was detected by PCR- restriction fragment-length polymorphism (PCR-RFLP). RESULTS: The proportions of DNA hypermethylation in P16, MGMT and hMLH1 in cancer tissues were significantly higher than in paracancerous normal tissue. The proportion of hypermethylation in at least one gene was 88.5% in cancer tissue, and was also significantly higher than that in paracancerous normal tissue. Our finding showed individuals with homozygotes (TT) of MTHFR C677T had significant risk of DNA hypermethylation of MGMT in cancer tissues, with an OR (95% CI) of 3.15 (1.12-6.87). Similarly, patients with high intake of folate also showed a slight high risk of DNA methylation of MGMT, with OR (95% CI) of 2.03 (1.05-4.57). CONCLUSION: Our study found the P16, MGMT and hMLH1 demonstrate a high proportion of hypermethylation in esophageal squamous cell cancer cancer tissues, which might be used as biomarkers for cancer detection.

Glulathione-S-transferases gene polymorphism in prediction of gastric cancer risk by smoking and Helicobacter pylori infection status.

AIM: To evaluate the association of glutathione S-transferases gene polymorphisms with the risk of gastric cancer, with reference to smoking and Helicobacter pylori infection. METHODS: We conducted a 1:1 matched case-control study with 410 gastric cancer cases and 410 cancer-free controls. Polymorphisms of GSTM1, GSTT1 and GSTP1 were determined using PCR-CTPP. RESULTS: The GSTM1 and GSTT1 null genotypes were significantly associated with the risk of gastric cancer after adjusting for potential confounding factors (OR=1.68, 95% CI=1.32-2.23 for null GSTM1, OR=1.73; 95% CI=1.24-2.13 for null GSTT1). The combination of null GSTM1 and null GSTT1 conferred an elevated risk (OR=2.54, 95% CI=1.55-3.39). However, no association was found for GSTP1 polymorphism The smoking modified the association of GSTM1 and GSTT1 null genotypes with the risk of gastric cancer. CONCLUSION: GSTM1 and GSTT1 null genotypes are associated with increased risk of gastric cancer, and smoking modifies the association.

Contribution of NAD(P)H quinone oxidoreductase 1 (NQO1) Pro187Ser polymorphism and risk of colorectal adenoma and colorectal cancer in Caucasians: a meta-analysis.

BACKGROUND AND AIMS: The effects of polymorphism of NAD(P)H quinone oxidoreductase 1 (NQO1 Pro187Ser, rs1800566) on the risks of colorectal adenoma and cancer have been widely studied and results remain controversial. Therefore, the aim of this meta-analysis was to quantitatively assess the relationships. METHODS: Databases of Medline, Embase and Wanfang were retrieved until May 15, 2011. Pooled odds ratio (OR) and 95% confidence interval (95% CI) as effect sizes were calculated by using fixed- or random-effect model. Cochrane Q-test was used to explore between-study heterogeneity; p <0.10 indicated statistical significance. RESULTS: A total of 12 case-control studies with 11,700 individuals (including 5528 cases and 6172 controls) were included in this meta-analysis. Of these studies, four studies conducted in Caucasian populations were for colorectal adenoma, and eight studies were for colorectal cancer. NQO1 187Ser allele was significantly associated with increased risk of colorectal adenoma in co-dominant and dominant comparison models (OR = 1.07, 95% CI = 1.04-1.32 for ProSer vs. ProPro and OR = 1.19, 95% CI = 1.06-1.33 for Ser carries vs. ProPro), without between-study heterogeneity. Overall, NQO1 Pro187Ser was not associated with risk of colorectal cancer, without between-study heterogeneity. Subgroup analyses indicated that Ser allele was significantly associated with increased risk of colorectal cancer for Caucasians (OR = 1.14, 95% CI = 1.00-1.30 for ProSer vs. ProPro and OR = 1.16, 95% CI = 1.02-1.31 for Ser carries vs. ProPro). CONCLUSIONS: This meta-analysis suggested that Ser allele of NQO1 Pro187Ser significantly contributed to the increased risks of colorectal adenoma and cancer in Caucasians.

[The effect of protein metabolism and immunologic function of glutamine after operation in elder gastrointestinal tumor].

AIM: To explore the effect of protein metabolism and immunologic function of glutamine after operation in elder gastrointestinal tumor. METHODS: Form march 2007 to 2010, 87 cases of elder gastrointestinal tumor were given parenteral nutrition and glutamine 0.6 g/( Kg x d).The period of treatment were 8 days. IgA, IgG, IgM were CD4, measured by single immunodiffusion, CD3(+), CD4(+), CD8(+), CD4(+) /CD8(+) were measured by immunohistochemical method, and the index(Alb, PAB, TF, nitrogen equilibrium) were monitored the proteid catabolism distribution. RESULTS: After the treatment, CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), IgG, IgA, IgM were evidently declined( P <0.05). Alb, PAB, TF were evidently declined in 4 days postoperatively (P < 0.05), the restore were more obvious in 8 days postoperatively (P < 0. 05). Nitrogen equilibrium was worse in the early postoperative and the restore were more obvious in 8 days postoperatively (P < 0.05). CONCLUSION: Glutamine can improve patient's nutrition, enhance their immunologic function.