DNA STRUCTURE, REPLICATION AND GENOME VARIABILITY CORRELATION

The study of special features of a new molecular DNA structure synthesis based on the fact that monomers transpositions can occur in the backbone of polymer chains according to the mathematical law known as a Fibonacci numerical series and «the Golden ratio» was performed. The example of the formation of a new DNA model demonstrates that there are dimers of three types in DNA structure: • Dimers with phosphodiester bond P-O-C, [(s-p) + (s-p)]; [(p-s)+(p-s)]; • Dimers with phosphatic bond P-O-P, [(s-p) + (p-s)]; • Dimers with glycosidic bond C-O-C, [(p-s)+(s-p)]. Dimers of the [(s-p) + (p-s)] type are of special importance for the process of replication. For example, if an enzyme catalyst (DNA polymerase) interacts in the backbone of matrix thread with a dimer of [(s-p) + (p-s)] type during the replication process it leads to a thread break. The growth of the daughter thread does not occur until the enzyme catalyst finds the transition point to another matrix thread of DNA, which contains in its backbone monomers similar to those, necessary for the activity of the given DNA polymerase. Thus, during the process of replication the genetic material is redistributed in the cell, and each daughter thread gets the information about genes belonging to both matrix threads of DNA molecule. This pattern of cell genome changing may manifest itself in phenotype or genotype of the body in different ways

CT and MRI Imaging of Theranostic Bimodal Fe₃O₄@Au NanoParticles in Tumor Bearing Mice

Gold-containing nanoparticles are proven to be an effective radiosensitizer in the radiotherapy of tumors. Reliable imaging of nanoparticles in a tumor and surrounding normal tissues is crucial both for diagnostics and for nanoparticle application as radiosensitizers. The Fe3O4 core was introduced into gold nanoparticles to form a core/shell structure suitable for MRI imaging. The aim of this study was to assess the in vivo bimodal CT and MRI enhancement ability of novel core/shell Fe3O4@Au theranostic nanoparticles. Core/shell Fe3O4@Au nanoparticles were synthesized and coated with PEG and glucose. C57Bl/6 mice bearing Ca755 mammary adenocarcinoma tumors received intravenous injections of the nanoparticles. CT and MRI were performed at several timepoints between 5 and 102 min, and on day 17 post-injection. Core/shell Fe3O4@Au nanoparticles provided significant enhancement of the tumor and tumor blood vessels. Nanoparticles also accumulated in the liver and spleen and were retained in these organs for 17 days. Mice did not show any signs of toxicity over the study duration. These results indicate that theranostic bimodal Fe3O4@Au nanoparticles are non-toxic and serve as effective contrast agents both for CT and MRI diagnostics. These nanoparticles have potential for future biomedical applications in cancer diagnostics and beyond

Therapy-induced secretion of spliceosomal components mediates pro-survival crosstalk between ovarian cancer cells

Abstract Ovarian cancer often develops resistance to conventional therapies, hampering their effectiveness. Here, using ex vivo paired ovarian cancer ascites obtained before and after chemotherapy and in vitro therapy-induced secretomes, we show that molecules secreted by ovarian cancer cells upon therapy promote cisplatin resistance and enhance DNA damage repair in recipient cancer cells. Even a short-term incubation of chemonaive ovarian cancer cells with therapy-induced secretomes induces changes resembling those that are observed in chemoresistant patient-derived tumor cells after long-term therapy. Using integrative omics techniques, we find that both ex vivo and in vitro therapy-induced secretomes are enriched with spliceosomal components, which relocalize from the nucleus to the cytoplasm and subsequently into the extracellular vesicles upon treatment. We demonstrate that these molecules substantially contribute to the phenotypic effects of therapy-induced secretomes. Thus, SNU13 and SYNCRIP spliceosomal proteins promote therapy resistance, while the exogenous U12 and U6atac snRNAs stimulate tumor growth. These findings demonstrate the significance of spliceosomal network perturbation during therapy and further highlight that extracellular signaling might be a key factor contributing to the emergence of ovarian cancer therapy resistance