No abstract

e15023 Background: Long non-coding RNAs (lncRNA) play an important role in many biological processes, and their dysregulation can lead to various diseases, including colorectal cancer (CRC). In recent years, interactions between lncRNA, miRNA and mRNAs in development of CRC have attracted more and more attention. However, the currently obtained data on the complex regulatory interactions between lncRNA and microRNA during metastasis in patients with CRC are fragmentary, often contradictory and obtained on samples that are not significant in size. Therefore, the aim of the study was to analyze the features of lncRNA expression in CRC patients without metastases, with lymph nodes metastases and with liver metastases. Methods: The study included 200 patients with colon adenocarcinoma. The patients were divided into 3 groups: without metastases (T2N0MO, group 1, n = 100), with lymph node metastases (T2-3N1-2M0, group 2, n = 60) and with liver metastases (T3N2M1-2, group 3, n = 40). RNA isolation was performed by guanidine-thiocyanate-phenol-chloroform extraction. The lncRNA list was generated based on bioinformatic analysis. The relative expression of 20 lncRNAs (NEAT1, HELLPAR, AP000766.1, LINC00265, MIRLET7BHG, OLMALINC, AC245884.8, MEOX2-AS1, MEG3, NORAD, HCG11, WASIR2, AC005332.7, PURLN, OIP5-AS1, SNHG14, TUG1, XIST, MALAT1, FAM66E) was evaluated by RT-qPCR method. Differences were assessed using the Mann-Whitney test, and the Bonferroni correction was used to correct multiple comparisons. Results: Differential expression of 5 lncRNA (MALAT1, TUG1, XIST, LINC00265, HELLPAR) was found between CRC patients without metastases and patients with metastases to lymph nodes and liver. Thus, in group 1, expressions of MALAT1, TUG1 and HELLPAR were lower by 2.5, 4.0 and 5.5 times (p < 0.005) than in combined group of patients with metastases to lymph nodes and liver, and XIST and LINC00265 expressions were higher by 2.2 and 3.4 times (p < 0.05), respectively. Differential expression of 2 lncRNA (NORAD, WASIR2) was also found between group 2 and group 3. The NORAD expression in patients in group 3 was 5.5 times (p < 0.05) lower than in patients in group 2, and WASIR2 expression, on the contrary, was 2.5 times (p < 0.05) higher in patients in group 3. Conclusions: Thus, differential expression of lncRNA (MALAT1, TUG1, XIST, LINC00265, HELLPAR, NORAD and WASIR2), associated with regulation of proliferation and invasive ability of tumor cells, was found in 3 groups of CRC patients.

Лучевая терапия является одним из методов лечения аденокарциномы толстой кишки. Большое влияние на эффективность подобной терапии оказывает радиорезистентность опухолевых клеток, зависящая от их молекулярно-генетических особенностей, к которым относится показатель копийности генов (CNV). Целью работы явилось исследование влияния копийности генов, ответственных за репарации ДНК, регуляцию клеточного цикла и апоптоза, на радиорезистентность клеток линии HT-29 в условиях воздействия стандартных доз лучевой терапии 5 и 7 Гр на протяжении 5 дней. Культивирование клеток HT-29 проходило в стерильных флаконах в среде RPMI-1640 c 10%-ной фетальной телячьей сывороткой и 50 мкг/мл гентамицина. Облучение проводили на линейном ускорителе Novalis TX. Определение относительной копийности 32 генетических локусов (AKT, ATM, BRIP, BRCA1, BRCA2, CDK1, CDKN1B, CCND1 и др.) проводили методом Real-Time qPCR. На разных уровнях кластеризации выявлено сходство по уровню копийности некоторых генов в интактных и облученных образцах. Получены данные о дифференциальном показателе копийности 5 генов в интактных и облученных при 5 и 7 Гр клетках HT-29. В клетках НТ-29, подвергнутых облучению 7 Гр, статистически значимо была повышена копийность генов BRCA2, H2AX, CASP9 и RBBP8: в 2,5 раза; 3,2 раза; 1,6 раза и 1,6 раза соответственно (р<0,05), и снижена копийность гена BCL2 в 3,6 раза (р<0,05) относительно интактных клеток. В клетках НТ-29, подвергнутых облучению 5 Гр, статистически значимо была повышена копийность CASP9 и RBBP8-в 1,5 и 1,4 раза соответственно (р<0,05). Таким образом, проведенное исследование позволило установить, что линия клеток НТ-29 исходно гетерогенна по копийности некоторых генов и лучевая терапия приводит к селективному выживанию клеток, обладающих повышенной копийностью генов BRCA2, H2AX, RBBP8 CASP9 и сниженной копийностью гена BCL2. Ключевые слова: лучевая терапия, аденокацинома толстой кишки, культура клеток, апоптоз, репарация ДНК, радиорезистентность, копийность генов.

e17514 Background: Malignant pelvic tumors account for more than 25% of cancer incidence in Russia. Radiation therapy is the most common treatment for such patients; however, 10-15% of patients develop radiation-induced complications of the pelvic organs, and more effective treatments are required to manage these complications. Methods: The study included 30 patients with cervical cancer T3NхM0 after combination treatment. 7-10 months after combined radiation treatment (total radiation dose to the primary focus 80 Gy), patients developed erosive ulcerative radiation rectitis (RTOG grade 1 and 2). Patients were divided into 2 groups: main group (n = 15) – conservative treatment combined with LILEDR. Each course included 10 LILEDR sessions, the red spectrum λ = 640 nm on the cubital vein projection (exposure time 5 minutes, dose 6.86 J/cm2) and locally on the ulcerated zones (exposure time 3 minutes, dose 3.96 J/cm2). Patients received 2 LILEDR courses with a 1-month interval. The control group received only conservative therapy. Results: Main clinical manifestations of rectitis (tenesmus, bloody mucous discharge) disappeared in the main group already on the 3-4th day of the first course, epithelialization of ulcerative defects occurred in a shorter period of 7-10 days. Soft superficial scars not causing rectal stenosis formed at the site of the ulcer by the end of LILEDR courses. The control group showed long periods of the ulcer epithelialization up to 30 days, late remission and a lingering recurrent character of the disease. Conclusions: LILEDR in combination with the main conservative therapy allows rapid managing with the clinical symptoms of radiation rectitis and regression of disorders developed after the complex treatment, which improves the quality of life of patients and shortens the rehabilitation period.

No abstract