Vol 5, No 3 (2018)

Cover Page

Full Issue

REVIEW ARTICLES

Clinical, morphological, and molecular genetic predictors of metastatic lesions in the regional lymph nodes in breast cancer

Dergunova Y.A., Podionov V.V., Bozhenko V.K., Kometova V.V., Dardyk M.V.

Abstract

Despite the sufficient amount of data accumulated in the literature, there are still no factors, on the basis of which it would be possible to estimate the regional lymph nodes status in breast cancer with a high degree of accuracy. The review presents literature data relating to the influence of clinicopathological, molecular-biological and genetic characteristics of primary tumor on lymph node metastases. Data of 66 foreign and Russian articles are included.

Advances in Molecular Oncology. 2018;5(3):8-16
pages 8-16 views

The mechanisms of acquired resistance to anti-EGFR drugs in non-small cell lung cancer not associated with T790m mutation and their significance in clinical practice

Karabina E.V., Lubchenko L.N., Davydov M.M.

Abstract

The prospects of treatment strategies for patients with non-small cell lung cancer (NSCLC) featuring the acquired resistance to tyrosine kinase inhibitors, not associated with the Т790М mutation, are quite vast from a scientific point of view, but in routine clinical practice they are not yet available in full. Understanding the mechanisms of acquired resistance to tyrosine kinase inhibitors is important for clinicians from the perspective of the possibility of forming more effective options for the second and subsequent treatment of NSCLC. The most studied and frequent mechanism causing the formation of the acquired resistance is the appearance of the Т790М mutation in 20 exons of the EGFR gene. This article describes the current understanding of the mechanisms of acquired resistance to tyrosine kinase inhibitors not associated with the mutation of T790M, the evolution of views concerning the treatment of NSCLC, progressing in the course of the treatment by this group of drugs. Taking into account the diversity of unresolved issues and directions of further scientific research, we should not forget about the available research results and the ability to use the described options in routine clinical practice in a proper way.

Advances in Molecular Oncology. 2018;5(3):17-24
pages 17-24 views

Healthcare workers: occupational carcinogenic factors and cancer risk

Solenova L.G., Nekrasova L.A.

Abstract

The number of healthcare workers is over two million in Russia. Many of them are exposed to hazardous physical, chemical and biological occupational factors acting along with psychological strain. The results of large epidemiological studies carried out in various countries revealed greater cancer risk in physicians and nurses: cancer of the breast, skin, brain and other sites. Higher cancer risk of lung, breast, uterine, ovary, brain is considered to be associated with ionizing radiation. The female healthcare workers who handle antineoplastic drugs showed a greater risk of birth defects in offspring, spontaneous abortions and breast cancer. In Russia, the growing number of accidents among healthcare workers following transmission of infection by carcinogenic biological factors such as HBV and HIV is observed. Higher risk of reproductive impairments, hyperplasia of the breast and uterine tissues, breast cancer are revealed in nurses working the night shift. In Russia, there is lack of epidemiological studies of cancer risk among healthcare workers, the number of medical personal exposed to occupational carcinogens is unknown. That all does not show the actual situation in our country and does not allow setting priorities in cancer prevention among medical workers.

Advances in Molecular Oncology. 2018;5(3):25-39
pages 25-39 views

RESEARCH ARTICLES

Relation of EGFR/PI3K/AKT signaling components with tamoxifen efficacy in patients with estrogen-dependent breast cancer

Dronova T.A., Babyshkina N.N., Zavyalova M.V., Patalyak S.V., Slonimskaya E.M., Cherdyntseva N.V., Kzhyshkowska J.G.

Abstract

Advances in Molecular Oncology. 2018;5(3):40-50
pages 40-50 views

Molecular and genetic diversity in melanoma of eye

Mazurenko N.N., Tsyganova I.V., Nazarova V.V., Utyashev I.A., Orlova K.V., Ponkratova D.A., Martinkov D.V., Demidov L.V.

