Economic Zones as a Factor of Increased Economic Competitiveness of the Region

One of the most promising and effective ways to raise state and foreign investment holdings for further development of economic potential and opportunities of the region, promoting innovative development and transformation of the region, its economic system there can be formation and development of special economic zones (SEZ). This dynamics of economic zones assumes their further development in the structure of the region as a center of industrial and innovative cluster development which operation is a driving force promoting the domestic economic system on the way of its modernization and advance. Each economy of the region possesses specific peculiarities of available resource and potential development, and also conducts its own policy of development of innovative enterprises, companies and other organizations. All inherent distinctive features and potentials of economic development of the region allow to qualify this or that region as the most competitive one. The paper considers special economic zones of regions of the Russian Federation, their development in the modern conditions of world fluctuations. It reveals the main problems in the field of realization and introduction of SEZ, and the ways of their elimination. The paper also describes priorities for of economic zone realization efficiency their further development both in economy of the region, being a factor of increased competitive advantages, and in the whole state. Keywords: region, special economic zone, innovation, cluster, competitiveness JEL Classifications: O30, O40, G2

Психосоциальное консультирование при тестировании на вирус иммунодефицита человека: на что обратить внимание?

Introduction. Voluntary anonymous HIV counseling and testing can be an effective tool to reduce the behavior that has high risks of HIV, hepatitis C (HCV) and B (HBV) transmission. The dissemination of general information on HIV, HCV, HBV to reduce risky behavior is not as much of importance as counseling on specific individual infection-related sexual risk behavior. The objective was to identify HIV/HCV/HBV-related risk factors that have to be discussed during psychosocial counselingto help the individual to focus on his/her sexual risk behavior.Methods and materials. The study was conducted on the base of Saint-Petersburg Center for Control of AIDS with participation of 90 individuals who voluntary applied for HIV counseling and testing. Participants’ behavioral risks and HIV knowledge were assessed by the specifically developed structured questionnaire. The level of anxiety was measured by State-Train Anxiety Inventory (STAI adapted by Hanin), the level of need for extreme-risk behavior was measured by the Sensation Seeking Scale (Zuckerman).Results. Only 50 % of participants use condom with their steady sexual partner always or almost always. In 62 % cases, the steady sexual partner’s HIV-status is unknown. Many participants agree that HIV transmission occurs always after sexual contact with HIV-infected person. The level of situational anxiety is higher by those who do HIV testing repeatedly. Those who are more likely to seek new sensations use condom with their steady or other partner more often.Conclusion. Motivational intervention during pre- and post-counseling by HIV/HCV/HBV testing has to focus on the discussion of individual difficulties of condom use as the means for protection and on the individual’s resources for changing sexual behavior to protect him/her-self and his/her partner from infection with HIV and viral hepatitis.Введение. Консультирование при добровольном анонимном обследовании на вирус иммунодефицита человека (ВИЧ) может быть эффективным способом снижения частоты совершения поступков, имеющих высокие риски заражения ВИЧ и вирусными гепатитами В и С (ВГВ и ВГС). Для снижения частоты рискованных поступков имеют значение не столько предоставление общей профилактической информации о ВИЧ, ВГВ и ВГС, сколько обсуждение специфических особенностей сексуального рискованного поведения, опасного для инфицирования этими вирусами.Цель исследования – изучение факторов, связанных с рисками инфицирования ВИЧ и гепатитами В и С, обсуждение которых в процессе психосоциального консультирования поможет человеку обратить внимание на свое рискованное поведение в сексуальных отношениях с партнером.Методы и материалы. В исследовании, проведенном в Санкт-Петербургском Центре по профилактике и борьбе со СПИД и инфекционными заболеваниями, приняли участие 90 человек, добровольно обратившихся за анонимным консультированием и тестированием на ВИЧ. Поведенческие риски участников и уровень их осведомленности о ВИЧ оценивали с помощью специально разработанной структурированной анкеты. Уровень тревожности измеряли по методике Спилбергера – Ханина, склонность к экстремально-рискованному поведению – по методике Цукермана.Результаты. Лишь 50 % участников используют средства предохранения всегда или почти всегда при сексуальных контактах с постоянным партнером. В 62 % случаев ВИЧ-статус постоянного полового партнера неизвестен. Многие допускают мысль, что заражение ВИЧ-инфекцией происходит всегда при половом контакте с ВИЧ-инфицированным человеком. Уровень ситуационной тревоги выше у людей, кто обследуется на ВИЧ повторно. Люди, склонные к поиску новых или острых ощущений, чаще используют средства защиты при сексуальных контактах с постоянным или «другим» партнером.Заключение. Мотивационные вмешательства во время до- и послетестового консультирования приьобследовании на ВИЧ, ВГВ и ВГС должны быть направлены на обсуждение специфических трудностей, связанных с использованием презервативов в качестве средства предохранения, и на возможность пересмотра своего сексуального поведения с целью защиты себя и своего полового партнера от инфицирования ВИЧ и вирусными гепатитами

Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open -label phase III study

Background: Targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis has demonstrated clinical benefit in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Combining immunotherapies targeting PD-L1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has shown evidence of additive activity in several tumor types. This phase III study evaluated the efficacy of durvalumab (an anti-PD-L1 monoclonal antibody) or durvalumab plus tremelimumab (an anti-CTLA-4 monoclonal antibody) versus standard of care (SoC) in R/M HNSCC patients. Patients and methods: Patients were randomly assigned to receive 1 : 1 : 1 durvalumab (10 mg/kg every 2 weeks [q2w]), durvalumab plus tremelimumab (durvalumab 20 mg/kg q4w plus tremelimumab 1 mg/kg q4w 4, then durvalumab 10 mg/kg q2w), or SoC (cetuximab, a taxane, methotrexate, or a fluoropyrimidine). The primary end points were overall survival (OS) for durvalumab versus SoC, and OS for durvalumab plus tremelimumab versus SoC. Secondary end points included progression-free survival (PFS), objective response rate, and duration of response. Results: Patients were randomly assigned to receive durvalumab (n 1⁄4 240), durvalumab plus tremelimumab (n 1⁄4 247), or SoC (n 1⁄4 249). No statistically significant improvements in OS were observed for durvalumab versus SoC [hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.72e1.08; P 1⁄4 0.20] or durvalumab plus tremelimumab versus SoC (HR: 1.04; 95% CI: 0.85e1.26; P 1⁄4 0.76). The 12-month survival rates (95% CI) were 37.0% (30.9e43.1), 30.4% (24.7e36.3), and 30.5% (24.7 e36.4) for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Treatment-related adverse events (trAEs) were consistent with previous reports. The most common trAEs (any grade) were hypothyroidism for durvalumab and durvalumab plus tremelimumab (11.4% and 12.2%, respectively), and anemia (17.5%) for SoC. Grade !3 trAE rates were 10.1%, 16.3%, and 24.2% for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Conclusion: There were no statistically significant differences in OS for durvalumab or durvalumab plus tremelimumab versus SoC. However, higher survival rates at 12 to 24 months and response rates demonstrate clinical activity for durvalumab

ПРЕДИКТИВНОЕ ЗНАЧЕНИЕ МАРКЕРОВ КЛЕТОЧНОГО ЦИКЛА ПРИ РАКЕ СЛИЗИСТОЙ ОБОЛОЧКИ ПОЛОСТИ РТА

The aim of our study was to identify the most significant biological markers characterizing the behavior of the tumor and to forecast its clinical course and to specify an individual therapy regimen for each patient.Работа посвящена выявлению наиболее значимых биологических маркеров клеточного цикла, характеризующих поведение опухоли, с целью прогноза клинического течения опухолевого процесса и индивидуализации схем лечения

Оценка влияния экспрессии хемокиновых рецепторов CXCR4, ССR10 в опухолевой ткани на показатель безрецидивной выживаемости больных раком ободочной кишки

Considering a rise in colon cancer rates, searching for new treatment options remains highly relevant for this patient cohort. Determination of chemokine receptors in tumor tissue may become an additional prognostic tool that can be used for planning adjuvant therapy.Учитывая рост заболеваемости раком ободочной кишки, поиск новых вариантов лечения остается высоко актуальным для данной группы пациентов. Определение хемокиновых рецепторов в опухолевой ткани может стать дополнительным фактором прогноза и использоваться при планировании адъювантной терапии

Cистемное воспаление и иммунологическое микроокружение в прогнозе течения солидных опухолей

