Особенности тестирования мутаций BRCA1 / 2 у больных распространенным HER2-негативным раком молочной железы в Российской Федерации (результаты опроса онкологов России)

Hereditary BRCA1 / 2 mutations affect the strategy of surgical treatment in early cancer and systemic treatment in advanced HER2-negative breast cancer. The article presents the results of a survey of Russian oncologists on various aspects of genetic testing for hereditary BRCA1 / 2 mutations in real-world clinical practice. Indications for testing, testing methods, and funding sources were discussed.Наличие у пациентов наследственных мутаций в генах BRCA1 / 2 влияет на тактику хирургического лечения при раннем раке и лекарственного лечения при распространенном HER2-негативном раке молочной железы. В статье представлены результаты опроса российских онкологов, посвященного различным аспектам генетического тестирования на наследственные мутации в генах BRCA1/ 2 в реальной клинической практике. Обсуждены вопросы показаний к тестированию, методы тестирования, источники финансирования

QUALITY OF LIFE EVALUATION IN RECIPIENTS AFTER KIDNEY TRANSPLANTATION

Quality of life analysis of kidney graft recipients includes complex assessment of physical, psychological and social status and also certain laboratory and clinical studies. However we suppose that significance of the study might increase considerably if it would be multicenter. The objective of the present publication is to organize such a multicenter study. Obviously, quality of life of recipients with functioning transplanted kidney is undoubtedly of scientific interest and needs further extended studies that might contribute to better interpretation of long-term results after kidney transplantation

Markers of early cardiotoxicity in patients with breast cancer undergoing chemotherapy depending on blood pressure level

Objective. To study the possibility of the 2D Speckle Tracking Imaging in early detection of cardiotoxicity in patients with triple negative breast cancer and arterial hypertension (AH) during anthracycline-containing chemotherapy. Materials and methods. 70 women (mean age 48.6±13.3 years) with triple negative breast cancer were enrolled. All patients underwent chemotherapy, including anthracycline, taxan, platinum-based agent. Echocardiography, including 2D Speckle Tracking Imaging, was performed on Vivid-E 9 ultrasound machine before and after 8 weeks of chemotherapy. Left ventricular ejection fraction (LVEF) (the biplane Simpson`s method) and global longitudinal strain (GLS) (mean normal GLS of -22.1±1.8 for women) were analysed. Patients were divided into two groups: group 1 - with AH (n=18) and group 2 - with normal blood pressure (n=52). Results. Before chemotherapy in group 1 GLS was lower than normal value (-19.1±2.8% vs -22.1±1.8%; p0.05). After chemotherapy in all patients GLS decrease was observed from -20.0±2.8% to -18.5±2.9% (

НЕКОТОРЫЕ АСПЕКТЫ ИЗУЧЕНИЯ КАЧЕСТВА ЖИЗНИ РЕЦИПИЕНТОВ ПОСЛЕ ТРАНСПЛАНТАЦИИ ПОЧКИ

Quality of life analysis of kidney graft recipients includes complex assessment of physical, psychological and social status and also certain laboratory and clinical studies. However we suppose that significance of the study might increase considerably if it would be multicenter. The objective of the present publication is to organize such a multicenter study. Obviously, quality of life of recipients with functioning transplanted kidney is undoubtedly of scientific interest and needs further extended studies that might contribute to better interpretation of long-term results after kidney transplantation. Анализ качества жизни реципиентов почечных трансплантатов предполагает комплексную оценку физи- ческого, психологического и социального статуса. Он также включает ряд лабораторно-клинических по- казателей. Однако мы полагаем, что достоверность исследования могла бы существенно возрасти, если бы оно носило многоцентровой характер. Целью настоящей публикации является организация такого многоцентрового исследования. Очевидно, что изучение качества жизни реципиентов с функционирую- щей трансплантированной почкой представляет несомненный научный интерес и требует в дальнейшем расширения исследований, что способствовало бы лучшей интерпретации результатов, характерных для отдаленного периода после трансплантации почки.

