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The role of machine learning (a part of artificial intelligence-AI) in the diagnosis and treatment of various types of oncology is steadily increasing. It is expected that the use of AI in oncology will speed up both diagnostic and treatment planning processes. This review describes recent applications of machine learning in oncology, including medical image analysis, treatment planning, patient survival prognosis, and the synthesis of drugs at the point of care. The fast and reliable analysis of medical images is of great importance in the case of fast-flowing forms of cancer. The introduction of ML for the analysis of constantly growing volumes of big data makes it possible to improve the quality of prescribed treatment and patient care. Thus, ML is expected to become an essential technology for medical specialists. The ML model has already improved prognostic prediction for patients compared to traditional staging algorithms. The direct synthesis of the necessary medical substances (small molecule mixtures) at the point of care could also seriously benefit from the application of ML. We further review the main trends in the use of artificial intelligence-based technologies in modern oncology. This review demonstrates the future prospects of using ML tools to make progress in cancer research, as well as in other areas of medicine. Despite growing interest in the use of modern computer technologies in medical practice, a number of unresolved ethical and legal problems remain. In this review, we also discuss the most relevant issues among them.

Objective: To evaluate surgical and oncological results of standard and extended lymph node dissection (D2 and D3) in patients with colon cancer., Material and Methods: We analyzed treatment outcomes in 74 patients with colon cancer stage T1-4aN0-2M0 who underwent right- and left-sided hemicolectomy, resection of sigmoid colon with standard and extended lymph node dissection (D2 and D3)., Results: Surgical approach and level of D3 lymph node dissection did not increase intra- and postoperative morbidity. Laparoscopic interventions were followed by significantly lower intraoperative blood loss and earlier gas discharge. Metastatic lesion of apical lymph nodes was observed in 5 out of 36 patients who underwent D3 lymph node dissection (13.8%), and metastases in regional lymph nodes rN1-2 were found in all these patients. Overall 5-year survival was 86%. Disease-free and overall 5-year survival were similar after D2 and D3 lymph node dissection., Conclusion: D3 lymph node dissection is safe for colon cancer. Metastatic lesions of apical lymph nodes during D3 lymph node dissection were detected only in patients with lesions of regional lymph nodes (rN1-2). Disease-free and overall 5-year survival were similar after D2 and D3 lymph node dissection.

Alkylresorcinols (ARs) are polyphenolic compounds with a wide spectrum of biological activities and are potentially involved in the regulation of host metabolism. The present study aims to establish whether ARs can be produced by the human gut microbiota and to evaluate alterations in content in stool samples as well as metabolic activity of the gut microbiota of C57BL, db/db , and LDLR (-/-) mice according to diet specifications and olivetol (5-n-pentylresorcinol) supplementation to estimate the regulatory potential of ARs. Gas chromatography with mass spectrometric detection was used to quantitatively analyse AR levels in mouse stool samples; faecal microbiota transplantation (FMT) from human donors to germ-free mice was performed to determine whether the intestinal microbiota could produce AR molecules; metagenome sequencing analysis of the mouse gut microbiota followed by reconstruction of its metabolic activity was performed to investigate olivetol's regulatory potential. A significant increase in the amounts of individual members of AR homologues in stool samples was revealed 14 days after FMT. Supplementation of 5-n-Pentylresorcinol to a regular diet influences the amounts of several ARs in the stool of C57BL/6 and LDLR (-/-) but not db/db mice, and caused a significant change in the predicted metabolic activity of the intestinal microbiota of C57BL/6 and LDLR (-/-) but not db/db mice. For the first time, we have shown that several ARs can be produced by the intestinal microbiota. Taking into account the dependence of AR levels in the gut on olivetol supplementation and microbiota metabolic activity, AR can be assumed to be potential quorum-sensing molecules, which also influence gut microbiota composition and host metabolism.

We present a rare case of postoperative diaphragmatic hernia in a patient with colon infringement 3 years after surgery for cardioesophageal cancer accompanied by extensive diaphragmotomy. The diagnosis of diaphragmatic hernia with colon infringement was based on a combination of anamnestic, clinical and radiological data, as well as results of diagnostic pleural puncture. This clinical case is of interest due to small incidence of disease and difficult interpretation of clinical and diagnostic data.

Background: Currently, rectal tumors radiotherapy effectiveness reaches an acceptable level only in a small number of patients (they have a complete clinical response), which is associated with the formation of malignant cells radioresistance. A comprehensive study that integrates various epigenetic parameters would explain a number of molecular mechanisms of rectal tumor cells radioresistance and identify new bio-markers. In the last decade, using high-through-put sequencing, the competitively interacting RNAs regulatory network (long non-coding RNAs, miRNAs and mRNAs) has been shown., Purpose: The aim of the study was to analyze the features of competitively interacting RNAs regulatory network functioning in patients with rectal cancer who are radioresistant and sensitive to radiotherapy. The study was performed on 500 patients with dia-gnosed rectal cancer. Radiotherapy was performed on a Novalis TX linear particle accelerator according to the standard protocol (single focal dose 2.4 Gy, total focal dose 54.0 Gy). Total RNA preparations were isolated from paired bio-psy fragments of tumor and non-tumor tissues of the rectum (obtained by video-colonoscopy). The relative abundance of mRNA, miRNA and lncRNA transcripts was assessed by the RT-qPCR method. Using bio-informatic analysis, the probability of potential interactions between the investigated mRNA, miRNA and lncRNA was determined. It has been shown that the effectiveness of radiotherapy depends on the level of miRNA (miRNA-195-5p; miRNA-4257; miRNA-5187-5p; miRNA-149-5p; miRNA-138 -1-3p; miRNA-6798-5p; miRNA-6819-5p; miRNA-4728-5p; miRNA-1249-5p; miRNA-557; miRNA-1273h-5p; miRNA-6737-5p; miRNA-6808-5p; miRNA-3202; miRNA-5195-3p; miRNA-130b-3p) and lncRNA (XIST, HELLPAR, NEAT1, AC008124. 1, LINC01089, LINC01547, and VASH1-AS1) expression, which regulate the DNA repair system (H2AX, RBBP8) and apoptosis (BCL2)., Conclusion: A comprehensive study of competitively interacting RNAs regulatory network and radiotherapy effectiveness of rectal tumors made it possible to establish the mechanisms of radioresistance formation and its bio-markers.

