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Biomedical subjects

E Balázová

Publications and source records attributed to E Balázová.

At least 19 recordsLinked to original sources
PubMed1994

Effect of arabinosylcytosine derivative cyclocytidine on hepatal functions in rats and on Zajdela hepatoma.

1. The effectivity of the arabinosylcytosine (araC) derivative, cyclocytidine (cC), against Zajdela hepatoma was evaluated. It was established that the cC effect was dose-dependent. 2. Zajdela hepatoma-bearing rats, given a single dose of 500 mg of cC per kg of body weight, showed an increased life span of 48 and 39%. 3. cC significantly decreased the number of Zajdela hepatoma cells in ascitic fluid and affected the cytochrome content in hepatal mitochondria. 4. The overall cC effect on the hepatal function of normal and hepatectomized liver was marginal, thus making this araC derivative an interesting candidate for further evaluation of its effectivity against non-hematological tumors.

Ancitabine↗
PubMed1993

DNA breakage and inactivation resulting from hydroxylamine and/or cis-diamminedichloroplatinum(II) interactions with plasmid DNA.

1. Occurrence of lesions induced in plasmid DNA by cis-DDP and by HA was quantified both as a transforming activity and as conformation integrity of supercoiled pBR322 DNA. Fifty per cent decrease of the biological activity of plasmid DNA, not accompanied by measurable change of DNA conformation, was observed after a single exposure of DNA to cis-DDP (1 hr/37 degrees C). 2. HA induced conversion of supercoiled DNA to other topological forms in a dose-dependent manner. 3. One- and two-strand DNA breaks were determined electrophoretically with high sensitivity. Cis-DDP exposed DNA relaxed at 30 times lower HA concentration compared to intact DNA. 4. This effect may be connected with a local distortion of DNA structure at the cis-DDP--DNA bond, which makes possible high effectivity of HA-DNA interaction. 5. On other hand, biological activity stayed at the 50% level despite breaks induced in DNA. 6. This finding supports the idea that DNA breaks occur at the locations which were modified during the exposure of DNA to cis-DDP. 7. The importance of the DNA structure during interaction with HA may be seen during HA-DNA interaction at heat-denaturation of supercoiled DNA. At this condition, the DNA breaks were induced at 100 times lower concentration of HA. 8. We conclude, on the basis of these results published earlier, that local distortion of supercoiled DNA structure, which is caused by the cis-DDP bond, and the local DNA uncoiling caused by heat-denaturation are related to high HA-DNA reactivity.

Cisplatin↗
PubMed1993

Potentiation of cis-DDP and pyridoxal effect on isolated DNA during simultaneous application.

Pyridoxal and cis-diamminedichloroplatinum (II) (cis-DDP) have a different mode of interaction with DNA. Cis-DDP caused extensive transforming inactivation of pBR322 DNA but did not form strand breaks in DNA molecules. On the other hand, pyridoxal formed frank strand breaks in the DNA chains and decreased DNA transforming activity. A higher level of DNA transforming inactivation was obtained during simultaneous application of both compounds than would be an additive effect of these compounds applied to DNA independently. This synergistic effect can be ascribed to the introduction of thermolabile sites by the combined action of cis-DDP and pyridoxal. These lesions were converted by heat-treatment to DNA strand breaks and detected electrophoretically. Using two different methods, cis-DDP and pyridoxal, during simultaneous application, interacted with DNA with higher efficiency.

Cisplatin↗
PubMed1992

Acute development of low T3 syndrome and changes in pituitary-adrenocortical function after elective cholecystectomy in women: some differences between young and elderly patients.

From two groups of female patients (young group: 15 patients aged less than 25 years; elderly group: 15 patients aged more than 65 years) who were subjected to cholecystectomy, blood samples were obtained on the day before surgery, on the day of surgery before premedication and after waking up from anaesthesia and also on days 1, 3 and 7 after surgery. In aliquots of sera the levels of TSH, ACTH, thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and cortisol were estimated with the aid of radio-immunoassay (RIA). The differences between the young and elderly subjects were evaluated with the aid of four different statistical tests. Though no changes in the level of T4 were found, the level of T3 was significantly decreased and that of rT3 was significantly increased on Day 1 after surgery. However, the decrease of T3 was expressed more significantly in the young group and, in addition, an increase of rT3 in the same group was found even before premedication. The level of TSH showed a sharp increase at the end of surgery, which was expressed more in the young group. Though no differences between groups were observed in a sharp peak of the ACTH level during surgery, the increase of cortisol level in the elderly group was significantly higher and remained so during the post-operative period.

