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Background: Ras oncogene mutations leading to hyperactivation of the MAPK/ERK signaling pathway occur in 25% of all human tumors, and for gastrointestinal tumors, the frequency of Ras mutations amounts to 60%. The introduction of a Ras-GTPase inhibitor into clinical practice would increase the effectiveness of the treatment of socially significant diseases such as stomach and intestinal cancer. Aim: To select the optimal dose with a subsequent assessment of the safety of iRAS when administered to patients with gastrointestinal tract tumors, including those with peritoneal carcinomatosis. Materials and methods: This was a prospective open-label non-randomized phase I study for the assessment of safety and tolerability, with an adaptive design and determination of the maximally tolerated dose of the iRAS. Three dose levels were used (0.45 mg/kg, 0.9 mg/kg, 1.8 mg/kg) according to the "3 + 3" scheme. The study included 11 patients after surgery for stomach or colorectal cancer. The patients were administered PIPAC therapy with iRAS twice with a 7-days interval. The study duration was 28 ± 1 days. During the study, the patient monitoring included physical examination, assessment of vital signs, electrocardiography and echocardiography, laboratory parameters (hematology, clinical chemistry, coagulation tests, and urine analysis). Results: The anti-tumor iRAS agent demonstrated satisfactory tolerability of all doses studied, including the maximal 1.8 mg/kg dose. Vital sign and laboratory abnormalities were clinically non-significant and did not require additional therapeutic interventions. Statistically significant abnormalities were registered for total protein (p = 0.00028), white blood cell counts (p = 0.007), lymphocyte counts (p = 0.0008), and a number of other blood parameters; however, most of these abnormalities were within the physiological normal ranges. Vital signs such as electrocardiography and echocardiography parameters remained stable throughout the entire follow-up period (28 days after administration of the drug). There were short-term rises in body temperature, minor pains in the postoperative scar area. Conclusion: This trial of safety and tolerability of iRAS showed that no cases of dose-limiting toxicity in the studied dose range. The 1.8 mg/kg dose can be recommended for further clinical studies.

Background: Differences in the embryonic development of the colonic mucosa determine the physiological embryonic-anatomical asymmetry of its structure and can manifest themselves via different molecular phenotypes (expression profiles) of the colon segments. These molecular characteristics are hypothesized to determine differences in the carcinogenesis mechanisms and influence the prognosis of right- or left-sided colorectal cancer (CRC). Studies of the tumors molecular phenotypes depending on their localization may be of interest for assessment of the prognosis and choice of treatment for CRC. Aim: To perform comparative analysis of molecular phenotypes of the normal colonic mucosa and adenocarcinoma CRC tissues depending on the natural embryonic anatomic asymmetry of the colon. Materials and methods: We performed a retrospective study of molecular phenotypes (mRNA expression of 61 genes) from different embryonic-anatomical parts of healthy colon and CRC. The normal group included 254 samples of mucosa from three different parts of the colon from 74 healthy donors who had no cancer and no organic abnormalities of the colon, including 90 samples from the right colon, 116 from the left colon, and 48 from the rectum. The CRC group consisted of 154 samples of localized stage T1–4N0–2M0 adenocarcinoma from 154 patients who had not received neoadjuvant radio- and chemotherapy, including 40 samples from the right colon, 54 from the left colon, and 60 from the rectum. The relative mRNA abundance of 61 genes was assessed by reverse-transcriptase polymerase chain reaction. In both groups, the resulting expression phenotypes were compared between the anatomical parts of the colon. Statistical management of the data included the discriminant analysis with stepwise inclusion of variables. Results: Based on the assessment of the mRNA level of the studied genes, a discriminant model was built that allows for classification of the normal group samples according to their anatomic origin in the colon with an accuracy of 95.8%. The most significant (p 0.05) for classification are the following 19 genes: CCND1, SCUBE2, TERT, BAG1, NDRG, IL1b, IL2Ra, IL7, ESR1, TGFb, IGF1, MMP9, MMP11, PAPPA, CD45, CD69, TLR2, TLR4, LIFR. The discriminant model built for the CRC group included 27 genes and made it possible to differentiate samples from three parts of colon with an accuracy of 75.2%. A statistically significant (p 0.05) contribution to the samples differentiation by the discriminant model was made by the COX-2, BIRC5, LIFR, TPA, IL1b, MMP11, MMP7, and P16INK4A genes. When combining samples from the two groups into one model in accordance with their embryonic-anatomical origin, there was a clear separation of tumor tissue samples and healthy colonic mucosa in the discriminant function space. Conclusion: The analysis of CRC gene expression profiles using the discriminant model showed that genetic changes in the colonic mucosa in CRC flatten the molecular phenotypic boundaries of the embryonic-anatomical parts. These changes are specific to CRC, forming a particular “pathological” molecular phenotype.

