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Primerjava učinkov visokofrekvenčnih bipolarnih in nizkofrekvenčnih monopolarnih električnih pulzov na preživetje celice
ID Polajžer, Tamara (Author), ID Miklavčič, Damijan (Mentor) More about this mentor... This link opens in a new window

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Abstract
Elektroporacija je pojav, kjer izpostavljenost celice zunanjemu električnemu polju povzroči povečano prepustnost membrane, zato v celico lahko vstopijo molekule, za katere je drugače membrana neprepustna. Če po prenehanju delovanja električnega polja celica preživi govorimo o reverzibilni elektroporaciji, o ireverzibilni elektroporaciji pa, če celica umre. Pred kratkim se je pojavila nova oblika ireverzibilne elektroporacije - visokofrekvenčna ireverzibilna elektroporacija, pri kateri naj ne bi prišlo do nenadzorovanega mišičnega krčenja in občutka bolečine, kot smo tega navajeni pri monopolarnih pulzih. Namen doktorske disertacije je bilo preučiti učinek nove oblike elektroporacijskih pulzov in ga primerjati z učinkom uveljavljenih monopolarnih pulzov, ovrednotiti učinkovitost ponovnega zdravljenja z elektroporacijo v primeru delnega odgovora tumorja ali ponovnem pojavu tumorja in preučiti vzrok za aktivacijo imunskega sistema po elektroporaciji. Rezultati kažejo, da je učinkovitost visokofrekvenčnih bipolarnih pulzov ob povečanju amplitude primerljiva z monopolarnimi pulzi. Vzrok za potrebovano višjo amplitudo bi se lahko skrival v izničevalnemu učinku. Ta je odvisen od elektroporacijskega pufra. Zdravljenje z elektroporacijskim metodami lahko uporabimo večkrat, učinek vsakega nadaljnjega zdravljenja pa bo primerljiv s prvotnimi zdravljenjem. Celice pri elektroporaciji umrejo tudi po poti imunogene celične smrt, ki preko sproščanja DAMP molekul lahko aktivirajo imunski sistem in s tem pripomorejo k boljšem izidu zdravljenja tumorjev z elektroporacijo.

Language:Slovenian
Keywords:Elektroporacija, ireverzibilna elektroporacija, povečana prepustnost membrane, visokofrekvenčni bipolarni pulzi, DAMP molekule, imunogena celična smrt
Work type:Doctoral dissertation
Typology:2.08 - Doctoral Dissertation
Organization:BF - Biotechnical Faculty
Publisher:[T. Polajžer]
Year:2022
PID:20.500.12556/RUL-144366 This link opens in a new window
UDC:576
COBISS.SI-ID:144138755 This link opens in a new window
Publication date in RUL:16.02.2023
Views:332
Downloads:42
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Secondary language

Language:English
Title:The effects of high-frequency bipolar and low-frequency monopolar electric pulses on cell survival
Abstract:
Electroporation is a phenomenon in which exposure of a cell to an external electric field causes the formation of pores in the membrane. This allows molecules to which the membrane is otherwise impermeable to enter the cell. If the cell survives, this is called reversible electroporation; if the cell dies, this is considered irreversible electroporation. Recently, a new form of irreversible electroporation has emerged - high-frequency irreversible radiofrequency electroporation. These pulses do not cause involuntary muscle contractions or pain, which is inevitable when using established monopolar pulses. The aim of this dissertation is to compare the efficacy of the novel pulses with monopolar pulses, to evaluate the efficacy of repeat treatment with electroporation in case of partial response or tumor recurrence, and to understand the cause of immune system activation after electroporation. The results show that the efficacy of high-frequency bipolar pulses is comparable to that of monopolar pulses, although a higher amplitude is required. Possible reason for the higher amplitude is the cancellation effect. However, it seems that this effect depends on the electroporation buffer. Electroporation therapies with long monopolar pulses can be applied multiple times, achieving the same treatment efficacy as the original treatment. Cells killed by electroporation may die by immunogenic cell death, in which the release of DAMP molecules may activate the immune system and affect the outcome of electroporation therapy.

Keywords:Electroporation, irreversible electroporation, permeabilization, high frequency bipolar pulses, DAMP molecules, immunogenic cell death

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