Experimental oncology (Exp Oncol)

Publications in this journal

• Article: Activity of thymidilate "salvage pathway" enzymes in human gastric cancer and blood serum: correlation with treatment modalities.

  B G Borzenko, E M Bakurova, Yu A Popovich, E A Sidyuk, A Y Popovich
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  ABSTRACT: A comparative study of enzyme activity features of thymidilate "salvage pathway" synthesis in blood serum and tissues of different age patients with gastric cancer (T3-4N0-xM0) was carried out. Aim: To evaluate the diagnostic relevance of thymidilate metabolism enzymes activities and their association with tumor growth. Methods: Enzymes activities were determined by the radioisotope method and spectrophotometrically in tumor tissues and blood serum of 74 patients. Results: It was demonstrated that thymidine phosphorylase activity in gastric tumors is lower by 2.6 times as compared to non-neoplastic mucosa of resection margin. This being accompanied by decrease of its activity in the blood serum (from 47.9 ± 2.6 to 14.65 ± 2.4 nmol/min·mg, p < 0.001). An increase of thymidine kinase activity was revealed both in tumor tissues (more than 3.5 times) and in blood serum (from 3.9 ± 0,7 nmol/mg·h, to 6.8 ± 1.0 nmol/mg·h, p < 0.01). Changes in their activity in the postoperative period depended on the type of surgical procedure and tumor eradication. Conclusion: It could be suggested that control of individual dynamics of the enzymes activities in blood serum may be used as informative tool for monitoring of patients and treatment optimization.
  Experimental oncology 03/2013; 35(1):37-40.
• Article: Impact of dihydropyrrol derivative on the normal colonic mucosa of DMH-induced colon cancer rats compared with 5-fluorouracil.

  H M Kuznietsova, O V Ogloblya, V K Rybalchenko
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  ABSTRACT: Aim: To compare the effects of cytostatic compound dihydropyrrol derivative (D1, 5-amyno-4-(1,3-benzothyazol-2-yl)-1-(3-methoxyphenyl)-1,2-dihydro-3Н-pyrrol-3-one) and 5-fluorouracil (5-FU) on the normal colonic mucosa of tumor-bearing rats and to estimate the relationships between proliferation of normal colonic mucosa and tumor growth parameters. Methods: 1,2-dimethylhydrazine (DMH) carcinogenic model was used. Male Wistar rats were treated by dimethylhydrazine (20 mg/kg of body weight (b.w.) weekly) for 20 weeks, by D1 (2.3 mg/kg of b.w. daily) for 7 or 27 weeks, and by 5-FU (45 mg/kg of b.w. weekly) for 7 weeks. The number of tumor and tumor total area in dissected colon, mitotic and crypt fission indices in surrounding colon mucosa were measured and correlations between these parameters were computed. Results: The number of tumor node and tumor total area under the influence of D1 and 5-FU were decreased by 40-54%. D1 administration has resulted in the more gentle effect on surrounding healthy colon mucosa comparing to 5-FU, particularly, on vascular bed and proliferative activity. The changes in colon mucosa proliferative activity correlate with tumor growth parameters depending on the action of D1 or 5-FU. Conclusions: D1 manifests the same antitumor activity but less toxicity comparing to 5-FU that allow to suggest its possible use as an anticancer mean. Obtained correlations could be useful for better understanding of the processes preceeding the malignant transformation and their pharmaceutical correction.
  Experimental oncology 03/2013; 35(1):25-9.
• Article: Repression of matrix metalloproteinases and inhibition of cell invasion by a nutrient mixture, containing ascorbic acid, lysine, proline, and green tea extract on human fanconi anemia fibroblast cell lines.

  M W Roomi, N W Roomi, B Bhanap, A Niedzwiecki, M Rath
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  ABSTRACT: Aim: Fanconi Anemia, an autosomal recessive disorder, is characterized by chromosomal abnormality leading to birth defects, progressive bone marrow failure, and a high probability of developing malignancy at an early age. Head and neck squamous cell carcinoma and myeloid leukemia are the major causes of cancer related morbidity and mortality in Fanconi anemia patients. Me-thods: We investigated the effect of a nutrient mixture on Fanconi Anemia human fibroblast cell lines FA-A:PD20 and FA-A:PD220 on matrix metalloproteinase expression, invasion, cell proliferation, morphology and apoptosis. The cell lines were grown in a modified Dulbecco's Eagle medium and at near confluence were treated with the nutrient mixture at increasing doses: 0; 10; 50; 100; 500; 1000 µg/ml. The cells were also treated with PMA to induce MMP-9 expression. Results: Zymography demonstrated MMP-2 and PMA-induced MMP-9 activity. The nutrient mixture inhibited expression of both, MMP-2 and MMP-9, in a dose dependent manner with virtually total inhibition observed at 500 µg/ml. Matrigel invasion was inhibited in both cells lines; with 100% inhibition for FA-A:PD20 at 500 µg/ml and 100% inhibition of FA-A:P220 cells at 100 µg/ml. H&E staining did not indicate any change in cell morphology and causes apoptosis at higher doses. Conclusion: Our data demonstrated that the nutrient mixture inhibited matrix metalloproteinase expression, invasion and induced apoptosis, the important parameters for cancer prevention. The results suggest that the nutrient mixture may have therapeutic potential in Fanconi Anemia associated neoplasia.
  Experimental oncology 03/2013; 35(1):20-4.
• Article: Influence of polychemotherapy on the morphology of metastases and kidney of resistant RLS-bearing mice.