Herein we report the development of a nanocomposite for X-ray-induced photodynamic therapy (X-PDT) and computed tomography (CT) based on PEG-capped GdF 3 :Tb 3+ scintillating nanoparticles conjugated with Rose Bengal photosensitizer via electrostatic interactions. Scintillating GdF 3 :Tb 3+ nanoparticles were synthesized by a facile and cost-effective wet chemical precipitation method. All synthesized nanoparticles had an elongated "spindle-like" clustered morphology with an orthorhombic structure. The structure, particle size, and morphology were determined by transmission electron microscopy (TEM), X-ray diffraction (XRD), and dynamic light scattering (DLS) analysis. The presence of a polyethylene glycol (PEG) coating and Rose Bengal conjugates was proved by Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG), and ultraviolet-visible (UV-vis) analysis. Upon X-ray irradiation of the colloidal PEG-capped GdF 3 :Tb 3+ -Rose Bengal nanocomposite solution, an efficient fluorescent resonant energy transfer between scintillating nanoparticles and Rose Bengal was detected. The biodistribution of the synthesized nanoparticles in mice after intravenous administration was studied by in vivo CT imaging.

Squamous cell carcinoma in Zenker's diverticulum was first described in 1933. No large studies have yet been conducted due to rarity of this disease. There are a lot of unresolved issues regarding diagnosis and treatment of this pathology. In the literature, there are only few reports on cancer of Zenker diverticulum. It is only known that clinical symptoms are not specific, and diagnosis of carcinoma is traditionally correlated with age and male sex. Despite esophageal localization of primary tumor, its development can take up to 10 years. The authors report squamous cell carcinoma in Zenker diverticulum, discuss the main difficulties of morphological verification of this disease and choice of surgical approach.

Objective: To analyze the issue of gastrointestinal stromal tumors (GISTs) and potential of minimally invasive surgical interventions., Material and Methods: We analyzed postoperative outcomes in 97 patients with gastric and intestinal GISTs who underwent surgical treatment at the National Medical Research Centre for Oncology between 2015 and 2020., Results: Twenty (24.7) patients with gastric GISTs underwent laparoscopic partial and distal gastric resections. Five (35.7%) patients with GISTs of the small intestine underwent minimally invasive segmental bowel resections. Only minimally invasive interventions were performed in patients with rectal GISTs. Analysis of laparoscopic and open surgeries for GISTs found no significant differences. Analysis of laparoscopic and open surgeries for gastric and small bowel GISTs revealed the obvious advantages of minimally invasive access regarding postoperative outcomes. Indeed, we found no need for nasogastric drainage in 50% of patients ( p <0.001), earlier recovery of intestinal motility and oral feeding ( p <0.001), lower postoperative morbidity ( p =0.036), fast recovery of motor activity ( p <0.001) and shorter postoperative hospital-stay ( p <0.001)., Conclusion: Despite small incidence, GISTs are a complex problem in modern oncology. Diagnosis and treatment require a multidisciplinary medical team (morphologists, geneticists, radiologists, surgeons, chemotherapists, gastroenterologists and other specialists) that is possible in a reference center. Minimally invasive interventions for GISTs of the stomach, small intestine and rectum improve postoperative course.

Objective: To analyze patients undergoing redo liver resections for metastatic colorectal cancer., Material and Methods: The study included 14 patients with colorectal cancer who underwent several redo liver resections for metastatic lesions between September 2011 and June 2021. Mean age of patients was 63.5 years. Left-sided colonic G2 adenocarcinoma T4N1-2 prevailed (wild-type KRAS)., Results: Fourteen patients (100%) underwent two liver resections, 7 (50%) - three resections, 1 (7.1%) - four resections. Mean period between the first and the second liver resections was 16.2 months, between the second and the third resections - 9.9 months, between the third and the fourth resections - 5 months. Maximum follow-up period after primary surgery was 9 years and 9 months. Seventy-five percent of patients were alive after 34.2 months, 50% - after 58.9 months. N+ status of colorectal tumor decreased survival while KRAS mutation and synchronous metastatic liver lesions increased survival., Conclusion: Redo liver resections for metastatic colorectal cancer are safe and ensure favorable long-term survival in certain patients.

