The opposite association of HRAS and KRAS mutations with clinical variables of bladder cancer

HRAS, KRAS and NRAS gene products belong to the superfamily of small GTPases. These proteins regulate cellular response to extracellular stimuli by means of activation of different signaling pathways. Although the role of RAS gene mutations in the pathogenesis of various human cancers has been established, the clinical significance of these molecular alterations in bladder cancer remains unclear. The aim of this study was to determine the frequency and spectrum of HRAS, KRAS and NRAS mutations, to analyze their relationships with clinicopathological variables and to determine the prognostic value of these alterations in terms of recurrence, progression and mortality, in a prospective cohort of 249 bladder cancer patients. The frequency of RAS mutations detected by the SNaPshot method, was found to be 11.2 %, of which HRAS mutations accounted for 64.3 %, KRAS, for 28.6 % and NRAS, for 7.1 %. We failed to find any correlation between all RAS mutations and pathomorphological characteristics. However, when analyzed separately, HRAS and KRAS mutations were for the first time shown to be associated with the opposite clinical parameters of bladder cancer: HRAS mutations were significantly associated with low-stage low-grade papillary tumors of a small size (р < 0.05), whereas KRAS mutations were associated with non-papillary urothelial carcinomas and the presence of metastasis (р < 0.05). Analysis of the prognostic value of molecular alterations revealed an association of KRAS mutations with decreased cancer-specific survival in both the whole group of patients and the subgroup with non-muscle invasive disease. The data obtained suggest that HRAS and KRAS gene mutations may characterize alternative pathways of bladder cancer pathogenesis: HRAS mutations indicating benign and KRAS mutations, aggressive disease course

ВОЗМОЖНОСТИ ТЕЛЕМЕДИЦИНСКИХ ТЕХНОЛОГИЙ В ЛУЧЕВОЙ ДИАГНОСТИКЕ

The paper reviewed the definition of terminology and the history of the development of telemedicine. The main directions of development of telemedicine technologies in Russia and abroad. Provides information about the different areas of information and communication technologies in health care. Presented as a variety of telemedicine services for medical purposes. The main problem hindering the development of Telemedicine and Medical Radiology in particular.В работе рассмотрены терминология и история развития телемедицины в России и за рубежом. Указаны сведения о различных направлениях применения информационно-телекоммуникационных технологий в здравоохранении. Представлены разновидности телемедицины как услуги медицинского назначения. Приведены основные проблемы, сдерживающие развитие телемедицины и телерадиологии в частности

Evaluation of methods for detection of fluorescence labeled subcellular objects in microscope images

<p>Abstract</p> <p>Background</p> <p>Several algorithms have been proposed for detecting fluorescently labeled subcellular objects in microscope images. Many of these algorithms have been designed for specific tasks and validated with limited image data. But despite the potential of using extensive comparisons between algorithms to provide useful information to guide method selection and thus more accurate results, relatively few studies have been performed.</p> <p>Results</p> <p>To better understand algorithm performance under different conditions, we have carried out a comparative study including eleven spot detection or segmentation algorithms from various application fields. We used microscope images from well plate experiments with a human osteosarcoma cell line and frames from image stacks of yeast cells in different focal planes. These experimentally derived images permit a comparison of method performance in realistic situations where the number of objects varies within image set. We also used simulated microscope images in order to compare the methods and validate them against a ground truth reference result. Our study finds major differences in the performance of different algorithms, in terms of both object counts and segmentation accuracies.</p> <p>Conclusions</p> <p>These results suggest that the selection of detection algorithms for image based screens should be done carefully and take into account different conditions, such as the possibility of acquiring empty images or images with very few spots. Our inclusion of methods that have not been used before in this context broadens the set of available detection methods and compares them against the current state-of-the-art methods for subcellular particle detection.</p

