Репозиторий Университета

© 2018 Media Sphera Publishing Group. All rights reserved. Development and use of new anticancer drugs has resulted in the improving of 5-year survival rates in patients with cancer. However, many of the modern chemotherapies are associated with cardiovascular toxicities that increases cardiovascular risk in cancer patients, including hypertension, heart failure, thrombosis and thromboembolism, cardiomyopathy, and arrhythmias. These side effects limitation restrict treatment options and farther perspectives. With increasing use of modern chemotherapies and prolongation of the cancer patients survival, the incidence of cardiovascular disease in this patient population will continue to increase. Accordingly,careful assessment and management of cardiovascular risk factors in cancer patients by oncologists and cardiologists working together is essential for optimal care.

© Bionika Media Ltd. Objective. To carry out a systems analysis of the data available in the current literature on the impact of vitamin D deficiency on the risk of endometriosis and reproductive cancer, as well as on the possibilities of vitamin D supplementation in order to treat and prevent these diseases. Material and methods. The review includes the data of foreign and Russian articles published in the past 10 years and found in Pubmed on this topic. Results. The paper describes the mechanisms by which vitamin D is involved in the processes of inflammation, immunomodulation, and proliferation, as well as the role of its deficiency in pathogenesis of pathological proliferation and inflammation in endometriosis, breast cancer, and ovarian cancer. It gives the data of clinical trials confirming the role of vitamin D deficiency in the progression and negative effects of endometriosis and carcinogenesis, the possibility of vitamin D supplementation for the prevention and adjunct therapy of reproductive cancer and endometriosis. Conclusion. It is necessary to conduct further studies to experimentally and clinically evaluate vitamin D deficiency in endometriosis and cancer. Currently, vitamin D supplements should be prescribed to patients with this pathology if they have been found to have a low blood level of 25(OH)D3.

© 2018 ABC-press Publishing House. All rights reserved. The objective is to perform comparative analysis of intra- and postoperative complications of retroperitoneoscopic radical nephrectomy (RRN) and laparoscopic radical nephrectomy (LRN) for large tumors. Materials and methods. The study includes examination and treatment data for 108 patients with stage T1–3a renal cell carcinoma. Results and conclusion. A number of advantages of RRN compared to LRN were demonstrated associated with shorter surgery duration with fast processing of the renal pedicle, lower blood loss, lower use of analgesics in the postoperative period, shorter duration of hospitalization, and quick recovery after the surgery. The rate of intra- and postoperative complications for RRN was 19.2 and 17.3 %, for LRN – 33.9 and 37.5 %, respectively. Complications associated with abdominal organs were absent for RRN. After LRN, the rate of serious complications was significantly higher than after RRN.

© 2018 Russian Electronic Journal of Radiology. All Rights Reserved. Purpose. To present abilities and limitations of Whole body MRI and FDG-PET/CT in the setting of sarcoid reaction and to stress the importance of use of broader differential diagnosis during interpreting its results. Materials and methods. The observation is introduced from clinical practice, examination was performed on 1.5 Tesla MRI scanner with the acquisition of four regions of interest: head and neck, thorax, abdomen, pelvis and upper thigh. Scanning protocol included diffusion-weighted imaging sequence. Results. The examination has let us exclude the presence of the active tumor tissue in breast cancer patient after systemic neoadjuvant treatment and drew our attention to false positive PET/CT result, which in turn led to change of further treatment strategy. Conclusions. Interpretation of FDG-PET/CT should be done in a complex manner with clinical, laboratory and radiological data correlation.

© 2018 Tomsk National Research Medical Center of the Russian Academy of Sciences. All Rights Reserved. The differential diagnosis of pulmonary diseases is extremely difficult and requires high qualifications of the radiologist and clinician. The differential diagnosis is used to distinguish different lung diseases: nonspecific inflammatory lung diseases (empyema, abscess, pneumonia), tuberculosis, sarcoidosis, benign tumors, lung cancer, lymphogranulomatosis, metastatic changes, and inflammatory changes in lung tissue. We present a clinical case, in which the differential diagnosis between tumor and inflammatory changes in lung tissue allowed the choice of optimal treatment tactics.