Non-small cell lung cancer (NSCLC) has limited treatment options. Expression of the RNA-binding protein (RBP) Musashi-2 (MSI2) is elevated in a subset of non-small cell lung cancer (NSCLC) tumors upon progression, and drives NSCLC metastasis. We evaluated the mechanism of MSI2 action in NSCLC to gain therapeutically useful insights. Reverse phase protein array (RPPA) analysis of MSI2-depleted versus control Kras LA1/+ ; Trp53 R172HΔG/+ NSCLC cell lines identified EGFR as a MSI2-regulated protein. MSI2 control of EGFR expression and activity in an NSCLC cell line panel was studied using RT-PCR, Western blots, and RNA immunoprecipitation. Functional consequences of MSI2 depletion were explored for cell growth and response to EGFR-targeting drugs, in vitro and in vivo. Expression relationships were validated using human tissue microarrays. MSI2 depletion significantly reduced EGFR protein expression, phosphorylation, or both. Comparison of protein and mRNA expression indicated a post-transcriptional activity of MSI2 in control of steady state levels of EGFR. RNA immunoprecipitation analysis demonstrated that MSI2 directly binds to EGFR mRNA, and sequence analysis predicted MSI2 binding sites in the murine and human EGFR mRNAs. MSI2 depletion selectively impaired cell proliferation in NSCLC cell lines with activating mutations of EGFR (EGFR mut ). Further, depletion of MSI2 in combination with EGFR inhibitors such as erlotinib, afatinib, and osimertinib selectively reduced the growth of EGFR mut NSCLC cells and xenografts. EGFR and MSI2 were significantly co-expressed in EGFR mut human NSCLCs. These results define MSI2 as a direct regulator of EGFR protein expression, and suggest inhibition of MSI2 could be of clinical value in EGFR mut NSCLC.

Lung surgeries following pneumonectomy using veno-venous extracorporeal membrane oxygenation (V-V ECMO) are described in the literature. The authors report a 62-year-old man with bilateral metachronous primary multiple lung cancer after previous extended lower lobectomy combined with sublobar resection of the upper lobe for squamous cell carcinoma of the left lung. Despite satisfactory functional status and heart function, the patient had poor lung function. Therefore, we decided to increase safety of resection using extracorporeal respiratory support. Extended right lower lobectomy was carried out under V-V ECMO. Surgery was followed by intrapleural bleeding that required urgent surgical hemostasis with completion of perioperative V-V ECMO. Postoperative ventilation lasted for 33 days but the patient was discharged later in a satisfactory condition.

Despite advances in classification, treatment, and imaging, neuroendocrine tumours remain a clinically complex subject. In this work, we studied the genetic profile of well-differentiated pancreatic neuroendocrine tumours (PanNETs) in a cohort of Caucasian patients and analysed the signalling pathways and candidate genes potentially associated with the development of this oncological disease. Twenty-four formalin-fixed paraffin-embedded (FFPE) samples of well-differentiated PanNETs were subjected to massive parallel sequencing using the targeted gene panel (409 genes) of the Illumina NextSeq 550 platform (San Diego, USA). In 24 patients, 119 variants were identified in 54 genes. The median mutation rate per patient was 5 (2.8-7). The detected genetic changes were dominated by missense mutations (67%) and nonsense mutations (29%). 18% of the mutations were activating, 35% of the variants led to a loss of function of the encoded protein, and 52% were not classified. Twenty-six variants were described as new. Functionally significant changes in the tertiary structure and activity of the protein molecules in an in silico assay were predicted for 5 new genetic variants. The 5 highest priority candidate genes were selected: CREB1, TCF12, PRKAR1A, BCL11A, and BUB1B. Genes carrying the identified mutations participate in signalling pathways known to be involved in PanNETs; in addition, 38% of the cases showed genetic changes in the regulation of the SMAD2/3 signalling pathway. Well-differentiated PanNETs in a Russian cohort demonstrate various molecular genetic features, including new genetic variations and potential driver genes. The highlighted molecular genetic changes in the SMAD2/3 signalling pathway suggest new prospects for targeted therapy.

Anthracyclines are effectively used in many therapeutic regimens for breast cancer (BC). However, the dose-dependent cardiotoxic effect causes certain limitations on their use. Laboratory tests for risk prediction and early diagnosis of anthracycline-induced cardiotoxicity (ACIC) based on measuring the activity and concentration of topoisomerase 2β, the levels of troponins T and I (TnT и TnI), N-terminal fragment of brain natriuretic peptide progenitor, remain relevant, but complicate the risk stratification with low specificity. Recently, the number of works devoted to the study of new biomarkers ACIC has been growing: galectin-3, soluble ST-2 (sST-2), and myeloperoxidase (MPO). In this review we analyzed current understanding of the classical markers ACIC and the results of recent studies dedicated to new predictors., Competing Interests: The authors declare no conflict of interest.

Copy number variation of some gene loci in lung tumor cells extracted by laser capture microdissection and in cell-free DNA in the plasma of patients with lung cancer was analyzed for identification of potential molecular markers. Tissue specimens fixed in formalin and embedded in paraffin blocks (FFPE-blocks) from 90 patients and extracellular DNA from plasma samples of 70 patients and 30 donors were used. Copy number variation was assayed for 30 genes (BAX, BCL2, C-FLAR, P53, MDM2, CASP9, CASP3, CASP8, SOX2, OCT4, PIK3, MKI67, HV2, HIF1A1, XRCC1, MMP1, TERT, CTNNB1, KRAS, EGFR, GRB2, SOS1, MAPK1, STAT1, BRAF, FTO, and mir3678) and reference loci (ACTB, B2M, and GAPDH) by the real-time quantitative PCR. Changed copy numbers were detected for genes responsible for apoptosis regulation (BAX, P53, and CASP3), proliferation (SOX2), DNA reparation (XRCC1), oxidative phosphorylation (HV2), EGFR signaling pathway (GRB2, SOS1, MAPK1, STAT1, and BRAF), and for mir3678 gene in lung tumor cells and extracellular DNA.

