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A series of thiazolo[5,4- d ]pyrimidine derivatives were designed through the atom replacement strategy based on biologically validated scaffolds and then evaluated for their antiproliferative activities on cancer cell lines. The structure-activity relationship studies were conducted, leading to the identification of compound 22 , which exhibited good antiproliferative activity against HGC-27 with an IC 50 value of 1.22 μM and low toxicity against GES-1 cells. Mechanistic studies showed that compound 22 inhibited the colony formation and migration of HGC-27 as well as induced apoptosis. The western blot experiments proved that compound 22 up-regulated expression of Bax, down-regulated expression levels of Bcl-2 and cleaved caspased-3/9. These findings indicate that compound 22 may serve as a template for designing new agents for the treatment of human gastric cancers. The atom replacement strategy could be viable strategy for designing new anticancer drugs and may find its applications in drug design. [ABSTRACT FROM AUTHOR]

Objective: MicroRNAs (miRNAs) are small noncoding RNA molecules that participate in vital cell processes such as proliferation, apoptosis, and differentiation. In recent years, they have been proven to play vital roles in haematological malignancies. In this review we briefly introduce some basic knowledge of microRNAs and summarize their ectopic expression in haematological malignancies, especially in leukaemia. We will also discuss the potential of microRNAs in the diagnosis of leukaemia, in the determination of the clinical prognosis of diverse subtypes, and in targeted therapy. Discussion: Despite current adoption of novel biological agents combining traditional chemotherapy regimens, leukaemia remains to have undesirable clinical outcomes due to inaccurate diagnosis, invasiveness of the disease, and patients' intolerance to chemotherapy, thus brand new therapeutic directions are urgently needed. MiRNAs regulate gene expression by means of binding to the 3'- untranslated regions of corresponding mRNAs, leading to the degradation of targeted mRNA or the inhibition of translation. It has been confirmed that they can either function as tumour inhibitors, or may trigger tumourigenesis in certain situations, this specific dual characteristic undoubtedly attract scientists to explore their roles in haematological malignancies. It is of great necessity to summarize the roles of miRNAs in haematological malignancies diagnosis, prognosis evaluation, and clinical treatment. Conclusions: Future studies may take full advantage of miRNAs detection in diagnosing, in choosing targeted biological therapy, and in avoiding predictable side effect, thus the overall survival rate and cure efficiency of leukaemia should improve. [ABSTRACT FROM AUTHOR]

A new series of 6-chloro-2-(propylthio)-8,9-dihydro-7H-purine-8-caboxamide derivatives were designed, synthesized, and further evaluated for their antiproliferative activities on four human cancer cell lines (A549, MGC803, PC-3 and TE-1). The structure-activity relationships (SARs) studies were conducted through the variation in the two regions, which including position 8 and 9, of purine core. One of the compounds, 8 , containing a terminal piperazine appendage with a carboxamide moiety at position 8 and phenyl group at position 9 of 6-chloro-8,9-dihydro-7H-purine core, showed the most potent antiproliferative activity and good selectivity between cancer and normal cells (IC 50 values of 2.80 μM against A549 and 303.03 μM against GES-1, respectively). In addition, compound 8 could inhibit the colony formation and migration of A549 cells in a concentration-dependent manner, as well as induce the apoptosis possibly through the intrinsic pathway. [ABSTRACT FROM AUTHOR]

Introduction Pre-eclampsia (PE) can endanger the survival of the mother and fetus. Currently, the pathogenesis of PE is not completely understood and no fundamental therapeutics are available. The present study was performed to determine the function of miR-128a in HTR-8/SVneo trophoblast cells and to ascertain its underlying role in the pathogenesis of PE. Methods We investigated the function of miR-128a in HTR-8/SVneo cells by overexpressing. We analyzed the apoptosis of HTR-8/SVneo cells by performing apoptosis assays and measured the loss of mitochondrial membrane potential (Δym), the generation of reactive oxygen species (ROS) and caspase activity. In addition, miR-128a target genes were predicted. Results Using computer-based programs, we identified Bax as a direct target of miR-128a. In the apoptosis assays of HTR-8/SVneo cells, miR-128a decreased the Δψm, depleted ATP levels and increased ROS generation, cytochrome c release as well as caspase activation. Further studies showed that miR-128a induced the apoptosis of HTR-8/SVneo cells by down-regulating Bax through the mitochondrial apoptosis pathway. Conclusions miR-128a is an up-regulated miRNA in patient with PE. Our study demonstrated that the miR-128a-induced apoptosis of HTR-8/SVneo cells may contribute to PE and miR-128a may be a novel potential therapeutic target for PE. [ABSTRACT FROM AUTHOR]