BIOMAGNETISM OF DRUG-SENSITIVE AND DRUG-RESISTANT MALIGNANT TUMORS AFTER INJECTION OF FERROMAGNETIC NANOCOMPOSITE.

Unlabelled: Magnetic signals emitted by living organisms, regardless of a biological species, are important biophysical indicators. The study of these indicators is very relevant and promising for the visualization of the tumor process and the development of technologies using artificial intelligence when it comes to malignant neoplasms, particularly resistant to chemotherapy.

Aim: To measure magnetic signals from transplantable rat tumors and their counterparts resistant to cytostatics for evaluating the features of the accumulation of iron-containing nanocomposite Ferroplat.

Biomagnetism of tumor in rats with Guerin's carcinoma after injection of ferromagnetic nanocomposite (Ferroplat): contactless measurement.

Aim: In order to develop fundamentally new technologies for non-invasive and safer diagnosis of cancer, we aimed to detect non-contact magnetic signals from a malignant tumor in animals treated or not-treated with the ferromagnetic nanocomposite Ferroplat.

Materials And Methods: Guerin's carcinoma was used as a model of tumor growth. The biomagnetism of the tumor was evaluated in the dynamics of its growth.

Cerium Oxide Nanoparticles and Their Efficient Antibacterial Application against Gram-Positive and Gram-Negative Pathogens.

In this study, the antibacterial activity of cerium oxide nanoparticles on two Gram-negative and three Gram-positive foodborne pathogens was investigated. CeO nanoparticles (CeO nps) were synthesized by a Wet Chemical Synthesis route, using the precipitation method and the Simultaneous Addition of reactants (). The as-obtained precursor powders were investigated by thermal analysis (TG-DTA), to study their decomposition process and to understand the CeO nps formation.

The influence of lactoferrin on elemental homeostasis and activity of metal-containing enzymes in rats with Walker-256 carcinosarcoma.

Aim: To investigate the content of essential elements (EE): copper, zinc, magnesium, iron and calcium and the evaluation of the activity of metal-containing enzymes - ceruloplasmin (CP), myeloperoxidase (MPO) and the content of transferrin (TF) in blood plasma (BP) and tumor tissue (TT) of animals with Walker-256 carcinosarcoma treated with lactoferrin (LF).

Materials And Methods: The study of the EE content and the activity of the abovementioned enzymes was carried out on rats with Walker-256 carcinosarcoma treated with LF at the doses of 1 and 10 mg/kg of body weight. The quantitative content of EE in BP and TT of animals was determined using the inductively coupled plasma atomic emission spectroscopy (ICP-AES).

Influence of ferromagnetic nanocomposite (Ferroplat) on human breast cancer cells of different malignancy degrees: pro/antioxidant balance and energy metabolism.

Aim: To study the effect of Ferroplat (FrP) on the indexes of pro/antioxidant balance and energy metabolism in breast cancer cells of different malignancy degree and different sensitivity to drug therapy.

Materials And Methods: The study was carried out on breast cancer cells of low (T47D, MCF-7) and high malignancy degree (MCF-7/DDP (cisplatin-resistant), MDA-MB-231, MDA-MB-468) using cell culture techniques, immunocytochemical, biochemical, biophysical methods, flow cytometry and polarography.

Results: We established that the addition of FrP to the culture medium reduces the activity of glucose-6-phosphate dehydrogenase (G6PDH), superoxide dismutase (SOD) and the level of non-protein thiols by 32-41% (p < 0.

Antitumor and genotoxic effects of lactoferrin in Walker-256 tumor-bearing rats.

Aim: To investigate the influence of exogenous lactoferrin (LF) on tumor growth, energy and lipid metabolism of Walker-256 carcinosarcoma and to assess genotoxic effects of LF.

Materials And Methods: The study was performed on Walker-256 tumor-bearing rats. Total lipids and phospholipids were determined by thin-layer chromatography.

The role of adatoms in chloride-activated colloidal silver nanoparticles for surface-enhanced Raman scattering enhancement.

