Prevalence of certain forms of obstetric pathology and incidence of their implementation at pregnant women with infertility history

The article presents data on the frequency prediction of pregnancy in women with a history of infertility, complications of pregnancy and labor. The study showed a higher frequency of the projected implementation obstetric pathologies in women with impaired reproductive function, hence the need to improve the quality of medical care provided since the preparation for pregnancy

Cytotoxic effect of the VVGMCSF-Lact oncolytic virus against 3D cultures of human glioblastoma cells U-87 MG

Background. One of the promising methods of treating tumors is virotherapy, which is based on direct lysis of cancer cells by a virus and a virus-mediated antitumor immune response of the body. For the recombinant vaccinia virus strain VVGMCSF-Lact, producing human GMCSF and the oncotoxic protein lactaptin, cytotoxic and antitumor effects were shown in experiments in vitro and in vivo, respectively, when using adhesive cultures of U-87 MG human glioblastoma cells. 3D cultures are a more relevant tumor model than adhesive models, as they more fully reflect the realistic scenario of cancer development, as well as the response of the tumor to anticancer therapy.The aim. To evaluate the cytotoxic effect of the oncolytic virus VV-GMCSF-Lact against 3D cultures of human glioblastoma U-87 MG.Materials and methods. The following methods were used in the work: cultivation of 3D cell cultures, cytofluorometry, microscopic analysis, virus titration, statistical analysis.Results. U-87 MG cells were transduced with a lentiviral vector carrying the GFP reporter gene. The cytotoxicity of the VV-GMCSF-Lact virus (IC50) against the studied cells was 0.024 PFU/cell. U-87 MG cells were cultured under conditions for the formation of 3D structures. Microscopic analysis showed the oncolytic effect of the virus on the cells of 3D cultures as early as 24 hours after the start of incubation. Flow cytometry showed an increase in the granularity of glioblastoma cells under the action of the virus, which indicates active replication of the virus in the cells. The virus titer was 0.44 PFU/cell.Conclusions. The recombinant VV-GMCSF-Lact virus has a cytotoxic effect on 3D human glioblastoma U-87 MG cell cultures and actively replicates in them. In the future, to test the oncolytic effect of VV-GMCSF-Lact, it is planned to use not only 3D human glioblastoma cultures, but also cerebral organelles obtained in the process of cocultivation of glioblastoma cells and induced human pluripotent cells

CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors: Australian Breast Cancer Family Study

INTRODUCTION: Because CYP17 can influence the degree of exposure of breast tissues to oestrogen, the interaction between polymorphisms in this gene and hormonal risk factors is of particular interest. We attempted to replicate the findings of studies assessing such interactions with the -34T→C polymorphism. METHODS: Risk factor and CYP17 genotyping data were derived from a large Australian population-based case-control-family study of 1,284 breast cancer cases and 679 controls. Crude and adjusted odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analyses. RESULTS: We found no associations between the CYP17 genotype and breast cancer overall. Premenopausal controls with A(2)/A(2 )genotype had a later age at menarche (P < 0.01). The only associations near statistical significance were that postmenopausal women with A(1)/A(1 )(wild-type) genotype had an increased risk of breast cancer if they had ever used hormone replacement therapy (OR 2.40, 95% CI 1.0 to 5.7; P = 0.05) and if they had menopause after age 47 years (OR 2.59, 95% CI 1.0 to 7.0; P = 0.06). We found no associations in common with any other studies, and no evidence for interactions. CONCLUSION: We observed no evidence of effect modification of reproductive risk factors by CYP17 genotype, although the experiment did not have sufficient statistical power to detect small main effects and modest effects in subgroups. Associations found only in subgroup analyses based on relatively small numbers require cautious interpretation without confirmation by other studies. This emphasizes the need for replication in multiple and large population-based studies to provide convincing evidence for gene–environment interactions

