Soluble B7-H3 in Colorectal Cancer.

We present the results of comparative ELISA of the concentration of soluble form of immunity checkpoint B7-H3 (sB7-H3) in the serum of patients with colorectal cancer (CRC) at different stages before treatment and healthy control donors. The analysis revealed a statistically significant difference between the median levels of sB7-H3 in the blood serum of CRC patients (19.66 ng/ml) and healthy donors (16.76 ng/ml) (p=0.0025). ROC analysis showed 62.9% sensitivity and 56.7% specificity for CRC patients (cut-off 17.62 ng/ml; p=0.0028). An association of sB7-H3 levels with tumor progression was revealed. We demonstrated that sB7-H3 levels were significantly lower in patients with regional metastases than in patients without metastases (p=0.039) and that sB7-H3 concentration tends to decrease at the late stages of the disease. Thus, high serum level of sB7-H3 in CRC patients can be a favorable prognostic factor in future.

[Obstructive uropathia in pregnant women: results of treatment depending on the etiopatogenetic factor of development].

Actuality. The development of renal colic in pregnant women is one of the most common reasons for visiting a hospital that is not associated with obstetric pathology. Given the pharmacological and diagnostic limitations during gestation, the problem of expanding the renal cavitary system in pregnant women, as well as the choice of treatment tactics, remains a difficult clinical task. MATERIALS AND METHODS: The study group included 537 patients with obstructive uropathy with a gestation period of 5 to 36 weeks, who were hospitalized from January 2018 to January 2022 at the GBUZ GKB named after. S.S. Yudina DZM. Depending on the etiopathogenetic obstructive uropathy, the patients were divided into 3 groups: group I - 201 (37.4%) patients with gestational pyelonephritis (the presence of a systemic inflammatory response syndrome) and expansion of the renal cavitary system without confirming the diagnosis of urolithiasis; group II - 216 (40.2%) patients with renal colic (presence of pain without signs of a systemic inflammatory reaction) and enlargement of the renal cavitary system not associated with urolithiasis; group III - 120 (22.4%) pregnant women with an expansion of the cavitary system of the kidney caused by urolithiasis, both with and without signs of a systemic inflammatory reaction. Age, body mass index and previous number of pregnancies in all groups did not differ. The mean age of the patients in the three groups was 26.1 years, with a mean gestational age of 20.8 weeks. In 433 (80.6%) patients, pain was observed in the lumbar region on the right, in 83 (15.5%) - on the left, the bilateral nature of the process - in 21 (3.9%) patients. RESULTS: In group I, despite ongoing conservative therapy, 129 (64.2%) pregnant women received an internal ureteral stent. After 2-4 weeks of follow-up, the ureteral stent was removed in all patients. As a result, a short-term drainage method (up to 4 weeks) was effective in 90.1% of pregnant women, and in 13 (9.9%) patients, it was necessary to re-insert the stent, followed by a routine replacement of the drain every month. Considering the pain syndrome among patients of group II, drainage was performed in 80 (37%) pregnant women. Routine stent replacement was required in 2 (2.3%) patients. In group III, the location of the calculus in the pyelocaliceal system was in 28 (23.3%) patients, in the ureter - in 92 (76.7%) patients. Independent passage of the calculus was noted in 8 (6.7%) pregnant women, ureteroscopy without prior stenting was performed in 31 (25.8%) pregnant women with ureteral calculus. The remaining 81 (67.5%) pregnant women underwent stent placement at the first stage. When the stone was localized in the ureter, 32 (22.7%) patients underwent contact laser ureterolithotripsy and 21 (17.5%) patients underwent ureterolithoextraction. When a stone was located in the kidney, 28 (23.3%) pregnant women underwent pyelocalicolithotripsy. Achievement of the stone-free status was observed in 92.8%. CONCLUSION: Obstructive uropathy in pregnant women requires identification of the cause and a multidisciplinary approach. Long-term drainage of the urinary tract should be avoided and short-term drainage should be preferred. Surgical treatment of urolithiasis, regardless of gestational age, is an effective and safe method.

[Integral scales in assessing the risk of postoperative morbidity and mortality]. / Primenenie integral'nykh shkal v otsenke riska posleoperatsionnykh oslozhnenii i posleoperatsionnoi letal'nosti.