© ABC-press Publishing House. All rights reserved. Objectives to enhance the morphological diagnostic complex in order to predict postoperative outcomes in a more accurate way and to optimize patients with non-muscular invasive bladder cancer treatment. Materials and methods. The study included 34 patients from 25 to 71 years old underwent laser en-block resection, the most of them were males - 28. In 9 cases multiple carcinomas (2 or more) were found. Huge tumors (2 cm or more in one dimension) were resected in 6 patients. Results. The major part of tumors removed (n = 22) histologically appeared to be papillary urothelial carcinomas with low grade of malignancy and PUNLMP; in 6 cases G2 was verified, one tumor with high malignancy potention - G3. In 3 patients intramuscular invasion was found (invasive carcinoma T2) excluding them from the study. Discussion. Laser en-block resection of non-muscle-invasive bladder cancer appears to be the most optimal approach in operative treatment that provides representative histological material. For correct morphological estimate we recommend either to expand the resection zone to 1 cm which allows to remove circular resection margin or to take extra pinch biopsy from tumor crater (vertical margin). In 3 patients from our study positive circular margin was revealed histologically whereas foci of perineural and perivascular invasion were found in one case. A new subgrading of stage T1 depending on intramuscular invasion depth was suggested whereas the main criteria is the muscularis mucosae involvement. Conclusion. Morphological estimate of circular resection margin provides an ability to predict postoperative outcomes and correct the treatment in one or another way. Subgrading for T1-stage tumors is recommended for following correct postoperative prognosis and possibility of tumor recurrence.

© ABC-press Publishing House. All rights reserved. Prostate cancer is the most common cancer among men. Radical prostatectomy (open, laparoscopic, or robotic) remains the main method of surgical treatment for prostate cancer. However, minimally invasive therapies for prostate cancer are becoming increasingly popular in recent years, because they have similar efficacy as open surgery. The most studied minimally invasive therapies are cryoablation, high intensity focused ultrasound (HIFU), and brachytherapy. Despite the minimization of damage to neighboring structures, minimally invasive procedures can cause a number of complications, like any other surgical interventions. Each method has specific limitations and the most typical complications. Since multiple minimally invasive methods are currently available, we can ensure an individual approach to each particular patient, thus using the advantages of the methods and avoiding possible complications. This article covers the most frequent and severe complications of minimally invasive therapies for prostate cancer, as well as the methods of their prevention and treatment.

Research objective was assessment of a possibility of primary diagnosis of viruses Epstein-Burr, a cytomegalovirus, a virus of herpes of the 6th type in oral liquid and also influences of herpes infection on development and the clinical course of precancer diseases of the oral mucosa and the red border of lips (RBL). Profound clinic-immunological examination is conducted to 60 patients: the first group are have made 20 patients with an erosive and ulcer form of the lichen planus, the second - 20 people with an erosive form of a leukoplakia, a third - 20 people without diseases of the oral mucosa. As a result of work detection herpes infection is revealed high (90%). The combined infection with a virus Epstein-Burr and a virus of herpes of the 6th type was observed more than at a half of patients. The imbalance of factors of local immunity of the oral cavity in the form of increase in the IgG profile, decrease in concentration of IGA, lysozyme, and increase in an indicator of Ksb three times in comparison with norm and also substantial increase of level of pro-inflammatory cytokin IL 1β and FNO-α is found in patients with precancer diseases of the oral mucosa. Characteristic clinical feature of the precancer diseases associated with latent herpes infection is the long, recidivous current, persistent to traditional therapy. The research of oral liquid and blood on herpes viruses and consultation of the infectiologist is recommended to all patients with precancer diseases.