Influence of the Water Content on the Diffusion Coefficients of Li⁺ and Water across Naphthalenic Based Copolyimide Cation-Exchange Membranes

The transport of lithium ions in cation-exchange membranes based on sulfonated copolyimide membranes is reported. Diffusion coefficients of lithium are estimated as a function of the water content in membranes by using pulsed field gradient (PFG) NMR and electrical conductivity techniques. It is found that the lithium transport slightly decreases with the diminution of water for membranes with water content lying in the range 14 < λ < 26.5, where λ is the number of molecules of water per fixed sulfonate group. For λ < 14, the value of the diffusion coefficient of lithium experiences a sharp decay with the reduction of water in the membranes. The dependence of the diffusion of lithium on the humidity of the membranes calculated from conductivity data using Nernst–Planck type equations follows a trend similar to that observed by NMR. The possible explanation of the fact that the Haven ratio is higher than the unit is discussed. The diffusion of water estimated by 1H PFG-NMR in membranes neutralized with lithium decreases as λ decreases, but the drop is sharper in the region where the decrease of the diffusion of protons of water also undergoes considerable reduction. The diffusion of lithium ions computed by full molecular dynamics is similar to that estimated by NMR. However, for membranes with medium and low concentration of water, steady state conditions are not reached in the computations and the diffusion coefficients obtained by MD simulation techniques are overestimated. The curves depicting the variation of the diffusion coefficient of water estimated by NMR and full dynamics follow parallel trends, though the values of the diffusion coefficient in the latter case are somewhat higher. The WAXS diffractograms of fully hydrated membranes exhibit the ionomer peak at q = 2.8 nm⁻1, the peak being shifted to higher q as the water content of the membranes decreases. The diffractograms present additional peaks at higher q, common to wet and dry membranes, but the peaks are better resolved in the wet membranes. The ionomer peak is not detected in the diffractograms of dry membranes.The authors acknowledge financial support provided by the DGICYT (Dirección General de Investigación Cientifíca y Tecnológica) through Grant MAT2011-29174-C02-02

Thrombospondin-4 is a putative tumour-suppressor gene in colorectal cancer that exhibits age-related methylation

<p>Abstract</p> <p>Background</p> <p><it>Thrombospondin-4 </it>(<it>THBS4</it>) is a member of the extracellular calcium-binding protein family and is involved in cell adhesion and migration. The aim of this study was to evaluate the potential role of deregulation of <it>THBS4 </it>expression in colorectal carcinogenesis. Of particular interest was the possible silencing of expression by methylation of the CpG island in the gene promoter.</p> <p>Methods</p> <p>Fifty-five sporadic colorectal tumours stratified for the CpG Island Methylator Phenotype (CIMP) were studied. Immunohistochemical staining of THBS4 protein was assessed in normal and tumour specimens. Relative levels of <it>THBS4 </it>transcript expression in matched tumours and normal mucosa were also determined by quantitative RT-PCR. Colony forming ability was examined in 8 cell lines made to overexpress THBS4. Aberrant promoter hypermethylation was investigated as a possible mechanism of gene disruption using MethyLight. Methylation was also assessed in the normal colonic tissue of 99 patients, with samples biopsied from four regions along the length of the colon.</p> <p>Results</p> <p><it>THBS4 </it>expression was significantly lower in tumour tissue than in matched normal tissue. Immunohistochemical examination demonstrated that THBS4 protein was generally absent from normal epithelial cells and tumours, but was occasionally expressed at low levels in the cytoplasm towards the luminal surface in vesicular structures. Forced THBS4 over-expression caused a 50-60% repression of tumour colony growth in all eight cell lines examined compared to control cell lines. Tumours exhibited significantly higher levels of methylation than matched normal mucosa, and <it>THBS4 </it>methylation correlated with the CpG island methylator phenotype. There was a trend towards decreased gene expression in tumours exhibiting high <it>THBS4 </it>methylation, but the correlation was not significant. <it>THBS4 </it>methylation was detectable in normal mucosal biopsies where it correlated with increasing patient age and negatively with the occurrence of adenomas elsewhere in the colon.</p> <p>Conclusions</p> <p><it>THBS4 </it>shows increased methylation in colorectal cancer, but this is not strongly associated with altered gene expression, either because methylation has not always reached a critical level or because other factors influence <it>THBS4 </it>expression. <it>THBS4 </it>may act as a tumour suppressor gene, demonstrated by its suppression of tumour colony formation <it>in vitro</it>. <it>THBS4 </it>methylation is detectable in normal colonic mucosa and its level may be a biomarker for the occurrence of adenomas and carcinoma.</p

Роль неоадъювантного подхода в лечении первично операбельного HER2-позитивного рака молочной железы

