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Biomedical subjects

A Opolski

Publications and source records attributed to A Opolski.

At least 19 recordsLinked to original sources
PubMed2006

Synthesis and antiproliferative activity in vitro of diacetylenic thioquinolines.

A series of new acetylenic thioquinolines containing propargyl, 2-butynyl, or 4-bromo-2-butynyl groups has been prepared and tested for antiproliferative activity in vitro against the cells of human [SW707 (colon cancer), CCRF/CEM (leukemia)] and murine [P388 (leukemia), B16 (melanoma)] cancer lines. All the compounds obtained exhibited antiproliferative activity. The most active compounds 4h and 41-m have ID50 values ranging from 0.2 to 3.6 microg/ml, comparable to that of the reference compound cisplatin.

Animals↗
PubMed2005

Possible association between phages, Hoc protein, and the immune system.

Mammals have become "an environment" for enterobacterial phage life cycles. Therefore it could be expected that bacteriophages adapt to them. This adaptation must comprise bacteriophage proteins. Gp Hoc seems to have significance neither for phage particle structure nor for phage antibacterial activity. It is evidently not necessary for the "typical" antibacterial actions of bacteriophages. But the rules of evolution make it improbable that gp Hoc really has no function, and non-essential genes of T4-type phages are probably important for phages' adaptation to their particular lifestyle. More interesting is the eukaryotic origin of gp Hoc: a resemblance to immunoglobulin-like proteins that reflects their evolutionary relation. Substantial differences in biological activity between T4 and a mutant that lacks gp Hoc were observed in a mammalian system. Hoc protein seems to be one of the molecules predicted to interact with mammalian organisms and/or modulate these interactions.

Animals↗
PubMed2005

Erythrocyte magnesium fluxes in mice with nutritionally and genetically low magnesium status.

Low intracellular magnesium (Mg) contents may be observed in case of severe Mg insufficient intake or because of genetic regulation. This work was conducted to investigate the influence of intracellular Mg content on erythrocyte Mg(2+) influx and efflux in mice with low nutritionally and genetically (MGL and MGH mice) Mg status. C57BL6 mice were fed for 2 wks a diet containing 1000 mg Mg/kg diet Mg (control group), 100 mg Mg/kg diet (Mg-marginal group) or 30 mg Mg/kg diet (Mg deficient group), while mice with low (MGL) and high (MGH) Mg levels were fed a control diet for 2 wks. The quantification of erythrocyte Mg(2+) influx and efflux was performed using a stable isotope of Mg. Our results showed that erythrocyte Mg(2+) influx and efflux were respectively increased and decreased in nutritional Mg deficiency; while in genetically determined Mg status Mg(2+) fluxes were lower in MGL mice compared to MGH mice. Moreover Mg(2+) efflux was significantly correlated to Mg level in erythrocytes in all the mice studied (p < 0.001). In conclusion, erythrocyte Mg(2+) influx and efflux are modulated by low Mg status, namely decreased Mg(2+) efflux compensate for nutritional Mg deficiency, while the genetic regulation of erythrocyte Mg(2+) content depends on modification of Mg(2+) influx.

Animals↗
PubMed2005

Erythrocyte magnesium influx and efflux in solid tumor bearing mice.

Mg metabolism is modified in tumors and tumor-bearing organisms. In particular cancer patients often display elevated erythrocyte Mg levels. For a better understanding of the increased erythrocyte Mg content, we attempted to determine Mg fluxes in erythrocytes from tumor-bearing mice by Mg stable isotopes, using a method developed in our laboratory. To characterize the animal Mg status, blood and tissue Mg levels and hematological parameters were assayed. Results showed that in tumor-bearing mice total erythrocyte Mg was about 46% higher than in controls, whereas plasma and tissues Mg levels were not modified; red blood cells and hemoglobin as well as hematocrits were significantly decreased, while mean corpuscular volume and mean corpuscular hemoglobin were slightly but significantly increased in tumor-bearing mice compared to controls (by 3% and 4%, respectively), a picture corresponding to a normochromic, slightly macrocytic anemia. Erythrocyte Mg efflux was about 20% higher (404 + 59 versus 330 + 45 micromol/L, respectively, p < 0.05) in tumor-bearing mice compared to controls, whereas influx was not significantly modified (130 + 11 versus 122 + 19 micromol/L, respectively). Our data therefore exclude that the increased Mg content observed in erythrocytes of tumor-bearing mice is due to decrease of Mg efflux, or to an increase of Mg influx. On the other hand, the increased Mg content observed in erythrocytes of tumor-bearing mice could simply result from an increase of young Mg-enriched erythrocytes produced by the enhanced erythropoiesis which follows tumor-induced anemia.