© 2018, Media Sphera Publishing Group. All rights reserved. The review of the literature deals with the participation of Clara cells now called club cells (CCs) of the epithelium in the respiratory and terminal bronchioles in the pathogenesis and morphogenesis of chronic inflammatory diseases, precancer, and cancer of the lung, which develop in the respiratory segments. The review summarizes data on the histophysiology of CCs and their participation in the pathogenesis and morphogenesis of chronic interstitial lung diseases, pneumoconiosis, chronic obstructive diseases, adenomatosis, and adenocarcinoma of the lung. In this area, there is a bronchioloalveolar junction area (BAJA), one of the most important stem cell niches. CCs are located in the BAJA; they are progenitor tissue stem cells and play an important role in the regeneration of the epithelium of the respiratory bronchioles and alveoli. Pathology of CCs in the BAJA leads to the maintenance of chronic inflammation, to the destruction of the lung elastic frame, and to impaired epithelial regeneration, interstitial fibrosis, and adenomatosis. In this case, decompensated inflammation, pathological regeneration, and fibrosis develop, which, along with the action of carcinogenic agents, can contribute to the accumulation of mutations and epigenetic rearrangements in the CCs, which subsequently results in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

© 2018 State Research Center, Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. All rights reserved. Purpose: To increase the effectiveness and quality of surgery treatment for patients with early stages of breast cancer. Material and methods: Since 2016, 25 patients with breast cancer were examined and went through surgery. A lymphotropic colloidal radiopharmaceutical labeled with 99mTc was used; it was administered (150 MBq) the day before the operation. 20 patients received this injection intradermally into periareolar zone, 4 patients received it peritumourally (under control of ultrasound), 1 - paratumorally. Lymphoscintigraphy was performed 3 hours after injection, the images were acquired using dualhead gamma camera Symbia E (Siemens, Germany). A static multiplanar imaging (scintigraphy) (anterior, posterior, lateral projections) was performed for the sentinel nodes (SN) mapping. 25 planar examinations were performed. In 3 cases additional SPECT/CT study was performed using a hybrid SPECT/CT Symbia T2 (Siemens, Germany). Surgical intervention was done on the next day after scintigraphy. During the surgery the handheld gamma probe NEO 2000 (Johnson & Johnson, USA) was used to localize radioactivity. The lymph nodes with the highest count (hot lymph nodes) were removed and sent for immediate histological examination. The results of immediate histological examination were evaluated again during next studies of gross specimen and slides. Results: During scintigraphy studies planar and SPECT/CT, 26 SN were detected in 20 women (80 %). In 15 patients only one SN lymph node was found, in 4 patients - 2, and in one case 3 SN were found. Intraoperative search of SN and immediate histological examination was conducted in 22 cases, 33 SN were found, while during planar scintigraphy only 26. In three cases, after histological examination (after obtaining examination results), patient surveillance was changed, these patients did not undergo through intraoperative radiometry and a decision was to conduct a onestage mastectomy with regional lymphadenectomy. 10 out of 22 patients which underwent intraoperative radiometry and sentinel node biopsy, with immediate histological examination had metastases in the removed nodes, therefore lymphadenectomy had been performed. In the rest 12 patients after immediate histological examination of SN no evidence of tumor growth was found, thus lymphadenectomy was not performed. In case of three patients which did not undergo through intraoperative radiometry, lymphadenectomy was performed and after histological examination only two patients had tumorinvolved SN, and one patient was clear. All intraoperative results were confirmed with next followup histological examinations. In 5 out of 25 patients (20 %) sentinel nodes were not founded. In these 5 cases during follow up period metastases were found in regional lymph nodes, and one patient had tumor emboli in lymphatic vessels, this considered being the cause of negative scintigraphy result. In 12 cases out of 25 (48 %) it was possible to minimize surgical management, and 13 (52 %) undergo lymphadenectomy. Conclusion: 1) The integration of SPECT/CT method of sentinel nodes search allows to plan an optimal surgical management, and can positively affect the longterm followup result of treatment of patients with breast cancer, and improve the quality of life. 2) The sensitivity and positive prognostic value (PPV) of planar scintigraphy and intraoperative radiometry of searching for SN are 80, 100 and 73.3, 100 %, respectively. 3) Thanks to the method of lymphoscintigraphy, 12 (48 %) of 25 women it was possible to minimize surgical management without lymphadenectomy.

