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Introduction. Glucocorticoids are actively used in the treatment of various diseases, however their long-term use leads to numerous negative side-effects, the molecular mechanisms of which remain poorly understood.Aim. Study of the short-term (1–10 days) effects of various doses of dexamethasone (Dex) (0,1–10 mg/kg) on the expression of the glucocorticoid receptor (GR, Nr3c1), core proteins of main proteoglycans and heparan sulfate metabolism-involved genes, as well as the content of carbohydrate macromolecules of glycosaminoglycans in the brain tissue of experimental animals.Materials and methods. In the study, C57Bl/6 mice were used. The expression of GR, proteoglycan core proteins and heparan sulfate metabolism-involved genes was determined by real-time polymerase chain reaction with reverse transcription. The content and localization of GR protein molecule were studied by Western blot and immunohistochemical analysis, and the glycosaminoglycan content was determined by dot-blot analysis and Alcian Blue staining.Results. It was shown that a single Dex administration leads to fast (1–3 days) short-term activation of GR expression (+1.5 times, p Conclusion. In general, the effect of a single injection of Dex on the transcriptional activity of GR, proteoglycan core proteins and heparan sulfate metabolism-involved genes were short-termed, and the genes expression quickly returned to the normal levels. However, even a single use of Dex significantly increased the content of total as well as highly sulfated glycosaminoglycans in the mouse brain tissue, which can lead to the changes in the composition and structure of the brain tissue, as well as its functional characteristics.

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Background. The use of targeted sequencing panels makes it possible to optimize and personalize the treatment strategy for cancer patients. Given the lack of a clear «portrait of the patient», the role of large panels (200 or more genes) in the treatment of a patient has not yet been determined.Aim. Assessment of the relationship between the results of targeted sequencing of tumor tissue or ctDNA and the treatment carried out after obtaining these data in patients with various solid tumors.Materials and methods. We retrospectively evaluated the NGS results and the treatments, provided to the 184 patients after NGS testing between 06.2016 and 06.2021. For analysis, one of two methods is used: a histological sample or the patient’s blood plasma. Evaluation of the results and determination of treatment tactics were carried out within the framework of a multidisciplinary commission. The frequency of detection of molecular disorders, the number of mutations in each sample, and the frequency of detection of targets for targeted therapy were assessed.Results. Molecular disorders were detected in 88.5 % (n = 163). The average number of mutations in one sample was 6. The maximum was detected in colorectal cancer patients; their average value was 8. The minimum was determined in non-small cell lung cancer and ovarian cancer patients, the average number of mutations was 3 in each localization. The average time from the moment the material was received by the laboratory to the generation of the report was 11 days. Targeted targets were identified in 25 (13.6 %) patients and therapy was started. Therapy with tyrosine kinase inhibitors of the first – third generations were performed in 12 (48 %) patients, PARP inhibitors – in 3 (24 %), BRAF and MEK inhibitors – in 2 (8 %), anti-HER2 therapy – in 1 (4 %). Targeted therapy within international clinical trials was initiated in 4 (16 %) patients. Immunotherapy was recommended in 3 (12 %) patients. In multivariate analysis, the chance of prescribing therapy based on the results of FM1 analysis was influenced by: mRAS (odds ratio 0.08; 95 % confidence interval 0.01–0.65; p = 0.018) and mEGFR (odds ratio 4.8; 95 % confidence interval 1.4–16.3; p = 0.012).Conclusion. The effectiveness of the FM1 test in real clinical practice in the Russian Federation corresponds to international data. In the presence of a mutation in the RAS genes, an additional FM1 test determines a low chance of detecting clinically significant disorders for which personalized treatment can be prescribed. The high frequency of prescription of therapy based on the results of blood plasma tests is due to the cohort of patients with non-small cell lung cancer and the detection of a mutation in the EGFR gene.

