44 research outputs found

    Morphology, mineralogical composition and genesis of vertisols in liman Bolshoi (Volgograd region)

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    The morphological structure of the profiles of two vertisols on microelevations of the gilgai complex of the Bolshoi liman (Svetloyarsk district of the Volgograd region) was studied. Despite the same microrelief position and equal relative heights of microelevations, morphological differences in the profiles at the subtype level were revealed. In one of the profiles, due to the higher humidity, the signs of vertisol genesis were less pronounced. Whereas in the second, more pronounced signs of vertic processes were described – slickensides with 15–30 cm length, smaller slickensides up to 10 cm, wedge-shaped aggregates. The proportion of the clay fraction in the mixed horizons, obtained by the Gorbunov method, was 45– 52%. Analysis of the qualitative mineralogical composition of the clay (<1ΞΌm) fractions showed that the smectite phase is represented mainly by disordered and mixed-layered smectite-illite formations. Individual illite belongs to the biotite variety according to the filling of the octahedral layer. Analysis of the ratio of the main mineral phases showed the predominance of illite (53–87%) in all soil samples. In the first pit an increase in the proportion of the smectite component with depth (from 1 to 35%) is noted. In the second pit, there are no regularities in the distribution of mineral phases (fluctuations within 24–37%), which may be associated with the involvement of chocolate clays layers in the profile during soil formation. Mineralogical analysis of chocolate clays (parent rocks) showed their high heterogeneity depending on the depth of the studied layer. No correlation was found between the severity of the signs of vertic processes and the proportion of the swelling component. Illustration of the stages of the formation of the soil cover on the investigated plot of the liman is given. The main reasons that led to the formation of different soils on microelevations are the unevenness of the β€œsqueezing out” of soil blocks upward in the process of microrelief formation in combination with local erosion

    Current determinants of the national accounting system transformation in Iraq

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    The article examines the most relevant issues of the external and internal factors’ influence on the accounting current development in Iraq. Historically, Iraq’s accounting system has been shaped by cultural traditions, religion, economic development and political trends over a long period, from ancient times to the present. Its origins date back to the Sumerian kingdom and before the overthrow of the S. Hussein regime. At present, not only national priorities but also global accounting trends have changed. Being formed in parallel with the development of the Republic of Iraq, the current accounting system is not oriented towards the requirements of International Financial Reporting Standards. In order to identify the current determinants of the national accounting system development, the actual model features and the conditions for consolidation with international standards have been analysed. The main directions of accounting harmonisation in the Republic of Iraq towards the international standards integration into the national system have been identified. The main steps of the transformation of national standards to international standards have been presented

    Glucocorticoids prime the inflammatory response of human hippocampal cells through up-regulation of inflammatory pathways

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    Increased pro-inflammatory cytokines and an overactive hypothalamic-pituitary-adrenal (HPA) axis have both been implicated in the pathogenesis of depression. However, these explanations appear contradictory because glucocorticoids are well recognised for their anti-inflammatory effects. Two hypotheses exist to resolve this paradox: the mediating presence of glucocorticoid receptor resistance, or the possibility that glucocorticoids can potentiate inflammatory processes in some circumstances. We sought to investigate these hypotheses in a cell model with significant relevance to depression: human hippocampal progenitor cells. We demonstrated that dexamethasone in vitro given for 24 hours and followed by a 24 hours rest interval before an immune challenge potentiates inflammatory effects in these neural cells, that is, increases the IL-6 protein secretion induced by stimulation with IL-1\u3b2 (10 ng/mL for 24 hours) by + 49% (P < 0.05) at a concentration of 100 nM and by + 70% (P < 0.01) for 1 \u3bcM. These effects are time- and dose-dependent and require activation of the glucocorticoid receptor. Gene expression microarray assays using Human Gene 2.1st Array Strips demonstrated that glucocorticoid treatment up-regulated several innate immune genes, including chemokines and Nod-like receptor, NLRP6; using transcription factor binding motifs we found limited evidence that glucocorticoid resistance was induced in the cells. Our data suggests a mechanism by which stress may prime the immune system for increased inflammation and suggests that stress and inflammation may be synergistic in the pathogenesis of depression

    The Effectiveness of Biopreparations on the Qualitative Properties of Feedstuff

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    It has been shown that in the process of enrichment of different green grass (silage), using a consortium endemic probiotic LAB strains (which sintesized bacteriocins) and yeast strain of Kluveromyces marxsianus 83(which synthesizing mycocin) led to increasing amounts of essential amino acids (in particular lysine and methionine) and protein. It has been shown that in the content of spore microflora, mold, bacteria contaminating silage was decreased with respect to the control. The technological parameters of silage have been determined

