b'\n_START_ARTICLE_\nElektrokemoterapija\n_START_SECTION_\nOpis delovanja\n_START_PARAGRAPH_\n\xc4\x8ce biolo\xc5\xa1ko celico izpostavimo elektri\xc4\x8dnemu polju zadostne jakosti, na membrani vsilimo transmembransko napetost, kar vodi do strukturnih sprememb v celi\xc4\x8dni membrani [17-22]. Te spremembe povzro\xc4\x8dijo pove\xc4\x8danje prepustnosti membrane, ki omogo\xc4\x8di, da molekule, ki normalno ne morejo prehajati v celico, lahko vstopijo v celico [1,23,24]. Ta pojav imenujemo elektroporacija (ali elektropermeabilizacija). Uporaba elektroporacije se je mo\xc4\x8dno pove\xc4\x8dala, ko so pojav za\xc4\x8deli izrabljati za izbolj\xc5\xa1anje vnosa kemoterapevtikov v celice, kar imenujemo elektrokemoterapija. V biomedicinskih aplikacijah elektroporacije se uporabljajo kratki visokonapetostni enosmerni elektri\xc4\x8dni pulzi. Amplituda pulzov je odvisna od lastnosti tkiva in od oblike ter polo\xc5\xbeaja elektrod in mora biti, glede na rezultate raziskav na tumorjih v in vivo pogojih, zadosti velika, da na celotnem podro\xc4\x8dju tumorja dose\xc5\xbeemo elektri\xc4\x8dno polje velikosti 400 V/cm (8 pulzov s trajanjem 100 mikrosekund) [25]. Trajanje pulzov je po navadi 100 mikrosekund. V prvih eksperimentih so bili pulzi dovedeni na 1 sekundo (ponavljalna frekvenca 1 Hz), danes pa so pulzi, ki jih dovajamo na ko\xc5\xbene ali podko\xc5\xbene tumorje, dovedeni s ponavljalno frekvenco 5000 Hz, da dose\xc5\xbeemo \xc4\x8dim manj\xc5\xa1e nelagodje za pacienta zaradi elektri\xc4\x8dne stimulacije bli\xc5\xbenjih mi\xc5\xa1ic in \xc4\x8dim kraj\xc5\xa1i postopek zdravljenja [26,27]. Za namene zdravljenja globoko le\xc5\xbee\xc4\x8dih, notranjih tumorjev, ki le\xc5\xbeijo relativno blizu srca, pa je dovajanje pulzov sinhronizirano z absolutno refraktorno dobo posameznega sr\xc4\x8dnega utripa v elektrokardiogramu z namenom, da zagotovimo \xc4\x8dim ve\xc4\x8djo varnost za pacienta [28, http://www.clinicaltrials.gov/ct2/show/NCT01264952]. Pulzi so dovedeni v serijah po osem pulzov, dovajanje pa po potrebi lahko tudi ponovimo.\n_START_SECTION_\nOpis zdravljenja\n_START_PARAGRAPH_\nPostopek zdravljenja z elektrokemoterapijo vsebuje lokalno ali sistemsko dovajanje kemoterapevtika, ki druga\xc4\x8de ne more prehajati celi\xc4\x8dne membrane (npr. bleomicina), ali kemoterapevtika, ki slabo prehaja v celice (npr. cisplatin), ter dovajanje elektri\xc4\x8dnih pulzov na zdravljeno podro\xc4\x8dje, ko koncentracija zdravila v tumorju dose\xc5\xbee najvi\xc5\xa1jo vrednost [12]. Z dovajanjem elektri\xc4\x8dnih pulzov izpostavimo celice elektri\xc4\x8dnemu polju, ki povzro\xc4\x8di, da na celi\xc4\x8dni membrani nastanejo nanospremembe, ki pove\xc4\x8dajo prepustnost membrane. Zaradi pove\xc4\x8dane prepustnosti membrane lahko molekule kemoterapevtika prosto preidejo v citoplazmo in izrazijo svoj citotoksi\xc4\x8dni efekt. Tumor lahko pozdravimo, \xc4\x8de vanj in okrog njega razporedimo ve\xc4\x8d elektrod in dovajamo pulze med vsakim parom elektrod, pri tem pa je v tumorju prisotna ustrezna koncentracija kemoterapevtika [25]. Postopek lahko ponovimo \xc5\xbee \xc4\x8dez nekaj tednov, v primeru, ko prvo zdravljenje ni bilo v celoti uspe\xc5\xa1no bodisi zaradi velikosti tumorja bodisi zaradi nepopolne dostopnosti tumorja.