Glioblastoma (GB) is an aggressive cancer with a high probability of recurrence, despite active chemoradiotherapy with temozolomide (TMZ) and dexamethasone (DXM). These systemic drugs affect the glycosylated components of brain tissue involved in GB development; however, their effects on heparan sulfate (HS) remain unknown. Here, we used an animal model of GB relapse in which SCID mice first received TMZ and/or DXM (simulating postoperative treatment) with a subsequent inoculation of U87 human GB cells. Control, peritumor and U87 xenograft tissues were investigated for HS content, HS biosynthetic system and glucocorticoid receptor (GR, Nr3c1). In normal and peritumor brain tissues, TMZ/DXM administration decreased HS content (5–6-fold) but did not affect HS biosynthetic system or GR expression. However, the xenograft GB tumors grown in the pre-treated animals demonstrated a number of molecular changes, despite the fact that they were not directly exposed to TMZ/DXM. The tumors from DXM pre-treated animals possessed decreased HS content (1.5–2-fold), the inhibition of HS biosynthetic system mainly due to the -3–3.5-fold down-regulation of N-deacetylase/N-sulfotransferases (Ndst1 and Ndst2) and sulfatase 2 (Sulf2) expression and a tendency toward a decreased expression of the GRalpha but not the GRbeta isoform. The GRalpha expression levels in tumors from DXM or TMZ pre-treated mice were positively correlated with the expression of a number of HS biosynthesis-involved genes (Ext1/2, Ndst1/2, Glce, Hs2st1, Hs6st1/2), unlike tumors that have grown in intact SCID mice. The obtained data show that DXM affects HS content in mouse brain tissues, and GB xenografts grown in DXM pre-treated animals demonstrate attenuated HS biosynthesis and decreased HS content.

In the treatment of coronary heart disease, the most promising approach for replacing lost contractile elements involves obtaining cardiomyocytes through cardiac differentiation of pluripotent cells. The objective of this study is to develop a technology for creating a functional layer of cardiomyocytes derived from iPSCs, capable of generating rhythmic activity and synchronous contractions. To expedite the maturation of cardiomyocytes, a renal subcapsular transplantation model was employed in SCID mice. Following explantation, the formation of the cardiomyocyte contractile apparatus was assessed using fluorescence and electron microscopy, while the cytoplasmic oscillation of calcium ions was evaluated through visualization using the fluorescent calcium binding dye Fluo-8. The results demonstrate that transplanted human iPSC-derived cardiomyocyte cell layers, placed under the fibrous capsules of SCID mouse kidneys (for up to 6 weeks), initiate the development of an organized contractile apparatus and retain functional activity along with the ability to generate calcium ion oscillations even after removal from the body.

Currently, gallstone ileus is an unusual complication of cholelithiasis (0.3–3.0 %) and a rare cause of mechanical bowel obstruction (0.1–4.0 %). The rarity of the condition makes it impossible to plan the large prospective randomized clinical trials, so the analysis of case reports is significant for decision making in the management of gallstone ileus. We report a case of gallstone ileus in a middle-aged male who had a history of surgery for duodenal ulcer perforation in past. A combination of peptic ulcer disease and cholelithiasis is based on a reduced gastrointestinal hormones secretion. Clinical specialists need to consider information about the greater frequency and asymptomatic clinical course of gallstone disease against a background of duodenal ulcer. Duodenal ulcer scar and bulbar deformity may promote to the cholecystoduodenal fistula formation. In the presence of an acute bowel obstruction symptoms and the absence of gallbladder instrumental examination results, it is possible to recommend the prior gastroduodenoscopy for the pre-operative pneumobilia detection. The optimal surgical approaches for acute gallstone ileus are still controversial.

