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Advances in Molecular Oncology

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Vol 7, No 1 (2020)
View or download the full issue PDF (Russian)
https://doi.org/10.17650/2313-805X-2020-7-1

REVIEW ARTICLES

8-16 1369
Abstract

Glioblastoma multiforme (GBM), a grade IV astrocytoma, is the most common and deadly type of primary malignant brain tumor, with a patien’s median survival rate ranging from 12 to 15 months. Over the last fifteen years, the treatment for GBM has included maximal safe surgical resection with combination radiotherapy and adjuvant temozolomide chemotherapy. The low efficacy of mentioned therapies has forced researchers to explore an appropriate alternative or complementary treatment for GBM. It has been shown that curcumin has therapeutic potentials to fight against GBM via affecting on cell proliferation, apoptosis, cell cycle, invasion and angiogenesis pathways. In addition, curcumin possess a synergistic impact with chemotherapeutic agents. Herein, we summarized the current findings on curcumin as potential therapeutic agent in the treatment of GBM.

17-22 797
Abstract

The current estimates of the contribution of the environmental contamination to cancer mortality range from 1 to 20 %, being a function of the ecological conditions, the density of industrial enterprises, occupational composition of the population, and others. Assessment of the impact of environmental contamination on cancer risk includes: •setting research priorities on the local, regional, and on the all-Russian levels; •the selection of the research that may be maximally socially profitable; •the choice of the research method that the most adequately meets the research objectives; •systemic analysis of the planed research to determine the availability of the resources, personnel, and information; •monitoring of atmospheric pollutions with analysis of the fraction composition of the particulate matters; •coordination of available data basis on environment and the population health conditions; •the implementation of the of molecular biology to determine prenosological manifestation of carcinogenesis and development of fine and diverse research methods on relationships between the environment and cancer risk.

For effective implementation of the research objectives aimed to decrease the impact of hazard factors with special reference on cancer risk in the Russian population, it is necessary: to create training personnel capable of providing epidemiologic studies, using up-to day methods, publication of methodological materials, text books, and sufficient funding of studies.

RESEARCH ARTICLES

23-31 682
Abstract

Objective of the study. In our work we investigated the effect of pre-existing drug resistance by the mechanism of activation of ABC transporters – P-glycoprotein (Pgp) overexpression – on the development of resistance to the proteasome inhibitor bortezomib.

Materials and methods. Cultures RPMI8226 and K562 / i-S9 (with Pgp overexpression) and their bortezomib-resistant sublines RPMI8226 / btz-6 and K562 / i-S9vlc were used as models. The methods used were MTT test, flow cytometry, Western blot and real-time polymerase chain reaction using the Human Signal Transduction Pathway Finder system.

Results. The expression of the main PI3K-AKT and NF-κB signaling pathways did not change in RPMI8226 / btz-6 subline cells. However, AKT kinase expression was significantly increased and PTEN protein expression was reduced in K562 / i-S9vlc cells with Pgp-overexpression. Significant changes in gene expression (42 %) were found in RPMI8226 / btz-6 cells related to a number of main signaling pathways in the tumor cell, namely: activation of 3–4 genes in signaling pathways related to hypoxia, oxidative stress, PPAR and p53. The highest activation in these cells was found in the TGFβ signaling pathway. In resistant K562 / i-S9vlc cells, expression of only 5 genes (10 %) increased: Fas, HMOX1, CPT2, ICAM, and SOCS3. Three genes were also identified that changed in both resistant sublines: Fas, HMOX1 and CPT2. Further, we showed that in the RPMI8226 / btz-6 subline, along with changes in the expression of signal transduction genes, there is a large pool of CD138-negative cells, and in the K562 / i-S9vlc subline, the number of cells expressing CD34 increases and the number of CD13 decreases.

Conclusion. We found that different signaling pathways are involved in the formation of resistance to bortezomib in the absence of Pgp expression and its overexpression. In addition, a cell line without activated resistance pathways requires more extensive rearrangements in the signal system to acquire resistance to bortezomib. However, in both cases, bortezomib leads to a change in the immunophenotype of the cells – to the appearance of dedifferentiated subpopulations.

32-37 2208
Abstract

Background. Tumors of stroma of the sex cord include a family of tumors that are diverse in structure and biological characteristics, including hormone-active ovarian tumors, such as granulosa cell tumor (GCT) of the ovary and a tumor from Sertoli–Leydig cells. For these types of tumors, of particular importance is the analysis of biochemical markers, among which the most promising is inhibin B.

The objective of the study. Comparative analysis of inhibin B levels in the blood serum of patients with stromal cell tumors and other types malignancies.

Materials and methods. 64 patients with primary ovarian tumors were examined: 31 – GCT of the ovary, 16 – tumors from Sertoli–Leydig cells, 17 – adenocarcinomas. Comparison group – 20 patients with malignant tumors of other localizations, control – 74 healthy women and 37 patients with benign ovarian tumors. Inhibin B was determined in blood serum using the standardized Inhibin B Gen II ELISA (Beckman Coulter, USA) immunoassay.

Results. The analysis of inhibin B levels in last days of the luteal phase, show an increase of marker level in patients with GCT and tumors from Sertoli–Leydig cells, while in ovarian adenocarcinomas and malignant tumors of other locations inhibin B secretion doesn’t differ from the control. The sensitivity of inhibin B in diagnostics of GCT was 93.5 %, in tumor from Sertoli–Leydig cells – 81.3 % with specificity – 100 %.

Conclusion. Inhibin B is an effective biomarker of GCT and ovarian tumors from Sertoli–Leydig cells, which results must be interpreted according the functional state of the ovaries.

38-46 897
Abstract

Objective: to study the state of cellular immunity in patients with gastric adenocarcinoma.

Materials and methods. From 2017 to 2018, 45 previously untreated patients with gastric adenocarcinoma (25 with stage I–III, 20 with stage IV) received surgical / combined treatment or independent chemotherapy, respectively, at the N. N. Blokhin National Medical Research

Center of Oncology. Peripheral blood sampling was carried out before starting treatment. We studied the cellular composition of peripheral blood, as well as systemic immunity parameters determined by flow cytometry (CD3+CD4+; CD3+CD8+; CD4+CD8+; CD4+/CD8+; CD3CD16+CD56+; CD3CD19+), and their prognostic significance in relation to overall survival and progression-free survival.

Results. The prognostic value of the relative indicator of platelet lymphocytic index was determined: progression-free survival in patients with a high level of platelet-lymphocytic index (>208.7) was higher: 8.1 months versus 4.5 months (p = 0.0027). A favorable prognosis for overall survival was an increase in the number of CD3CD19+ lymphocytes (hazard ratio (HR) 0.91; 95 % confidence interval (CI) 0.85–0.97; p = 0.007), and an unfavorable prognosis was an increase in the number of neutrophils (HR 1.26; 95 % CI 1.05–1.50; p = 0.012), platelet count (HR 1.01; 95 % CI 1.0–1.01; p = 0.043), as well as an increase in the number of NK cells (HR 1.04, 95 % CI 1.0–1.09; p = 0.029).

Conclusion. Indicators of the cellular composition of peripheral blood, characterizing a systemic inflammatory reaction, as well as indicators of systemic immunity, can serve as additional prognostic factors for gastric cancer.



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ISSN 2313-805X (Print)
ISSN 2413-3787 (Online)