A5080349640- Cancer, Hypoxia, and Metabolism
- Adrenal and Paraganglionic Tumors
- Neuroblastoma Research and Treatments
- Glioma Diagnosis and Treatment
- Hormonal Regulation and Hypertension
- Virus-based gene therapy research
- Peroxisome Proliferator-Activated Receptors
- Pituitary Gland Disorders and Treatments
- Enzyme function and inhibition
- Signaling Pathways in Disease
- Histone Deacetylase Inhibitors Research
- ATP Synthase and ATPases Research
- Eicosanoids and Hypertension Pharmacology
- Ubiquitin and proteasome pathways
- PI3K/AKT/mTOR signaling in cancer
- Renal cell carcinoma treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Retinoids in leukemia and cellular processes
- Heat shock proteins research
- Mitochondrial Function and Pathology
- Immune cells in cancer
- Fibroblast Growth Factor Research
- High Altitude and Hypoxia
- Protein Degradation and Inhibitors
- RNA modifications and cancer
Karolinska Institutet
2019-2022
Slovak Academy of Sciences
2013-2020
Institute of Virology of the Slovak Academy of Sciences
2013-2020
Biomedical Research Center of the Slovak Academy of Sciences
2016-2020
National Institutes of Health
2013-2018
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2013-2018
Context:Germline mutations in genes coding succinate dehydrogenase (SDH) subunits A, B, C, and D have been identified familial paragangliomas (PGLs)/pheochromocytomas (PHEOs) other tumors. We described a GH-secreting pituitary adenoma (PA) caused by SDHD mutation patient with PGLs. Additional patients PAs SDHx defects since reported.
Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. Here we study single-cell and single-nuclei transcriptomes different clinical risk groups stages, including healthy adrenal gland. We compare tumor cell populations embryonic mouse sympatho-adrenal derivatives, post-natal human provide evidence that low high-risk have identities, representing two...
// Chao Zhang 1,2,* , Chunzhang Yang 3,* Michael J. Feldman 4 Herui Wang Ying Pang 2 Dominic M. Maggio Dongwang Zhu Cody L. Nesvick Pauline Dmitriev Petra Bullova 2,5 Prashant Chittiboina Roscoe O. Brady Karel Pacak and Zhengping Zhuang 1 Department of Orthopedics, Xinqiao Hospital, The Third Military Medical University, Chongqing, China Program in Reproductive Adult Endocrinology, Eunice Kennedy Shriver National Institute Child Health Human Development, Bethesda, Maryland, USA 3...
Purpose: Cluster I pheochromocytomas and paragangliomas (PCPGs) tend to develop malignant transformation, tumor recurrence, multiplicity. Transcriptomic profiling suggests that cluster PCPGs other related tumors exhibit distinctive changes in the tricarboxylic acid (TCA) cycle, hypoxia signaling pathway, mitochondrial electron transport chain, methylation status, suggesting therapeutic regimen might be optimized by targeting these signature molecular pathways.Experimental Design: In present...
Pheochromocytomas (PHEOs) and paragangliomas (PGLs; extra-adrenal tumors) are rare neuroendocrine chromaffin cell tumors with a hereditary background in about 30%-35%. Those caused by succinate dehydrogenase subunit B (SDHB) germline mutations associated high metastatic potential ultimately higher patient mortality. Succinate converts to fumarate, uniquely linking the Krebs cycle oxidative phosphorylation. SDH result accumulation of various metabolic disturbances shift aerobic glycolysis...
Solid tumors, including breast cancer, are characterized by the hypoxic microenvironment, extracellular acidosis, and chemoresistance. Hypoxia marker, carbonic anhydrase IX (CAIX), is a pH regulator providing selective survival advantage to cancer cells through intracellular neutralization while facilitating tumor invasion acidification. The expression of CAIX in patients associated with poor prognosis metastases. Importantly, CAIX-positive regions enriched stem (CSCs). Here we investigated...
Several lines of evidence, including the recent discovery novel susceptibility genes, point out an important role for mammalian target rapamycin (mTOR) signaling pathway in development pheochromocytoma. Analyzing a set pheochromocytomas from patients with different genetic backgrounds, we observed and confirmed significant overexpression key mTOR complex (mTORC) mediators. Using selective ATP-competitive inhibitors targeting both mTORC1 mTORC2, significantly arrested vitro cell proliferation...
// Ying Pang 1 , Chunzhang Yang 2 Jan Schovanek 3 Herui Wang 4 Petra Bullova 5 Veronika Caisova Garima Gupta Katherine I. Wolf Gregg L. Semenza 6 Zhengping Zhuang and Karel Pacak Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health Human Development, Institutes Health, Bethesda, Maryland, USA Neuro-Oncology Branch, Center for Cancer Research, Institute, Department Internal Medicine III-Nephrology, Rheumatology, Endocrinology, Faculty Dentistry,...