Chiral effects originate from the lack of inversion symmetry within the lattice unit cell or sample’s shape. Being mapped onto magnetic ordering, chirality enables topologically non-trivial textures with a given handedness. Here, we demonstrate the existence of a static 3D texture characterized by two magnetochiral parameters being magnetic helicity of the vortex and geometrical chirality of the core string itself in geometrically curved asymmetric permalloy cap with a size of 80 nm and a vortex ground state. We experimentally validate the nonlocal chiral symmetry breaking effect in this object, which leads to the geometric deformation of the vortex string into a helix with curvature 3 μm−1 and torsion 11 μm−1. The geometric chirality of the vortex string is determined by the magnetic helicity of the vortex texture, constituting coupling of two chiral parameters within the same texture. Beyond the vortex state, we anticipate that complex curvilinear objects hosting 3D magnetic textures like curved skyrmion tubes and hopfions can be characterized by multiple coupled magnetochiral parameters, that influence their statics and field- or current-driven dynamics for spin-orbitronics and magnonics.

Background: Iron has dual properties: it may promote both tumor growth and cell apoptosis. Compared to healthy cells, cancer cells are more dependent on the iron levels. Ferroptosis can be triggered directly in cancer cells, which would result in their self-destruction. Identification of iron balance abnormalities and their correction could impact the effects of specific treatments in cancer patients. Aim: To assess the prevalence of iron deficiency in patients with metastatic colorectal cancer (mCRC) and to identify an association of low serum iron levels with clinical and morphological characteristics of the disease. Materials and methods: The study included 69 treatment-nave patients with mCRC. Iron deficiency was defined as low serum iron levels before the initiation of any specific therapy: serum iron concentration 10.7 mcmol/L in men and 9.0 mcmol/L in women. Results: The mean age of the mCRC patients was 61.1 years (range, 28 to 83 years), 35/69 (50.7%) were men. The bigger proportion of the tumors was left-sided (62.3%). In 48.3% of the patients, the disease was diagnosed at the metastatic stage. The most frequent locations of metastasis were liver (41.3%) and lungs (32.1%). 55.1% (38/69) of the patients had undergone a non-radical resection or primary curative surgery. KRAS mutations were found in 37.7% of the patients. Low serum iron levels were found in 53.6% (37/69) of the total sample of the mCRC patients and in 72.4% (19/38) of the patients with a non-resected primary tumor (p = 0.05). Conclusion: Irrespective on the clinical and morphological characteristics, the majority of patients with metastatic colorectal cancer have iron deficiency anemia before the initiation of specific anti-tumor therapy.

Rationale: Non-small cell lung cancer (NSCLC) is an aggressive disease with median survival of 1214 months in inoperable patients in the pre-immunotherapy era. Nowadays, under treatment with checkpoint inhibitors median survival is 1922 months. However, only a proportion of patients are sensitive to immune therapy. In this regard, inclusion into clinical trials remains a priority option for patients from medical perspective. Aim: To compare the results in NSCLC patients treated in accordance with the current clinical guidelines and in international clinical trials using the propensity score matching. Materials and methods: The study included data from 344 patients with histologically verified unresectable advanced NSCLC without activating mutations, who received the 1st line systemic medical therapy at various combinations (single agent chemotherapy, platinum doublet-based therapy, chemoimmunotherapy, single agent immunotherapy) within the compulsory health insurance (CHI), and from 90 patients, who received therapy in clinical trials. A direct comparison of long-term treatment results was carried out with the log-rank method. To exclude any influence of individual factors on survival rates, an univariate regression analysis and pseudorandomization accounting for these factors were carried out. Results: The direct comparison of the treatment results showed a higher progression-free survival rate in the patients treated according to clinical trial protocols, than in those treated under CHI (13.3 [95% confidence interval (CI) 8.118.5] months vs 6.4 [95% CI 5.96.9] months). Pseudorandomization of patients based on a combination of statistically significant parameters from the CHI and clinical trial groups showed a significantly longer time to progression in the trial group (13.3 [95% CI 8.318.3] vs 6.3 [95% CI 4.87.7] months). Conclusion: Participation in clinical trials is per se a factor that can significantly impact the longer duration of the treatment effect. This indicates the necessity of the most active use of this tool in clinical practice.

