Regenerative medicine represents the field of medicine that aims to grow lost or damaged human organs and tissues. The promise of regenerative medicine focuses on the development of therapy that can regenerate and restore tissues and organs in the human body. The regenerative medicine  has the potential of cell renewal in our body, reaching about a kilogram per day, tens of tons in our life. Recent data indicate that a tumor is a tissue that largely repeats the pattern of growth and regeneration of normal tissue. Similar to normal stem cells, tumor stem cells are capable of initiating tumor and its growth. Scientists consider that cancer is a payment for multicellularity [1]. Undoubtedly, this potential must be learned to manage. This is a very difficult problem, since many fundamental mechanisms of cell formation and death have not been fully understood. The development of regenerative medicine as a fundamentally new type of medicine will make it  possible not only to control stem cell renewal, but also to prevent malignant transformation. The identification of proteins, micro-RNAs and other factors that regulate the formation and death of cells will identify potential targets  for both stimulating endogenous regeneration and controlling cancer. 

 Background. For the proper diagnosis and optimal prognosis of acute leukemia (AL), a complex of clinical and laboratory methods is used. Among them, chromosomal analysis plays an important role. Cytogenetic markers of leukemic cells are widely used in clinical settings. WHO classification of Tumors of Haematopoietic and Lymphoid Tissues is based on a combined analysis of clinical, cytomorphological, immunophenotypic and cytogenetic findings. Immunophenotyping of blast cells using monoclonal antibodies has significantly improved the diagnosis of leukemia by detecting the grade of tumor differentiation.

Aim: based on the results of immunophenotypic and cytogenetic examinations, to describe the structure of AL and to study the effect of cytogenetic abnormalities on the prognosis of acute leukemia in the child population of the Arkhangelsk region.

Material and Methods. Archived data were used to analyze the results of cytogenetic and immunophenotypic examinations of all children aged 0–17 years in the Arkhangelsk region, who were diagnosed with AL in the period from January, 2004 to december, 2018.

Results. Immunophenotypic examination of bone marrow blast cells in patients with AL revealed that B-linear lymphoblastic leukemia was the most common (74.8 %). Among the quantitative anomalies, hyperploidy was the most common (additional chromosomes 4, 10 and 17 were observed). The t(12; 21) was the most frequent structural chromosomal abnormality. The  philadelphia chromosome (ph) (9;22) was found in 6.5 % of cases. The highest risk of death was observed in AL patients with the acute myeloid leukemia phenotype (p<0.001). The overall survival in AL patients  significantly improved over the study period (p<0.001).

Conclusion. No specific differences in the structure of chromosomal abnormalities were detected. All chromosomal abnormalities which usually have negative effects on the prognosis of the disease also showed negative impacts on the prognosis. Survival of AL patients significantly increased over the study period. The lowest survival was in patients with the acute myeloid leukemia phenotype. 

 Background. Giant cell tumor of bone (GCTB) is a common benign lesion accounting for 4–9.5 % of all primary bone tumors. Although surgery is considered the method of choice in the treatment of GCT, however, denosumab, a genetically engineered drug with a novel mechanism of  action, has been recently used to treat GCTB. Histological examination of a surgical specimen is undoubtedly the most objective method for assessing the effectiveness of the treatment. However, in some cases it is necessary to assess the effectiveness of conservative therapy at the stages of its implementation.

The purpose of the study was to compare CT-densitometry findings with histological findings in GCTB patients treated with denosumab.

Material and Methods. The study included 30 patients aged from 28 to 59 years with histologically verified GCTB, who received targeted therapy with denosumab followed by surgery. The changes in tumor structure during denosumab therapy and surgical specimens of the tumor were assessed.

Results. The relationship between the CT-densitometry findings and histopathological findings of surgical specimens was revealed in GCTB patients treated with denosumab.

Conclusion. CT-densitometry findings were shown can be used to
predict pathological response of the tumor to denosumab treatment. 

 Purpose: to assess the efficacy and toxicity of concurrent  chemoradiotherapy with accelerated hyperfractionation in the treatment of  oral cancer.

Material and Methods. A total of 79 patients with oral cancer were enrolled in this study. Accelerated hyperfractionated radiation therapy was administered using terabalt unit concurrently with two cycles of pF chemotherapy. The daily dose of 2.5 Gy was divided into two fractions of 1.0 Gy and 1.5 Gy which were delivered to high- and low-risk areas with 5–6-hour-interval between each treatment, 5 days per week to a total dose of 60.0 Gy and 50.0 Gy, respectively.

