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11 záznamů v Medvik Filtry

Článek

Anthracyclines suppress pheochromocytoma cell characteristics, including metastasis, through inhibition of the hypoxia signaling pathway

Pang, Ying
Autor Pang, Ying Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
Yang, Chunzhang
Autor Yang, Chunzhang Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA
Schovanek, Jan
Autor Schovanek, Jan Department of Internal Medicine III-Nephrology, Rheumatology, and Endocrinology, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
Wang, Herui
Autor Wang, Herui Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
Bullova, Petra
Autor Bullova, Petra Department of Molecular Medicine, Institute of Virology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic
Caisova, Veronika
Autor Caisova, Veronika Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
Gupta, Garima
Autor Gupta, Garima Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
Wolf, Katherine I
Autor Wolf, Katherine I Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
Semenza, Gregg L
Autor Semenza, Gregg L McKusick-Nathans Institute of Genetic Medicine and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Zhuang, Zhengping
Autor Zhuang, Zhengping Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

Oncotarget. 2017 ; 8 (14) : 22313-22324.

ISSN 1949-2553
Medvik
Zdroj

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine tumors derived from adrenal or extra-adrenal chromaffin cells, respectively. Metastases are discovered in 3-36% of patients at the time of diagnosis. Currently, only suboptimal treatment options exist. Therefore, new therapeutic compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we investigated if anthracyclines were able to suppress the progression of metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells using in vitro and in vivo models, and demonstrated that anthracyclines, particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia response element (HRE) sites on DNA. This resulted in reduced transcriptional activation of HIF target genes, including erythropoietin (EPO), phosphoglycerate kinase 1 (PGK1), endothelin 1 (EDN1), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and vascular endothelial growth factor (VEGFA), which consequently inhibited the growth of metastatic PHEO. Additionally, IDA downregulated hypoxia signaling by interfering with the transcriptional activation of HIF1A and HIF2A. Furthermore, our animal model demonstrated the dose-dependent suppressive effect of IDA on metastatic PHEO growth in vivo. Our results indicate that anthracyclines are prospective candidates for inclusion in metastatic PHEO/PGL therapy, especially in patients with gene mutations involved in the hypoxia signaling pathway.

Článek

Ložisková patologie nadledvin u novorozence

Neonatologické listy. 2017 ; 23 (1) : 3-5.

ISSN 1211-1600
Medvik
Zdroj

MeSH
dítě MeSH
krvácení diagnostické zobrazování etiologie MeSH
lidé MeSH
nadledviny diagnostické zobrazování patologie MeSH
nádory nadledvin * diagnostické zobrazování farmakoterapie chirurgie patologie MeSH
nemoci novorozenců MeSH
neuroblastom diagnostické zobrazování farmakoterapie chirurgie MeSH
novorozenec MeSH
Check Tag
dítě MeSH
lidé MeSH
novorozenec MeSH
Publikační typ
kazuistiky MeSH

Článek

Nieman, L. K., Biller, B. M. K., Findling, J. W. F., Murad, H., Newell-Price, J., Savage, M. O., Tabarin, A.: Léčba Cushingova syndromu: doporučení Endocrine Society pro klinickou praxi

Kršek, Michal
Autor Autorita ORCID II. interní klinika FNKV Praha

Revue endokrinologie. 2016 ; 19 (1) : 37-39.

Rev. Endokrin.
ISSN 1801-6413
Medvik
Zdroj

MeSH
adrenalektomie MeSH
Cushingův syndrom terapie MeSH
endokrinologie normy MeSH
indukce remise MeSH
konsensus MeSH
lidé MeSH
medicína založená na důkazech MeSH
nádory hypofýzy farmakoterapie chirurgie radioterapie MeSH
nádory nadledvin farmakoterapie chirurgie radioterapie MeSH
plánování péče o pacienty MeSH
recidiva MeSH
Check Tag
lidé MeSH
Publikační typ
souhrny MeSH

Článek

Diabetes mellitus u Cushingova syndromu
[Diabetes mellitus and Cushing´s syndrome]

Kršek, Michal
Autor Autorita ORCID Univerzita Karlova v Praze, 1. lékařská fakulta a Všeobecná fakultní nemocnice, 3. interní klinika

Postgraduální medicína. 2016 ; 18 (1) : 43-50.

Postgraduální med.
ISSN 1212-4184
Medvik
Zdroj

Cushingův syndrom je vzácné onemocnění spojené s významně zvýšenou morbiditou a mortalitou v porovnání s běžnou populací, především v důsledku kardiovaskulárních poruch. Hlavní příčinou jsou pravděpodobně metabolické změny spojené s hypersekrecí kortizolu a zahrnující poruchu glukózové tolerance a diabetes mellitus, obezitu, poruchu metabolismu tuků, katabolismus proteinů a retenci sodíku a vody. Tento článek shrnuje současné poznatky o poruše glukózové homeostázy u Cushingova syndromu a její klinické důsledky.

