ОЦЕНКА СОЦИАЛЬНО-ЭКОНОМИЧЕСКОГО УЩЕРБА, СВЯЗАННОГО СО СМЕРТНОСТЬЮ ОТ РАКА ОРГАНОВ ДЫХАНИЯ В ТОМСКОЙ ОБЛАСТИ В 2005–2016 ГГ.

Introduction. A significant component in the system analysis of anti-cancer activities is the assessment of the impact of mortality on life expectancy, which indicates the social and economic situation in the region.Material and methods. The economic damage caused by laryngeal and lung cancer mortality in the Tomsk region for the period 2005–2016 was analyzed using the database of the regional cancer registry and local agency of federal state statistics service of the tomsk region.Results. The loss of the male working population ranged from 106.0 (2012–2013) to 161.5 (2008–2009) person/years of lifetime from larynx cancer and from 1058.5 (2013–2014) to 1576.3 (2006–2007) person/years of lifetime from lung cancer. The female working population lost up to 34.0 (2013–2014) person/years of lifetime due to mortality from larynx cancer and from 1445.3 (2005–2006) to 2553.9 (2015–2016) person/years of lifetime from lung cancer. The average number of undelivered years in working age due to the premature death of one man averaged 6.1 ± 2.0 years from larynx cancer and 11.1 ± 1.3 from lung cancer, one woman averaged 4.6 ± 0.9 years from larynx cancer and 6.2 ± 0.3 years from lung cancer. Economic losses associated with mortality from cancer of the respiratory system amounted to 2.251.97 million rubles: 202.07 million rubles from laryngeal cancer and 2.049.90 million rubles from lung cancer.Conclusion. The quantitative analysis of social and economic losses associated with mortality from cancer of the respiratory system enables the regional health authorities to develop and implement anti-cancer interventions to maximize the use of funds for the prevention, treatment and rehabilitation of cancer patients. Актуальность. Для системного анализа проводимых противораковых мероприятий значимой составляющей  является оценка влияния смертности на среднюю  продолжительность предстоящей жизни, свидетельствующей о социально-экономическом состоянии в регионе. Материал и методы. Проведен анализ социально-экономического ущерба, причиненного смертностью от рака гортани (РГ) и легкого (РЛ) в Томской области с 2005 по 2016 г. на основании базы данных популяционного  областного ракового регистра и территориального органа  Федеральной службы государственной статистики по  Томской области. Результаты. С 2005 по 2016 г. потери мужского трудоспособного населения варьировали от 106,0 (2012–13 гг.) до 161,5 (2008–09 гг.) человеко-лет жизни в связи со смертностью от РГ и от 1058,5 (2013–14 гг.) до 1576,3 (2006–07 г.) человеко-лет – от РЛ. Женская популяция в трудоспособном возрасте теряла до 34,0 (2013–14 гг.) человеко-лет жизни в связи со смертностью от РГ и от 1445,3 (2005–06 гг.) до 2553,9 (2015–16 гг.) человеко-лет – от РЛ. Среднее количество недожитых лет в трудоспособном  возрасте в связи с преждевременной гибелью одного  мужчины составило 6,1 ± 2,0 года от РГ и 6,2 ± 1,3 – от РЛ, одной женщины – 4,6 ± 0,9 года от РГ и 6,2 ± 0,3 года – от РЛ. Экономические потери, связанные со смертностью от рака органов дыхания (РОД), составили 2 251,97 млн руб.: 202,07 млн руб. – от РГ и 2049,9 млн руб. – от РЛ. Заключение. Анализ количественной оценки потерь, в том числе финансовых, связанных со смертностью от РГ и РЛ, позволяет региональным органам здравоохранения  разрабатывать и внедрять противораковые мероприятия с  целью максимально эффективного использования средств на профилактику, лечение и реабилитацию онкологических больных.