Results. Complete response, partial response and stable disease were achieved in 63.3 %, 35.4 % and 1.3 % of and relapse-free survival rates for the entire group of patients were 54.5 % and 50.4 %, respectively. In the subgroup of patients with T3–4 stage tumors, the five-year overall survival rate was 50.8 %, and the five-year relapse-free survival rate was 47.2 %. Severe oral mucositis (grade 3) was noted in 36.7 % of patients. Grade 1 dermal toxicity was observed in 85 % of patients who experienced radiation-induced skin reactions. In 8.9 % of patients, osteoradionecrosis of the mandible occurred. All the patients included in the study completed the course of chemoradiotherapy as planned.

Conclusion. Concurrent chemoradiotherapy with accelerated hyperfractionation (1.0 Gy + 1.5 Gy) appears to be an effective treatment option for oral cavity cancer patients in whom surgery is contraindicated. 

 Purpose of the study: to assess whether the determination of the grade of dNA damage in the blood lymphocytes of patients with metastatic melanoma can be a criterion for assessing the effectiveness of therapy.

Material and Methods. The grade of dNA damage in blood mononuclear cells was studied using the comet assay in 10 patients with progressive metastatic melanoma before therapy with Nivolumab and 3–4 months after Nivolumab therapy.

Results. It was revealed that prior to treatment the level of dNA damage in blood mononuclears was higher in patients with melanoma than in controls (healthy subjects). This level significantly decreased when stable disease or complete regression were reached, while it changed less significantly or increased in cases with disease progression.

Сonclusion. The initial level and changes in lymphocyte dNA damage in patients with melanoma can serve as a criterion for assessing tumor  response to immunotherapy with Nivolumab. 

 Introduction. Identification of persons with a high oncological risk to squamous cell carcinoma of the head and neck region is an urgent problem for the early diagnosis of this disease. The activity of circulating proteasomes can be a criterion for predicting the risk of the larynx and oral cavity cancers in patients with precancerous diseases of the upper respiratory and gastrointestinal tracts.

The aim of the study is to investigate the chymotrypsin-like and caspase-like activities of circulating serum proteasomes depending on the localization of precancerous and neoplastic diseases of the larynx and oral cavity.

Material and Methods. The study population consisted of 35 patients with histologically verified HNSCC (T1–3N0–3M0), 15 patients with chronic hyperplastic laryngitis (CHL) and oral leukoplakia, and 10 healthy volunteers  who did not have chronic upper respiratory tract diseases in the acute stage. The median age of the patients was 53 ± 5.3 years.

Results. An increase in the studied proteasome activities was found in the blood serum of patients with malignant tumors as compared with patients with chronic hyperplastic diseases associated with precancerous changes, as well as in the larynx and oral cavity cancers groups as compared with healthy donors. At the same time, depending on the localization of the pathological process, it was shown that only the chymotrypsin-like activity of the circulating pool of proteasomes significantly differs both in the groups of oral cancer leukoplakia, and in the groups of laryngeal cancer chronic hyperplastic laryngitis with dysplastic epithelial lesions. In addition, differences were found between chymotrypsin-like and caspase-like activities of circulating serum proteasomes in patients with chronic hyperplastic laryngitis with oral dysplasia and leukoplakia.

Conclusion. The results obtained indicate that the determination of the CTp activity of the circulating pool of proteasomes can be used as a criterion for predicting the risk of the larynx and oral cavity cancers in patients with  precancerous diseases of the larynx and oral cavity. 

To date, the role of human papillomavirus (HpV) in the development of lung cancer is still under investigation. The available published data do not provide evidence of the involvement of HpV in lung cancer pathogenesis. In Russia, there are no reports regarding the studies of viral contribution to lung carcinogenesis.

The aim of the present study was to examine the presence of high-risk HpV infection in patients with non-small cell lung cancer (NSCLC).

Material and Methods. The study included 30 patients with histologically verified stage IIBIIIA NSCLC. Normal and tumor lung tissue samples as well as whole blood samples from each patient were used. dNA was isolated from tissue samples using the QIAamp dNA mini Kit (Qiagen, Germany). Amplisens® reagent kits (Moscow, Russia) were used for dNA isolation and genotyping.

Results. The presence of HpV dNA was detected in 3 (10.0 %) patients. HpV dNA was not detected in 27 (90.0 %) patients. HpV-16 genotype was observed in 2 HpV-positive patients, and HpV-33 was observed in 1 patient. A clinically insignificant viral load was found in almost all HpV-positive samples. The assessment of the virus integration in HpV16-positive lung cancer patients revealed mixed and integrated forms of the virus in the tumor tissue of these patients. The 5-year metastasis-free survival rate in all HpV-positive patients was 100 %.