  E V Zonov, E I Voronina, M A Zenkova, T A Ageeva, E I Ryabchikova
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  ABSTRACT: Aim: Polychemotherapy (PCT), widely used for the antitumor treatment has a pronounced toxic effect on the organism, and its cytostatic effect sometimes is canceled by multidrug resistance of a neoplasia. Comprehension of the nature and development of pathological changes caused by the PCT during the treatment of cancer is very important to improve the efficiency of the therapy and to clarify the mechanisms of tumor-host interactions. This study was aimed to examine PCT impact on kidney cells and tissues in mice with transplanted resistant lymphosacroma (RLS) and to analyze morphology of metastases of the tumor in kidney during PCT. Materials and Methods: Male mice CBA/LacSto (55 animals) were intramuscularly implanted in the right hind paw by 105 cells/ml of tumor RLS (a diffuse large B-cell lymphosarcoma) with multi-drug resistance (MDR) phenotype. Mice received combination of cyclophosphamide (50 mg/kg), oncovin (0.1 mg/kg), hydroxydaunorubicin (4 mg/kg), and prednisone (5 mg/kg) accordingly to CHOP scheme each 7 days after inoculation of the tumor. The kidneys were sampled on days 1, 3 and 7 after each series of injection of PCT preparations and processed for light and electron microscopy, immunohistochemical analysis of Ki-67 and Apaf-1 proteins also was performed. Results: Tumor RLS produced metastases comprised of small cells in the kidneys of mice after 8 days post inoculation. Application of PCT resulted in destruction of small-cell metastases and development of many large-cell metastases in kidney. Application of PCT induced the development of prominent damage of nephron cells, primarily in S3 segments of proximal tubules. Even one series of PCT caused reduction of basal plasma folds in these cells and alteration of mitochondria. Damage of proximal tubules and involvement of distal tubules, renal bodies and interstitial tissue in the pathologic process, increased during the experiment. This work presents the description of morphological changes in kidney as well as of the tumor metastases under PCT influence. Conclusion: The obtained data should be considered while designing of remedies for recovery of internal organs functions after antitumor PCT.
  Experimental oncology 03/2013; 35(1):30-6.
• Article: In vitro modification of cisplatin cytotoxicity with magnetic fluid.

  V F Chekhun, O V Yurchenko, L A Naleskina, D V Demash, N Yu Lukianova, Yu V Lozovska
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  ABSTRACT: Aim: To study cytotoxicity of cisplatin conjugated with magnetic fluid (nanocomposite) upon exposure to magnetic field on sensitive and resistant to cisplatin MCF-7 human breast cancer cells. Methods: Cytotoxic activity was evaluated by MTT-test, intracellular iron accumulation was analyzed cytochemically, genotoxicity was studied by micronucleus test and DNA comet assay, ultrastructure was studied by electron microscopy techniques. Results: Nanocomposite of cisplatin was more toxic to MCF-7/S and MCF-7/CP cells compared to cisplatin in conventional pharmaceutical form. In nanocomposite-treated cells we observed more expressed signs of dystrophy (especially following application of magnetic field) and drastic alterations of nuclei ultrastructure with significant accumulation of iron nanoparticle clusters. The potent toxic action of nanocomposite is confirmed by electron microscopy and by marked genotoxicity, especially against MCF-7/CP cells. Conclusion: The enhancement of cyto- and genotoxicity of cisplatin nanocomposite combined with magnetic field in comparison with effect of convetntional cisplatin alone was demonstrated.
  Experimental oncology 03/2013; 35(1):15-9.
• Article: Endoscopic method of intestinal decompression with the use of entero- and colonosorption in treatment of rectal cancer complicated with intestinal obstruction.