Objective: To confirm simplicity, safety and efficacy of stapling devices for gastroesophageal anastomosis (including those formed in mediastinum) in the treatment of gastroesophageal junction cancer., Material and Methods: There were 147 patients with cardioesophageal cancer. Tumors Siewert type II and III were predominant (44.2 and 40.3%, respectively). Simultaneous procedures were performed in 30.6% of cases., Results: Postoperative complication rate was 42.2%. Pneumonia was the most common. Postoperative mortality was 2.7%.

Aim: To analyze the problem of access conversion in laparoscopic surgery for colorectal cancer., Material and Methods: There were 876 procedures for colorectal cancer T14N01M0 performed at the Rostov Research Institute of Oncology in 2015-2017. Open and laparoscopic surgery was applied in 562 and 309 patients, respectively. Conversion of laparoscopic procedures was required in 35 (10.2%) patients., Results: Conversions were 2.7 times more frequent in men (p<0.05) (probably due to anatomical features - a narrow pelvis) and predominantly with rectosigmoid (22.2%, 2 patients) and rectal cancer (12%, 22 patients). Conversions in women were as well in right-sided colon cancer (9.7%, 3 cases) and sigmoid cancer (7.4%, 4 patients). Conversions were performed mostly due to locally advanced tumors (37.1%, 13 patients) which are especially baffling in case of narrow pelvis. Visceral obesity (20%, 7 patients) and abdominal adhesions (17.1%, 6 patients) were also important causes of conversions. Conversions did not affect time of surgery (256 min vs. 240 min in laparoscopic and 237 min in open surgery). Intraoperative blood loss (284 ml) was higher than in laparoscopy (240 ml) but did not exceed that in open surgery (291 ml)., Conclusion: It is necessary to assess risks and benefits of laparoscopy in patients with high probability of conversion in colorectal cancer surgery.

Cancer-testis antigens, effective markers of tissue malignant transformation, are characterized by heterogonous transcription depending on the pathological features of breast cancer. We performed screening of transcription profile of cancer-testis antigens specific for breast tumor tissues in female patients with and without regional metastasis. The relative expression of 16 genes (MAGEA1, MAGEA2, MAGEA3, MAGEA4, MAGEB1, MAGEB2, GAGE1, GAGE3, GAGE4, MAGEC1, BAGE, XAGE3, NY-ESO1, SSX2, SYCP1, and PRAME1) was analyzed by RT-qPCR method in biopsy specimens of the mammary gland tissues obtained during surgery from 25 patients. Differential transcription activity of cancer-testis antigens genes was observed in patients with metastatic (enhanced expression of MAGEA2, MAGEB1, and XAGE3 genes) and non-metastatic (enhanced expression of GAGE3 and PRAME1 genes) breast cancer.

Aim: The urgency of the problem of familial adenomatosis of the colon (FAC) is caused both by the severity of the disease with the inevitable development of cancer without timely treatment, and the involvement of the patient's blood relatives in this problem. Due to the rare inci- dence of this disease, many issues require discussion. To determine the possibility of timely treatment of FAC patients maintaining a satisfactory quality of life., Materials and Methods: The data on 5 FAC patients and 12 their blood relatives were studied. Clinical, endoscopic and genetic characteristics of the disease and treatment were analyzed. Results. Demonstrated that family history, genetic and endoscopic examinations allow diagnosis of FAC. Colectomy with rectal resection and the creation of a small intestine reservoir with reservoir-rectal anastomosis provide a sufficient quality of life for patients. Examination of the patient's blood relatives reveals new patients requiring additional examination and treatment., Conclusion: The problem of FAC is multidisciplinary and involves therapists, gastroenterologists, pediatricians, geneticists, endoscopists, radi- ologists, surgeons and oncologists. Only a timely diagnosis can help the patient to undergo radical treatment before the development of colon cancer.

Colorectal cancer is the second most common cancer in women and third most common cancer in men. Cell signaling alterations in colon cancer, especially in aggressive metastatic tumors, require further investigations. The present study aims to compare the expression pattern of proteins associated with cell signaling in paired tumor and non-tumor samples of patients with colon cancer, as well as to define the cluster of proteins to differentiate patients with non-metastatic (Dukes' grade B) and metastatic (Dukes' grade C&D) colon cancer. Frozen tumor and non-tumor samples were collected after tumor resection from 19 patients with colon cancer. The Panorama™ Antibody Microarray-Cell Signaling kits were used for the analyses. The expression ratios of paired tumor/non-tumor samples were calculated for the each protein. We employed R packages 'samr', 'gplots', 'supclust' (pelora, wilma algorithms), 'glmnet' for the differential expression analysis, supervised clustering and penalized logistic regression. Significance analysis of microarrays revealed 9 significantly up-regulated proteins, including protein kinase C gamma, c-Myc, MDM2, pan cytokeratin, and 1 significantly down-regulated protein (GAP1) in tumoral mucosa. Pan-cytokeratin and APP were up-regulated in tumor versus non-tumor tissue, and were selected in the predictive cluster to discriminate colon cancer type. Higher levels of S-100b and phospho-Tau-pSer199/202 were confirmed as the predictors of non-metastatic colon cancer by all employed regression/clustering methods. Deregulated proteins in colon cancer are involved in oncogenic signal transduction, cell cycle control, and regulation of cytoskeleton/transport. Further studies are needed to validate potential protein markers of colon cancer development and metastatic progression.

