Innovative policy of european institutes in solving cancer problems. The General Assembly of OECI, Genoa, Italy, May 21–24

The General Assembly and Scientific week of OECI (Organization of European Cancer Institutes) took place in Genoa (Italy) on 21–24 of May. The membership of OECI comprises 58 European cancer institutions, including R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine as the only representative from Ukraine. In the frames of Scientific week several important events took place: meeting on translational oncogeno­mics, workshop on cancer biotherapy, symposium on nanotechnology application in oncology, seminar on accreditation. OECI General Assembly closed the Scientific week

Morphological features of doxorubicin-resistant Walker 256 carcinosarcoma and response of mast cells

Background: The mechanisms of drug resistance of cancer have not been yet elucidated in details. Recently, the role of mast cells (MCs) in the development of drug resistance has been brought in the limelight. The aim of the study was to examine the morphological features of doxorubicin (DOX)-resistant Walker 256 carcinosarcoma and to assess the response of MCs and histamine content in these cells in relation to the development of resistance to DOX as well as in DOX-resistant tumors. Materials and Methods: The DOX resistance was induced by serial passages of Walker 256 carcinosarcoma in rats in the setting of DOX treatment in vivo. MCs in tumors were detected in the sections by staining with Toluidine Blue O. Histamine content in MCs stained with solution of Water Blue-Orcein was assessed by Astaldi semiquantitative method taking into account different staining intensity. Results: Formation of DOX resistance in the course of serial passages of Walker 256 carcinosarcoma was accompanied by the increase in the number of MCs in tumors and histamine content. Nevertheless, in tumors with phenotype of complete DOX resistance the number of histamine-containing MCs decreased to the same level as in tumors of the original strain that are DOX-sensitive. Conclusion: MCs are involved in formation of DOX resistance in Walker 256 carcinosarcoma

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

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 sensiti­vity assay), by taking into account the additional effect of co-mutagens, and with the use of non-toxic effective radioprotectors

Expression of CD40 and CD40L on tumor cells: the role of their interaction and new approach to immunotherapy

In the review the modern insights on the role of expression of CD40 and CD40L and the role of their interaction on tumor cells growth are analyzed. Information about the structure and biologic properties of these molecules and their interaction is presented. The question on the role of CD40/CD40L interaction is highlighted in two aspects – the possibility of tumor growth inhibition and its stimulation. According to the mentioned aspects, immunologic mechanisms providing tumor growth inhibition (the role of dendritic cells, macrophages, monocytes, cytotoxic T-lymphocytes, natural killer cells etc.), and also the possibility of apoptotic events are discussed. Possibility of tumor growth stimulation upon the influence of CD40/CD40L interaction that could occur in some cases is analyzed as well. The data of literature about new approaches to immunotherapy of cancer based on CD40/CD40L interactionare summarized.В обзоре представлены современные данные об экспрессии CD40 и CD40L опухолевыми клетками и значении взаимодействия указанных молекул на этих клетках. Приведена информация о структуре и биологических свойствах этих молекул и их взаимодействия. Вопрос о взаимодействии CD40/CD40L рассматривали в двух аспектах — возможность ингибиции роста опухоли и стимуляции. В соответствии с этим изучают иммунологические механизмы, обеспечивающие торможение роста опухоли (роль дендритных клеток, макрофагов, моноцитов, цитотоксических Т-лимфоцитов, естественных киллеров и др.), а также возможность развития апоптоза. Рассматривают возможность стимуляции роста опухоли под влиянием CD40/CD40L взаимодействия, что отмечают в отдельных случаях. Обобщены существующие данные доступной литературы о новых подходах к иммунотерапии на основе анализа механизмов вышеуказанного взаимодействия. Ключевые слова: CD40, CD40L, CD40/CD40L-взаимодействие, опухоль, иммунотерапия

Association of cd44⁺cd24⁻/low with markers of aggressiveness and plasticity of cell lines and tumors of patients with breast cancer

