Ubiquitination is a post-translational modification that plays a role in several cellular processes including cell cycle progression, cell proliferation, DNA replication and apoptosis. Ubiquitin-mediated signaling is frequently altered in cancer cells. Several tumor suppressors and oncogenes interact with enzymes of the ubiquitin-proteasome pathway that function in ubiquitin conjugation and deconjugation. Increasing evidence indicates that the ubiquitin-proteasome system (UPS) plays an important role in cancer development. Several small molecule inhibitors of the UPS have been applied to the treatment of cancer. The current review focuses on the role of the UPS in cancer development and the development of UPS inhibitors for cancer treatment.

Abnormal folate metabolism and common variants of folate-metabolizing enzymes have been described as possible risk factors for congenital heart disease (CHD). Two important folate-metabolizing enzymes involved in the folate/homocysteine metabolic pathway are 5,10-methylenetetrahydrofolate reductase (MTHFR) and methylenetetrahydrofolate dehydrogenase 1 (MTHFD1). and polymorphisms may be associated with CHD susceptibility. To evaluate the impact of and single-nucleotide polymorphisms (SNPs) on CHD susceptibility, we genotyped functional SNPs rs1801133 C>T, rs1801131 A>C and rs2274976 G>A, and SNPs rs2236225 C>T, rs1950902 G>A and rs1076991 A>G in a hospital-based case-control study of 173 tetralogy of Fallot (TOF) cases and 207 non-CHD controls. When rs1801133 CC homozygote genotype was used as the reference group, the TT genotype was associated with a significantly increased risk for TOF [TT vs. CC: odds ratio (OR)=1.67; 95% confidence interval (CI): 1.01-2.75; P=0.046]. In the recessive model, when rs1801133 CC/CT genotype was used as the reference group, the TT homozygote genotype was associated with a significantly increased risk for TOF (OR=1.81, 95% CI: 1.15-2.84; P=0.010). In conclusion, our findings suggest that rs1801133 C>T polymorphism may play a role in susceptibility for TOF. Large-scale studies with a more rigorous study design including diverse ethnic populations are required to confirm these findings.

Purpose: To investigate the prognostic implications of plasma fibrinogen and serum C-reactive protein (CRP) levels in tumour resection and survival following successful tumour resection in patients with nonsmall cell lung cancer (NSCLC

Cisplatin-based chemotherapy is considered a golden standard for treatment of advanced non-small cell lung cancer (NSCLC). However, drug resistance is one of the major problems in NSCLC chemotherapy. The mechanisms and related biological pathways that contribute to chemoresistance are relatively poorly understood. Here, we demonstrated that the phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) suppresses cisplatin-induced A549 cell apoptosis. Cisplatin induced eIF2α phosphorylation through protein kinase RNA. Importantly, phospho-eIF2α inhibited cisplatin-induced A549 cells apoptosis, at least in part, by suppressing the p38 pathway. Moreover, analysis of tissue microarrays information demonstrated that phospho-eIF2α predicted a poor prognosis in patients with NSCLC. Taken together, these results provide a potential mechanism that is used for explaining how eIF2α promotes cisplatin resistance in A549 cells. Therefore, the regulation of eIF2α may improve treatment outcomes of cisplatin-based chemotherapy for patients with NSCLC.