Purpose: To assess the frequencies of somatic EGFR mutations in the tumor tissues of patients with non-small cell lung cancer (NSCLC) residing in the South of Russia (SR), and to define the relationship between genetic subtypes of NSCLC and the emergence of different types of metastases., Methods: DNA was extracted from formalin-fixed parrafin embedded (FFPE) samples of 721 patients. A total of 29 somatic EGFR mutations were detected using commercial Therascreen EGFR RGQ PCR Kit., Results: EGFR mutations were significantly more frequent in females and non-smokers even when considering the combination of both factors. The frequency of activating EGFR mutations across three age groups (<51, 51-61, >61 years) of women with NSCLC was significantly different (x 2 =10.94, p=0.004) and became higher with increasing age. Both activating and resistance mutations of EGFR were not associated with the frequency of regional or distant metastases. The frequencies of both regional and distant metastases were associated with higher disease stage (odds ratio/OR)=16.71; 95% confidence interval (CI): 9.5-29.38; p<0.0001, and OR=2.94; 95% CI: 2.22-3.88; p<0.0001, respectively) and adenocarcinona histology (OR=6.52; 95% CI: 2.03-20.92; p=0.002, and OR=1.99; 95% CI: 0.91-4.34; p=0.083, respectively) even when adjusted for age, gender, and smoking status. The risk for regional metastases development was associated with poor tumor differentiation (OR=2.91; 95% CI: 1.21-7.02; p=0.017)., Conclusion: EGFR mutations were not associated with the frequency of regional or distant metastases in SR patients with NSCLC.

Gliomas are invasive brain tumors with high rates of recurrence and mortality. Glioblastoma multiforme (GBM) is the most deadly form of glioma with nearly 100% rate of recurrence and unfavorable prognosis in patients. Micro-RNAs (miR) are the class of wide-spread short non-coding RNAs that inhibit translation via binding to the mRNA of target genes. The aim of the present review is to analyze recent studies and experimental results concerning aberrant expression profiles of miR, which target components of the signaling pathways Hedgehog, Notch, Wnt, EGFR, TGFb, HIF1a in glioma/glioblastoma. Particularly, the interactions of miR with targets of 2-hydroxyglutarate (the product of mutant isocytrate dehydrogenase, R132H IDH1, which is specific for the glioma pathogenesis) have been considered in the present review. Detecting specific miRNAs in tissue and serum may serve as a diagnostic and prognostic tool for glioma, as well as for predicting treatment response of an individual patient, and potentially serving as a mechanism for creating personalized treatment strategies.

We developed a model of experimental melanoma. Intralienal xenogeneic transplantation of a suspension of melanoma cells B16 in physiological saline (0.1 ml; 1:10) was conducted to outbred male rats. In 6 months, histologically confirmed melanoma B16 in the spleen and its metastases in the liver, intestine, pancreas, adrenal glands, and lungs (hematogenous metastasis), as well as in the thymus and lymph nodes (lymphogenous metastasis) were revealed in rats. The proposed rat model of melanoma B16 metastasizes by the hematogenous and lymphogenous pathways, develops over 6 months, and allows receiving sufficient volume of material for analysis.

The aim of this study was to determine the role remaxol in complex intensive therapy of various jorms gipoergosis dur- ing the perioperative period in patients with hepatopancreatoduodenal zone malignancies. The treatment of 48 patients was analyzed. Immediately prior to surgery, at random, patients were divided into primary (n = 26) and control group (n = 22). In the study group for compensation the energy deficient states and organ hypoxia in the pancreas and the liver during the intra- and postoperative periods remaxol was included in the infusion therapy, the introduction ofwhich had been began before the start of anesthesia. In the control group antihypoxants weren't used. Integral assessment of prognosis and severity on a scale SAPS II and APACHE II. Status of energy and the type of energy deficit was estimated by the transport of oxygen and the concentration of lactate. In order to determine the level of stress exposure and the for- mation of adaptive reactions examined quantitative and qualitative composition of the peripheral blood. The study was conducted prior to surgery, on the 2nd and 5th day perioperative period. Inclusion in the scheme of metabolic remaxol program in the perioperative period in patients with malignant diseases of hepatopancreatoduodenal zone promotes the reduction of different types ofgipoergosis, efficient delivery and oxygen consumption, the adequacy of tissue oxygenation and restoration of adaptive physiological reactions such as.

