The exon 1 polymorphism (49A/G) of ctla-4 gene corresponds to an amino acid exchange (threonine to alanine) in the leader peptide of the expressed protein. There are reports concerning the higher level of G allele in subjects with various autoimmune diseases, which has resulted in the hypothesis that CTLA-4 may play a role in regulating self-tolerance by the immune system and in the pathogenesis of autoimmune disorders. This study was undertaken to investigate the correlation of exon 1 (49A/G) polymorphism in the ctla-4 gene and breast cancer. The ctla-4 49A/G polymorphism was studied in 197 women with primary breast cancer and 151 age/sex matched normal individuals. The results indicated a significant difference between frequency of ctla-4 genotypes in patients and controls. The frequency of GG genotype was significantly decreased in breast cancer patients compared to controls (4.6% v.s. 12.6%, P = 0.012). There was also a significant positive correlation between tumor size and the existence of AA genotype in patients (P = 0.016). In addition, a positive correlation between AA genotype and lymph node involvement was observed (P = 0.042). The observed decrease in the frequency of GG genotype in the breast cancer patients is contrary to the frequently reported increase of GG genotype in autoimmune diseases. In addition, the data implies that polymorphism of ctla-4 exon 1 contributes in tumor progression.

Immunotherapy with dendritic cells (DCs) that have been manipulated ex vivo to become immunogenic or tolerogenic, has been tested in clinical trials for disease therapy. DCs are sentinels of the immune system, which after exposure to antigenic or inflammatory signals and crosstalk with effector CD4+ T cells express high levels of costimulatory molecules and cytokines. Suppression of either costimulatory molecules or cytokines generates tolerogenic DCs (TDCs), which induce T regulatory cells (Tregs) and a state of tolerance. Nevertheless, DC vaccination is still at an early stage, and improvements are mainly needed in generating clinical-grade DC products and in quality control of monitoring assays to assess the effect of DC vaccination in future clinical trials. Here, we review the recent work in DC generation and monitoring approaches for DC-based trials with immunogenic or tolerogenic DCs.

In the present investigation, polyethylenimine (PEI) was conjugated with succinic anhydride at four substitution degrees and the efficiency of the modified PEI derivatives in transferring the plasmid encoding interleukin-12 gene was evaluated. The results revealed that the conjugated PEI derivatives enhanced the transfection efficiency by up to 3-fold relative to unmodified PEI, with the highest increase occurring at conjugation degrees around 30%. The results demonstrated the ability of the modified PEI derivatives in condensation of the plasmid into the nanoparticles in the size range of approximately 100 nm. Also, the PEI derivatives exhibited substantial decrease in cell-induced toxicity.

BackgroundSome Bacillus strains have recently been identified for potential use as probiotics and food additives. The present study evaluated the antimicrobial effects of Bacillus subtilis ATCC 6633 and its metabolite on the enterotoxin and vegetative cells, spore and germinated spore of Clostridium perfringens type A in Caco-2 cells.ResultsWe used flow cytometry and MTT assays to evaluate the cytotoxicity effect of treatments. According to the results, the most cell survival was found in the 4% crude antimicrobial substance (CAS) with the vegetative form of C. perfringens among co-cultured groups. Furthermore, the apoptosis and necrosis in co-cultured groups were significantly decreased (P < 0.05).ConclusionThe present results suggested the crucial role of the current probiotic in the control of various forms of C. perfringens type A which was investigated for the first time. Also, the majority of treatments showed higher cell viability in flow cytometry compared to the MTT assay.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-017-1051-1) contains supplementary material, which is available to authorized users.