    The Effectiveness of Biopreparations on the Qualitative Properties of Feedstuff

    Get PDF
    It has been shown that in the process of enrichment of different green grass (silage), using a consortium endemic probiotic LAB strains (which sintesized bacteriocins) and yeast strain of Kluveromyces marxsianus 83(which synthesizing mycocin) led to increasing amounts of essential amino acids (in particular lysine and methionine) and protein. It has been shown that in the content of spore microflora, mold, bacteria contaminating silage was decreased with respect to the control. The technological parameters of silage have been determined

    Molecular genetic characteristics of colorectal cancer depending on the status of microsatellite instability

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    Introduction. The emergence of new markers that determine the choice of therapy for metastatic colorectal cancer (CRC) has led to an increase in overall survival. The optimal treatment tactics now take into account both clinical and molecular-genetic characteristics of the tumor.Aim. Investigation of the features of the KRAS, NRAS and BRAF mutations and amplification of the HER2 gene depending on microsatellite instability (MSI) in CRC.Materials and methods. The study included 400 patients with CRC. MSI, BRAF V600E mutation, mutations in the KRAS and NRAS genes was identified to them. MSI was determined by fragment analysis, and mutations in the KRAS, NRAS, BRAF genes by realtime PCR. HER2 amplification was determined in 100 patients with a negative RAS/BRAF. NTRK translocations were determined in all patients with MSI. Data on preoperative levels of CEA and CA19-9 were obtained from 185 patients.Results and discussion. The prevalence of MSI was 6.8%. The prevalence of KRAS, NRAS, BRAF mutations in CRC with MSI was 66.7%, and in CRC with MSS - 52.3%. In patients with MSI, the level of CEA was lower than in MSS (p = 0.0061). The overall prevalence of KRAS and NRAS mutations was 45% and 2.5%. The overall prevalence of the BRAF V600E mutation was 5.8% and was more common in MSI-positive tumors (p < 0.0001). Regardless of MSI, BRAF-positive tumors were characterized by right-sided localization (p < 0.0001), category T3-4 (p = 0.013), lymph node involvement (p = 0.004), carcinomatosis (p = 0.046), high levels of CA19-9 (p = 0.014). HER2 amplification was found in 7% of wild-type RAS/BRAF cases and was associated with rectal cancer (p = 0.044), category T3-4 (p = 0.041), and distant metastases (p = 0.038). HER2 amplifications and NTRK translocations were not detected in cases with MSI.Conclusion. MSI-positive CRC had a higher prevalence of mutations in major genes. CRC with the BRAF V600E mutation and HER2 amplification had aggressive clinical and morphological parameters

    БЛУЧАЙ Π£Π‘ΠŸΠ•Π¨ΠΠžΠ“Πž ΠšΠ£ΠŸΠ˜Π ΠžΠ’ΠΠΠ˜Π― Π—Π›ΠžΠšΠΠ§Π•Π‘Π’Π’Π•ΠΠΠžΠ™ Π“Π˜ΠŸΠ•Π Π’Π•Π ΠœΠ˜Π˜ Π‘Π•Π— Π˜Π‘ΠŸΠžΠ›Π¬Π—ΠžΠ’ΠΠΠ˜Π― Π”ΠΠΠ’Π ΠžΠ›Π•ΠΠ (клиничСскоС наблюдСниС)

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    The article describes the clinical case when malignant hyperthermia was diagnosed in the patients during the cardiac surgery. The patient had anesthesia with desflurane. The state of the patient was stabilized due to timely diagnostics and aggressive therapy with non-specific agents and cardiopulmonary bypass. The article presents different variants of clinical manifestations of this complication, ways of diagnostics and specific therapy.Β ΠŸΡ€Π΅Π΄ΡΡ‚Π°Π²Π»Π΅Π½ клиничСский случай лСчСния больного, Ρƒ ΠΊΠΎΡ‚ΠΎΡ€ΠΎΠ³ΠΎ Π±Ρ‹Π»Π° диагностирована злокачСствСнная гипСртСрмия Π²ΠΎ врСмя кардиохирургичСского Π²ΠΌΠ΅ΡˆΠ°Ρ‚Π΅Π»ΡŒΡΡ‚Π²Π°. Π‘ΠΎΠ»ΡŒΠ½ΠΎΠΌΡƒ ΠΏΡ€ΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ Π°Π½Π΅ΡΡ‚Π΅Π·ΠΈΡŽ с использованиСм дСсфлурана. БостояниС ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚Π° ΡƒΠ΄Π°Π»ΠΎΡΡŒ ΡΡ‚Π°Π±ΠΈΠ»ΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ Π·Π° счСт своСврСмСнной диагностики ΠΈ агрСссивной Ρ‚Π΅Ρ€Π°ΠΏΠΈΠΈ нСспСцифичСскими срСдствами с ΠΏΡ€ΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ искусствСнного кровообращСния. РассмотрСны Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Π΅ Π²Π°Ρ€ΠΈΠ°Π½Ρ‚Ρ‹ клиничСских проявлСний этого ослоТнСния, способы диагностики ΠΈ направлСния Ρ‚Π΅Ρ€Π°ΠΏΠΈΠΈ.