Conclusion. Our data showed HpV dNA prevalence rate of 10 % among NSCLC patients in the Russian population. The presence/absence of a viral component for lung cancer patients is a clinically significant parameter.

 Introduction. Colorectal cancer is one of the most common cancers worldwide. In the Republic of Kazakhstan, over the past decade, the incidence rates of colon and rectal cancers have increased by 23 % and 17 %, respectively. Although colorectal cancer screening rates have increased over time, it is necessary to identify new serum markers for early detection and prognosis of this cancer.

The aim of the study was to evaluate the  diagnostic value of serum biomarkers for colorectal cancer.

Material and Methods. Biomarkers were studied by immunofluorescence method using xMap technology, which included simultaneous immunofluorescence determination on magnetic spheres CA125, CA15–3, CA19–9, CEA, CYFRA21–1, sFAS, sFasL, HE4, Osteopontin, VEGF-A, pd-L1.

Results. The study showed no significant differences in the levels of markers
between healthy subjects (control group) and patients with bowel diseases. In cancer patients, СEA and OpN markers increased with increasing tumor stage, and were significantly higher than those observed in patients with bowel diseases and controls. The CA125 marker was significantly higher in patients with stage IV cancer then in patients with I–III stages.

Conclusion. Our study revealed that the new pd-L1 marker can serve as a significant biomarker for colorectal cancer. 

 Challenges of early kidney cancer detection and screening significantly increase morbidity and mortality rates, thus dictating the need to improve prevention, early diagnosis and organization of medical care for the population of primorsky Krai.

The aim of the study was to create a model for improving early diagnosis of kidney cancer in the primorsky Krai using the program for assessing the risk of kidney cancer (ARKC). The model included a population questionnaire to identify risk factors and algorithm of patient routing («roadmap») with suspected kidney cancer for in-depth examination and treatment.

Material and Methods. 2982 residents of the primorsky Krai (women – 1950, men – 1032) in the age range 29–75 took part in the questionnaire survey using the ARKC program.

Results. No risk factors were identified in 1879 (63.0 %) individuals. All patients at high risk for kidney cancer (656 – 22.0 %) and patients of the uncertainty group (447 – 15.0 %) were referred for physical and ultrasound examination to exclude kidney tumors. Non-tumor pathology of the kidneys was revealed in 156 (14.0 %) patients. Renal mass suspicious for renal cell carcinoma was revealed in 21 (1.9 %) patients (later confirmed in 17 patients with stage I–II cancer, in 3 patients with stage III, in 1 patient with stage IV). According to the results of the factor analysis, two main groups of factors had a predominant effect on the rise in the overall kidney cancer incidencer. The first group of factors (65.0 %) is caused by smoking, excessive alcohol consumption, overweight, unbalanced nutrition, and the influence of carcinogens. The second group of factors (35.0 %) is caused by problems of a medical and social nature: the low material and technical base of primary care medical organizations, the insufficient professional training of medical workers on the issues of cancer prevention and treatment, including kidney cancer.

Conclusion. To improve the early detection of kidney cancer, a prognostic model with computer program for assessing the individual risk of developing kidney cancer was developed. population survey using the ARKC computer program allowed us to narrow the diagnostic search, form risk groups and effectively route patients with suspected kidney cancer for in-depth examination in accordance with the «road map». 

 The main objective of this study was to determine the place and role of neutron radiation therapy in the treatment of patients with recurrent high-grade glioma.

Material and Methods. Treatment outcomes were analyzed in 40 patients who were treated at Oncology Center (Chelyabinsk) and Center for Neutron Therapy (Snezhinsk) from 2005 to 2015. The median age of patients was 45 years. The male to female ratio was 1:1. Recurrent glioblastoma was diagnosed in 19 patients, and anaplastic astrocytoma was revealed in 21 patients. Twenty patients underwent neutron therapy alone,and 20 patients underwent combined neutronphoton radiation therapy. The median overall survival time for all patients with recurrent high-grade glioma was 50 months. The 1-year, 2-year and 3-year survival rates were 94.1 %, 77.8 % and 66.7 % respectively.

Results. The median survival time after treatment for relapse was 27 months. The main prognostic factors affecting the treatment outcomes were the age of the patients, histological verification and time to relapse. The method-specific overall survival rate was significantly higher in patients who underwent combined neutron-photon radiation therapy than in patients who underwent neutron therapy alone (48 months versus 20 months, p=0.05). 