Animals↗
PubMed2004

The biological functions of beta3 integrins.

Integrins comprise a large family of alphabeta heterodimeric cell-surface receptors that are found in many animal species. They are expressed on a wide variety of cells. There are two members in the beta3 integrin family: alphaIIb beta3 and alpha(v)beta3. This class of adhesion receptors mediates cell-cell and cell-extracellular matrix interactions. Dysregulation of the beta3 integrins is involved in the pathogenesis of many diseases (including cancer) and in transplant rejection. Integrins also play a key role in many virus infectious cycles. In this paper the biological functions of the beta3 family are reviewed, with particular interest in its role in cancer progression and metastasis.

Animals↗
PubMed2004

Changes in gene expression in the lungs of Mg-deficient mice are related to an inflammatory process.

It has been well documented that experimental hypomagnesemia in rodents evokes, as an early consequence, an inflammatory response. This also leads to the activation of cells producing reactive species of oxygen and, as a result, to the oxidative damage of tissues. Several studies have shown that lungs might be a specific target of Mg deficiency. Here, we report that 3 weeks of Mg deficiency in mice resulted in inflammatory processes in the lungs, including interstitial and perivascular pneumonia, manifested by the infiltration of leukocytes, plasmocytes and histiocytes, as well as the phenomenon of disseminated intravascular coagulation (DIC). These phenomena were accompanied by changes in gene expression assessed by cDNA array. In this study we identified 26 genes significantly changed by Mg deficiency, mostly involved in the anti-oxidative response, regulation of cell cycle and growth, apoptosis as well as cell-cell and cell-matrix interactions. We conclude that these changes are related to the phenomena of inflammatory and oxidative processes and consecutive remodeling occurring in the tissues as a result of Mg deficiency. This may have implications for at least several lung pathologies, including allergies, asthma, SIDS (Sudden Infant Death Syndrome) or facilitate formation of lung metastases.

Animals↗
PubMed2004

Antitumor activity of bacteriophages in murine experimental cancer models caused possibly by inhibition of beta3 integrin signaling pathway.

Bacteriophages (phages) as bacterial viruses are generally believed to have no intrinsic tropism for mammalian cells. In this study the interactions between phages and various eukaryotic cells were investigated. Binding of phages to the membranes of cancer and normal blood cells was observed. Moreover, it was shown that the wild-type phage T4 (wtT4) and its substrain HAP1 with enhanced affinity for melanoma cells inhibit markedly and significantly experimental lung metastasis of murine B16 melanoma cells by 47% and 80%, respectively. A possible molecular mechanism of these effects, namely a specific interaction between the Lys-Gly-Asp motif of the phage protein 24 and beta3-integrin receptors on target cells is proposed. It was also shown that anti-beta3 antibodies and synthetic peptides mimicking natural beta3 ligands inhibit the phage binding to cancer cells. This is in line with the well-described beta3 integrin-dependent mechanism of tumor metastasis. It is concluded that the blocking of beta3 integrins by phage preparations results in a significant decrease in tumor invasiveness.

Animals↗
PubMed2003

New insights into the possible role of bacteriophages in transplantation.

Due to the increasing prevalence of drug-resistant bacterial infections in the "post-antibiotic era," bacteriophages (bacterial viruses, BP) may be useful to administer to transplant recipients without exposing them to an increased risk of rejection, which occurs consequent to some viral infections. Herein we present evidence that at least some coliphages (T4) do not pose such risk. Interestingly, they may produce immunosuppressive effects extending transplant survival. Our data suggest that BP may be used in clinical transplantation to treat drug-resistant bacterial infections and perhaps as an adjunct to immunosuppressive therapy.

Animals↗
PubMed2002

Synthesis and antiproliferative activity in vitro of new propargyl thioquinolines.

The series of new 3,4-disubstituted thioquinolines which possess one or two O, S, Se-propargyl groups has been synthesized on the basis of the reaction of thioquinanthrene with alkoxides. All the compounds obtained were tested for their antiproliferative activity in vitro against the cells of three human cancer cell lines: SW707 (colon cancer), T47D (breast cancer), and HCV29T (bladder cancer). Two compounds, 4-(3-hydroxypropoxy)-3'-propargylthio-3,4'-diquinolinyl sulfide (3) and 3-methylthio-4-propargylselenoquinoline (13) exhibited significant cytostatic activity (ID50 < 4 micrograms/ml) against the cells of all the human cancer lines used and are good candidates for further anticancer activity studies in vitro using a broad panel of human and murine cell lines and for in vivo preclinical screening in different mouse transplantable tumor models.

