Today's Hours: 8:00am - 10:00pm
Lane Medical Library

Search

Filter Applied Clear All

Filter Results

Did You Mean:

Search Results

Sort by
relevance
  • Article
    Givechian KB, Garner C, Garban H, Rabizadeh S, Soon-Shiong P.
    Oncotarget. 2018 Jul 03;9(51):29743-29752.
    Somatic mutations in DNA repair genes have been clinically associated with chemosensitivity, although few studies have interrogated the nucleotide synthesis pathways that supply DNA repair processes. Previous work suggests that bladder urothelial carcinoma is uniquely enriched for mutations in nucleotide excision repair genes, and that these mutations are associated with response to platinum-based therapy and favorable survival. Conversely, the de novo pyrimidine synthesis pathway has recently emerged as a putative clinical target. This anabolic process is thought to supply DNA repair processes such as nucleotide excision repair; that is, DNA repair enzymes may require a sufficient nucleotide supply available to reverse the intended genotoxic damage of systemic chemotherapy in rapidly proliferating cancer cells. Therefore, we explored the prognostic complementarity between de novo pyrimidine synthesis and nucleotide excision repair expression in a total of 570 bladder urothelial carcinoma patients. Ultimately, we show that the de novo pyrimidine synthesis gene CAD is associated with poor survival (P = 0.008) and is co-altered with the nucleotide excision repair gene POLD2. High expression of POLD2 was also associated with poor overall survival (P = 0.019) and was significantly correlated with CAD expression in pre-treatment patient tumor samples (P = 2.44e-4). Expression of each gene was associated with cisplatin-based therapy resistance, and accordingly, CADhighPOLD2high patients were associated with worse survival than CADhighPOLD2low and CADlowPOLD2high patients. Together, these biomarkers could help elucidate mechanisms of chemoresistance to further personalize therapeutic strategies in bladder urothelial carcinoma.
    Digital Access Access Options
  • Article
    Döppler H, Bastea L, Borges S, Geiger X, Storz P.
    Oncotarget. 2015 Oct 06;6(30):29740-52.
    Vasodilator-stimulated phosphoprotein (VASP) signaling is critical for dynamic actin reorganization processes that define the motile phenotype of cells. Here we show that VASP is generally highly expressed in normal breast tissue and breast cancer. We also show that the phosphorylation status of VASP at S322 can be predictive for breast cancer progression to an aggressive phenotype. Our data indicate that phosphorylation at S322 is gradually decreased from normal breast to DCIS, luminal/ER+, HER2+ and basal-like/TN phenotypes. Similarly, the expression levels of PKD2, the kinase that phosphorylates VASP at this site, are decreased in invasive ductal carcinoma samples of all three groups. Overall, the phosphorylation status of this residue may serve as an indicator of aggressiveness of breast tumors.
    Digital Access Access Options