PRDX1 Influences The Occurrence and Progression of Liver Cancer by Inhibiting Mitochondrial Apoptosis Pathway.

OBJECTIVE: The aim of this study is to elucidate the role of PRDX1 in hepatocellular carcinoma using hepatoma cells. MATERIALS AND METHODS: In this experimental study, we elucidated role of PRDX1, using hepatoma cell lines. RESULTS: PRDX1 was upregulated in different types of cancers, including lung adenocarcinoma, breast cancer and liver cancer reported by several studies. nevertheless, mechanism of inducing liver cell death by PRDX1 remains largely unknown. Here, we showed that PRDX1 expression is enhanced in different cell lines. Here, we used western blot, quantitative real time polymerase chain reaction (qRT-PCR) and different biochemical assays to explore the role of PRDX1. We observed that overexpression of PRDX1 significantly enhanced proliferation of hepatoma cell lines, while knock-down of this gene showed significant inhibitory effects. We found that knock-down of PRDX1 activated cleaved caspase-3, caspase-9 proteins and Poly [ADP-ribose] polymerase 1 (PARP-1), which further executed apoptotic process, leading to cell death. We found that PRDX1 knock-down significantly produced mitochondrial fragmentation. We showed that silencing PRDX1 led to the loss of B-cell lymphoma 2 (Bcl-2) and activated Bcl-2-like protein 11 (Bim) which further induced Bax activation. Bax further released cytochrome c from mitochondria and induced apoptotic proteins, suggesting a significant role of PRDX1 knock-down in apoptosis. Finally, we showed that knock-down of PRDX1 significantly activated expression of Dynein-related protein 1 (Drp1), fission 1 (Fis1) and dynamin-2 (Dyn2) suggesting a crucial role of PRDX1 in mitochondrial fragmentation and apoptosis conditions. This study highlighted an important role of PRDX1 in regulating proliferation of hepatoma cells and thus future studies are required to validate its effect on hepatcoytes. CONCLUSION: We propose that future works on PRDX1 inhibitors may act as a therapeutic candidate for treatment of liver cancer.

Correlation between HER-2/neu(erbB-2) expression level and therapeutic effect of combination treatment with HERCEPTIN and chemotherapeutic agents in gastric cancer cell lines.

INTRODUCTION: Although advanced gastric cancer has many limitations and response rate is marginal in chemotherapy. Overexpression of human epidermal growth factor receptor 2(HER-2/neu) gene and its protein are associated with increased cell division and a high rate of tumor growth and have been reported in several malignancies. Especially, approximately 30% of breast cancer patients have overexpression of HER-2/neu protein and the overexpression metastasize faster, induces resistance of the chemotherapy and down-regulate function of estrogen receptor. Recombinant humanized anti-HER2 antibody (Herceptin) inhibits proliferation of HER-2/neu overexpressing tumor cells and the use of that in combination in metastatic breast cancer have increased cytotoxicity of chemotherapeutic agents. METHODS: We evaluated the expression of HER-2/neu protein in gastric cell lines by FACS and then comparing the cytotoxicity in chemotherapeutics (doxorubicin, cisplatin, paclitaxel, 5-FU) alone and in combination with Herceptin according to the expression of HER-2/neu protein by MTT assay. RESULTS: 1. NCI-N87 (88%) gastric cancer cell line and SK-BR-3 (89%) breast cancer cell line with strong positivity of HER-2/neu expression. YBC-2 (55%) and YBC-3 (48%) gastric cancer cell line with intermediated, weak positivity respectively. Negative control U-87 MG (6%) brain cancer cell line were showed low expression of HER-2/neu. 2. Cell growth was dose-dependently inhibited in HER-2/neu positive, control cell line SK-BR-3 by Herceptin treatment but not observed in HER-2/neu negative control cell line U-87 MG. Effective growth inhibition was not observed in gastric cancer cell lines with single treatment of Herceptin, all cell lines observed the dose-dependent growth inhibition to chemotherapeutic agents (doxorubicin, cisplatin, paclitaxel and 5-FU). 3. Combination of Herceptin with doxorubicin observed synergistic effects in all cancer cell lines except YBC-3, combination of Herceptin with cisplatin observed NCI-N87 and SK-BR-3 and combination of Herceptin with paclitaxel observed synergistic effects in YBC-2. Combination of Herceptin with 5-FU observed antagonistic effects in all cancer cell lines. CONCLUSIONS: According to HER-2/neu expression level, effect of anti-cancer agents was observed differently in combination of Herceptin with chemotherapeutic agents. This suggests that HER-2/neu expression level can be applied standard of combination drug selection in combination of Herceptin With chemotherapeutic agents in gastric cancer.

