Radioprotection: the non-steroidal anti-inflammatory drugs (NSAIDs) and XXXX .

@entity32 @entity1356 @entity5 @entity1457 @entity1161 @entity1421 @entity26 @entity1426 @entity2918 @entity310 @entity396 @entity2367 @entity5015 @entity224
Clinical and experimental studies of the acute and late effects of radiation on cells have enhanced our knowledge of radiotherapy and have led to the optimisation of radiation treatment schedules and to more precise modes of radiation delivery. However, as both normal and cancerous tissues have similar response to radiation exposure, radiation-induced injury on normal tissues may present either during, or after the completion of, the radiotherapy treatment. Studies on both NSAIDs and @entity2918 have indeed shown some evidence of radioprotection. Both have the potential to increase the survival of cells but by entirely different mechanisms. Studies of cell kinetics reveal that cells in the mitotic (M) and late G2 phases of the cell cycle are generally most sensitive to radiation compared with cells in the early S and G1/G0 phases. Furthermore, radiation leads to a mitotic delay in the cell cycle. Thus, chemical agents that either limit the proportion of cells in the M and G2 phases of the cell cycle or enhance rapid cell growth could in principle be exploited for their potential use as radioprotectors to normal tissue during irradiation. NSAIDs have been shown to exert anti- @entity5 effects by causing cell-cycle arrest, shifting cells towards a quiescence state (G0/G1). The same mechanism of action was observed in radioprotection of normal tissues. An increase in @entity1426 concentrations after exposure to NSAIDs also leads to the production of an apoptosis-inducer @entity2367 . NSAIDs also elevate the level of @entity224 dismutase in cells. Activation of @entity1457 proteins by NSAIDs increases cell survival by alteration of cytokine expression. A role for NSAIDs with respect to inhibition of cellular proliferation possibly by an anti-angiogenesis mechanism has also been suggested. Several in-vivo studies have provided evidence suggesting that NSAIDs may protect normal tissues from @entity1161 . @entity2918 do not regulate the cell cycle, but they do have a variety of effects on cell growth and differentiation. @entity1421 mediates angiogenesis, increasing the supply of @entity26 and nutrients, essential for cellular survival and growth. Accordingly, @entity1421 at sufficiently high plasma concentrations enhances cellular survival by inhibiting pro-inflammatory cytokines such as @entity310 and @entity1356 . Thus, @entity1421 acts as a modulator, rather than a mediator, of @entity32 . Prospective studies have suggested the potential use of @entity396 , a @entity5015 analogue, before irradiation, in prevention of radiation-induced side effects. The current understanding of the pharmacology of NSAIDs and @entity2918 shows great potential to minimise the adverse effects of radiotherapy on normal tissue.