This study aimed to analyze changes in the plasma concentration of EGFR-mutated circulating tumor DNA (ctDNA) occurring immediately after the start of therapy with EGFR tyrosine kinase inhibitors (TKIs).Serial plasma samples were collected from 30 patients with EGFR-driven non-small cell lung cancer before intake of the first tablet and at 0.5, 1, 2, 3, 6, 12, 24, 36 and 48 h after the start of the therapy. The content of EGFR alleles (exon 19 deletions or L858R) in ctDNA was measured by ddPCR.ctDNA was detected at base-line in 25/30 (83%) subjects. Twelve (50%) out of 24 informative patients showed 25% reduction of the ctDNA content at 48 h time point; all these patients demonstrated disease control after 4 and 8-12 weeks of therapy. The remaining 12 individuals showed either stable content of EGFR-mutated ctDNA (n = 5) or the elevation of ctDNA concentration (n = 7). 10 of 12 patients with elevated or stable ctDNA level achieved an objective response at 4 weeks, but only 5 of 10 evaluable patients still demonstrated disease control at 8-12 weeks (p = 0.032, when compared to the group with ctDNA decrease). The decline of the amount of circulating EGFR mutant copies at 48 h also correlated with longer progression-free survival (14.7 months vs. 8.5 months, p = 0.013).Comparison of concentration of EGFR-mutated ctDNA at base-line and at 48 h after the start of therapy is predictive for the duration of TKI efficacy.

Introduction. Intratumor heterogeneity is one of the key reasons for unfavourable prognosis in malignant tumors. Astrocytic tumors are known to develop therapy resistance inevitably during the course of disease. One of possible reason is tumor heterogeneity. Purpose. The aim of this work was to assess the intratumor morphologic and molecular heterogeneity in diffuse astrocytoma, anaplastic astrocytomas and primary glioblastomas. Material and methods. We conducted morphologic (n=22) and molecular-genetic (n=8) analysis of surgical specimens obtained from primarily operated glioblastoma giv (gb), anaplastic astrocytomas giii (aa) and diffuse astrocytoma gii (da) patients aged 18 years and older in whom total or subtotal tumor resection was performed. Tissue sampling for the analysis was performed from 5 equidistant areas of each tumor. Morphologic diagnosis was established according to who classification of central nervous system tumors (2007/2016). Mgmt, c-kit, top2a, pdgfr-α, ercc1, vegf genes mrnaexpression was assessed by rt-pcr. Idh1 and idh2 mutational status was evaluated by allele-specific pcr. Results. Morphologic heterogeneity was evident in 72,7 % tumors (16/22) overall. Heterogeneity was observed in 68,8 % (11/16) of gb, 80 % (4/5) of aa and in the only case of da. In 50 % of cases at least 3 different morphologic variants were seen in different areas of the tumor. This morphologic heterogeneity presented as the combination of different grades of anaplasia (gii – giv) in one tumor. Molecular profile was assessed in 48 expression analysis of genes: mgmt, c-kit, top2a, pdgfr-α, ercc1, vegf from 8 patients. Intratumoral molecular heterogeneity was revealed in 41,7 % of cases (20/48). Conclusion. The presence of intratumoral heterogeneity should be taken into account during surgery for adequate tumor sampling for histologic and molecular analysis which is critical for proper assessment of prognosis and following treatment planning.