    ΠœΠΎΠ»Π΅ΠΊΡƒΠ»ΡΡ€Π½Ρ‹Π΅ ΠΌΠ°Ρ€ΠΊΠ΅Ρ€Ρ‹ ΠΎΡ‚Π²Π΅Ρ‚Π° Π½Π° ΠΏΠ΅Ρ€ΠΈΠΎΠΏΠ΅Ρ€Π°Ρ†ΠΈΠΎΠ½Π½ΡƒΡŽ Ρ…ΠΈΠΌΠΈΠΎΡ‚Π΅Ρ€Π°ΠΏΠΈΡŽ ΠΏΡ€ΠΈ мСстно-распространСнном Ρ€Π°ΠΊΠ΅ ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ°

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    Introduction. Perioperative FLOT chemotherapy has improved prognosis in patients with locally advanced resectable gastric cancer (GC). However, in 80 % of cases, the tumor is resistant to the therapy, resulting in unnecessary toxicity and delayed surgical treatment.Aim. Evaluation of clinico-morphological patterns of microsatellite instability, HER2 gene amplification, changes in gene copy number and their relationship with the response to perioperative FLOT chemotherapy in patients with locally advanced resectable GC.Materials and methods. The retrospective study included 185 patients. All tumor samples were assessed for HER2 and microsatellite instability status. Among all cases there were 45 patients with locally advanced T2–4N1–2 M0 GC, who underwent a total or subtotal gastrectomy with D2 lymphadenectomy and perioperative chemotherapy with FLOT. Microsatellite instability detection was performed using fragment analysis, HER2 gene amplification testing – fluorescent in situ hybridization. Also 19 patients were tested for copy number changes of the FGFR1, FGFR2, KRAS, MET, EGFR, CCND1, MYC genes using Multiplex ligation-dependent probe amplification. The endpoints were progression-free survival and objective response rate.Results. Microsatellite instability was detected in 4.8 % (9/185) of GC cases. Microsatellite instability was associated with advanced age (p = 0.005), low grade of differentiation (p = 0.011), presence of tumor-infiltrating lymphocytes (p = 0.0004), and high preoperative CA 72–4 levels (p = 0.025). Prevalence of HER2 amplification was 7.5 % (14/185). It was associated with low grade of differentiation (p = 0.048) and metastasis in regional lymph nodes (p = 0.037). PFS in patients with HER2-positive (HER2 – human epidermal growth factor receptor 2) GC treated with perioperative FLOT chemotherapy (4/45) was significantly lower than in patients with HER2-negative GC: the median was 156 and 317 days, respectively (hazard ratio 0.49; 95 % confidence interval 0.16–1.47; p = 0.0006). There was no correlation between the presence of the alteration and ORR (p = 1.0). Progression-free survival in GC patients with KRAS amplification (3/19) was significantly lower comparing with patients without it: the median was 98 and 327 days, respectively (hazard ratio 0.29; 95 % confidence interval 0.07–1.19; p <0.0001). There was no association between an increase in KRAS copy number and objective response rate (p = 1.0). For microsatellite instability and other studied markers no statistically significant correlation with progression-free survival and objective response rate was found (p >0.05).Conclusion. The presence of HER2 and KRAS amplification have been shown as promising predictive markers of the treatment failure in patients treated with perioperative FLOT chemotherapy for locally advanced resectable GC.