- Cancer, Hypoxia, and Metabolism
- Adrenal and Paraganglionic Tumors
- Glioma Diagnosis and Treatment
- Hormonal Regulation and Hypertension
- Heme Oxygenase-1 and Carbon Monoxide
- Neonatal Health and Biochemistry
- Neuroblastoma Research and Treatments
- Immunotherapy and Immune Responses
- Mitochondrial Function and Pathology
- Education, Psychology, and Social Research
- Sarcoma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Metabolism and Genetic Disorders
- Radiomics and Machine Learning in Medical Imaging
- Alcohol Consumption and Health Effects
- Cancer, Lipids, and Metabolism
- ATP Synthase and ATPases Research
- Eicosanoids and Hypertension Pharmacology
- CAR-T cell therapy research
- interferon and immune responses
- Vitamin C and Antioxidants Research
- Liver Disease Diagnosis and Treatment
- Folate and B Vitamins Research
- Chromatin Remodeling and Cancer
- Thermal Regulation in Medicine
National Institutes of Health
2021-2025
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2021-2025
Czech Academy of Sciences, Institute of Biotechnology
2018-2024
Charles University
2010-2022
University Hospital in Motol
2020-2022
Czech Academy of Sciences
2018-2021
Comer Children's Hospital
2019
General University Hospital in Prague
2016
King's College Hospital
2009
Karolinska University Hospital
2009
Spirulina platensis is a blue-green alga used as dietary supplement because of its hypocholesterolemic properties. Among other bioactive substances, it also rich in tetrapyrrolic compounds closely related to bilirubin molecule, potent antioxidant and anti-proliferative agent. The aim our study was evaluate possible anticancer effects S. platensis-derived tetrapyrroles using an experimental model pancreatic cancer. components [phycocyanobilin (PCB) chlorophyllin, surrogate molecule for...
Abstract Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors derived from neural crest cells adrenal medullary chromaffin tissues extra-adrenal paraganglia, respectively. Although the current treatment for PPGLs is surgery, optimal options advanced metastatic cases have been limited. Hence, understanding role of immune system in PPGL tumorigenesis can provide essential knowledge development better therapeutic tumor management strategies, especially those with PPGLs....
Spirulina platensis, a water blue-green alga, has been associated with potent biological effects, which might have important relevance in atheroprotection. We investigated whether S. platensis or phycocyanobilin (PCB), its tetrapyrrolic chromophore, can activate atheroprotective heme oxygenase-1 (Hmox1), key enzyme the catabolic pathway responsible for generation of antioxidant bilirubin, endothelial cells and mouse model atherosclerosis. In vitro experiments were performed on EA.hy926...
Abstract Cell growth and survival depend on a delicate balance between energy production synthesis of metabolites. Here, we provide evidence that an alternative mitochondrial complex II (CII) assembly, designated as CII low , serves checkpoint for metabolite biosynthesis under bioenergetic stress, with cells suppressing their utilization by modulating DNA cell cycle progression. Depletion leads to imbalance in synthesis, evidenced recovery the de novo pyrimidine pathway unlocking arrest from...
Abstract Despite strides in immunotherapy, glioblastoma multiforme (GBM) remains challenging due to low inherent immunogenicity and suppressive tumor microenvironment. Converting “cold” GBMs “hot” is crucial for immune activation improved outcomes. This study comprehensively characterized a therapeutic vaccination strategy preclinical GBM models. The vaccine consists of Mannan‐BAM‐anchored irradiated whole cells, Toll‐like receptor ligands [lipoteichoic acid (LTA), polyinosinic‐polycytidylic...
Paragangliomas and pheochromocytomas (PPGLs) are chromaffin tumors associated with severe catecholamine-induced morbidities. Surgical removal is often curative. However, complete resection may not be an option for patients succinate dehydrogenase subunit A-D ( SDHx ) mutations. mutations a high risk multiple recurrent, metastatic PPGLs. Treatment options in these cases limited prognosis dismal once metastases present. Identification of new therapeutic targets candidate drugs thus urgently...
Pheochromocytomas and paragangliomas (PCPG) are usually benign neuroendocrine tumors. However, PCPGs with mutations in the succinate dehydrogenase B subunit (SDHB) have a poor prognosis frequently develop metastatic lesions. SDHB-mutated exhibit dysregulation oxygen metabolic pathways, including pseudohypoxia formation of reactive species, suggesting that targeting redox balance pathway could be potential therapeutic approach.We studied genetic alterations cluster I compared II PCPGs, which...
Abstract Background Pheochromocytoma and paraganglioma (PPGL) are neuroendocrine tumors with frequent mutations in genes linked to the tricarboxylic acid cycle. However, no pathogenic variant has been found date succinyl-CoA ligase (SUCL), an enzyme that provides substrate for succinate dehydrogenase (SDH; mitochondrial complex II [CII]), a known tumor suppressor PPGL. Methods A cohort of 352 patients apparently sporadic PPGL underwent genetic testing using panel 54 developed at National...
High plasma concentrations of bile acids (BA) and bilirubin are hallmarks cholestasis. BA implicated in the pathogenesis cholestatic liver damage through mechanisms involving oxidative stress, whereas is a strong antioxidant. We evaluated roles on mediating stress rats following duct ligation (BDL). Adult female Wistar Gunn intraperitoneally anaesthetized with ketamine xylazine underwent BDL or sham operation. Cholestatic markers, antioxidant capacity, lipid peroxidation heme oxygenase (HO)...
Abstract Complex II (CII) activity controls phenomena that require crosstalk between metabolism and signaling, including neurodegeneration, cancer metabolism, immune activation, ischemia-reperfusion injury. CII can be regulated at the level of assembly, a process leverages metastable assembly intermediates. The nature these intermediates how subunits transfer complexes remains unclear. In this work, we identify species containing SDHA subunit its factors, assign preferred temporal sequence...
Estrogen-induced cholestasis is characterized by impaired hepatic uptake and biliary bile acids secretion because of changes in hepatocyte transporter expression. The induction heme oxygenase-1 (HMOX1), the inducible isozyme catabolism, mediated via Bach1/Nrf2 pathway, protects livers from toxic, oxidative inflammatory insults. However, its role remains unknown. Here, we investigated effects HMOX1 on ethinylestradiol-induced possible underlying mechanisms. Wistar rats were given...
Cancer immunotherapy has shown remarkable clinical progress in recent years. Although age is one of the biggest leading risk factors for cancer development and older adults represent a majority patients, only few new immunotherapeutic interventions have been preclinically tested aged animals. Thus, lack preclinical studies focused on age-dependent effect during could lead to different therapeutic outcomes young animals future modifications human trials. Here, we compare efficacy previously...