Neoadjuvant chemotherapy (NACT) for breast cancer (BC) often results in pathologic complete response (pCR), i.e., the complete elimination of visible cancer cells. It is unclear whether the use of ultrasensitive genetic methods may still detect residual BC cells in complete responders. Breast carcinomas arising in BRCA1 mutation carriers almost always carry alterations of the TP53 gene thus providing an opportunity to address this question. The analysis of consecutive BC patients treated by NACT revealed a higher pCR rate in BRCA1-driven vs. BRCA1-wildtype BCs (13/24 (54%) vs. 29/192 (15%), p < 0.0001). Twelve pre-/post-NACT tissue pairs obtained from BRCA1 mutation carriers were available for the study. While TP53 mutation was identified in all chemonaive tumors, droplet digital PCR (ddPCR) analysis of the post-NACT tumor bed revealed the persistence of this alteration in all seven pCR-non-responders but in none of five pCR responders. Eleven patients provided to the study post-NACT tissue samples only; next-generation sequencing (NGS) analysis revealed mutated TP53 copies in all six cases without pCR but in none of five instances of pCR. In total, TP53 mutation was present in post-NACT tissues in all 13 cases without pCR, but in none of 10 patients with pCR (p < 0.000001). Therefore, the lack of visible tumor cells in the post-NACT tumor bed is indeed a reliable indicator of the complete elimination of transformed clones. Failure of ultrasensitive methods to identify patients with minimal residual disease among pCR responders suggests that the result of NACT is a categorical rather than continuous variable, where some patients are destined to be cured while others ultimately fail to experience tumor eradication.

Background: The technique of regional isolated perfusion makes it possible to increase local levels of an anti-tumor agent, to perform the treatment procedure under hypothermia or hyperthermia, to reduce or even eliminate any systemic effect of a cytostatic on the patient. In this context, the use of isolated perfusion to modify the pH milieu of the tumor seems to be a promising strategy that could potentially ensure the anti-tumor effect. Aim: To evaluate the efficacy of a rat limb perfusion with 4% NaHCO3 solution in vivo in the Pliss' lymphosarcoma rat graft model. Materials and methods: The experiment was carried out in Wistar rats with Pliss' lymphosarcoma graft. The isolated limb was perfused with an isotonic sodium chloride solution (the control group) or a 4% sodium bicarbonate solution (the treatment group). The following parameters were assessed: tumor node growth over time, survival rate, hematology analysis at various time points of the experiment, and histological examination of autopsy samples from the tumor. Results: Median survival in the group perfused with 4% NaHCO3 (N = 6) was 17.2 days, whereas in the non-perfused group (the pathogenesis group) (N = 4) and in the group perfused with isotonic saline (N = 5) they were 13.2 and 13.6 days, respectively. The risk of death in the treatment group was lower compared to that in the control group (Cox regression model, hazard ratio 0.129; 95% confidence interval 0.0280.583; p = 0.0079). There were no significant differences in the tumor growth rate over time in the perfused groups. Conclusion: A single exposure of the tumor micro-milieu in the model with isolated perfusion of the limb with Pliss' lymphosarcoma graft does not lead to any changes in the tumor growth kinetics, but is associated with a change in the animal survival.

Lung cancer has the highest morbidity rate among all malignant tumors in men and the highest mortality rate in men and women in Russia. In total, 49 145 new cases of lung cancer were registered (diagnosed) in Russia in 2019. The majority of cases are related to exogenic carcinogens and mainly tobacco smoke. For several decades surgical resection with preoperative cytotoxic therapy was an optimal approach for maximal cure rate. This year recommendations were updated with new strategies including adjuvant anti-PD-L1 atezolizumab following completion of chemotherapy in PD-L1 positive patients and osimertinib for EGFR mutated cases. For this moment available data suggest the increase in disease free survival. Strategic approach to treatment for inoperable patients varies according to the status of driver mutations. New approach includes pretreatment option of testing for a wide spectrum of alterations with NGS based panels. Significant changes were incorporated into treatment of ALK mutated NSCLC with two new options of brigatinib for TKI naive patients and lorlatinib for those who progress on second generation drugs. Treatment strategy for patients without activating mutations is based on PD-L1 status. Tsis year recommendations included atezolizumab as a new monotherapy option for patients with high depression of PD-L1. Also treatment options for pembrolizumab, nivolumab and atezolizimab were widened with prolonged treatment schedules.