The purpose of the research. To study prognostic significance of indicators of systemic inflammation of peripheral blood and relative indicators: neutrophil‑lymphocytic and platelet‑lymphocytic ratio, the course of squamous cell carcinoma of the oral mucosa and gastric adenocarcinoma.Materials and methods. Prospective analysis of patients with squamous cell carcinoma of the oral mucosa and disseminated gastric adenocarcinoma was performed. Patients with verified diagnosis, without signs of inflammatory diseases in anamnesis, not receiving antibacterial and immunomodulatory therapy were selected. Overall survival and survival without progression were considered as the main estimated parameters.Results. The selection criteria were met by 32 patients with disseminated gastric adenocarcinoma and 60 patients with squamous cell carcinoma of the oral mucosa. The prognostic value of relative indicators is determined: overall survival of patients with gastric adenocarcinoma with a low value of the neutrophil‑lymphocytic index is significantly higher than that of the rest of the cohort of patients: 16 months vs. 8 and 7 months (95 % CI (confidence interval) from 12 to 23 months, p=0.0382). Overall survival of patients with low platelet‑lymphocytic index was also higher: 16 months vs. 8 months (95 % CI from 11 to 24 months, р=0,0026). Different relapse‑free survival was noted in the group of patients with squamous cell head and neck cancer: patients with low index value it is 7 months vs. 2 months (95 % CI from 5 to 9 months, p=0.0499).Conclusions. The results show the possibility of using immunological microenvironment of the tumor and indices, characterizing the systemic inflammation, for prognosis of gastric adenocarcinoma and squamous cell carcinoma of the oral mucosa.Цель исследования. изучить прогностическую значимость показателей системного воспаления периферической крови и относительных показателей: нейтрофильно-лимфоцитарное и тромбоцитарно-лимфоцитарное соотношение, на течение плоскоклеточного рака слизистой оболочки полости рта и аденокарциномы желудка.Материалы и методы. Произведен проспективный анализ больных плоскоклеточным раком слизистой оболочки полости рта и диссеминированной аденокарциномой желудка. Были отобраны пациенты с верифицированным диагнозом, без признаков воспалительных заболеваний в анамнезе, не получающие антибактериальную и иммуномодулирующую терапию. В качестве основных оцениваемых параметров рассматривали общую выживаемость и выживаемость без прогрессирования.Результаты. Критериям отбора соответствовали 32 больных диссеминированной аденокарциномой желудка и 60 больных плоскоклеточным раком слизистой оболочки полости рта. Определена прогностическая ценность относительных показателей: общая выживаемость пациентов с аденокарциномой желудка с низким значением нейтрофильно-лимфоцитарного индекса достоверно выше, чем у остальной когорты пациентов: 16 месяцев против 8 и 7 месяцев (95 % ДИ от 12 до 23 месяцев, р=0,0382). Общая выживаемость пациентов с низким уровнем тромбоцитарно-лимфоцитарным индексом также была выше: 16 месяцев против 8 месяцев (95% ДИ от 11 до 24 месяцев, р=0,0026). В группе больных плоскоклеточным раком головы и шеи достоверно отличалась безрецидивная выживаемость: у пациентов с низким значением показателя — 7 месяцев против 2 месяцев (95 % ДИ от 5 до 9 месяцев, р=0,0499).Выводы. Полученные результаты говорят о возможности использования показателей иммунологического микроокружения опухоли и индексов, характеризующих системное воспаление, для прогнозирования течения аденокарцином желудка и плоскоклеточного рака слизистой оболочки полости рта

Системное воспаление в течении аденогенного рака слюнных желез

Relevance. The inflammatory process and endogenous intoxication of the patient’s body has a negative impact on the course of many malignant neoplasms, including salivary gland cancer.The objective of the study was to determine the influence of some factors of systemic inflammation and endogenous intoxication in salivary gland cancer.Methods and materials. A prospective study included the data of 59 patients with salivary gland cancer. The influence of peripheral blood parameters and relative indicators characterizing systemic inflammation on overall and disease-free survival was assessed.Results. As a result of the multivariate analysis, it was revealed that an increase in the level of the relative number of peripheral blood neutrophils by more than 60.08 % increases the risk of death in patients from salivary gland cancer by 3.90 times (p=0.0456; HR 3.90: 95 % CI 1.03–14.79). The level of the absolute number of peripheral blood lymphocytes, not exceeding 1.49x109 /l, increases the risk of disease progression by 8.72 times (p=0.0002, R 8.72: 95 % CI 2.78–27.28).Conclusion. Individual factors of systemic inflammation and endogenous intoxication, it is advisable to evaluate at the stage of planning the primary treatment of patients with salivary gland cancer, in order to determine the prognosis of the disease and optimize the choice of tactics for the primary treatment of patients. Введение. Воспалительный процесс и эндогенная интоксикация организма больного оказывает негативное влияние на течение многих злокачественных новообразований, в том числе и на течение аденогенного рака слюнных желез.Цель исследования – определение влияния некоторых факторов системного воспаления и эндогенной интоксикации на течение аденогенного рака слюнных желез.Методы и материалы. В проспективном исследовании проанализированы данные 59 больных с аденогенным слюнных желез. Оценено влияние показателей периферической крови и относительных показателей, характеризующих системное воспаление, на общую и безрецидивную выживаемость.Результаты. В результате проведенного многофакторного анализа выявлено, что, повышение уровня относительного числа нейтрофилов периферической крови выше 60,08 % увеличивает риск смерти больных от аденогенного рака слюнных желез в 3,90 раза (р=0,0456; ОР 3,90: 95 % ДИ 1,03–14,79). Уровень абсолютного числа лимфоцитов периферической крови, не превышающий 1,49∙109 /л, увеличивает риск прогрессирования заболевания в 8,72 раза: р=0,0002, ОР 8,72: 95 % ДИ 2,78–27,28.Заключение. Отдельные факторы системного воспаления и эндогенной интоксикации целесообразно оценивать на этапе планирования первичного лечения больных аденогенным раком слюнных желез с целью определения прогноза заболевания и оптимизации выбора тактики первичного лечения больных.

Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study

Head and neck squamous cell carcinoma (HNSCC) is among the 10 most common cancers worldwide, with increasing incidence.1 Approximately 10% of patients with HNSCC will be diagnosed with metastatic disease, and even when treated early, around half will have disease recurrence.2,3 The platinum-based doublet chemotherapy with cetuximab regimen has been the most widely-used therapy and considered standard of care (SoC) since it was proven effective in 2007 for recurrent/metastatic (R/M) HNSCC in the first-line setting.3,4 However, patients typically progress even after aggressive first-line therapy, and, until recently, the available options (e.g. cetuximab, methotrexate, and taxanes) have delivered limited survival benefits.3 Durvalumab is an immunotherapeutic agent that blocks the interaction between programmed cell death ligand 1 (PD-L1) and its receptors.5 Durvalumab demonstrated encouraging response rates and duration of response (DoR) with a manageable safety profile in patients with HNSCC.6 Although monotherapy agents that block the programmed cell death protein 1 (PD-1)/PD-L1 axis have shown clinical activity, immunotherapy combinations have the potential to improve upon monotherapy activity.7e9 Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and PD-L1/PD-1 pathways have largely non-redundant roles, suggesting that blockade of both could have additive or synergistic effects.10 Indeed, the combination of durvalumab and tremelimumab, an anti-CTLA-4 monoclonal antibody, was explored based on improved efficacy over monotherapy in other solid tumor types.7 This observation, in addition to the activity demonstrated by durvalumab in earlier R/M HNSCC studies, served as the rationale to evaluate durvalumab and tremelimumab in patients with R/M HNSCC. Several studies, including the EAGLE study, were initiated to evaluate combination immunotherapy regimens in various patient groups.11,12 The EAGLE study was the first phase III study to investigate durvalumab and tremelimumab in patients with R/M HNSCC who had progressed after platinumbased therapy. During the conduct of the EAGLE study, anti-PD-1 monoclonal antibodies were approved for use for R/M HNSCC progression following a platinum-based regimen. Treatment with these immunotherapies resulted in a median overall survival (OS) of 7.5e8.4 months.13,14 These immunotherapies are now recommended for second-line treatment as monotherapies for patients with R/M HNSCC.3,13,14 More recently, immunotherapy alone or in combination with platinum-based chemotherapy has shown improvements in OS in the first-line setting, underscoring the clinical utility of immunotherapy in HNSCC.15 Here, we report the results of the randomized phase III EAGLE trial evaluating durvalumab and durvalumab plus tremelimumab versus SoC therapies in patients with R/M HNSCC who have progressed following a platinumcontaining regimen

Application of the bacteriophage Mu-driven system for the integration/amplification of target genes in the chromosomes of engineered Gram-negative bacteria—mini review

The advantages of phage Mu transposition-based systems for the chromosomal editing of plasmid-less strains are reviewed. The cis and trans requirements for Mu phage-mediated transposition, which include the L/R ends of the Mu DNA, the transposition factors MuA and MuB, and the cis/trans functioning of the E element as an enhancer, are presented. Mini-Mu(LR)/(LER) units are Mu derivatives that lack most of the Mu genes but contain the L/R ends or a properly arranged E element in cis to the L/R ends. The dual-component system, which consists of an integrative plasmid with a mini-Mu and an easily eliminated helper plasmid encoding inducible transposition factors, is described in detail as a tool for the integration/amplification of recombinant DNAs. This chromosomal editing method is based on replicative transposition through the formation of a cointegrate that can be resolved in a recombination-dependent manner. (E-plus)- or (E-minus)-helpers that differ in the presence of the trans-acting E element are used to achieve the proper mini-Mu transposition intensity. The systems that have been developed for the construction of stably maintained mini-Mu multi-integrant strains of Escherichia coli and Methylophilus methylotrophus are described. A novel integration/amplification/fixation strategy is proposed for consecutive independent replicative transpositions of different mini-Mu(LER) units with “excisable” E elements in methylotrophic cells