Extended disease-free interval of 6 years in a recurrent glioblastoma multiforme patient treated with G207 oncolytic viral therapy.

Background: Glioblastoma multiforme (GBM) is a relentless primary central nervous system malignancy that remains resistant to conventional therapy despite major advances in clinical neurooncology. This report details the case of a patient who had failed conventional treatment for recurrent GBM and was ultimately treated with a genetically engineered herpes simplex virus (HSV) type 1 vector, G207.

Methods: Case report detailing the outcomes of one patient enrolled into the gene therapy arm of the Neurovir G207 protocol whereby stereotactic injection of 120 µL G207 viral suspension containing 1×10(7) plaque-forming units (or active viral particles) was made into the enhancing region of the tumor.

O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling.

The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. Although it is known that Groucho/TLEs are recruited to target genes by pathway-specific transcription factors, molecular events after the corepressor recruitment are largely unclear. We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression.

Neurosurgical injuries resulting from the 2011 tornados in Alabama: the experience at the University of Alabama at Birmingham Medical Center.

Object: The April 27, 2011, tornados that affected the southeastern US resulted in 248 deaths in the state of Alabama. The University of Alabama at Birmingham (UAB) Medical Center, the largest Level I trauma center in the state, triaged and treated a large number of individuals who suffered traumatic injuries during these events, including those requiring neurosurgical assessment and treatment.

Methods: A retrospective review of all adult patients triaged at UAB Medical Center during the April 27, 2011, tornados was conducted.

Massive pediatric neurosurgical injuries and lessons learned following a tornado disaster in Alabama.

Object: A large volume of patients presented to a Level I pediatric trauma center during and after a recent tornado disaster. Injuries of the central and peripheral nervous systems and the medical responses of a pediatric neurosurgical team are reviewed.

Methods: The clinical courses of patients who suffered cranial, spinal, and peripheral nerve injuries due to the tornado storm are reported.

O-GlcNAcylation enhances FOXO4 transcriptional regulation in response to stress.

The FOXO4 transcription factor plays an important role in cell survival in response to oxidative stress. The regulation of FOXO4 is orchestrated by post-translational modifications including phosphorylation, acetylation, and ubiquitination. Here, we demonstrate that O-GlcNAcylation also contributes to the FOXO4-dependent oxidative stress response.

Disrupting the enzyme complex regulating O-GlcNAcylation blocks signaling and development.

Although the knowledge that nuclear and cytoplasmic proteins are modified with N-acetylglucosamine has existed for decades, little has been shown as to its function until recently. There are now substantial data highlighting the significance of proper regulation of this modification in multiple cellular processes. Currently, only two enzymes are known that regulate this modification.

Characterization of the histone acetyltransferase (HAT) domain of a bifunctional protein with activable O-GlcNAcase and HAT activities.

Histones and transcription factors are regulated by a number of post-translational modifications that in turn regulate the transcriptional activity of genes. These modifications occur in large, multisubunit complexes. We have reported previously that mSin3A can recruit O-GlcNAc transferase (OGT) along with histone deacetylase into such a corepressor complex.

Inactivation of wild-type p53 protein function by reactive oxygen and nitrogen species in malignant glioma cells.

Malignant gliomas are the most common primary brain tumors in adults, and the most malignant form, glioblastoma multiforme (GBM), is usually rapidly fatal. Most GBMs do not have p53 mutations, although the p53 tumor suppressor pathway appears to be inactivated. GBMs grow in a hypoxic and inflammatory microenvironment, and increased levels of the free radicals nitric oxide (NO) and superoxide () occur in these malignancies in vivo.