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Biomedical subjects

M Hrubisko

Publications and source records attributed to M Hrubisko.

At least 37 records · Page 2Linked to original sources

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↗

Growth, flow cytometric, and karyological characterization of L1210 cell sublines resistant to various Pt derivatives.

Growth, flow cytometric, and karyological characteristics were analyzed with respect to differences between sensitive L1210 cells and eight sublines resistant to cisplatin (DDP), 1,2-diaminocyclohexane(DACH)-Pt(II) citrate, DACH-Pt(II) glucarate, cis-dichloro-bis-(isopropylamine)-trans-dihydroxyplatinum (IV) (CHIP, iproplatin), and methotrexate (MTX). No great differences were found in growth properties. The sensitive and a majority of resistant sublines displayed similar flow cytometric and karyological characteristics, major differences were found only in the sublines resistant to CHIP. The relationship between the mechanism(s) of resistance and different pharmacokinetics of the drugs is discussed with special reference to DNA content and chromosome structure.

Animals↗

Fibrinolytic activity disturbances in malignant blood diseases.

Repeated investigation of 105 patients suffering from different blood disorders demonstrated a more frequent occurrence of disturbances in fibrinolysis (66% as in blood clotting tests (40%) indicating a compensated or decompensated intravascular blood clotting. In the group of patients with thrombocythaemia the disturbance of fibrinolysis as much as in 83% was present, and always in sense of insufficiency. In myeloproliferative diseases without proliferation of megakaryocytes the antithrombotic treatment improved both the fibrinolysis as well as the clotting disturbances. In thrombocythaemia the long-termed treatment with anti-platelet drugs, eventually with other antithrombotics favourably influenced the blood clotting parameters as well as the symptomatology from vascular occlusion, however the euglobulin lysis remained unchanged. In sense of the idea on the ineffective megakaryocytopoiesis in primary and other myeloproliferative diseases accompanying thrombocythaemia attention is called to the specificity of the fibrinolytic insufficiency in thrombocythaemia in comparison with other myeloproliferative diseases without thrombocythaemia.

Anemia↗

Results and further perspectives of plasmocytoma chemotherapy.

Polychemotherapy has improved prognostic parameters of survival in patients with plasmocytoma. The mean survival in patients given long-time prednisone and melphalan treatment is 20 months, in those given polychemotherapy over 30 months. In patients with a slow disease progression the combinations COPP and VMCP give satisfactory results in about 40%, but in a majority of patients more effective treatment is necessary. The authors compare the 5-year survival of two polychemotherapy groups with the prednisone and melphalan group. The mean survival after prednisone and melphalan was 33 months, after polychemotherapy (groups COPP, VMCP) 46 months and 57 months (VMCP + M2), respectively. Survival time was influenced by the clinical stage.

Antineoplastic Combined Chemotherapy Protocols↗

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↗

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↗

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↗