A5055499202- Adenosine and Purinergic Signaling
- Nanoplatforms for cancer theranostics
- Neuroscience of respiration and sleep
- Pancreatic function and diabetes
- RNA Interference and Gene Delivery
- Platelet Disorders and Treatments
- Neurological Complications and Syndromes
- Retinal Diseases and Treatments
- Cytomegalovirus and herpesvirus research
- Blood Coagulation and Thrombosis Mechanisms
- Pneumocystis jirovecii pneumonia detection and treatment
- Click Chemistry and Applications
- Fish Biology and Ecology Studies
- Genetics and Neurodevelopmental Disorders
- Marine and environmental studies
- Polyomavirus and related diseases
- Extracellular vesicles in disease
- Amino Acid Enzymes and Metabolism
- Heme Oxygenase-1 and Carbon Monoxide
- Neuroendocrine Tumor Research Advances
- Biochemical and Molecular Research
- Ichthyology and Marine Biology
- Adolescent and Pediatric Healthcare
- Calcium signaling and nucleotide metabolism
- Blood properties and coagulation
University of Turku
2018-2024
Kamchatka State Technical University
2012
Cluster of differentiation 73 (CD73) converts adenosine 5′-monophosphate to immunosuppressive adenosine, and its inhibition was proposed as a new strategy for cancer treatment. We synthesized 5′-O-[(phosphonomethyl)phosphonic acid] derivatives purine pyrimidine nucleosides, which represent nucleoside diphosphate analogues, compared their CD73 inhibitory potencies. In the adenine series, most ribose modifications 1-deaza 3-deaza were detrimental, but 7-deaza tolerated. Uracil substitution...
The extracellular ATP/adenosine axis in the tumor microenvironment (TME) has emerged as an important immune-regulatory pathway. Nucleoside triphosphate diphosphohydrolase-1 (NTPDase1), otherwise known CD39, is highly expressed TME, both on infiltrating immune cells and across a broad set of cancer indications. CD39 processes pro-inflammatory ATP to ADP AMP, which then processed by Ecto-5ʹ-nucleotidase/CD73 immunosuppressive adenosine. Directly inhibiting enzymatic function via antibody...
Extracellular adenosine mediates diverse anti-inflammatory, angiogenic and vasoactive effects, has become an important therapeutic target for cancer, which been translated into clinical trials. This study was designed to comprehensively assess metabolism in prostate breast cancer cells. We identified cellular turnover as a complex cascade, comprising (1) the ectoenzymatic breakdown of ATP via sequential ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1, officially known ENPP1),...
Background and objective For many pathological states, microparticles are supposed to be one of the causes hypercoagulation. Although there some indirect data about participation in coagulation activation propagation, integral hemostasis test Thrombodynamics allows measure micropaticles these two phases directly. Demonstrates by influence on appearance centres plasma volume rate clot growth from surface with immobilized tissue factor.Methods: Microparticles were obtained platelets...
Abstract Ecto-5’-nucleotidase (CD73) is a potential new drug target for cancer immunotherapy. Its overexpression associated with various aggressive cancers, including triple-negative breast (TNBC) and pancreatic cancer, making it promising diagnostic imaging. Besides antibodies, small molecule CD73 inhibitors have been developed are currently in clinical trials. This study aimed to develop evaluate fluorine-18 labeled high-affinity as tracers the non-invasive positron emission tomography...
ATP and adenosine are important signaling molecules involved in vascular remodeling, retinal function, neurovascular coupling the eye. Current knowledge on enzymatic pathways governing duration magnitude of ocular purinergic is incompletely understood. By employing sensitive analytical assays, this study dissected purine homeostasis as a complex coordinated network. Along with previously characterized ecto-5′-nucleotidase/CD73 adenylate kinase activities, other enzymes have been identified...
