Intravenous Formulation of HET0016 Decreased Human Glioblastoma Growth and Implicated Survival Benefit in Rat Xenograft Models.

Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPßCD and tested in animal models of human and syngeneic GBM.

Reducing Functional MR Imaging Acquisition Times by Optimizing Workflow.

Functional magnetic resonance (MR) imaging is a complex, specialized examination that is able to noninvasively measure information critical to patient care such as hemispheric language lateralization ( 1 ). Diagnostic functional MR imaging requires extensive patient interaction as well as the coordinated efforts of the entire health care team. We observed in our practice at an academic center that the times to perform functional MR imaging examinations were excessively lengthy, making scheduling of the examination difficult.

Combination of vatalanib and a 20-HETE synthesis inhibitor results in decreased tumor growth in an animal model of human glioma.

Background: Due to the hypervascular nature of glioblastoma (GBM), antiangiogenic treatments, such as vatalanib, have been added as an adjuvant to control angiogenesis and tumor growth. However, evidence of progressive tumor growth and resistance to antiangiogenic treatment has been observed. To counter the unwanted effect of vatalanib on GBM growth, we have added a new agent known as N-hydroxy-N'-(4-butyl-2 methylphenyl)formamidine (HET0016), which is a selective inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis.

Effects of tyrosine kinase inhibitors and CXCR4 antagonist on tumor growth and angiogenesis in rat glioma model: MRI and protein analysis study.

The aim of the study was to determine the antiangiogenic efficacy of vatalanib, sunitinib, and AMD3100 in an animal model of human glioblastoma (GBM) by using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and tumor protein expression analysis. Orthotopic GBM-bearing animals were randomly assigned either to control group or vatalanib, sunitinib, and AMD3100 treatment groups. Following 2 weeks of drug treatment, tumor growth and vascular parameters were measured using DCE-MRI.

Measurement of rat brain tumor kinetics using an intravascular MR contrast agent and DCE-MRI nested model selection.

Purpose: Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in a rat glioma model, and nested model selection (NMS), to compare estimates of the pharmacokinetic parameters vp , K(trans) , and ve for two different contrast agents (CAs)-gadofosveset, which reversibly binds to human serum albumin, and gadopentetate dimeglumine, which does not.

Materials And Methods: DCE-MRI studies were performed on nine Fisher 344 rats inoculated intracerebrally with 9L gliosarcoma cells using both gadofosveset and gadopentetate. The parameters vp , K(trans) , and ve were estimated using NMS.

Anomalous lobar pulmonary vein resembling pulmonary arteriovenous malformation.

We present a case report of a 72-year-old man with an anomalous lobar pulmonary vein which was initially misdiagnosed as a pulmonary arteriovenous malformation on chest computed tomography. This uncommon condition was correctly diagnosed during pulmonary angiography performed as workup for the computed tomography finding. In this report, we describe the imaging findings in this case and discuss congenital anomalies of the pulmonary veins.

The nuclear kinase mitogen- and stress-activated protein kinase 1 regulates hippocampal chromatin remodeling in memory formation.

The extracellular signal-regulated kinase (ERK)/MAPK (mitogen-activated protein kinase) cascade has been established as a potent regulator of gene transcription in long-term memory formation, but the precise mechanisms of this regulation are poorly understood. ERK does not directly affect many of its nuclear targets, but rather must act through intermediary kinases. In this study, we investigated the role of mitogen- and stress-activated protein kinase 1 (MSK1), a nuclear kinase downstream of ERK, in chromatin remodeling during hippocampus-dependent memory formation.

ERK/MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning.

Long-term memory formation is regulated by many distinct molecular mechanisms that control gene expression. An emerging model for effecting a stable, coordinated pattern of gene transcription involves epigenetic tagging through modifications of histones or DNA. In this study, we investigated the regulation of histone phosphorylation in the hippocampus by the ERK/MAPK (extracellular signal-regulated kinase/mitogen-activated protein kinase) pathway.