Лучевые методы в диагностике и стадировании рака желудка

Purpose. To assess the possibilities of methods of radiation diagnosis in the recognition and staging of gastric cancer.Material and methods. The results of inspection of 307 patients with cancer of a stomach at which endoscopic, radiological and computer tomography researches on purpose, both primary diagnosis of gastric cancer, and establishment of a staging of process have been executed have been analyzed from 2014 to 2017.Results. At a radiological research proximal cancer of a stomach is revealed at 63 (20,5%) patients, a body – at 202 (65.8%) and distally – at 42 (13.7%) patients. In all cases we managed to diagnose precisely stomach cancer, its localization and distribution on stomach walls. MSCT allowed to determine the spread of the tumor beyond the organ. Results of comprehensive examination of patients with cancer of a stomach have allowed to stage the process. The first stage has been established at 40 (13.0%) patients, second – at the 117 (38.2%), third – at the 102 (33.2%), fourth – at 48 (15.6%). Of the 307 patients with gastric cancer, various types of interventions were subsequently performed in 254 (83%), chemotherapy, as an independent type of treatment was performed in 49 (16%), refused any treatment of 4 (1%) patients.Conclusion. Complex radiation diagnosis is highly informative for the detection and staging of stomach cancer.Цель исследования: оценить возможности лучевой диагностики в распознавании и стадировании рака желудка.Материал и методы. Проанализированы результаты обследования 307 больных раком желудка, у которых были выполнены эндоскопические, рентгенологические и компьютерно-томографические исследования с целью как первичной диагностики рака желудка, так и установления стадии процесса, пролеченных за период с 2014 по 2017 г.Результаты. При рентгенологическом исследовании проксимальный рак желудка выявлен у 63 (20,5%) больных, тела – у 202 (65,8%) и дистальный – у 42 (13,7%) больных. Во всех случаях нам удалось точно диагностировать рак желудка, установить его локализацию и распространение по стенкам желудка. МСКТ позволила определить распространение опухоли за пределы органа. В результате комплексного лучевого обследования больных раком желудка удалось установить стадию процесса. I стадия была выявлена у 40 (13,0%) больных, II – у 117 (38,2%), III – у 102 (33,2%), IV – у 48 (15,6%). Из 307 больных раком желудка в последующем были выполнены различные виды хирургических вмешательств у 254 (83%), химиотерапия, как самостоятельный вид лечения выполнялась у 49 (16%), отказались от какого-либо лечения, 4 (1%) больных.Заключение. Комплексная лучевая диагностика высокоинформативна для выявления и стадирования рака желудка

Анализ экспрессии матричной РНК панели генов морфологически неизмененного эпителия прямой кишки как метод ранней диагностики патологии толстой кишки

Introduction. The absence of specific clinical symptoms in the early stages of colorectal cancer development leads to the fact that a quarter of patients who seek help for the first time have a metastatic stage of the disease. For the timely detection of pre-tumor disorders or hidden foci of malignancy, the possibilities of modern molecular biological technologies are being actively studied today.Aim. To develop a method for diagnosing tumor diseases of the colon based on molecular genetic analysis of morphologically unchanged intestinal epithelium distant from the focus of the tumor lesion.Materials and methods. We examined the matrix RNA (mRNA)  expression profile of 63 candidate genes potentially associated with the pathogenesis of neoplastic changes in rectal mucosal samples. Samples were obtained during prophylactic and/or diagnostic video colonoscopy of 122 patients, 41 of whom had no history of breast cancer (“Normal”), 32 patients were diagnosed with breast cancer polyps (“Polyposis”) and 49 patients were diagnosed with breast cancer (“colorectal cancer”). mRNA expression was assessed by reverse transcription polymerase chain reaction.Results. Using the discriminant analysis method, it was established that  the cellular material of scrapings from the rectum in the “colorectal cancer” group reliably, with a classification accuracy above 96 %, differs in expression phenotype from the “Normal” and “Polyposis” groups.Conclusion. The data obtained are a prerequisite for the development of a minimally invasive diagnostic method that can be used as part of an outpatient  examination to assess the risk of colon tumor disease.Введение. Отсутствие специфических  клинических симптомов на ранних стадиях развития колоректального рака приводит к тому, что четверть пациентов, впервые обращающихся за помощью, имеют метастатическую стадию заболевания. Для своевременного обнаружения предопухолевых нарушений или скрытых очагов малигнизации сегодня активно изучаются возможности современных молекулярно-биологических технологий.Цель исследования – разработка метода диагностики опухолевых заболеваний толстой кишки на основе молекулярно-генетического анализа морфологически неизмененного кишечного эпителия, отдаленного от очага опухолевого поражения.Материалы и методы. Исследован профиль экспрессии матричной РНК (мРНК) 63 генов-кандидатов, потенциально связанных с патогенезом неопластических изменений, в образцах слизистой оболочки прямой кишки. Образцы получены в ходе профилактической и/или диагностической видеоколоноскопии 122 пациентов, из которых у 41 в анамнезе не было заболеваний толстой кишки (группа «Норма»), у 32 – установлен диагноз «полипы толстой кишки» (группа «полипоз»), у 49 – диагноз «карцинома толстой кишки» (группа «колоректальный рак»). Экспрессию мРНК оценивали методом полимеразной цепной реакции с обратной транскрипцией.Результаты. С помощью дискриминантного  анализа установлено, что клеточный материал соскобов из прямой кишки в группе колоректального рака достоверно, с точностью выше 96 %, отличается  по экспрессионному фенотипу от групп нормы и полипоза.Заключение. Полученные данные являются предпосылкой к разработке малоинвазивного метода диагностики, который может быть использован в рамках амбулаторного обследования для оценки риска наличия опухолевого заболевания толстой кишки

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants.