Annual number of surgeries exceeds 10 million In Russia, and this number is increasing every year. Searching for a scale or index determining the risk of postoperative complications and mortality is an important issue all over the world. The authors analyzed all available risk assessment scales for postoperative morbidity and mortality. The most significant ones in historical aspect and modern perspective grading systems were highlighted. We compared these indices with clinical recommendations and necessary preoperative preparation. Thus, these scales are valuable for surgeons and anesthesiologists to assess the risk, volume of surgical intervention and methods of preoperative management. However, they are not perfect and require improvement. Therefore, development of such scales is a priority objective of medicine in the foreseeable future.

Dynamics of Soluble Forms of the Immune Checkpoint Components PD-1/PD-L1/B7-H3, CD314/ULBP1, and HLA-G in Peripheral Blood of Melanoma Patients Receiving Blockers of Programmed Cell Death Protein PD-1.

The content of the soluble forms of immune checkpoint components sPD-1, sPD-L1 in blood serum, and sB7-H3, sCD314, sULBP1, sHLA-G in blood plasma of 30 melanoma patients receiving immunotherapy with anti-PD-1 antibodies (nivolumab, pembrolisumab) was measured before and in 4 and 8 weeks after the start of immunotherapy. The control group comprised 70 practically healthy donors. Standard immunoassay kits were used. In melanoma patients, the levels of sPD-L1 and sB7-H3 were significantly higher than in the control group (p<0001), sPD-1 level did not differ from the control, while sCD314 and sHLA-G levels were insignificantly decreased. During therapy, opposite changes in the levels of markers in individual patients were observed, and frequently after the initial increase (or decrease) after the first 4 weeks normalization did occur in the further 4 weeks. No statistically significant associations between the initial levels of markers and direction of their changes during treatment were found, but some trends indicating to the potential benefits from assessment of soluble forms of immune checkpoint proteins for evaluation and monitoring of the efficiency of the therapy with immune checkpoint blockers were revealed: significant decrease of sB7-H3 and sPD-1 levels in the course of treatment, higher initial sPD-1 level in patients with future progression than in those with stabilization or partial effect, and lower progression frequency in patients with increasing sPD-1 and sPD-L1 levels than in those with decreasing markers levels.

[Mechanisms of development of side effects and drug resistance to asparaginase and ways to overcome them]. / Mekhanizmy razvitiia pobochnykh éffektov i lekarstvennoi ustoichivosti k asparaginazam i puti ikh preodoleniia.

Asparaginase is one of the most important chemotherapeutic agents against acute lymphoblastic leukemia, the most common form of blood cancer. To date, both asparaginases from E. coli and Dickeya dadantii (formerly known as Erwinia chrysanthemi), used in hematology, induce chemoresistance in cancer cells and side effects in the form of hypersensitivity of immune reactions. Leukemic cells may be resistant to asparaginase due to the increased activity of asparagine synthetase and other mechanisms associated with resistance to asparaginase. Therefore, the search for new sources of L-asparaginases with improved pharmacological properties remains a promising and prospective study. This article discusses the mechanisms of development of resistance and drug resistance to L-asparaginase, as well as possible ways to overcome them.

Soluble forms of PD-1/PD-L immune checkpoint receptor and ligand in blood serum of breast cancer patients: association with clinical pathologic factors and molecular type of the tumor.

Results of enzyme-linked immunosorbent assay of the soluble forms of PD-1/PD-L immune checkpoint receptor and ligand (sPD-1 and sPD-L1) in pretreatment blood serum of 88 breast cancer patients at various disease stages aged 30-83 years are presented. The control group included 55 practically healthy women aged 19-82 years. Serum sPD-1 and sPD-L1 levels in breast cancer patients highly significantly (p<0.0001) differ from control and these changes are opposite: soluble receptor level is more than 6-fold decreased, while soluble ligand concentration - 5.5 fold increased. Both markers separately, as well as their ratio demonstrate very high sensitivity (94-100%) and specificity (95-100%) in relation to healthy control. No statistically significant associations of sPD-1 and sPD-L1 levels with clinical stage, individual TNM system criteria, tumor histological structure, grade, receptor status, and molecular type were established. In particular, no significant peculiarities of the markers' levels in triple negative breast cancer successfully treated with anti-PD-1/PD-L1 preparations were revealed. Long-term follow-up and dynamic studies of sPD-1 and sPD-L1serum levels in the course of treatment are required for evaluation of their independent from clinical and morphological factors prognostic significance and the possibility of application as low invasive tests for prediction and monitoring of corresponding targeted therapy efficiency.