Mitochondria are the main consumers of oxygen within cell. How mitochondria sense levels remains unknown. Here we show an oxygen-sensitive regulation TFAM, activator mitochondrial transcription and replication, whose alteration is linked to tumours arising in von Hippel-Lindau syndrome. TFAM hydroxylated by EGLN3 subsequently bound tumour-suppressor protein, which stabilizes preventing proteolysis. Cells lacking wild-type VHL or inactivated have reduced mass. Tumorigenic variants leading...
The paucity of recurrent mutations has hampered efforts to understand and treat neuroblastoma. Alternative splicing splicing-dependent RNA-fusions represent mechanisms able increase the gene product repertoire but their role in neuroblastoma remains largely unexplored. Here we investigate presence possible roles aberrant RNA-fusion transcripts In addition, attend establish whether spliceosome can be targeted Through analysis RNA-sequenced show that elevated expression factors is a strong...
Metastatic pheochromocytoma represents one of the major clinical challenges in field neuroendocrine oncology. Recent molecular characterization suggests new treatment options with targeted therapies. In this study we investigated 90 kDa heat shock protein (Hsp90) as a potential therapeutic target for advanced pheochromocytoma. Both first generation, natural product Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), and second-generation synthetic STA-9090...
Despite the discovery of oxygen-sensitive regulation HIFα by von Hippel-Lindau (VHL) protein, mechanisms underlying complex genotype/phenotype correlations in VHL disease remain unknown. Some germline mutations cause familial pheochromocytoma and encode proteins that preserve their ability to down-regulate HIFα. While type 1, 2A, 2B mutants are defective regulating HIFα, 2C Here, we identified an function is abolished mutations. We found BIM-EL, a proapoptotic BH3-only hydroxylated EglN3...
Currently, there are no reliably effective therapeutic options for metastatic pheochromocytoma (PCC) and paraganglioma. Moreover, therapies that may prevent the onset or progression of tumors in patients with succinate dehydrogenase type B mutations, which associated very aggressive tumors. Therefore, we tested approved well-tolerated drugs lovastatin 13-cis-retinoic acid (13cRA) vitro an PCC mouse cell line, tumor tissue-derived (MTT) cells, vivo a allograft nude model, therapeutically...
Metastatic pheochromocytoma continues to be an incurable disease, and treatment with conventional cytotoxic chemotherapy offers limited efficacy. In the present study, we evaluated a novel topoisomerase I inhibitor, LMP-400, as potential for this devastating disease. We found high expression of in human metastatic pheochromocytoma, providing basis evaluation 1 inhibitor therapeutic strategy. LMP-400 inhibited cell growth established mouse lines primary tumor tissue cultures. study performed...
Objective: To report the functional imaging experience with a 29-year-old woman carrying mutation in fumarate hydratase (FH)-encoding gene and history of pheochromocytoma (PHEO) retroperitoneal paraganglioma (PGL).
Hypoxia is a common feature of solid tumors that activates plethora pathways, resulting in proliferation and resistance cancer cells to radio- chemotherapy. Pheochromocytomas/paragangliomas (PHEOs/PGLs) with mutations the gene coding for subunit B succinate dehydrogenase (SDHB) are most aggressive forms disease, which partially due their pseudohypoxic character, metabolic abnormalities, elevated reactive oxygen species (ROS) levels. We investigated effect piperlongumine (PL), natural product...
Proteasome inhibitors have been frequently used in treating hematologic and solid tumors. They are administered individually or combination with other regimens, to prevent severe side effects resistance development. Because they shown be efficient pharmaceutically available, we tested the first Food Drug Administration–approved proteasome inhibitor bortezomib alone another inhibitor, salinosporamid A, pheochromocytoma cells. Pheochromocytomas/Paragangliomas (PHEOs/PGLs) neuroendocrine tumors...
Drug repurposing or repositioning is an important part of drug discovery that has been growing in the last few years for development therapeutic options oncology. We applied this paradigm a screening library about 3,800 compounds (including FDA-approved drugs and pharmacologically active compounds) employing model metastatic pheochromocytoma, most common tumor adrenal medulla children adults. The collection approved was screened quantitative mode, testing compound-titration series...
Hypoxia-inducible factors (HIFs) regulate oxygen sensing and expression of genes involved in angiogenesis erythropoiesis.Polycythemia has been observed patients with hepatocellular carcinoma (HCC), but the underlying molecular basis remains unknown.Liver tissues from 302 HCC patients, including 104 polycythemia, were sequenced for HIF2A mutations.A germline mutation was detected one patient concurrent polycythemia.Three additional family members carried this mutation, none exhibited...
Abstract Childhood neuroblastoma has a remarkable variability in outcome. Age at diagnosis is one of the most important prognostic factors, with children less than 1 year old having favorable outcomes. We studied single-cell and single-nuclei transcriptomes different clinical risk groups stages, including healthy adrenal gland. compared tumor cell populations embryonic mouse sympatho-adrenal derivatives, post-natal human provide evidence that low high-risk have identities, representing two...