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41.
Shepelev MV Korobko EV Korobko IV 《Molekuliarnaia genetika, mikrobiologiia i virusologiia》2006,(4):3-7
Changes in the intracellular signaling cascades underlay many human pathologies including oncological diseases. Modification of the Wnt-signaling pathway are often associated with development of tumor and may play a significant role in carcinogenesis. This gives rise to a significant interest to studies of regulators and components of the Wnt-signaling pathway and search for approaches to practical implementation of the properties of the regulators. The goal of this work was to review the properties of WIF1 (Wnt inhibitor factor-1), a regulator of Wnt-signaling pathway, as a possible diagnostic and prognostic marker of human tumors, as well as basis for development of novel antitumoral preparations. 相似文献
42.
SV Tillib TI Ivanova EY Lyssuk SS Larin AV Kibardin EV Korobko PN Vikhreva NV Gnuchev GP Georgiev IV Korobko 《Biochemistry. Biokhimii?a》2012,77(6):659-665
Nanoantibodies (single-domain antibodies, nanobodies) derived from noncanonical single-chain immunoglobulins provide an attractive
tool for in vitro and in vivo diagnostics as well as for development of targeted drugs for clinical use. Nanoantibodies against several clinically important
targets have been developed and are actively investigated. However, no development of nanoantibodies against vascular endothelial
growth factor VEGF-A165 has been reported. We describe here the generation of nanoantibodies derived from single-chain Bactrian camel immunoglobulins
directed against VEGF-A165. We demonstrate that these nanoantibodies are suitable for enzyme-linked immunoassay to quantify human VEGF-A165 as well as for blocking its activity. Our results provide a basis for diagnostic kit development for quantification of VEGF-A165, which emerges as a biomarker useful in various pathological conditions. In addition, the nanoantibodies might be used for
development of therapeutic molecules targeting VEGF-A165-dependent pathological neoangiogenesis. 相似文献
43.
K. Evangelou J. Bramis I. Peros P. Zacharatos D. Dasiou-Plakida N. Kalogeropoulos PJ Asimacopoulos C. Kittas E. Marinos VG Gorgoulis 《Biotechnic & histochemistry》2004,79(1):5-10
It is well established that p16INK4A protein acts as a cell cycle inhibitor in the nucleus. Therefore, cytoplasmic localization of p16 INK4A usually is disregarded by investigators as nonspecific. Three recent studies reported findings that differ from the current view concerning p16INK4A immunohistochemical localization. All three demonstrated that breast and colon cancers expressing cytoplasmic p16INK4 represent distinct biological subsets. We previously detected in a percentage of non-small cell lung carcinomas simultaneous nuclear and cytoplasmic p16INK4A staining. In view of the reports concerning breast and colon carcinomas, we conducted an ultrastructural re-evaluation of our cases to clarify the specificity of p16INK4A cytoplasmic expression. We observed p16 INK4A immunolocalization in both the nucleus and the cytoplasm of a proportion of tumor cells. Diffuse dense nuclear staining was detected in the nucleoplasm, whereas weaker granular immunoreactivity was observed in the cytoplasm near the rough endoplasmic reticulum. Negative tumor cells also were visible. In the tumor-associated stromal, cells p16INK4A immunoreactivity was detected only in the nuclei. We have demonstrated that p16INK4A cytoplasmic staining is specific and suggest that it represents a mechanism of p16INK4A inactivation similar to that observed in other tumor suppressor genes. 相似文献
44.
Secretion of Recombinant Proteins via the Chaperone/Usher Pathway in Escherichia coli 总被引:2,自引:0,他引:2 下载免费PDF全文
Anton V. Zavialov Natalia V. Batchikova Timo Korpela Lada E. Petrovskaya Vyacheslav G. Korobko Joanne Kersley Sheila MacIntyre Vladimir P. Zav'yalov 《Applied microbiology》2001,67(4):1805-1814
F1 antigen (Caf1) of Yersinia pestis is assembled via the Caf1M chaperone/Caf1A usher pathway. We investigated the ability of this assembly system to facilitate secretion of full-length heterologous proteins fused to the Caf1 subunit in Escherichia coli. Despite correct processing of a chimeric protein composed of a modified Caf1 signal peptide, mature human interleukin-1β (hIL-1β), and mature Caf1, the processed product (hIL-1β:Caf1) remained insoluble. Coexpression of this chimera with a functional Caf1M chaperone led to the accumulation of soluble hIL-1β:Caf1 in the periplasm. Soluble hIL-1β:Caf1 reacted with monoclonal antibodies directed against structural epitopes of hIL-1β. The results indicate that Caf1M-induced release of hIL-1β:Caf1 from the inner membrane promotes folding of the hIL-1β domain. Similar results were obtained with the fusion of Caf1 to hIL-1β receptor antagonist or to human granulocyte-macrophage colony-stimulating factor. Following coexpression of the hIL-1β:Caf1 precursor with both the Caf1M chaperone and Caf1A outer membrane protein, hIL-1β:Caf1 could be detected on the cell surface of E. coli. These results demonstrate for the first time the potential application of the chaperone/usher secretion pathway in the transport of subunits with large heterogeneous N-terminal fusions. This represents a novel means for the delivery of correctly folded heterologous proteins to the periplasm and cell surface as either polymers or cleavable monomeric domains. 相似文献
45.
