This review considers approaches for detection of modified monomers in the RNA structure of living organisms. Recently, some data on dynamic alterations in the pool of modifications of the key RNA ...species that depend on external factors affecting the cells and physiological conditions of the whole organism have been accumulated. The recent studies have presented experimental data on relationship between the mechanisms of formation of modified/minor nucleotides of RNA in mammalian cells and the development of various pathologies. The development of novel methods for detection of chemical modifications of RNA nucleotides in the cells of living organisms and accumulation of knowledge on the contribution of modified monomers to metabolism and functioning of individual RNA species establish the basis for creation of novel diagnostic and therapeutic approaches. This review includes a short description of routine methods for determination of modified nucleotides in RNA and considers in detail modern approaches that enable not only detection but also quantitative assessment of the modification level of various nucleotides in individual RNA species.
The high mortality rate that accompanies cancer spurs the search for new methods that can be used to treat malignant neoplasms. In addition to chemotherapy, electrophysical techniques for tumor ...treatment appear rather promising. The results of in vitro exposure of A549 human lung adenocarcinoma cells to cold atmospheric plasma (CAP) are hereby presented. A gas-discharge device that generates a sequence of streamers propagating along a stream of inert gas in the ambient air was used. In the zone where the plasma jet came into contact with the target object, there were high-intensity electric fields and high plasma concentrations, while the gas temperature changed by less than a degree. In this study, we compared the cytotoxic effect of CAP in helium and argon. Direct irradiation of cells by CAP with U = 4.2 kV for 30-120 s was shown to reduce cell viability by 25%. Variation of the amplitude of the AC voltage in the plasma device in argon within a range of 3.8-5.6 kV did not significantly alter the cell death rate. Further optimization of the modes of CAP generation in gas-discharge devices with various geometries for the treatment of a tumor cell and animal tumor models can underlie the development of antitumor plasma medicine.
Abstract Objectives Analysing the influence of additional carcinoma in situ (CIS) and background parenchymal enhancement (BPE) in preoperative MRI on repeated surgeries in patients with invasive ...lobular carcinoma (ILC) of the breast. Methods Retrospective analysis of 106 patients (mean age 58.6 ± 9.9 years) with 108 ILC. Preoperative tumour size as assessed by MRI, mammography and sonography was recorded and compared to histopathology. In contrast-enhanced MRI, the degree of BPE was categorised by two readers. The influence of additionally detected CIS and BPE on the rate of repeated surgeries was analysed. Results Additional CIS was present in 45.4% of the cases (49/108). The degree of BPE was minimal or mild in 80% of the cases and moderate or marked in 20% of the cases. In 17 cases (15.7%) at least one repeated surgery was performed. In n = 15 of these cases, repeated surgery was performed after BCT (n = 9 re-excisions, n = 6 conversions to mastectomy), in n = 2 cases after initial mastectomy. The initial surgical procedure (p = 0.008) and additional CIS (p = 0.046) significantly influenced the rate of repeated surgeries, while tumour size, patient age and BPE did not (p = ns). Conclusions Additional CIS was associated with a higher rate of repeated surgeries, whereas BPE had no influence.
Magnetoresistance (MR) of ion irradiated monolayer graphene samples with a variable-range hopping (VRH) mechanism of conductivity was measured at temperatures down to T=1.8K in magnetic fields up to ...B=8T. It was observed that in perpendicular magnetic fields, hopping resistivity R decreases, which corresponds to negative MR (NMR), while parallel magnetic field results in positive MR (PMR) at low temperatures. NMR is explained on the basis of the “orbital” model in which perpendicular magnetic field suppresses the destructive interference of many paths through the intermediate sites in the total probability of the long-distance tunneling in the VRH regime. At low fields, a quadratic dependence (|ΔR/R|∼B2) of NMR is observed, while at B>B⁎, the quadratic dependence is replaced by the linear one. It was found that all NMR curves for different samples and different temperatures could be merged into common dependence when plotted as a function of B/B⁎. It is shown that B⁎∼T1/2 in agreement with predictions of the “orbital” model. The obtained values of B⁎ also allowed us to estimate the localization radius ξ of charge carriers for samples with a different degree of disorder. PMR in parallel magnetic fields is explained by suppression of hopping transitions via double occupied states due to alignment of electron spins.
•Magnetoresistance of ion irradiated graphene samples with VRH mechanism of conductivity was measured.•In perpendicular magnetic fields negative magnetoresistance was observed.•In parallel magnetic fields positive magnetoresistance was observed.•Theoretical interpretation of the observed results was proposed.