Immunosuppression Factors PD-1, PD-L1, and IDO1 and Colorectal Cancer.

Due to the low efficiency of immunotherapy for colorectal cancer (CRC), it is extremely promising and relevant to study the mechanisms of immunosuppression. In this work, a comprehensive study of the expression of soluble and tissue forms of PD-1 and PD-L1 in blood serum and tumors of patients with CRC, as well as IDO1 in tumors was performed for the first time. The diagnostic and prognostic significance of the studied parameters was determined. A statistically significant decrease in the number of soluble forms of PD-1 and PD-L1 in the blood serum and the association of the number of PD-L1+ cells in the stroma of tumors with the CRC stage were established. The absence of correlations between soluble and tissue forms of the studied proteins was shown, indicating the presence of independent mechanisms of immunosuppression in CRC, which may explain the ineffectiveness of immunotherapy for this type of tumor.

Prognostic significance of soluble forms of immune checkpoint PD-1/PDL1 receptor and ligand in blood plasma of gastric cancer patients.

Analysis of long-term treatment results of 101 primary gastric cancer patients at various stages of the tumor process followed during 1 - 41 months (median - 6,4 months) from the onset of specific treatment are presented depending on the levels of soluble forms (s) of PD-1 receptor and its ligand PD-L1 in blood plasma. Overall survival assessed by Kaplan-Meyer analysis and with the help of Cox multiparametric regression model was applied as the criterion of prognostic value. It was found that at high (≥ 35 pg/ml) sPD-L1 levels in blood plasma, the overall survival of patients with gastric cancer was statistically significantly lower than at the marker's levels below 35 pg / ml (p <0.045): 1-year survival comprised 78 and 96%, 2-year - 52 and 78%; 3-year - 40 and 61% at high and low sPD-L1 respectively. Median survival of patients with high plasma sPD-L1 comprised 29 months, of those with low sPD-L1 was not achieved during the whole follow-up period. This trend was observed not only in the total group of stage I-IV gastric cancer patients, but also in patients at the early stages of the disease, though sPD-L1 did not show an independent prognostic value in multiparametric model. At the same time, the overall survival of patients with gastric cancer did not depend on the baseline levels sPD-1 in blood plasma. Thus, soluble ligand sPD-L1 can be considered as a potentially valuable factor for prognosis of gastric cancer patients' survival, and, probably, of anti-PD-1/PD-L1 treatment efficiency, but further studies and patients' monitoring are required to prove this statement.

Soluble forms of immune checkpoints in ovarian cancer.

The data of a complex immunoassay comparative study of the content of soluble forms of sPD-1, sPD-L1, sNKG2D, sNKG2DL1, sB7-H3 and sHLA-G in the blood plasma of 75 patients with epithelial ovarian cancer and 20 healthy donors of the control group are presented. The diagnostic significance of the studied proteins was determined. The study showed that the profile of soluble immunity checkpoints differs when malignant ovarian pathology occurs. There was a statistically significant decrease in the content of sPD-L1, sNKG2DL1, sB7-H3, and sHLA-G in the blood plasma of patients compared with the control group. Differences were found in the content of the studied markers depending on the histological type of tumors. Correlations between the soluble forms of some of the studied proteins are shown, indicating the presence of independent mechanisms of immune regulation in ovarian cancer, which may explain the insufficient effectiveness of the existing immunotherapy for this type of tumor. The results obtained will undoubtedly facilitate the development of new effective methods for the diagnostics and therapy of ovarian cancer.

Comparative analysis of the levels of soluble forms of receptor and ligand of the immunity control point PD-1/PD-L1 in the blood serum of patients with typical bone osteosarcoma and chondrosarcoma.

