N-Glycoside of Indolo[2,3-]pyrrolo[3,4-]carbazole LCS1269 Exerts Anti-Glioblastoma Effects by G2 Cell Cycle Arrest and CDK1 Activity Modulation: Molecular Docking Studies, Biological Investigations, and ADMET Prediction.

Indolo[2,3-]pyrrolo[3,4-]carbazole scaffold is successfully used as an efficient structural motif for the design and development of different antitumor agents. In this study, we investigated the anti-glioblastoma therapeutic potential of glycosylated indolocarbazole analog LCS1269 utilizing in vitro, in vivo, and in silico approaches. Cell viability was estimated by an MTT assay.

Clinical Relevance of Differential and Expression in Myelodysplastic Syndromes.

Background/aim: Myelodysplastic syndromes (MDS) are clinically heterogeneous hematological malignancies with an increased risk of transformation to acute myeloid leukemia, emphasizing the importance of identifying new diagnostic and prognostic markers. This study sought to investigate the predictive ability of all-trans retinoic acid (ATRA)-dependent nuclear transcription factors RARα and PPARβ/δ gene expression in MDS patients.

Materials And Methods: Peripheral blood specimens were collected from 49 MDS patients and 15 healthy volunteers.

The Molecular Mechanisms of Oleanane Aldehyde-β-enone Cytotoxicity against Doxorubicin-Resistant Cancer Cells.

Oleanane aldehyde-β-enone (), being the semi-synthetic derivative of the triterpenoid betulin, effectively inhibits the proliferation of HBL-100 and K562 cancer cells (IC 0.47-0.53 µM), as well as the proliferation of their resistant subclones with high P-gp expression HBL-100/Dox, K562/i-S9 and K562/i-S9_Dox (IC 0.

Evaluation of and gene expression as prognostic markers in low and intermediate‑1 risk patients with myelodysplastic syndromes.

Vascular endothelial growth factors (VEGFs) are angiogenic factors playing a key role in tumor development. VEGFs are produced by different normal and tumor cells, including platelets, lymphocytes and mononuclear cells of peripheral blood. ( and ) and ( and ) gene expression was studied in patients with myelodysplastic syndrome (MDS) to evaluate the possible prognostic role of the expression of these genes.

A novel glycosylated indolocarbazole derivative LCS1269 effectively inhibits growth of human cancer cells in vitro and in vivo through driving of both apoptosis and senescence by inducing of DNA damage and modulating of AKT/mTOR/S6K and ERK pathways.

In recent decades, indolocarbazole glycosides containing sugar moieties have attracted attention due to their diverse anti-tumor activities. In the present study, a series of new indolo [2,3-a]pyrrolo [3,4-c]carbazole derivatives were synthesized for the first time. First of all, we have shown that compound 6e (LCS1269) had the most pronounced effect on inhibiting tumor growth in the transferable solid and non-solid murine tumors as compared with other synthesized indolocarbazole derivatives.

Triterpenoids with modified A-ring as modulators of P-gp-dependent drug-resistance in cancer cells.

Semi-synthetic A-cycle modified triterpenic derivatives with A-cycle condensed with a heterocyclic fragment (compound 1) and fragmented A-ring (compound 2) were tested for cytotoxicity against several tumor cell cultures and doxorubicin (Dox)-resistant cell lines. The equal cytotoxicity of the tested compounds to the parental tumor cell lines (HBL-100, K562) and their resistant subclones (HBL-100/Dox, K562/i-S9) was revealed. The overexpression of ABCB1 (MDR1) gene and P-glycoprotein (P-gp) was confirmed for both resistant subclones of tumor cells.

[Analysis of VEGF-A/VEGFR1/VEGFR2 gene expression in patients with myelodysplastic syndrome].

Aim: To assess the significance of gene expression of the vascular endothelial growth factor-A (VEGF-A) and its interacting receptors VEGFR1 and VEGFR2 as potential diagnostic and prognostic molecular markers in patients with myelodysplastic syndrome (MDS).

Material And Methods: A real time polymerase chain reaction (RT-PCR) assay was used to investigate the gene expression of VEGF-A, VEGFR1, and VEGFR2 in the mononuclear cell fractions obtained from 24 patients with MDS.