© 2018 ABC-press Publishing House. All rights reserved.  Background. There is a category of patients with renal masses, due to severe concomitant diseases, can not perform the operation or may be associated with a threat to life. In addition, many patients with small tumor sites are extremely concerned about their disease and are negative about the tactics of active observation and insist on treatment. These patients can be offered alternative methods of treatment of renal cell carcinoma (RCC), the leading of which is cryoablation. Objective: to evaluate the effectiveness and safety of percutaneous cryoablation of the kidney tumor under ultrasound control. Materials and methods. In the Urology Clinic of the I.M. Sechenov First Moscow State Medical University during the period from 2015 to 2017 performed 23 percutaneous cryoablation of RCC, 7 (men - 4, women - 3) of which were performed under local anesthesia. In 4 patients due to severe concomitant diseases, general anesthesia was associated with an extremely high risk. Three patients refused from dynamic observation and from traditional surgical treatment; preferred an alternative treatment in the form of a percutaneous cryoablation under local anesthesia. In 4 cases, the formations were located in the lower segment along the posterior surface of the kidney, in 3 - along the lateral surface in the middle segment. The size of the formations was not used 4 cm (T1a). The age of the patients was 62.3 years (51 to 83 years). Right-sided localization of the tumor was noted in 3 patients, left-sided - in 4. One patient had a single kidney. At the preoperative stage and 6 months after the operation, all patients underwent ultrasound with dopplerography, multislice computerized tomography with contrast, and computer 3D modeling, which helped to clearly assess the size of the tumor, clarify the prevalence of the tumor process and the spatial ratio of the internal surface of the tumor node to the elements of the bowl-and-pelvis system. In all the observations, the formations were located along the posterior or lateral surface of the kidney; in the lower or middle segment; without invasion of the sine. We used a 3 rd generation cryomash machine SeedNet gold (Galil Medical), cryoprobes IceSeed and IceRod. Intraoperative, immediately before cryoablation, a tumor biopsy was performed, the presence of RCC in all patients was confirmed morphologically. Results. According to the ultrasound examination with echodopplerography at 6 months after the operation, the size of the tumor node's formations decreased on average by 6-8 mm, while there was no blood flow in them. When multislice computerized tomography with 3D modeling was performed, the formation was reduced and the accumulation of the contrast preparation was completely absent or their accumulation gradient did not exceed 10 HU (initially it was about 200 HU). There were no intraoperative complications. In 1 observation, a postoperative hematoma measuring 7 × 3 cm was resolved conservatively and did not require surgical treatment. Conclusions. Percutaneous cryodestruction under local anesthesia using ultrasound guidance seems to be an effective and safe technique for treating patients with stage T1a RCC with localization in the posterior or lateral surface in the lower or middle segments without invasion of the renal sinus and surrounding tissues. It is planned to continue monitoring patients to assess the long-term effectiveness of cryoablation.

© 2018 Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved. The purpose of the study was to present data on polymixin-based antibiotics with activity against infections caused by multidrug-resistant Gram-negative bacteria, such as Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Material and methods. The review includes data from clinical as well as in vitro studies for the period 1998–2017. The search for relevant sources was carried out in the Medline, Cochrane Library, Elibrary and other databases. Results. The analysis of the data showed the presence of synergism and additive activity of polymyxin in combination with carbapenems, rifampicin and azithromycin. However, experimental data showed no direct positive correlation between combination of polymyxim and azithromycin/ rifampicin. In clinical studies, in hospital-acquired pneumonia, including ventilator-associated pneumonia, the clinical response rate of polymyxin B combined with other antibiotics ranged from 38 % to 88 %. High nephro- and neurotoxicity of polymyxin observed in previous studies can be explained by a lack of understanding of its toxicodynamics or the use of an incorrect dose. Conclusion. Polymyxin B in combination with other antibiotics is a promising treatment against infectious complications caused by multidrug resistant Gram-negative bacteria.