Results of ELISA investigation of the pretreatment sPD-1 and sPD-L1 content in blood serum of 133 bone neoplasms patients aged 6-70 years and 57 practically healthy control persons aged 12-70 years are described. In 14 patients the neoplasms were of a benign character, in 16 - borderline giant-cell bone tumor was diagnosed, and in 103 - malignant bone lesions including 39 osteosarcomas and 42 chondrosarcomas were revealed. The sPD-1 receptor concentrations in blood serum did not differ between control healthy persons and primary bone tumor patients, while serum sPD-L1 level in bone tumor patients was statistically significantly increased (p<0.0000001). By means of ROC curve construction a cut-off sPD-L1 level of 16.5 pg/ml was found that imposed 75,9% sensitivity and 75,4% specificity in relation to healthy control. However, the frequency of sPD-L1 levels exceeding 16.5 pg/ml was approximately similar in benign, borderline and malignant bone tumor patients. Analysis of the pattern of sPD-1 and sPD-L1 circulation in the peripheral blood of patients with the most prevalent malignant bone tumors - osteosarcoma and chondrosarcoma - demonstrated that in both sarcoma types sPD-L1 level was significantly higher than in control, but in patients with chondrogenic tumors the soluble ligand sPD-L1 dominates in the circulation, while in those with osteogenic tumors - sPD-1 receptor prevails. In particular, sPD-1 level is statistically significantly higher in patients with typical osteosarcoma than in those with typical chondrosarcoma (p=0.002437), and sPD-L1/sPD-1 concentration ratio in chondrosarcoma is highly significantly more than 2-fold higher than in osteosarcoma (0.81 and 0.35 respectively; p=0.000284). The sensitivity of sPD-L1 ≥16.5 pg/ml test in typical osteosarcoma patients' group comprised only 70.2%, and in those with typical chondrosarcoma - 84.6%. Serum sPD-1 and sPD-L1 concentrations in osteosarcoma and chondrosarcoma patients were not associated with the indices of tumor advancement, its histological grade, localization in the osseous system, and type of affected bone. Thus, it can be concluded that the ratio between circulating soluble forms of the receptor and the ligand of PD-1/PD-L signaling pathway differs between patients with chondrogenic and those with osteogenic tumors, sPD-L1 being diagnostically valuable mostly for chondrogenic bone neoplasms.

Key Immune Checkpoint PD-1/PD-L1 Signaling Pathway Components in the Blood Serum from Patients with Bone Tumors.

The levels of sPD-1 and sPD-L1 were analyzed in blood serum of 132 patients (age 14-70 years) with primary bone tumors: osteosarcoma (N=39), chondrosarcoma (N=42), Ewing sarcoma (N=9), chordoma (N=12), giant-cell bone tumor (GCBT) (N=16), benign neoplasms (N=14) and in and practically healthy subjects (age 19-58 years; N=27). sPD-L1 levels in all studied bone neoplasms were significantly higher than in the control. Serum sPD-1 level in GCBT patients was significantly higher than in the control, benign neoplasms, chondrosarcoma, and chordoma patients, but did not differ from osteosarcoma group. sPD-1 concentration in Ewing sarcoma was significantly higher than in chordoma and chondrosarcoma, but did not differ from the control. sPD-1 level in chondrosarcoma patients was also lower than in osteosarcoma, Ewing sarcoma, and in the control. Both sPD-1 and sPD-L1 concentrations were not significantly associated with the type of affected bone, process localization, disease stage, tumor histological grade, patients' age and sex. These results suggest the possibility of using these biological markers for preliminary assessment of the character of the process in the bone.

[L-asparaginases of extremophilic microorganisms in biomedicine]. / L-asparaginazy ékstremofil'nykh mikroorganizmov v biomeditsine.

L-asparaginase is extensively used in the treatment of acute lymphoblastic leukemia and several other lymphoproliferative diseases. In addition to its biomedical application, L-asparaginase is also of prospective use in food industry to reduce the formation of acrylamide, which is classified as probably neurotoxic and carcinogenic to human, and in biosensors for determination of L-asparagine level in medicine and food chemistry. The importance of L-asparaginases in different fields, disadvantages of commercial ferments, and the fact that they are widespread in nature stimuli the search for biobetter L-asparaginases from new producing microorganisms. In this regard, extremofile microorganisms exhibit unique physiological properties such as thermal stability, adaptability to extreme cold conditions, salt and pH tolerance and so provide one of the most valuable sources for novel L-asparaginases. The present review summarizes the recent results on studying the structural, functional, physicochemical and kinetic properties, stability of extremophilic L-asparaginases in comparison with their mesophilic homologues.

[The content of the soluble forms PD-1 and PD-L1 in blood serum of patients with gastric cancer and their relationship with clinical and morphological characteristics of the disease.]

