In vitro and in vivo activity of the nuclear factor-kappaB inhibitor sulfasalazine in human glioblastomas.

Glioblastomas, the most common primary brain cancers, respond poorly to current treatment modalities and carry a dismal prognosis. In this study, we demonstrated that the transcription factor nuclear factor (NF)-kappaB is constitutively activated in glioblastoma surgical samples, primary cultures, and cell lines and promotes their growth and survival. Sulfasalazine, an anti-inflammatory drug that specifically inhibits the activation of NF-kappaB, blocked the cell cycle and induced apoptosis in several glioblastoma cell lines and primary cultures, as did gene therapy with a vector encoding a super-repressor of NF-kappaB. In vivo, sulfasalazine also significantly inhibited the growth of experimental human glioblastomas in nude mice brains. Given the documented safety of sulfasalazine in humans, these results may lead the way to a new class of glioma treatment.

Role of p53 in the sensitization of tumor cells to apoptotic cell death.

Immunotherapy of cancer has always represented a very attractive fourth-modality therapeutic approach. Over the past few years, advances in the identification of tumor antigens have opened new perspectives and provided new opportunities for a more accurate immunotherapy of cancer. However, when applied to patients with established tumors, it rarely leads to an objective response. This is in part due to the fact that tumors evade host immunity at both the induction and effector phases. In this regard, several different functional defects in T-lymphocytes that infiltrate cancers have been reported. Indeed, lymphocytes of patients with advanced malignancies are hyporeactive and functionally compromised. Furthermore, it has become clear that immunotherapeutic and gene therapeutic approaches aimed at the induction of anti-tumor cytotoxic responses should consider the resistance of tumor cells to cytotoxic mechanisms. Thus, understanding of tumor escape mechanisms may be the key to a successful immunotherapy for cancer. How tumors escape immunological destruction following the acquisition of resistance to cell death and the potential role the tumor suppressor p53 protein in immunosensitization of tumor cells will be discussed.