Animals↗
PubMed2002

New propargyl thioquinolines--synthesis, antiproliferative activity in vitro and structure-activity relationships.

The series of the propargyl thioquinolines has been prepared on the basis of the reaction of thioquinanthrene (1) (1,4-dithiino[2,3-c:5,6-c']-diquinoline) with sodium alkoxides. Some of these compounds have revealed good antiproliferative activity in vitro against the cells of human and murine cancer lines. 13C NMR spectra were measured for the studied compounds to examine the electronic properties-activity relationships. A regression study on 10 compounds showed a linear correlation of antiproliferative activity with electronic properties, expressed as the 13C NMR chemical shift for C-4 carbon atom (R2 = 0.97). It was found that compounds with chemical shift for C-4 value falling in the range of 135-140 ppm exhibited significant antiproliferative activity, while compounds which possess moderate or low activity are located in the range 140-165 ppm. This finding leads to the expectation that the antiproliferative activity of propargyl thioquinolines can be predicted using the 13C NMR chemical shift value of their C-4 carbon atom.

Animals↗
PubMed2001

Synthesis and antiproliferative activity in vitro of novel 1,5-benzodiazepines. Part II.

The reaction of 2,2,4-trimethyl-1H-2,3-dihydro-1,5-benzodiazepine (1) with cinnamoyl chloride leading to the formation of 1-cinnamoyl derivative 2 is described. Two novel benzodiazepines, 2,2,4-trimethyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepine (3) and 1-cinnamoyl-2,2,4-trimethyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepine (4), were synthesized by the reduction of 1 and 2 using NaBH4 in i-PrOH and two other derivatives 5 and 6 were obtained by reaction of 4 with equimolar and dimolar quantity of cinnamoyl chloride, respectively. The structures of 1-6 were confirmed by analytical and spectral data (IR, 1H NMR, and MS). 7-Carboxy-2,2,4-trimethyl-1H-2,3-dihydro-1,5-benzodiazepine (7) was synthesized and its crystals were subjected to X-ray analysis. Benzodiazepines 1-6 were evaluated for antiproliferative activity in vitro. Among the compounds tested, 4-6 exhibited cytotoxic activity against human cancer cell lines, namely SW707 (colon cancer), MCF-7 (breast cancer), A549 (lung cancer), and HCV29T (bladder cancer).

Antineoplastic Agents↗
PubMed2001

Synthesis and antiproliferative activity in vitro of new derivatives of 3-aminopyrazolo[3,4-b]pyridine. Part 1. Reaction of 3-aminopyrazolo[3,4-b]pyridine with 1,3-, 1,4-diketones and alpha,beta-unsaturated ketones.

The synthesis of several new pyrazolo[3,4-b]pyridine, pyrido[2',3':3,4]-pyrazolo[1,5-a]pyrimidine and imidazo[1',2':1,5]pyrazolo[3,4-b]pyridine derivatives is described. The obtained compounds were tested for their antiproliferative activity in vitro. One of them, 4-phenyl-2-(3,4,5-trimethoxy-beta-styrylo)pyrido- [2',3':3,4]pyrazolo[1,5-a]pyrimidine (9), revealed cytotoxic properties against the cells of all three human cancer cell lines applied. Another one, 2,4-dimethyl-pyrido[2',3':3,4]pyrazolo[1,5-a]-pyrimidine (2), revealed weak cytotoxic activity only against the cells of human bladder cancer cell line HCV29T. All other compounds tested did not reveal any cytotoxic activity.

Animals↗
PubMed2001

[Inhibitors of neoangiogenesis in antineoplastic therapy].

The role of angiogenesis in tumor growth and metastasis is discussed. The endogenous activators and inhibitors of tumor angiogenesis are presented and their mechanisms of action are reviewed. An overview on angiogenesis as a new potential target of antitumor therapy is described. The clinical trials of various antiangiogenic agents are briefly summarized and their differential mechanisms of action are discussed.

Angiogenesis Inhibitors↗
PubMed2000

Cytotoxic and antitumor effect of fibrinogen-methotrexate conjugate.