Results of comparative ELISA investigation of pretreatment sPD-1 and sPD-L1 content in blood plasma of 100 gastric cancer patients at various disease stages aged 25 to 81 years are presented. Control group included 60 practically healthy donors aged 18 - 68 years. Plasma sPD-L1 concentrations did not differ between gastric cancer patients and control group, and sPD-1 levels were statistically significantly lower in patients than in healthy donors (p<0.0001). Positive correlation (R=0.38; p=0.003) was revealed between plasma sPD-1 и sPD-L1 levels in control group and negative (R= -0.26; p=0,009) - in gastric cancer patients. ROC curve revealed the best sPD-1 cut-off level (< 21 pg/ml) with 77% sensitivity and 63.3% specificity, which is not sufficient for its application as diagnostic marker. Statistically significant increase of plasma sPD-L1 from stage I to stage IIIC (R=0.50; p=0.000011) was found. Analysis of associations between the evaluated markers' levels and indices of gastric cancer expansion according to TNM system revealed statistically significant positive associations of plasma sPD -L1 levels with T (tumor invasiondepth) and N (number of affected lymph nodes) indices: R=0.33; p=0.00093, and R=0.27; p=0.0099 respectively. sPD-L1 level was significantly increased in patients with low differentiated adenocarcinoma and cricoid-cell cancer as compared to highly differentiated adenocarcinoma (p=0.02 and p=0.004 respectively); in patients with cricoid-cell cancer it was also higher than in those with moderately differentiated adenocarcinoma (p=0.043) and undifferentiated cancer (p=0.049). Plasma sPD-1 level did not depend on disease stage, TNM system indices and tumor histological structure. Thus, soluble ligand sPD-L1, but not its receptor sPD-1, plasma level is increased in patients with unfavorable clinical and morphological characteristics, may be regarded as potentially valuable prognostic factor for gastric cancer patients' survival, and probably as a predictor of anti - PD-1/PD-L1 treatment efficiency.

Report on the CCT Supplementary comparison S2 on thermal conductivity measurements of insulating materials by guarded hot plate.

Seven National Metrology Institutes (NMIs) from France, United States, United Kingdom, Russia, Mexico, China and Germany participated in an inter-laboratory comparison on thermal conductivity measurements by the Guarded Hot Plate method. This action was part of a series of supplementary inter-laboratory comparisons (including infrared spectral emittance and thermal diffusivity) sponsored by the Consultative Committee on Thermometry (CCT) Task Group on Thermophysical Quantities (TG-ThQ). The objective of this collaborative work was to strengthen the consistency of thermal conductivity measurements carried out worldwide on low conductive materials. Measurements were conducted successively by all participants on the same sets of specimens of insulating materials (mineral wool and expanded polystyrene) at temperatures ranging from 10 °C to 40 °C, according to the International Standard ISO 8302. This protocol aimed to minimize issues of material variability by circulating the same pairs of specimens among the laboratories following the strict format of a round-robin test program. More than 120 data points (combinations of material, thickness and temperature) were compared. 92 % of the data points were in agreement, with differences to weighted mean values less than the expanded uncertainties calculated from the individual NMI uncertainties and uncertainties related to the comparison process.

Effect of Heterologous Expression of Chemotaxis Proteins from Genus Thermotoga on the Growth Kinetics of Escherichia coli Cells.

In the process of optimization of heterologous expression of thermostable chemotaxis proteins CheW and CheY as industrially useful polypeptides, their direct influence on the cell growth kinetics and morphology of Escherichia coli was observed. CheW and CheY of bacteria of the genus Thermotoga, being expressed in recombinant form in E. coli cells, are involved in the corresponding signal pathways of the mesophilic microorganisms. The effects of such involvement in the metabolism of "host" cells are extremely diverse: from rapid aging of the culture to elongation of the stationary growth phase. We also discuss the mechanisms of the influence of the heterologous chemotaxis proteins on cells, their positive and negative effects, as well as potential applications in industry and biomedicine.

[Preparation and characterization of a new mutant homolog of chemotaxis protein CheY from anaerobic hyperthermophilic microorganism Thermotoga naphthophila]. / Poluchenie i kharakteristika novogo mutantnogo gomologa khemotaksisnogo belka CheY iz gipertermofil'nogo anaérobnogo mikroorganizma Thermotoga naphthophila.

