The rs1131878C bigger than T polymorphism (NT_016354.20: g.10558805C bigger than T) in UGT2B4 was associated with an increased pancreatic cancer risk. Compared to the C/C genotype, the C/T genotype conferred 1.39 times higher the pancreatic cancer risk (95% CI = 1.09-1.77; P = 0.007), and the T/T genotype conferred 2.97 times higher the pancreatic cancer risk (95% CI = 1.24-7.08; P = 0.014). In contrast, compared with the A/A genotype, the A/C genotype at the rs3822179 locus Selleck APR-246 in UGT2B4 (NT_016354.20: g.10569096C bigger than A) bestowed a 20% risk reduction
(OR = 0.80, 95% CI = 0.67-0.95; P = 0.011). However, the risk was not significantly AZD8186 concentration reduced with the C/C genotype (OR = 0.77, 95% CI = 0.52-1.14, P = 0.191). Polymorphisms in UGT2B4 affect the risk of pancreatic cancer occurrence in Han Chinese individuals.”
“Ceramides are known to be key players in intracellular signaling and are involved in apoptosis, cell senescence, proliferation, cell growth and differentiation. They are synthesized by ceramide synthases
(CerS). So far, six different mammalian CerS (CerS1-6) have been described. Recently, we demonstrated that human breast cancer tissue displays increased activity of CerS2, 4, and 6, together with enhanced generation of their products, ceramides C-16:0, C-24:0, and C-24:1. Moreover, these increases were significantly associated with tumor dignity. To clarify the impact of this observation, we manipulated cellular ceramide levels by overexpressing C188-9 clinical trial ceramide synthases 2, 4 or 6 in MCF-7 (breast cancer) and HCT-116 (colon cancer) cells, respectively. Overexpression of ceramide synthases 4 and 6 elevated generation of short chain ceramides C-16:0, C-18:0 and C-20:0, while overexpression of ceramide synthase 2 had no
effect on ceramide production in vivo, presumably due to limited substrate availability, because external addition of very long chain acyl-CoAs resulted in a significant upregulation of very long chain ceramides. We also demonstrated that upregulation of CerS4 and 6 led to the inhibition of cell proliferation and induction of apoptosis, whereas upregulation of CerS2 increased cell proliferation. On the basis of our data, we propose that a disequilibrium between ceramides of various chain length is crucial for cancer progression, while normal cells require an equilibrium between very long and long chain ceramides for normal physiology. (C) 2012 Elsevier Ltd. All rights reserved.”
“The immunogenic heat shock proteins (HSPs) gp96, hsp70 and calreticulin (CRT) bind to CD91 on antigen-presenting cells (APCs) for cross-presentation of the HSP-chaperoned peptides. This event leads to priming of T-cell responses.