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

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. MATERIALS AND METHODS: Doxorubicin (Dox)-sensitive and Dox-resistant Walker-256 carcinosarcoma and cisplatin-sensitive and cisplatin-resistant Guerin's carcinoma transplanted in female Wistar rats were studied. The magnetism of tumors, liver and heart was determined using Superconductive Quantum Interference Device (SQUID) - magnetometry in a non-contact (13 mm over the tumor) way using specially designed computer programs. In a group of the experimental animals, a ferromagnetic nanocomposite (Ferroplat) was administered as a single intravenous injection and biomagnetism was assessed in 1 h. RESULTS: The magnetic signals coming from Dox-resistant Walker-256 carcinosarcoma in the exponential growth phase were significantly higher in comparison with sensitive tumor. Intravenous administration of Ferroplat increased biomagnetism by at least an order of magnitude, especially in resistant tumors. At the same time, the magnetic signals of the liver and heart were within the magnetic noise. CONCLUSION: The use of SQUID-magnetometry with ferromagnetic nanoparticles as a contrast agent is a promising approach for visualization of malignant neoplasms with varying sensitivity to chemotherapy.

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. Ten days after tumor transplantation, Ferroplat was administered intravenously to half of the animals with the tumor and to half of the control animals. The magnitude of the magnetic signals was determined 1 h and every two days after administration of the nanocomposite using a Superconducting Quantum Interference Device magnetometer of the original design. RESULTS: We have found that the magnetic signals coming from the tumor are significantly higher compared to control tumor-free animals. Intravenous administration of a ferromagnetic nanocomposite (Ferroplat: Fe3O4 + cisplatinum) led to a significant increase of the magnetic signal, especially in the tumor tissue, and inhibition of Guerin's carcinoma growth. Ferromagnetic nanoparticles (32.7 nm) are retained in malignant cells for a longer time than in normal ones. CONCLUSION: Tumor cells accumulate iron nanoparticles more intensively than normal ones. Nanocomposite Ferroplat can be used for a targeted delivery of cisplatin to malignant cells.

Significance of iodine symporter for prognosis of the disease course and efficacy of neoadjuvant chemotherapy in patients with breast cancer of luminal and basal subtypes.

The aim of the research was to study the relation between expression of Na.

Ultrastructural changes in tumor cells treated with liposomal forms of anticancer drugs.

AIM: To determine the main ultrastructural changes in MCF-7 sublines sensitive and resistant to cytotoxic action of anticancer drugs, resulting from the treatment with conventional and liposomal forms of cisplatin and doxorubicin. METHODS: Electron microscopy, light microscopy, MTT-test. RESULTS: It has been shown that the phenomenon of drug resistance is associated with complication of ultrastructural organization of cells and more high differentiation by the main cytomorphologic characteristics which promote their resistance to cytotoxic action of anticancer preparations. Cytoarchitectonics of all resistant cells possesses common patterns and doesn't depend on the particular drugs toward which the resistance has been developed. It has been shown that the cells of the parental form MCF-7 line are more sensitive to cytotoxic action of doxorubicin than to cisplatin. Liposomal forms of anticancer drugs used at the same concentrations that the conventional ones, especially that of doxorubicin, caused more expressed alterations in ultrastructural organization of cells of all studied sublines with dominance of apoptotic processes. CONCLUSION: Evaluating an effect of equal concentrations of cisplatin and doxorubicin in conventional and liposomal forms, one may conclude on higher cytotoxic action of doxorubicin vs. cisplatin that is expressed in a wider spectrum of ultrastructural changes of cell architectonics in different sublines of MCF-7 cells and higher rate of apoptosis.

Relation between pathomorphological response in tumors after neoadjuvant chemotherapy and clinico-morphological and molecular prognostic factors in patients with breast cancer.

AIM: To determine the correlation between tumor pathomorphological response (PMR) after neoadjuvant chemotherapy (NACT) and clinico-morphological and molecular prognostic factors in patients with breast cancer (BC), and to determine the possible impact of the PMR and estrogen receptors (ER), progesterone receptors (PR) and Her-2/neu BC status on the disease course. METHODS: The data from the medical history of patients on IIB stage (T2N1M0, T3N0M0) (n = 247), who received treatment with NACT, were used. The correlation between the parameters was determined using the Spearman's coefficient. Patient's survival was analyzed by Kaplan - Meier method. The association between PMR grades with the risk of disease relapse was estimated by Cox's regression analysis. RESULTS: PMR grade correlated with tumor differentiation grade (rho = 0.38; p 0.05) and BC subtypes (rho = 0.05; p > 0.05). The patients with the same PMR grades didn't differ by the number of lymph node metastases (p > 0.05) and differed by the presence of embolus in tumor vessels (p 0.05). The risk of disease relapse depended on PMR grade: for grade 2-3 it was significantly decreased (HR = 0.71, 95% CI - 0.25-2.9, p = 0.0037), and for grade 4-5 it was the highest (HR = -1.23, 95% CI - 0.24-5.05, P = 0.0001), while 0-1 grade had no impact on the risk of disease relapse (HR = 0.22, 95% CI 0.08-0.38; p = 0.7). CONCLUSION: The data of combined clinical, histological and immunohistochemical analysis have shown that PMR grades may serve as the criteria for individualization of adjuvant treatment of the patients with locally advanced BC.

