Wyniki wyszukiwania

1

Biological effects of liposomal formulation of DIMIQ potential antitumor indolo[2,3-B]quinoline agent on hepatoma morris 5123 cells

100%

Suchoszek-Lukaniuk K., Jaromin A., Peczynska-Czoch W., Kaczmarek L., Malicka-Blaszkiewicz M., Kozubek A.

Cellular and Molecular Biology Letters

|

2005

|

tom 10

|

nr Suppl.

2

Aza and diaza bioisosteric anthracene-9,10-diones as antitumor agents

100%

Krapcho A. P., Maresch M. J., Hacker M. P., Menta E., Oliva A., Giuliani F. C., Spinelli S.

Acta Biochimica Polonica

|

1995

|

tom 42

|

nr 4

Synthetic routes to aza and diaza bioisosteres related to the anthracene-9,10-dione, mitoxantrone, have been developed. The antitumor properties of these chemotypes are compared with those exhibited by the corresponding carbocyclic analogues. The sensitivity of the expressed cytotoxicities on the position(s) of the nitrogen atom(s) are discussed in terms of potential cellular targets. Several analogues show potential for clinical evaluations.

3

Single-electron reduction of quinone and nitroaromatic xenobiotics by recombinant rat neuronal nitric oxide synthase

86%

Anusevicius Z., Nivinskas H., Sarlauskas J., Sari M.-A., Boucher J.-L., Cenas N.

Acta Biochimica Polonica

|

2013

|

tom 60

|

nr 2

We examined the kinetics of single-electron reduction of a large number of structurally diverse quinones and nitroaromatic compounds, including a number of antitumour and antiparasitic drugs, and nitroaromatic explosives by recombinant rat neuronal nitric oxide synthase (nNOS, EC 1.14.13.39), aiming to characterize the role of nNOS in the oxidative stress-type cytotoxicity of the above compounds. The steady-state second-order rate constants (kcat/Km) of reduction of the quinones and nitroaromatics varied from 102 M-1s-1 to 106 M-1s-1, and increased with an increase in their single-electron reduction potentials (E17). The presence of Ca2+/calmodulin enhanced the reactivity of nNOS. These reactions were consistent with an "outer sphere" electron-transfer mechanism, considering the FMNH·/FMNH2 couple of nNOS as the most reactive reduced enzyme form. An analysis of the reactions of nNOS within the 'outer sphere' electron-transfer mechanism gave the approximate values of the distance of electron transfer, 0.39-0.47 nm, which are consistent with the crystal structure of the reductase domain of nNOS. On the other hand, at low oxygen concentrations ([O2] = 40-50 µM), nNOS performs a net two-electron reduction of quinones and nitroaromatics. This implies that NOS may in part be responsible for the bioreductive alkylation by two-electron reduced forms of antitumour aziridinyl-substituted quinones under a modest hypoxia.

4

Interactions of antitumour triazoloacridinones with DNA

86%

Koba M., Konopa J.

Acta Biochimica Polonica

|

2007

|

tom 54

|

nr 2

Triazoloacridinones (TA) are a new group of potent antitumor compounds, from which the most active derivative, C-1305, has been selected for extended preclinical trials. This study investigated the mechanism of TA binding to DNA. Initially, for selected six TA derivatives differing in chemical structures as well as cytotoxicity and antitumor activity, the capability of noncovalent DNA binding was analyzed. We showed that all triazoloacridinones studied stabilized the DNA duplex at a low-concentration buffer but not at a salt concentration corresponding to that in cells. DNA viscometric studies suggested that intercalation to DNA did not play a major role in the mechanism of the cytotoxic action of TA. Studies involving cultured cells revealed that triazoloacridinone C-1305 after previous metabolic activation induced the formation of interstrand crosslinks in DNA of some tumor and fibroblast cells in a dose dependent manner. However, the detection of crosslink formation was possible only when the activity of topoisomerase II in cells was lowered. Furthermore, it was impossible to validate the relevance of the ability to crosslink DNA to biological activity of TA derivatives.

5

Gemcitabine affects the detection of deoxyribonucleotides with a DNA polymerase elongation assay

86%

Van Moorsel C. J. A., Smid K., Pinedo H. M., Peters G. J.

Cellular and Molecular Biology Letters

|

1999

|

tom 04

|

nr 3

6

Metabolic transformations of antitumor imidazoacridinone, C-1311, with microsomal fractions of rat and human liver

72%

Wisniewska A., Chrapkowska A., Kot-Wasik A., Konopa J., Mazerska Z.

Acta Biochimica Polonica

|

2007

|

tom 54

|

nr 4

831-838

The imidazoacridinone derivative C-1311 is an antitumor agent in Phase II clinical trials. The molecular mechanism of enzymatic oxidation of this compound in a peroxidase model system was reported earlier. The present studies were performed to elucidate the role of rat and human liver enzymes in metabolic transformations of this drug. C-1311 was incubated with different fractions of liver cells and the reaction mixtures were analyzed by RP-HPLC. We showed that the drug was more sensitive to metabolism with microsomes than with cytosol or S9 fraction of rat liver cells. Incubation of C-1311 with microsomes revealed the presence of four metabolites. Their structures were identified as dealkylation product, M0, as well as a dimer-like molecule, M1. Furthermore, we speculate that the hydroxyl group was most likely substituted in metabolite M3. It is of note that a higher rate of transformation was observed for rat than for human microsomes. However, the differences in metabolite amounts were specific for each metabolite. The reactivity of C-1311 with rat microsomes overexpressing P450 isoenzymes, of CYP3A and CYP4A families was higher than that with CYP1A and CYP2B. Moreover, the M1 metabolite was selectively formed with CYP3A, whereas M3 with CYP4A. In conclusion, this study revealed that C-1311 varied in susceptibility to metabolic transformation in rat and human cells and showed selectivity in the metabolism with P450 isoenzymes. The obtained results could be useful for preparing the schedule of individual directed therapy with C-1311 in future patients.

