17 research outputs found
Aspirin-induced nuclear translocation of NFκB and apoptosis in colorectal cancer is independent of p53 status and DNA mismatch repair proficiency
Substantial evidence indicates nonsteroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer (CRC). However, the molecular basis for this anti-tumour activity has not been fully elucidated. We previously reported that aspirin induces signal-specific IκBα degradation followed by NFκB nuclear translocation in CRC cells, and that this mechanism contributes substantially to aspirin-induced apoptosis. We have also reported the relative specificity of this aspirin-induced NFκB-dependent apoptotic effect for CRC cells, in comparison to other cancer cell types. It is now important to establish whether there is heterogeneity within CRC, with respect to the effects of aspirin on the NFκB pathway and apoptosis. p53 signalling and DNA mismatch repair (MMR) are known to be deranged in CRC and have been reported as potential molecular targets for the anti-tumour activity of NSAIDs. Furthermore, both p53 and MMR dysfunction have been shown to confer resistance to chemotherapeutic agents. Here, we set out to determine the p53 and hMLH1 dependency of the effects of aspirin on NFκB signalling and apoptosis in CRC. We specifically compared the effects of aspirin treatment on cell viability, apoptosis and NFκB signalling in an HCT-116 CRC cell line with the p53 gene homozygously disrupted (HCT-116p53−/−) and an HCT-116 cell line rendered MMR proficient by chromosomal transfer (HCT-116+ch3), to the parental HCT-116 CRC cell line. We found that aspirin treatment induced apoptosis following IκBα degradation, NFκB nuclear translocation and repression of NFκB-driven transcription, irrespective of p53 and DNA MMR status. These findings are relevant for design of both novel chemopreventative agents and chemoprevention trials in CRC
Structures, physico-chemical properties, production and (potential) applications of sucrose-derived α-d-glucans synthesized by glucansucrases
Glycoside hydrolase family 70 (GH70) glucansucrases produce α-d-glucan polysaccharides (e.g. dextran), which have different linkage composition, branching degree and size distribution, and hold potential applications in food, cosmetic and medicine industry. In addition, GH70 branching sucrases add single α-(1→2) or α-(1→3) branches onto dextran, resulting in highly branched polysaccharides with "comb-like" structure. The physico-chemical properties of these α-d-glucans are highly influenced by their linkage compositions, branching degrees and sizes. Among these α-d-glucans, dextran is commercially applied as plasma expander and separation matrix based on extensive studies of its structure and physico-chemical properties. However, such detailed information is lacking for the other type of α-d-glucans. Aiming to stimulate the application of α-d-glucans produced by glucansucrases, we present an overview of the structures, production, physico-chemical properties and (potential) applications of these sucrose-derived α-d-glucan polysaccharides. We also discuss bottlenecks and future perspectives for the application of these α-d-glucan polysaccharides
Common Variant in Myocilin Gene Is Associated with High Myopia in Isolated Population of Korčula Island, Croatia
Aim To study the association between genetic variants in
myocilin and collagen type I alpha 1 genes and high myopia
in an isolated island population.
Methods A total of 944 examinees from the genetic epidemiology
study conducted on the island of Korčula, Croatia,
were included in the study. We selected 2 short nucleotide
polymorphisms (SNP) available in our genome-wide
scan set of SNPs that were previously associated with high
myopia and used them to replicate previous claims of possible
association.
Results Nineteen cases of high myopia, defined as the refraction
of ≤-6.00 diopters, were identified and included
in the analysis. We showed that rs2075555 in the COL1A1
gene was not associated with high myopia. In contrast,
rs2421853 in the myocilin gene was significantly associated
in both bivariate (P = 0.006) and age- and sex-adjusted
analysis (P = 0.049).
Conclusion Myocilin seems to be a very strong candidate
for explaining some of the pathophysiological pathways
leading to the development of both glaucoma and high
myopia. As our finding was obtained in a relatively underpowered
sample, further research and replication of these
results is needed