Mouse Anti-Human IL-6 monoclonal Antibody, clone C21

Objective: Autophagy and apoptosis play key roles in cancer survival and pathogenesis and are governed by specific genes which have a dual role in both cell death and survival. Arsenic trioxide (ATO) and thalidomide (THAL) are used for treatment of many types of hematologic malignancies. ATO prevents the proliferation of cells and induces apoptosis in some cancer cells. Moreover, THAL has immunomodulatory and antiangiogenic effects in malignant cells. The aim of present study was to examine the effects of ATO and THAL on U937 and KG-1 cells, and evaluation of mRNA expression level of VEGFs genes, PI3K genes and some of autophagy genes. Materials and Methods: In this in vitro experimental study, U937 and KG-1 cells were treated by ATO (0.4-5 mu M) and THAL (5-100 mu M) for 24, 48 and 72 hours. Cell viability was measured by MTT assay. The apoptosis rate and cell cycle arrest were evaluated by flow cytometry (Annexin/PI) and cell cycle flow cytometry analysis, respectively. The effect of ATO/THAL on mRNAs expression was evaluated by real-time polymerase chain reaction (PCR). Results: ATO/THAL combination enhanced cell apoptosis in a dose-dependent manner. Also, ATO/THAL induced SubG1/G1 phase arrest. mRNA expression levels of VEGFC (contrary to other VEGFs isoform), PI3K, AKT, mTOR, MEK1, PTEN, IL6, LC3 and P62 genes were upregulated in acute myeloid leukemia (AML) cells following treatment with ATO/THAL. Conclusion: Combined treatment with ATO and THAL can inhibit proliferation and invasion of AML cells by down-regulating ULK1 and BECLINI and up-regulating PTEN and IL6, and this effect was more marked than the effects of ATO and THAL alone.

Aim:Given the immunosuppressive nature of pancreatic cancer, we investigated the relationship between epigenetic modification of immune-regulatory cytokine genes and pancreatic cancer outcomes.Materials & methods:We evaluated DNA methylation of 184 pancreatic tumor samples from The Cancer Genome Atlas for 111 CpG loci in seven cytokine genes:IL10,IL6,IL8,TGF beta 1,TGF beta 2,TGF beta 3andTNF. We used Cox regression to evaluate the associations between methylation and overall survival, disease-specific survival and disease progression (alpha = 0.05).Results:Poorer survival was associated with increased methylation in fifteen CpG probes inTGF beta 1,TGF beta 2,TGF beta 3andTNF. We also detected improved outcomes for three loci inIL10,IL8andIL6.Conclusion:Epigenetic regulation of cytokine-related gene expression may be associated with pancreatic cancer outcomes.