Introduction. The incidence and mortality of malignant melanoma have increased steadily over the last decades; therefore, the development of novel diagnostic markers for malignant melanoma is of great importance. The purpose of the study was to assess whether the development of melanoma before any treatment is accompanied by the body changes and, in particular, DNA damage in the mononuclear cells of the peripheral blood of patients. Material and Methods. In 93 patients (26 men and 67 women) admitted to the N.N. Petrov National Medical Research Center of Oncology for surgical treatment of stage T1c-2a-b-3a-b4a-bN0-1 cutaneous malignant melanoma, and in 118 healthy people as a comparison group, the level of damage to DNA in peripheral blood mononuclear cells was studied using the “comet” method. All patients were divided into two groups: group 1 included 45 patients (13 men and 32 women) who were examined before a decision on treatment was made and group 2 consisted of 48 patients (13 men and 35 women) who previously underwent excision biopsy for melanoma. Results. The level of DNA damage in peripheral blood mononuclear cells, assessed by the comet assay, was found to be signifcantly higher in patients with melanoma than in the comparison group. Moreover, the increase in the level of DNA damage was similar both in patients with a primary tumor before starting any treatment and in those who previously underwent excision biopsy for melanoma. The relationship between the level of DNA damage in peripheral blood mononuclear cells and the morphological characteristics of the tumor cells was revealed. The Spearman correlation analysis showed that all parameters that determined DNA damage positively correlated with the thickness of melanoma according to the Breslow’s depth, and the percentage of DNA in the comet and the comet tail moment correlated with the stage of the disease. Conclusion. The development of cutaneous melanoma is accompanied by an increase in the level of DNA damage in peripheral blood mononuclear cells. The level of DNA damage in peripheral blood mononuclear cells refects the changes that occur in the patient’s body under the infuence of the tumor process, which may allow using this indicator as an additional criterion for the diagnosis and aggressiveness of melanoma.

P urpose 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.

The study objective is to evaluate the results of using the Petrov Thyroid Cancer Score (PTCS) in 2018 and assess the diagnostic value of the original PTCS and modified PTCS.Materials and methods. PTCS, proposed in the N.N. Petrov National Medical Research Center of Oncology in early 2018, was tested in this institution in 310 patients, 99 of whom underwent surgery, mainly due to suspected malignancy of thyroid nodules or at the request of patients.Results. According to the standard histological evaluation, in 35 cases the process was considered benign (group Д), while in 61 cases — after exclusion of 3 medullary carcinomas — regarded as highly differentiated (according to previous classification) thyroid cancer (group Р). The average values of such components of PCTS as BethesdaScore, TI-RADSScore, ElastoScore and body mass index (BMI) in group Р were significantly higher than in group Д. The sum of the scores of the used four parameters was not only higher in group Р, but also at a magnitude of ≥5.0 (62.3 % of observations in this group) it always corresponded to the diagnosis of thyroid carcinoma. At the same time, a similar histological conclusion was made, in particular, in respect of 14 patients (23 % of the group Р contingent) with the value of the mentioned sum <3.5. Of note, according to the preoperative cytological study, among these 14 cases 11 follicular neoplasms and 3 colloid nodules were found.Conclusion. A high value (≥5.0) of the sum of four selected parameters (3 from PTCS + BMI_Score) indicates an extremely high probability of detecting a tumor process, while in other cases (and not only under the assumption of follicular neoplasia presence), an additional diagnostic methods of research are needed.

A method for assessing the likelihood of finding a differentiated thyroid cancer based on the use of the Petrov Thyroid Cancer Score (PTCS) is proposed. The individual components of the score are divided into 4 groups in terms of their diagnostic significance. PTCS reflects the opinions of specialists working in the different areas of oncology and needs further approbation based on retro- and prospective studies

Clinical trials of metformin efficacy in breast cancer were reviewed in this article. According to some data from cohort and case-controlled studies, the use of metformin with combined therapy of breast cancer improves overall and disease-free survival. Initial data from randomized clinical trials of metformin in adjuvant and neoadjuvant therapy of breast cancer are expected in the nearest future.

