47 Othe otherhand, etoposde decreases CAM 1 and, despite the fact that t doesn’t impact cell survval, markedly lowers the cell nvasveness.In all probability, the effect of etoposde s the consequence of the stability betweethe ncreased expressoof COX 2, lnked to a serious survval and mgratory abty, plus the lowered CAM one expresson, leadng to a reductoof the metastatc potental of tumor cells.The cotreatment of etoposde wth SB203580, by downregulatng the expressoof both protens, othe onehand, determnes a cytotoxc and antangogenetc effect and, othe otherhand, minimizes the nvasve and metastatc propertes.The demonstratothat p38MAPK may regulate NB cell mgratoand nvasveness s conrmed from the nhbtory effect of SB203580 othe MM9 actvty.For that reason, these effects strongly suggest the combna toof etoposde wth SB203580 mght be effectve blockng tumor development and metastases.
Some preclncal studeshave demonstrated that SB203580 s pharmacologcally actve vvo various anmal models and s a potent nhbtor of cytokne productowth only mnor results othe mmune program.48 Several p38 nhbtors tested for your enzyme inhibitor therapy of nammatory dseaseshave beewell tolerated wth mnmal sde results.49 Of partcular note, there s ncreasng evdence the dfferent pronammatory chemoknes are mplcated the development and nvasvty of NB.50 concluson, we beleve that, as a result of the dual actvty ocancer cells and tumor mcroenvronment, normal chemotherapy combned wth p38 nhbtors could signify an effective therapeutc approach for the therapy of stage NB.Neuropathc pas assocated additional info wth nerve njury of multple aetology that ncludes acute trauma, dabetes, cancer, nfectoand autommune pathology.
1 Pathogeness of neuropathc pareects complex remodellng from the spnal cord, wth prmary part attrbuted to alter of

synaptc transmssoand actvatoof neuroglal cells, astrocytes and mcrogla.2 4 Glutamate, the major exctatory neurotransmtter the braand spnal cord, exerts ts postsynaptc effects va a dverse set of onotropc and metabotropc membrane receptors.The glutamate onotropc methyl D aspartate receptors, speccally those localzed the dorsalhorof the spnal cord, are crtcally nvolved nocceptve transmssoand synaptc plastcty andhave prolonged beeconsdered a target to the treatment method of neuropathc pan.5,six The natve neuronal NMDAR s a tetramer that conssts of two NR1 and two NR2 subunts.eight ten There are many reports that nerve njury trggers reactve improvements perpheral mmune program and neuroglal cells the two perpheral and central nervous techniques.