According to the World Health Organization, pathologies associated with ischemia/reperfusion occupy the leading position in the structure of mortality. The efficiency of localized kidney cancer surgery is limited by the damaging effects of prolonged warm ischemia and reperfusion. Ischemia/reperfusion damage to renal tissue may be related to changes in the expression profiles of pro- and antiapoptotic genes. Here, we have presented the longitudinal expression profiles of apoptosis-related genes in tissues of left and right (intact) kidneys of male rats exposed to unilateral ischemia followed by reperfusion. The profiles have been assessed at time points of 1, 3, and 48 h after the ischemic/reperfusion exposure by RT-qPCR quantification of mRNAs encoded by 13 genes, including BAX, p53, AIFM1, APAF1, CASP8, CASP3, CASP9,CASP7, MDM2, BCL2, CIAP1, XIAP, and ICAD, after normalization with respect to a reference gene ACTB. The study revealed a shift in the expression of pro- and antiapoptotic genes toward the predominance of proapoptotic processes, as was evinced by the increase in expression detected for the BAX, p53, AIFM1, APAF1, and CASP8 genes. One hour after the reperfusion, activation of mitochondrial, or intrinsic apoptosis was detected, while р53-dependent and extrinsic, i.e., receptor-driven, apoptosis joined at later time points. Changes in the level of expression of caspase 7 (CASP7)-encoding mRNA have only been detected 48 h after the restoration of blood flow. Changes have been observed in the transcription of pro- and antiapoptotic genes in tissues of both kidneys, which suggests the involvement of the contralateral kidney in systemic pathological process that develops during unilateral ischemia/reperfusion.

Introduction: Tumor progression and neovascularization during malignant processes are believed to be associated with plasminogen activators and the PAI-1 inhibitor, but their role and interactions in various types of brain tumors have been studied insufficiently., Aim: To conduct a comparative study of plasminogen regulation in optic nerve sheath meningiomas, glioblastomas, and brain metastases of breast cancer, as well as in perifocal tissues surrounding the tumors., Material and Methods: Tumors and perifocal areas of 19 breast cancer (BC) metastases, 24 glioblastomas, and 13 meningiomas without perifocal edema were investigated by ELISA in 56 patients aged 35-72 years. Histological control was carried out in each case., Results: Significant differences were found in the levels of urokinase (uPA), tissue plasminogen activator (tPA), and PAI-1 inhibitor between glioblastomas and breast cancer metastases and the histologically unaltered (relatively intact) tissue around meningioma lesions (p≤0.05 in all cases). The levels of uPA-AG and uPA-act in meningioma were higher than those in the relatively intact tissue, while the levels of both tPA forms were reduced. The levels of uPA-AG and uPA-act in both malignant tumors and their perifocal areas were elevated compared to those in the relatively intact tissue. The levels of both tPA forms were reduced in all other tissues, except for glioblastoma. The level of PAI-1 inhibitor in malignant tissues was higher (being predominant in tumors) compared to that in the intact tissue surrounding meningioma, as well as relative to that in meningioma. The study proves that uPA and its inhibitor PAI-1 are directly involved in the metabolism of malignant gliomas and brain metastases of breast cancer. The role of tPA is to protect meningiomas; tPA activation in malignant brain tumors is suppressed.

Adenocarcinoma and squamous cell carcinoma are the most common types of esophageal cancer with a constant tendency to increase the incidence of growth on the background of the high mortality, which makes particularly the development of new biomarkers that complement and improve the early diagnosis of this disease. Despite the impressive number of studies in routine clinical practice is used only marker of esophageal cancer - ERBB2/HER2 status. This review summarizes data on the identified epigenetic markers of the aberrant methylation of the genome, which may be useful for early detection of esophageal cancer, prognosis estimation and / or prediction of response to treatment. The development of new high-tech genome-wide screening, such as beadarray and immunoprecipitation sequencing method used for the wideband genotyping, but for the analysis of transcriptome and metilom, provides a comprehensive picture of genetic and epigenetic changes during tumorigenesis. Note the need to verify the most biomarkers on large representative samples for the development of valid diagnostic panels, suitable for large-scale screening of risk groups.

The last decade is characterized by development of such technologies as RNA-sequencing and biochips which resulted in discovery of new perspective biomarkersfor personalized diagnostic of cancer. Among them, the long non-coding RNA (IncRNA) are of special interest because according the recent studies they are positioned as important regulators of gene expression on epigenetic, transcription and post-transcription levels. The review considers the role of long non-coding RNA in cancerogenesis. The corresponding of their application in diagnostic is evaluated. A number of examples ofperspective diagnostic and prognostic markers. Their degree of implementation in oncological practice is discussed.

A comparative analysis of available classifications of gastric neuroendocrine tumors was performed. It was showed that there were many contradictions regarding the issues of termi- nology and, in particular, criteria for determining the degree of differentiation of these tumors that significantly influenced on the choice of methods of treatment. There were unclearly marked symptoms of benign tumors, treatment of which could be conducted by endoscopy removal. There was absent the category of high- and moderately differentiated neuroendocrine tumors that metastasized by lymph and blood. Malignant tumors were represented by just low-differentiated malignancies although now many researchers noted the heterogeneity of this group and a different response to therapeutic agents. Up to now there were no standard methods for determining the pro- liferative level because any discrepancies between a number of mitoses and Ki67 index might be. Proliferative activity in tumor itself was often heterogeneous and it was necessary to select a specific point in tumor to determine its grade. Despite a proof of endodermal origin and the presence of combined tumors with epithelial component (mucocarcinoid, adenoneuroendocrine, amphicrine carcinoma) gastric neuroendocrine tumors were considered as a separate group in contrast to such standard symbols in pathology as adenomas and carcinomas. Thus it is necessary to accumulate further material for the standardization of nomenclature and more accurate determina- tion of malignant potential of tumors with the aim of studying the effect of various methods of treatment.