Introduction. In clinical practice, differential diagnosis of nodular thyroid diseases poses a serious problem which can be solved by development of new, safe, and specific thyroid tumor markers. Small regulatory RNAs (microRNA, miRNA) are a class of molecules that control gene expression at the post-transcriptional level. miRNAs, both intracellular and secreted into the extracellular space, can be used as markers of various diseases, including cancer. Stability of extracellular miRNAs is determined by binding to proteins and lipoproteins, or by “packing” into membrane microvesicles – exosomes. It is considered that exosomes with specific miRNA content are a result of active and biologically significant secretion, while release of other forms of miRNA is associated with apoptotic or necrotic cell death. This determines diagnostic value of exosomal fraction of circulating miRNAs, which may reflect presence or clinically significant properties of a tumor.The study objective was to explore a method of exosomal miRNA isolation, identify marker miRNAs, and estimate diagnostic value of their analysis.Methods. We used serum samples from 57 patients with nodular thyroid diseases and 13 healthy donors. Exosomes were isolated from serum by ultracentrifugation and analyzed by atomic force microscopy, laser correlation spectroscopy, and western blotting. Analysis of exosomal miRNAs was carried out by RT-PCR.Results. We have identified a specific correlation between certain miRNAs and status of thyroid nodular disease. Expression profiles of three miRNAs (miRNA-21, miRNA-146a, and miRNA-181a) exhibited specific characteristics for different forms of nodular thyroid disease and their analysis may have diagnostic value.Conclusions. Exosomes isolated by ultracentrifugation from serum are a source of RNA suitable for subsequent analysis of miRNA. The levels of different miRNAs in serum exosomes may differ by 1–2 times. «Marker» exosomal miRNAs have specific profiles in circulating exosomes of patients with different thyroid nodules. Clinical significance of testing exosomal miRNAs in patients with benign and malignant nodules of the thyroid gland can be increased by a parallel assessment of several molecules and analysis of the profile of their representation in exosomes. MiRNA-181a, -146a, and -21 form a diagnostic combination of «marker» molecules present in the circulating exosomes, which can be extended and used for diagnosis (differential diagnosis) of thyroid nodules.

Background. Malignant phenotype of cancer cells and metastatic potency of the tumor are determined by genetic factors. In addition, normal biological environment, including the nano-vesicles or exosomes, plays an important role in regulation of the structural and functional characteristics of malignant cells. Objective: presented study was aimed to evaluate mechanisms and to estimate effect of interaction of plasma exosomes and breast cancer cells in experimental conditions. Materials and methods. We used breast cancer cell culture MDA-MB-231 and exosomes isolated from plasma and cultural medium. Exosomes were analyzed by dynamic light scattering method and western blotting. Functional effects of exosomes were evaluated in in vitro and in vivo models. Results. In the present study we demonstrated that plasma exosomes stimulate the adhesion and the motility of breast cancer cells and induce the process of metastatic dissemination. Contact interaction of exosomes with cell surface is sufficient for stimulatory effect that is mediated by exosomal fibronectin and FAK-dependent signaling cascade. Conclusions. Further investigation of plasma exosomes structure and functions is required to better understand their input in regulation of malignant cell phenotype. This research has a potential to provide novel approaches for cancer therapy.

Over the few past years there have been passed many significant and positive changes in various fields of oncology due to both the use of achievements, stimulated by previous generations, and the progress of modern technology. This largely concerns endocrinology of malignant tumors, which is reflected in this article on the basis of the experience of the N.N.Petrov Research Institute of Oncology gained during recent times. Above all it is about the features of tumors of hormone-dependent tissues, hormonal and metabolic shifts, associated with them, and the ways of their correction based on the principles of personalized medicine.

The state of the viscosity of erythrocyte membranes in breast cancer patients (68--in menopause and 32--with menstrual cycle) was studied in comparison with the content of steroid hormone receptors in the tumor tissue and the age of patients. It is showed that the less hormone dependence of the tumor the higher viscosity of erythrocyte membranes that manifested by a decrease in the coefficient of eximerization (CE) of pyrene in the protein/lipid and in particular, lipid/lipid membrane layers. Increasing CE of pyrene in lipid/lipid layer of erythrocyte membranes above 1.7 units, reflecting a decline in their microviscosity, could be considered as an additional extra-tumor criterion for identification of the tumor as of hormone dependent type.

The paper presents the results of a study of the ovarian reserve in young women who received treatment for malignant tumors in childhood and adolescence and are in complete clinical remission. The function of the reproductive system was evaluated by serum concentrations of gonadotropins, estradiol, anti-Müllerian hormone (AMH) and inhibin B. The results were compared to the treatment, patients' age at the beginning of therapy and at the time of the examination. AMH level in serum was the most informative indicator of ovarian reserve in patients treated for malignant tumors.

Preliminary data are confirmed on the more rare prevalence of family history of diabetes mellitus (DM) in cancer patients, mainly females, with diabetes in comparison with diabetics without cancer pathology. Familial diabetes does not worsen additionally tumor characteristics against the same in patients with non-familial diabetes. More than that, familial diabetes in diabetics with breast cancer goes together with lesser size of tumor and demonstrates an inclination to the rarer distant metastases in breast and endometrial cancer patients. The signs of systemic DNA damage (evaluated, in particular, on the basis of 8-OH-dG serum levels) are pronounced in postmenopausal diabetic cancer patients with familial diabetes in lesser degree than in non-familial variant of DM. In toto, this allows to consider family history of DM in patients with type-2 diabetes as a particular factor of tumor growth containment, which mechanisms and causes, warrant further studies.

85 females were studied, 35 females had new onset of diabetes (DM2) and in 50 women DM2 was associated with recently diagnosed cancer (C+DM2). Group C+DM2 was characterized by higher levels ofbody mass index, insulinemia, estradiolemia, interleukin 6 in serum, and glyoxalase I activity in mononuclears. At the same time patients in C+DM2 group who had familial predisposition to DM2 were characterized by lower body mass index, body fat content, waist circumference, insulinemia, serum interleukin 6, viscosity of erythrocyte membranes and percent of comets in mononuclears in comparison with patients without familial predisposition to DM2. These trends were mostly opposite to the data of subgroups comparison (with or without relatives with DM2) in females with DM2 without cancer. The conclusion is made that the hereditary load with DM2 is differently realized in diabetics with higher or lower predisprosition to cancer that deserves further study.