Π’Π²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠŸΠ΅Ρ€ΠΈΠΎΠΏΠ΅Ρ€Π°Ρ†ΠΈΠΎΠ½Π½Π°Ρ химиотСрапия ΠΏΠΎ схСмС FLOT ΡƒΠ»ΡƒΡ‡ΡˆΠ°Π΅Ρ‚ ΠΏΡ€ΠΎΠ³Π½ΠΎΠ· Ρƒ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с мСстно-распространСнным Ρ€Π°ΠΊΠΎΠΌ ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ° (Π Π–). Однако Π±ΠΎΠ»Π΅Π΅ Ρ‡Π΅ΠΌ Π² 50 % случаСв Π½ΠΎΠ²ΠΎΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠ΅ Π½Π΅Ρ‡ΡƒΠ²ΡΡ‚Π²ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎ ΠΊ Π΄Π°Π½Π½ΠΎΠΉ Ρ‚Π΅Ρ€Π°ΠΏΠΈΠΈ, Ρ‡Ρ‚ΠΎ, Π² свою ΠΎΡ‡Π΅Ρ€Π΅Π΄ΡŒ, обусловливаСт Ρ‚ΠΎΠΊΡΠΈΡ‡Π½ΠΎΡΡ‚ΡŒ ΠΈ отсрочку ΠΎΠΏΠ΅Ρ€Π°Ρ‚ΠΈΠ²Π½ΠΎΠ³ΠΎ Π²ΠΌΠ΅ΡˆΠ°Ρ‚Π΅Π»ΡŒΡΡ‚Π²Π°. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ молСкулярно-гСнСтичСских ΠΏΡ€Π΅Π΄ΠΈΠΊΡ‚ΠΎΡ€ΠΎΠ² ΠΎΡ‚Π²Π΅Ρ‚Π° Π½Π° Ρ…ΠΈΠΌΠΈΠΎΡ‚Π΅Ρ€Π°ΠΏΠΈΡŽ Π² Ρ€Π΅ΠΆΠΈΠΌΠ΅ FLOT являСтся Π²Π°ΠΆΠ½ΠΎΠΉ Π·Π°Π΄Π°Ρ‡Π΅ΠΉ, ΠΏΠΎΡΠΊΠΎΠ»ΡŒΠΊΡƒ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΡ‚ ΠΎΠΏΡ‚ΠΈΠΌΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ ΠΏΠΎΠ΄Ρ…ΠΎΠ΄Ρ‹ ΠΊ Π»Π΅Ρ‡Π΅Π½ΠΈΡŽ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с мСстно-распространСнным Ρ€Π΅Π·Π΅ΠΊΡ‚Π°Π±Π΅Π»ΡŒΠ½Ρ‹ΠΌ Π Π–.ЦСль исслСдования – ΠΎΡ†Π΅Π½ΠΊΠ° ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-морфологичСских особСнностСй микросатСллитной Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΠΈ, Π°ΠΌΠΏΠ»ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠΈ Π³Π΅Π½Π° HER2, измСнСния копийности Π³Π΅Π½ΠΎΠ², Π° Ρ‚Π°ΠΊΠΆΠ΅ ΠΈΡ… взаимосвязи с ΠΎΡ‚Π²Π΅Ρ‚ΠΎΠΌ Π½Π° ΠΏΠ΅Ρ€ΠΈΠΎΠΏΠ΅Ρ€Π°Ρ†ΠΈΠΎΠ½Π½ΡƒΡŽ Ρ…ΠΈΠΌΠΈΠΎΡ‚Π΅Ρ€Π°ΠΏΠΈΡŽ Π² Ρ€Π΅ΠΆΠΈΠΌΠ΅ FLOT Ρƒ Π±ΠΎΠ»ΡŒΠ½Ρ‹Ρ… мСстно-распространСнным Π Π–.ΠœΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»Ρ‹ ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹. В рСтроспСктивноС исслСдованиС Π²ΠΊΠ»ΡŽΡ‡Π΅Π½Ρ‹ 185 ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ², Ρƒ ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… исслСдован статус HER2 ΠΈ микросатСллитной Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΠΈ. Из Π½ΠΈΡ… 45 ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с Π Π– T2–4N1–2M0, ΠΊΠΎΡ‚ΠΎΡ€Ρ‹ΠΌ ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½Ρ‹ ΡΡƒΠ±Ρ‚ΠΎΡ‚Π°Π»ΡŒΠ½Π°Ρ рСзСкция ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ° ΠΈΠ»ΠΈ гастрэктомия с лимфадСнэктомиСй D2 ΠΈ химиотСрапия Π² Ρ€Π΅ΠΆΠΈΠΌΠ΅ FLOT. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ микросатСллитной Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΠΈ ΠΏΡ€ΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΎΡΡŒ ΠΏΡƒΡ‚Π΅ΠΌ Ρ„Ρ€Π°Π³ΠΌΠ΅Π½Ρ‚Π½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π°, Π°ΠΌΠΏΠ»ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠΈ Π³Π΅Π½Π° HER2 ΠΌΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ флуорСсцСнтной Π³ΠΈΠ±Ρ€ΠΈΠ΄ΠΈΠ·Π°Ρ†ΠΈΠΈ in situ (fluorescence in-situ hybridization, FISH). Π’Π°ΠΊΠΆΠ΅ Ρƒ 19 Π±ΠΎΠ»ΡŒΠ½Ρ‹x ΠΏΡ€ΠΎΠ°Π½Π°Π»ΠΈΠ·ΠΈΡ€ΠΎΠ²Π°Π½Ρ‹ измСнСния копийности Π³Π΅Π½ΠΎΠ² KRAS, FGFR1, FGFR2, EGFR, MET, MYC, CCND1 с использованиСм ΠΌΠ΅Ρ‚ΠΎΠ΄Π° ΠΌΡƒΠ»ΡŒΡ‚ΠΈΠΏΠ»Π΅ΠΊΡΠ½ΠΎΠΉ лигазозависимой Π°ΠΌΠΏΠ»ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠΈ Π·ΠΎΠ½Π΄ΠΎΠ² (multiplex ligation-dependent probe amplification, MLPA).Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹. ΠœΠΈΠΊΡ€ΠΎΡΠ°Ρ‚Π΅Π»Π»ΠΈΡ‚Π½Π°Ρ Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΡŒ выявлСна Π² 4,8 % (9/185) случаСв Π Π–. Показана Π΅Π΅ взаимосвязь с ΠΏΠΎΠΆΠΈΠ»Ρ‹ΠΌ возрастом (p = 0,005), Π½ΠΈΠ·ΠΊΠΎΠΉ ΡΡ‚Π΅ΠΏΠ΅Π½ΡŒΡŽ Π΄ΠΈΡ„Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΡ€ΠΎΠ²ΠΊΠΈ (Ρ€ = 0,011), Π½Π°Π»ΠΈΡ‡ΠΈΠ΅ΠΌ ΠΎΠΏΡƒΡ…ΠΎΠ»ΡŒ-ΠΈΠ½Ρ„ΠΈΠ»ΡŒΡ‚Ρ€ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… Π»ΠΈΠΌΡ„ΠΎΡ†ΠΈΡ‚ΠΎΠ² (Ρ€ = 0,0004) ΠΈ высоким ΠΏΡ€Π΅Π΄ΠΎΠΏΠ΅Ρ€Π°Ρ†ΠΈΠΎΠ½Π½Ρ‹ΠΌ ΡƒΡ€ΠΎΠ²Π½Π΅ΠΌ CA 72–4 (Ρ€ = 0,025). Π Π°ΡΠΏΡ€ΠΎΡΡ‚Ρ€Π°Π½Π΅Π½Π½ΠΎΡΡ‚ΡŒ Π°ΠΌΠΏΠ»ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠΈ HER2 составила 7,5 % (14/185) ΠΈ Π±Ρ‹Π»Π° ассоциирована с Π½ΠΈΠ·ΠΊΠΎΠΉ ΡΡ‚Π΅ΠΏΠ΅Π½ΡŒΡŽ Π΄ΠΈΡ„Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΡ€ΠΎΠ²ΠΊΠΈ (p = 0,048) ΠΈ мСтастазированиСм Π² Ρ€Π΅Π³ΠΈΠΎΠ½Π°Ρ€Π½Ρ‹Π΅ лимфатичСскиС ΡƒΠ·Π»Ρ‹ (Ρ€ = 0,037). Π£Β ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с HER2-ΠΏΠΎΠ»ΠΎΠΆΠΈΡ‚Π΅Π»ΡŒΠ½Ρ‹ΠΌ Π Π– (HER2 – human epidermal growth factor receptor 2), ΠΏΠΎΠ»ΡƒΡ‡Π°Π²ΡˆΠΈΡ… ΠΏΠ΅Ρ€ΠΈΠΎΠΏΠ΅Ρ€Π°Ρ†ΠΈΠΎΠ½Π½ΡƒΡŽ Ρ…ΠΈΠΌΠΈΠΎΡ‚Π΅Ρ€Π°ΠΏΠΈΡŽ Π² Ρ€Π΅ΠΆΠΈΠΌΠ΅ FLOT (4/45), ΠΏΠΎΠΊΠ°Π·Π°Ρ‚Π΅Π»ΠΈ выТиваСмости Π±Π΅Π· прогрСссирования Π±Ρ‹Π»ΠΈ достовСрно Π½ΠΈΠΆΠ΅, Ρ‡Π΅ΠΌ Ρƒ Π±ΠΎΠ»ΡŒΠ½Ρ‹Ρ… с HER2-ΠΎΡ‚Ρ€ΠΈΡ†Π°Ρ‚Π΅Π»ΡŒΠ½Ρ‹ΠΌ Π Π–: ΠΌΠ΅Π΄ΠΈΠ°Π½Π° составила 156 ΠΈ 317 Π΄Π½Π΅ΠΉ соотвСтствСнно (ΠΎΡ‚Π½ΠΎΡˆΠ΅Π½ΠΈΠ΅ рисков 0,49; 95 % Π΄ΠΎΠ²Π΅Ρ€ΠΈΡ‚Π΅Π»ΡŒΠ½Ρ‹ΠΉ ΠΈΠ½Ρ‚Π΅Ρ€Π²Π°Π» 0,16–1,47; p = 0,0006). Π£Β Π±ΠΎΠ»ΡŒΠ½Ρ‹Ρ… с Π°ΠΌΠΏΠ»ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΠ΅ΠΉ KRAS (3/19) эти ΠΏΠΎΠΊΠ°Π·Π°Ρ‚Π΅Π»ΠΈ Π±Ρ‹Π»ΠΈ достовСрно Π½ΠΈΠΆΠ΅ ΠΏΠΎ ΡΡ€Π°Π²Π½Π΅Π½ΠΈΡŽ с Π±ΠΎΠ»ΡŒΠ½Ρ‹ΠΌΠΈ с Π΅Π΅ отсутствиСм: ΠΌΠ΅Π΄ΠΈΠ°Π½Π° составила 98 ΠΈ 327 Π΄Π½Π΅ΠΉ соотвСтствСнно (ΠΎΡ‚Π½ΠΎΡˆΠ΅Π½ΠΈΠ΅ рисков 0,29; 95 % Π΄ΠΎΠ²Π΅Ρ€ΠΈΡ‚Π΅Π»ΡŒΠ½Ρ‹ΠΉ ΠΈΠ½Ρ‚Π΅Ρ€Π²Π°Π» 0,07–1,19; p <0,0001).Π—Π°ΠΊΠ»ΡŽΡ‡Π΅Π½ΠΈΠ΅. Амплификации HER2 ΠΈ KRAS ΠΌΠΎΠ³ΡƒΡ‚ ΡΠ»ΡƒΠΆΠΈΡ‚ΡŒ пСрспСктивными ΠΌΠ°Ρ€ΠΊΠ΅Ρ€Π°ΠΌΠΈ ΠΎΡ‚Π²Π΅Ρ‚Π° Ρƒ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с мСстнораспространСнным Π Π– ΠΏΡ€ΠΈ ΠΏΡ€ΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ ΠΏΠ΅Ρ€ΠΈΠΎΠΏΠ΅Ρ€Π°Ρ†ΠΈΠΎΠ½Π½ΠΎΠΉ Ρ…ΠΈΠΌΠΈΠΎΡ‚Π΅Ρ€Π°ΠΏΠΈΠΈ ΠΏΠΎ схСмС FLOT