 Background. Breast cancer is one of the most common malignancies and one of the leading causes of cancer deaths among women in the Russian Federation. The prognosis of the disease is largely determined by the
biological subtype of the tumor. Her2-positive breast cancer is characterized by an aggressive course and unfavorable prognosis. The use of pertuzumab, a recombinant humanized monoclonal antibody to the human epidermal growth factor receptor 2, significantly improved immediate and long-term treatment outcomes.

The aim of the study was to evaluate treatment outcomes in patients with Her2-positive molecular subtype of breast cancer receiving chemotherapy combined with a dual anti-Her2 blockade, and to assess the intensity
and incidence of side effects.

Material and methods. Between 2015 and 2018, 37 patients with Her2-positive breast cancer received chemotherapy combined with a dual anti-HER2 blockade (docetaxel 75 mg/m2 i/v on day 1 + trastuzumab 6 mg/kg (loading dose 8 mg/kg) i/v on day 1 + pertuzumab 420 mg (loading dose 840 mg) i/v on day 1 once every 3 weeks). The mean age of the patients was 45.6 ± 11.6 years.

Results. Neoadjuvant pertuzumab in combination with trastuzumab and docetaxel resulted in pathological complete response in 12 % of patients and pathological partial response in 36 % of patients. Among patients who received the above neoadjuvant therapy regimen, disease progression was observed in 4 % of patients. The most common side effects were weakness and fatigue (5.4 % of cases) and grade I–II leukopenia (5.4 %).

Conclusion. The study demonstrated the efficacy of antitumor therapy with pertuzumab in combination with trastuzumab and docetaxel as well as the absence of severe side effects associated with this treatment regimen in patients with Her2-positive breast cancer. 

 Background. Malignant dysphagia caused by the extrinsic compression of the esophagus and esophageal anastomoses is a rare complication of malignant neoplasms. Studies on the safety and efficacy of esophageal stenting for extra-organ esophageal compression have contradictory results.

The aim of the study was to analyze the life expectancy and complications after stenting in patients with malignant extra-organ compression of the esophagus and esophageal anastomoses.

Material and Methods. From 2011 to 2019, 19 patients with extrinsic compression of the esophagus and esophageal anastomoses caused by malignant neoplasms underwent ultrasound-guided implantation of self-expandable metallic stents.

Results. No complications were observed during stent implantation procedure. The mean dysphagia score decreased by 1.9 points. Short-and long-term complications, such as stent migration, profuse esophageal bleeding with lethal outcome, dysphagia relapse, tracheo-esophageal fistula, pronounced and granulation growth causing recurrent dysphagia, were observed in 5 patients. The median survival time was 55.9 days.

Conclusion. placement of metal stents in patients with malignant dysphagia due to extrinsic esophageal compression was shown to be safe and effective in relieving the symptoms of dysphagia. 

 The review highlights contemporary concepts about the role of atmospheric air pollution by particulate matter (pM) in cancer pathogenesis. We used publications from the pubMed and RISC databases. The impact of pMs on the development and progression of cancer was examined with respect to their size, origin, chemical composition and concentration in air. pMs with an aerodynamic diameter of ≤2.5 microns are recognized as the most dangerous. Epidemiological studies revealed a dose-dependent effect of pM on cells. dNA damage and pM-induced epigenetic changes are important components of cancer pathogenesis. Systematized scientific data, especially in the form of formalized descriptions, provide additional insights about concept of cancer pathogenesis and can be used in practical medicine for risk evaluation, early diagnostics, prognosis and increase of the treatment effectiveness. 

 Certain histological variants of tumors have a correlation between the values of the apparent diffusion coefficients (AdC), cell density and the proliferative activity index MIB-I (Ki67). The results of studies on the relationship between the values of the AdC and the Ki67 index in brain  tumors are ambiguous and largely contradictory.

The purpose of this study was to perform a systematic review based on the results of clinical studies that examined the relationship between AdC values  and the Ki67 proliferative activity index in brain tumors.

Material and Methods. Clinical studies were searched in the databases pubmed, EMBASE, Cohrane Library and eLibrary published from January 2000 to January 2020,  which studied the relationship between AdC values and the Ki67 proliferative activity index in brain tumors.

Results. A systematic review included 17 retrospective cohort nonrandomized clinical studies. The average value of the coefficient of reliable correlation between AdC and the mitotic index Ki67 in the group of meningiomas was -0.493. The indicated dependence was more often found in groups of typical (MI) and atypical (MII) brain meningiomas. The average coefficient of statistically significant correlation between the studied parameters in the group of brain gliomas was -0.443. The relationship between the AdC values and the Ki67 proliferative activity index was observed both in the glioma group of low (GI–II) and high (GIII–IV) grade of malignancy. In groups of patients with pituitary adenomas, primary lymphomas and brain metastases, the relationship between the studied parameters was not reliably confirmed.