\n_START_SECTION_\nU\xc4\x8dinkovitost, klini\xc4\x8dni pomen\n_START_PARAGRAPH_\nV \xc5\xa1tevilnih klini\xc4\x8dnih \xc5\xa1tudijah (v fazi II in III) so raziskovalci ugotovili, da je odzivnost tumorjev zdravljenih z elektrokemoterapijo ko\xc5\xbenih in podko\xc5\xbenih metastaz ali tumorjev z bleomicinom ali cisplatinom okrog 80\xc2\xa0% [29]. Z elektrokemoterapijo dose\xc5\xbeemo hitrej\xc5\xa1e in bolj u\xc4\x8dinkovito zmanj\xc5\xa1anje velikosti tumorjev kot s standardno kemoterapijo za zdravljenje ko\xc5\xbenih ali podko\xc5\xbenih tumorjev. Uspe\xc5\xa1no so bili zdravljeni pacienti s ko\xc5\xbenimi metastazami melanoma, s Kaposi sarkomom, s plo\xc5\xa1\xc4\x8datoceli\xc4\x8dnim karcinomom, z bazalnoceli\xc4\x8dnim karcinomom, z adenokarcinomom in z rakom dojke [4-7,9,10,30]. Prvi klini\xc4\x8dni rezultati elektrokemoterapije notranjih tumorjev (jetrnih metastaz) so prav tako obetavni in spodbudni.\n_START_SECTION_\nVarnost\n_START_PARAGRAPH_\nPri elektrokemoterapiji se uporabljajo ni\xc5\xbeje doze kemoterapevtika kot pri standardnem protokolu kemoterapije. Pri uporabi elektrokemoterapije v kliniki je tako zaznati le manj\xc5\xa1e stranske u\xc4\x8dinke. \xc4\x8ce je uporabljena ustrezna anestezija za bla\xc5\xbeenje simptomov povezanih z dovajanjem elektri\xc4\x8dnih pulzov, potem je kontrola nad nivojem bole\xc4\x8dine med elektrokemoterapijo dobra in je postopek sprejemljiv za pacienta. Poleg bole\xc4\x8dine, ki je omejena na zdravljen tumor in okoli\xc5\xa1ko tkivo, se med dovajanjem elektri\xc4\x8dnih pulzov pojavlja tudi mi\xc5\xa1i\xc4\x8dna kontrakcija, ki pri pacientih povzro\xc4\x8da le manj\xc5\xa1e nelagodje [4]. Ob dovajanju pulzov med elektrokemoterapijo se pojavi tudi prekinitev pretoka v \xc5\xbeilah (angl. vascular lock): za nekaj minut se krvni pretok v zdravljenem tumorju in okoli\xc5\xa1kem normalnem tkivu prekine [31,32]. Prekinitev pretoka je prekratka, da bi lahko s tem povzro\xc4\x8dili \xc5\xa1kodljive u\xc4\x8dinke, vendar pa v tumorjih traja dlje kot v normalnem tkivu, kar prispeva k ve\xc4\x8dji u\xc4\x8dinkovitosti elektrokemoterapije. Zdravljenje z elektrokemoterapijo je za pacienta sprejemljiv postopek, saj bi bila ve\xc4\x8dina vpra\xc5\xa1anih pacientov vklju\xc4\x8denih v klini\xc4\x8dno \xc5\xa1tudijo za namene dolo\xc4\x8ditve Evropskih standardnih operativnih postopkov za elektrokemoterapijo (ESOPE) pripravljena postopek zdravljenja ponoviti, \xc4\x8de bi bilo to potrebno [4].\n_START_SECTION_\nUporaba v veterini\n_START_PARAGRAPH_\nElektrokemoterapija se uporablja tudi v onkologiji na podro\xc4\x8dju veterine, in sicer na psih, ma\xc4\x8dkah in konjih. Centri, kjer je tako zdravljenje mo\xc5\xbeno, se nahajajo v Braziliji, Franciji, Italiji, Sloveniji, Veliki Britaniji in na Irskem. Uporablja se za zdravljenje razli\xc4\x8dnih tumorjev [33].\n_START_SECTION_\nReference\n_START_PARAGRAPH_\n[1] Mir, L.M., Orlowski, S., Belehradek Jr, J. & Paoletti, C. Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. Eur J Cancer 27, 68-72 (1991)._NEWLINE_[2] Sersa, G., Cemazar, M. & Miklavcic, D. Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum(II) in mice. Cancer Res 55, 3450-3455 (1995)._NEWLINE_[3] Gehl, J. & Geertsen, P.F. Palliation of haemorrhaging and ulcerated cutaneous tumours using electrochemotherapy. Eur J Cancer Suppl 4, 35-37 (2006)._NEWLINE_[4] Marty, M. et al. Electrochemotherapy - An easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: Results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. 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