МЕТОДЫ РАННЕЙ ДИАГНОСТИКИ РАКА ЛЕГКОГО (ОБЗОР ЛИТЕРАТУРЫ)

Macrophages are key components of the innate immune system. The variability of the macrophage’s participation in tumor progression, determined by their functional polarization, opens up a wide prospect for modulating their functional profile, primarily in the direction of increasing antitumor activity.The purpose of the studywas to provide up-to-date data on the process of macrophage polarization, mechanisms of its regulation, polarization markers and induction factors.Material and methods. A search was made for available literature sources published in Web of Science, Scopus and other databases. more than 160 sources devoted to the study of the process of macrophage polarization were found, of which 121 were included in this review.Results. This review presents data on the molecular mechanisms and gene signatures associated with M1 and M2 polarization of macrophages. We displayed information on metabolic, phenotypic characteristics and cytokine profile of M1- and M2-macrophages, as well as highlighted data on polarization factors and targets of their action.Conclusion. The information presented in the review can serve as an information base for the development of experimental and clinical approaches for editing the functional profile of macrophages in order to control their involvement in various pathological processes.

Along with other malignant diseases, lung cancer arises from the precancerous lung tissue state. Aberrant DNA methylation (hypermethylation of certain genes and hypomethylation of retrotransposons) is known as one of the driving forces of malignant cell transformation. Epigenetic changes were shown to be detectable in DNA, circulating in the blood (cirDNA) of cancer patients, indicating the possibility to use them as cancer markers. The current study is the first to compare the Long interspersed nuclear element-1 (LINE-1) methylation level in the blood from lung cancer patients before treatment versus different control groups as healthy subjects, patients with bronchitis and patients with chronic obstructive pulmonary disease (COPD). The concentration of LINE-1 methylated fragments, region 1 (LINE-1 methylated, LINE-1-met) was estimated by quantitative methyl-specific PCR. The total concentration of the circulating LINE-1 copies was measured by qPCR specific for LINE-1 region 2, which was selected due to its CpG methylation–independent sequence (LINE-1-Ind). Both LINE-1 methylation level and LINE-1 methylation index (LINE-1-met/LINE-1-Ind ratio) was decreased in lung cancer patients compared with the joint control group (healthy subjects + patients with bronchitis + COPD patients) (Mann–Whitney U-test, P = 0.016). We also found that the tendency of LINE-1 methylation index decreases in the cirDNA from lung cancer patients versus COPD patients (Mann–Whitney U-test, P = 0.07). Our data indicate that the quantitative analysis of the LINE-1 methylation level in the cirDNA is valuable for discrimination of lung cancer patients from patients with chronic inflammatory lung diseases.

Objectives: A growing body of evidence suggests the important role of chemosensitive gene expression in the prognosis of patients with lung cancer. However, studies on combined gene expression assessments for personalized prescriptions of chemotherapy regimens in patients have not yet been conducted. The aim of this work was to conduct a prospective study on the appointment of personalized chemotherapy in patients with non-small-cell lung cancer. Materials and methods: The present study analyzed 85 patients with lung cancer (stage IIB-IIIB). Within this group, 48 patients received individualized chemotherapy, and 37 patients received classical chemotherapy. In the individualized chemotherapy group, the mRNA expression levels of ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 in lung tissues were measured by quantitative real-time PCR (qPCR), and an individual chemotherapy regimen was developed for each patient according to the results. Patients in the classical chemotherapy group received the vinorelbine/carboplatin regimen. Survival analyses were performed using the Kaplan–Meier method. Prognostic factors of metastasis-free survival (MFS) and overall survival (OS) of patients were identified via Cox’s proportional hazards regression model. Results: MFS and OS were significantly better in the personalized chemotherapy group compared to the classic chemotherapy group (MFS, 46.22 vs. 22.9 months, p = 0.05; OS, 58.6 vs. 26.9 months, p < 0.0001). Importantly, the best metastasis-free survival rates in the group with personalized ACT were achieved in patients treated with the paclitaxel/carboplatin regimen. Based on an assessment of chemosensitivity gene expression in the tumors, the classical chemotherapy strategy also increased the risk of death (HR = 14.82; 95% CI: 3.33–65.86; p < 0.000) but not metastasis (HR = 1.95; 95% CI: 0.96–3.98; p = 0.06) compared to the group of patients with chemotherapy. Conclusions: The use of combined ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 gene expression results for personalized chemotherapy can improve treatment efficacy and reduce unnecessary toxicity.

Novel non-invasive methods for the diagnosis of malignancies should be effective for early diagnosis, reproducible, inexpensive, and independent from the human factor. Our aim was to establish the applicability of the non-invasive method, based on the analysis of air exhaled by patients who are at different stages of oropharyngeal, larynx and lung cancer. The diagnostic device includes semiconductor sensors capable of measuring the concentrations of gas components in exhaled air, with the high sensitivity of 1 ppm. The neural network uses signals from these sensors to perform classification and identify cancer patients. Prior to the diagnostic procedure of the non-invasive method, we clarified the extent and stage of the tumor according to current international standards and recommendations for the diagnosis of malignancies. The statistical dataset for neural network training and method validation included samples from 121 patients with the most common tumor localizations (lungs, oropharyngeal region and larynx). The largest number of cases (21 patients) were lung cancer, while the number of patients with oropharyngeal or laryngeal cancer varied from 1 to 9, depending on tumor localization (oropharyngeal, tongue, oral cavity, larynx and mucosa of the lower jaw). In the case of lung cancer, the parameters of the diagnostic device are determined as follows: sensitivity—95.24%, specificity—76.19%. For oropharyngeal cancer and laryngeal cancer, these parameters were 67.74% and 87.1%, respectively. This non-invasive method could lead to relevant medicinal findings and provide an opportunity for clinical utility and patient benefit upon early diagnosis of malignancies.

Peritoneal carcinomatosis is associated with poor prognosis in gastric cancer patients. Stage IV gastric cancer (GC) is diagnosed in 39.8 % of patients; local metastases without evidence of distant metastases occur only in 18–20 % of stage IV gastric cancer patients.The purpose of the study was to estimate the efficacy of personalized chemotherapy in the combined modality treatment of patients with stage IV GC with peritoneal carcinomatosis.Material and Methods. Cytoreductive surgery was performed in 70 patients with GC with peritoneal dissemination. The control group patients (n=35) received postoperative chemotherapy with the FOLFOX regimen. The study group patients (n=35) received personalized systemic and intraperitoneal chemotherapy based on the expression of chemosensitivity and resistance genes.Results. The median survival time (18.7 months) in the study group patients was higher than that in the control group and in studies described in the world literature (CRS + HIPEC). Personalized chemotherapy improved median progressionfree survival (PFS) by 4.6 months (29.1 %) and median overall survival (OS) by 6 months (32 %) compared to FOLFOX regimen chemotherapy. In the study group, the 1-, 2and 3-year survival rates were observed in 35 (100 %), 9 (27 %) and 1 (3 %) patients, respectively.Conclusion. Personalized chemotherapy in the combined modality treatment can improve long-term treatment outcomes (longer median PFS and OS) in GC patients with peritoneal dissemination.