Aim: To study the types and early outcomes of combined interventions for locally advanced colorectal cancer., Material and Methods: Since 2009 four hundreds and ninety eight patients underwent surgery in the Rostov Research Institute of Oncology for locally advanced colorectal cancer. Most cases of surgical procedures on adjacent organs included resection of small intestine (23.69%), supravaginal hysterectomy (16.47%), resection of bladder (12.25%), total hysterectomy (11.45%)., Results: Postoperative complications occurred in 178 (35.7%) patients. Their incidence was significantly lower in case of laparoscopic approach (12.5%). Functional-sparing interventions on bladder followed by its augmentation with enteric graft improves rehabilitation., Conclusion: Laparoscopic approach and functional-sparing surgery improve the results of locally advanced colorectal cancer management.

Aim: To compare early results after pancreaticoduodenectomy depending on variant of pancreatico-digestive anastomosis., Material and Methods: It was analyzed early results of 207 pancreaticoduodenectomies for cancer which were performed for the period 2010-2014. Pancreatointestinal and pancreatogastric anastomoses were applied in 165 and 42 patients respectively., Results: Complications were observed in 73 (44.2%) and 18 (38.3%) patients after pancreatointestinal and pancreatogastric anastomoses respectively. Six patients died after pancreatointestinal anastomosis. At the same time there were no deaths in the group of pancreatogastric anastomosis. Differences were significant. Postoperative hospital-stay was similar in both groups.

Aim of the study was to analyze the dynamics of thyroid hormones in the pituitary gland, thyroid gland (TG) and blood serum (BS) in liver metastases to reveal thyroid profile of metastasis and to find thyroid markers-of metastasis in BS., Material and Methods: The experiment included 44 white male rats weighing 180-250 g. Sarcoma 45 (S-45) was transplanted intrasplenically after the spleen was brought under the skin. Levels of thyroid hormones: thyroid stimulating hormone (TSH) in the pituitary gland, TG, BS; free (FT4) and total (T4) thyroxine and free (FT3) and total (T3) triiodothyronine in TG and BS were studied by radioimmunoassay (Immunotech, Czech Republic; Arian analyzer, Russia)., Results: From the first days of the tumor development, pituitary gland strain with TSH hyperproduction was observed, and later TG hypofunctioning developed. Quantitative changes of thyroid hormones in organs did not correspond to their dynamics in BS. First diagnostic signs of experimental liver metastases, under the absence of formed metastases in the organ, were hyper-TSH-emy and the tendency to FT3 decreasing in BS. Typical characteristics of the "climax" of liver metastasis included formation of a marked "low TB" syndrome which transformed into a more severe "lowT3/lowT4" syndrome in secondary metastasis to the lungs., Conclusions: Thus, primary tumor growth and development of metastases are accompanied by the strain and imbalanced functioning of the thyroid system. Analysis of dynamics of the thyroid axis hormones in BS allows prognosis of liver metastases, as well as contributes to identifying the point of no return for the disease development which leads to secondary metastasis and irreversible progression of the process.

Aim: to define some clinical characteristics of synchronous and metachronous colorectal cancer (CRC)., Material and Methods: The investigation was concerned with the data of 150 patients with T1-4N0-2M0-1 multiple primary CRC. The clinical, biological, and morphological characteristics of synchronous and metachronous tumors were analyzed., Results: Multiple primary tumors were 6.01% of all the cases of CRC. There was a preponderance of synchronous CRC (63.75%) with the tumor localized in the sigmoid colon and rectum. In women, synchronous colorectal tumors were more often concurrent with breast tumors; metachronous ones were detected after treatment for genital tumors. In men, synchronous colorectal tumors were more frequently concurrent with kidney cancer; metachronous ones were identified after treatment for gastric cancer., Conclusion: The found characteristics of multiple primary colorectal tumors may be taken in account in programs for both primary diagnosis and follow-up after treatment for malignant tumors, which will be able to improve the early detection of cancer patients and their treatment results.

The differences in the type and tension of the general unspecific adaptational reactions in cancer patients with varying prevalence of the process in biliopancreaticoduodenal zone and volume of surgical intervention were revealed. It was shown prognostic significance of the numerical score of the type and tension of the adaptational reaction a day after pancreatoduodenal resection for the development of postoperative complications.

The review summarizes current data on the molecular genetic mechanisms underlying the pathogenesis of colorectal cancer (CRC) and addresses the connections between these mechanisms and biomarkers used for predictive diagnosis, risk stratification, prognosis, and predicting response to chemotherapy and tar-geted therapy. Evidence of microRNA involvement in the regulation of major signaling pathways affected by CRC pathogenesis is discussed, and signaling pathways that can be used as targets in the therapy of colorectal cancer are examined.

It is assumed that changes in the number of copies that belong to the basic mechanisms that control the expression of genes are important for malignization. Therefore, the characterization of these genes and the precise assessment of the number of copies are important for understanding the molecular basis of tumor emergence and progression in the human organism, as well as for the identification of predictive markers of malignization. In the present study, the relative number of copies of 19 loci (BAX, GSTP1, CASP3, CASP8, HIF1A, OCT4, C-MYC, SOX2, BCL2, CASP8/FADD, NANOG, P53, CASP9, IL-10, NFKB1, HV2, and ACTB) in cancerous and conventionally healthy tissues from 25 residents of southern Russia with a histologically confirmed diagnosis of adenocarcinoma (stages G1-G2 and G3) or signet cell gastric cancer were determined by quantitative real-time PCR. Changes in the number of copies of the gene were shown to be specific to particular histological types of cancer, as well as to depend on the stage of tumor cell differentiation. The data suggest that the number of copies of changes in the BAX, CASP3, CASP8, OCT4, C-MYC, SOX2, BCL2, NANOG, CASP9, NFKB1, HV2, ACTB, MKI67, IL-10, GSTP1, and P53 genes play an important role in the malignization of gastric tissue.