Petrovskaia LE Kriukova EA Kaiushin AL Rodina AV Moskaleva EIu Korobko VG 《Bioorganicheskaia khimiia》2002,28(5):440-446
To study the structure-function relationship of the human granulocyte-macrophage colony-stimulating factor (GM-CSF), genes were constructed that encode its three deletion mutants: D1, a mutant with the deletion of six amino acid residues (37-42) some of which are a part of a beta-structural region; D2, a mutant with the deletion of the unstructured six-aa sequence of a loop (45-50); and D3, a mutant with the deletion of 14 aa residues (37-50) corresponding to the A-B loop and encoded by the second exon of the gmcsf gene. The expression products of these genes in E. coli were accumulated in a fraction of insoluble proteins. The secondary structures of the mutant proteins were similar to that of the full-size GM-CSF, but the biological activity of the deletion mutants was 130 times lower than that of the GM-CSF: they stimulated the proliferation of the TF-1 cell line at 3 ng/ml concentration. The resulting proteins displayed antagonistic properties toward the full-size GM-CSF, with the inhibition degree of its colony-stimulating activity being 27%. A decrease in the mutant activity in the row D2 > D1 > D3 implies the importance of the conserved hydrophobic residues involved in the formation of the beta-structure for the formation of the GM-CSF functional conformation. 相似文献
46.
Petrovskaya L. E. Kryukova E. A. Kayushin A. L. Rodina A. V. Moskaleva E. Yu. Korobko V. G. 《Russian Journal of Bioorganic Chemistry》2002,28(5):397-403
To study the structure–function relationship of the human granulocyte-macrophage colony-stimulating factor (GM-CSF), genes were constructed that encode its three deletion mutants: D1, a mutant with the deletion of six amino acid residues (37–42) some of which are a part of a -structural region; D2, a mutant with the deletion of the unstructured six-aa sequence of a loop (45–50); and D3, a mutant with the deletion of 14 aa residues (37–50) corresponding to the A–B loop and encoded by the second exon of the gmcsf gene. The expression products of these genes in E. coli were accumulated in a fraction of insoluble proteins. The secondary structures of the mutant proteins were similar to that of the full-size GM-CSF, but the biological activity of the deletion mutants was 130 times lower than that of the GM-CSF: they stimulated the proliferation of the TF-1 cell line at 3 ng/ml concentration. The resulting proteins displayed antagonistic properties toward the full-size GM-CSF, with the inhibition degree of its colony-stimulating activity being 27%. A decrease in the mutant activity in the row D2 > D1 > D3 implies the importance of the conserved hydrophobic residues involved in the formation of the -structure for the formation of the GM-CSF functional conformation. 相似文献
47.
Current interest in the potential use of pancreatic stem-cells in the treatment of insulin dependent diabetes mellitus has led to increased research into normal pancreatic development. Pancreatic organogenesis involves branching morphogenesis of undifferentiated epithelium within surrounding mesenchyme. Current understanding is that the pancreatic islets develop exclusively from the epithelium of the embryonic buds. However, a cellular contribution to islets by mesenchyme has not been conclusively excluded. We present evidence that the mesenchyme of both the dorsal pancreatic bud and stomach rudiment make a substantial contribution of cells to islets during development in a three-dimensional avian model. These data suggest that mesenchyme can be a source not only of signals but also of cells for the definitive epithelia, making pancreatic organogenesis more akin to that of the kidney than to other endodermal organs. This raises the possibility for the use of mesenchymal cells as stem-or progenitor-cells for islet transplantation.Key Words: islets, stem-cells, development, epithelium, mesenchyme, pancreas, stomach, chick-quail, 3-dimensional, endocrine 相似文献
48.
49.
Lúcia de Paula Célio L Silva Daniela Carlos Camila Matias-Peres Carlos A Sorgi Edson G Soares Patrícia RM Souza Carlos RZ Bladés Fábio CS Galleti Vânia LD Bonato Eduardo DC Gonçalves Érika VG Silva Lúcia H Faccioli 《Genetic vaccines and therapy》2007,5(1):1-7
The great challenges for researchers working in the field of vaccinology are optimizing DNA vaccines for use in humans or large animals and creating effective single-dose vaccines using appropriated controlled delivery systems. Plasmid DNA encoding the heat-shock protein 65 (hsp65) (DNAhsp65) has been shown to induce protective and therapeutic immune responses in a murine model of tuberculosis (TB). Despite the success of naked DNAhsp65-based vaccine to protect mice against TB, it requires multiple doses of high amounts of DNA for effective immunization. In order to optimize this DNA vaccine and simplify the vaccination schedule, we coencapsulated DNAhsp65 and the adjuvant trehalose dimycolate (TDM) into biodegradable poly (DL-lactide-co-glycolide) (PLGA) microspheres for a single dose administration. Moreover, a single-shot prime-boost vaccine formulation based on a mixture of two different PLGA microspheres, presenting faster and slower release of, respectively, DNAhsp65 and the recombinant hsp65 protein was also developed. These formulations were tested in mice as well as in guinea pigs by comparison with the efficacy and toxicity induced by the naked DNA preparation or BCG. The single-shot prime-boost formulation clearly presented good efficacy and diminished lung pathology in both mice and guinea pigs. 相似文献
50.