Comparative Analysis of the Efficiency of the Binding of Phage Particles Displaying Tumor-Targeting Peptides to Cancer and Healthy Brain Cells

Applied Biochemistry and Microbiology - The efficiency of the binding of tumor-targeting phage particles displaying tumor-targeting peptides, which were obtained with phage-display technology, to...     

Tumor Specific Peptides Selected for Targeted Delivery of Therapeutic Agents to Glioma Human Cells

Russian Journal of Bioorganic Chemistry - Brain tumors are among the most intractable types of malignant neoplasms. Despite advances in the treatment of cancer, in particular, the development of...     

Human anti-DNA secretory immunglobulins A possess endonuclease activity and they are able to cause the destruction of nuclear chromatin in vitro

sIgA possessing ability to hydrolyse plasmid DNA to linear forms was purified from human milk by sequential chromatography on protein A-sepharose, DEAE-Fractogel and DNA-cellulose. It was discovered that incubation of sIgA with nuclei of porcine embryo kidney cells permeabilized by Triton X-100 causes formation of electrophoretically mobile forms of nuclear nucleic acids and inhibition of phosphorylation of nuclear proteins. We suppose that sIgA possessing affinity to DNA and endonuclease activity can cause degradation of cell nuclear chromatin.     

The analysis of biochemical markers of MCF-7 cells apoptosis induced by recombinant analog of lactaptin

Earlier we isolated and characterized human milk pro-apoptotic peptide - lactaptin and generated its engineered analog - RL2. It was shown that both lactaptin and RL2 are capable to induce apoptotic death of MCF-7 cells. In this report we have analyzed biochemical markers of RL2 induced MCF-7 apoptosis. The activation of initiator and effector caspases as well as mitochondrial membrane potential and cytoplasm membrane changes were analyzed using flow cytometry and Western-blot methods. We have found that RL2 induced apoptotic death of MCF-7 cells was accompanied by PS exposure on the plasma membrane surface. It also was shown that RL2 has induced dissipation of mitochondrial membrane potential and resulted in activation of initiator caspases 8, 9 and effector caspase 7.     

Immunogenicity of recombinant analog of antitumor protein lactaptin

Therapeutic monoclonal antibodies and recombinant proteins including cytokines are commonly used in the treatment of cancer and inflammatory diseases. In most cases, these protein-based drugs exhibit a high therapeutic efficacy, which is unfortunately frequently associated with a variety of side effects. We have investigated the in vitro and in vivo immunogenicity of recombinant antitumor protein lactaptin (RL2). Based on the qRT-PCR analysis, we have shown that, in MDA-MB-231 human breast adenocarcinoma cells, RL2 suppresses the NF-kB signaling cascade that regulates the reactions of innate immunity. RL2 inhibits the expression of the CXCL1 protein and apoptosis inhibitor A20 and enhances expression of IkB, NF-kB repressor. The ELISA method has been used to evaluate the antibody titer in the blood of mice, which received single and triple intravenous or intraperitoneal injections of RL2. The multiplex immunoassay of 23 cytokines in the mice blood has shown that the RL2 injections lead to a slight increase in the levels of systemic pro-inflammatory cytokine interleukin-5 (IL-5) and keratinocyte chemoattractant (KC), a homologue of human macrophage inflammatory protein-1 (MIP-1). These observations indicate the low immunogenicity of the recombinant lactaptin analog, which can be considered to be a potential molecular drug candidate for further clinical development.     

The effect of the acute and chronic administration of dalargin to mongrel rats on cardiac chronotropism at rest and under physical loading]

In chronic experiments on untrained awakening males of white rats it has been shown that the prolonged intraperitoneal injection of the opiate receptor agonist delargin (during 4, 5 days; 10 mkg/kg; twice a day) leads the chronotropic heart response to the maximum level of exercises and simultaneous decrease of heart rate variability. All this is accompanied by animals' undue fatiguability. It has been concluded that the chronic injection of opioid agonist receptors causes the decrease of sensitivity of these receptors to the action of endogenic opioids and as a consequence--the increase of sympathetic regulatory action on the heart rate at physical exercises and growth of fatiguability.     

Endogenous oligonucleotides of human milk and their possible biological function.

Oligonucleotides (ON) 4 to 60 nucleotides in length were isolated by ion-exchange chromatography on a column with Fractogel TSK DEAE-650 (M) from human milk which was hydrolyzed with proteinase K. ON from 60 to 16 nucleotides were degraded by RNase A but were resistant to DNase I, and, thus, they were ribooligonucleotides. In the presence of [gamma-32P]ATP, ON and heparin inhibited the phosphorylation of 38- and 20-kD milk proteins and failed to affect the phosphorylation of a 76-kD protein. Human milk is believed to contain polyanion-dependent and polyanion-independent protein kinases. The influence of the ON on the activity of the cytotoxic fraction of human milk alpha-lactalbumin towards human mammary gland carcinoma MCF-7 cells was studied. The ON inhibited the cytostatic and cytotoxic effects of alpha-lactalbumin. Synthetic oligonucleotides and heparin had similar effects. The endogenous ON are suggested to be involved in the regulation of cytotoxic activity of human milk.