Of examined 37 breast cancer patients (average age 42,3 +/- 1,2 years) 25 had not had any specific therapy by the date of investigation and the rest 12 had received in average 5,3 +/- 0,6 cycles of neoadjuvant chemotherapy mainly TAC and FAC. It was revealed that such kind of treatment conformed to valid decrease of both testosterone level and ratio value [(testosterone concentration/follicle stimulating hormone concentration, FSH) x 100] in blood serum. Testosterone level in blood of patients in fact decreased to similar values both in amenorrhea induced by adjuvant chemotherapy and saving menorrhea. This is a confirmation that maintenance of menorrhea does not mean intactness of ovarian function (ovarian reserve) and indicates that evaluation of testosteronemia in these circumstance at least does not give in estimation of estradiol and FSH's content in blood. Further attention could be paid to study testosteronemia before and after neoadjuvant chemotherapy as a potential additional prognostic factor of efficacy of this treatment for breast cancer patients.

The coexistence of type 2 diabetes with breast cancer may result in poorer cancer-related survival due to a number of mediating factors including an alteration of tumor tissue hormonal sensitivity. Previous studies have shown that receptor status of breast tumors in diabetics may be changed; however, the mode of therapy for diabetes was usually ignored. This work presents the results of an analysis of the receptor status of breast carcinomas in 90 postmenopausal women suffering with diabetes mellitus type 2 who had been cured, for not less that 1 year prior to surgery, with different modes of antidiabetic therapy, including a dietary treatment only, sulfonylurea preparations, insulin therapy, and metformin as a monotherapy or in combination with sulfonylurea derivatives. No differences in estrogen receptors occurrence in tumor tissue were found in different treatment groups. The frequency of progesterone receptor-positive mammary carcinomas in women who were treated with metformin, irrespective of whether it was combined with sulfonylurea preparations, was significantly higher than in the sulfonylurea only group (P=0.043) and in the combined group of patients treated with either sulfonylurea or insulin (P=0.041). The exclusion of the patients who received neoadjuvant chemotherapy (24 persons) did not significantly affect the above results. The data may be used as an explanation of the distinctions in cancer characteristics and course between diabetic patients treated with either metformin or sulfonylurea derivatives and insulin.

The gadolinium endometallofullerene/empty fullerene hydroxylated mixtures were prepared and studied as MRI-contrasting agents. The mixtures were prepared with metallofullerene enrichment of more than 80 mol.% by simple liquid extraction. The hydroxylation was performed by H2O2 oxidation at elevated temperature. Nanoaggregation of mixed fullerenes in water solution was studied by SANS. It was observed that at pH = 7 the cluster correlation diameter is 25 nm. NMR tomography in-vivo reveals that contrasting action of hydroxylated gadofullerene mixtures is 15-30 times its commercial "Gadovist" contrasting agent.

According to some existing data, unlike sulphonylurea (SU) and insulin derivatives, treatment with biguanide metformin, for reasons still unknown, may diminish breast cancer (BC) morbidity in diabetic females. For its part, diabetes is known to worsen survival of BC patients although there is no evidence of a pathway by which antidiabetic therapy might influence the key prognostic feature of BC tissue--the tumor receptor phenotype. Combination of BC and diabetes (n=90) was studied. SU drugs were received for at least 12 months by 22 patients, biguanide metformin alone or in conjunction with SU by 15, insulin by 5, and dietary treatment alone--by 48 pts. Percentage of estrogen receptor-positive tumors did not vary significantly from group to group. However, progesterone receptor-positive (PR+) tumors in metformin-treated patients were revealed more often than in those receiving SU alone (p = 0.43) or with insulin (p = 0.041), respectively. Hence, previous treatment with metformin is expected lead to higher incidence of PR+ tumors which in turn may stimulate efficiency of hormonal therapy only in relevant group of diabetic BC patients.

Gail coefficient (GC) generally used in breast cancer predictions for the next 5 year--or entire survival was determined in both patients and healthy controls of the same age, residents of St. Petersburg. Simultaneously, a correlation was established with hormono-metabolic indices, receptor pattern, tumor stage and size and some other characteristics. GC in cancer patients with age <50 was significantly higher than in control. In menopausal cancer patients, greater GC correlated with such parameters as body mass, weight index, glucose, total cholesterol and low density lipoproteids after fasting. The latter group showed a tendency towards enhanced estradiol and testosterone in blood serum. In reproductive patients with elevated GC, estradiol level rise was significantly lower and most tumors were receptor-negative. However, involvement of regional nodes was relatively rare. To summarize, GC determination characterizes risk and certain clinico-morphological features of distinction between reproductive and menopausal patients.