Cyclophilin A as a Pro-Inflammatory Factor Exhibits Embryotoxic and Teratogenic Effects during Fetal Organogenesis.

The precise balance of Th1, Th2, and Th17 cytokines is a key factor in successful pregnancy and normal embryonic development. However, to date, not all humoral factors that regulate and influence physiological pregnancy have been completely studied. Our data here pointed out cyclophilin A (CypA) as the adverse pro-inflammatory factor negatively affecting fetal development and associated with pregnancy complications.

Physiological and Functional Effects of Dominant Active TCRα Expression in Transgenic Mice.

A T cell receptor (TCR) consists of α- and β-chains. Accumulating evidence suggests that some TCRs possess chain centricity, i.e.

Targeting Features of Curaxin CBL0137 on Hematological Malignancies In Vitro and In Vivo.

The anticancer activity of Curaxin CBL0137, a DNA-binding small molecule with chromatin remodulating effect, has been demonstrated in different cancers. Herein, a comparative evaluation of CBL0137 activity was performed in respect to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia and multiple myeloma (MM) cultured in vitro. MTT assay showed AML and MM higher sensitivity to CBL0137's cytostatic effect comparatively to other hematological malignancy cells.

Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity.

7-Methylguanine (7-MG) competitively inhibits the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) and RNA-modifying enzyme tRNA-guanine transglycosylase (TGT) and represents a potential anticancer drug candidate. Furthermore, as a natural compound, it could escape the serious side effects characteristic for approved synthetic PARP inhibitors. Here we present a comprehensive study of toxicological and carcinogenic properties of 7-MG.

Cyclophilin A is a factor of antitumor defense in the early stages of tumor development.

Cyclophilin A (CypA) is a pro-inflammatory factor with multiple immunomodulating effects. Here, we investigated the effects of recombinant human CypA (rhCypA) as a factor of antitumor host defense. Our results demonstrated that rhCypA dramatically inhibited the growth of murine transplantable tumors (mammary adenocarcinoma Ca755, melanoma B16, Lewis lung carcinoma (LLC), and cervical cancer CC-5).

Prevention of Colorectal Carcinogenesis by DNA-Binding Small-Molecule Curaxin CBL0137 Involves Suppression of Wnt Signaling.

Chemoprevention is considered a valid approach to reduce the incidence of colorectal cancer, one of the most common malignancies worldwide. Here, we investigated the tumor-preventive activity of curaxin CBL0137. This compound represents a new class of nonmutagenic DNA-binding small molecules that alter chromatin stability and inhibit the function of the histone chaperone FACT.

Analyses of the toxic properties of recombinant human Cyclophilin A in mice.

Cyclophilin A (CypA), an 18 kDa multi-functional protein with - isomerase activity, is both a ligand for cyclosporine A and a proinflammatory factor. CypA is also a chemoattractant for hemopoietic stem cells and progenitors of different lineages, and can mediate regenerative processes in an organism. Accumulated experimental data have suggested there are practical applications for this protein in the treatment of several diseases (i.

Re-Examination of the Esophageal Squamous Cell Carcinoma Model in Rats Induced by N-Nitrososarcosine Ethyl Ester Precursors.

Studies of the molecular mechanisms of esophageal cancer development have to be carried out on sufficient amount of tumor material, obtained under conditions of controlled exposure to carcinogenic factors. Esophageal cancer models on laboratory animals serve an indispensable source of this material. One of these models is esophageal cancer induction in rats by N-nitroso compound precursors.

Rapatar, a nanoformulation of rapamycin, decreases chemically-induced benign prostate hyperplasia in rats.

Benign prostatic hyperplasia (BPH) is the most common age-related disease in men. Here we tested the efficacy of Rapatar, a micellar nanoformulation of rapamycin, in two rat models of BPH: testosterone-induced and sulpiride-induced hyperplasia in ventral lobes and lateral/dorsal lobes, respectively. We found that Rapatar prevented hypertrophic and hyperplastic abnormalities and degenerative alterations in both BPH models.

[Inhibitory effect of human lactoferrin (neolactoferrin) on the growth of transplantable tumor in the uterine cervix of mice].