Increased plasma concentrations of circulating adhesion molecules in patients with Type II (non-insulin-dependent) diabetes mellitus could be associated with the increased cardiovascular risk in ...these patients. However, it is controversial whether increased adhesion molecule plasma concentrations are primarily related to hyperglycaemia or to hyperinsulinaemia.
We evaluated the plasma concentrations of soluble E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) at baseline and during euglycaemic hyperinsulinaemic clamp in three different groups without additional cardiovascular risk factors: group A (control group), 28 healthy volunteers with normal glucose tolerance; group B, 24 subjects with fasting hyperinsulinaemia, normal fasting glucose but impaired glucose tolerance; group C, 32 patients with Type II diabetes, fasting hyperinsulinaemia and chronic hyperglycaemia.
Plasma soluble E-selectin, ICAM-1, and VCAM-1 concentrations were higher ( p < 0.05) in patients with Type II diabetes (group C) compared with the other groups. The adhesion molecule concentrations correlate with the fasting plasma glucose ( r = 0.59, p < 0.001), the 2-h OGTT plasma glucose ( r = 0.70, p < 0.01), and the HbA(1 c) value ( r = 0.61, p < 0.05). The E-selectin but not the ICAM-1 and VCAM-1 plasma concentrations correlated with the fasting insulin concentrations ( r = 0.62, p < 0.05) or the whole body glucose uptake ( r = 0.59, p < 0.05) in the clamp. The hyperinsulinaemia during the euglycaemic hyperinsulinaemic clamp had no significant effect on the plasma concentrations of E-selectin, ICAM-1, and VCAM-1 in all three groups.
Our results suggest that increased E-selectin concentrations are related to hyperglycaemia, hyperinsulinaemia and insulin resistance, whereas increased ICAM-1 and VCAM-1 plasma concentrations in patients with Type II diabetes are rather related to hyperglycaemia than to hyperinsulinaemia or insulin resistance.
A new species of the genus Oligopogon Loew, O. armeniacus sp. n., is described from Armenia. The holotype is deposited in the Zoological Institute of the Russian Academy of Sciences, St. Petersburg.
Antimetastatic effect of the liposomal form of recombinant lactaptin RL2 (a proteolytic fragment of human breast milk κ-casein; 8.6 kDa) was studied in A/Sn mice after intravenous transplantation of ...GA-1 tumor with high rate of liver metastases. Tumor growth in the liver was found in all mice. In animals dying early, the tumors were presented by multiple nodes of about the same size; in mice dying later, the tumors in the liver were presented by just few large nodes formed by cells that survived chemotherapy. A single intravenous injection of RL2 lactaptin in liposomes prolonged lifespan of animals with liver metastases of GA-1 tumor by 1.5 times in comparison with that in untreated animals.
One of the dominant trends in modern pharmacology is the creation of drugs that act directly on the lesion focus and have minimal toxicity on healthy tissues and organs. This problem is particularly ...acute in relation to oncologic diseases. Short tissue- and organ-specific peptides capable of delivering drugs to the affected organ or tissue are considered promising targeted agents that can be used in the diagnosis and therapy of diseases, including cancer. The review discusses in detail the technology of phage display as a method for obtaining specific targeted peptide agents and offers examples of their use in diagnostic and clinical practice.
The purpose of this work was to study the formation and growth of mono- (3D) and heterogeneous (3D-2) spheroids composed of stromal and tumor cells that mimic three types of breast cancer: ER+/PR+, ...HER2+, and ER
-
/PR
-/
HER2 when spheroids are exposed to 17-β estradiol (E2) and TGF-β. Breast cancer cell lines MCF7, MDA-MB-231, SK-BR-3 and non-transformed BN120f fibroblasts were used to generate 3D and 3D-2 heterogeneous cultures. Uniform conditions for 3D culturing of all three breast-cancer cell lines are proposed that results in, proliferating spheroids. When tumor cells and healthy fibroblasts were mixed in a ratio of 1 : 4, the inner core of 3D-2 structures contained fibroblasts and the epithelial tumor cells formed outer layer of spheroids. The morphological analysis of spheroids showed that such co-cultivation of tumor and stromal cells in the 3D-2 model, produced more rounded and well-structured spheroids that is typical for self-organization into microtissue in comparison with 3D tumor cell model. It was found that E2 stimulated tumor cell proliferation in 3D and 3D-2 spheroids, regardless of that breast-cancer type these cells imitate. , while in 2D model, MDA-MB-231 cells were resistant to E2. In 3D models MDA-MB-231 cells lost, and SK-BR-3 cells acquired sensitivity to the pro-proliferative effect of TGF-β. Thus, it has been shown that 3D and 3D-2 cell models of breast cancer are an important tool to study the tumor progression and for testing new antitumor approaches, despite the existing 2D models.
PDF
