P2Y12 receptor-mediated cyclooxygenase 2 (COX-2) expression enhances tumor cell progression in a mouse model of lymphoma.

The pro-inflammatory enzyme cyclooxygenase 2 (COX-2) has been known to impart metastatic property to cancer cells. However, blocking of COX-2 with nonsteroidal anti-inflammatory drugs or COX-2-specific inhibitors has failed in clinical trials due to adverse effects associated with their prolonged use. We have previously shown that extracellular ATP (eATP), a major component of the tumor microenvironment, enhances COX-2 expression several-fold, both in macrophages and in various cancer cells, by acting on purinergic (P2) receptors.

Imidazopyridazine Acetylcholinesterase Inhibitors Display Potent Anti-Proliferative Effects in the Human Neuroblastoma Cell-Line, IMR-32.

Imidazo[1,2-]pyridazine compounds are a new class of promising lead molecules to which we have incorporated polar nitro and amino moieties to increase the scope of their biological activity. Two of these substituted 3-nitro-6-amino-imidazo[1,2-]pyridazine compounds (5c and 5h) showed potent acetylcholinesterase (AChE) inhibitory activity (IC 40-50 nM), which we have previously reported. In this study, we wanted to test the biological efficacy of these compounds.

Mutant Ataxin-3-Containing Aggregates (MATAGGs) in Spinocerebellar Ataxia Type 3: Dynamics of the Disorder.

Spinocerebellar ataxia type 3 (SCA3) is the most common type of SCA worldwide caused by abnormal polyglutamine expansion in the coding region of the ataxin-3 gene. Ataxin-3 is a multi-faceted protein involved in various cellular processes such as deubiquitination, cytoskeletal organisation, and transcriptional regulation. The presence of an expanded poly(Q) stretch leads to altered processing and misfolding of the protein culminating in the production of insoluble protein aggregates in the cell.

Extracellular ATP Mediates Cancer Cell Migration and Invasion Through Increased Expression of Cyclooxygenase 2.

The tumor microenvironment plays a major role in the ability of the tumor cells to undergo metastasis. A major player of tumors gaining metastatic property is the inflammatory protein, cyclooxygenase 2 (COX-2). Several tumors show upregulation of this protein, which has been implicated in mediating metastasis in various cancer types such as of colon, breast and lung.

Exogenous ATP modulates PGE release in macrophages through sustained phosphorylation of CDK9 and p38 MAPK.

An important mediator of inflammation is prostaglandin E (PGE ), whose levels are determined by the activity of the enzyme cyclooxygenase (COX). Of the two isoforms of the enzyme, COX-2 has been shown to be induced in macrophages during inflammation. Although general COX inhibitors, belonging to the class of nonsteroidal anti-inflammatory drugs, or specific COX-2 inhibitors, called coxibs, are useful in the control of acute inflammation, adverse reactions were seen when used chronically in the treatment of rheumatoid arthritis or neurodegenerative diseases.