    Клинико-морфологичСский ΠΏΠΎΡ€Ρ‚Ρ€Π΅Ρ‚ ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅ΠΉ с микросатСллитной Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΡŒΡŽ

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    Background. Microsatellites are short tandem nucleotide repeats, the change in length of which plays a key roles in the pathogenesis of various malignant neoplasms. This change is called microsatellite instability. It is caused by aberrations in the genes of DNA mismatch repair system. Tumors with microsatellite instability are a special subtype regardless of location and are characterized by high sensitivity to immune checkpoint inhibitors.Objective – determination of characteristic clinical and morphological patterns of tumors of various localizations with microsatellite instability.Materials and methods. The study included 512 patients with malignant tumors of different localizations. Of these, 359 patients were diagnosed with colorectal cancer, 57 with uterine body cancer, and 57 with stomach cancer. Determination of the status of microsatellite instability was performed by a PCR-based method using 5 mononucleotide markers: BAT-25, BAT-26, NR-21, NR-24, NR-27.Results. The prevalence of microsatellite instability in colorectal cancer, uterine neoplasm and gastric cancer was 6.4; 22.8 and 1.75 %, respectively. Patients with MSI-positive colorectal cancer are characterized by yonger age (p = 0.023), right-sided localization of the tumor (p <0.0001), presence of multiple primary tumors (p = 0.0299), poorly differentiation (p = 0.0025), mucinous component (p <0.0001), tumor-infiltrating lymphocytes (p <0.0001) and Crohn-like reaction (p = 0.0006). Patients with uterine neoplasms with microsatellite instability are characterized by the presence of endometrial adenocarcinoma (p = 0.047), as well as the presence of tumor-infiltrating lymphocytes (p = 0.0022) and cribriform growth (p = 0.0011).Conclusion. A common pattern for colorectal cancer and uterine neoplasms is the presence of tumor-infiltrating lymphocytes. Certain clinical and morphological features of tumors of these localizations will more accurately identify candidates for microsatellite instability status determination for further immunotherapy.