Design, synthesis and biological evaluation of ezrin inhibitors targeting metastatic osteosarcoma.

Respiratory failure due to pulmonary metastasis is the major cause of death for patients with osteosarcoma. However, the molecular basis for metastasis of osteosarcoma is poorly understood. Recently, ezrin, a member of the ERM family of proteins, has been associated with osteosarcoma metastasis to the lungs.

Parkin reverses TDP-43-induced cell death and failure of amino acid homeostasis.

The E3 ubiquitin ligase Parkin plays a central role in the pathogenesis of many neurodegenerative diseases. Parkin promotes specific ubiquitination and affects the localization of transactivation response DNA-binding protein 43 (TDP-43), which controls the translation of thousands of mRNAs. Here we tested the effects of lentiviral Parkin and TDP-43 expression on amino acid metabolism in the rat motor cortex using high frequency ¹³C NMR spectroscopy.

Expression of Voltage-Gated Sodium Channel Na1.8 in Human Prostate Cancer is Associated with High Histological Grade.

Voltage-gated sodium (Na) channels are required for impulse conductance in excitable tissues. Nas have been linked to human cancers, including prostate. The expression and distribution of Na isoforms (Na1.

Parkin prevents cortical atrophy and Aβ-induced alterations of brain metabolism: ¹³C NMR and magnetic resonance imaging studies in AD models.

Alzheimer's disease (AD) is a neurodegenerative aging disorder characterized by extracellular Aβ plaques and intraneuronal neurofibrillary tangles. We conducted longitudinal studies to examine the effects of Aβ on brain amino acid metabolism in lentiviral Aβ(1-42) gene transfer animals and transgenic AD mice. We also performed lentiviral parkin gene delivery to determine the effects of Aβ clearance in AD models.

APOE genotype affects the pre-synaptic compartment of glutamatergic nerve terminals.

Apolipoprotein E (APOE) genotype affects outcomes of Alzheimer's disease and other conditions of brain damage. Using APOE knock-in mice, we have previously shown that APOE-ε4 Targeted Replacement (TR) mice have fewer dendritic spines and reduced branching in cortical neurons. As dendritic spines are post-synaptic sites of excitatory neurotransmission, we used APOE TR mice to examine whether APOE genotype affected the various elements of the glutamate-glutamine cycle.

Effect of the leukotriene A4 hydrolase aminopeptidase augmentor 4-methoxydiphenylmethane in a pre-clinical model of pulmonary emphysema.

The leukotriene A(4) hydrolase enzyme is a dual functioning enzyme with the following two catalytic activities: an epoxide hydrolase function that transforms the lipid metabolite leukotriene A(4) to leukotriene B(4) and an aminopeptidase function that hydrolyzes short peptides. To date, all drug discovery efforts have focused on the epoxide hydrolase activity of the enzyme, because of extensive biological characterization of the pro-inflammatory properties of its metabolite, leukotriene B(4). Herein, we have designed a small molecule, 4-methoxydiphenylmethane, as a pharmacological agent that is bioavailable and augments the aminopeptidase activity of the leukotriene A(4) hydrolase enzyme.

Histone deacetylase cytoplasmic trapping by a novel fluorescent HDAC inhibitor.

Inhibitors of histone deacetylases (HDAC) are an important emerging class of drugs for the treatment of cancers. HDAC inhibitors are currently under evaluation in clinical trials as single agents and as sensitizers in combinations with chemotherapies and radiation therapy. Although these drugs have important effects on cancer cell growth and functions, the mechanisms underlying HDAC inhibitor activities remain to be fully defined.

Three-dimensional prostate mapping biopsy has a potentially significant impact on prostate cancer management.

Purpose: To compare a new staging, three-dimensional prostate mapping biopsy (3D-PMB) method with traditional transrectal ultrasound (TRUS) biopsy and assess its possible impact on patient management.

Patients And Methods: One hundred eighty patients with unilateral cancer on TRUS biopsy, who were considering conservative management, underwent restaging with 3D-PMB. The 3D-PMB was carried out transperineally using a brachytherapy grid under TRUS guidance.