This study aimed to analyze changes in the plasma concentration of EGFR-mutated DNA occurring immediately after the start of therapy with EGFR tyrosine kinase inhibitors (TKIs). The study included 30 patients with EGFR mutation-driven non-small cell lung cancer (NSCLC). Serial plasma samples were collected before intake of the first tablet and at 0.5, 1, 2, 3, 6, 12, 24, 36 and 48 hours after the start of the therapy. EGFR-mutated plasma DNA (EGFR+ ctDNA) was detectable at diagnosis in 25 out of 30 study participants. There were different patterns of changes of the amount of circulating tumor DNA, i.e., the consistent decline of ctDNA content, or continuing increase of the number of circulating EGFR mutant copies, or alternating spikes and drops in the ctDNA concentration. Correlation with the disease outcome was observed only for the measurement performed at 48 hours. Twelve (50%) out of 24 informative patients showed >25% reduction of the ctDNA content at 48 h time point; all these patients demonstrated disease control after 4 and 8-12 weeks of therapy. The remaining 12 individuals showed either stable content of circulating EGFR+ DNA (n = 5) or the elevation of ctDNA concentration (n = 7). 10 of 12 patients with elevated or stable ctDNA level achieved an objective response at 4 weeks, but only 5 of 10 evaluable patients still demonstrated disease control at 8-12 weeks (p = 0.014, when compared to the group with ctDNA decrease). The decline of the amount of circulating EGFR mutant copies also correlated with longer progression-free survival (PFS; 14.7 months vs. 8.5 months, p = 0.013). Conclusion: Monitoring of plasma EGFR-M+ concentration within the first hours of the TKI therapy may be used as an immediate predictor of tumor response to the treatment.

In Russian Federation, lung cancer is the most frequently diagnosed malignant tumor among men and the fourth in the structure of morbidity among women, also occupying a leading position in the structure of mortality [1]. Non-small cell cancer (NSCLC) accounts for about 80 % of all lung tumors. In turn, in the structure of NSCLC, the most common types are adenocarcinoma (50 %) and squamous cell lung cancer (30 %). The appearance of drugs based on blocking immune checkpoints, in particular PD-1 and PD-L1, has changed the approach to the treatment of NSCLC. Currently, the determination of the optimal tactics for treatment tumors without activated mutations is based on predicting the sensitivity of the tumor to immunotherapy. Evaluation of PD-L1 expression makes it possible to divide patients with NSCLC into several groups of the level of sensitivity to modern immune checkpoint inhibitors. Thus, three groups are distinguished: with negative (≤ 1 %), intermediate (1–49 %) and high (≥ 50 %) expression of PD-L1. The latter includes 23–28 % of patients with advanced NSCLC, regardless of the histological form of the tumor [3]. There are also reasons to believe that in the near future a subgroup of patients with ultra-high expression (> 75 %) PD-L1 will be identifid, in which it is expected to achieve the maximum advantage from treatment with monoimmunotherapy. Pembrolizumab was approved for the treatment of advanced NSCLC with high level of PD-L1 expression (≥ 50 %) with the absence of EGFR / ALK mutations in the fist line of therapy following the publication of the results of the randomized phase III clinical trial KEYNOTE-024. In this study, the median overall survival in the pembrolizumab monotherapy arm was 30.0 months compared with 14.2 months with standard platinum-containing therapy [5]. These data formed the basis for the registration of the fist cytostatic-free regimen in patients with NSCLC without activating mutations. The subsequent study KEYNOTE-042 was an attempt to assess the effect of pembrolizumab in a wider group of patients – with a positive level of PD-L1 expression (PD-L1 ≥ 1 %; ≥ 20 %; ≥ 50 %). In general, the results of the study were positive, but many authors drew attention to the fact that the greatest effect of monoimmunotherapy with pembrolizumab is obtained by patients with a high level of PD-L1 expression. Median overall survival in this study was 20.0 months in the pembrolizumab group and 12.2 months in the chemotherapy group for all patients regardless of PD-L1 status. In this article two clinical cases of the use of the PD-L1 inhibitor pembrolizumab in patients with non-small cell lung cancer and high levels of PD-L1 expression are presented.

