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An efficient palladium-copper catalyzed regioselective C–C bond cleavage/C–H bond activation/C–C bond reformation reaction to synthesize 9,9-diaryl-xanthenes has been developed. A variety of 9,9-diaryl-xanthenes were synthesized in moderate to good yields by 9H-xanthene-9-carboxylic acid/2-(9H-xanthen-9-yl)-cycloketones and aromatics bearing electron-donating functional groups through the decarboxylation/de-cycloalkanonylative coupling reactions. [ABSTRACT FROM AUTHOR]

One bonded- and one discreted-Lindqvist hexatungstate-based copper hybrids (Cu-POMs) ([Cu2(O)OH(phen)2]2[W6O19]·6H2O (1) and [Cu2(phen)4Cl] [HW6O19]·2H2O (2) (phen = 1,10-phenanthroline)) were controllably synthesized and routinely characterized. Cu-POMs 1–2 consisted of identical [W6O19] unit and similar copper–phen complexes, the two units are bonded via four Cu–O chemical bonds in compound 1; however, compound 2 is discreted and stabilized by intermolecular electrostatic interactions. Importantly, these Cu-POMs catalysts were first applied in the novel reaction for the preparation of 2-phenylquinoxalines via the one-pot coupling and oxidation reactions of 2-haloanilines with vinyl azides or 3-phenyl-2H-azirines under mild conditions, and Cu-POMs 1 showed higher catalytic performance in good yields (79–84%). The reactions exhibit some functional group tolerance and allow for the preparation of a number of 2-phenylquinoxalines. [ABSTRACT FROM AUTHOR]

Inactivated LRRC4 has been clinically detected in gliomas, and promoter hypermethylation has been implicated as the mechanism of inactivation in some of those tumors. Our previous researches indicated that LRRC4 is a target gene of miR-381, the interaction of miR-381 and LRRC4 is involved in glioma growth. In this study, we demonstrate that LRRC4 is a target gene of the other microRNA, miR-182. We found that the high expression of miR-182 and miR-381 in gliomas are involved in pathological malignant progression. The silencing of miR-182 and miR-381 inhibited the proliferation in vitro and growth of glioma cell with in vivo magnetic resonance imaging by intracranial transplanted tumor model in rats. We also demonstrated that BRD7, a transcriptional cofactor for p53, is highly expressed and negatively correlated with LRRC4 expression in gliomas. Disturbing miR-182 and miR-381 affected transcriptional regulation of the BRD7 gene. This finding was verified by ectopic overexpression of LRRC4 or restoration of endogenous LRRC4 expression by treatment with the DNA demethylating agent 5-Aza-dC. Taken together, miR-182 and miR-381 may be a useful therapeutic target for treatment of glioma. [ABSTRACT FROM AUTHOR]

Simple reaction conditions and recyclable reagents are crucial for environmentally friendly industrial applications. An environment-friendly, recyclable and economic strategy was developed to synthesize diaryl chalcogenides by the CuCl2-catalyzed C–S bond-formation reaction via iodobenzenes and benzenethiols/1,2-diphenyldisulfanes using N , N ′-dimethylethane-1,2-diamine (DMEDA) as ligand, base, and solvent. For these reactions, especially the reactions of diiodobenzenes and aminobenzenethiols/disulfanediyldianilines, a range of substrates are compatible and give the corresponding products in good to excellent yields. Both of the reagents in the catalytic system (CuCl2 /DMEDA) are inexpensive, conveniently separable, and recyclable for more than five cycles. [ABSTRACT FROM AUTHOR]

MicroRNA-21 was upexpressed in gastric cancer (GC) indicating that it is a potential diagnostic biomarker for GC. In this study, 50 GC patients and 50 healthy controls were recruited. miR-21 levels in serum and peripheral blood mononuclear cells (PBMCs) were quantified using quantitative real-time PCR. CA199, and CEA were measured using electrochemiluminescence assay. The sensitivity and specificity of circulating miR-21, CA199 and CEA in GC diagnosis, the correlation of circulating miR-21 to clinicopathological features, and the diagnostic value of miR-21 in different GC stages were determined. The levels of miR-21 in both serum and PBMCs increased significantly in GC patients comparing to healthy controls; however, no correlation was observed between circulating miR-21 level and clinicopathological features. The sensitivity and specificity of miR-21 in serum and PBMCs, and CA199 and CEA in GC diagnosis were 88.4%, 79.6%, 81.3%, 73.4%, 60.5%, 55.9%, and 68.6%, 59.3%, respectively. The positive prediction rates of circulating miR-21 in GC stages I to IV were all around 90%, while those of CA199 and CEA were around or less than 50%. Our data suggest circulating miR-21 (both in serum and in PBMCs) can serve as a good biomarker for GC and could be used in diagnosis of early (stage I) and late GC (stage IV). [ABSTRACT FROM AUTHOR]

