The apoptotic signal is further enhanced by the caspases dependent activation of pro apoptotic proteins such as Bid and Bimel and inactivation of anti apoptotic proteins such as XIAP, Bcl xL, RIP, and survivin. It results a change in the equilibrium of pro to anti apop totic molecules that lowers the cell death threshold and strongly favours apoptosis. These selleck chemicals findings may have important implications for the use of TRAIL in cancer therapeutic using recombinant sol uble TRAIL. As HDACIs strongly enhance the apoptotic action of TRAIL even at low concentrations, HDACIs may be used in combination with TRAIL to reduce the doses of TRAIL required for inhibition of tumour growth. Recently, several HDAC inhibitors have entered Phase I and Phase II clinical trials and are demonstrating encouraging anti tumour activity in a variety of cancer types.

The com bination of TRAIL and HDACIs may therefore be an inter esting and soft inoffensive new anti tumour strategy particularly relevant in the treatment of children with highly malignant neuroblastoma. Background We know that various factors can influence and promote regeneration of peripheral axons. In addition to soluble factors, the extracellular environment in which growth occurs is critically important. Axonal regeneration does not occur to any great extent in the CNS, and while this is due to a number of factors, the most prominent is a non permissive growth environment as well as an unavailabil ity of appropriate growth promoting factors. In the PNS, on the other hand, peripheral axons generally regenerate quite well.

Growth factors and extracellular matrix molecules like laminin act through cell surface receptors that activate often convergent signalling pathways to elicit neurite growth in sensory neurons. Among the targets of these pathways are the cytoskeletal elements responsible for ini tiating and maintaining the structure of growing proc esses. Actin, tubulin and intermediate filaments all play a part in growth processes. There are also a variety of other molecules that interact with these components to modulate or protect the cytoskeleton from deleterious stresses. One class of molecules known to act as chaperones include the small heat shock protein family, of which heat shock protein 27 is a member. Hsp27, in addition to its roles in regulating apoptosis and protein folding, interacts with different cytoskeletal elements.

Much of this work has been carried out using non neural cells, particu larly fibroblast and epithelial derived cells. Part of its pro tective role in stressed cells has been attributed to its actions as an actin capping protein. Hsp27 Brefeldin_A has been reported to be a component of focal contacts, play an important role in smooth muscle contraction and be important for cellular migration in endothelial cells.