23 KB218 KB19 KB199220252003Čemažar, MajaMiklavčič, DamijanSerša, Gregorštevilka:1letnik:376 stranistr. 43-48ISSN:1318-2099COBISSID:16233177URN:URN:NBN:SI:doc-M6TGFW64enAssociation of Radiology and OncologyRadiology and oncology (Ljubljana)BleomicinBleomycinBlood SupplyCisplatinDrug Delivery SystemsDrug TherapyElectroporationelektrokemoterapijaElektroporacijaMiceMišineoplasmSarcoma, ExperimentalSarkom eksperimentalniTherapytumorZdravilo, sproščanje, sistemizdravljenjeTumor blood flow modifying effects of electrochemotherapy| a potential vascular targeted mechanism|Background. The aim of this study was to determine the tumor blood flow modifying, and potential vascular targeted effect of electrochemotherapy with bleomycin or cisplatin. Materials and methods. Electrochemotherapy was performed by application of short intense electric pulses to the tumors after systemic administration of bleomycin or cisplatin. Evaluated were antitumor effectiveness of electrochemotherapy by tumor measurement, tumor blood flow modifying effect by Patent blue staining technique, and sensitivity of endothelial and tumor cells to the drugs and electrochemotherapy by clonogenicity assay. Results. Electrochemotherapy was effective in treatment of SA-1 tumors in A/J mice resulting in substantial tumor growth delay and also tumor cures. Tumor blood flow reduction following electrochemotherapy correlated well with its antitumor effectiveness. Virtually complete shut downof the tumor blood flow was observed already at 24 h after electrochemotherapy with bleomycin whereas only 50% reduction was observed after electrochemotherapy with cisplatin. Sensitivity of human endothelial HMEC-1 cells to electrochemotherapy suggests a vascular targeted effect for electrochemotherapy in vivo with bleomycin as well as with cisplatin. Conclusion. These results show that in addition to direct electroporation of tumor cells, other vascular targeted mechanisms are involved in electrochemotherapy with bleomycin or cisplatin, potentially mediated by tumorblood flow reduction, and enhanced tumor cell death as a result of endothelial damage by electrochemotherapyIzhodišča. Namen naše raziskave je bil določiti vplive elektrokemoterapije s cisplatinom ali bleomicinom na pretok krvi v tumorjih in določiti njene možne mehanizme delovanja ciljane na žilje tumorja. Materiali in metode. Elektrokemoterapija je kombinirano zdravljenje sistemskega vbrizganja bleomicina in cisplatina nato pa sledi lokalna aplikacija električnih pulzov na tumor. V študiji smo ovrednotili protitumorski učinek elektrokemoterapije zmerjenjem velikosti tumorjev, učinek na pretok krvi v tumorjih z barvanjem tumorjev s Patentnim modrilom ter občutljivost endotelnih celic na citostatikain elektrokemoterapijo z merjenjem preživetja celic. Rezultati. Elektrokemoterapija je imela učinkovito protitumorsko delovanje, povzročila jevelik zaostanek v rasti tumorjev, nekateri tumorji so bili celo pozdravljeni. Zmanjšanje pretoka krvi v tumorjih je sovpadalo s protitumorsko učinkovitostjo elektrokemoterapije. Zaznali smo skoraj popoln zastoj pretoka krvi v tumorjih že po 24 urah po elektrokemoterapiji z bleomicinom, medtem ko je elektrokemoterapija s cisplatinom povzročila samo 50% zmanjšanje pretoka krvi v tumorjih. Občutljivost humanih endotelnih celic HMEC-1 na elektrokemoterapijo nakazuje ciljano delovanje te terapije na žilje tumorja invivo. Zaključki. Podatki kažejo, da je v protitumorskem delovanju elektrokemoterapije udeleženih več mehanizmov. Poleg povečanega dostavljanja kemoterapevtikov v tumorske celice z elektroporacijo, elektrokemoterapija tudizmanjša prekrvavitev tumorjev. Ta mehanizem je verjetno posredovan s smrtjo endotelnih celic, kar prav tako posredno povzroča smrt tumorskih celicTEXTznanstveno časopisjejournalsSlovenian National E-content AggregatorNational and University Library of SloveniaDruštvo radiologije in onkologije