Conclusion. The use of diffusion-weighted magnetic resonance imaging
techniques with subsequent calculation of AdC values can be recommended for use in the clinical practice of oncologists in order to assess the proliferative potential of brain meningiomas and gliomas. 

Background. Neoadjuvant chemotherapy (NACT) is a standard of care for locally advanced breast cancer patients. One of the main advantages of NACT is the reduction of the tumor size and regression of lymph node metastasis.

The aim of the study was to analyze the outcomes of breast-conserving surgery after NACT compared to adjuvant chemotherapy, including the examination of the width of resection margins and the frequency of re-operations, the volume of tissue removed and cosmetic outcomes.

Material and Methods. We analyzed 1219 publications available from pubMed, Medline, Cochrane Library, 1057 of them did not meet the inclusion criteria, 162 publications were selected to cover all the following inclusion criteria: surgical margin status, frequency of re-operations, volume of tissue removed and cosmetic outcomes. Finally, 22 studies met fully specified criteria.

Results. Studies included in this review demonstrated a different frequency of positive resection margins (2–39.8 %), reoperations (0–45.4 %), the volume of tissue removed (43.2–268 cm3), and the weight of the resected breast tissue (26.4–233 grams) after NACT.  

Conclusion. The data obtained showed a decrease in the frequency of positive resection margins and re-operations in patients who received NACT compared to patients who did not receive NACT (5–39.8 % versus 13.1–46 % and 0–45.4 % versus 0–76.5 %, respectively), as well as a decrease in the amount of the removed breast tissue without the negative effect on the frequency of resection margins, thus allowing minimization of the extent of surgery and improvement of cosmetic outcomes.

Owing to the development of molecular genetics, the role of radiation therapy and chemotherapy in treatment of patients with glioma (WHO Grade I–IV) has become more understandable. The overall survival among glioma patients has increased. As overall survival increases, oncologists are more likely to detect manifestations of late radiation toxicity that has a huge impact on Quality of Life in patients who have undergone radiation therapy in the past. In this regard, the question of finding more adequate radiation therapy techniques remains relevant. photon radiation therapy is the standard method; however, considering dosimetric advantages of proton therapy over photon therapy, its widespread use can potentially lead to the increased overall survival, decreased number of late radiation-induced complications and improved quality of life in the post-radiation period. This article presents some comparative characteristics of proton and photon radiation therapy in patients with gliomas (WHO Grade I–IV). dosimetry characteristics of protons in tissues were compared, data showing differences in survival of patients treated with photons versus patients treated with protons were presented, and general information on early and late  radiation-induced toxicity arising from the treatment by these methods was disclosed.

In this paper, we describe the case of successful surgical treatment of a rare combination of three malignant tumors of the major duodenal papilla in one patient. A 59-year-old woman presented with abdominal pain, fever, nausea, vomiting, weight loss and obstructive jaundice. After routine examination, the patient with suspected cancer of the major duodenal papilla underwent pylorus-sparing pancreatoduodenal resection. Final histology revealed a rare collision of three types of cancer in the major duodenal papilla invading the pancreatic head: moderately-differentiated adenocarcinoma (30 %), moderately differentiated squamous cell carcinoma (20 %) and poorly differentiated small cell neuroendocrine cancer (50 %), surgical resection margins were intact. Immunohistochemical analysis revealed positivity for synaptophysin, chromogranin A and cytokeratin 5/6. The tumor diameter of 2 cm and the absence of signs of locoregional spread allowed the process to be staged as T2N0M0, so the patient did not receive any adjuvant treatment. Follow-up CT performed 6 months later showed two lesions in the liver, and biopsy of one of them was performed. Metastasis of neuroendocrine cancer was histologically and immunohistochemically verified. She started first-line chemotherapy with etoposide + cisplatin.

Background. T-cell lymphoma with small and/or large bowel perforation is classified as a rare and extremely aggressive malignant non-Hodgkin’s lymphoma (NHL). There are two types of T-cell lymphomas:  enteropathyassociated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). The most common site of involvement is the small intestine.

Case presentation. A 63-year-old woman and a 50-year-old woman presented with a rare form of primary peripheral T-cell extranodal enteropathy-associated lymphoma (EATL) positive for Cd20 and Cd30. postoperative histological and immunohistochemical examinations of the small intestine resection specimens revealed intestinal perforation.

Conclusion. The delay in diagnosis, multiple lesions, complications, and the rapid disease progression ultimately led to the death of the patients.