  O E Kalinin
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  ABSTRACT: The treatment of rectal cancer patients with large bowel obstruction (LBO) is a serious health care problem. That's why we have studied a possibility of conservative LBO treatment by the method of endoscopic recanalization. Patients and Methods: In the study there have been enrolled 47 rectal cancer patients with acute or partial LBO who were treated with endoscopic recanalization of lumen and following sessions of entero- and colonosorption. After enteric decompression there has been performed preoperative chemoradiotherapy session, and then - planned surgical treatment. Results: Decompression was successful in all 47 patients, however, it's necessary to note that experimental group has been composed in part from the patients with obstructing rectal tumors with exophytic or mixed growth types. In 5 patients there was a partial effect, and this allowed perform chemoradiotherapy and planned surgical treatment. Conclusion: It has been demonstrated that the use of proposed method of enteric decompression allows quickly eliminate the symptoms of intestinal insufficiency syndrome, perform adequate chemo- and radiotherapy in preoperative period directed on decrease of tumor volume and invasion, facilitate the performance of primary reparative operation and the course of post-operative period, and achieve a decrease number of obstructive resections without worsening the prognosis of the main disease.
  Experimental oncology 03/2013; 35(1):53-7.
• Article: Enterosorption as a method to decrease the systemic toxicity of cisplatin.

  L A Sakhno, O V Yurchenko, V N Maslenniy, K I Bardakhivskaya, V V Nikolaeva, A A Ivanyuk, O O Shevchuk, V G Korotich, V G Nikolaev
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  ABSTRACT: A perspective adsorptive method to minimize systemic toxic effects of chemotherapy is enterosorption (ES). However, the capabilities of this method are far from being completely studied. The question remains opened - should ES be initiated in the first hours on completing cytostatic infusion without the risk of their anticancer activity to be decreased. Aim: to analyze ES influence on anticancer activity and toxic reactions of cisplatin (CP) upon the use of carbon enterosorbent in 1 h after intravenous administration of cytostatic. Methods: CP at the dose of 1 mg/kg body weigh (BW) was administered to Guerin carcinoma-bearing rats each second day for two weeks. Enterosorbents on the basis of highly activated carbon fibers were administered by per os daily 1 h after CP injection. 3 days after the last CP administration the rats were weighted and blood under ether narcosis has been taken for biochemical examination. Tumors and innate organs were isolated, weighted, and fixed in 4% buffered formalin for morphologic examination. Results: In rats administered with CP at the background of ES, BW loss was in 1.6 times lower than in animals after CP session. Relative kidney weight in CP-treated rats was 33.9% higher than in normal ones (p ≤ 0.05). No significant differences were detected between relative kidney weights in the CP + ES-treated and intact animals. Introduction of ES allowed prevent an 30% increase of creatinin content observed in blood plasma after CP treatment (р ≤ 0.05). Urea content was 1.7 times lower in blood plasma of CP + ES-treated rats than after CP treatment. CP caused significant toxic injuries in kidneys, liver, and spleen tissues. Morphologic structure of organs in rats treated with CP at the background of ES was affected at much lower degree. In tumors, large areas of newly formed connective tissue and blood vessels have been fixed after the CP+ES action instead of large necrotic area observed after CP treatment. ES caused insignificant suppression of Guerin carcinoma growth and had additional impact to inhibitory action of CP. Conclusion: Active carbon enterosorbents which are administrated just 1 h after CP administration possesses detoxicating potential sufficient for significant elimination of toxic effect of the cytostatic at the background of complete preservation of its antitumor activity.
  Experimental oncology 03/2013; 35(1):45-52.
• Article: Immunohistochemical evaluation of p53 expression in lung cancer of patients with paraneoplastic rheumatic syndrome.

  S A Lysenko
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  ABSTRACT: Aim: To study p53 expression in the tumor tissue of lung cancer (LC) patients with paraneoplastic rheumatic syndrome (PNRS). Materials and Methods: There have been used either biopsy or surgically resected tumor samples of 140 LC patients (83 patients without PNRS, 57 patients with PNRS). For evaluation of p53 expression in LC samples, immunohistochemical analysis was performed. Results: It has been shown that p53 expression in tumor samples from LC patients with PNRS was significantly higher compared to that in LC patients without PNRS. It has been shown that p53 expression is more frequently registered in patients with lung adenocarcinoma with PNRS than in patients with lung adenocarcinoma without this syndrome. Conclusion: The presence of PNRS in LC patients with p53 expression is associated with higher aggressiveness of tumor.
  Experimental oncology 03/2013; 35(1):41-4.
• Article: Experimental validation of prevention of the development of stochastic effects of low doses of ionizing radiation based on the analysis of human lymphocytes' chromosome aberrations.