Abstract: LRRC4 is not only a brain-specific gene, but it has also been identified as a tumor suppressor gene for glioma. Promoter methylation of LRRC4 is frequently involved in the inactivation in glioma. MiRNA-mediated gene regulation has recently been demonstrated to play an important role in multiple biological processes related to cancer, including glioma. In this study, we demonstrated that a small regulatory microRNA, hsa-miR-381, an “oncomir”, had a major role in glioma progression and that LRRC4 was a target of hsa-miR-381. By regulating LRRC4, hsa-miR-381 increased the in vitro and in vivo proliferation of glioma cells, and this action was associated with decreased inhibition of MEK/ERK and AKT signaling. Conversely, LRRC4, as a glioma suppressor, inhibited the endogenous expression of hsa-miR-381 and decreased cell proliferation and tumor growth. The interaction of hsa-miR-381 and LRRC4 is involved in the pathogenesis of glioma. In addition, the stable expression of hsa-miR-381 in blood provides a novel and promising diagnostic biomarker, and anti-hsa-miR-381 “antagomir” may be an ideal target for glioma therapy. [Copyright &y& Elsevier]

Glioblastoma (GBM) is the most lethal brain tumor due to the resistance to conventional therapies, such as radiotherapy and chemotherapy. TAZ, an important mediator of the Hippo pathway, was found to be up-regulated in diverse cancers, including in GBM, and plays important roles in tumor initiation and progression. However, little is known about the regulation of TAZ expression in tumors. In this study, we found that miR-125a-5p is an important regulator of TAZ in glioma cells by directly targeting the TAZ 3′ UTR. MiR-125a-5p levels are inversely correlated with that of TAZ in normal astrocytes and a panel of glioma cell lines. MiR-125a-5p represses the expression of TAZ target genes, including CTGF and survivin, and inhibits cell proliferation and induces the differentiation of GBM cells; whereas over-expression of TAZ rescues the effects of miR-125a-5p. This study revealed a mechanism for TAZ deregulation in glioma cells, and also demonstrated a tumor suppressor role of miR-125a-5p in glioblastoma cells. [ABSTRACT FROM AUTHOR]

Context: The sensitivity and specificity of blood microRNA-421 (miR-421) as a gastric cancer (GC) biomarker has not been determined. Objective: To investigate the diagnostic value of blood miR-421 as GC biomarker. Materials and methods: miR-421 in serum and peripheral blood mononuclear cells (PBMCs) of 90 GC patients and 90 controls was detected by quantitative real-time PCR. The correlation of miR-421 to GC clinicopathological features as well as the diagnostic value of miR-421 comparing to carcinoembryonic antigen (CEA) and cancer antigen 125 (CA-125) were analyzed. Results: miR-421 increased significantly in GC patients than in controls. miR-421 in either serum or PBMCs had higher sensitivity and specificity than CEA and CA-125 in GC diagnosis. The GC positive prediction rates of miR-421 were also significantly higher than those of CEA and CA-125. Discussion and conclusions: miR-421 in serum or PBMCs may be a new potential diagnostic biomarker for GC. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a common malignant gastrointestinal cancer. Efforts for preventive and personalized medicine have intensified in the last decade with attention to novel forms of biomarkers. In the present study, microRNA and genetic analyses were performed in tandem for differential transcriptome profiling between primary tumors with or without nodes or distant metastases. Serial Test Cluster (STC) analysis demonstrated that 20 genes and two microRNAs showed distinctive expression patterns associated with the tumor, node, and metastasis (TNM) stage. The selected target genes were characterized by GO and Pathway analysis. A microRNA-target gene network analysis showed that miR-429 resided in the center of the network, indicating that miR-429 might serve important roles in the development of CRC. Real-time PCR and tissue microarrays showed that miR-429 had a dynamic expression pattern during the CRC progression stage, and was significantly downregulated in stage II and stage III clinical progression. The low expression of miR-429 was correlated with poor prognosis for CRC. Taken together, miR-429 warrant further clinical translation research as a candidate biomarker for CRC prognosis. Additional downstream targets and attendant gene function also need to be discerned to design a sound critical path to personalized medicine for persons susceptible to, or diagnosed with CRC. [ABSTRACT FROM AUTHOR]

Abstract: POTE ankyrin domain family, member H (POTEH) belongs to POTE family, which expresses in many cancers. In this study, methylation status of POTEH promoter and its correlation with clinicopathological parameters were evaluated in glioma tissues and cells. Bisulfite sequencing PCR was carried out to investigate the promoter methylation status of POTEH in tumor of 96 glioma patients and glioma cells U251, SF767, and SF126. The effect of promoter hypomethylation on protein expression was evaluated by immunohistochemistry. POTEH was hypomethylated in 81.3% gliomas and none in normal brain tissues, and correlated significantly with its protein expression. But there was no remarkable relationship between sex, age, advanced tumor grade and POTEH hypomethylation. With the grade progressing, POTEH protein expression was enhanced. The correlation between POTEH hypomethylation, protein expression and overall survival was statistically significant. In POTEH hypomethylation group, patients with POTEH high expression had shorter overall survival than those with low expression. Hypomethylation of POTEH promoter in gliomas accounted for POTEH protein overexpression and poor outcome in a subset of patients. Detection of these epigenetic changes in tumors may provide information regarding prognosis. [Copyright &y& Elsevier]