Adrenocorticotropic Hormone↗
PubMed1991

Treatment of leukemia L1210 and P388 by arabinosylcytosine-polysaccharide conjugates.

Conjugates of 1-beta-D-arabinofuranosylcytosine (araC) with two polysaccharides such as polygalacturonic acid (PGA) and carboxymethylated yeast beta-D-glucan (CMG) were tested for their antileukemic activity in vitro on a L1210 cell line in suspension culture, in soft agar assay and in vivo on L1210, L1210/araC- and P388-leukemia-bearing mice. Both conjugates showed high activity in vitro in soft agar assay, compared with araC. Single administration of PGA-araC or CMG-araC increased the survival time 1.5 x or 1.7 x, respectively, compared with araC in vivo in L1210-leukemia-bearing mice. The conjugates were not active against araC-resistant leukemia line L1210/araC. The marked effect of both PGA-araC and CMG-araC against leukemia L1210 and P388 is probably due to the prolonged release of free araC from conjugates caused by hydrolysis.

Animals↗
PubMed1991

Evaluation of synergism of drugs cis-diamminedichloroplatinum (II) and arabinosylcytosine on the level of chemical interaction with DNA and on the growth of mouse leukemia.

1. Cytotoxic synergism of drugs cis-diamminedichloroplatinum(II) (cis-DDP) and arabinosylcytosine (araC) was studied both on the level of interaction with DNA in chemically determined conditions and on leukemia L1210 bearing mice. 2. AraC and its structural natural precursor cytidine were tested for the modulation of kinetics of bifunctional adducts production induced by cis-DDP in DNA. 3. This process plays the basic role in cytotoxic mechanism and antitumor activity of cis-DDP. 4. No interaction was seen between cis-DDP and araC. Further, presence of araC in reaction mixture had no effect on cis-DDP-DNA interaction. 5. Therefore, cytotoxic synergism does not arise in the araC-cis-DDP-DNA interaction and its origin is different. 6. Finding that cytidine has no synergistic effect on life span of leukemia L1210 bearing mice when administered together with cis-DDP it shows the difference between cytidine and araC. 7. The small structural difference between cytidine and araC is very important for synergism of cytotoxicity.

Animals↗
PubMed1991

Biotransformation and in vitro activity of an arabinosylcytosine 5'-chloro-5'-deoxy analog.

5'-Chloro-5'-deoxyarabinosylcytosine (5'-chloro-araC), a lipophilic and cytidine-deaminase resistant analog of the cytotoxic agent arabinosylcytosine (araC) was evaluated in terms of bioactivation, transformation and its cytotoxic activity in vitro. 5'-Chloro-araC interferes with DNA synthesis (IC50 = 2.8 mumol/l) and inhibits the growth of L1210 cells in suspension culture (IC50 = 1.05 mumol/l) and in the soft agar assay (IC50 = 0.65 mumol/l). Being phosphorylated to the triphosphate of araC-araCTP (5'-triphosphate of araC), 5'-chloro-araC has the same mechanism of action as arabinosylcytosine. In alkaline solutions 5'-chloro-araC is transformed to another (cytostatically inactive) araC analog--2',5'-anhydroarabinosylcytosine--but at physiological pH and temperature conditions, it has sufficient stability to be phosphorylated and thus activated. A lower rate of araCTP formation from 5'-chloro-araC explains the somewhat lower cytotoxic effect of this compound against various established cell lines in vitro compared to araC. Lipophilicity that would allow an oral drug formulation and certain other superior physico-chemical and biochemical characteristics of 5'-chloro-araC make this compound an interesting candidate for further investigations.

Animals↗
PubMed1990

Preparation, properties and antileukemic activity of arabinosylcytosine polysaccharide conjugates.