7

The hidden side of disodium cromolyn: from mast cell stabilizer to an angiogenic factor and antitumor agent

72%

Cimpean A. M., Raica M.

Archivum Immunologiae et Therapiae Experimentalis

|

2016

|

tom 64

|

nr 6

8

Specific killing of mouse leukemic cells with ricin A-chain immunotoxin

72%

Wiedlocha A., Salwa J., Paprocka M., Steuden I., Radzikowski C.

Archivum Immunologiae et Therapiae Experimentalis

|

1989

|

tom 37

|

nr 1-2

9

Cancer immunotherapy using cells modified with cytokine genes

72%

Kowalczyk D. W., Wysocki P. J., Mackiewicz A.

Acta Biochimica Polonica

|

2003

|

tom 50

|

nr 3

The ability of various cytokines to hamper tumor growth or to induce anti-tumor immune response has resulted in their study as antitumor agents in gene therapy approaches. In this review we will concentrate on the costimulation of antitumor immune responses using modification of various cell types by cytokine genes. Several strategies have emerged such as (i) modification of tumor cells with cytokine genes ex vivo (whole tumor cell vaccines), (ii) ex vivo modification of other cell types for cytokine gene delivery, (iii) delivery of cytokine genes into tumor microenvironment in vivo, (iv) modification of dendritic cells with cytokine genes ex vivo. Originally single cytokine genes were used. Subsequently, multiple cytokine genes were applied simultaneously, or in combination with other factors such as chemokines, membrane bound co-stimulatory molecules, or tumor associated antigens. In this review we discuss these strategies and their use in cancer treatment as well as the promises and limitations of cytokine based cancer gene therapy. Clinical trials, including our own experience, employing the above strategies are discussed.

10

The effect of new non-cross resistant antitumour agents on the energy state of human erythrocytes

72%

Nowak R., Baranowska-Bosiacka I., Stefanska B., Machalinski B., Hlynczak A. J., Tarasiuk J.

Acta Biochimica Polonica

|

2005

|

tom 52

|

nr 4

Multidrug resistance (MDR) of tumour cells is related to the overexpression of ATP-dependent pumps responsible for the active efflux of antitumour agents out of resistant cells. Benzoperimidine and anthrapyridone compounds exhibit comparable cytotoxic activity against sensitive and MDR tumour cells. They diffuse extremely rapidly across the plasma membrane and render the ATP-dependent efflux inefficient. Such uptake could disturb an energy metabolism of normal cells possessing an elevated level of ATP-dependent proteins, especially erythrocytes having a high level of the MRP1, MRP4 and MRP5 proteins. In this study the effect of five antitumour agents: benzoperimidine (BP1), anthrapyridones (CO1, CO7) and reference drugs used in the clinic: doxorubicin (DOX) and pirarubicin (PIRA), on the energetic state in human erythrocytes has been examined. These compounds have various types of structure and kinetics of cellular uptake (slow - DOX, CO7, moderate - PIRA, fast - BP1, CO1) resulting in their different ability to saturate ATP-dependent transporters. The energetic state of erythrocytes was examined by determination of purine nucleotide contents (ATP, ADP, AMP), NAD+ and values of adenylate energy charge (AEC) using an HPLC method. It was found that the level of nucleotides as well as the AEC value of erythrocytes were not changed during 24 h of incubation with these agents independently of their structure and ability to saturate ATP-dependent pumps. This is a very promising result in view of their potential use in the clinic as antitumour drugs against multidrug resistant cancers.

11

Robot-based discovery of protein kinase inhibitors as novel anti-tumor agents

72%

Schachtele C., Totzke F., Marme D.

Cellular and Molecular Biology Letters

|

1998

|

tom 03

|

nr 3

12

Artykuł dostępny w postaci pełnego tekstu - kliknij by otworzyć plik

Ancient history of X-ray crystal structure of B-DNA oligomers and its perspective

58%

Grzeskowiak K., Ohishi H.

BioTechnologia. Journal of Biotechnology Computational Biology and Bionanotechnology

|

2011

|

tom 92

|

nr 3

Ograniczanie wyników

Biological effects of liposomal formulation of DIMIQ potential antitumor indolo[2,3-B]quinoline agent on hepatoma morris 5123 cells

Aza and diaza bioisosteric anthracene-9,10-diones as antitumor agents

Single-electron reduction of quinone and nitroaromatic xenobiotics by recombinant rat neuronal nitric oxide synthase

Interactions of antitumour triazoloacridinones with DNA

Gemcitabine affects the detection of deoxyribonucleotides with a DNA polymerase elongation assay

Metabolic transformations of antitumor imidazoacridinone, C-1311, with microsomal fractions of rat and human liver

The hidden side of disodium cromolyn: from mast cell stabilizer to an angiogenic factor and antitumor agent

Specific killing of mouse leukemic cells with ricin A-chain immunotoxin

Cancer immunotherapy using cells modified with cytokine genes

The effect of new non-cross resistant antitumour agents on the energy state of human erythrocytes

Robot-based discovery of protein kinase inhibitors as novel anti-tumor agents

Ancient history of X-ray crystal structure of B-DNA oligomers and its perspective