Results: The expression of the 3 genes was identified in all the patients examined.

Iodide-Iodates M[IO]·AgI, M = Bi, Tb, with a Framework Structure and High Second-Harmonic Generation Optical Response.

Single crystals of two new iodide-iodates, Bi[IO]·AgI and Tb[IO]·AgI, are synthesized in hydrothermal systems. The anionic parts in both iodide-iodates are characterized as a complex charged framework of isolated IO umbrella-like groups and large Bi(Tb)-O polyhedra similar to those previously found in La[IO][IO](PbO). Broad channels along the c-axis contain compensators: (AgI) umbrella-like groups and additional Ag ions which form Ag tetrahedral clusters augmented with I halogen.

RARα mediates all-trans-retinoic acid-induced VEGF-C, VEGF-D, and VEGFR3 expression in lung cancer cells.

The regulation of vascular endothelial growth factors C (VEGF-C) and D (VEGF-D), and their receptor VEGFR3 gene and protein expression by all-trans-retinoic acid (atRA) in A549 lung cancer cells, was investigated. We showed that atRA treatment increased VEGF-C, VEGF-D, and VEGFR3 protein and mRNA contents in dose-dependent manner. atRA-mediated increase of both ligands and receptor expression correlated with the elevated level of retinoic acid receptor α (RARα) expression, while the level of another atRA receptor, peroxisome proliferator-activated receptor β/δ (PPARβ/δ), was decreased.

[Some molecular and genetic properties of progenitor cells in sarcomas induced with foreign body].

One of the important questions in understanding the mechanisms of carcinogenesis induced with foreign body (or plastic carcinogenesis), is a question about normal progenitor cells in sarcomas (FB sarcomas) appearing in close proximity to the plastic plate implanted under the skin of an experimental animal. There is an assumption in literature that progenitor cells in FB sarcomas originate from vascular endothelium cells feeding a connective tissue capsule that forms around foreign body. In our research, we studied mRNA expression of one of the endothelial cell markers--receptor VEGFR2/FIk1--and growth factor VEGF-A, which interacts with it, in precancerous cells of FB sarcomas in mice.

[Gene expression of vascular endothelial growth factors and their receptors in different variants of the course of multiple myeloma].

Aim: To determine the significance of the angiogenic activity estimated from the gene expression of the vascular endothelial growth factors (VEGFs) VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR1, VEGFRls, VEGFR2, and VEGFR3 in the mononuclear cell fraction of bone marrow (BM) aspirates with tumor plasma cells predominating in different variants of the course of multiple myeloma (MM).

Materials And Methods: The gene expression of VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFRI, VEGFRls, VEGFR2, and VEGFR3 was determined by reverse-transcription polymerase chain reaction (RT-PCR).

Results: VEGF-A, VEGF-C, VEGF-D, as well as VEGFR1, VEGFRls, VEGFR2, and VEGFR3 were expressed showing different intensities in the mononuclear cell fraction of BM aspirates with a predominance of tumor plasma cells in the patients with MM, which allowed patient groups to be identified.

[Expression of VEGFA during 1,2-dimethylhydrazine induction of malignant hemangioendothelioma in the renal capsule in mice].

There was examined the role of VEGFA in the induction of malignant hemangioendothelioma (HAE) in the nonvascular tissue of renal capsule (RC) in mice. Expression mRNA VEGFA and its receptor Flk1 in RC and the kidneys in male mice of CBA and C57B1/6 lines was studied at different stages of the administration of a chemical carcinogen 1,2-dimethylhydrazine (DMH), which induced HAE of PC in CBA males with a high frequency, and in C57B1/6 line--with a low frequency. In the kidneys of male mice of both lines at all stages there was observed significant expression both VEGFA and Flk1 but no linear differences were found.

Expression of vascular endothelial growth factor receptors VEGFR1 in cultured multiple myeloma cells: correlation with immunophenotype and drug resistance.

We studied the expression of genes encoding vascular endothelial growth factors VEGF-A, VEGF-C, VEGF-D and their receptors in cell cultures of human multiple myeloma IM9, RPMI 1640, RPMI 8226. The studied cells did not differ by the expression of growth factors. Expression of VEGFR1 receptor was detected only in IM9 cells and VEGFR2 and VEGFR3 receptors were not expressed in multiple myeloma cells.