Identification of differentially expressed genes in gastric cancer by high density cDNA microarray.

The identification of molecular markers for diagnosis, treatment, and prognosis is a significant issue in the management of patients with gastric cancer. We compared the expression profiles of 23 gastric cancers and 22 normal gastric tissues using cDNA microarrays. We divided the samples into two sets, 11 pairs as a training set and 12 unpaired gastric cancer and 11 unpaired normal gastric tissues as a test set. We selected significant genes in the training set and validated the significance of the genes in the test set. We obtained 238 classifier genes that showed a maximum cross-validation probability and clear hierarchical clustering pattern in the training set, and showed excellent class prediction probability in the independent test set. The classifier genes consisted of known genes related to the biological features of cancer and 28% unknown genes. We obtained genome-wide molecular signatures of gastric cancer, which provides preliminary exploration data for the pathophysiology of gastric cancer.

2,2'-{[4,6-Bis(octyl-amino)-1,3,5-triazin-2-yl]aza-nedi-yl}diethanol.

In the title compound, C(23)H(46)N(6)O(2), the two hy-droxy groups are located on opposite sides of the triazine ring. One of the hy-droxy groups links with the triazine N atom via an intra-molecular O-H⋯N hydrogen bond. Inter-molecular O-H⋯N and N-H⋯O hydrogen bonding is observed in the crystal structure. π-π stacking is also observed between parallel triazine rings of adjacent mol-ecules, the centroid-centroid distance being 3.5944 (14) Å.

Application of mesenchymal stem cells as a vehicle to deliver replication-competent adenovirus for treating malignant glioma.

Although gene therapy was regarded as a promising approach for glioma treatment, its therapeutic efficacy was often disappointing because of the lack of efficient drug delivery systems. Mesenchymal stem cells(MSCs) have been reported to have a tropism for brain tumors and thus could be used as delivery vehicles for glioma therapy. Therefore, in this study, we attempted to treat glioma by using MSCs as a vehicle for delivering replication-competent adenovirus. We firstly compared the infectivity of type 3, type 5, and type 35 fiber-modified adenoviruses in MSCs. We also determined suitable adenovirus titer in vitro and then used this titer to analyze the ability of MSCs to deliver replication-competent adenovirus into glioma in vivo. Our results indicated that type 35 fiber-modified adenovirus showed higher infectivity than did naked type 3 or type 5 fiber-modified adenovirus. MSCs carrying replication-competent adenovirus significantly inhibited tumor growth in vivo compared with other control groups. In conclusion, MSCs are an effective vehicle that can successfully transport replication-competent adenovirus into glioma, making it a potential therapeutic strategy for treating malignant glioma.

Genetic analysis of liver metastatic cell lines with different metastatic potential.

Metastasis is the major feature of malignant tumors that causes 90% of cancer deaths. Our laboratory has already established liver metastatic clones with YCC-16, isolated from the blood of a gastric cancer patient and expanded in vitro culture using a repeated orthotopic implantation method, and had reported biologic behaviour of the parental YCC-16, the orthotopic primary S1L0, and S1L1, S2L2 and S3L3 liver metastatic clones. Here, using these cell lines, we screened from chromosomal abnormalities using karyotype analysis and micro-CGH matching. There were 31 genes screened using PCA method which were functionally related to cell adhesion. Also, there were 23 genes selected which were related to the liver specific metastasis but excluded genes related to adhesion. There were 4 genes which demonstrated reduced or increased expression stepwise with passage. In conclusion, our results should contribute to exploring the mechanisms of liver metastasis by gastric cancer.