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Articles by G. L Delclos
Total Records ( 3 ) for G. L Delclos
  M Chen , A Cassidy , J Gu , G. L Delclos , F Zhen , H Yang , M. A.T Hildebrandt , J Lin , Y Ye , R. M Chamberlain , C. P Dinney and X. Wu
 

Genetic variations in phosphoinositide-3 kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathway may affect critical cellular functions and increase an individual's cancer risk. We systematically evaluate 231 single-nucleotide polymorphisms (SNPs) in 19 genes in the PI3K-AKT-mTOR signaling pathway as predictors of bladder cancer risk. In individual SNP analysis, four SNPs in regulatory associated protein of mTOR (RAPTOR) remained significant after correcting for multiple testing: rs11653499 [odds ratio (OR): 1.79, 95% confidence interval (CI): 1.24–2.60, P = 0.002], rs7211818 (OR: 2.13, 95% CI: 1.35–3.36, P = 0.001), rs7212142 (OR: 1.57, 95% CI: 1.19–2.07, P = 0.002) and rs9674559 (OR: 2.05, 95% CI: 1.31–3.21, P = 0.002), among which rs7211818 and rs9674559 are within the same haplotype block. In haplotype analysis, compared with the most common haplotypes, haplotype containing the rs7212142 wild-type allele showed a protective effect of bladder cancer (OR: 0.83, 95% CI: 0.70–0.97). In contrast, the haplotype containing the rs7211818 variant allele showed a 1.32-fold elevated bladder cancer risk (95% CI: 1.09–1.60). In combined analysis of three independent significant RAPTOR SNPs (rs11653499, rs7211818 and rs7212142), a significant trend was observed for increased risk with an increase in the number of unfavorable genotypes (P for trend <0.001). Compared with the subjects without any of the unfavorable genotypes, those carrying all three unfavorable genotypes showed a 2.22-fold (95% CI: 1.33–3.71) increased bladder cancer risk. This is the first study to evaluate the role of germ line genetic variations in PI3K-AKT-mTOR pathway as cancer susceptibility factors that will help us identify high-risk individuals for bladder cancer.

  M Chen , J Gu , G. L Delclos , A. M Killary , Z Fan , M. A. T Hildebrandt , R. M Chamberlain , H. B Grossman , C. P Dinney and X. Wu
 

The phosphoinositide-3 kinase (PI3K)–AKT– mammalian target of rapamycin (mTOR) pathway is an important cellular pathway controlling cell growth, tumorigenesis, cell invasion and drug response. We hypothesized that genetic variations in the PI3K–AKT–mTOR pathway may affect the survival in muscle invasive and metastatic bladder cancer (MiM-BC) patients. We conducted a follow-up study of 319 MiM-BC patients to systematically evaluate 289 single-nucleotide polymorphisms (SNPs) of 20 genes in the PI3K–AKT–mTOR pathway as predicators of survival. In multivariate Cox regression, AKT2 rs3730050, PIK3R1 rs10515074 and RAPTOR rs9906827 were significantly associated with survival. In combined analysis, we found a cumulative effect of these three SNPs on survival. With the increasing number of unfavorable genotypes, there was a significant trend of higher risk of death in multivariate Cox regression (P for trend <0.001) and shorter median survival time in Kaplan–Meier estimates (P log rank <0.001). This is the first study to evaluate the role of germ line genetic variations in the PI3K–AKT–mTOR pathway genes as predictors of MiM-BC clinical outcomes. These findings warrant further replication in independent populations and may provide information on disease management and development of target therapies.

 
 
 
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