Search

The review presents data on studies of the role of mycoplasmas as infectious agents in carcinogenesis, as well as their participation in cancer drug therapy and the impact on the outcome of treatment. Mycoplasmas are of particular interest because they have unique abilities to readily attach to and enter eukaryotic cells, modulate their functional state, and induce chronic inflammation while evading the host’s immune system. The review will highlight the data confirming the increased colonization of tumor tissue by mycoplasmas compared to healthy ones, describe the molecular mechanisms by which mycoplasmas activate the expression of oncogenes and growth factors, inactivate tumor suppressors, promote NF-κB-dependent migration of cancer cells and modulate apoptosis, which results in abnormal growth and transformation of host cells. The review also presents data on the effectiveness of anticancer drugs in mycoplasmal infections.

Cardiovascular and oncological diseases are the leading causes of adult death in the world. Despite proven efficacy, anticancer drugs can cause severe cardiovascular complications. Recently, data have appeared on the possible vasotoxic effects of chemotherapy drugs, which can manifest themselves as the progression of arterial hypertension and atherosclerosis, the development of myocardial ischemia and acute coronary syndrome, the formation of venous and arterial thrombosis. The key mechanism for the development of vasotoxicity is endothelial dysfunction, and anticancer drugs can also affect the processes of thrombosis. The review presents the results of 12 selected observational retro- and prospective studies involving cancer patients receiving presumably vasotoxic therapy. Data on the frequency of occurrence and possibilities for the prevention of vasotoxicity are presented.

In modern medical practice, the treatment of cancer is one of the most pressing issues. Many of the drugs used in the treatment of cancer have a toxic effect on the cardiovascular system of patients. The main clinical manifestations of cardiotoxicity are ischemic heart damage, rhythm disturbances, thrombosis, angina, asymptomatic changes in the electrocardiogram, and others. Side effects can develop both during the treatment period and months after the end of the course of chemotherapy. This is especially important for patients with concomitant cardiac or vascular pathology, since the severity of developing side effects can lead to disability or death of cancer survivors. The article discusses the data on the frequency of detection of the negative effect of pyrimidine, purine and folic acid antagonists on the cardiovascular system of cancer patients, the mechanisms of cardiotoxic effects of drugs in such patients, the possibilities of preventing heart damage and correcting for already developed lesions. The aim of this work is to collect, compare and systematize the available disparate data on the cardiotoxic effects of antitumor drugs of the antimetabolite group. An important condition for saving and preserving the quality of life of cancer patients is the identification of cardiovascular pathologies at the stage of preparation for chemotherapy, which can be facilitated by the active cooperation of oncologists and cardiologists. The search for information was carried out on the bases of scientific medical publications (eLibrary.ru, PubMed) taking into account the clinical recommendations for the treatment of malignant neoplasms.

Despite the development of biotherapy, chemotherapy remains one of the main methods of treatment of cancer patients. Currently, there are more than 100 anticancer drug substances, however, every year new drugs enter clinical practice and various therapeutic regimens are tested, expanding the possibilities of therapy and improving the results of treatment. Therefore, the adequate use of modern chemotherapy requires constant updating of information about anticancer drugs and methods of their use. Oral administration of drugs is the most natural and convenient way to introduce drugs into the human body. There are about 75% of orally administered drugs that have the ability to be absorbed in the gastrointestinal tract within 1−3 hours after administration. Oral dosage forms (DF) are most common due to the relative simplicity of their production, convenience of use, accuracy of dosing and high stability. Therefore, pharmaceutical companies often reproduce generics in the form of tablets and capsules for oral administration. However, most active pharmaceutical ingredient (API) are destroyed by the action of the gastrointestinal tract environment, which makes it impossible to use the oral administration. This review of the literature describes the main groups of anticancer drugs that are effective when taken orally. The aim of the study is to compile the information on the main groups of anticancer drugs used internally. Materials and methods. The object of the study was well-known anticancer drugs approved for oral administration. The study was conducted using search information and library databases (eLibrary, PubMed, CyberLeninka, ResearchGate), as well as State Register of Medicinal Remedies. Results and discussion. Analyzing the arsenal of cytotoxic drugs, it should be noted that antitumor substances are characterized by high chemical lability they are photosensitive, heat-labile, hygroscopic and hydrolytically unstable. These properties complicate both obtaining reproducible therapeutic effect when taken orally and technological inprocesses. In addition, anticancer drugs have mutagenic, teratogenic, sensitizing and allergenic effects. Conclusion. Lack of sufficient selectivity of the antitumor effect of cytotoxic drugs and a small breadth of pharmacological action require the use of DF, ensuring control of drug delivery to the body, including dosage accuracy and standard bioavailability. DF plays a very important role in the delivery of drugs to the lesion site. Capsules and coated tablets are necessarily created to avoid high toxicity of anticancer drugs and local tissue reactions when taken orally.