© 2018 Tomsk National Research Medical Center of the Russian Academy of Sciences. All rights reserved. Reconstruction of head and neck defects after surgery for cancer remains challenging. The choice of the reconstruction technique depends on the tumor size and localization, type of the defect, patient’s age, concomitant diseases, and disease prognosis. Surgeons have currently a broad range of material for reconstructive surgery, from free flaps to revascularized flaps. Microsurgical reconstruction has made a revolution in treatment of patients with complex head and neck defects. However, the use of this technique may not be advisable for some patients. The search for new techniques is needed to improve functional and aesthetic results and reduce traumatism without compromising oncologic outcomes. Thirty-six patients underwent surgery with reconstruction using the submental island flap, a new alternative in the reconstruction of various head and neck defects. The graft was taken after making a neck incision for neck lymph node dissection. A few patients develop total and marginal necrosis of the graft. Short- and long-term results showed no worsening of oncologic outcomes in the selected group of patients.

© 2018 ABC-press Publishing House. All rights reserved. Objective: to compare the predictive value of RENAL, PADUA, C-index nephrometry score systems according to projection of complexity of operative measure in terms of warm ischaemic time, extent of blood loss and rate of postoperative complications. Materials and methods. Information for the research was collected from 314 patients with localized kidney cancer, who had laparoscopic partial nephrectomy from January 2012 to May 2017. In 210 (66.8 %) cases, in addition to the routine examinations, 3D modelling and operative measure planning were carried out. The average tumor volume of the patients was equal to 62.5 ± 33.5 mm3. All patients before the operation were estimated the complexity of operative measure on the nephrometry score systems: PADUA, RENAL, C-index. The average sum of balls according to scale RENAL - 7.56 ± 1.12, on scale PADUA - 7.98 ± 1.55, on scale C-index - 2.76 ± 1.14. Then in retrospect by the method of logistic regression analysis was determined predictive value of RENAL, PADUA, C-index nephrometry score systems for prediction of warm ischaemic time, duration of operative measure, extent of intraoperative blood loss and possibility of rate of postoperative complications. Results. In 265 (84.4) cases transperitoneal approach was perfomed and in 49 (15.6 %) cases it was retroperitoneal approach. The average time of laparoscopic partial nephrectomy is 140.15 ± 55.8 min, the average time of ischaemic warm is 13.35 ± 7,65 min. The average extent of blood loss during the laparoscopic partial nephrectomy is 291.95 ± 196.5 ml. Intraoperative complications were found in 8 (2.54 %) cases. Postoperative complications were estimated according to the Clavien-Dindo classification of surgical complications and were found in 31 (9.9 %) cases, among them 12 (3.8 %) patients had surgical complications. The index of the RENAL nephrometry scoring system had the highest predictive value in the multivariant analysis for warm ischaemic time, extent of intraoperative blood loss and possibility of development after complications (p = 0.049; 0.028; 0.046). None of indices were significant for multivariant analysis of prognosis the duration of laparoscopic partial nephrectomy. The indices of the RENAL (p = 0.032) and C-index (p = 0.040) nephrometry score systems were significant for univariate analysis of prognosis the duration of the laparoscopic partial nephrectomy. Conclusion. The usage of RENAL, PADUA, C-index nephrometry score systems is useful for the prediction of warm ischaemic time, extent of blood loss, duration of operative measure and possibility of rate of postoperative complications at laparoscopic partial nephrectomy. According to our data the index of RENAL nephrometry scoring system has the highest predictive value. Applications of 3D modelling for counting nephrometry indices in preoperative period makes the process of counting balls easier on all three nephrometry score systems.