Аптамеры для диагностики и лечения глиальных опухолей человека

Purpose of the study: to evaluate the feasibility of using functional analogues of protein antibodies – dNa/ RNa aptamers in diagnostics, treatment and prognosis of human brain glial tumors.Material and Methods. The relevant literature sources were searched in scopus, Web of science, pubmed, elibrary with inclusion of publications from 2000 to 2023. sixty articles are presented in the review.Results. The analysis of the literature devoted to classification, diagnostics and therapy of brain glioblastomas was carried out and the feasibility of using for in vivo diagnostics and therapy of this disease aptamers, which are molecular recognition elements based on DNA/RNA oligonucleotides, capable of binding to the given molecular targets and distinguishing even separate functional groups in them, was studied. A list of aptamers to human glial brain tumors and their molecular targets that can be used for diagnostics and therapy of glioblastoma, including tumor imaging by pet/ct, mRi, plasmon resonance, fluorescence and confocal microscopy, etc., is presented. literature data suggest that DNA/RNA aptamers can be used to search for circulating tumor cells in the blood of glioblastoma patients, to target therapeutic drugs to the tumor and to inhibit tumor growth.Conclusion. Brain glioblastoma is a heterogeneous tumor consisting of cells at different stages of malignancy and, accordingly, with a different set of oncogenes. For this reason, a multitarget strategy that includes combined suppression of angiogenesis, invasion, metastasis, proliferation and survival of tumor cells should be proposed for the therapy of this disease. DNA/RNA aptamers tailored to key proteins involved in oncogenic transformation may be suitable candidates for the implementation of multitarget therapy for brain glioblastoma.Цель исследования – оценить возможность использования функциональных аналогов белковых антител – ДНК/РНК-аптамеров в диагностике, лечении и прогнозировании развития глиальных опухолей головного мозга человека.Материал и методы. Поиск соответствующих источников литературы проводили в системах scopus, Web of science, pubmed, elibrary с включением публикаций с 2000 по 2023 г. В обзоре представлены данные из 60 статей.Результаты. Проведен анализ литературы, посвященной классификации, диагностике и терапии глиобластом головного мозга и изучению возможности использования для in vivo диагностики и терапии этого заболевания аптамеров, которые представляют собой молекулярные распознающие элементы на основе ДНК/РНК-олигонуклеотидов, способных связываться с заданными молекулярными мишенями и различать в них даже отдельные функциональные группы. Приведен список из аптамеров к глиальным опухолям головного мозга человека и их молекулярных мишеней, которые могут быть использованы для диагностики и терапии глиобластомы, в том числе для визуализации опухоли методами ПЭТ/КТ, МРТ, плазмонного резонанса, флуоресцентной и конфокальной микроскопии и др. Данные литературы свидетельствуют о том, что с помощью ДНК/РНК-аптамеров можно осуществлять поиск циркулирующих опухолевых клеток в крови больных глиобластомой, адресную доставку к опухоли терапевтических препаратов и подавлять опухолевый рост.Заключение. Глиобластома головного мозга – гетерогенная опухоль, состоящая из клеток, находящихся на разной стадии злокачественности и, соответственно, с различным набором онкогенов. Именно поэтому для терапии этого заболевания должна быть предложена мультитаргетная стратегия, которая включает в себя комбинированное подавление ангиогенеза, инвазии, метастазирования, пролиферации и выживаемости опухолевых клеток. Подходящими кандидатами для реализации мультитаргетной терапии глиобластомы головного мозга могут стать ДНК/РНК-аптамеры, подобранные к ключевым белкам, участвующим в онкогенной трансформации

Multiple Pathway-Based Genetic Variations Associated with Tobacco Related Multiple Primary Neoplasms

BACKGROUND: In order to elucidate a combination of genetic alterations that drive tobacco carcinogenesis we have explored a unique model system and analytical method for an unbiased qualitative and quantitative assessment of gene-gene and gene-environment interactions. The objective of this case control study was to assess genetic predisposition in a biologically enriched clinical model system of tobacco related cancers (TRC), occurring as Multiple Primary Neoplasms (MPN). METHODS: Genotyping of 21 candidate Single Nucleotide Polymorphisms (SNP) from major metabolic pathways was performed in a cohort of 151 MPN cases and 210 cancer-free controls. Statistical analysis using logistic regression and Multifactor Dimensionality Reduction (MDR) analysis was performed for studying higher order interactions among various SNPs and tobacco habit. RESULTS: Increased risk association was observed for patients with at least one TRC in the upper aero digestive tract (UADT) for variations in SULT1A1 Arg²¹³His, mEH Tyr¹¹³His, hOGG1 Ser³²⁶Cys, XRCC1 Arg²⁸⁰His and BRCA2 Asn³⁷²His. Gene-environment interactions were assessed using MDR analysis. The overall best model by MDR was tobacco habit/p53(Arg/Arg)/XRCC1(Arg³⁹⁹His)/mEH(Tyr¹¹³His) that had highest Cross Validation Consistency (8.3) and test accuracy (0.69). This model also showed significant association using logistic regression analysis. CONCLUSION: This is the first Indian study on a multipathway based approach to study genetic susceptibility to cancer in tobacco associated MPN. This approach could assist in planning additional studies for comprehensive understanding of tobacco carcinogenesis

APEIRON Nr. 20 October 1994 Page 21 Epistemology and Special Relativity

Introduction The history of science testifies to the pernicious influence of epistemological errors on the progress of science. Such errors lead to incorrect interpretations of scientific facts and applications of natural laws. Epistemology has two significant objectives: 1. Epistemology studies the processes, methods and laws of knowledge and objective truth. 2. Epistemology seeks and studies indications which may be reduced to the attributes of objective (scientific) truth. Using attributes as criteria, we can recognize objective truth. When we make hypotheses, epistemology analyzes these hypotheses and identifies epistemological errors. If there are no errors, the hypothesis acquires the status of a scientific truth. Otherwise, we must consider that the thesis is an error. For example, we consider the Copernican heliocentric system and the Ptolemaic geocentric system. We ask the question: What epistemological error caused Ptolemy&apos;s system to collapse? We answer this quest

Introduction Analysis of the Lorenz Gauge

The multivaluedness of solutions of the wave equation, which depend on a gauge choice, is established. It is shown that the Lorenz gauge of the Maxwel