The article describes modern approaches for controlling wound healing after fistulizing glaucoma surgery. The review recounts international experience of steroidal and nonsteroidal anti-inflammatory drug and their efficacy research study results. Much attention is given to new strategies of wound healing regulation after fistulizing glaucoma surgery, aimed at enhancing its results. The article describes characteristics and modes of action of medicinal agents effecting the cytoskeleton, such as Rho-kinase inhibitors and taxane anticancer agents. A detailed account of modes of effecting wound healing through regulating the process growth factors, proteinases and cytokines is also given. Possible strategies include antifibrotic cytokine interferon-α application and inhibiting the following agents: transforming growth factor β; connective tissue growth factor (CTGF), that controls extracellular matrix components production and cicatrical tissue formation; vascular endothelial growth factor (VEGF), that indirectly influences fibrotic activit y through its angiogenic effect and also has a supposed direct effect on fibroblast activit y; proinflammatory placental growth factor (PIGF), that increases bleb area size and its survival time, and decreases postoperative angiogenesis, inflammation and fibrosis intensit y. The last part of the article gives a brief report on less widespread and researched methods of wound healing regulation, such as suppressing the activit y of matrix metalloproteinases and amniotic membrane application.

The article describes modern approaches to controlling wound healing after fistulizing glaucoma surgery. It provides a classification of refractory glaucoma degrees and summarizes risk factors for excessive scarring. Author describes various applications of widely administered in clinical practice antimetabolites (5 fluorouracil, mitomycin C) in patients with different degrees of excessive wound healing risk. The review also recounts international experience of steroidal and nonsteroidal anti-inflammatory drug use and their efficacy research study results. Much attention is given to new strategies of wound healing regulation after fistulizing glaucoma surgery, aimed at enhancing its results. The article describes characteristics and modes of action of medicinal agents effecting the cytoskeleton, such as Rho-kinase inhibitors and taxane anticancer agents. A detailed account of modes of effecting wound healing through regulating the process growth factors, proteinases and cytokines is also given. Possible strategies include antifibrotic cytokine interferon-α application and inhibiting the following agents: transforming growth factor β; connective tissue growth factor (CTGF), that controls extracellular matrix components production and cicatrical tissue formation; vascular endothelial growth factor (VEGF), that indirectly influences fibrotic activity through its angiogenic effect and also has a supposed direct effect on fibroblast activity; proinflammatory placental growth factor (PIGF), that increases bleb area size and its survival time, and decreases postoperative angiogenesis, inflammation and fibrosis intensity. The last part of the article gives a brief report on less widespread and researched methods of wound healing regulation, such as suppressing the activity of matrix metalloproteinases and amniotic membrane application.

This is a review on Ahmed valve application in glaucoma surgery. It contains, in particular, data on the Ahmed valve efficiency, results of experimental and histological studies of filtering bleb encapsulation, examines the use of antimetabolites and anti-VEGF agents, and discusses implantation techniques. The current appraisal of antimetabolites delivery systems integrated into the Ahmed valve is presented. Various complications encountered in practice and preventive measures are also covered.

