Norman L. Lehman

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BACKGROUND Diffuse low-grade and intermediate-grade gliomas (which together make up the lower-grade gliomas, World Health Organization grades II and III) have highly variable clinical behavior that is not adequately predicted on the basis of histologic class. Some are indolent; others quickly progress to glioblastoma. The uncertainty is compounded by(More)
Therapy development for adult diffuse glioma is hindered by incomplete knowledge of somatic glioma driving alterations and suboptimal disease classification. We defined the complete set of genes associated with 1,122 diffuse grade II-III-IV gliomas from The Cancer Genome Atlas and used molecular profiles to improve disease classification, identify molecular(More)
The objective of this study was to demonstrate 1H MR spectroscopy (MRS) changes in cerebral metabolites after acute head trauma. Twenty-five patients (12 children, 13 adults) were examined with quantitative 1H MRS after closed head injury. Clinical grade (Glasgow Coma Scale [GCS]) and outcome (Rancho Los Amigos Medical Center Outcome Score [ROS]) were(More)
The periodic destruction of mitotic cyclins is triggered by the activation of the anaphase-promoting complex/cyclosome (APC/C) in mitosis. Although the ability of the APC/C to recognize destruction box (D-box) substrates oscillates throughout the cell cycle, the mechanism regulating APC/C binding to D-box substrates remains unclear. Here, we show that the(More)
The ubiquitin proteasome system (UPS) orchestrates the turnover of innumerable cellular proteins. In the process of ubiquitination the small protein ubiquitin is attached to a target protein by a peptide bond. The ubiquitinated target protein is subsequently shuttled to a protease complex known as the 26S proteasome and subjected to degradative proteolysis.(More)
We have studied the cytotoxicity of 5,10-dideazatetrahydrofolate (DDATHF) and of D-1694 to human WiDr colonic carcinoma cells as a model system for the effects of pure inhibitors of either the de novo purine synthesis pathway or thymidylate synthesis. The growth of this cell line was inhibited by very low concentrations of either agent and the lethality of(More)
Cancer stem cells (CSCs) are characterized by their self-renewing potential and by their ability to differentiate and phenocopy the original tumor in orthotopic xenografts. Long-term propagation of glioblastoma (GBM) cells in serum-containing medium results in loss of the CSCs and outgrowth of cells genetically and biologically divergent from the parental(More)
The fidelity of cell division is dependent on the accumulation and ordered destruction of critical protein regulators. By triggering the appropriately timed, ubiquitin-dependent proteolysis of the mitotic regulatory proteins securin, cyclin B, aurora A kinase, and polo-like kinase 1, the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase plays an(More)
The anaphase promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls the cell cycle by directing the ubiquitin-dependent proteolysis of S-phase and mitosis promoting factors. Emi1 is an E2F transcriptional target that drives cell cycle progression from G1/S through early mitosis by inhibiting the APC/C's ubiquitin ligase activity, and(More)
Exogenous 20-hydroxyeicosatetraenoic acid (20-HETE) increases the growth of human glioma cells in vitro. However, glioma cells in culture show negligible 20-HETE synthesis. We examined whether inducing the expression of a 20-HETE synthase in a human glioma U251 cell line would increase proliferation. U251 cells transfected with CYP4A1 cDNA (termed U251 O)(More)