We recently reported N4-substituted 3-methylcytidine-5′-α,β-methylenediphosphates as CD73 inhibitors, potentially useful in cancer immunotherapy. now expand the structure–activity relationship of pyrimidine nucleotides human inhibitors. 4-Chloro (MRS4598 16; Ki = 0.673 nM) and 4-iodo (MRS4620 18; 0.436 substitution N4-benzyloxy group decreased by ∼20-fold. Primary alkylamine derivatives coupled through a p-amido with varying methylene chain length (24 25) were functionalized congeners, for...
Ecto-5′-nucleotidase (CD73) catalyzes the hydrolysis of AMP to anti-inflammatory, immunosuppressive adenosine. It is expressed on vascular endothelial, epithelial, and also numerous cancer cells where it strongly contributes an microenvironment. In present study we designed synthesized fluorescent-labeled CD73 inhibitors with low nanomolar affinity high selectivity based N6-benzyl-α,β-methylene-ADP (PSB-12379) as a lead structure. Fluorescein was attached benzyl residue via different linkers...
ATP and adenosine have emerged as important signaling molecules involved in vascular remodeling, retinal functioning neurovascular coupling the mammalian eye. However, little is known about regulatory mechanisms of purinergic Here, we used three-dimensional multiplexed imaging, situ enzyme histochemistry, flow cytometric analysis, single cell transcriptomics to characterize whole pattern purine metabolism mouse human eyes. This study identified ecto-nucleoside triphosphate...
Abstract The ATP/Adenosine pathway in the tumor microenvironment (TME) has emerged as an important immune-regulatory pathway. ATPase CD39 is highly expressed TME, both on infiltrating immune cells and across a broad set of cancer indications. processes pro-inflammatory extracellular ATP to ADP AMP, which then processed by CD73, immunosuppressive adenosine. Inhibiting enzymatic function potential shift milieu TME 2-pronged fashion: 1) Enhancement immunostimulatory released damaged and/or...
Background and objective For many pathological states, microparticles are supposed to be one of the causes hypercoagulation. Although there some indirect data about participation in coagulation activation propagation, integral hemostasis test Thrombodynamics allows measure micropaticles these two phases directly by influence on appearance centers plasma volume rate clot grown from surface with immobilized tissue factor. Methods Microparticles were obtained platelets erythrocytes stimulation...
The ATP/Adenosine pathway in the tumor microenvironment (TME) has emerged as an important immune-regulatory pathway. ATPase CD39 is highly expressed TME, both on infiltrating immune cells and across a broad set of cancer indications. processes pro-inflammatory extracellular ATP to ADP AMP, which then processed by CD73, immunosuppressive adenosine. Inhibiting enzymatic function potential shift milieu TME 2-pronged fashion: 1) Enhancement immunostimulatory released damaged and/or dying 2)...
ABSTRACT First Person is a series of interviews with the first authors selection papers published in Journal Cell Science, helping early-career researchers promote themselves alongside their papers. Karolina Losenkova author on ‘Compartmentalization adenosine metabolism cancer cells and its modulation during acute hypoxia’, JCS. PhD student lab Gennady Yegutkin at Medicity Research Laboratory, University Turku, Finland, investigating role purine-converting enzymes tumorigenesis.
Adenosine in the tumor microenvironment acts on A2A and A2B adenosine receptors (ARs) immune cells (T cells, dendritic NK macrophages neutrophils) to prevent their activation. Therefore, a means of lowering extracellular would be beneficial cancer immunotherapy either as co-therapy or monotherapy. Inhibitors CD73 (ecto-5'-nucleotidase, main adenosine-forming enzyme) are already clinical trials for immunotherapy. Many purine (ADP) analogues have been shown inhibit this enzyme, but we explored...
Abstract Ocular ATP and adenosine have emerged as important signalling molecules involved in vascular remodeling, retinal functioning neurovascular coupling the mammalian eye. However, little is known about regulatory mechanisms of purinergic signaling Here, we used three-dimensional multiplexed imaging combination with situ enzyme histochemistry, flow cytometric analysis single cell transcriptomics to characterize pattern purine metabolism mouse human eyes. This study identified...