Mechanisms of angiogenesis.

Tissue activity of angiogenesis depends on the balance of many stimulating or inhibiting factors. The key signaling system that regulates proliferation and migration of endothelial cells forming the basis of any vessel are vascular endothelium growth factors (VEGF) and their receptors. The VEGF-dependent signaling system is necessary for formation of the embryonic vascular system.

[Antibacterial therapy of acute sinusitis in outpatient practice: results of a multicenter trial].

Now there is no generally accepted practice of antibacterial therapy of acute sinusitis in outpatient clinics of Russia. Choice of antibacterial drugs is often made without consideration of the most probable causative agents of the infection. Out-of-date antibiotics used in many cases do not satisfy modern requirements.

[Analysis of parameters of the antibacterial treatment of acute otitis media in adults: results of a multicenter study].

The programme was aimed at audit of the parameters of antibacterial therapy for acute otitis media in adult outpatients in 8 cities of Russia (Smolensk, Volgograd, Ekaterinburg, Yaroslavl, Nizhny Novgorod, Tyumen, Ryazan, Vladivostok). The information sources were the case records. The data from the records were structurally fixed in specially designed individual registration charts for further computer processing.

VEGFc and VEGFR3 expression in human thyroid pathologies.

In vertebrates, vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are major determinants of angiogenesis. In adults, the interaction between VEGFc and VEGFR3 (previously FLT4) is more specifically involved in the biology of lymphatics. Using PCR amplification of reverse-transcribed mRNA, we studied the expression of the VEGFR3 (including its short and long forms) and VEGFc genes in 38 samples of various human thyroid pathologies.

Expression of the FLT4/VEGFR3 receptor tyrosine kinase encoding gene in hepatic tumors.

The FLT4/VEGFR3 tyrosine kinase receptor belongs to a class of receptors for growth factors of the vascular endothelial growth factor family and is important for the biology of lymphatic endothelium. It may play an important role in tumor growth. We have looked for the expression of the FLT4 gene in tumors of various origins.

The FLT4 gene encodes a transmembrane tyrosine kinase related to the vascular endothelial growth factor receptor.

Three receptor tyrosine kinases, FLT1, FLK1 and FLT4, contain seven immunoglobin-like domains in their extracellular region and are strongly related by sequence similarities to each other and, to a lesser degree, to the class III receptors CSF1R/FMS, PDGFR, SLFR/KIT and FLT3/FLK2. They constitute a family of receptors putatively involved in the growth regulation of endothelial cells. We describe here the structure and pattern of expression of the human FLT4 gene.

Chromosomal localization of FLT4, a novel receptor-type tyrosine kinase gene.

A new human gene encoding a putative receptor-type tyrosine kinase (RTK) was isolated by screening a placenta cDNA library with a mouse Flt3 probe. The deduced amino acid sequence of the intracellular region of the molecule showed that it was strongly related to the FLT1 and KDR/FLK1 gene products and to a lesser degree to members of the class III RTKs: FMS/CSF1R, PDGFRA/B, KIT, and FLT3. The gene was named FLT4.

[Effect of sex hormones on the 1,2-dimethylhydrazine metabolic activity in the kidneys of CBA-strain mice].

1,2-dimethylhydrazine (DMH) metabolizing activity of kidney microsomes was shown to be two times higher in male, than in female CBA mice. Castration decreased DMH metabolizing activity of male kidney microsomes to the females' level. DMH metabolizing activity of castrated males treated with testosterone propionate was identical to that of intact males.

[Specificity of cytochrome P-450 isoforms contained in endoplasmic reticulum membranes and nuclear membranes in relation to benzo(a)pyrene].

The metabolic activation of benz(a)pyrene (BP) catalyzed by rat liver microsomes and isolated liver nuclei in the presence of certain inhibitors of the monooxygenase system was studied. Several forms of cytochrome P-450 are supposed to participate in metabolic conversion of BP. The specificity of cytochrome P-450 isoforms contained in the endoplasmic reticulum and in nuclear membranes is discussed.