Aim of the Study: determination of levelsofsometissuegrowth factors, fibrinolyticsystemindicesand MMP-3 for specifi- cation of the role of their changes in moderately differentiated adenocarcinoma of the rectum. MATERIALS AND METHODS. Levels of growth factors and neoangiogenesis, tissue fibrinolyticsystemindicesand MMP-3were studiedin cytosols of tissue obtained from 73 patients (primary adenocarcinomas, st. III, G2, 47 men and 26 women aged 38-74 years, T1-3N0M0) by the ELISA method using standard test kits., Results: Increase in the content of growth factors VEGF-A, IGF and TGF-β1, the receptor protein VEGF-R, plasminogen activator uPA and metalloproteinases MMP-3 was detected inadenocarcinoma of the rectum. Gender differences inVEGF-Aand TGF-β1 content were found. Increase in levels and activity of uPA and MMP-3 only was detected in perifocal zone of the tumor. Changes in EGF content were found neither in adenocarcinoma tissue nor in its perifocal zone. No significant gender differenceswere observed intissue fibrinolyticsystemandMMP-3. Age differenceswere not found either. CONCLUSION. I. Concurrent expressionof IGF-I, IGF-II, TGF-β1 and VEGF-Aanditsreceptorinmalignanttumortissue, as well as increasedplasmin release from proenzyme and MMP-3 activationis apparently associatedwith the formation ofpathogenic mechanism of vasculature development in moderately differentiated adenocarcinoma of the rectum. 2. Activation of uPA and MMP-3 in perifocal zone of the tumor can serve as an indexof its invasive activity. 3. Genderdifferencesin VEGF-A and TGF-β1, content in tumor tissue were observed; significant association between natient gender and levels of IGF, EGF. fibinolvsis indices and MMP-3 was not found.

There was performed a molecular genetic study of UGTlAl gene allelic variants polymorphism in patients with colorectal cancer who had had chemotherapy irinotecan-containing regimens FOLFIRI. Comparison of toxicity and the results of polymorphism of UGTlAl showed that dose-limiting hematologic and non-hematologic toxicities in patients with moderate and high risk of toxicity were higher (p = 0.050- 0.061) and the frequency of thrombocytopenia (p = 0.0257) and hyperbilirubinemia (p = 0.0439) were significantly higher compared to the low-risk group. Molecular genetic study of a complex examination of patients, which was planned to irinotecan should be performed to select the optimal dose and reduce the risk of toxicity of chemotherapy.

Skin melanoma is an etiologically heterogeneous disease, the development of which is related to a complex interaction of environmental factors and individual genetic characteristics. This article provides current molecular-genetic aspects of familial cases of melanoma and polymorphism of genes directly related to the risk of developing this hereditary disease. The studies of hereditary cancer cases add our knowledge of mechanisms oncotransformation, genetic changes in signaling pathways, which are responsible for invasiveness, metastasis and drug resistance of melanoma cells of the skin.

Applying the method of multiple parallel sequencing on the MiSeq platform (Illumina, United States), a comparative analysis of miRNA expression in tumor and normal colon tissuie cells was performed. Forty miRNAs aberrantly expressed in cancer were detected. Among them, 15 and 25 miRNAs showed increased arid decreased expression, respectively, for all or most of the cases. Sixteen miRNA clusters were identified, which showed a coordinated or incompletely coordinated aberrant expression in colorectal cancer cells. In two (miR-183/182 and miR-106b/25) and four (miR-143/145, miR-497/195, miR-30e/30c-1, and miR-30a/30c-2) miRNA clusters, respectively, a statistically significant coordinated increase or decrease in expression was iegistered for all miRNAs withini the corresponding cluster. Three aberrantly expressed well-known miRNAs (miR-100-5p, mil-30d-5p, and miR-204-5p) were identified, which, however, had never 'before been associated with coloreictal cancer. The obtained results demonstrate the potential and promising application of 6 miRNA clusters with' coordinated aberrant expression as markers for colorectal cancer.

A new method for reproduction of metastatic involvement of the liver in outbred albino rats is proposed. The use of the method rules out the effects of stress factors (surgical intervention, total anesthesia) on malignant tumor metastasizing, making it maximally similar to the natural process. The method allows visual evaluation of the time course of the primary tumor node growth. The metastatic involvement of the liver develops only by the most significant route, hematogenic. The method can be used for the development of experimental therapy for this condition.

We performed a complex morphoimmunohistochemical study of synchronous bilateral breast cancer (diagnosed in 0.69% cases in women of the postproductive period after the age of 50). The molecular genetic characteristics of this cancer were detected and the algorithm of diagnostic studies was suggested. We have demonstrated that bilateral breast cancer was in 75% cases estrogen- and progesterone-positive, but androgen-negative. The HER-2/neu status of the tumor was negative in 75% cases, but expression of HER-2/neu was detected in the tumor of one mammary gland in 20% cases. Membrane expression of E-cadherin in infiltrative ductal cancer cells significantly decreased up to its complete disappearance with the decrease in tumor cell differentiation degree. The data provide new insight into prognostic value of the studied biomarkers and help to develop treatment protocol with consideration for the molecular biology of this group of tumors.