BACKGROUND: In recent years, there has been a notable increase in the number of articles using the term “dosiomics”. However, there are no literature reviews on this topic in the Russian language. AIM: This study aims to describe the basic principles of dosiomics as a derivative of radiomics and to analyze studies devoted to assessing the possibilities of its application in clinical practice. MATERIALS AND METHODS: A systematic literature search was performed in the PubMed database using the search query “dosiomics OR dosiomic”, and in the eLibrary database using the search query “dosiomics”. By April 2023, 43 foreign articles and 1 Russian article had been published. RESULTS: The analysis encompassed 43 foreign studies investigating the use of dosiomics in clinical practice, alongside one Russian article that provided a definition of the term “dosiomics”. The analyzed papers were divided into three groups according to their subject matter, and two tables describing the results of 27 studies on the prediction of clinical outcomes were created. CONCLUSION: Currently, dosiomics is a new and promising derivative of radiomics used in the textural analysis of medical images associated with radiation treatment of cancer patients. Dosiomics can contribute to the development of a more personalized approach to the planning of radiotherapy, the prediction of radiation damage of normal tissues, and the diagnosis of recurrence.

Background: Papillary thyroid cancer (PTC) course and outcome very much depend on prognosis factors. One of the most significant factors is extrathyroidal extension (ETE), which can be local or extensive. In the view of some authors, tumor grow beyond the thyroid capsule is associated with high risk locoregional and distant metastasis, which increase disease recurrence and reduce survival. Some others do not see influence of minimal ETE on disease prognosis, so we need more trials to clarify the role of ETE in PTC. Aims: To evaluate the ETE role in development of metastasis in PTC patients. Materials and methods: The study includes 233 patients with PTC who receive treatment in RSCRR. 185 patients had clinical N0 stage, 48 patients were with verified N1a1b. All patients with cN0 underwent thyroidectomy with central neck dissection, patients with N1 thyroidectomy combined with different neck dissections, also superior mediastinal lymphadenectomy if required. Within combination treatment the radioiodine therapy was carried out. The histology evaluated thyroid capsule involvement and lymph node metastasis. Data processing was carried out in a Microsoft Access database, a one-factor dispersion analysis was used for the analysis of the quantitative signs, and a -square criterion was used for qualitative ones. Multifactor analysis was done in SPSS20 program. Results: Thyroid capsule extension was detected in 111 cases (47.6%), from which 92 were microscopic. 122 patients did not have ETE. The frequency of lymph node metastasis with or without ETE was 62.2% and35.8% respectively, which is significantly more often (р = 0.000, 2 = 21.342). In microscopic and macroscopic extension regional metastasis were 56.5% and 94.7%, distant metastasis 1.1 and 21% respectively. Statistically significant, the ETE was more prevalent in non-encapsulated tumor cases (р = 0.000, 2=15.122), and if the tumor size was more than 1cm (р = 0.026, 2 = 7.293). Only 41% of patients with cN0 had ETE, and patients with N1 72.9%, which is statistically significant (р = 0.000, 2 = 14.235). Conclusion: ETE is a predictor of PTC metastasis. The presence of ETE requires the necessity to apply the more aggressive treatment of PTC including thyroidectomy with central neck dissection and radioiodine therapy. Gross ETE significantly increases the risk of regional together with distant metastasis.

Background. The regional lymph node metastasis in differentiated thyroid cancer (DTC) is still very high: 5060%, especially in papillary form. Averagely, after central neck lymph node dissection (CNLD), in 3040% cases hidden metastasis in lymph nodes of VI zone of neck were revealed. But they were not indicated by preoperative diagnostic procedures: ultrasound (US) and computer tomogpraphy (CT). Aims. To define the factors associated with the increased risk of lymph node metastasis for specification of indications to CNLD performance. Materials and methods. The study covers 105 patients with clinical stages of DTC T1-2N0M0, who received a thyroidectomy (TE) with preventive bilateral CNLD in RSCRR since 2012 till 2017. Patients older than 45 y.o. prevailed (66 patients (62.9%)). Data processing was carried out in a Microsoft Access database, a one-factor dispersion analysis was used for the analysis of the quantitative signs, and a c-square criterion was used for the qualitative ones. Results. The hidden metastasizes are founded by 32 (30.5%) patients. Multifocality is registered in 29 (27.6%) cases, lack of the tumor node capsule is registered in 65 (61.9%) and an invasion of the thyroid gland capsule is registered in 38 (36.2%) patients. Background diseases of the thyroid gland (TG) have 69 (65.7%) patients. According to the multifactorial analysis reliable independent predictors of the hidden metastasis of central neck lymph nodes were invasion of the anatomic capsule of TG (р = 0.003), age of patients 45 y.o. (р = 0.005), nonincapsulated form of tumor (р = 0.007). Conclusion. Use of TE in combination with CNLD allowed to restage at 46.7% of patients due to TG capsule invasion (28.6%) and hidden metastasis in VI group lymph nodes (30.5%) identification.