Using genetic engineering methods the expression vectors structures have been designed to produce recombinant proteins TnaCheY and Tna CheY-mut, the homologues of the chemotaxis protein CheY from the hyperthermophilic organism Thermotoga naphthophila in Escherichia coli BL21(DE3) cells. The cultivation conditions of transformed strains were optimized. The influence of episomal expression of the heterologous chemotaxis protein CheY on growth kinetics parameters of the culture of mesophilic bacteria E. coli was studied. The optimal purification flowchart of the obtained proteins using thermolysis is proposed. Using the E. coli BL21(DE3) laboratory strain as an example, the possibility of employment the episomal expression of such proteins to control the cultivation and production time of pharmaceutically and industrially valuable metabolites due to the impact on some stages of the bacterial chemotaxis is experimentally proved.

Thermostable Recombinant Polypeptides as the Source of L-Amino Acids for Culture Media.

Mutant homologues of small chemotactic and DNA-binding proteins from thermophilic bacteria Thermotoga petrophila RKU-1 and Thermotoga naphthophila were obtained. These proteins can be expressed in the recombinant form in E. coli cells. A wide range of properties and parameters that are important for isolation of these proteins were revealed: stability in a wide temperature and pH range, high level of expression, solubility, and the possibility of using simple purification schemes with low number of successive steps. The positive effect of proteins on in vitro fibroblasts growth was demonstrated. The described properties of the target proteins indicate the possibility of their use in different biotechnology industries as an inexpensive source of L-amino acids.

Induction of Alternative Splicing and Inhibition of Activity of Telomerase Catalytic Subunit by Apoptotic Endonuclease EndoG in Human T, B, and NK Cells.

The effect of apoptotic endonuclease EndoG on alternative splicing of mRNA of human telomerase catalytic subunit hTERT (human telomerase reverse transcriptase) and telomerase activity in normal human lymphocytes were studied. Human CD4+, CD8+, B, and NK cells were transfected with a plasmid pEndoG-GFP containing EndoG gene or control plasmid pGFP. The levels of mRNA of EndoG or hTERT splicing variants were analyzed by real-time PCR. Protein content was assessed by Western blotting. Telomerase activity was measured by the telomere repeats amplification protocol. EndoG overexpression reduced the expression of active full-length hTERT and increased the expression of inactive splice variant. Shifted balance of hTERT splice variants in cells led to a significant decrease in telomerase activity within 72 h after transfection.

[Construction and characterization of a recombinant mutant homolog of the CheW protein from Thermotoga petrophila RKU-1]. / Poluchenie i kharakteristika rekombinantnogo mutantnogo gomologa belka CheW iz gipertermofil'nogo mikroorganizma Thermotoga petrophila RKU-1.

In the work a recombinant chemotaxis protein CheW from Thermotoga petrophila RKU-1 (TpeCheW) and its mutant homolog (TpeCheW-mut) were created. It was shown that, despite the low homology with CheW prototypes from intestinal bacteria, these proteins didn't cause metabolic overload and were well expressed by cells of E. coli laboratory strains. We have discovered a broad spectrum of industrial valuable properties of the TpeCheW-mut protein such as stability in a wide range of temperatures and pH, high expression level, solubility and possibility of the application of a simple low-stage purification methodology with the use of preliminary heat treatment. Possible directions of the scientific and industrial application of this protein were claimed.

Intracellular Localization of Apoptotic Endonuclease EndoG and Splice-Variants of Telomerase Catalytic Subunit hTERT.

The activity of telomerase catalytic subunit hTERT (human telomerase reverse transcriptase) can be regulated by alternative splicing of its mRNA. The mechanism of hTERT splicing is not understood in detail. Apoptotic endonuclease EndoG is known to participate in this process. In the present work, the intracellular colocalization and mRNA levels of EndoG and hTERT splice-variants in normal and apoptotic cancer cells were studied. We found that the development of apoptosis increased the expression of EndoG and changed the ratio of hTERT splice-variants, which decreased the telomerase activity in the cells. The development of apoptosis was accompanied by changes in the amount of mRNA and in the localization of EndoG and hTERT splice-variants in the cytoplasm, nuclei, and mitochondria of the cells. The suppression of EndoG expression using RNA interference prevented induction of the α+ß- splice-variant of hTERT and inhibition of the telomerase activity. A high degree of the intracellular colocalization of EndoG and hTERT was shown. The changes in the expression and localization of EndoG corresponded with changes in the amount and localization of hTERT splice-variants. These data confirm the participation of EndoG in the alternative splicing of mRNA of the telomerase catalytic subunit and in regulation of the telomerase activity.