The immunosuppressive effect of adenosine in the microenvironment of a tumor is well established. Presently, researchers are developing approaches in immune therapy that target inhibition of adenosine or its signaling such as CD39 or CD73 inhibiting antibodies or adenosine A2A receptor antagonists. However, numerous enzymatic pathways that control ATP-adenosine balance, as well as understudied intracellular adenosine regulation, can prevent successful immunotherapy. This review contains the latest data on two adenosine-lowering enzymes: adenosine kinase (ADK) and adenosine deaminase (ADA). ADK deletes adenosine by its phosphorylation into 5′-adenosine monophosphate. Recent studies have revealed an association between a long nuclear ADK isoform and an increase in global DNA methylation, which explains epigenetic receptor-independent role of adenosine. ADA regulates the level of adenosine by converting it to inosine. The changes in the activity of ADA are detected in patients with various cancer types. The article focuses on the biological significance of these enzymes and their roles in the development of cancer. Perspectives of future studies on these enzymes in therapy for cancer are discussed.
The paper analyzes inventories of the late 15th–17th centuries from four major Russian monasteries: St Cyril’s of Belozersk, The Solovetsky monastery, Joseph-Volokolamsk monastery, and The Holy Trinity – St Sergius monastery. These inventories list the monasteries’ property for its safekeeping. The inventories of monastic libraries contain valuable information about the system of book keeping and the development of bibliography in Old Rus’. They also provide some clues for attribution of books, which can help in reconstructing the concepts of bookmaking technologies in Early Modern period. These technological notes in descriptions of books are organized according to the system created by the inventories compilers: the format, the binding, the artistic values, the type and technique of writing, the page’s composition, the writing material, the state of preservation. The paper shows that the major goal in creating these inventories was to single out the most important elements allowing to recognize the book. Yet the description of these elements was not uniform. The attention was mainly directed to external attribution of a book. From the second half of the 16th century the cursive writing and the so-called metnoe pismo (a sort of scrittura usuale) were already recognized as different from standard book writing and had to be distinguished and indicated in book inventories. The inventories reflected those characteristics of books that were important for the librarians and therefore shaped certain semantic structures in professional mentality of Old Russian bookmen. For modern scholars they can serve as markers that follow the process of the development of book technologies in Early Modern period.
Tumor cells have the capacity to create an adenosine-rich immunosuppressive environment, which can interfere with antitumor immunotherapy. Approaches are currently being developed with a view to suppressing the production of adenosine or its signals. Such approaches include the use of antibodies to inhibit CD39, CD73, and adenosine-receptor antagonists. However, the abundance of enzymatic pathways that control the ATP-adenosine balance, as well as the still poorly understood intracellular adenosine regulation, makes the hoped-for success unlikely. In the present study, the enzyme adenosine kinase (ADK) needed to convert adenosine to adenosine monophosphate, thereby regulating its levels, was investigated. To do so, peripheral blood samples from patients with colorectal cancer (CRC) (n = 31) were collected with blood samples from healthy donors (n = 17) used as controls. ADK gene expression levels and those of its long (ADK-L) and short (ADK-S) isoforms were measured. The relationship between the levels of ADK gene expression and that of CD39, CD73, and A2aR genes was analyzed. It turned out that in the group of CRC patients (stages III-IV), the level of ADK-L mRNA was lower (p 0.0011) when compared to that of the control. For the first time, an average correlation was found between the level of expression of CD39 and ADK-S (r = -0.468 at p = 0.043) and between CD73 and ADK-L (r = 0.518 at p = 0.0232) in CRC patients. Flow cytometry was used to assess the content of CD39/CD73-expressing CD8+, CD4+ and Treg lymphocytes, as well as their relationship with the level of ADK gene expression in CRC patients. But no significant correlations were found.
There is analyzed the problem of theoretical understanding of the "Moskovian Poluustav" in the Russian historiography. This term began to be used by specialists in the area of Old Russian manuscripts sporadically yet in the first half of the 20th century, for example by V.N. Shchepkin, and was finally established through the influence of one of the most popular and authoritative textbooks on paleography by M.N. Tikhomirov. There are discussed the works of L.M. Kostyukhina, A.A. Turilov and M.G. Galchenko, which address theoretical issues of the evolution of Poluustav in the Old Russian manuscripts. As a result of historiographical analysis, there is made conclusion on the absence of clear definition for the term "Moskovian poluustav" in the domestic palaeographic science. Recently the researchers, dedicated to the graphic-orthographic features of the Russian medieval script, as well as the authors of several textbooks and manuals on palaeography, try not to use this term at all. In the opinion of the author, the most perspective approach to form this definition is to comparatively analyze correlation of the script graphics of the Old Russian manuscripts and the early printed book fonts of the middle of the 16th century.
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