Conference proceedings. Рубрика в журнале - Cardiometry
A modern approach to disease modeling for the development of oncology drugs
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Oncological diseases are characterized by the complexity of pathogenesis and demonstrate a number of specific signs, such as uncontrolled proliferation, stimulation of angiogenesis, activation of invasion and metastasis. Molecular genetic testing to examine genetic abnormalities in tumor cells has been increasingly using in oncology.
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Numerous studies have shown that the presence of homologous recombination deficiency (HRD) in breast tumors may be a good marker of the effectiveness of chemotherapy with DNA-damaging agents such as platinum-based and anthracycline- containing medication regimens. However, the formation of HRD due to disruptions in the BRCA1/2 genes is typical not only for breast cancer and ovarian cancer, but also for other cancer localizations, in particular for non-small cell lung cancer (NSCLC). Since the use of platinum-based drugs in patients with NSCLC is a standard treatment protocol, studying the expression profile of homologous recombination genes and the presence of chromosomal aberrations therein will allow us to fully study HRD in these patients and identify new prognostic markers.
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is known that Parkinson’s disease (PD) being a neurodegenerative disease is accompanied by increased levels of reactive oxygen species, oxidative stress and impaired mitochondrial activity. It has been shown that the development of malignant tumors can be accompanied by disorders that mimic PD.
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Boron neutron capture therapy (BNCT) is a binary radiation therapy modality based on the high capability of the non-radioactive isotope 10B to absorb thermal neutrons. The use of alternative isotope 6Li for lithium neutron capture therapy (LiNCT) may be a promising area in the treatment of oncological diseases, but at present the data on the possibilities of lithium accumulation in tumor cells are limited to some sporadic studies.
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Escape from cell death is one of the most prominent features of tumor cells and is closely related to the dysregulation of Bcl-2 family proteins. Among them, the anti-apoptotic protein Mcl-1 (myeloid cell leukaemia-1) acts as a master regulator of apoptosis in various human malignancies. The Mcl-1 -1 protein, whose main function is to protect tumor cells from apoptosis, is not the only product of the anti-apoptotic gene MCL1. On the contrary, another product of this gene, the shortened Mcl-1S protein, formed by alternative splicing, serves as a negative regulator of Mcl-1. Increased levels of Mcl-1S lead to inhibition of apoptosis-protective Mcl-1 and, consequently, tumor cell death by apoptosis (Senichkin, 2018). Mcl-1 inhibitors are currently being developed, which opens new perspectives to fight the hitherto untreatable addiction of cancer cells.
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Dendritic cells and their role in cancer immunotherapy
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Cytotoxic CD8+ T lymphocytes (CD8+ CTLs) are key effector cells, which recognize and kill tumor cells, and are therefore preferred targets for improved cancer immunotherapy.
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Features of biochemical homeostasis in rats with anti-tumor effect produced by iron nanoparticles
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Overloading a tumor with iron (Fe) is a promising strategy for cancer therapy. A number of papers have demonstrated a self-dependent anti-tumor effect of Fe nanoparticles (NPs) in vivo. However, an excessive amount of this trace metal can produce a negative effect on the organism. The aim of our study was to evaluate the metabolic changes in the rats with lymphosarcoma when exposed to FeNPs with anti-tumor activity.
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It is well known that extraordinary stress or chronic exposure to stressors is characterized by adverse immunological consequences due to stress-induced immunosuppression. It has been established that stress causes an increased incidence of malignant tumors and also worsens the prognosis in patients with already existing tumors. Among the mechanisms of carcinogenesis under stress, there is an increase in the level of cortisol, which has a significant inhibitory effect on the immune system and the secretion of pro-inflammatory interleukins. Post-traumatic stress disorder (PTSD) involves inactivation of the hypothalamic-pituitary-adrenal (HPA) axis and decreased secretion of cortisol in humans, or corticosterone in rats and mice. However, the question of whether PTSD is a risk factor for the development of cancer or tumor growth remains practically undeveloped.
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The 20th century was skeptical about magnetobiology. But the early experiments conducted by the American couple Barnothy, M. F., & Barnothy, J. M, who presented their data on the possibility of inhibiting the growth of tumors using strong magnetic fields, excited the world, and in the 60s last century, 3 international symposiums were held in Chicago, Rome, and Moscow to discuss that topical issue. By that time, a great progress in that scientific area was made by researchers from the Rostov Scientific School of Experimental Oncology
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KIM-1 is a marker of nephrotoxicity in patients receiving cisplatin-containing chemotherapy
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Drug-induced nephrotoxicity is a common side effect in chemotherapy treatment for cancer patients. Every year the relevance of this problem increases due to the widespread use of various chemotherapy (CT) protocols, including nephrotoxic drugs, in particular cisplatin. Standard measures of kidney function include glomerular filtration rate (GFR), serum creatinine (sCr) and blood urea nitrogen concentrations. However, their changes are revealed after a rather long period after nephrotoxic exposure only; in addition, they deviate significantly from the norm only with a significant degree of kidney damage. Therefore, the search for new markers of nephrotoxicity for early and reliable diagnostics of renal dysfunction is an extremely urgent task. One such promising marker is KIM-1.