1. Conjugates of 1-beta-D-arabinofuranosylcytosine (araC) with polysaccharides containing carboxyl groups, such as polygalacturonic acid (PGA) and carboxymethylated yeast beta-D-glucan (CMG) were prepared. 2. Activation of the polysaccharidic carboxyl group by isobutylchloroformiate and formation of a peptide bond via 4-NH2 group of araC was used for a coupling reaction. 3. Elementary analysis, u.v. and i.r. spectra confirmed the structures of the conjugates. 4. The conjugates were most stable against the hydrolysis under the mild acid conditions. 5. It was also shown that under the physiological conditions trypsin catalyze the conjugate hydrolysis and the catalytic effect is higher than that of chymotrypsine. 6. It is suggested that trypsin or trypsin-like proteases could participate in the hydrolysis of the conjugates in vivo. PGA-araC and CMG-araC showed 1.5- or 2.5-times higher antileukemic activity than both free araC or polysaccharides.

Animals↗
PubMed1990

Comparison of some biochemical parameters of arabinosylcytosine and cyclocytidine in L1210 murine leukemia cells.

The basic biochemical characteristics of cyclocytidine hydrochloride (cC.HCl) and arabinosylcytosine (araC) were compared. It was demonstrated that despite different lipophilicity and different pK (4.15 for araC and 6.60 for cC.HCl), the mechanism of inhibition of DNA synthesis by both compounds is the same (ID50 for araC was 0.048 mumol/l and for cC. HCl 0.23 mumol/l). The compounds had a different mechanism of inhibition of RNA synthesis (ID50 for araC was 2.69 mmol/l and for cC.HCl 1.08 mmol/l) and showed a marginal effect on protein synthesis. Hydrolysis of the 0(2),2'-anhydro bond in cC.HCl and formation of araC in vivo was characterized by a Km = 280 mumol/l using HPLC. Deamination of araC in vivo was studied in healthy mice (Km = 247 mumol/l), 8.6% of arabinosyluracil 15 minutes after araC administration) and in mice with sensitive and araC resistant leukemia L1210 (15.5% and 8.5% of arabinosyluracil 15 minutes after araC administration, respectively). On the basis of different physico-chemical properties of cC.HCl and different mechanisms of inhibition of RNA synthesis it can be assumed that cC.HCl, when therapeutically used, may have its own mechanism of biological effect(s) and that its application may be therapeutically advantageous in some aspects as compared to araC.

Ancitabine↗
PubMed1989

Antitumor activity and cross-resistance studies with Pt-ascorbato complexes.

Two ascorbatoplatinum complexes, cis-diammineascorbatoplatinum(II) (AMA) and cis-bis(ascorbato)-trans-diaminocyclohexaneplatinum(II) (CHA), were tested for antitumor activity in vivo on P388 leukemia and in vitro in suspension culture and soft agar assay. Sensitive line of L1210 and sublines with resistance induced against cis-diamminedichloroplatinum(II) (DDP) and two derivatives of trans-1,2-diaminocyclohexane (DACH) were used for the in vitro tests. DNA synthesis inhibition in both sensitive and resistant cells was tested. The results are compared with DDP and DACH-Pt(II)-4-carboxyphtalate (TMA). Both tested complexes proved their antitumor activity in our experimental systems. The CHA complex was more effective than AMA and its effectiveness is comparable with that of DDP and TMA. Cross-resistance was found between DDP and AMA as well as TMA and CHA. There was no cross-resistance between DDP versus CHA, and TMA versus AMA.

Animals↗
PubMed1988

Therapy of P388 leukemia with benzaldehyde.

Optimal schedules of benzaldehyde (50-100 mg kg-1 intraperitoneally) on day 1 or on several days after inoculation of 10(5) P388 leukemia cells to DBA 2J mice increased survival by 70-100%. No significant prolongation of survival was observed between the various schedules of benzaldehyde treatment. Significantly longer survival was observed on day 30 after benzaldehyde treatment with 100 mg kg-1 on day 1 or 50 mg kg-1 on days 1-4 as compared to untreated controls, but no cure was achieved with any schedule and dose of benzaldehyde. No or minimal activity of benzaldehyde on L1210 and L5178Y leukemias, Ehrlich adenocarcinoma and Yoshida sarcoma was observed.

Animals↗
PubMed1986

Antitumor activity of four polymer bound trans-1,2-diaminocyclohexaneplatinum(II)-4-carboxyphtalate complexes tested in different model systems.