Neoadjuvant systemic therapy is an essential component of the comprehensive treatment of primary operable HER2‑positive breast cancer. Therefore, it is extremely important to search for treatment efficacy predictors and optimal system for assessing tumor response to treatment. The study analyzed factors predicting pathological complete response (pCR) in patients with luminal and non‑luminal HER2‑positive tumor subtypes. The morphological assessment of the tumor response to treatment was carried out using the RCB system; additional characteristics of the residual tumor were studied as well. It was shown that a comprehensive assessment involving the use of the RCB system and determination of the Ki ‑ 67 level helps to divide patients into prognostic groups and individualize the adjuvant therapy plan.Неоадъювантная системная терапия является важной составляющей комплексного лечения первично операбельного HER2-позитивного рака молочной железы (РМЖ). В связи с этим чрезвычайно важным представляется поиск факторов, предсказывающих эффективность лечения, а также оптимальной системы оценки ответа опухоли. В исследовании проведен анализ факторов, предсказывающих достижение полной патоморфологической регрессии (пПР) при люминальном и нелюминальном HER2-позитивных подтипах. Морфологическая оценка ответа опухоли на лечение проводилась по системе RCB, также изучены дополнительные характеристики резидуальной опухоли. Показано, что комплексная оценка, включающая систему RCB и уровень Ki67, позволяет разделить больных на прогностические группы и индивидуализировать тактику адъювантной терапии

Лекарственные препараты, отпущенные больным раком молочной железы в рамках программ лекарственного обеспечения населения

The purpose of our research was to analyze the actual practice of medicine in patients with breast cancer in various regions of the Russian Federation in the framework of state programs of drug provision (procurement of essential drugs (EDPP) and of regional benefits (RBP)).Materials and Methods. We collected data on dispensed medicines from 42 regions of the Russian Federation, which accounted for 57.58% of the total population and 58.20% of the total number of breast cancer patients who had been registered in the oncological institutions of the Russian Federation in 2013. We collected and studied data on the antineoplastic agents (L01) and hormonal antineoplastic drugs (L02) dispensed through programs of drug supply from federal and regional budgets in 2013 in the regions of the Russian Federation for patients with a diagnosis of «malignant neoplasm of the breast» (C50 International Classification of Diseases, 10th revision).Results. The number of drugs prescribed to patients with breast cancer in studied regions ranged from 3 to 39 INNs. Among the most commonly used antineoplastic agents were trastuzumab and capecitabine (both used in 92.86% of the regions), and among hormonal antineoplastic drugs were aromatase inhibitors and tamoxifen (95.24% and 100% of the regions of the Russian Federation). Consumption of drugs varied significantly between theregions.Conclusion. Our study revealed significant differences in the consumption of antineoplastic medications among outpatients with breast cancer in different regions of the Russian Federation whose care was funded by federal and regional budgets.Цель исследования – анализ реальной практики лекарственного обеспечения больных раком молочной железы (РМЖ) в субъектах РФ в рамках программ лекарственного обеспечения (обеспечения основными лекарственными средствами (ОНЛП) и региональной льготы).Материалы и методы. Собраны данные об отпущенных лекарственных препаратах в 42 субъектах РФ, в которых проживает 57,58% от общей численности населения страны и 58,20% от общего числа женщин, больных РМЖ и состоявших на учете в онкологических учреждениях РФ в 2013 г. Изучены данные о противоопухолевых (L01) и противоопухолевых гормональных (L02) лекарственных препаратах, отпущенных в 2013 г. в субъектах РФ больным с диагнозом «злокачественные новообразования молочной железы» (C50 по международной классификации болезней 10-го пересмотра) в рамках программ лекарственного обеспечения за счет средств федерального и регионального бюджетов. Проанализировано потребление лекарственных препаратов, включенных и не включенных в стандарты медицинской помощи, перечни лекарственных препаратов, клинические рекомендации.Результаты. Количество препаратов, закупленных для больных РМЖ, варьировало в субъектах от трех до 39 МНН. Наиболее часто используемые противоопухолевые препараты – капецитабин и трастузумаб (использовались в 92,9% регионов), гормональные – ингибиторы ароматазы (анастрозол, летрозол, эксеместан) и тамоксифен (в 95,2-100% субъектов РФ). Потребление лекарственных препаратов значительно варьирует между регионами. В рамках программ лекарственного обеспечения закупались препараты как включенные, так и не включенные в перечни, стандарты и клинические рекомендации.Заключение. Выявлены значительные расхождения в потреблении лекарственной терапии среди больных РМЖ в различных регионах РФ в рамках лекарственного обеспечения льготных категорий граждан в амбулаторных условиях, а также потребление лекарственных препаратов, не упомянутых в клинических рекомендациях и не включенных в стандарты медицинской помощи и перечни лекарственных препаратов