ADENO p53 GENE TRANSFER IN A PHASE I/II TRIAL OF PATIENTS WITH ADVANCED RECURRENT HEAD AND NECK SQUAMOUS CARCINOMA

p21Waf1/Cip1 protects against p53-mediated apoptosis of human melanoma cells

“…These di erences may be attributed, at least in part, to the di erential expression of p21 Waf1/Cip1 . Similar opposing e ects of p53 overexpression have been described in other systems where rapidly growing cancerous cells generally undergo death in response to chemotherapeutic agents, while normal (untransformed) cells survive the treatment (Hainaut, 1995;Drazan et al, 1994;Clayman et al, 1995). Important questions remain concerning why elevated p53 results in increased p21 Waf1/Cip1 expression in certain cell types, while failing to do so in others.…”

Wild-type p53 gene transfer is not detrimental to normal cells in vivo: implications for tumor gene therapy

“…In the absence of vectors that specifically target tumor cells, to bypass potential problems of toxicity due to gene transfer into normal cells, these trials have adopted different routes of intratumor delivery of the p53-carrying vectors. Surprisingly, even the vast majority of the basic and preclinical studies centered on replacement of p53 or other oncosuppressor genes have focused on the effects on cancer cells, while the response of normal cells has been rarely assessed, mostly by using in vitro cultured fibroblasts (Wills et al, 1994;Clayman et al, 1995;Zhang et al, 1995). Thus, no clear data on p53 toxicity in normal cells in vivo are available.…”