Chloride-capped silver nanoparticles (Cl-AgNPs) allow for high-intensity surface-enhanced Raman scattering (SERS) spectra of cationic molecules to be obtained (even at nanomolar concentration) and may also play a key role in understanding some fundamental principles behind SERS. In this study, we describe a fast (<10 min) and simple protocol for obtaining highly SERS-active colloidal silver nanoparticles (AgNPs) with a mean diameter of 36 nm by photoconversion from AgCl precursor microparticles in the absence of any organic reducing or capping agent. The resulting AgNPs are already SERS-activated by the Cl ions chemisorbed onto the metal surface where the chloride concentration in the colloidal solution is 10 M.

Influence of exogenous lactoferrin on the oxidant/antioxidant balance and molecular profile of hormone receptor-positive and -negative human breast cancer cells in vitro.

Aim: To investigate the mechanisms of cytotoxic activity and pro-/antioxidant effect of lactoferrin on hormone receptor-positive and receptor-negative breast cancer cells in vitro.

Materials And Methods: The study was performed on receptor-positive (MCF-7, T47D) and receptor-negative (MDA-MB-231, MDA-MB-468) human breast cancer cell lines. Immunocytochemical staining, flow cytometry, low-temperature electron paramagnetic resonance, and the Comet assay were used.

Enhanced antitumor activity of surface-modified iron oxide nanoparticles and an α-tocopherol derivative in a rat model of mammary gland carcinosarcoma.

Maghemite (γ-FeO) nanoparticles were obtained by coprecipitation of ferrous and ferric salts in an alkaline medium followed by oxidation; the nanoparticles were coated with poly(-dimethylacrylamide) (PDMA) and characterized by transmission electron microscopy, attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering, thermogravimetric and elemental analyses, and magnetic measurements in terms of particle morphology, size, polydispersity, amount of coating, and magnetization, respectively. The effects of α-tocopherol (Toc) and its phenolic (Toc-6-OH) and acetate (Toc-6-Ac) derivatives on Fe release from γ-FeO@PDMA, as well as from γ-FeO and CuFeO nanoparticles (controls), were examined in vitro using 1,10-phenanthroline. The presence of tocopherols enhanced spontaneous Fe release from nanoparticles, with Toc-6-OH exhibiting more activity than neat Toc.

Investigation of a Potential Pharmacokinetic Interaction Between Nebivolol and Fluvoxamine in Healthy Volunteers.

Purpose: To investigate whether fluvoxamine coadministration can influence the pharmacokinetic properties of nebivolol and its active hydroxylated metabolite (4-OH-nebivolol) and to assess the consequences of this potential pharmacokinetic interaction upon nebivolol pharmacodynamics.

Methods: This open-label, non-randomized, sequential clinical trial consisted of two periods: Period 1 (Reference), during which each volunteer received a single dose of 5 mg nebivolol and Period 2 (Test), when a combination of 5 mg nebivolol and 100 mg fluvoxamine was given to all subjects, after a 6-days pretreatment regimen with fluvoxamine (50-100 mg/day). Non-compartmental analysis was used to determine the pharmacokinetic parameters of nebivolol and its active metabolite.

Modifying effects of 5-azacytidine on metal-containing proteins profile in Guerin carcinoma with different sensitivity to cytostatics.

Aim: To assess the influence of the treatment with 5-azacytidine (5-aza) on the profile of metal-containing proteins and factors of their regulation in Guerin carcinoma cells in vivo.

Materials And Methods: The study was conducted on Wistar rats transplanted with wild-type Guerin carcinoma (Guerin/WT) and its strains resistant to cisplatin (Guerin/CP) or doxorubicin (Guerin/Dox). Animals were distributed in 6 groups treated with 5-aza and control animals without treatment.

Evaluation of the Potential Pharmacokinetic Interaction between Atomoxetine and Fluvoxamine in Healthy Volunteers.

Background/aims: Attention deficit hyperactivity disorder (ADHD) is frequently associated with other psychiatric pathologies. Therefore, the present study investigated a possible pharmacokinetic interaction between atomoxetine (ATX), a treatment option for ADHD, and an antidepressant, namely, fluvoxamine (FVX).