© Bionika Media Ltd. Objective. To carry out a systematic analysis of the data available in the current literature on the modern view on Trousseau’s syndrome Material and methods. The review included the data of foreign and Russian articles published in the past 10 years and found in e-Library and PubMed on this topic. Results. This paper provides a pathogenetic explanation for the increased thrombotic potential in cancer patients, which underlies tumor growth and metastasis. In addition to direct thrombotic events, the paper also describes hemorrhagic complications resulting from systemic coagulopathy, including disseminated intravascular coagulation, hemolytic thrombotic microangiopathy, and excessive fibrinolysis. Conclusion. At present, any manifestation of thrombohemorrhagic complications in patients with malignant tumors can be classified as a paraneoplastic syndrome (Trousseau’s syndrome). In addition to Virchow’s classic triad, hyperproduction of tissue factor (TF), the main initiator of the extrinsic coagulation pathway, underlies the pathophysiology of Trousseau’s syndrome. At the same time, the substantial release of microparticles from TF-bearing tumor cells is critical not only for clot formation, but also for the progression of tumor growth.

© 2018 ABC-press Publishing House. All rights reserved. Background. The high recurrence rate after conventional transurethral resection (cTUR) for bladder cancer (BC) requires search for more effective methods of surgical treatment. Objective: to evaluate the feasibility, safety, and efficacy of cTUR versus thulium laser en bloc resection of bladder tumors using new fiber laser "Urolaz". Materials and methods. 129 patients, who underwent surgical treatment for BC between 2015-2017 in urological department of I.M. Sechenov First Moscow State Medical University were included in the study. The cTUR were performed for 58 patients, 71 patients underwent thulium laser en bloc resection of bladder tumors. Results. The presence of detrusor muscle in specimen was 58.62 % in cTUR group and 91.55 % in thulium laser en bloc resection group respectively. Obturator nerve reflex, bladder perforation, and bleeding in thulium laser en bloc resection group were absent, therefore immediate instillation of chemotherapy was made in all these cases. Recurrence rate after 12 and 18 months after surgery in the group of en bloc resection was statistically lower compared to the cTUR group. Conclusion. The results, obtained in our study shows that thulium en bloc resection using thulium fiber laser "Urolaz" is feasible, effective and safe procedure for patients with BC. Thulium en bloc resection has a number of advantages over the cTUR: Absence of obturator nerve reflex, high quality of specimen for pathological examination (presence of detrusor muscle in specimen was 91.55 %) and low recurrence rate.

© 2018, Polish Urological Association. All rights reserved. Introduction Oncological remission along with high postoperative functionality [continence and erectile function (EF)] are the main aspects of prostate cancer (PCa) treatment. The aim of this study was to compare functional and oncological treatment results achieved after a nerve-sparing radical prostatectomy (RP) via transperitoneal (TPRP), extraperitoneal (EPRP) and robot-assisted (RARP) approach. Material and methods From March 2015 to March 2016, 507 RP were performed at the Institute for Urology and Reproductive Health (Moscow, Russia). A total of 264 patients with localized (cТ1а–2с) prostate cancer [prostate-specific antigen (PSA) <20 ng/ml, Gleason score ≤7], intact prostate capsule (according to MRI), International Index of Erectile Function (IIEF-5) ≥19 and a life expectancy >10 years were included into the retrospective study. All the surgeries were performed by a single surgeon. The outcomes were evaluated after urethral catheter removal and 3–6–12 months after RP. Results Nerve preservation (NP) was performed for 153 patients without significant distinctions in time (р = 0.064) and blood loss (р = 0.073). The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-SF) score was lower for NP: 9.23 ±6.59 and 3.86 ±5.38 after 3 and 12 months respectively compared with continence after RP without nerve preservation (NP): 14.27 ±5.1 vs. 6.15 ±4.76 (р <0.001). Continent was 52.2% vs. 83.3% vs. 81.8% in TPRP, RARP and EPRP groups; р <0.001. IIEF-5 scores were 14.67 ±9.4, 4.2 ±4.26 and 4.0 ±2.07 after RARP, TPRP and EPRP respectively (р = 0.002). After 12 months the PSA: TPRP = 0.11 ±0.19, RARP = 0.03 ±0.05 and EPRP = 0.53 ±1.87 ng/ml (р <0.001). Outcomes depend on surgical approach and was better in the RARP-group (AUC = 0.768 ±0.034 (CI 95% 0,701–0.834; р <0.001). Conclusions We suggest RARP with NP as a method of choice for treatment of prostate cancer in patients interested in preservation of EF and quality of life in general.