The reaction of 2'-deoxy-5-trimethylsilyl(Tms)uridine with methanesulfonyl chloride led to the corresponding 3',5'-di-O-mesyl derivative, which was treated with lithium toluylate in DMF to give 2,3'-anhydro-1-(2-deoxy-5-O-p-toluyl-beta-D-xylofurano- syl)-5-Tms-uracil. Under these conditions 1-(2,3-dideoxy-5-O-p-toluyl-alpha-D- glycero-pent-2-enofuranosyl)-5-Tms-uracil was obtained from 1-(2-deoxy-alpha-D-ribofuranosyl)-5-Tms-uracil. Interaction of 2,3'-anhydronucleoside with LiN3 in DMF and successive deacylation with MeONa-MeOH gave 3'-azido-2',3'-dideoxy-5-Tms-uridine. Hydrogenation of this compound with 10% Pd/C in ethanol gave 3'-azido-2',3'-dideoxy-5-Tms-uridine. From 2,4,5-tris-Tms-uracil and 2,3-didehydrofurane in 1,2-dichloroethane in the presence of SnCl4 1-(2-tetrahydrofuranyl)-5-Tms-uracil was prepared. In a similar way 1-[(1,3-dioxy-2-propoxy)methyl]-5-Tms-uracil was synthesized by condensation of silylated uracil with 1,3-dibenzyloxy-2-acetoxymethylglycerol followed by the hydrogen transfer hydrogenolysis with cyclohexene--20% Pd(OH)2/C. None of the compounds exhibits cytotoxic activity against CaOv in vitro. The acycloderivative in concentration of 250 micrograms/ml has no effect on the HSV-1 and vaccinia virus replication in vitro. 3'-Azidonucleoside in dose of 100-750 mg/kg as well as 1-(2-tetrahydrofuranyl)-5-Tms-uracil in dose of 160-800 mg/kg were devoid of antitumour activity against P388 in vivo.

It is shown in the system with partially purified pyridoxal kinase from mouse liver, that the presence of one alkyl group in the 2nd or 6th positions of pyridine cycle in pyridoxole and pyridoxamine derivatives and pyridoxal oximes is a necessary condition which determines relatively high affinity of structural vitamin B6 analogues to the enzyme. 2'-n-Propylpyridoxal was phosphorylated by pyridoxal kinase with a relatively high rate, while 2-nor-6-methylpyridoxal, having a similar affinity to pyridoxal kinase, was not phosphorylated at all. The data obtained indicate an important role of the methyl group in the 2nd position of pyridine cycle in vitamin B6 molecule for its fixation in the enzyme active site and for the proper orientation, which provides enzymatic substrate phosphorylation. Some structural peculiarities of vitamin B6 analogues are considered, pre-determining their low or high efficiency as vitamin B6 antimetabolite in vivo.

Effects of energy metabolism inhibitors on the granule formation of neutral red in Ehrlich ascite carcinoma cells have no relation with the action of these agents on the ATP formation. Accumulation of neutral red by cells has no relation with granule formation and does not depend on the energy metabolism of cells. The action of 2,4-dinditrophenol, oligomycin, Tween-20, Tween-80 and sodium deoxycholate on the granule formation may be linked with direct action of these agents on the cell membranes, for example, on the Golgi membranes.

It has been shown that the active principle of imuran, 6-mercaptopurine, exerts a similar though less pronounced effect on viability and proliferative activity of Chinese hamster cells by affecting them preferentially in the stationary phase of growth. This effect cannot be attributed to the inhibition by imuran of xanthine oxidase, as proposed earlier, since another inhibitor of this enzyme, allopurinol, appears more effective, causing more cell deaths during exponential growth phase rather than during stationary growth. Other possible grounds for different cytotoxic effects of imuran depending upon the proliferative status of a cell have been discussed.