The p75 neurotrophin receptor (p75) functions as a tumor suppressor in prostate epithelial cells, where its expression declines with progression to malignant cancer. Previously, we showed that treatment with R-flurbiprofen or ibuprofen induced p75 expression in several prostate cancer cell lines leading to p75-mediated decreased survival. Using the 2-phenyl propionic acid moiety of these profen...

A number of recent studies have demonstrated that cellular responses to tumor necrosis factor (TNF) mediated by the p55 and the p75 TNF receptors are distinct. To evaluate the relative in vivo toxicities of wild-type TNF alpha (wtTNF alpha) and a novel p55 TNF selective receptor agonist, healthy, anesthetized baboons (Papio sp.) were infused with a near-lethal dose of either wtTNF alpha or a TN...

Apoptosis of neointimal smooth muscle cells is a well-recognized component of the pathogenesis of vascular lesions. In recent studies, we have identified the neurotrophin receptor, p75(NTR), as a mediator of apoptosis of neointimal smooth muscle cells. Neurotrophin ligands and p75(NTR) are selectively expressed in areas of atherosclerotic lesions with increased smooth muscle cell apoptosis and ...

The p75 neurotrophin receptor (p75(NTR); also known as NGFR) can mediate neuronal apoptosis in disease or following trauma, and facilitate survival through interactions with Trk receptors. Here we tested the ability of a p75(NTR)-derived trophic cell-permeable peptide, c29, to inhibit p75(NTR)-mediated motor neuron death. Acute c29 application to axotomized motor neuron axons decreased cell dea...

Treatment of acute cardiac ischemia focuses on reestablishment of blood flow in coronary arteries. However, impaired microvascular perfusion damages peri-infarct tissue, despite arterial patency. Identification of cytokines that induce microvascular dysfunction would provide new targets to limit microvascular damage. Pro-nerve growth factor (NGF), the precursor of NGF, is a well characterized c...

Epidemiologic studies show that patients chronically consuming nonsteroidal anti-inflammatory drugs (NSAID) for arthritis exhibit a reduced incidence of prostate cancer. In addition, some NSAIDs show anticancer activity in vitro . NSAIDs exert their anti-inflammatory effects by inhibiting cyclooxygenase (COX) activity; however, evidence suggests that COX-independent mechanisms mediate decreased...

Subcellular compartmentalization of PDEs (phosphodiesterases) is a major mechanism for the regulation of cAMP signalling. The identification of the proteins that recruit specific PDE isoforms to subcellular compartments can shed light on the regulation of spatial and temporal cAMP gradients in living cells and provide novel therapeutic targets for inhibiting functions of PDEs. We showed recentl...

Similar to other parts of the central nervous system, there are two types of programmed cell death during retinal development. In early development, the neuronal progenitor population is affected. In the mouse eye, this kind of programmed cell death begins at around embryonic day (E) 12.5 and peaks between E14.5 and E16.5. The second phase of programmed cell death occurs during synaptogenesis w...

Background : Nerve growth factor (NGF) has been suggested to participate in tumor progression and it can interact with its receptor p75. In the present study, we investigated the expressions of NGF and p75 in hepatocellular carcinoma (HCC). Methods : We performed immunohistochemistry for NGF, p75 and PCNA in 45 cases of HCCs, and examined the relationships between the clinicopathologic factors ...

Alzheimer's disease is characterized by the accumulation of neurotoxic amyloidogenic peptide Abeta, degeneration of the cholinergic innervation to the hippocampus (the septohippocampal pathway), and progressive impairment of cognitive function, particularly memory. Abeta is a ligand for the p75 neurotrophin receptor (p75(NTR)), which is best known for mediating neuronal death and has been consi...