Π’Π²Π΅Π΄Π΅Π½ΠΈΠ΅. ΠœΠΈΠΊΡ€ΠΎΡΠ°Ρ‚Π΅Π»Π»ΠΈΡ‚Ρ‹ ΠΏΡ€Π΅Π΄ΡΡ‚Π°Π²Π»ΡΡŽΡ‚ собой ΠΊΠΎΡ€ΠΎΡ‚ΠΊΠΈΠ΅ Ρ‚Π°Π½Π΄Π΅ΠΌΠ½Ρ‹Π΅ ΠΏΠΎΠ²Ρ‚ΠΎΡ€Ρ‹ Π½ΡƒΠΊΠ»Π΅ΠΎΡ‚ΠΈΠ΄ΠΎΠ², ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π΄Π»ΠΈΠ½Ρ‹ ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… ΠΈΠ³Ρ€Π°Π΅Ρ‚ ΠΊΠ»ΡŽΡ‡Π΅Π²ΡƒΡŽ Ρ€ΠΎΠ»ΡŒ Π² ΠΏΠ°Ρ‚ΠΎΠ³Π΅Π½Π΅Π·Π΅ Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… злокачСствСнных Π½ΠΎΠ²ΠΎΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠΉ. Π’Π°ΠΊΠΎΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ называСтся микросатСллитной Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΡŒΡŽ. Она обусловлСна абСррациями Π² Π³Π΅Π½Π°Ρ… систСмы исправлСния ошибок Ρ€Π΅ΠΏΠ»ΠΈΠΊΠ°Ρ†ΠΈΠΈ. ΠžΠΏΡƒΡ…ΠΎΠ»ΠΈ с микросатСллитной Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΡŒΡŽ – это особый ΠΏΠΎΠ΄Ρ‚ΠΈΠΏ злокачСствСнных Π½ΠΎΠ²ΠΎΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠΉ, Ρ…Π°Ρ€Π°ΠΊΡ‚Π΅Ρ€ΠΈΠ·ΡƒΡŽΡ‰ΠΈΠΉΡΡ высокой Ρ‡ΡƒΠ²ΡΡ‚Π²ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒΡŽ ΠΊ ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€Π°ΠΌ ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½Ρ‹Ρ… Ρ‚ΠΎΡ‡Π΅ΠΊ ΠΈΠΌΠΌΡƒΠ½ΠΈΡ‚Π΅Ρ‚Π°.ЦСль исслСдования – ΠΎΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Ρ…Π°Ρ€Π°ΠΊΡ‚Π΅Ρ€Π½Ρ‹Ρ… ΠΊΠ»ΠΈΠ½ΠΈΠΊΠΎ-морфологичСских ΠΏΠ°Ρ‚Ρ‚Π΅Ρ€Π½ΠΎΠ² ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅ΠΉ Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°Ρ†ΠΈΠΉ с микросатСллитной Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΡŒΡŽ.ΠœΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»Ρ‹ ΠΈ ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹. Π’ исслСдованиС Π²ΠΊΠ»ΡŽΡ‡Π΅Π½Ρ‹ 512 ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² со злокачСствСнными новообразованиями Ρ€Π°Π·Π»ΠΈΡ‡Π½Ρ‹Ρ… Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°Ρ†ΠΈΠΉ. Π£ 359 ΠΈΠ· Π½ΠΈΡ… Π±Ρ‹Π» ΠΊΠΎΠ»ΠΎΡ€Π΅ΠΊΡ‚Π°Π»ΡŒΠ½Ρ‹ΠΉ Ρ€Π°ΠΊ, Ρƒ 57 – Ρ€Π°ΠΊ Ρ‚Π΅Π»Π° ΠΌΠ°Ρ‚ΠΊΠΈ, Ρƒ 57 – Ρ€Π°ΠΊ ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ°. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ статуса микросатСллитной Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΠΈ ΠΏΡ€ΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΎΡΡŒ Π½Π° основС ΠΌΠ΅Ρ‚ΠΎΠ΄Π° ΠΏΠΎΠ»ΠΈΠΌΠ΅Ρ€Π°Π·Π½ΠΎΠΉ Ρ†Π΅ΠΏΠ½ΠΎΠΉ Ρ€Π΅Π°ΠΊΡ†ΠΈΠΈ с использованиСм 5 ΠΌΠΎΠ½ΠΎΠ½ΡƒΠΊΠ»Π΅ΠΎΡ‚ΠΈΠ΄Π½Ρ‹Ρ… ΠΌΠ°Ρ€ΠΊΠ΅Ρ€ΠΎΠ²: BAT-25, BAT-26, NR-21, NR-24, NR-27.