This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.3448Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, with limited therapeutic options. Here we report on a study of >12 million variants, including 163,714 directly genotyped, mostly rare, protein-altering variants. Analyzing 16,144 patients and 17,832 controls, we identify 52 independently associated common and rare variants (P < 5 × 10(-8)) distributed across 34 loci. Although wet and dry AMD subtypes exhibit predominantly shared genetics, we identify the first genetic association signal specific to wet AMD, near MMP9 (difference P value = 4.1 × 10(-10)). Very rare coding variants (frequency <0.1%) in CFH, CFI and TIMP3 suggest causal roles for these genes, as does a splice variant in SLC16A8. Our results support the hypothesis that rare coding variants can pinpoint causal genes within known genetic loci and illustrate that applying the approach systematically to detect new loci requires extremely large sample sizes.We thank all participants of all the studies included for enabling this research by their participation in these studies. Computer resources for this project have been provided by the high-performance computing centers of the University of Michigan and the University of Regensburg. Group-specific acknowledgments can be found in the Supplementary Note. The Center for Inherited Diseases Research (CIDR) Program contract number is HHSN268201200008I. This and the main consortium work were predominantly funded by 1X01HG006934-01 to G.R.A. and R01 EY022310 to J.L.H

Исследование уровня экспрессии генов-маркеров пролиферативной активности в слизистой оболочке толстой кишки при различной патологии

Background. The search for molecular markers of colon diseases allowing highly specific and sensitive identification and differentiation of pathological processes is a clinically important problem. Expression levels of genes responsible for proliferation can reflect the changes in the affected tissues. The study objective is to perform comparative analysis of molecular and genetic markers of proliferative activity in benign and malignant neoplasms of the colon. Materials and methods. Analysis of the changes in proliferation markers (CCND1, с-MYC, Ki-67, HER2neu, TERT) in adenocarcinoma of the colon (n = 259), resection margin (about 15–20 cm from the tumor lesion) (n = 251), unchanged colon mucosa from healthy donors (n = 247), polyps (n = 28), unchanged colon mucosa intestinal polyposis (10–15 cm from the polyp) (n = 75) was performed using RT-PCR. Results and conclusion. It was shown that morphologically unchanged tissue of intestinal mucosa in malignant tumors has significant differences from normal tissue of healthy donors. Significant differences in the level of expression of genes responsible for the processes of proliferation, с-MYC, CCND1, TERT were found in benign hyperproliferative diseases (polyps). Moreover, these changes were specific to the type of pathological process, which allows us to consider these genes as the most promising candidates in the development of a differential method for diagnosing colon diseases.Введение. Поиск молекулярных маркеров диагностики заболеваний толстой кишки, способных с высокой чувствительностью и специфичностью выявлять и дифференцировать патологический процесс, является актуальной клинически важной задачей. Уровень экспрессии генов, ответственных за процессы пролиферации, может отражать картину изменений в тканях пораженного органа. Цель исследования – сравнительный анализ молекулярно-генетических маркеров пролиферативной активности при доброкачественных и злокачественных новообразованиях толстой кишки. Материалы и методы. Методом полимеразной цепной реакции в реальном времени проведен анализ изменений экспрессии маркеров пролиферации (CCND1, с-MYC, Ki-67, HER2neu, TERT) в следующих тканях: аденокарциномы толстой кишки (n = 259), края резекции (около 15–20 см от опухолевого узла) (n = 251), неизмененной слизистой оболочки толстой кишки здоровых доноров (n = 247), полипов (n = 28), неизмененной слизистой оболочки толстой кишки при полипах (10–15 см от полипа) (n = 75). Результаты и заключение. Установлено, что в тканях полипов толстой кишки наблюдаются достоверные различия в уровне экспрессии генов, ответственных за процессы пролиферации (с-MYC, CCND1, TERT). Выявленные различия специфичны для типа патологического процесса, что позволяет рассматривать данные гены в качестве наиболее перспективных кандидатов при разработке дифференциального метода диагностики заболеваний толстой кишки

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Method for optimizing mass and size characteristics of a high-pressure turbine disk

The article presents the results of weight and size optimization of a high-pressure turbine working disk for an augmented turbofan. The issues of modeling the operation of the engines first stage with a cover plate providing the delivery of cooling air to the blades are considered. Strength calculation of the stresses arising from the action of centrifugal forces under high-temperature conditions was carried out. A three-dimensional model of the disc was obtained. The finite element method was used. The pattern of temperature distribution in the disk body was obtained on the basis of heat calculation. Based on the strength calculation, the stresses and strains of the turbine disk were determined. Maximum stresses in the disc are located at the junction of the disc frontal area and the cooling air feed holes. Plastic deformation is observed in the area of the cavities for cooling air feed. It is shown that the stepped part of the disc should be made of a material with lower heat resistance and a higher value of permissible limit stress. Based on the study, a bimetallic disk design made by powder metallurgy was proposed