Objective comparison of methods to decode anomalous diffusion

Deviations from Brownian motion leading to anomalous diffusion are found in transport dynamics from quantum physics to life sciences. The characterization of anomalous diffusion from the measurement of an individual trajectory is a challenging task, which traditionally relies on calculating the trajectory mean squared displacement. However, this approach breaks down for cases of practical interest, e.g., short or noisy trajectories, heterogeneous behaviour, or non-ergodic processes. Recently, several new approaches have been proposed, mostly building on the ongoing machine-learning revolution. To perform an objective comparison of methods, we gathered the community and organized an open competition, the Anomalous Diffusion challenge (AnDi). Participating teams applied their algorithms to a commonly-defined dataset including diverse conditions. Although no single method performed best across all scenarios, machine-learning-based approaches achieved superior performance for all tasks. The discussion of the challenge results provides practical advice for users and a benchmark for developers. Deviations from Brownian motion leading to anomalous diffusion are ubiquitously found in transport dynamics but often difficult to characterize. Here the authors compare approaches for single trajectory analysis through an open competition, showing that machine learning methods outperform classical approaches

Objective comparison of methods to decode anomalous diffusion

Deviations from Brownian motion leading to anomalous diffusion are found in transport dynamics from quantum physics to life sciences. The characterization of anomalous diffusion from the measurement of an individual trajectory is a challenging task, which traditionally relies on calculating the trajectory mean squared displacement. However, this approach breaks down for cases of practical interest, e.g., short or noisy trajectories, heterogeneous behaviour, or non-ergodic processes. Recently, several new approaches have been proposed, mostly building on the ongoing machine-learning revolution. To perform an objective comparison of methods, we gathered the community and organized an open competition, the Anomalous Diffusion challenge (AnDi). Participating teams applied their algorithms to a commonly-defined dataset including diverse conditions. Although no single method performed best across all scenarios, machine-learning-based approaches achieved superior performance for all tasks. The discussion of the challenge results provides practical advice for users and a benchmark for developers

МЕТИЛИРОВАНИЕ ГЕНА RUNX3 КАК ФАКТОР ПРОГНОЗА ПРИ РАКЕ МОЧЕВОГО ПУЗЫРЯ БЕЗ МЫШЕЧНОЙ ИНВАЗИИ

The analysis of the RUNX3 gene methylation status was conducted in the prospective group of 262 bladder cancer patients. In comparison to normal urothelium, a high frequency (63 %) of RUNX3 promoter hypermethylation was observed in tumor tissues. А statistically significant association of RUNX3 epigenetic abnormalities with a more aggressive tumor phenotype – an advanced tumor stage and grade, as well as a large tumor size – was found. We have shown that RUNX3 hypermethylation is an independent risk factor for progression and cancer-specific survival in the group of patients with non-muscle invasive bladder cancer.Проведен анализ статуса метилирования гена RUNX3 в проспективной группе из 262 пациентов, страдающих раком мочевого пузыря (РМП). В отличие от нормального уротелия, в опухолевых клетках мочевого пузыря наблюдалась высокая частота гиперметилирования промоторной области гена RUNX3, равная 63 %. Выявлена статистически значимая ассоциация эпигенетических нарушений исследуемого гена с агрессивным опухолевым фенотипом: высокой степенью распространения, низкой степенью дифференцировки и большими размерами опухоли. Установлено, что гиперметилирование гена RUNX3 являлось независимым фактором риска в отношении прогрессирования и онкоспецифической выживаемости в группе пациентов с РМП без мышечной инвазии

An objective comparison of cell-tracking algorithms

We present a combined report on the results of three editions of the Cell Tracking Challenge, an ongoing initiative aimed at promoting the development and objective evaluation of cell segmentation and tracking algorithms. With 21 participating algorithms and a data repository consisting of 13 data sets from various microscopy modalities, the challenge displays today's state-of-the-art methodology in the field. We analyzed the challenge results using performance measures for segmentation and tracking that rank all participating methods. We also analyzed the performance of all of the algorithms in terms of biological measures and practical usability. Although some methods scored high in all technical aspects, none obtained fully correct solutions. We found that methods that either take prior information into account using learning strategies or analyze cells in a global spatiotemporal video context performed better than other methods under the segmentation and tracking scenarios included in the challenge