Effect of early-stage human breast carcinoma on monocyte programming

Circulating monocytes are a major source of tumor-associated macrophages (TAMs). TAMs in human breast cancer (BC) support primary tumor growth and metastasis. Neoadjuvant chemotherapy (NAC) is a commonly used treatment for BC patients. The absence of the response to NAC has major negative consequences for the patient: increase of tumor mass, delayed surgery, and unnecessary toxicity. We aimed to identify the effect of BC on the subpopulation content and transcriptome of circulating monocytes. We examined how monocyte phenotypes correlate with the response to NAC. The percentage of CD14-, CD16-, CD163-, and HLA-DR-expressing monocytes was quantified by flow cytometry for patients with T1-4N0-3M0 before NAC. The clinical efficacy of NAC was assessed by RECIST criteria of RECIST 1.1 and by the pathological complete response (pCR). The percentage of CD14+ and СD16+ monocytes did not differ between healthy women and BC patients and did not differ between NAC responders and non-responders. The percentage of CD163-expressing CD14lowCD16+ and CD14+CD16+ monocytes was increased in BC patients compared to healthy women (99.08% vs. 60.00%, p = 0.039, and 98.08% vs. 86.96%, p = 0.046, respectively). Quantitative immunohistology and confocal microscopy demonstrated that increased levels of CD163+ monocytes are recruited in the tumor after NAC. The percentage of CD14lowCD16+ in the total monocyte population positively correlated with the response to NAC assessed by pCR: 8.3% patients with pCR versus 2.5% without pCR (p = 0.018). Search for the specific monocyte surface markers correlating with NAC response evaluated by RECIST 1.1 revealed that patients with no response to NAC had a significantly lower amount of CD14lowCD16+HLA-DR+ cells compared to the patients with clinical response to NAC (55.12% vs. 84.62%, p = 0.005). NGS identified significant changes in the whole transcriptome of monocytes of BC patients. Regulators of inflammation and monocyte migration were upregulated, and genes responsible for the chromatin remodeling were suppressed in monocyte BC patients. In summary, our study demonstrated that presence of BC before distant metastasis is detectable, significantly effects on both monocyte phenotype and transcriptome. The most striking surface markers were CD163 for the presence of BC, and HLA-DR (CD14lowCD16+HLA-DR+) for the response to NAC

Новая мутация в гене PALB2, ассоциированная с наследственным раком молочной железы у молодой пациентки, принадлежащей к якутской этнической группе

Background. Breast cancer (BC) is the most common female malignancy worldwide. Partner And Localizer of BRCA2 gene (PALB2) is directly involved in DNA damage response. Germline mutation in PALB2 has been identified in breast cancer and familial pancreatic cancer cases, accounting for approximately 1–2% and 3–4%, respectively. The goal of this report was to describe new PALB2 mutation in a young Yakut breast cancer patient with family history of cancer. Material and Methods. Genomic DNA were isolated from blood samples and used to prepare libraries using a capture-based target enrichment kit, Hereditary Cancer Solution™ (SOP HiA GE NETICS , Switzerland), covering 27 genes (ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, PMS2CL, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53 and XRCC2). Paired-end sequencing (2 × 150 bp) was conducted using NextSeq 500 system (Illumina, USA ). Results. Here we describe a case of a never-before-reported mutation in the PALB2 gene that led to the early onset breast cancer. We report the case of a 39-year-old breast cancer Yakut woman with a family history of pancreatic cancer. Bioinformatics analysis of the NGS data revealed the presence of the new PALB2 gene germinal frameshift deletion (NM_024675:exon1:c.47delA:p.K16fs). In accordance with dbPubMed ClinVar, new mutation is located in codon of the PALB2 gene, where the likely pathogenic donor splice site mutation (NM_024675.3:c.48+1delG) associated with hereditary cancer-predisposing syndrome has been earlier described. Conclusion. We found a new never-before-reported mutation in PALB2 gene, which probably associated with early onset breast cancer in Yakut indigenous women with a family history of pancreatic cancer.Актуальность. Рак молочной железы занимает лидирующие позиции по уровню заболеваемости во всем мире. Ген онкосупрессор PALB2 наряду с такими генами, как BRCA1, BRCA2, вовлечен в процессы репарации поврежденной ДНК. Частота встречаемости герминальных мутаций гена PALB2 при раке молочной железы и семейных случаях рака поджелудочной железы составляет приблизительно 1–2 % и 3–4 % соответственно. Представлен клинический случай 39-летней женщины, принадлежащей к якутской этнической группе, с диагнозом рак молочной железы с семейной историей рака поджелудочной железы. Материал и методы. Геномная ДНК выделена из периферической крови, ДНК-библиотеки приготавливали с использованием набора Hereditary Cancer Solution™ (Sophia Genetics, Швейцария) для изучения статуса 27 генов (ATM, APC, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, FAM175A, MLH1, MRE11A, MSH2, MSH6, MUTYH, NBN, PALB2, PIK3CA, PMS2, PMS2CL, PTEN, RAD50, RAD51C, RAD51D, STK11, TP53 и XRCC2). Секвенирование (2 × 150 п.н.) проводилось с использованием системы NextSeq 500 (Illumina, США). Результаты. По результатам биоинформатического анализа данных NGS у 39-летней женщины, принадлежащей к якутской этнической группе, с диагнозом рак молочной железы с семейной историей рака поджелудочной железы обнаружена новая герминальная мутация гена PALB2 со сдвигом рамки считывания (NM_024675: Exon1: c.47delA: p.K16FS). В соответствии с dbPubmed ClinVar новая мутация гена PALB2 расположена в том же кодоне, где ранее была описана, вероятно патогенная, мутация сайта сплайсинга (NM_024675.3: Exon1: c.48+1delG), вовлеченная в патогенез наследственных форм рака молочной железы и яичника. Заключение. Впервые у 39-летней женщины, принадлежащей к якутской этнической группе, с диагнозом рак молочной железы и с семейной историей рака поджелудочной железы обнаружена новая, вероятно патогенная, герминальная мутация гена PALB2 со сдвигом рамки считывания (NM_024675: Exon1: c.47delA: p.K16FS)

