Antisense oligonucleotides targeting human telomerase mRNA increases the radiosensitivity of nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma (NPC) is associated with a high incidence rate in South China and is predominantly treated with radiotherapy; however, the survival rate remains low. The therapeutic effects of radiation and chemotherapy may be enhanced when combined with anti­sense oligonucleotides targeting human telomerase RNA (hTR ASODN). However, the influence of hTR ASODN on the anti­tumor effects of radiation in NPC remain unknown. The present study investigated the effects of hTR ASODN on the proliferation and radiosensitivity of NPC cells, and further explored the underlying mechanisms. hTR ASODN significantly inhibited the proliferation and decreased the telomere length of CNE­2 human NPC cells. Furthermore, combined treatment of hTR ASODN with radiation significantly enhanced anti­tumor efficacy. The apoptotic rate and cleavage of caspase 9 were increased in the cells treated with the combined therapy, as compared with the cells treated with hTR ASODN or radiotherapy alone. In conclusion, these results suggest that hTR ASODN may inhibit the proliferation of NPC cells and enhance the anti­tumor effects of radiation by inducing cell apoptosis. Therefore hTR ASODN may be a potential adjuvant agent for the treatment of NPC combined with radiation therapy, and these findings are of translational importance.

Evidence for a novel late-onset Alzheimer disease locus on chromosome 19p13.2.

Late-onset familial Alzheimer disease (LOFAD) is a genetically heterogeneous and complex disease for which only one locus, APOE, has been definitively identified. Difficulties in identifying additional loci are likely to stem from inadequate linkage analysis methods. Nonparametric methods suffer from low power because of limited use of the data, and traditional parametric methods suffer from limitations in the complexity of the genetic model that can be feasibly used in analysis. Alternative methods that have recently been developed include Bayesian Markov chain-Monte Carlo methods. These methods allow multipoint linkage analysis under oligogenic trait models in pedigrees of arbitrary size; at the same time, they allow for inclusion of covariates in the analysis. We applied this approach to an analysis of LOFAD on five chromosomes with previous reports of linkage. We identified strong evidence of a second LOFAD gene on chromosome 19p13.2, which is distinct from APOE on 19q. We also obtained weak evidence of linkage to chromosome 10 at the same location as a previous report of linkage but found no evidence for linkage of LOFAD age-at-onset loci to chromosomes 9, 12, or 21.