New insights into the synergism of nucleoside analogs with radiotherapy

Nucleoside analogs have been frequently used in combination with radiotherapy in the clinical setting, as it has long been understood that inhibition of DNA repair pathways is an important means by which many nucleoside analogs synergize. Recent advances in our understanding of the structure and function of deoxycytidine kinase (dCK), a critical enzyme required for the anti-tumor activity for many nucleoside analogs, have clarified the mechanistic role this kinase plays in chemo- and radio-sensitization. A heretofore unrecognized role of dCK in the DNA damage response and cell cycle machinery has helped explain the synergistic effect of these agents with radiotherapy. Since most currently employed nucleoside analogs are primarily activated by dCK, these findings lend fresh impetus to efforts focused on profiling and modulating dCK expression and activity in tumors. In this review we will briefly review the pharmacology and biochemistry of the major nucleoside analogs in clinical use that are activated by dCK. This will be followed by discussions of recent advances in our understanding of dCK activation via post-translational modifications in response to radiation and current strategies aimed at enhancing this activity in cancer cells

ВЛИЯНИЕ МЕТИЛИРОВАНИЯ ГЕНА р16 НА РИСК ПРОГРЕССИРОВАНИЯ РАКА МОЧЕВОГО ПУЗЫРЯ БЕЗ МЫШЕЧНОЙ ИНВАЗИИ

To accurately predict the tumor behavior and individualize the treatment approach, new methods for bladder cancer (BC) prognosis are required. The most promising prognostic markers are the mutational and epigenetic changes of genes involved in maintaining cellular homeostasis. In the present study, we evaluated the influence of p16 promoter hypermethylation on the risk of recurrence, progression and disease outcome in the group of 158 BC patients. p16 epigenetic changes were found in 11.4 % of urothelial carcinomas and did not depend on clinicоmorphological characteristics. However, in the subgroup of patients with non-muscle invasive tumors, p16 abnormal methylation was significantly associated with smoking, and in the subgroup of patients with muscle-invasive BC, it was linked to a high tumor grade (G3). In the multivariate Cox regression analysis, p16 promoter hypermethylation was an independent predictor for bladder cancer progression (HR 6.84; 95 % CI 1.6–29.9; р = 0.011). The use of the data on the p16 methylation status may improve the accuracy of prognosis of the bladder cancer clinical course and the selection of appropriate treatment strategy.Для более точного предсказания поведения опухоли и индивидуализации лечебного подхода необходима разработка новых методов прогноза клинического течения рака мочевого пузыря (РМП). В качестве перспективных прогностических маркеров рассматриваются мутационные и эпигенетические изменения генов, играющих ключевую роль в поддержании клеточного гомеостаза. В настоящем исследовании проведена оценка влияния метилирования промоторной области гена р16 на риск рецидивирования, прогрессирования и неблагоприятного исхода заболевания на примере выборки из 158 пациентов с РМП. Эпигенетические изменения исследованного гена выявлены в 11,4 % уротелиальных карцином и не зависели от клинико-морфологических характеристик. Вместе с тем в подгруппе пациентов с немышечно-инвазивными опухолями аномальное метилирование р16 статистически значимо связано с курением, а в подгруппе пациентов с мышечно-инвазивным РМП – с низкой степенью дифференцировки опухоли. В многофакторном регрессионном анализе пропорциональных рисков Кокса установлено, что гиперметилирование гена р16 является независимым предиктором прогрессирования РМП без мышечной инвазии (отношение рисков 6,84; 95 % ДИ 1,6–29,9; р = 0,011). Применение данных об эпигенетической изменчивости гена р16 позволит повысить точность прогноза клинического течения рака мочевого пузыря и подобрать адекватную тактику лечения