A5040043601- Cancer Immunotherapy and Biomarkers
- Phagocytosis and Immune Regulation
- CAR-T cell therapy research
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Pancreatic function and diabetes
- Monoclonal and Polyclonal Antibodies Research
- Liver physiology and pathology
- RNA Interference and Gene Delivery
- Immune Cell Function and Interaction
- Proteoglycans and glycosaminoglycans research
- Apelin-related biomedical research
- Magnesium Oxide Properties and Applications
- Analytical Chemistry and Sensors
- Inorganic Chemistry and Materials
- Layered Double Hydroxides Synthesis and Applications
- Cell death mechanisms and regulation
- Glycosylation and Glycoproteins Research
- Retinoids in leukemia and cellular processes
- Nanoplatforms for cancer theranostics
- Electrochemical Analysis and Applications
- Cancer Research and Treatments
- NF-κB Signaling Pathways
- Inflammasome and immune disorders
- Advanced Breast Cancer Therapies
Jagiellonian University
2006-2021
// Krzysztof M. Zak 1,2 , Przemyslaw Grudnik 2 Katarzyna Guzik 3 Bartosz J. Zieba 1,3 Bogdan Musielak Alexander Dömling 4 Grzegorz Dubin and Tad A. Holak 1,3,5 1 Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa, Krakow, Poland Faculty Biochemistry, Biophysics Department Organic Chemistry, Ingardena, for Drug Design, University Groningen, Deusinglaan The Netherlands 5 Max Planck Institute Am Klopferspitz, Martinsried, Germany Correspondence to: Dubin, email:...
Blockade of the PD-1/PD-L1 immune checkpoint pathway with monoclonal antibodies has provided significant advances in cancer treatment. The antibody-based immunotherapies carry a number disadvantages such as high cost antibodies, their limited half-life, and immunogenicity. Development small-molecule inhibitors that could overcome these drawbacks is slow because incomplete structural information for this pathway. first chemical have been recently disclosed by Bristol-Myers Squibb. Here we...
Antibodies targeting the PD-1/PD-L1 immune checkpoint achieved spectacular success in anticancer therapy recent years. In contrast, no small molecules with cellular activity have been reported so far. Here we provide evidence that are capable of alleviating checkpoint-mediated exhaustion Jurkat T-lymphocytes. The two optimized small-molecule inhibitors interaction, BMS-1001 and BMS-1166, developed by Bristol-Myers Squibb, bind to human PD-L1 block its interaction PD-1, when tested on...
Monocytes and granulocytes were incubated with suspensions of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, or Salmonella enteritidis and, after being washed free bacteria, cultured for up to 48 h. Every few hours, samples cells taken DNA isolation. which phagocytosed bacteria showed features apoptotic cells, as determined by light microscopy fragmentation detected gel electrophoresis. The phenomenon was observed 2 4 h phagocytosis, in contrast, control monocytes did not...
Pulmonary accumulation of neutrophils is typical for active smokers who are also predisposed to multiple inflammatory and infectious lung diseases. We show that human neutrophil exposure cigarette smoke extract (CSE) leads an atypical cell death sharing features apoptosis, autophagy necrosis. Accumulation tar-like substances in autophagosomes apparent. Before detection established markers, CSE-treated effectively recognized non-phlogistically phagocytosed by monocyte-derived macrophages....
Layered double hydroxides (LDHs) containing Mg2+, Cu2+ or Zn2+ cations in the MeII positions and Al3+ Fe3+ MeIII were synthesized by co-precipitation method. Detailed studies of thermal transformation obtained LDHs into metal oxide systems performed using high temperature X-ray diffraction oxidising reducing atmosphere, thermogravimetry coupled with mass spectrometry temperature-programmed reduction. The LDH samples calcined at 600 900 °C tested role catalysts for selective oxidation ammonia...
ABSTRACT Human peripheral blood monocytes become apoptotic following phagocytosis of Staphylococcus aureus . In this study, we investigated the mechanisms involved in phenomenon. Cells exposed to bacteria were examined for surface expression Fas and ligand (FasL). The level soluble form FasL was also measured culture supernatants. As Fas-mediated apoptosis involves activation caspases, activities caspase-8 caspase-3 determined. Finally, involvement oxidative stress infected investigated....
The tumor suppressor protein p53, the "guardian of genome", is inactivated in nearly all cancer types by mutations TP53 gene or overexpression its negative regulators, oncoproteins MDM2/MDMX. Recovery p53 function disrupting p53-MDM2/MDMX interaction using small-molecule antagonists could provide an efficient nongenotoxic anticancer therapy. Here we present syntheses, activities, and crystal structures inhibitors based on 1,4,5-trisubstituted imidazole scaffold which are appended with...
On the basis of our recently resolved first cocrystal structure Mdm4 in complex with a small molecule inhibitor (PDB ID 3LBJ), we devised an approach for generation potential selective ligands. We performed Ugi four-component reaction (Ugi-4CR) 96-well plates indole fragment, which is specially designed to mimic Trp23, key amino acid interaction between p53 and Mdm4. Generally yielded mostly precipitates collected by filter plates. The best hit compound was found be active (Ki = 5 μM,...
The production of acute phase cytokines, interleukin 6 (IL‐6), tumour necrosis factor (TNF α ) and 1 (IL‐1β ), was studied in primary cultures human skin fibroblasts, monocytic cell line U937 umbilical vein endothelial cells (HUVEC) after vitro infection with vaccinia virus. Significant increase IL‐6 mRNA followed by enhanced protein secretion into the culture media found cells, HUVEC. TNFα increased virus infected resembled closely pattern observed cells. Transient NF‐κB binding activity...
Introduction Programmed cell death-1 (PD-1, CD279) protein is a surface receptor belonging to immunoglobulin superfamily. The expressed mostly on activated T cells and serves as an emergency brake for turning off the destructive action of these cells. Its natural ligand, PD-L1, several types immune prevent from autoimmune reactions provide homeostasis. Due its immunosuppressive function, PD-L1 also utilised by variety cancer evade deadly impact In recent years immunotherapy utilising...