IKK-alpha/beta ELISA Kit

We found that regular use of aspirin may reduce the risk of Hodgkin lymphoma (HL), a common cancer of adolescents and young adults in the United States. To explore possible biological mechanisms underlying this association, we investigated whether polymorphic variation in genes involved in nuclear factor-kappa B (NF-kappa B) activation and inhibition, other inflammatory pathways, and aspirin metabolism influences HL risk. Twenty single nucleotide polymorphisms (SNP) in seven genes were genotyped in DNA from 473 classical HL cases and 373 controls enrolled between 1997 and 2000 in a population-based case-control study in the Boston, Massachusetts, metropolitan area and the state of Connecticut. We selected target genes and SNPs primarily using a candidate-SNP approach and estimated haplotypes using the expectation-maximization algorithm. We used multivariable logistic regression to estimate odds ratios (OR) for associations with HL risk. HL risk was significantly associated with rs1585215 in NFKB1 (AG versus AA: OR, 2.1; 95% confidence interval, 1.5-2.9; GG versus AA: OR, 3.5; 95% confidence interval, 2.2-5.7, P(trend) 1.7 X 10(-8)) and with NFKB1 haplotypes (P(global) = 6.0 X 10(-21)). Similar associations were apparent across categories of age, sex, tumor EBV status, tumor histology, and regular aspirin use, although statistical power was limited for stratified analyses. Nominally significant associations with HL risk were detected for SNPs in NFKBIA and CYP2C9. HL risk was not associated with SNPs in IKKA/CHUK, PTGS2/COX2, UDP1A6, or LTC4S. In conclusion, genetic variation in the NF-kappa B pathway seems to influence risk of HL. Pooled studies are needed to detect any heterogeneity in the association with NF-kappa B across HL subgroups, including aspirin users and nonusers. (Cancer Epidemiol Biomarkers Prev 2009;18(3):976-86)

CD176 (Thomsen-Friedenreich antigen) is a tumor-associated carbohydrate structure. In a previous study, we observed that the anti-CD176 antibody can induce the apoptosis of CD176-positive leukemic cells. In this study, we investigated the mechanisms of apoptosis induced by the CD176 antibody. We found that CD95 (FAS, APO-1) and the death receptor 4 (DR4) (TRAIL-R1) are co-expressed with CD176 on the surface of defined leukemic cells as observed by confocal microscopy and flow cytometry analyses. Furthermore, CD95, CD45, CD43 and DR4 are carrier proteins of CD176 in hematopoietic cells recognized by means of sandwich solid-phase enzyme linked irnmunosorbent assay and co-immunoprecipitation. As shown by microarray analysis, 20 genes which are directly related to the execution, induction or positive regulation of apoptosis, were up-regulated after CD176 antibody treatment of the KG1 cell line. Nine differentially expressed genes observed in the microarray analysis were verified by quantitative real-time polymerase chain reaction in the KG1 and MT4 cell lines. Six genes (DAXX, CASP3, CHUK, RIPK2, NFKBIA and DFFA) out of these nine are involved in five apoptotic pathways: The CD95 signaling pathway, the DR3 and DR4/5 death receptor pathway, caspase cascade in apoptosis, the mitochondrial signaling pathway, and apoptotic DNA fragmentation and tissue homeostasis. Thus, we hypothesized that the CD176 antibody binds to the CD176 carbohydrate structure present on apoptosis-associated glycoproteins, such as CD95 and DR4 at the cellular surface, which activates apoptotic pathways, and consequently results in the apoptosis of CD176-positive cells. CD176 is expressed at the surface of human leukemic cells, but is almost absent in normal and benign adult human tissues. Thus, CD176 could be a promising target for anti-tumor therapy based on the induction of tumor-specific apoptosis.