Adenovirus Serotype 5 Variants Defective in Early Genes: Selective Replication in p53-Deficient Human Tumor Cells

Site-directed mutagenesis was used to construct human adenovirus serotype 5 (Ad5) variants defective in E1A or E1B. Mutant Adel3 with deletion from E1A was markedly attenuated in permissive cell cultures regardless of the p53 status, and replicated efficiently only in cells of the complementing 293 line. Mutant Adel2 with deletion from E1B55K infected the 293 line cells and p53-deficient human tumor cells (A431, SW480, HEp2) with efficiencies similar to those of Ad5, whereas its replication in normal p53-positive cells was substantially limited. Thus, Adel2 proved to be capable of selective infection and lysis of p53-deficient human tumor cells in vitro. On intratumor injection, Adel2 dramatically suppressed the growth of human epidermoid carcinoma (A431) in nude mice. Adel2 is thus a promising model for designing therapeutic agents against p53-deficient human tumors.     

Activation of lipid peroxidation and changes in vitamin E contents in the lungs under oxidative stress]

The lipid peroxidation (LPO) of the lung tissue and the bronchoalveolar lavage in rats under the influence of immobilization has been investigated. The effects accompanying the development of oxidative stress in animals--an increase in the content of conjugated dienes and fluorescent LPO products in biological objects and a strong decrease in the content of vitamin E in the lung tissue were registered.     

Identification of the ORC Complex Subunits That Can Interact with the ENY2 Protein of <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

The interaction of the Drosophila ENY2 protein with the ORC complex subunits was investigated. It is found that ORC4 and ORC6 subunits directly interact with ENY2.     

Study of Biodistribution of the Modular Nanotransporters after Systemic Administration in Murine Cloudman S91 Melanoma Model

The distribution of modular nanotransporters (MNTs) that are used to deliver drugs into melanoma cell nuclei after their intravenous administration into mice with Cloudman S91 melanoma was studied. The modification of MNTs with polyethylene glycol (PEG) of different length and their administration during the treatment with docetaxel, nitroglycerin, and excess of nonspecific MNTs leads to an improved accumulation of MNTs in the tummor. Among the variants studied, the MNT with attached PEG with M_r 40 kDa exhibited the best properties.     

Targeting ncRNAs by plant secondary metabolites: The ncRNAs game in the balance towards malignancy inhibition

The current trend of combining state of the art technologies with quondam treatments in order to overcome existing gaps in the clinical area determined an increased interest into polyphenols, common dietary phytochemicals, for the prevention and treatment of chronic diseases, especially cancer. The reemergence of polyphenols in the cancer field is sustained by advanced-omics technologies able to identify coding and non-coding genes and their related signaling pathways modulated by natural compounds. Identification of the structural correspondence between interacting molecules will allow the development of more targeted and informed therapeutic strategies for cancer management.     

Notes on the biology and ecology of the parasitoids of the poplar clearwing moth, Paranthrene tabaniformis (Rott.) (Lep., Sesiidae) in Bulgaria. I. Apanteles evonymellae (Bouché, 1834) (Hym., Braconidae)

Aspects of the biology and ecology of Apanteles evonymellae (Bouché), a parasitoid of the poplar clearwing moth, Paranthrene tabaniformis (Rott.), were studied during the period 1987–96. One-year-old poplar ( Populus spp.) shoots infested with P. tabaniformis larvae were collected during the winter months at 11 localities in Bulgaria and examined in the field and laboratory. Apanteles evonymellae was recorded in all areas studied in Bulgaria. The mortality of P. tabaniformis caused by this parasitoid in various regions of Bulgaria varied from 2.4 to 35.4%; the average for the country was 17.3%. Laboratory observations showed that A. evonymellae is a solitary endoparasitoid of the poplar clearwing moth. It develops in early-stage (first- to fourth-instar) host larvae and overwinters as a larva in the host. Apanteles evonymellae is bivoltine, but only the second generation is associated with P. tabaniformis . In the field, adult parasitoids of first generation appear in April about 1 month before the emergence of P. tabaniformis . The longevity of A. evonymellae adults is a maximum of 6 days. Therefore, in the spring, A. evonymellae cannot attack neonate P. tabaniformis larvae and must develop in alternative hosts. Prior to their death the parasitized P. tabaniformis larvae construct conical structures, 'refuges' of frass and silk threads over the external openings of the larval galleries. Apanteles evonymellae pupates in these refuges after the host's death. This modified behaviour of the parasitized host larvae probably protects the pupae of A. evonymellae from hyperparasites and predators.