Author/Editor		Čemažar, Maja; Auersperg, Marija; Serša, Gregor
Title		Antitumor effectiveness of bleomycin on SA-1 tumor after pretreatment with vinblastine
Translated title		Protitumorsko delovanje bleomicina na SA-1 tumorjih po predhodni terapiji z vinblastinom
Type		članek
Source		Radiol Oncol
Vol. and No.		Letnik 34, št. 1
Publication year		2000
Volume		str. 49-57
Language		eng
Abstract		In our previous study, vinblastine (VLB) was shown to increase the plasma membrane fluidity. This effect of VLB might be exploited for better transport of drugs through the plasma membrane. The aim of the present study was to determine whether pretreatment with VLB can increase the cytotoxic effect of BLM on intraperitoneal SA-1 tumors in mice. Materials and methods. BLM and VLB were used as single agents or in various combinations, i.e. BLM injected 24 h before VLB or vice-versa, VLB injected 24 h before BLM. Cell and animal survival together with DNA histograms were the end-points used to determine the effect of these combined treatments. Results. Both drugs, either as single treatment or in different combined therapy schedules reduced significantly the number of cells in peritoneal lavage, compared to control, saline treated animals. The combination of VLB, followed by BLM after 24 h reduced significantly the number of cells in peritoneal lavage, compared to the treatment in which BLM was followed by VLB or to the treatment with single drugs alone. Median survival time of mice treated with VLB alone, BLM alone and combination of both drugs was significantly prolonged compared to the control untreated mice. When VLB and BLM were combined, both treatment combinations were more effective than monochemotherapies with VLB or BLM. The best results were obtained when VLB was followed by BLM after 24 h. The DNA histogram of cells treated with VLB showed a decreased number of cells in S phase and an increased number of cells with DNA values greater than in G2M compartment compared to the control untreated cells. BLM in the dosage used in these experiments did not affect the progression of cells through cell cycle. Both combinations of VLB and BLM produced similar cell kinetic effect as VLB alone. Conclusion. (Abstract truncated at 2000 characters.)
Summary		Izhodišča. V naši predhodni študiji smo ugotovili, da vinblastin (VLB) poveča fluidnost plazmaleme, kar bi lahko izkoristili za povečan transport zdravil preko plazmaleme. Namen naše raziskave je bil na mišjih intraperitonealnih tumorjih določiti, ali se poveča učinkovitost bleomicina (BLM) po predhodni terapiji z VLB. Materiali in metode. Mišim smo injicirali samo VLB ali samo BLM ter obe zdravili v dveh kombinacijah: VLB injiciran 24 h pred BLM in BLM injiciran 24 h pred VLB. Učinkovitost terapije smo ugotavljali s preživetjem živali, štetjem celic, izoliranih iz peritonealne votline miši, ter DNA histogrami. Rezultati. Obe zdravili, bodisi kot mono kemoterapiji ali v kombinaciji, sta povzročili značilno zmanjšanje števila celic v peritonealni votlini v primerjavi s kontrolno skupino. Ko smo injicirali VLB 24 h pred BLM je bilo število celic v izolatu peritonealne votline značilno zmanjšano v primerjavi z monokemoterapijama in s skupino, ko smo BLM injicirali 24 h pred VLB. Preživetje živali, zdravljenih samo z VLB ali samo z BLM ter obema kombinacijama zdravil, je bilo značilno podaljšano glede na kontrolno nezdravljeno skupino miši. Obe kombinaciji VLB in BLM sta bili tudi bolj učinkoviti kot monokemoterapiji. Najboljši rezultat pa smo dobili pri skupini, kjer smo injicirali VLB 24 h pred BLM. V primerjavi z DNA histogramom kontrolnih celic smo v DNA histogramu celic, ki so bile izpostavljene delovanju VLB, izmerili zmanjšano število celic v S fazi in povečano število celic z večjo količino DNA, kot jo imajo celice v G2M fazi celičnega ciklusa. Doza BLM, ki smo jo uporabili v naših poskusih, ni imela učinka na progresijo celic skozi celični ciklus. Obe kombinaciji VLB in BLM sta imeli podoben celično kinetični učinek kot sam VLB. Zaključek. Glede na naše rezultate lahko zaključimo, da je mehanizem odgovoren za povečan učinek terapije, v kateri smo dali VLB 24 h pred BLM, predvsem povečana fluidnost celične membrane in verjetno tudi celično kinetični učinek VLB.
Descriptors		SARCOMA, EXPERIMENTAL BLEOMYCIN VINBLASTINE PERITONEAL LAVAGE MICE FIBROSARCOMA FLOW CYTOMETRY CELL SURVIVAL SURVIVAL RATE