There was studied effect of recombinant form of human breast milk component-lactoferrin, received from milk of goats-producers (neolactoferrin), on growth of transplantable tumor of the cervix in mice (TTC-5). Neolactoferrin in dose of 100 mg/kg and 200 mg/kg of animals' mass inhibited the rate of tumor growth. The most effective was the dose of 200 mg/kg, which was entered a week before transplantation.

[The effect of preliminary administration of water with reduced deuterium content on the growth of transplantable tumors in mice].

It was investigated whether preliminary administration of water with reduced Deuterium content may modify the inhibitory effect of the water given to BDF1 and CDA mice on the day of tumor transplantation. Two models were used: Lewis lung carcinoma (LLC) and uterine cervical carcinoma (UCC). Experimental mice (20 per group) used the water with reduced Deuterium content.

[Low-deuterium water effect on transplantable tumors].

Such models of transplantable tumors as Lewis sarcoma, uterine sarcoma-322 and uterine carcinoma-5 were used to study possible inhibitory effect by low-deuterium water. Such water was given to experimental animals (20 mice in each group). Controls (30 in each group) received tap water with standard deuterium concentrations.

[Consideration of the deuterium-free water supply to an expedition to Mars].

Interplanetary missions, including to Mars, will put crews into severe radiation conditions. Search for methods of reducing the risk of radiation-induced cancer is of the top priority in preparation for the mission to Mars. One of the options is designing life support systems that will generate water with low content of the stable hydrogen isotope (deuterium) to be consumed by crewmembers.

TGF beta 1 induces growth arrest and apoptosis but not ciliated cell differentiation in rat tracheal epithelial cell cultures.

We are studying the regulation of ciliated cell differentiation using an in vitro model of tracheal regeneration. Previously, we reported that removal of growth stimulating compounds such as epidermal growth factor (EGF) and cholera toxin reduced DNA synthesis and cell number while increasing ciliated cell differentiation (Clark et al., 1995).

[Dynamics of proliferative activity of cultures of organotypic epithelial-mesenchymal recombinants from embryonic lungs of intact and urethane-receiving mice].

The dynamics of proliferative activity of cells was studied in the cultures of organotypic recombinants obtained from embryonic lung epithelium (E) and mesenchyma (M) of the intact and treated transplacentally by urethane mice (strain A). The labelling index (LI) of E and M in the aggregates obtained from treated embryonic lungs (EtMt) was significantly higher than LI in the aggregates from intact embryonic lungs (EiMi) in all days of cultivation (4-7-14). M from the treated embryonic lungs stimulated LI of the intact E (EiMt) but M from the intact embryonic lungs decreased LI of the treated E (EtMi).

[Morphogenetic characteristics of the aggregates formed in epithelial and mesenchymal recombinations of the lungs from intact and urethane-exposed mouse embryos].

A study was made of the morphogenesis of organotypic aggregates obtained by epithelial mesenchymal recombinations from the lungs of embryonic mice, intact and treated with urethane. Normal growth and differentiation of organotypic structures were observed in long-term cultures of aggregates obtained by recombinations of the lung epithelium (E) and mesenchyma (M) from intact (i) embryonic mice (EiMi). Hyperplasia and squamous-cell metaplasia (with or without keratinization) of the epithelium were found in aggregates obtained from E and M of the treated mouse embryos (EtMt) and in aggregates obtained by recombinations of lung E and M from intact and treated embryos (EtMi, EiMt).

[Characteristics of the proliferative activity of the aggregates forming during recombination of the epithelium and mesenchyma of embryonic lungs from intact and carcinogen-treated mice].

Methods of separation of the mouse embryonic lung mesenchyme (M) and epithelium (E) and obtaining homolinear and heterolinear organotypic aggregates of E and M from the intact and urethane-treated (transplacentally) A and C57BL mouse embryos. In the aggregates formed by E and M from the experimental A embryos, the index of labelled nuclei (3H-thymidine incorporation) in both the tissue components was several times that in the aggregates of E and M from the intact embryos. M from the experimental embryos aggregated with E from the intact embryos increased the proliferative activity of the latter 4 to 11 times, whereas M of the intact embryos aggregated with E of the experimental embryos decreased its proliferative activity to the normal level.