Mutations in a 23S rRNA Gene of Chlamydia trachomatis Associated with Resistance to Macrolides

For six clinical isolates of Chlamydia trachomatis, in vitro susceptibility to erythromycin, azithromycin, and josamycin has been determined. Four isolates were resistant to all the antibiotics and had the mutations A2058C and T2611C (Escherichia coli numbering) in the 23S rRNA gene. All the isolates had mixed populations of bacteria that did and did not carry 23S rRNA gene mutations

Рецептор эстрогенов ERα и киназа LYN: участие в механизмах канцерогенеза и использование в качестве мишеней в таргетной терапии при онкологических заболеваниях

Primary or secondary resistance is an important problem when treating any type of tumor. It is often associated with changes in target genes’ functioning. This raises the question of understanding functional intracellular interactions of genes and proteins in oncological processes and therapeutic resistance occurring. When searching target proteins of targeted therapy, it is necessary to identify biomolecules, participating in cell signaling life, which differ significantly in normal and oncological processes and interact with a large number of pathways. It is also important that these biomolecules are not an artifact of tumor therapy or cell line cultivation, and that it is possible to influence them directly, obtaining complex effect. In addition, it is important to study changes occurring during therapy with the biomolecules, which include proto-oncogene of SRC family kinase LYN and gene of the estrogen receptor α ESR1. All these factors may help to overcome the emerging resistance.Objective – to study the way genes of SRC kinase LYN and estrogen receptor α ESR1 influence oncological processes and occurrence of therapeutic resistance.Важной проблемой при терапии любого типа опухоли является возникновение первичной или вторичной резистентности, которая зачастую связана с изменением функционирования целевых генов. В связи с этим встает вопрос о понимании функциональных внутриклеточных взаимодействий генов и белков в онкологических процессах и возникновении резистентности к лечению. Для поиска целевых белков таргетной терапии необходимо идентифицировать таких участников сигнальной жизни клетки, функциональное состояние которых различно в норме и при канцерогенезе. также важно, чтобы определение этих участников не было артефактом вследствие терапии опухолей или культивирования клеточных линий и существовала возможность оказывать на них прямое воздействие, дающее комплексный эффект. кроме того, необходимо изучить изменения, происходящие с этими участниками, к которым относятся киназы семейства SRC LYN и ген эстрогенового рецептора α, во время терапии в целях преодоления возникающей резистентности.Цель обзора – изучение роли генов киназы семейства SRC LYN и эстрогенового рецептора α в онкологических процессах и возникновении резистентности к терапии

Sensitive Immunofluorescent Detection of the PRAME Antigen Using a Practical Antibody Conjugation Approach

Bioconjugation of antibodies with various payloads has diverse applications across various fields, including drug delivery and targeted imaging techniques. Fluorescent immunoconjugates provide a promising tool for cancer diagnostics due to their high brightness, specificity, stability and target affinity. Fluorescent antibodies are widely used in flow cytometry for fast and sensitive identification and collection of cells expressing the target surface antigen. Nonetheless, current approaches to fluorescent labeling of antibodies most often use random modification, along with a few rather sophisticated site-specific techniques. The aim of our work was to develop a procedure for fluorescent labeling of immunoglobulin G via periodate oxidation of antibody glycans, followed by oxime ligation with fluorescent oxyamines. Here, we report a novel technique based on an in situ oxime ligation of ethoxyethylidene-protected aminooxy compounds with oxidized antibody glycans. The approach is suitable for easy modification of any immunoglobulin G, while ensuring that antigen-binding domains remain intact, thus revealing various possibilities for fluorescent probe design. The technique was used to label an antibody to PRAME, a cancer-testis protein overexpressed in a number of cancers. A 6H8 monoclonal antibody to the PRAME protein was directly modified with protected-oxyamine derivatives of fluorescein-type dyes (FAM, Alexa488, BDP-FL); the stoichiometry of the resulting conjugates was characterized spectroscopically. The immunofluorescent conjugates obtained were applied to the analysis of bone marrow samples from patients with oncohematological diseases and demonstrated high efficiency in flow cytometry quantification. The approach can be applied for the development of various immunofluorescent probes for detection of diagnostic and prognostic markers, which can be useful in anticancer therapy