Aim: To search for additional molecular-biological markers of cancer stem cell (CSC) involved in the development of intra-tumor heterogeneity for the detection of features of the breast cancer (BC) pathogenesis. Materialts and Methods: Expression of estrogen receptors (ER), progesterone receptors (PR), Her2/neu, E- and N-cadherin, CD24, CD44, Bcl-2, Bax, Slug, P-gp, glutathioneS-transferase (GST) and metallothionein in cell lines was determined by the immunocytochemical method. Expression of ER, PR, Her2/neu, CD24 and CD44 in the surgical material of BC patients were determined by the immunohistochemical method. The levels of the miRNA were determined using real-time polymerase chain reaction. Results: Cells of high-grade malignancy (HGM), MDA-MB-231 and MDA-MB-468 are characterized by high expression of stem cell markers compared to the cells of low-grade malignancy (LGM), T47D and MCF-7: CD44 levels in T47D and MCF-7 cells were in range of 72–79 points, which is significantly lower than in HGM cells (p 0.05). Conclusions: The dependence between the expression of CSC markers and the degree of malignancy of tumor cells, development of resistance to cytostatics in vitro was established as well as the predictive value of the detection of the CSC for the individual prognosis of the BC course and sensitivity of the tumors to the treatment

The lipid content of cisplatin- and doxorubicin-resistant MCF-7 human breast cancer cells

Aim. To perform the comparative study both of qualitative and quantitative content of lipids in parental and drug resistant breast cancer cells. Materials and methods. Parental (MCF-7/S) and resistant to cisplatin (MCF-7/CP) and doxorubicin (MCF-7/Dox) human breast cancer cells were used in the study. Cholesterol, total lipids and phospholipids content were determined by means of thin-layer chromatography. Results. It was found that cholesterol as well as cholesterol ethers content are significantly higher but diacylglycerols, triacyl­glycerols content are significantly lower in resistant cell strains than in parental (sensitive) cells. Moreover the analysis of individual phospholipids showed the increase of sphingomyelin, phosphatidylserine, cardiolipin, phosphatidic acid and the decrease of phosphatidy­lethanolamine, phosphatidylcholine in MCF-7/CP and MCF-7/Dox cells. Conclusion. Obtained results allow to suggest that the lipid profile changes can mediate the modulation of membrane fluidity in drug resistant MCF-7 breast cancer cells

Distribution and accumulation of liposomal form of doxorubicin in breast cancer cells of MCF-7 line

Aim: To study distribution and accumulation of liposomal form of doxorubicin in human breast cancer cells of MCF-7 line and Dox-resistant subline MCF-7/Dox. Methods: High performance liquid chromatography and laser confocal microscopy were used. Results: It has been shown that conventional form of doxorubicin was more efficiently delivered to the MCF-7 cells already after 30 min of incubation amounting to its maximum concentration after 4 h. MCF-7/Dox cells are characterized by lower doxorubicin accumulation rate compared with parental cells. The quantity of accumulated liposomal form of doxorubicin is high in MCF-7 cells, and, what is important, Dox-resistant cells accumulated higher levels of liposomal form of doxorubicin than its conventional form. Conclusion: It has been shown that intracellular distribution and accumulation of liposomal forms of doxorubicin in parental and Dox-resistant MCF-7 cells differs from that of conventional doxorubicin

Vascular endothelial growth factor exression in uterine cervical cancer: correlation with clinicopathologic characteristics and survival

Aim: This retrospective study was performed to determine the vascular endothelial growth factor (VEGF) expression in cervical cancer cells, and to examine its correlation with clinicopathologic characteristics and survival of patients. Methods: Seventy-five paraffinembedded primary tumors were stained immunohistochemically for VEGF expression, which was analysed semiquantitatively. Results: The significant correlation between VEGF expression and stages of disease, as well as pelvic lymph node metastasis was observed. There were determined a negative correlations between VEGF expression in tumor cells and both overall and disease-free survival. Conclusion: VEGF expression in human cervical cancer may be used as a diagnostic parameter in the clinic. Our results are in accordance with literature data showing association of VEGF overexpression in tumor with a poorer patient survival