Age-related effects of methionine-enriched diet on plasma homocysteine concentration and methylation of hepatic DNA in rats.

In the present study we determined the age-related effect of methionine-enriched diet, a model of hyperhomocysteinemia, on the level of plasma homocysteine and hepatic global DNA methylation in rats. Feeding methionine diet to middle-aged rats for only 14 days resulted in a significant increase in plasma homocysteine level and DNA hypomethylation. In contrast, feeding the methionine-containing diet for 2 weeks to juvenile or post-pubertal animals did not alter the level of plasma homocysteine or hepatic DNA methylation. Supplementation of the methionine-enriched diet with vitamins B6, B12 and folic acid prevented both hepatic DNA hypomethylation and an increase of plasma homocysteine concentration in the middle-aged rats. These findings indicate that the elevated level of plasma homocysteine may be indicative of much broader and deeper alterations in intracellular methylation dysfunction, and suggest that dietary enrichment with B-vitamins is essential for the metabolism of homocysteine, especially in adult animals.

[The role of the mono-oxygenase system in realizing the biological effects of cisplatin]. / Rol' sistemy monooksigenaz v realizatsii biologicheskikh éffektov tsisplatina.

The toxic and antitumor effects of cisplatin were shown to depend upon the activity of microsomal oxidation system enzymes. Administration of the drug in combination with K-2-9 enterosorbent was followed by an increase in its antitumor effect and amelioration of toxicity.

[The mechanisms of a decrease in the toxic action of cisplatin when administered jointly with preparation K-2-9 to mice with melanoma B16]. / O nekotorykh mekhanizmakh snizheniia toksicheskogo deistviia tsisplatina pri sovmestnom vvedenii s preparatom K-2-9 mysham s melanomoi B-16.

The K-2-9 preparation was determined to change cis-platinum pharmacokinetics, that resulted in its pharmacodynamics alterations. The higher Pt concentrations in the blood of animals which were given the K-2-9 preparation provided selectivity of cytostatic accumulation in the tumour tissue, that was accompanied by more prolonged inhibition of the DNA synthesis. A decrease in the toxicity of cis-platinum is associated with a change in the elimination pathway and acceleration of its removal from the organism.

[Experimental modification of the nephro- and gastroenterotoxicity of cisplatin]. / Mofikatsiia nefro- i gastroenterotoksichnosti tsisplatina v éksperimente.

The effect of complex-forming sorbent K-2-9 on cisplatin toxicity was studied experimentally. Simultaneous treatment with the preparations was shown to lower the nephro- and gastroenterotoxicity of cisplatin did not detract from the antitumor effect of cisplatin.

[Modification of the determination of the quantitative characteristics of an experimental tumor process]. / Modifikatsiia opredeleniia kolichestvennykh kharakteristik éksperimental'nogo opukholevogo protsessa.

Modifications of the main quantitative characteristics of experimental tumour processes are proposed for the optimal assessment and comparison of various antitumoural effects.

[Modification of the toxic effects of cis-dichlorodiammineplatinum]. / Modifikatsiia toksicheskikh éffektov tsis-dikhlordiamminoplatiny.

It is established that the preparation K-2-9 being administered in combination with cis-dichlorodiaminoplatinum (DDP) lowers the DDP toxic effects, in particular nephrotoxicity and enterotoxicity, increases the activity of the enzymes participating in microsomal liver oxidation, the activity of kidney transamidinase, the quantity of SH-groups of the liver and kidney tissue, intensifies the antitumour effect of DDP.

[Nonspecific oxidase activity in the liver of rats undergoing chemotherapy with cis-dichlorodiammineplatinum]. / Aktivnost' nespetsificheskikh oksidaz pecheni krys pri khimioterapii tsis-dikhlordiaminoplatinoi.

A combined administration of cis-dichlorodiaminoplatinum (DDP) and phenobarbital increases the activity of nonspecific oxidases, decreases the toxic effect of DDP especially its nephrotoxic action, but does not decrease the antiblastic action of DDP in rats. On the basis of experimental data the optimum regime of DDP repeated administrations is suggested.