Methods: Designed as an open-label, non-randomized clinical trial, the study included 2 periods.

Evaluation of a Potential Metabolism-Mediated Drug-Drug Interaction Between Atomoxetine and Bupropion in Healthy Volunteers.

Purpose: To evaluate the impact of bupropion on the pharmacokinetic profile of atomoxetine and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide, in healthy volunteers.

Methods: An open-label, non-randomized, two-period, sequential clinical trial was conducted as follows: during Period I (Reference), each volunteer received a single oral dose of 25 mg atomoxetine, whilst during Period II (Test), a combination of 25 mg atomoxetine and 300 mg bupropion was administered to all volunteers, after a pretreatment regimen with bupropion for 7 days. Next, after determining atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations, their pharmacokinetic parameters were calculated using a noncompartmental method and subsequently compared to determine any statistically significant differences between the two periods.

Hepcidin as a possible marker in determination of malignancy degree and sensitivity of breast cancer cells to cytostatic drugs.

Aim: To investigate the role of hepcidin (Hepc) in the formation of cells malignant phenotype in vitro and its expression in the dyna-mics of growth of Walker-256 carcinosarcoma with different sensitivity to doxorubicin (Dox).

Materials And Methods: The cell lines used in the analysis included T47D, MCF-7, MDA-MB-231, MDA-MB-468, MCF/CP, and MCF/Dox. Hepc expression was studied by immunocytochemical method.

Better prognosis in overweight/obese coronary heart disease patients with high plasma levels of leptin.

Background And Aim: The involvement of leptin in atherosclerosis is very complex, including inflammation, the oxidative stress and thrombosis. Leptin has atherogenic and also antiatherogenic actions. In obesity elevated leptin levels are not sufficient to prevent disturbances of energy balance, suggesting that obese people are leptin resistant.

The influence of paroxetine on the pharmacokinetics of atomoxetine and its main metabolite.

Background And Aims: To evaluate the effects of paroxetine on the pharmacokinetics of atomoxetine and its main metabolite, 4-hydroxyatomoxetine-O-glucuronide, after coadministration of atomoxetine and paroxetine in healthy volunteers.

Methods: 22 healthy volunteers, extensive metabolizers, took part in this open-label, non-randomized, clinical trial. The study consisted of two periods: Reference, when a single oral dose of 25 mg atomoxetine was administrated to each subject and Test, when 25 mg atomoxetine and 20 mg paroxetine were coadministered.

Remodulating effect of doxorubicin on the state of iron-containing proteins, and redox characteristics of tumor with allowance for its sensitivity to cytostatic agents.

The study was aimed at determining the changes of metal-containing proteins in blood serum and tumor tissue of animals with parental and doxorubicin-resistant strains of Walker-256 carcinosarcoma before and after the cytostatic administration. It has been shown that upon doxorubicin action the levels of total iron and transferrin in the tissues from the both groups of animals decreased while that of ferritine simultaneously increased with more pronounced pattern in the group of animals with resistant tumor strain. It has been shown that upon the action of doxorubicin in tumor tissue of animals with different sensitivity to the cytostatic there could be observed oppositely directed changes in the redox state of these cells that in turn determined the content of “ free iron” complexes, RO S generation and concentration of active forms of matrix metaloproteinase- 2 and matrix metaloproteinase-9, namely, the increase of these indexes in animals with parental strain and their decrease in animals with the resistant one.

Green tea, red wine and lemon extracts reduce experimental tumor growth and cancer drug toxicity.

Aim: To evaluate antitumor effect of plant polyphenol extracts from green tea, red wine lees and/or lemon peel alone and in combination with antitumor drugs on the growth of different transplanted tumors in experimental animals.

Materials And Methods: Green tea extract (GTE) was prepared from green tea infusion. GTE-based composites of red wine (GTRW), lemon peel (GTRWL) and/or NanoGTE as well as corresponding nanocomposites were prepared.

