Targeting MicroRNAs in Cancer Gene Therapy

MicroRNAs (miRNAs) are a kind of conserved small non-coding RNAs that participate in regulating gene expression by targeting multiple molecules. Early studies have shown that the expression of miRNAs changes significantly in different tumor tissues and cancer cell lines. It is well acknowledged that such variation is involved in almost all biological processes, including cell proliferation, mobility, survival and differentiation. Increasing experimental data indicate that miRNA dysregulation is a biomarker of several pathological conditions including cancer, and that miRNA can exert a causal role, as oncogenes or tumor suppressor genes, in different steps of the tumorigenic process. Anticancer therapies based on miRNAs are currently being developed with a goal to improve outcomes of cancer treatment. In our present study, we review the function of miRNAs in tumorigenesis and development, and discuss the latest clinical applications and strategies of therapy targeting miRNAs in cancer

Clinicopathological and prognostic significance of survivin over-expression in patients with esophageal squamous cell carcinoma: a meta-analysis.

BACKGROUND:The prognostic significance of survivin for survival of patients with esophageal squamous cell carcinoma (ESCC) remains controversial. Thus, meta-analysis of the literatures was performed in order to demonstrate its expression impact on ESCC clinicopathological features and prognosis. METHODOLOGY:Relevant literatures were searched using PubMed, EMBASE and Medline Databases. Revman5.0 software was used to pool eligible studies and summary hazard ratio (HR). Correlation between survivin expression and clinicopathological features of ESCC was analyzed. PRINCIPAL FINDINGS:Final analysis of 523 patients from 7 eligible studies was performed. Combined HR of survivin location in nuclei suggested that survivin expression has an unfavorable impact on ESCC patients' survival (n = 277 in 3 studies; HR = 1.89, 95% CI: 1.45-2.96; Z = 4.69; P<0.0001). Nevertheless, combined HR of survivin location in cytoplasm displayed that survivin expression has no significance for prognosis of ESCC patients (n = 113 in 2 studies; HR = 0.96, 95% CI: 0.96-5.69; Z = 0.04; P = 0.97); Combined odds ratio (OR) of survivin location in cytoplasm indicated that survivin expression is associated with ESCC advanced stage (n = 113 in 2 studies; OR = 0.36, 95% CI: 0.14-0.93; Z = 2.10; P = 0.04). Whereas, combined OR of survivin location in nuclei exhibited that survivin over-expression has no correlation with cell differentiation grade, lymph node status, depth of invasion, stage, and metastasis of ESCC. CONCLUSIONS:This study showed that survivin expression detected by immunohistochemistry seems to be associated with a worse prognosis of ESCC patients. Survivin subcellular location may be an important factor impacting on ESCC development. Larger prospective studies should be performed to evaluate the status of survivin in predicting prognosis of patients with ESCC

Serum biomarker panels for the diagnosis of gastric cancer

Abstract Gastric cancer is a leading cause of mortality due to neoplastic disease. Although early detection of gastric cancers can decrease the mortality rate, it remains a diagnostic challenge because of the lack of effective biomarkers. In this study, fifteen gastric cancer patients and ten healthy subjects were recruited to assess novel serum biomarkers for gastric cancer using antibody microarray technology. ELISA was utilized to validate the antibody array results. As a result, compared to the controls, eleven cytokines were found to be significantly increased in gastric cancer, including interferon gamma receptor 1 (IFNGR1), neurogenic locus notch homolog protein 3 (Notch‐3), tumor necrosis factor receptor superfamily member 19L (TNFRSF19L), growth hormone receptor (GHR), signaling lymphocytic activation molecule family 8 (SLAMF8), folate receptor beta (FR‐beta), integrin alpha 5, galectin‐8, erythropoietin‐producing hepatocellular A1 (EphA1), epiregulin, and fibroblast growth factor 12 (FGF‐12) with P < 0.05. ELISA validation supported the results of the antibody array. More importantly, most of these eleven cytokines, including IFNGR1, TNFRSF19L, GHR, SLAMF8, FR‐beta, and integrin alpha 5 were discovered to be elevated in gastric cancer serum samples for the first time in this study, suggesting that these proteins may serve as novel biomarkers for the early diagnosis and prognosis determination of gastric cancer

A Novel Matrine Derivative WM130 Inhibits Activation of Hepatic Stellate Cells and Attenuates Dimethylnitrosamine-Induced Liver Fibrosis in Rats

Activation of hepatic stellate cells (HSCs) is a critical event in process of hepatic fibrogenesis and cirrhosis. Matrine, the active ingredient of Sophora, had been used for clinical treatment of acute/chronic liver disease. However, its potency was low. We prepared a high potency and low toxicity matrine derivate, WM130 (C30N4H40SO5F), which exhibited better pharmacological activities on antihepatic fibrosis. This study demonstrated that WM130 results in a decreased proliferative activity of HSC-T6 cells, with the half inhibitory concentration (IC50) of 68 μM. WM130 can inhibit the migration and induce apoptosis in HSC-T6 cells at both concentrations of 68 μM (IC50) and 34 μM (half IC50). The expression of α-SMA, Collagen I, Collagen III, and TGF-β1 could be downregulated, and the protein phosphorylation levels of EGFR, AKT, ERK, Smad, and Raf (p-EGFR, p-AKT, p-ERK, p-Smad, and p-Raf) were also decreased by WM130. On the DMN-induced rat liver fibrosis model, WM130 can effectively reduce the TGF-β1, AKT, α-SMA, and p-ERK levels, decrease the extracellular matrix (ECM) formation, and inhibit rat liver fibrosis progression. In conclusion, this study demonstrated that WM130 can significantly inhibit the activation of HSC-T6 cells and block the rat liver fibrosis progression by inducing apoptosis, suppressing the deposition of ECM, and inhibiting TGF-β/Smad and Ras/ERK pathways

Phase Analysis and Thermoelectric Properties of TiNiSn based half-Heusler Thermoelectric Materials

<p>Survivin subcellular location was not clear in the 3 studies, the combined HR demonstrated that over-expression of survivin in ESCC was associated with patients' worse prognosis.</p

Characteristics of enrolled studies.

<p>D, histologic differentiation; LN, lymph node metastasis; T, depth of tumor invasion; M, metastasis; S, stage.</p

Immunohistochemical technique used in these studies.

<p>Immunohistochemical technique used in these studies.</p