Vol 5, No 1 (2018)
- Year: 2018
- Published: 15.01.2018
- Articles: 6
- URL: https://umo.abvpress.ru/jour/issue/view/16
Full Issue
REVIEW ARTICLES
Proteoglycans in normal physiology and carcinogenesis
Abstract
Malignant transformation of any cell is associated with numerous physiological and morphological disorders at both genomic and protein levels, a variety of macromolecules being involved in. However, the tumour development and metastasis depends on not only the molecular characteristics of the tumour cell but also its interaction with the surrounding extracellular matrix (ECM), which is an important and necessary part of any tissue. An important role in this process belongs to the complex protein-carbohydrate molecules – proteoglycans (PG), which are one of the main component of ECM and cell surface of any tissue and are tightly involved in cell-cell and cell-matrix interactions and signaling. During carcinogenesis, significant changes in the PG structure and composition occur both at the surface of tumour cells and surrounding ECM, resulting in the transformation of normal ECM into a tumour microenvironment and deterioration of cell-cell and cell-matrix communication. Further, the tumorigenic niche contributes to active proliferation of the cancer cells, tumour development and metastasis. At present, many key PG are identified as possible diagnostic and prognostic molecular markers and target molecules for the creation of new antitumor drugs.
The review describes the main PG types, their structure, localisation, functional role in normal cell and tissue physiology and participation in molecular mechanisms of carcinogenesis.
8-25
Asynchronous replication in oncological patients
Abstract
Epigenetics is a science studying mechanisms of heritable changes in gene function that occur without a change in the DNA sequence. One of the most important marks of epigenetic misbalance of cell genome is an replication asynchrony of genes with biallelic expression. Interphase fluorescence in situ hybridization (I-FISH) in phytohaemagglutinin-stimulated lymphocytes of peripheral blood is a proper method of estimation of aberrant DNA replication time e. g. DNA replication asynchrony. In this review we analyzed reports referring to asynchronous DNA replication of biallelically expressed genes in lymphocytes of peripheral blood of cancer patients. Analysis shows the DNA replication asynchrony is a nonspecific tumor marker observing both in tumor cells and lymphocytes of peripheral blood in oncohematological patients and patients with solid tumors. It’s stated the frequency of lymphocytes with asynchronous DNA replication of studied genes in cancer patients is increased significantly compares with healthy donors and is enhanced during malignance process. It gives the opportunity of potential using asynchronous replication as molecular genetic marker for cancer patients early revealing.
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EXPERIMENTAL RESEARCH
Target liquid biopsy using “enriched” polymerase chain reaction and DNA melting analysis
Abstract
Objective: to evaluate the possibility of using a highly sensitive method of “enriched” polymerase chain reaction followed by DNA melting analysis (PCR-DMA) for target liquid biopsy of cancer patients.
Materials and methods. The “enriched” PCR-DMA was used for mutation scanning of KRAS (codons 12 and 13) in tumor and blood plasma of 20 patients with colorectal cancer.
Results. Activated oncogene was found in tumor tissue of 16 patients and in blood plasma of 5 patients (confirmed by sequencing). Mutant KRAS alleles were also found in tumor and plasma of another 2 patients, but in very low concentrations that did not allow their validation by Sanger sequencing. Thus, in our study the target liquid biopsy was successful in ~35 % patients. Since the plasma tests were carried out after repeated medical procedures causing mass death of tumor cells, the actual efficiency of this approach may appear significantly higher.
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Exosomal proteins as potential markers of multiple myeloma diagnostics
Abstract
Background. Multiple myeloma (MM) is a hematologic malignancy of plasma cells. The microenvironment plays a key role in MM cell survival and drug resistance through release of soluble factors, expression of adhesion molecules and release of exosomes (EXs). The role that EXs, released by MM cells have in cell-to-cell communication and signaling in the bone marrow is currently unknown. EXs as a source of markers for MM diagnostics are also not studied.
Objective: to use proteomic profiling of EXs as a tool to identify circulating tumor associated markers in MM patients.
Results. The proteome composition of EXs obtained from plasma of patients with MM and multiple sclerosis was studied for the first time. nano-HPLC–MS/MS analysis identified a total of 332 proteins in the EXs of both groups of patients and determined the proximity of their qualitative composition. For the first time, 12 differentially expressed proteins were detected, the levels of which were significantly increased in EXs from patients with MM. This allowed us to consider them as potential markers of the disease.
Conclusion. Proteomic analysis of EXs obtained from plasma of patients with MM is an important method for finding disease markers.
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