Four polymer bound Pt-complexes have been tested in in vivo and in in vitro systems. No substantial difference in effectivity against P388 leukemia in vivo was found when free trans-1,2-diaminocyclohexaneplatinum(II)-4-carboxyphtalate (TMA) was compared with the polymer bound complexes. The compound with the highest ID50 value in soft agar assay exhibited low effectivity in in vivo testing. Polymer bound Pt-complexes with faster release of the active molecule exhibited in in vivo and in soft agar assay slightly lower activity, when compared with suspension culture test system. Cross resistance of polymer bound complexes was investigated on three cell lines with induced drug resistance against different Pt-complexes. Cross resistance was found between TMA (free and polymer bound) and trans-1,2-diaminocyclohexaneplatinum(II)citrate (PEX) as well as trans-1,2-diaminocyclohexaneplatinum(II)glucarate (PTU) but there was no cross resistance between TMA and cis-diamminedichloroplatinum(II) (cis-DDP).

Animals↗
PubMed1985

Comparison of the effectivity of two diaminocyclohexane Pt-complexes.

A group of Pt-complexes was tested in various in vitro and in vivo systems. Murine P388 leukemia for the in vivo testing and three sublines of L1210 leukemia for the in vitro testing of two 1,2-diaminocyclohexane (DACH) derivatives of platinum were used. The effectivity of DACH-Pt(II) citrate and DACH-Pt(II) isocitrate with different ratio of trans- and/or cis-DACH was compared on the sensitive strain of L1210 and two resistant sublines: L1210 resistant to cis-diammine-dichloroplatinum(II) (cis-DDP) and L1210 resistant to trans-DACH-Pt(II) citrate. No cross-resistance was found between the DACH derivatives and cis-DDP. Slightly higher activity of citrate and trans-DACH in comparison with isocitrate and cis-DACH was found both in suspension culture and in vivo testing.

Animals↗
PubMed1984

In vivo and in vitro effectivity of some platinum complexes.

The following platinum complexes have been tested: cis-DDP--cis-diamminedichloroplatinum(II), Platinex--1,2-diaminocyclohexaneplatinum(II)citrate, Platuran--1,2-diaminocyclohexaneplatinum(II)-glucarate , TMA--1,2-diaminocyclohexaneplatinum(II)-4-carboxyphthalate,o xo-PT--cis-diamminedichloro-trans-dihydroxyplatinum(IV), CHIP--cis-dichloro-bis-(isopropylamine)-trans-dihydroxyplatinum(IV ), CBDCA--cis-diammine-cyclobutane-1,1-dicarboxylatoplatinum(II ). The activity of all tested complexes againt L1210 cells was higher in soft agar colony assay when compared with suspension culture of the same target cells. Using various doses and schedules oxo-Pt, CBDCA and cis-DDP exhibited the highest in vivo activity against P388 leukemia.

Animals↗
PubMed1984

Drug resistance induction and cross-resistance studies with Pt-complexes.

In vitro drug resistance was induced against cis-diamminedichloroplatinum(II) (cis-DDP), 1,2-diaminocyclohexaneplatinum-(II)citrate (PEX) and 1,2-diaminocyclohexaneplatinum(II)glucarate (PTU) in L1210 leukemia cell line. Using the resistant sublines cross-resistance was found between cis-DDP and cis-diamminecyclobutane-1,1-dicarboxylatoplatinum(II) (CBDCA) and between the three 1,2-diaminocyclohexane (DACH) derivatives tested. No (or low degree) cross-resistance was found between cis-DDP and DACH derivatives.

Animals↗
PubMed1983

Effect of combined chemotherapy tested in partially hepatectomized rats bearing Zajdela hepatoma.

Ascitic Zajdela hepatoma growing in partially hepatectomized rats was used for testing cytostatics in single and two-drugs combination chemotherapy. At the optimal dosage the highest selective activity against tumor cells (hepatoma) with low inhibition of normal cells (regenerating liver cells) was seen in the combination cis-platinum + methotrexate. Synergistic effect of this combination was found when suboptimal dose of MTX was combined with low doses of cis-Pt. Dose-dependent DNA synthesis inhibition following i.p. administration of cis-Pt was documented by 3H-thymidine incorporation. Although the content of platinum expressed per DNA amount was four times higher in regenerating hepatocytes when compared with hepatoma cells, the growth inhibiting effect of cis-Pt was selectively expressed against the hepatoma cells.

Animals↗