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Medicinal plants containing alkaloids: prospects for their use in oncology
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The aim of our study was to search and identify new promising plant species containing alkaloids in order to develop new effective herbal medicines for antitumor therapy.
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MicroRNA MIR-204-5P is a regulator of apoptosis in dacarbazine-resistant melanoma cells
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Therapy for skin melanoma in its disseminated form is ineffective, among other things, due to the development of tumor cell resistance, mediated by various mechanisms. The acquisition of a stable cell phenotype is associated both with genetic and epigenetic changes mediated by the regulatory non-coding microRNA molecules. The aim hereof is to investigate the ability of microRNA miR-204-5p to influence changes in the cell cycle and apoptosis of melanoma cells resistant to the chemotherapeutic alkylating agent dacarbazine, used in standard chemotherapy for melanoma.
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Molecular cellular effects by proton and у-irradiation in the B16 murine melanoma model in vivo
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Proton and photon (γ-) radiation is widely used in modern clinical practice for the treatment of malignant tumors of various locations. The relative biological effectiveness (RBE) of accelerated protons is about 1.1, as follows from the results of experimental studies of clonogenic survival of tumor cells in vitro. But however, despite the low RBE of proton radiation, a number of clinical studies have shown a significant increase in relapse-free and overall survival of patients after proton therapy compared with that after standard radiotherapy using photon radiation.
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Molecular genetic characteristics of ovarian cancer in Crimean patients
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The etiology of hereditary ovarian cancer is most often attributed to structural or functional inactivation of some tumor suppressors. An identification of the molecular genetic basis of the disease has prognostic significance, and it also influences the selection of the most effective therapeutic tactics. The rate of the occurrence of polymorphisms is variable and depends, among other things, on ethnicity and geography.
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Molecular profile of metastatic colon cancer
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Aim. Our aim was to assess the molecular subtypes of the primary CC tumors and liver metastases based on the transcriptomic analysis.
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Morphological studies represent the most important part of evidence-based medicine, and in oncology they are an essential attribute in the diagnostics of malignant neoplasms. In experimental oncology, current models of the tumor growth are developed to be as close as possible to the actual biological life conditions. There is a need to study the pathogenesis of tumors in various variants of their orthotopic growth, the formation of bi-model systems with a combination of the malignant growth and comorbid conditions (chronic neurogenic pain, diabetes mellitus, hypothyroidism, obesity), the use of subcellular substrates for the induction of carcinogenesis and biotherapy. Among the important methods for studying the pathogenesis of tumors, morphology is on a par with advanced molecular genetic and biochemical methods, as well as radioimmunoassay techniques.
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Giving an additional specific antitumor activity to biomaterials used to provide the local release of medical drugs into the bone defect in oncology, i.e. their functionalization is a promising, sought-after area in the modern biomaterials’ science
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To study the mechanisms of metastasis, one of the effective tools is mouse models using primary patient tumors (Patient-Derived Xenograft, PDX). The phenomenon of changes in the cell phenotype in response to the dynamic conditions of the tumor microenvironment is one of the key processes forming the basis for metastasis. The aim hereof is to investigate the phenotypic composition of tumor cells during the process of metastasis using an example of the PDX models of breast cancer.
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Quality control of NK cells produced ex vivo for malignant neoplasm therapy
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The process of transferring the technology for obtaining a drug from the laboratory to production and, then, to the clinical practice is always a very complicated and time-consuming way, requiring many adaptation solutions. Regarding biomedical cell products (BMCP), this is even a more complex process, requiring large-scale expansion of procedures to obtain clinically significant numbers of cells, adaptation to reagents and equipment, and establishment of safety parameters for reagents, equipment and the final product. Nevertheless
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The development of new therapeutic strategies for the treatment of various diseases associated with impaired protein kinase activity is one of the most urgent tasks in modern medicine. The search for new protein kinase inhibitors is an effective approach in the struggle against cancer. However, the existing protein kinase inhibitors may have limitations in their effectiveness or may produce undesired side effects. Therefore, the development of new methods for searching for new inhibitors, which should be more effective and safe, is a topical issue. One of the promising areas is the use of molecular modeling to search for new protein kinase inhibitors.
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