Персонализированная адъювантная химиотерапия немелкоклеточного рака легкого II–III стадий

Surgery is the standard of care for non-small cell lung cancer (NSCLC). The overall survival rates especially in patients with locally advanced lung cancer are low. The resistance of cancer cells to chemotherapeutic drugs reduces the efficacy of treatment. Special attention is paid to the feasibility of assessing the tumor sensitivity to certain chemotherapy drugs. Currently, the most studied predictors are monoresistance and multidrug resistance genes, such as ABCC5, RRM1, ERCC1, BRCA1, TOP1, TOP2a, TUBB3 and TYMS.The aim of the study was to analyze the outcomes of combined modality treatment using radical surgery and personalized adjuvant chemotherapy for stage II–III NSCLC.Material and Methods. The study included 120 patients with stage II–III NSCLC, who underwent radical lung resection with mediastinal ipsilateral lymph node dissection. The patients were then divided into two groups. The main group consisted of 60 patients who received personalized platinum-based adjuvant chemotherapy based on the expression levels of the genes, such as ABCC5, RRM1, ERCC1, BRCA1, TOP1, TOP2a, TUBB3 and TYMS. The control group consisted of 60 patients who received postoperative chemotherapy empirically.Results. In the main group, disease progression occurred in 14 out of 60 patients, three-year disease-free survival (DFS) was 76.7 % (the median was not reached). In the control group, DFS was 53.3 % (28 out of 60 patients), the median was 31.0 (4–36 months); the differences were statistically significant: Logrank test χ2 =4.382 p=0.036. The overall three–year survival rate was 90.0 % in the main group (6/60 patients died) and 61.7 % in the control group (23/60 patients died), the differences were statistically signifcant: Logrank test χ2 =6.915, p=0.009.Conclusion. The personalized adjuvant chemotherapy resulted in the improved three-year relapse-free and overall survival rates in NSCLC patients.Основным методом лечения немелкоклеточного рака легкого (НМРЛ) является хирургический, при этом показатели общей выживаемости, особенно при местнораспространенном процессе, низкие. Химиорезистентность опухоли определяет низкую эффективность проводимого адъювантного лекарственного лечения. Особое внимание исследователей привлекает возможность оценки чувствительности опухоли к определенным химиопрепаратам. Наиболее изученными предикторами в настоящее время являются такие гены монорезистентности и множественной лекарственной устойчивости, как АВСС5, RRM1, ERCC1, BRCA1, TOP1, TOP2α, TUBB3 и TYMS. Цель исследования – изучить результаты комбинированного лечения немелкоклеточного рака легкого II–III стадии с использованием радикального хирургического вмешательства и персонализированной адъювантной химиотерапии.Материал и методы. В исследование включены 120 больных с немелкоклеточным раком легкого II–III стадии, которым на первом этапе комбинированного лечения проводилось хирургическое лечение, включающее радикальную резекцию легкого в объеме лоб-, билоб- или пульмонэктомии с медиастинальной ипсилатеральной лимфодиссекцией. Далее больные были распределены на две группы. Основную группу составили 60 пациентов, которым после операции проведены курсы персонализированной адъювантной химиотерапии, назначенной на основании уровней экспрессии генов АВСС5, RRM1, ERCC1, BRCA1, TOP1, TOP2α, TUBB3 и TYMS в виде платиносодержащих дублетов. Контрольную группу составили 60 пациентов, которым послеоперационная химиотерапия назначалась эмпирически.Результаты. В основной группе прогрессирование заболевания зафиксировано у 14 из 60 пациентов, трехлетняя безрецидивная выживаемость (БРВ) – 76,7 % (медиана не достигнута). В группе контроля БРВ составила 53,3 % (28 из 60 пациентов), медиана составила 31,0 мес (от 4 до 36 мес); различия статистически значимы: Logrank test χ2 =4,382 р=0,036. Общая 3-летняя выживаемость в основной группе составила 90,0 % (умерло 6/60 пациентов), в группе контроля – 61,7 % (умерло 23/60 пациентов), различия статистически значимы: Logrank test χ2 =6,915, р=0,009.Заключение. Разработанная программа комбинированного лечения НМРЛ с персонализированным назначением послеоперационной химиотерапии позволяет добиться улучшения показателей 3-летней безрецидивной и общей выживаемости

