Эндометриоз наблюдается у 10% женщин репродуктивного возраста, у пациенток с болевым синдромом встречается заметно чаще и составляет 30-50%, вызывая значительное ухудшение здоровья и репродуктивного исхода. Вопросы клиники, патогенеза и методов лечения наружно-генитального эндометриоза широко представлены в литературе. Однако до настоящего времени нет единого мнения об этиологии и причинах возникновения этого заболевания. В представленном обзоре рассмотрены актуальные вопросы этиологии наружно-генитального эндометриоза и основные теории развития этого заболевания. Ключевые слов а: этиология, патогенез эндометриоза, иммунология эндометриоза, стволовые клетки эндометрия.
BackgroundPreviously we demonstrated that the resection of primary 4T1 tumors only slightly prolongs mouse survival, but importantly, creates a “window of opportunity” with attenuated suppressor cell and increased activated T cell populations. This suggests that additional activation of the immune system by immunostimulatory agents during this period may enhance anti-tumor immunity and potentially eradicate micro-metastatic disease in this stringent model.We hypothesized that the immunostimulator Immunomax®, which is comprised of a plant-derived polysaccharide, is non-toxic in humans and stimulates immune defense during the infectious diseases treatment, may have also anti-tumor activity and be beneficial in the adjuvant setting when endogenous anti-tumor responses are present and during the “window of opportunity” in post-resection metastatic breast cancer model. Here we provide the initial report that Immunomax® demonstrates the capacity to eliminate micro-metastatic disease in the post-resection, 4T1 mouse model of breast cancer.MethodsThe efficacy of Immunomax® was evaluated by analyzing survival rate and the number of spontaneous clonogenic tumor cells in the lung homogenates of mice. The frequencies of activated NK, CD4+ and CD8+ cells as well as myeloid-derived suppressor cells and Treg cells were evaluated using flow cytometry. Highly purified mouse and human dendritic and NK cells were sorted and the effect of Immunomax® on activation status of these cells was assessed by flow cytometry. The property of Immunomax® as TLR-4 agonist was determined by NF-κB/SEAP reporter gene assay, WB, RT-PCR.ResultsImmunomax® injections significantly prolonged overall survival and cured 31% of mice. This immunostimulator activates DCs via the TLR-4, which in turn stimulates tumoricidal NK cells and in vitro, completely inhibits growth of 4T1 cells. Incubation of PBMC from healthy donors with Immunomax® activates NK cells via activation of plasmacytoid DC leading significantly higher efficacy in killing of human NK-target cells K562 compared with non-treated cells.ConclusionThis is the first demonstration that Immunomax® is a TLR-4 agonist and the first report of a documented role for this pharmaceutical grade immunostimulator in augmenting anti-tumor activity, suggesting that incorporation of Immunomax® into developing breast cancer therapeutic strategies may be beneficial and with less potential toxicity than checkpoint inhibitors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-014-0322-y) contains supplementary material, which is available to authorized users.
SSAP method was used to study the genetic diversity of 22 Linum species from sections Linum, Adenolinum, Dasylinum, Stellerolinum, and 46 flax cultivars. All the studied flax varieties were distinguished using SSAP for retrotransposons FL9 and FL11. Thus, the validity of SSAP method was demonstrated for flax marking, identification of accessions in genebank collections, and control during propagation of flax varieties. Polymorphism of Fl1a, Fl1b, and Cassandra insertions were very low in flax varieties, but these retrotransposons were successfully used for the investigation of Linum species. Species clusterization based on SSAP markers was in concordance with their taxonomic division into sections Dasylinum, Stellerolinum, Adenolinum, and Linum. All species of sect. Adenolinum clustered apart from species of sect. Linum. The data confirmed the accuracy of the separation in these sections. Members of section Linum are not as closely related as members of other sections, so taxonomic revision of this section is desirable. L. usitatissimum accessions genetically distant from modern flax cultivars were revealed in our work. These accessions are of utmost interest for flax breeding and introduction of new useful traits into flax cultivars. The chromosome localization of Cassandra retrotransposon in Linum species was determined.
We describe a method of isolation of human mesenchymal stromal cells from the umbilical cord (Wharton's jelly) and human placenta: amnion, placental villi, and trophoblast. Morphology, immunophenotypic characteristics, and differentiation potencies of isolated cells were studied. The capacity of mesenchymal stromal cells from extraembryonic tissues to osteogenic, adipogenic, and chondrogenic differentiation was demonstrated and the dynamics of this process was described. The isolated cells met the criteria for multipotent mesenchymal stem cells.
Cell cultures isolated by the enzymatic method from the terminal placenta amnion consist mainly from epithelial cells, expressing cytokeratin-7, CD90, and CD73, are characterized by high viability and low proliferative potential. Adhesive cultures of umbilical (Wharton's jelly) cells, despite the fibroblast-like shape of the cells and expression of surface markers, intrinsic to mesenchymal stromal cells, are also characterized by high heterogeneity during the initial stages of culturing, judging by an appreciable share of cytokeratin-expressing cells. The terminal placenta chorionic villi can be a source of cells with the most typical morphology and immunophenotypical profile of the resident multipotent mesenchymal stromal cells, which retain high viability in vitro and have a high proliferative potential.
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