Extensive-stage small cell lung cancer (ES-SCLC) is characterized by an aggressive course, a high recurrence rate and fast progression. For a long time, the survival prognosis for the most patients suffering from this disease remained unfavorable. The situation changed with the appearance of chemoimmunotherapy in clinical practice. Chemotherapy based on durvalumab in comparison with the standard chemotherapy demonstrated the statistically and clinically significant increase in median overall survival in patients with previously untreated ES-SCLC in the CASPIAN international trial. This article deals with the case of the application of standard chemotherapy in combination with durvalumab as a first-line ES-SCLC therapy. The patient started receiving durvalumab therapy in June 2017 as a part of the CASPIAN international trial. In March 2021 the duration of therapy was 45 months, the patient had a complete regression of the disease.

The results of testing new generation Aerobor® II cubic boron nitride grinding wheels during machining of the locking element of turbine blades are presented. The advantages of using new high-porosity cubic boron nitride grinding wheels in comparison with abrasive grinding wheels in deep grinding of parts made of heat-resistant nickel alloys are described. Keywords: deep grinding, turbine blade, locking element, high-temperature nickel alloys, high-porosity cubic boron nitride grinding wheel d_i_volkov@rsatu.ru, boris_tsvetkov@mail.ru, uryadyshevaa@mail.ru

Background . Over the past 10–15 years, there has been a clearer understanding of the processes occurring in cells of the primary glioblastoma. However, the change in MGMT gene expression and its role after disease relapse remain understudied. Purpose : to study changes in MGMT gene expression in case of recurrent primary glioblastoma after the standard therapy; to determine influence of clinical factors and MGMt gene expression on relapse-free survival of patients. Materials and Methods . We carried out a prospective analysis of clinical and molecular genetic characteristics of 21 patients aged from 28 to 63 with primary glioblastoma before and after recurrence. Relative mRna expression of MGMT gene and mutations in IDH1/IDH2 genes were determined in surgical biopsies using PCR techniques. after the first surgery, all patients received radiation therapy (60 Gy) and chemotherapy with adjuvant temozolomide (2–18 cycles). the second-line chemotherapy was performed in 17 (80.9 %) patients, and 8 patients received (47 %, 8/17) temozolomide. Results. the relationship between the progression-free survival (PFs) and mRna expression of MGMT gene (73.5 vs 33 weeks, p=0.013) and objective response to therapy (88 vs 36 weeks, p=0.046) was found. The number of cycles of first-line chemotherapy with temozolomide influenced the duration of the first PFs (65 weeks vs 21.5 weeks, p=0,07). the first PFs was not affected by patients’ age (p=0.64), sex (p=0.17), Karnofsky performance scale index (p=0.43), extent of brain damage (p=0.41) and extent of the resection (p=0.27). after onset of relapse, mRna expression of MGMT gene remained the same, being 66.7 % (14/21). The increased expression was observed in 23.8 % (5/21) of cases, and decreased gene expression was observed in 9.5 % (2/21) of cases. the second PFs was affected by the extent of tumor resection, although there were no statistically significant differences (p=0.52). the effect of mRna expression of MGMT gene on the median second PFs was not revealed (p=0.39). no objective response to therapy was found in patients with a low mRna expression of MGMT gene. Conclusion . Recurrent glioblastoma becomes more resistant to further therapy. With the development of tumor recurrence, the predictive value of MGMT gene is lost and the role of the extent of cytoreductive surgery increases.