REVIEWS
Human epidermal growth factor receptor HER2, a proto-oncogene involved in the proliferation and differentiation signaling pathway. The overexpression and amplification of the HER2 gene and their significance have been studied in breast cancer. Data on HER2 over expression in gastric cancer vary widely, and the value is presented by inconsistent disparate data. The interpretation of HER2 in gastric cancer differs from the evaluation in breast cancer. The purpose of this review is to summarize current data on the evaluation of HER2 in gastric cancer for the selection of targeted therapy. The search in modern databases of medical literature was carried out, more than 100 modern literary sources on the above-mentioned topic were studied and analyzed in detail and carefully. The most significant data on the evaluation of HER2 expression in gastric cancer and its prognostic and predictive value were selected and presented. Selected options evaluate the expression of HER2 receptor in operating and biopsy material of stomach cancer. Comparative data on the use of different antibody clones to solve the above problem are presented. The most frequent and important errors and possible interpretation disorders in the expression of HER2 in gastric cancer are analyzed. The use of transtuzumab for targeted therapy in gastric cancer makes it mandatory to test surgical and biopsy samples of gastric cancer to assess their expression of HER2. The development of various methods and the progress of molecular biology, however, the main role of the immunohistochemical method in solving this problem still left. Gastric cancer needs a single accessible standardized system for evaluating HER2 expression, and, most importantly, expert level interpretation of these results.
The review reflects the history of phytoadaptogens studies (ginseng, eleutherococcus, etc.), which are considered to be geroprotectors by Eastern medicine for centures. They have a complex of protective effects on the body, as well as increasing its antitumor resistance. The first part of the review describes the antistress, immuno- and hormone-modulating, cognitive and neuroprotective properties of adapto gens. Together with the synchronizing effects on biorthms adaptogens are essential for preventive oncology.
The restoration of B-cell immunity is a key component of the success of allogeneic hematopoietic stem cell transplantation. In most cases, the restoration of B-lymphopoiesis is a slow and often incomplete process, which is accompanied by a decrease in the tolerance of the recipient to bacterial, viral, fungal pathogens. This process is influenced by a number of factors that determine its effectiveness and pace. It is important to restore not only the size of the B-cell population, but also their functional usefulness. The article provides an analysis of modern literature data on the significance of the restoration of B-cell immunity after allogeneic hematopoietic stem cell transplantation, a review of the main factors affecting the process of B-lymphopoiesis, and their prognostic component.
Cervical cancer (CC) incidence rate made up about 5 % in overall women cancer incidence in Russia in 2015. CC morbidity rose by 24.47 % during 2005–2015. Despite the fact that aggregated standardized cancer mortality rates for both men and women during 2005–2015 declined, women CC mortality increased by 8.3 %. CC is the leading cancer mortality cause in women aged 30–39 years. Moreover growth of oral and pharynx cancer incidence rates in both genders as well as penile cancer in men all indicate to an unfavorable trend. The present Review part contains data on HPV-associated cancers in Russia, vertical HPV transition as well as preventive HPV vaccines.
ORIGINAL REPORTS
Introduction Monoclonal antibodies (Mabs) are a good tool for diagnosing human pathologies. They are used as conjugates with fluorescent and other dyes. The classical approach of creating such conjugates is reduced to chemical reactions using the protein base of the Mab. At the same time, for a number of Mabs, conjugate production is accompanied by embedding the label into the antigen binding site, which leads to a decrease or complete loss of the specific activity of the conjugate. To get out of this situation, the synthesis of fluorescent conjugates by methods of carbohydrate chemistry through spatially distant from the active center oligosaccharides of antibodies is proposed.
Objective To obtain high activity ICO series Mab conjugates based on the reaction of covalent inclusion of the fluorescent label in the oligosaccharide sequence of the Mab.
Materials and methods We used Mab series ICO of high purity. Oligosaccharides Mabs oxidized to aldehyde groups, were subjected to interaction with fluoriscine-5-thiosemicarboside, followed by the reduction of hydrazone derivative borgidrides. The resulting covalent conjugate was investigated in a flow cytometry.
Results The synthesis of a fluorescent conjugate using monoclonal antibodies oligosaccharides was worked out. Modified monoclonal antibodies retain specific binding to target cells inherent in the native antibody. The resulting conjugates remained active for a long time during storage.
Conclusion An alternative method for conjugation of immunofluorescent, allowing to obtain conjugates of high activity, has been developed.
Introduction Generation of most immunocompetent cells takes place in bone marrow Bone marrow. As well, bone marrow is a peripheral lymphoid organ where antitumor effector cells and memory cells are present.
The aim of the work is to estimate peripheral lymphoid cell subpopulations in bone marrow of lung cancer patients.
