Pathogenesis of Skin Carcinomas and a Stem Cell as Focal Origin

Dermatology-oncolog

TCTAP A-046 Comparison of Two-and Three-dimensional Quantitative Coronary Angiography to Intravascular Ultrasound in the Assessment of Left Main Bifurcation Lesions

Sexual transmission is the primary route of HIV-1 infection, and DC subsets are thought to be involved in viral dissemination to T cells. In the genital mucosa, two main subsets of DCs are present: epithelial LCs capture and degrade HIV-1 through C-type lectin Langerin, whereas subepithelial DCs express DC-SIGN, which facilitates HIV-1 transmission to T cells. As there is currently no HIV-1 vaccine availab

Improved induction of anti-melanoma T cells by adenovirus-5/3 fiber modification to target human DCs

To mount a strong anti-tumor immune response, non T cell inflamed (cold) tumors may require combination treatment encompassing vaccine strategies preceding checkpoint inhibition. In vivo targeted delivery of tumor-associated antigens (TAA) to dendritic cells (DCs), relying on the natural functions of primary DCs in situ, represents an attractive vaccination strategy. In this study we made use of a full-length MART-1 expressing C/B-chimeric adenoviral vector, consisting of the Ad5 capsid and the Ad3 knob (Ad5/3), which we previously showed to selectively transduce DCs in human skin and lymph nodes. Our data demonstrate that chimeric Ad5/3 vectors encoding TAA, and able to target human DCs in situ, can be used to efficiently induce expansion of functional tumor-specific CD8⁺ effector T cells, either from a naïve T cell pool or from previously primed T cells residing in the melanoma-draining sentinel lymph nodes (SLN). These data support the use of Ad3-knob containing viruses as vaccine vehicles for in vivo delivery. "Off-the-shelf" DC-targeted Ad vaccines encoding TAA could clearly benefit future immunotherapeutic approaches

Tissue micro array analysis of ganglioside N-glycolyl GM3 expression and signal transducer and activator of transcription (STAT)-3 activation in relation to dendritic cell infiltration and microvessel density in non-small cell lung cancer

Background: Tumor immune escape and angiogenesis contribute to tumor progression, and gangliosides and activation of signal transducer and activator of transcription (STAT)-3 are implicated in these processes. As both are considered as novel therapeutic targets, we assessed the possible association of ganglioside GM3 expression and STAT3 activation with suppression of dendritic cell (DC) activation and angiogenesis in non-small cell lung cancer (NSCLC). Methods: Immunohistochemistry was performed on a tissue array to determine N-glycolyl GM3 (GM3) and phosphorylated STAT3 (pSTAT3) expression in 176 primary NSCLC resections. Median values of GM3 and pSTAT3 expression were used as cut off. Microvessel density (MVD) was determined by CD34 staining and morphology. CD1a and CD83 were used to determine infiltrating immature and mature dendritic cells, respectively. Results: 94% and 71% of the NSCLC samples expressed GM3 and nuclear pSTAT3, respectively. Median overall survival was 40.0 months. Both low GM3 expression and high pSTAT3 expression were associated with a worse survival, which reached near significance for GM3 (P = 0.08). Microvessel density (MVD), determined by CD34 staining and morphology, was lower in NSCLC samples with high GM3 expression. CD1a(+) cells (immature DCs) were more frequent in NSCLC tissues as compared to peritumoral lung tissue, while CD83(+) cells (mature DCs) were more frequent in peritumoral lung tissue. CD83(+) DCs were less frequent in NSCLC tissues with high GM3 expression. Conclusion: GM3 and pSTAT3 are widely expressed in NSCLC. Based on CD83 expression, GM3, but not pSTAT3, appeared to be involved in tumor-induced DC suppression. pSTAT3 expression was not associated with MVD, while GM3 might play an anti-angiogenic rol

Міжнародне співробітництво МВС України у сфері протидії корупції

У статті здійснено аналіз розвитку та сучасного стану міжнародної співпраці МВС України у сфері протидії корупції. Розглянуто формування нормативно-правової бази щодо боротьби з корупцією та пов’язаною з нею злочинністю, надано характеристику напрямів та шляхів співпраці органів внутрішніх справ нашої країни з іноземними державами, їх правоохоронними органами і спеціальними службами, а також із міжнародними організаціями, які здійснюють заходи із протидії корупції. Визначено перспективи подальшого розвитку міжнародного співробітництва МВС у протидії транснаціональним формам корупції.В статье осуществлен анализ развития и современного состояния международного сотрудничества МВД Украины в сфере противодействия коррупции. Рассмотрено формирование нормативно-правовой базы по борьбе с коррупцией и связанной с ней преступностью, дана характеристика направлений и путей сотрудничества органов внутренних дел Украины с зарубежными государствами, их правоохранительными органами и специальными службами, а также с международными организациями, которые осуществляют мероприятия по противодействию коррупции. Определены перспективные направления дальнейшего развития международного сотрудничества МВД Украины в сфере противодействия транснациональным формам коррупции.Development and modern state of the international cooperation of the Ukranian Ministry of Internal Affairs in the sphere of corruption counteraction is analyzed. It is considered the formation of normative and legal base concerning struggle against corruption and the criminality, it is given the characteristic of directions and ways of cooperation of law-enforcement bodies of Ukraine with the foreign states, their law enforcement bodies and special services, and also with the international organizations which carry out measures on counteraction of corruption. It is determined the perspective directions of the further development of the international cooperation of the Ministry of Internal Affairs in Ukraine in the sphere of counteraction to transnational forms of corruption