Faculty Bibliography

Primary spinal primitive neuroectodermal tumors (PNETs) are uncommon malignancies that are increasingly reported in the literature. Spinal PNETs, like their cranial counterparts, are aggressive tumors and patients with these tumors typically have short survival times despite maximal surgery, chemotherapy, and radiation. Because no standard management guidelines exist for treating these tumors, a multitude of therapeutic strategies have been employed with varying success. In this study the authors perform a comprehensive review of the literature on primary spinal PNETs and provide 2 new cases that highlight the salient features of their clinical management.

Chronic pelvic pain syndrome (CPPS) is a common condition that is encountered by a variety of healthcare professionals. Unfortunately, physicians often misdiagnose this problem or recommend inappropriate and sometimes dangerous treatments that offer little hope of successful outcome. In addition, CPPS is typically a multifaceted disorder, simultaneously compromising psychological, peripheral nerve, autonomic, central nervous, visceral, connective tissue, hormonal and other systems. Thus, solo practitioners who may correctly diagnose CPSS are often ill-equipped to provide adequate comprehensive, multidisciplinary treatment. This article is intended as an overview of the most recent literature in support of various treatment modalities for chronic pelvic pain in men and women. We advocate a team-oriented approach in the treatment of CPPS, which employs the coordinated efforts of multiple practitioners, ideally in a subspecialty care setting.

We have shown that a COOH-terminal peptide of p53 (amino acids 361-382, p53p), linked to the truncated homeobox domain of Antennapedia (Ant) as a carrier for transduction, induced rapid apoptosis in human premalignant and malignant cell lines. Here, we report that human and rat glioma lines containing endogenous mutant p53 or wild-type (WT) p53 were induced into apoptosis by exposure to this peptide called p53p-Ant. The peptide was comparatively nontoxic to proliferating nonmalignant human and rat glial cell lines containing WT p53 and proliferating normal human peripheral marrow blood stem cells. Degree of sensitivity to the peptide correlated directly with the level of endogenous p53 expression and mutant p53 conformation. Apoptosis induction by p53p-Ant was quantitated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay and Annexin V staining in human glioma cells in vitro and in a syngeneic orthotopic 9L glioma rat model using convection-enhanced delivery in vivo. The mechanism of cell death by this peptide was solely through the Fas extrinsic apoptotic pathway. p53p-Ant induced a 3-fold increase in extracellular membrane Fas expression in glioma cells but no significant increase in nonmalignant glial cells. These data suggest that p53 function for inducing Fas-mediated apoptosis in gliomas, which express sufficient quantities of endogenous mutant or WT p53, may be restored or activated, respectively, by a cell-permeable peptide derived from the p53 COOH-terminal regulatory domain (p53p-Ant). p53p-Ant may serve as a prototypic model for the development of new anticancer agents with unique selectivity for glioma cancer cells and it can be successfully delivered in vivo into a brain tumor by a convection-enhanced delivery system, which circumvents the blood-brain barrier.