Materials and methods Study has been done in 68 pts with lung cancer: squamous cell cancer (n = 28), adenocarcinoma (n = 38), other forms (n = 2). In all cases standard diagnostic and staging procedures were performed, as well as morphological (myelogram) and immunological study of bone marrow lymphocyte subpopulations. Multicolor Flow cytomtry was used for study of bone marrow lymphocyte populations. We studied T-cells and its subpopulations, B-cells, NK-cells, perforin-positive cells, and CD27-positive cells.
Results Squamous cell lung cancer was characterized by higher content of bone marrow mature T-cells (CD3), and CD8 lymphocytes. More typical for adenocarcinoma was mature B-cell reaction (CD20). Effector (perforin-positive) populations of lymphocytes also were related to histological type of cancer: for adenocarcinoma presence of CD4-positive cytotoxic lymphocytes and CD27-expression on effector cells. Perforin-containing lymphoid cells were in opposite correlation to erythrocaryocytes.
Conclusion Subpopulational lymphocyte content of bone marrow is related to histological variant of cancer and erythropoiesis in lung cancer patients.
The aim of the research was a comparative toxicological study of DOC-loaded particles and standard docetaxel solution form in acuteand subchronic experiments in mice after intravenous administration.
Materials and methods The research was conducted in female C57BL/6 mice. During the study of acute toxicity, drugs were administeredin the following dose range: 20, 60, 90, 120, 160 mg/kg. Over 30 days, mortality and body weight were evaluated, pathomorphologicalstudies were performed. The study of toxicity in conditions of subchronic administration of medicine was conducted using three timesdaily administration in single doses of 11 and 22 mg/kg. Subchronic toxicity of the drugs was studied with three times daily administrationin single doses of 11 and 22 mg/kg. The necessary studies were performed within 30 days.
Results With a single injection of PLGA-DOC-FAD in doses of 20, 60, 90 mg/kg, the death of animals wasn’t observed; at doses of 120 and160 mg/kg, the death of animals was detected in 1–4 days. In the case of administration of the DOC substance, the death of animalsoccurred within a day after the administration of doses of 60, 90, 120, 160 mg/kg. The pattern of intoxication was similar in case of compared drugs and manifested in hypodynamia, impaired movement coordination, hind limbs paresis, though the manifestation degreethereof was more expressed in the groups with the introduction of DOC than in the case of the introduction of PLGA-DOC-FAD. It wasdetected that the LD50 for PLGA-DOC-FAD is 140 mg/kg, and for the DOC substance – 112 mg/kg. In case of subchronic administration, the detected toxic properties of drug depend on the size of the dose applied. The administration of a single dose of 22 mg/kg of PLGA-DOC-FAD caused lethal effects (2/10), reversible delay in weight gain and leucopenia in surviving animals, and an increase in the relativemass of the spleen. The use of PLGA-DOC-FAD in a single dose of 11 mg/kg didn’t cause death, was well tolerated and characterizedby similar toxicity with the docetaxel substance.
Conclusion Based on experimental data, the toxic dose levels of PLGA-DOC-FAD were determined under acute and subchronic administration. The results obtained allowed us to recommend PLGA-DOC-FAD for further examination.
Introduction At the national medical research center of оncology N.N. Blokhin preclinical toxicological studies of a lyophilized dosage form of a drug based on acadesin, a new antitumor drug, were conducted.
The aim of the study to study the subchronic toxicity of the drug on the basis of acadesine in rats to evaluate its toxicity.
Materials and methods The study was conducted on 40 noninbred male mongrel rats. The drug was administered intraperitoneal daily 15-fold in total doses of 750, 1150 and 2300 mg/kg. Clinical and laboratory tests were performed during the entire observation period (30 days). The pathomorphological study was performed on the 1st and 30 th day of observation.
Results It was found that the drug based on acadesin, when applied repeatedly to rats in all the studied doses, did not cause changes in the indicators of peripheral blood of animals, morphological changes in all the studied organs and tissues of animals (except the kidneys), functional changes in the state of the liver, heart, kidneys and gastrointestinal tract. However, morphologically revealed changes in the kidneys when using the drug in the total dose of 1150 mg/kg on the 1st and 30 th day of observation, and in the total dose of 2300 mg/kg only on the 30 th day of observation.
Conclusion The detected toxic effect of the drug based on acadesin on the kidneys of rats is dose-dependent. When using the drug in the course of the course at a total dose of 750 mg/kg, which is 60 times higher than the single therapeutic dose for rats (12.5 mg/kg), toxic manifestations were completely absent during the entire period of observation. This allowed us to recommend a drug based on acadesin for further research.
ISSN 1726-9792 (Online)
