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In the ca se of VEGF, wh ich is a lso a potent va scu lar perme ability induci ng factor, unila te ralperipher al ed ema hasrecently been obse rv ed in apati entwi th seve re peripher alis ch em ia after Cabazitaxel arterialgene transfer. C are ful monitoring for thepres en ce of local ordistaled ema wi ll be import ant if po tentially seriouscomplic ations a re to be avo ided in anorgan orlimb in wh ich thecircu lation is alreadycompr omised.F inally, many gene therapy app roaches to da te have concentra ted ontrans ferr ing genes in to patien tswi th sin ally no rmal copy in to a cellwi th a defective or abno rmal genewi thout ac tually rep lac ing the defective gene itself.These are usuallysing le gene recess ivedi so rde rs but may a lso inc lude dom inantdi so rde rs in wh ich awi ldtype gene will overr ide the abno rmal dom inant ph enotyp e.O ther app roaches have been used tost imu la te the immunesyst em,treatchronicdise ase s, andprovide mole cularma rker s.With this app roach, it is poss ib le to deliverre comb in ant genesdi rectly into the va scu la tu re at spec if icsi tes by local application of thevi ru s, su rg ical insert ion of vascu lar grafts seededwi th endo thelial cells eng inee red to express thege ne ofinterest, orinduction of new ly fo rm edvesselscont ainingengineer edendothelial cells.De spite the fact that the du ration of gene exp ress ion aftertrans fer appea rs atpre sent to be alimit ing factor, as adrug delive ry sys tem for thetrea tm ent of local or syst em icvascular and nonv asculardise ase s, gene the rapy emp loy ing endo thelial cells mayprove to be an important alte rnative.In summa ry,st imu lation or inh ibit ion of ang iog enes is hasprov ided very en courag ing re sults in an imal mode ls of a var ie ty ofdise ases and appea rs to be meeting with a certa in deg ree of succe ss in the early ph ases ofcl in ical tr ia ls in hum ans as an ad junct toestabli sh ed conv en tion alfo rms ofther apy.However, theshortte rm pro spec ts for ther ap eutic angiogenesis looksl ightly bet ter than tho se for anti ang iog enesis.Thu s, as oppo sed to anti ang iog enes is therapy, wh ich is likely to require longterm a dministr ati on of inhibito ry ag ents, ther ap eutic ang iog enes is islike ly tonecessit a te on ly br ief periods oftrea tmen t.Bo th nonspec if ic and specificside effects of anti ang iog enes is therapy, inc lud esis, are the re fo re likely to po se mo re of aprob lem than side effects Loteprednol etabonate seenwi thst imu lation of ang iog enesis.It is in te rest ing to no te thathighci rculating levels of ang io gen ic fac to rs such as V EGF andbFGF as seen in patien ts wi th a varie ty of cance rs do not appear to promo te a gene ralized or system ic ang iog en icsta te.S im ilar ly, ove rtside effects assoc ia tedwi th un controll ed nonspecif ic ang iog enes is have not been reported in ani tion of ang iog en ic fac to rs or intran sgen icmice, wh ich system ically ove rexp ress human bFGF in a constitutive manner.On the other hand, long te rm use of I F N a a in child ren with complicatedhem ang iom as may resu lt in thedevelop log ical complication s, and it is likely that manyother anti ang iog en ic agen ts will have bo thpr edictab le as well as unpredictab le tox icityprofi les.

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