Π Π΅Π·ΡƒΠ»ΡŒΡ‚Π°Ρ‚Ρ‹. ΠŸΠΎΠΊΠ°Π·Π°Ρ‚Π΅Π»ΠΈ распространСнности микросатСллитной Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΠΈ ΠΏΡ€ΠΈ ΠΊΠΎΠ»ΠΎΡ€Π΅ΠΊΡ‚Π°Π»ΡŒΠ½ΠΎΠΌ Ρ€Π°ΠΊΠ΅, Ρ€Π°ΠΊΠ΅ Ρ‚Π΅Π»Π° ΠΌΠ°Ρ‚ΠΊΠΈ ΠΈ ΠΆΠ΅Π»ΡƒΠ΄ΠΊΠ° составили 6,4; 22,8 ΠΈ 1,75 % соотвСтствСнно. Для ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с ΠΊΠΎΠ»ΠΎΡ€Π΅ΠΊΡ‚Π°Π»ΡŒΠ½Ρ‹ΠΌ Ρ€Π°ΠΊΠΎΠΌ с микросатСллитной Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΡŒΡŽ Ρ…Π°Ρ€Π°ΠΊΡ‚Π΅Ρ€Π½Ρ‹ Π±ΠΎΠ»Π΅Π΅ ΠΌΠΎΠ»ΠΎΠ΄ΠΎΠΉ возраст (p = 0,023), правосторонняя локализация ΠΎΠΏΡƒΡ…ΠΎΠ»ΠΈ (p <0,0001), Π½Π°Π»ΠΈΡ‡ΠΈΠ΅ ΠΏΠ΅Ρ€Π²ΠΈΡ‡Π½ΠΎ-мноТСствСнных ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅ΠΉ (p = 0,0299), ΠΌΡƒΡ†ΠΈΠ½ΠΎΠ·Π½ΠΎΠ³ΠΎ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚Π° (p <0,0001), Π»ΠΈΠΌΡ„ΠΎΡ†ΠΈΡ‚ΠΎΠ², ΠΈΠ½Ρ„ΠΈΠ»ΡŒΡ‚Ρ€ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… ΠΎΠΏΡƒΡ…ΠΎΠ»ΡŒ (p <0,0001), ΠšΡ€ΠΎΠ½-подобная рСакция (p = 0,0006), Π° Ρ‚Π°ΠΊΠΆΠ΅ низкая ΡΡ‚Π΅ΠΏΠ΅Π½ΡŒ Π΄ΠΈΡ„Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΡ€ΠΎΠ²ΠΊΠΈ (p = 0,0025). Π£ Π±ΠΎΠ»ΡŒΠ½Ρ‹Ρ… Ρ€Π°ΠΊΠΎΠΌ Ρ‚Π΅Π»Π° ΠΌΠ°Ρ‚ΠΊΠΈ с микросатСллитной Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΡŒΡŽ Π±Ρ‹Π»ΠΈ ΠΎΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½Ρ‹ эндомСтриоидная Π°Π΄Π΅Π½ΠΎΠΊΠ°Ρ€Ρ†ΠΈΠ½ΠΎΠΌΠ° (p = 0,047), Π»ΠΈΠΌΡ„ΠΎΡ†ΠΈΡ‚Ρ‹, ΠΈΠ½Ρ„ΠΈΠ»ΡŒΡ‚Ρ€ΡƒΡŽΡ‰ΠΈΠ΅ ΠΎΠΏΡƒΡ…ΠΎΠ»ΡŒ (p = 0,0022) ΠΈ ΠΊΡ€ΠΈΠ±Ρ€ΠΈΡ„ΠΎΡ€ΠΌΠ½Ρ‹ΠΉ Ρ‚ΠΈΠΏ строСния ΠΎΠΏΡƒΡ…ΠΎΠ»Π΅ΠΉ (p = 0,0011).Π—Π°ΠΊΠ»ΡŽΡ‡Π΅Π½ΠΈΠ΅. ΠžΠ±Ρ‰ΠΈΠΌ ΠΏΠ°Ρ‚Ρ‚Π΅Ρ€Π½ΠΎΠΌ для ΠΊΠΎΠ»ΠΎΡ€Π΅ΠΊΡ‚Π°Π»ΡŒΠ½ΠΎΠ³ΠΎ Ρ€Π°ΠΊΠ° ΠΈ Ρ€Π°ΠΊΠ° Ρ‚Π΅Π»Π° ΠΌΠ°Ρ‚ΠΊΠΈ являСтся Π½Π°Π»ΠΈΡ‡ΠΈΠ΅ Π»ΠΈΠΌΡ„ΠΎΡ†ΠΈΡ‚ΠΎΠ², ΠΈΠ½Ρ„ΠΈΠ»ΡŒΡ‚Ρ€ΡƒΡŽΡ‰ΠΈΡ… ΠΎΠΏΡƒΡ…ΠΎΠ»ΡŒ. Клинико-морфологичСскиС особСнности Π½ΠΎΠ²ΠΎΠΎΠ±Ρ€Π°Π·ΠΎΠ²Π°Π½ΠΈΠΉ Π΄Π°Π½Π½Ρ‹Ρ… Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°Ρ†ΠΈΠΉ позволят Π²Ρ‹ΡΠ²ΠΈΡ‚ΡŒ ΠΏΠ°Ρ†ΠΈΠ΅Π½Ρ‚ΠΎΠ² с опухолями с ΠΌΠΈΠΊΡ€ΠΎΡΠ°Ρ‚Π΅Π»Π»ΠΈΡ‚Π½ΠΎΠΉΒ Π½Π΅ΡΡ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΡŒΡŽ ΠΈ провСсти Π² дальнСйшСм ΠΈΠΌΠΌΡƒΠ½ΠΎΡ‚Π΅Ρ€Π°ΠΏΠΈΡŽ
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