A5029104625- Cell death mechanisms and regulation
- Peptidase Inhibition and Analysis
- RNA Interference and Gene Delivery
- Cancer-related Molecular Pathways
- Glycosylation and Glycoproteins Research
- Phagocytosis and Immune Regulation
- Cancer Research and Treatments
- Nanoparticle-Based Drug Delivery
- Microbial Metabolites in Food Biotechnology
- TGF-β signaling in diseases
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Polymer Surface Interaction Studies
- NF-κB Signaling Pathways
- Enzyme Structure and Function
- Plant Reproductive Biology
- Enzyme Production and Characterization
- RNA and protein synthesis mechanisms
- Immunotherapy and Immune Responses
- ATP Synthase and ATPases Research
- Cell Adhesion Molecules Research
- Glioma Diagnosis and Treatment
- Curcumin's Biomedical Applications
- Bacterial Genetics and Biotechnology
- Immune Response and Inflammation
Institute of Bioorganic Chemistry
2013-2024
D. Mendeleyev University of Chemical Technology of Russia
2023-2024
Institute of Bioorganic Chemistry
2014-2022
Russian Academy of Sciences
2008-2009
United States Nuclear Regulatory Commission
2000
University of Padua
1997
Harvard University
1992
Tumor necrosis factor-associated ligand inducing apoptosis (TRAIL) induces through the death receptors (DRs) 4 and 5 expressed on cell surface. Upon stimulation, are rapidly internalized clathrin-dependent -independent mechanisms. However, there have been conflicting data role of receptor endocytosis in apoptotic TRAIL signaling possible type-specific differences proposed. Here we compared kinetics TRAIL-mediated internalization subsequent recycling DR4 DR5 resistant (HT-29 A549) sensitive...
Recently, biodegradable polyelectrolyte multilayer capsules (PMC) have been proposed for anticancer drug delivery. In many cases, microencapsulation allows to concentrate the substance locally and prolong its flow cells. To reduce systemic toxicity when delivering highly toxic drugs, such as doxorubicin (DOX), development of a combined delivery system is paramount importance. Many efforts made exploit DR5-dependent apoptosis induction cancer treatment. However, despite having high antitumor...
Proteasome inhibitor bortezomib is an anticancer agent approved for treatment of multiple myeloma and mantle cell lymphoma. However, its application in other types cancer, primarily solid tumors, limited due to poor pharmacokinetics, inefficient tissue penetration, low stability frequent adverse effects. In the present study, a novel micellar nano‑scaled delivery system was manufactured, composed amphiphilic poly(N‑vinylpyrrolidone) nanoparticles loaded with bortezomib. Similar...
The Na,K-stimulated ATPase is inhibited by extracellular cardiac glycosides, which bind to the enzyme's alpha subunit. We used a monoclonal antibody, VG4, as probe of surface. antibody was specific for Na,K-ATPase and bound intact cells. epitope mapped first loop (H1-H2) alpha, using combination techniques including trypsinolysis, N-terminal sequence fragment containing determinant, analysis effects species-specific differences. activity under certain circumstances, indicating that H1-H2...
Curcumin attracts huge attention because of its biological properties: it is antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, usage has been limited by poor water solubility low bioavailability. Herein, to solve these problems, we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone). Nanoparticles were obtained using the solvent evaporation method characterized dynamic electrophoretic light scattering,...
TRAIL is considered a promising antitumor agent because it causes apoptosis of transformed cells without affecting normal cells. However, many types tumors are cytokine resistant, and combination therapy with various chemotherapeutic drugs being developed to overcome the resistance. We have demonstrated that doxorubicin, bortezomib, panobinostat dramatically reduced viability TRAIL-resistant A549 HT-29 Chemotherapy even more efficiently sensitized DR5-specific mutant variant DR5-B, which...
TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) mediates apoptosis in cancer cells through death receptors DR4 and DR5 preferring often one receptor over another the expressing both receptors. Receptor selective mutant variants of agonistic antibodies against are highly promising anticancer agents. Here using specific variant - DR5-B we have demonstrated for first time that sensitivity can be shifted from to during co-treatment with drugs. First studied contribution HCT116...
ONC201, the anticancer drug, targets and activates mitochondrial ATP-dependent caseinolytic peptidase P (ClpP), a serine protease located in matrix. Given promise of ONC201 cancer treatment, we evaluated its effects on breast ductal carcinoma cell line (BT474). We showed that transient single-dose treatment BT474 cells by 10 µM for period less than 48 h induced reversible growth arrest activation an integrated stress response indicated increased expression CHOP, ATF4, GDF-15, reduced number...
Despite the weak clinical efficacy of TRAIL death receptor agonists, a search is under way for new agents that more efficiently activate apoptotic signaling. We previously created DR5-selective variant DR5-B without affinity DR4, DcR1, DcR2, and OPG receptors increased proapoptotic activity in tumor cells. Here we showed significantly inhibited growth HCT116 Caco-2 but not HT-29 xenografts. The antitumor was 2.5 times higher xenografts compared to TRAIL. at dose 2 or 10 mg/kg/d days by 26%...
Nanoparticles based on the biocompatible amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) derivatives are promising for drug delivery. Amph-PVPs self-aggregate in aqueous solutions with formation of micellar nanoscaled structures. Amph-PVP nanoparticles able to immobilize therapeutic molecules under mild conditions. As is well known, many efforts have been made exploit DR5-dependent apoptosis induction cancer treatment. The aim study was fabricate Amph-PVP-based covalently conjugated...
TRAIL (TNF-related apoptosis-inducing ligand) and its derivatives are potentials for anticancer therapy due to the selective induction of apoptosis in tumor cells upon binding death receptors DR4 or DR5. Previously, we generated a DR5-selective mutant variant DR5-B overcoming receptor-dependent resistance TRAIL. In current study, improved antitumor activity by fusion with tumor-homing iRGD peptide, which is known enhance drug penetration into tissues. The obtained bispecific protein...
In the last two decades, bifunctional proteins have been created by genetic and protein engineering methods to increase therapeutic effects in various diseases, including cancer. Unlike conventional small molecule or monotargeted drugs, increased biological activity while maintaining low systemic toxicity. The recombinant anti-cancer cytokine TRAIL has shown a limited effect clinical trials. To enhance efficacy of TRAIL, we designed HRH-DR5-B fusion based on DR5-selective mutant variant...