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000–14 (CONCORD-3) : analysis of individual data from 258 cancer registries in 61 countries

Background Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0–14 years) and adults (aged 15–99 years) diagnosed with a haematological malignancy during 2000–14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0–24 years). Methods We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0–14 years), adolescents (15–19 years), and young adults (20–24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. Findings 164563 young people were included in this analysis: 121328 (73·7%) children, 22963 (14·0%) adolescents, and 20272 (12·3%) young adults. In 2010–14, the most common subtypes were lymphoid leukaemia (28205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010–14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000–14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. Interpretation This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group.peer-reviewe

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000–2014 (CONCORD-3)

Background: Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. Methods: We analyzed individual data for adults (15–99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000–2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. Results: The study included 556,237 adults. In 2010–2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%–38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000–2004 and 2005–2009. These improvements were more noticeable among adults diagnosed aged 40–70 years than among younger adults. Conclusions: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines

Geochemistry of grass biocenoses: Biogenic cycles of chemical elements at contamination of the environment with heavy metals

The paper addresses the involvement of grass communities in biogenic cycles of chemical elements (Zn, Cu, Pb, Cd, Mn, Co, Cr, Ni, and Fe). Both the species composition and the suprasoil phytomass of phytocenoses in the Central Urals are modified in a gradient of contamination with heavy metals. The bioproductivity and subsequent mineralization of plant remnants are discussed with reference to two soil types that differ in agrochemical parameters. The contribution of agrobotanical groups to the biological exchange of chemical elements is proved to be controlled not only by the volume of annually dying suprasoil biomass but also by the intensity of processes mineralizing plant remnants in the contamination gradient. This modifies the cycles of chemical elements in natural contaminated biocenoses. The reaction of grass communities on environmental contamination can be viewed as partial counterbalancing of the adverse effect of chemical stress via maintaining a high enough level of the biological exchange of chemical elements. © 2015, Pleiades Publishing, Ltd.Russian Academy of Sciences, РФФИ: 12-I-4-2051Russian Foundation for Basic Research, 13-04-960056-r_ural_a

Soil microbiocenosis as an indicator of stability of meadow communities in the environment polluted with heavy metals

The soil microbiota, a key component of natural ecosystems, is considered as a factor determining the stability of meadow communities. The diversity and abundance of the main ecologically significant groups of microorganisms in meadow soils have been studied along a gradient of long-term soil pollution with heavy metals in the Middle Urals. The results provide evidence for stability of the microbial assemblage formed in these soils. It has been found that the functional activity of certain physiological groups of microorganisms (nitrogen-fixing, denitrifying, and cellulolytic bacteria) and the respiratory activity of microbial communities are stimulated under conditions of heavy-metal soil pollution. Probable effects of the observed changes on mineralization of plant remains in meadow communities are discussed. © 2014 Pleiades Publishing, Ltd.13 04 96056ACKNOWLEDGMENTS This study was supported by the Russian Founda tion for Basic Research (project no. 13 04 96056 r_ural_a), Scientific School Support Program (project no. NSh 5325.2012.4), and the Presidium of the Ural Branch of the Russian Academy of Sciences (project no. 12 I 4 2051)

Biogeochemistry of Impact Regions: the Role of Edaphic and Phytocoenotic Environmental Factors

The paper addresses the removal of chemical elements by suprasoil and subsoil phytomasses of herbaceous phytocenoses and their subsequent return to soil during decomposition of plant remnants. The obtained results allowed us to evaluate the biogeochemical cycles of essential (Zn, Cu) and toxic (Pb, Cd) elements in natural biogeocenoses of the Middle Urals. It has been shown that the intensity of such an exchange in areas subjected to variable anthropogenic impact is determined not only by the direct influence of mobile forms of chemical elements, which are contained in soils and operate as environmental pollutants, but also by a combination of edaphic (physicochemical parameters of soils), coenotic (abundance and correlation of agrobotanical groups in phytocenosis) and microbiological (level of evolution of soil microbiocenosis) conditions. © 2020, Pleiades Publishing, Ltd