In this paper we describe the chemical procedure of fibrinogen-methotrexate (F-MTX) conjugate preparation and its in vitro and in vivo antitumor activity. F-MTX conjugates were synthesized in reaction of fibrinogen with MTX N-hydroxysuccynimide ester. The conjugates were not cross-linked and were soluble in water. The results of the in vitro and in vivo studies have shown: (1) a lower in vitro cytotoxicity of the F-MTX conjugate as compared with MTX alone; (2) a significantly higher in vivo antitumor activity of the F-MTX conjugate in mice with P388 leukemia as compared with MTX alone; (3) a significantly increased in vivo lethal toxicity of F-MTX as compared with MTX. The results suggest the therapeutic utility of the fibrinogen-methotrexate conjugate and the usefulness of fibrinogen as a chemotherapeutic drug carrier. However, a new effort in the preparation of F-MTX conjugate should be made to decrease its in vivo toxicity.

Animals↗
PubMed2000

Antiproliferative activity in vitro of new malatoplatinum(ll) complexes.

The results of studies on antiproliferative activity in vitro of nine new platinum(II) complexes against cells of eight human and six murine neoplastic cell lines are described. New complexes with the anionic rest originating from enantiomeric forms of hydroxydicarboxylic malic acid were synthesized to obtain agents with increased water solubility and decreased toxicity. Three compounds, coded 1-3, with ethylenediamine as a neutral ligand, showed cytotoxic activity against 12 out of 14 target cell lines. Their cytotoxic activity was similar or even slightly higher than that of the reference carboplatin. The remaining six compounds, coded 4-9, with 1-alkylimidazole as a neutral ligand, revealed rather low cytotoxic activity, and only against the cells of the human bladder cancer cell line Hu1703He, ovarian cancer cell line OAW-42 and mouse leukemia P388. Most of them appeared to be negative against all other cell lines. No compounds, including reference carboplatin, showed any cytotoxicity against the cells of the T47D human breast cancer cell line or B16F-10 mouse melanoma cell line. The results obtained are in accordance with common opinion, i.e. that the presence of neutral amine ligands with NH groups is required for the cytotoxic activity of platinum complexes. Compounds with a primary amine (ethylenediamine) showed higher cytotoxic activity in vitro than complexes with a tertiary amine (1alkylimidazole).

Animals↗
PubMed2000

Biological activity in vitro of side-chain modified analogues of calcitriol.

The results of our studies on the biological activity of side-chain modified analogues of vitamin D are reviewed. These analogues appeared to be effective in induction of cell differentiation, inhibition of tumour cell proliferation in vitro and in increasing of antitumour effect of cytostatics. On the other hand, inhibition of cytostatic-induced apoptosis by these compounds was observed. The mechanism of the antiproliferative effect of calcitriol analogues in vitro is discussed. The induction of antigens CD14 and CD11b expression and phagocytic activity of HL-60 cells after exposure to these compounds is related to their effect on cell differentiation. The differentiation of the HL-60 leukaemia cells induced by side-chain modified analogues of calcitriol increases their sensitivity to the antiproliferative effect of cisplatin, doxorubicin and genistein, despite of that this pretreatment causes resistance of these cells to cytostatics-induced apoptosis. We observed a synergistic antiproliferative effect of the combined therapy using analogues of calcitriol with subsequent treatment with the above-mentioned cytostatics. This effect was measured as a significant decrease of the ID50 values for each cytostatic applied after pretreatment of the tumour cells with the calcitriol analogues. The results presented suggest that the improved therapeutic effect may be achieved also in vivo by the combined application of the analogues (without calcemic activity) of calcitriol with antitumour agents.

Antineoplastic Agents↗
PubMed2000

Novel Ru(III), Rh(III), Pd(II) and Pt(II) complexes with ligands incorporating azole and pyrimidine rings. I. Antiproliferative activity in vitro.

A number of co-ordination compounds of Ru(III), Rh(III), Pd(II) and Pt(II) with ligands incorporating azole and pyrimidine rings has been synthesized. The in vitro cell proliferation-inhibitory activity of these compounds was examined against human cancer cell lines: A 549 (lung carcinoma), LS-180 (colon cancer) and MCF-7 (breast cancer), using SRB technique. Six out of 13 compounds studied revealed cytotoxic activity in vitro. Inhibitory dose 50% (ID50) was lower than 4 microg/ml, which is an activity criterion accepted in conventional in vitro cytotoxic screening tests. Two compounds revealed weak cytotoxic activity with ID50 higher than 4 microg/ml and five compounds were inactive.

Antineoplastic Agents↗