Incidence and Survival of Pediatric Soft Tissue Sarcomas in Moscow Region, Russian Federation, 2000–2009

The aim of the study was to assess the incidence and survival rates of soft tissue sarcomas (STSs) in children 0–14 years of age in Moscow Region, Russian Federation. The database of childhood population-based cancer registry of Moscow Region was used as a data source. Tumors were stratified according to International Classification of Childhood Cancer, 3d ed. Sixty-eight cases of STS were registered from 2000 to 2009. Crude incidence rate was 0,78, and age-standardized incidence rate using World Standard Population was 0,81 per 100.000 children/year. The highest age-specific incidence was observed in infants: 1,76 per 100.000 children/year. Rhabdomyosarcoma (RMS) was the most common histological type comprising 54,4% of all STS. 5-year observed survival (OS) of all patients with STS was 64,1 (95% CI 55,0–73,2). There was no statistically significant difference in OS between RMS—59,2 (95% CI 47,0–71,4) and nonrhabdomyosarcoma STS—69,3 (95% CI 55,8–82,8) (=0.63). Incidence and survival rates of STS observed in the study were comparable to the other Eastern European countries

Epidemiology of childhood lymphomas in Moscow region (population-based study)

The aim of the study was to analyze the main epidemiologic characteristics of lymphomas in children 0–14 years of age in Moscow Region (MR). The database of childhood population-based cancer registry of MR served as a data source. 136 cases of lymphomas were identified during 2000–2008 years. Hodgkin disease constitutes of 55.8 % of cases. Age-standardized incidence rate (ASR) of all types of lymphomas was 1.47 per 100,000 children. ASR of Hodgkin disease was 0.77 per 100,000 children; ASR of non-Hodgkin’s lymphomas was 0.70 per 100,000 children. Distinct epidemiologic features of Hodgkin disease in different gender's and age groups were shown. 5-year observed survival (OS) of all patients with lymphomas was 0.83 ± 0.03. 5-year OS of patients with Hodgkin disease and non-Hodgkin lymphomas was 0.86 ± 0.04 and 0.80 ± 0.05 respectively.</p

Geopolitical games in Eurasian regionalism: ideational interactions and regional international organisations

This paper analyses the ideational interaction underlying attempts at regional integration and cooperation in Eurasia. While the ideas and values of the European Union have been relatively well-studied within the theory of Europeanisation, the key concepts, ideas, values and principles driving Eurasian regionalism have remained out of the main focus of Western scholarship. This paper aims to shed more light on this ideational basis of Eurasian regionalism by unveiling the discourse developed in Russian scholarship and available only in Russian. Understanding interactions between institutions will always remain partial as long as the ideational interaction is not addressed. Such concepts as ‘integrative mentality’, as a segment of the wider category ‘foreign policy mentality’, and the theory of neo-Eurasianism have been incorporated into Russian political discourse and therefore affect public opinion through specific interpretation of economic, political and cultural processes in the EU’s near neighbourhood and the EU as an actor. The analysis presented in this paper indicates the development of new ideational competition, in addition to the well-documented geopolitical one. The paper also aspires to contribute to emerging research on public support to governmental strategic choices and self-legitimation of international organisations in Eurasia

Preclinical characterization and clinical translation of pharmacodynamic markers for MK-5890: a human CD27 activating antibody for cancer immunotherapy

Background Immune checkpoint inhibitors (ICI) have radically changed cancer therapy, but most patients with cancer are unresponsive or relapse after treatment. MK-5890 is a CD27 agonist antibody intended to complement ICI therapy. CD27 is a member of the tumor necrosis factor receptor superfamily that plays a critical role in promoting responses of T cells, B cells and NK cells. Methods Anti-CD27 antibodies were generated and selected for agonist activity using NF-kB luciferase reporter assays. Antibodies were humanized and characterized for agonism using in vitro T-cell proliferation assays. The epitope recognized on CD27 by MK-5890 was established by X-ray crystallography. Anti-tumor activity was evaluated in a human CD27 knock-in mouse. Preclinical safety was tested in rhesus monkeys. Pharmacodynamic properties were examined in mouse, rhesus monkeys and a phase 1 dose escalation clinical study in patients with cancer. Results Humanized anti-CD27 antibody MK-5890 (hIgG1) was shown to bind human CD27 on the cell surface with sub-nanomolar potency and to partially block binding to its ligand, CD70. Crystallization studies revealed that MK-5890 binds to a unique epitope in the cysteine-rich domain 1 (CRD1). MK-5890 activated CD27 expressed on 293T NF-kappa B luciferase reporter cells and, conditional on CD3 stimulation, in purified CD8+ T cells without the requirement of crosslinking. Functional Fc-receptor interaction was required to activate CD8+ T cells in an ex vivo tumor explant system and to induce antitumor efficacy in syngeneic murine subcutaneous tumor models. MK-5890 had monotherapy efficacy in these models and enhanced efficacy of PD-1 blockade. MK-5890 reduced in an isotype-dependent and dose-dependent manner circulating, but not tumor-infiltrating T-cell numbers in these mouse models. In rhesus monkey and human patients, reduction in circulating T cells was transient and less pronounced than in mouse. MK-5890 induced transient elevation of chemokines MCP-1, MIP-1 alpha, and MIP-1 beta in the serum of mice, rhesus monkeys and patients with cancer. MK-5890 was well tolerated in rhesus monkeys and systemic exposure to MK-5890 was associated with CD27 occupancy at all doses. Conclusions MK-5890 is a novel CD27 agonistic antibody with the potential to complement the activity of PD-1 checkpoint inhibition in cancer immunotherapy and is currently undergoing clinical evaluation.Tumorimmunolog