METALLOPROTEINS DURING DEVELOPMENT OF WALKER-256 CARCINOSARCOMA RESISTANT PHENOTYPE.

The study was focused on the detection of changes in serum and tumor metal-containing proteins in animals during development ofdoxorubicin-resistant phenotype in malignant cells after 12 courses of chemotherapy. We found that on every stage of resistance development there was a significant increase in content of ferritin and transferrin proteins (which take part in iron traffick and storage) in Walker-256 carc'inosarcoma tissue. We observed decreased serumferritin levels at the beginning stage of the resistance development and significant elevation of this protein levels in the cases withfully developed resistance phenotype.

Prevention of myelosuppression by combined treatment with enterosorbent and granulocyte colony-stimulating factor.

Unlabelled: Hematotoxicity and its complication are the prominent limiting factors for rational treatment of malignancies. Granulocyte colony-stimulating factor (G-CSF) is used to increase granulocyte production. It has been shown previously that enterosorption causes prominent myeloprotective activity also.

Pharmacological effect of aminoferrocene in mice with L1210 leukemia.

Aim: To study the cytostatic and some biological effects of aminoferrocene using mice with L1210 lymphoid leukemia.

Materials And Methods: Experiments were performed on BDF1 male mice (DBA/2, female × C57Bl/6, male) with transplantable L1210 lymphoid leukemia. Determination of antitumor activity of Benzyl-Fc Boron (Bn), it was injected intraperitoneally 6 times daily, starting on day 2 after L1210 leukemia cell transplantation.

Metabolic changes during development of Walker-256 carcinosarcoma resistance to doxorubicin.

Aim: To study indices of energy metabolism, content of K(+) and Mg(++) both in peripheral blood and in Walker-256 carcinosarcoma during development of resistance to doxorubicin.

Methods: Resistance of Walker-256 carcinosarcoma to doxorubicin has been developed through 12 subsequent transplantations of tumor after the chemotherapy. Parental strain was inhibited by drug by 65%, while transitional resistant substrains - by 30% and 2%, respectively.

Improved synthesis of N-benzylaminoferrocene-based prodrugs and evaluation of their toxicity and antileukemic activity.

We report on an improved method of synthesis of N-benzylaminoferrocene-based prodrugs and demonstrate its applicability by preparing nine new aminoferrocenes. Their effect on the viability of selected cancer cells having different p53 status was studied. The obtained data are in agreement with the hypothesis that the toxicity of aminoferrocenes is not dependent upon p53 status.

Peculiarities of antioxidant system and iron metabolism in organism during development of tumor resistance to cisplatin.

Aim: To study in vivo the peculiarities of changes of iron metabolism and antioxidant system in dynamics of growth of Guerin carcinoma with different sensitivity to cisplatin.

Materials And Methods: In order to evaluate the content of metallothionein-1 (MT-1) in tumor homogenates and blood serum of rats with cisplatin-sensitive and cisplatin-resistant Guerin carcinoma the immunoenzyme method was used. The evaluation of ceruloplasmin activity, content of "free iron" complexes, superoxide and NO-generating acti-vity of NADPH-oxidase and iNOS activity in neutrophils, blood serum and tumor homogenates was measured by EPR-spectro-scopy.

Increase of antitumor activity of cisplatin using agonist of gonadotropin-realising hormone and inhibitor of aromatase on the model of ascites ovarian tumor.

Aim: To study antitumor activity of triptorelin - agonist of gonadotropin-releasing hormone and exemestane - inhibitor of aromatase in monotherapy and in combination with cisplatin on the model of receptor-positive for estrogens and progesterone malignant ascites transplantable ovarian tumor (TOT), to assess therapeutic pathomorphosis and level of VEGF expression in tumor cells using diffe-rent combinations of cytostatics and hormonal drugs.

Materials And Methods: 72 female Wistar rats, which underwent intraperitoneal transplantation of ascitic TOT, by 5·10(6) cells per animal, have been involved in the study. Rats were divided into 8 groups, 9 rats in each group.