Abstract

Background. Ocular melanoma is the most common cancer of adult eye and is represented by two main subtypes of uveal (UM) and conjunctival (CM) melanoma with distinct clinical (frequency, localization, histology) and genomic features. The objective is to compare molecular and genetic characteristics of tumors in patients with melanoma of the eye. Materials and methods. In this study molecular profiling of 78 tumors including 73 UM (choroidea, ciliar body and iris) and 5 СM, was evaluated. DNA was isolated from tumor cells collected by macrodissection of FEPE sections of tumor biopsies using proteinase K. The following genes were studied by Sanger sequencing: GNAQ, GNA11, KIT, BRAF, NRAS. Results. Mutations in GNAQ and GNA11 were found in 81 % (59/73) of UM, in 42 % (31/73) and 38 % (28/73) of cases correspondently. GNAQ mutations were more frequent in primary UM (63 %), while GNA11 mutations dominated in metastatic UM (42 %). There was а correlation between frequency of GNAQ/GNA11 mutations and histologic type of UM. GNAQ mutations were identified in 55 % of spindle cell UM, while GNA11 mutations were more frequent in epithelioid cell UM (42 %). There were no differences in frequency of GNAQ/GNA11 mutations in UM of patients of different age (younger and elder 50 years). There was no statistically difference in UM patient outcome with GNAQ or GNA11 mutations. We also detected 3 UM with KIT mutations and 2 UM with BRAF mutations. There was no big difference in frequency of «driver mutations» in UM of choroidea, ciliar body and iris. Molecular profiling of conjunctival melanoma (CM) resembles that of cutaneous melanoma of skin: in 3 (60 %) CM BRAF V600E was identified and in 1 (20 %) – NRAS Q61K. Conclusion. Genetic analysis reveals wide diversity of melanoma of eye and is important for it characterization and treatment.

Advances in Molecular Oncology. 2018;5(3):51-58
pages 51-58 views

Cytotoxic cationic peptides as а ligands for receptor nucleolin

Lushnikova A.A., Kostarev A.V., Ponkratova D.A., Onyan A.V., Glubokova E.G., Andreev S.M.

Abstract

Background. Chaperone proteins nucleolin (NCL, or C23) and nucleophosmin (NPM, or B23) regulate key cell functions. The most tumors are characterized by over-expression of these proteins, especially in cell nuclei and on the сell surface, as NCL. Differential expression of NCL/NPM in tumor and normal cells is the basis of selective cytotoxicity of cationic peptides – expected ligands for these proteins. Objective. Analysis of the interactions between nucleolin and some peptides with high nonspecific toxicity for tumor cells. Materials and methods. The interaction of 4 previously characterized cationic peptides with nucleolin dimer was analyzed by pair molecular docking using Maestro 11 program. Results and conclusion. It is shown that these peptides can associate with receptor nucleolin molecules, forming energy-stable complexes. In the active centre of NCL molecule were found, at least, 7 positions of amino acids, which bind to the tested peptides at a high frequency (43–100 %). This indicates the conservative structure of dimer NCL, its stable binding to peptide ligands and the possibility of design the optimal structure of cationic peptides that induce tumor cell death due to competing binding to the target proteins.

Advances in Molecular Oncology. 2018;5(3):59-64
pages 59-64 views

Epstein–Barr virus in the ethnic Tatars population: the infection and sequence variants of LMP1 oncogene

Smirnova K.V., Senyuta N.B., Botezatu I.V., Dushenkina T.E., Lubenskaya A.K., Frolovskaya A.A., Petrov S.V., Lichtenstein A.V., Gurtsevitch V.E.

Abstract

Advances in Molecular Oncology. 2018;5(3):65-74
pages 65-74 views

Interrelation of HPV-infection of endometry carcinoma and its clinical-morphological features

Zykova T.A., Moiseenko T.I., Frantsiyants E.M., Vovkochina M.A.

Abstract

Background. There are contradictory data on the detection of human papillomavirus (HPV) in the tumor tissue in endometrial cancer (EС). Objective: to assess HPV infection rates in EC tumor tissues and to establish the relationship between the status of HPV infection and tumor morphological characteristics. Materials and methods. 57 formalin-fixed paraffin-embedded (FFPE) tissue samples of EC patients aged 47–78 years were studied. HPV DNAs were found in 54.4 % of samples. Results and conclusion. We did not reveal an association between the HPV tumor status and age, metastasis or invasion depth. However, there was an interdependence between HPV infection and some morphological characteristics of the tumor: its histological type (adenocarcinomas with squamous cell differentiation were HPV-positive 1.8 times more frequent compared to adenocarcinomas without one; in the first case, tumor tissues were more often infected with HPV 16, and in the second case with HPV 18); tumor grade (in the total cohort and in serous-papillary adenocarcinomas, tumors with higher grades were more often HPV-infected: from 0 to 81.8 % and from 0 to 100 % respectively); disease stage (in the total cohort the percentage of HPV-positive tumors in stage II was 2.4 times and in stage III – 1.6 times higher than in stage I, and stage IA tumors were HPV-positive 2.3 times more often than IB tumors); type of tumor growth (tumors with infiltrative growth type were HPV-positive 1.7 times more often than with exophytic growth, and 2.2 times more often than with mixed growth). The achieved results do not allow us to conclude with confidence that HPV is the main tumor forming factor in EC.

Advances in Molecular Oncology. 2018;5(3):75-82
pages 75-82 views

Ability to form duplexes as a factor of intracellular microRNA distribution

Kuzmichev S.A., Komelkov A.V., Tchevkina E.M.

Abstract

Advances in Molecular Oncology. 2018;5(3):83-91
pages 83-91 views