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Vol 9, No 6 (2022)
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CANCER

5-15 625
Abstract

This review overview current epidemiology data of malignant tumors of the central nervous system, and determines the significance of molecular diagnostics and expression of heat shock proteins in tumorigenesis. Particular attention is paid to the description of molecular chaperones as diagnostic and prognostic markers, as well as the prospects for chaperones using in personalized therapy the central nervous system tumors. The search for literature was carried out on the database platforms Medline (via PubMed) and Scopus, Cochrane Library, The Lancet Public Health Journal published between 1988 and 2022. The material was searched for keywords and terms, including “heat shock proteins”, “tumors of the central nervous system”, “brain tumors”, “molecular diagnostics”, “expression of molecular chaperones”, Hsp110, Hsp90, Hsp70, Hsp60, Hsp40, small HSPs. Molecular chaperones, due to their important role in physiological processes in the cell, are highly expressed in brain tumors, and the expression level of HSPs strongly correlates with the degree of malignancy, invasive potential, and resistance to radiochemotherapy. For some HSPs (i.e. HSP10, HSPB1, DNAJC10, HSPA7, HSP90) a direct correlation has been found between the level of protein expression (based on IHC analysis) and a poor overall survival prognosis for patients with glial tumors. This indicates the prognostic value of these markers, which in the future may be included in the diagnostic panel when examining a tumor sample.

16-25 857
Abstract

Pancreatic cancer, despite its low prevalence, is the fourth most common cause of cancer death, with a 5-year survival rate of no more than 10 %. Experts predict that by 2030, pancreatic cancer will become the second most common cause of death from malignant neoplasms, surpassing colorectal and breast cancers. Thus, pancreatic cancer is characterized by very unfavorable prognosis, primarily due to the chemoresistant nature of the tumor.

Only a few treatment options for pancreatic cancer are currently available, with low response rates, short progression-free survival and short overall survival, and severe toxicity. In order to improve clinical outcomes, a number of studies on the use of regional chemotherapy as a treatment option for pancreatic cancer have demonstrated dose-dependent tumor sensitivity. Chemotherapy by intra-arterial perfusion of the pancreas made it possible to increase local concentrations of chemotherapeutic agents with minimal effect on healthy tissues and a lower incidence of side effects compared to systemic chemotherapy. This therapeutic approach has demonstrated a good therapeutic effect in the treatment of malignant neoplasms of other localizations. This review summarizes clinical approaches to chemotherapeutic administration by intra-pancreatic intra-arterial perfusion in terms of methods, pharmacokinetics, and clinical outcomes.

CARDIOVASCULAR MEDICINE

26-35 631
Abstract

Alterations in the proteostasis network and accumulation of misfolded protein aggregates — is one of the new pathogenesis concepts of chronic heart failure. We hypothesis in addition to well-known transthyretin (ATTR) and AL-amyloidosis some patients may represent amyloid lesion in myocardium came from undescribed amyloidogenic precursors due to misfolding of myocardial structural proteins.

Here, we report on the case of patient with hypertrophic and restrictive phenotype of cardiomyopathy, biventricular heart failure, considered for heart transplant, and excluded known types of amyloidosis. Genetic testing revealed extended deletion in the gene of giant protein titin (TTN).

We present with the use of bioinformatic analysis and molecular modeling how this mutation could lead to unfolding of corresponding protein and open its amyloidogenic motifs for intermolecular interactions, therefore, provide amyloidogenic ability. This data enables in more detail to decipher the pathogenesis of chronic heart failure on the background of cardiomyopathy, planning further studies for development of personalized risk profiling in different types of amyloidosis and elaborate more personalized treatment approach for such patients in the future.

NEUROLOGY

36-43 376
Abstract

Background. Pharmacoresistant epilepsy, i.e. failure to achieve adequate seizure control with antiepileptic drugs develops in 30–40 % of patients. The surgical treatment for these patients are of particular importance. The relevance of studying the emotional sphere of neurosurgical patients with drug-resistant epilepsy stems from the high incidence of this pathology and its impact on patients’ quality of life.

Objective. To investigate comorbidity indicators: depression and anxiety in neurosurgical patients with drug-resistant epilepsy during the preoperative and postoperative periods of epilepsy treatment.

Design and methods. In 2019–2020, Polenov Neurosurgical Institute studied comorbid affective pathology in 46 neurosurgical patients with drug-resistant epilepsy in 2 groups: Group 1 — preoperative and Group 2 — postoperative patients, using HADS for screening.

