A5056157315- Cell death mechanisms and regulation
- RNA Interference and Gene Delivery
- Cancer Research and Treatments
- Phagocytosis and Immune Regulation
- Ubiquitin and proteasome pathways
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Immunotherapy and Immune Responses
- Cancer-related Molecular Pathways
- PARP inhibition in cancer therapy
- Bacteriophages and microbial interactions
- Click Chemistry and Applications
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Peptidase Inhibition and Analysis
- GDF15 and Related Biomarkers
- CAR-T cell therapy research
- Glioma Diagnosis and Treatment
- Antimicrobial Resistance in Staphylococcus
- Monoclonal and Polyclonal Antibodies Research
- Advanced Biosensing Techniques and Applications
- Nanoplatforms for cancer theranostics
- CRISPR and Genetic Engineering
- ATP Synthase and ATPases Research
- Cell Adhesion Molecules Research
Institute of Bioorganic Chemistry
2017-2024
Institute of Bioorganic Chemistry
2022
Lomonosov Moscow State University
2020-2021
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...
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...
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...
The development of therapeutic bispecific antibodies and hybrid proteins is one the most urgent biomedical technologies with obvious clinical prospects. At same time, advanced strategies molecular design drugs new properties are coming to forefront. tumour necrosis factor-related apoptosis inducing ligand (TRAIL) receptor pathways important components immune system involved in surveillance selective elimination transformed cells. TRAIL-based therefore promising drug candidates for treatment...
A technique for the expression of bispecific fusion protein SRH-DR5-B by autoinduction in E. coli strain BL21(DE3)pLys has been developed. The new technologically simple and economical allows to obtain high amounts active target from a soluble cell fraction.