  E A Diomina, V F Chekhun
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  ABSTRACT: Aim: On the basis of the cytogenetic research, to develop and validate the strategy of the measures to prevent the stochastic effects of low-doses radiation on humans. Methods: Test system with human peripheral blood lymphocytes, metaphase analysis of chromosomal aberrations was used. Cells were cultured according to the standard procedures with modifications. The analysis of painted chromosome preparations was carried out according to the conventional requirements to metaphase spread. Results: The experimental material, obtained on chromosomal level of radiosensitive cells, concerning validation of prevention strategy of stochastic effects of low doses of ionizing radiation, primarily cancer, is discussed. Its key phases are the following: estimation of individual radiosensitivity, accounting of the co-mutagens influence and use of effective atoxic radioprotectors. The practicability of the primary prevention strategy of radiogenic cancer has been evidence based, especially in case of the influence of small doses of ionizing radiation. Cytogenetic studies using G2-radiation sensitivity assay are essential component of priority populations' health monitoring for formation high cancer risk groups and implementation developed strategies of stochastic effects prevention, including radiogenic cancer, among persons with known hypersensitivity to ionizing radiation. It applies the nuclear industry workers, medical staff (radiation oncologists, radiologists), and priority populations living in areas contaminated with radionuclides. Conclusion: Strategy for the prevention of stochastic effects of low-doses radiation, especially cancer risk, is elaborated on the cytogenetic studies basis, implies that cancer risk reduction is provided by assessment of individual radiation sensitivity (G2-radiation sensiti-vity assay), by taking into account the additional effect of co-mutagens, and with the use of non-toxic effective radioprotectors.
  Experimental oncology 03/2013; 35(1):65-8.
• Article: Vitamin C: attenuating effect on growth and proliferation in systemic malignancies.

  S Kapoor
  Experimental oncology 03/2013; 35(1):72.
• Article: Search for potential gastric cancer markers using miRNA databases and gene expression analysis.

  V Volkomorov, E Grigoryeva, G Krasnov, N Litviakov, M Tsyganov, M Karbyshev, M Zavyalova, S Afanasуev, N Cherdyntseva, N Lisitsyn, S Beresten
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  ABSTRACT: Aim: The aim of this study was to identify genes that are differentially expressed in gastric tumors and to analyze the association of their expression level with tumor clinicopathologic features. Methods: In the present research, we used bioinformatic-driven search to identify miRNA that are down-regulated in gastric tumors and to find their potential targets. Then, the expression levels of some of the target mRNAs were investigated using reverse transcription polymerase chain reaction (RT-PCR) analysis. Results: As a result of the bioinformatics analysis, fifteen genes were found to be potentially differentially expressed between the tumors and normal gastric tissue. Five of them were chosen for the further analysis (WNT4, FGF12, EFEMP1, CTGF, and HSPG2) due to their important role in cell proliferation and differentiation. Expression levels of these genes were evaluated in our collection of frozen tissue samples of gastric tumor and paired normal stomach epithelia. Increased FGF12 expression was observed in diffuse type of gastric cancer while WNT4 mRNA was found to be down-regulated in intestinal type of gastric cancer. Besides, CTGF gene overexpression was revealed in diffuse type of stomach cancer in comparison with that in intestinal type. Up-regulation of CTGF was also associated with lymph node metastasis. Conclusions: The findings show its expedient to perform further investigations in order to clarify diagnostic and prognostic value of CTGF, FGF12, and WNT4's in stomach cancer as well as the role of these genes in carcinogenesis.
  Experimental oncology 03/2013; 35(1):2-7.
• Article: WHO classification of lymphoid malignancies.

  D F Gluzman
  Experimental oncology 12/2012; 34(4):377-8.
• Article: Relationship between NF-κB, ER, PR, Her2/neu, Ki67, p53 expression in human breast cancer.

  D O Shapochka, S P Zaletok, M I Gnidyuk
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  ABSTRACT: Aim: The aim of the present study was to investigate expression patterns of transcription factor NF-κB (p50 and p65), ER, PR, Her2/neu, Ki-67 and p53 in tumor tissue of patients with breast cancer (BC) and analyze correlation between these markers. Patients and Methods: 62 BC patients previously nottreated with chemo- or radiotherapy were included in the study. All tumors belong to invasive ductal carcinoma of different grade. Expression of molecular markers was determined by immunohistochemical analysis on paraffin-embedded tissue sections. Results: The correlation between tumor grade and expression of ER, PR, Ki-67 and p53 was defined. NF-κB expression was found to be changed dependent on expression of ER, PR and p53 and also on molecular subtype (luminal, Her2-positive, hybrid, basal-like). The highest levels of NF-κB, Ki-67 and p53 were found in Her2/neu+ and basal-like tumor subtypes. Conclusion: The increase of nuclear expression of NF-κB correlates with a decrease of expression of steroid hormone receptors (ER and PR), increase of p53 accumulation, and is associated with Her2-positive and basal-like tumor types.
  Experimental oncology 12/2012; 34(4):358-63.
• Article: Primary gastrointestinal lymphomas.

  E Vandenberghe
  Experimental oncology 12/2012; 34(4):385-6.
• Article: Leukemic phase of B-lineage NHL.

  E Kimby
  Experimental oncology 12/2012; 34(4):384-5.