© 2019, SPb RAACI. Inhibitory receptors CTLA-4 and PD-1 (immune checkpoints) play a key role in regulation of immune reactions. They suppress excessive immune response against pathogenic microbes and prevent autoimmune reactions. The immune checkpoints are targets of the modern effective therapy based on human and humanized monoclonal antibodies (ipilimumab and nivolumab, tremelimumab, pembrolizumab, etc). However, despite its high efficiency compared to standard chemotherapy, the therapy based on blocking immune check points is facing several problems, i.e., high therapy cost and severe negative autoimmune-related side effects. Unfortunately, this therapy helps to minority of the patients. Hence, further studies are required to improve its efficiency and safety, as well as to search for selection criteria of the patients who would benefit from the therapy. An appealing approach to reduce negative side effects from immune checkpoint inhibition is application of the blocking antibodies, aiming for ex vivo generation of patients’ activated immune cells for cancer therapy, thus avoiding systemic drug administration. Our aim was to elucidate influence of immune checkpoint blocking antibodies on the expression of CTLA-4 and PD-1 in such an in vitro model. First of all, we have determined quantities of lymphocyte receptors in peripheral blood of healthy volunteers, or cancer patients with disseminated melanoma. Moreover, we defined effect from the addition of antibodies against immune checkpoints on proportions of cells expressing CTLA-4 and PD-1 in the population of phytohemagglutinin-activated lymphocytes. Our study demonstrated that, in presence of antibodies to either of the two checkpoints during in vitro cell activation, the blockade of specific target receptor is accompanied by reduced number of cells positive for another checkpoint. Hence, the antibodies directed against PD-1 or CTLA-4 seem to suppress both negative signal cascades at once, if tested under such experimental conditions. Noteworthy, the response to blocking antibodies for different immune checkpoints varied for different donors. Our data may be used for development of effective combinations of lymphocyte activators and immune check-point inhibitors, for in vitro generation of activated lymphocytes applied for adoptive cancer therapy, as well as for prediction of possible responses to antibodies against CTLA-4 or PD-1, aiming to select the best personalized cancer immunotherapy.

© 2018 Russian Academy of Medical Sciences. All Rights Reserved. Cancer immunotherapy represents a promising and rapidly developing approach for the treatment of oncological diseases. Among the methods of personalized adjuvant immunotherapy, neoantigenic peptide-based drugs have demonstrated substantial efficiency. These drugs are designed to target mutant proteins arising from somatic alterations in the genome of tumor cells and thus stimulate immune response against tumor tissues. The methods of individual screening for potentially immunogenic mutations are mostly based on next-generation exome sequencing of tumor samples, which is a complex and costly procedure for clinical application. Targeted gene sequencing panels limited to a certain set of genes represent a reasonable alternative to WES. Targeted sequencing is also more efficient when there is a low amount of the sample DNA available. We have estimated the potential efficiency of targeted oncological panels in terms of somatic neoantigen profiling in colorectal cancer (colon and rectal adenocarcinoma). The clinical practice of identification of frequent somatic variants does not provide enough data for designing an efficient personalized drug when applied to low and medium mutated cancers such as colorectal cancer. Our analysis of 11 commercially available panels containing different number of genes has shown that neither the larger size of a panel nor its initial customization for colorectal cancer provides a significantly better estimation of an individual somatic mutation profile. The optimal approach is to use the general-purpose medium-sized cancer panels (2300-11200 amplicons and/or 150-600 genes). These panels allow to detect a sufficient number of immunogenic epitopes (>3) per patient for over 30-50% of patients.