Results. The study included 46 patients in 2 groups. Group1 — 56.5 %, Group2 — 43.5 %. The mean age of the participants in the study was 30.8 ± 1.1 years. The sex ratio in the cohort was 1.7 males to 1 female. In the cohort, no anxiety was observed in 71.7 % and depression in 84.8 %, severe anxiety in 13 % and depression in 8.7 %.

Conclusion. Among the neurosurgical patients with drug-resistant epilepsy, patients without symptoms of anxiety and depression predominated. There is a need to expand the sample and investigate further.

ЛУЧЕВАЯ ДИАГНОСТИКА И ТЕРАПИЯ

44-58 582
Abstract

Sleep is an important and complex physiological process that is necessary for the normal functioning of any organism. Sleep disorders diagnostics is an issue of interest in patients with acute ischemic stroke management. Currently these disorders are considered not only as a consequence of earlier stroke but as an acute cerebrovascular disease risk factor itself. Sleep disorders in patients with acute cerebrovascular disease can be presented in different types, including: insomnia, sleep apnea, central disorders of hypersomnolence, circadian rhythm sleep-wake disorders, parasomnias, sleep related movement disorders, unspecified sleep related disorders.

There are very few publications on the subject of sleep disorders associated with acute ischemic stroke, despite the fact that imaging of each of these conditions separately occupies a significant place in radiology.

Polysomnography is considered to be the gold standard in sleep disorders diagnostics. Contrary to that, the precise imaging of acute cerebrovascular accidents requires high-technology modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI).

The article represents a current literature review regarding radiologic methods in diagnostics of sleep disorders in patients with acute ischemic stroke anamnesis.

Experimental studies

59-70 610
Abstract

Background. Research in oncology assumes establishment and usage of xenograft animal models, meeting the requirements of humanity and rationality. Although praised as promising field of research, preclinical studies of low-molecular-weight inhibitors, antitumor monoclonal antibodies, vaccines, cellular therapy products, CAR-T cells entail continuous control of tumor growth dynamics. Luciferase detection of bioluminescence requires injection of a reporter substrate. However, injections not only are laborious, time-consuming and expensive, but are also stressful for animals. Thus, a vast variety of new visualization methods is employed, including proteins of the far-red spectrum.

Objective. The study aimed to compare detection efficiency of tumor growth dynamics in mice models of cervical cancer, applying a commercially available line of fluorescent red protein derivatives of Katushka clade and Renilla luciferase, that is commonly used in in vivo studies.

Design and methods. Xenograft mice models were derived injecting modified HeLa cell line, that expresses fluorescent reporter proteins: Katushka, Katushka2S, TurboRFP, TurboFP650 and Renilla enzyme.

Results. Spectral properties and emission wavelength of far-red fluorescent protein Katushka and Katushka2S outlines these markers within RFP derivatives lineage as outstanding instrument for in vivo tumor visualization.

Conclusion. Detection of fluorescent far-red reporters Katushka and Katushka2S can be considered as a credible alternative to Renilla luciferase bioluminescence in experimental models in vivo on the part of immunotherapy research.

МОЛЕКУЛЯРНАЯ БИОЛОГИЯ И ГЕНЕТИКА

71-94 667
Abstract

Genetic variants in the SCN5A gene, encoding the cardiac isoform of the NaV1.5 voltage-gated sodium channel, were observed in patients with various hereditary heart diseases. Actual problems of modern electrophysiology covers the search for mechanisms of the disease development and the search for approaches to correct sodium current dysfunction in pathological conditions.

In recent decades, significant progress has been achieved in understanding the life cycle of NaV1.5 and the distribution of channels in various microdomains of the plasma membrane.

NaV1.5 is regulated at all possible levels from SCN5A expression to control of ubiquitin-dependent degradation. Depending on the microdomain of the plasma membrane, NaV1.5 is part of various macromolecular complexes. Thus, in the lateral membrane, NaV1.5 is co-localized with the dystrophin-syntrophin complex, and in the region of the intercalated disc, sodium channels are surrounded by desmosomal proteins, G-ankyrin, and gap junction proteins. This review systematizes knowledge about NaV1.5 protein partners in different regions of the cardiomyocyte membrane, as well as about post-translational modifications of NaV1.5. Special attention is paid to potential clinical applications. Therapy strategies targeting SCN5A synthesis, NaV1.5 transport, and late sodium current are considered. Thus, the study of the mechanisms regulating the functioning of α-NaV1.5 in the future will play an important role not only in understanding the biology and pathophysiology of NaV1.5, but also in the search for new promising methods of therapy.



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ISSN 2311-4495 (Print)
ISSN 2410-5155 (Online)