Our findings suggest that elevated Δ133p53β is an alternative pathway to TP53 mutation in glioblastoma that aids tumor progression by promoting an immunosuppressive and chemoresistant environment.
We analyzed the extent and cell type specificity of p53 accumulation in subcortical white matter of ten AIDS patients that had previously been shown to demonstrate white matter p53 accumulation.
Act D treatment of AIDS-KS cells markedly and selectively down-regulated Bcl-xL expression, while the expressions of decoy receptors 1 and 2, Bax, cellular FLICE (Fas-associated death domain protein-like IL-1-converting enzyme) inhibitory protein, FADD (Fas-associated death domain protein), procaspase 8, and p53 were not affected.
Several studies have shown that AIDS-SNCCL is associated with the clonal accumulation of multiple genetic lesions, including Epstein-Barr virus (EBV) infection, activation of the c-MYC and RAS oncogenes, as well as inactivation of the p53 tumor suppressor gene at variable frequencies.
Thus, the present study was designed to investigate the presence of HPV and p53 gene mutations in 17 formalin-fixed, paraffin-embedded KS [7 acquired immunodeficiency syndrome-KS (AIDS-KS) and 10 classic KS] specimens.
These lesions are not uniformly distributed, but, rather, cluster with specific types of AIDS-NHL: EBV infection is preferentially associated with LC-IBPL (4/4; 100%), while it is present in only a fraction of SNCCL (5/16; 31.2%) and LNCCL (1/4; 25%); c-myc oncogene activation clusters with SNCCL (16/16; 100%), whereas it is less frequent in LC-IBPL (1/4; 25%) and LNCCL (2/4; 50%); p53 inactivation is restricted to SNCCL (10/16; 62.5%) and consistently associated with c-myc activation.