Cushing's syndrome is a rare disorder associated with significantly increased morbidity and mortality in comparison with general population, mainly due to cardiovascular disorders. Metabolic changes associated with cortisol oversecretion and consisting of glucose intolerance and diabetes, obesity, lipid metabolism disturbances, protein catabolism and sodium and fluid retention, are probably main reason. This article reviews current knowledge about glucose homeostasis disturbances in Cushing's syndrome and its clinical consequences.

Článek

Inhibitory Effect of the Noncamptothecin Topoisomerase I Inhibitor LMP-400 on Female Mice Models and Human Pheochromocytoma Cells

Endocrinology. 2015 ; 156 (11) : 4094-104. [pub] 20150812

ISSN 1945-7170
Medvik
Zdroj

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 a potential treatment for this devastating disease. We found a high expression of topoisomerase I in human metastatic pheochromocytoma, providing a basis for the evaluation of a topoisomerase 1 inhibitor as a therapeutic strategy. LMP-400 inhibited the cell growth of established mouse pheochromocytoma cell lines and primary human tumor tissue cultures. In a study performed in athymic female mice, LMP-400 demonstrated a significant inhibitory effect on tumor growth with two drug administration regimens. Furthermore, low doses of LMP-400 decreased the protein levels of hypoxia-inducible factor 1 (HIF-1α), one of a family of factors studied as potential metastatic drivers in these tumors. The HIF-1α decrease resulted in changes in the mRNA levels of HIF-1 transcriptional targets. In vitro, LMP-400 showed an increase in the growth-inhibitory effects in combination with other chemotherapeutic drugs that are currently used for the treatment of pheochromocytoma. We conclude that LMP-400 has promising antitumor activity in preclinical models of metastatic pheochromocytoma and its use should be considered in future clinical trials.

Článek

Combination of 13-Cis retinoic acid and lovastatin: marked antitumor potential in vivo in a pheochromocytoma allograft model in female athymic nude mice

Endocrinology. 2014 ; 155 (7) : 2377-90.

ISSN 1945-7170
Medvik
Zdroj

Currently, there are no reliably effective therapeutic options for metastatic pheochromocytoma (PCC) and paraganglioma. Moreover, there are no therapies that may prevent the onset or progression of tumors in patients with succinate dehydrogenase type B mutations, which are associated with very aggressive tumors. Therefore, we tested the approved and well-tolerated drugs lovastatin and 13-cis-retinoic acid (13cRA) in vitro in an aggressive PCC mouse cell line, mouse tumor tissue-derived (MTT) cells, and in vivo in a PCC allograft nude mouse model, in therapeutically relevant doses. Treatment was started 24 hours before sc tumor cell injection and continued for 30 more days. Tumor sizes were measured from outside by caliper and sizes of viable tumor mass by bioluminescence imaging. Lovastatin showed antiproliferative effects in vitro and led to significantly smaller tumor sizes in vivo compared with vehicle treatment. 13cRA promoted tumor cell growth in vitro and led to significantly larger viable tumor mass and significantly faster increase of viable tumor mass in vivo over time compared with vehicle, lovastatin, and combination treatment. However, when combined with lovastatin, 13cRA enhanced the antiproliferative effect of lovastatin in vivo. The combination-treated mice showed slowest tumor growth of all groups with significantly slower tumor growth compared with the vehicle-treated mice and significantly smaller tumor sizes. Moreover, the combination-treated group displayed the smallest size of viable tumor mass and the slowest increase in viable tumor mass over time of all groups, with a significant difference compared with the vehicle- and 13cRA-treated group. The combination-treated tumors showed highest extent of necrosis, lowest median microvessel density and highest expression of α-smooth muscle actin. The combination of high microvessel density and low α-smooth muscle actin is a predictor of poor prognosis in other tumor entities. Therefore, this drug combination may be a well-tolerated novel therapeutic or preventive option for malignant PCC.

Článek

High-throughput screening for the identification of new therapeutic options for metastatic pheochromocytoma and paraganglioma

PLoS One. 2014 ; 9 (4) : e90458.

ISSN 1932-6203
Medvik
Zdroj

Drug repurposing or repositioning is an important part of drug discovery that has been growing in the last few years for the development of therapeutic options in oncology. We applied this paradigm in a screening of a library of about 3,800 compounds (including FDA-approved drugs and pharmacologically active compounds) employing a model of metastatic pheochromocytoma, the most common tumor of the adrenal medulla in children and adults. The collection of approved drugs was screened in quantitative mode, testing the compounds in compound-titration series (dose-response curves). Analysis of the dose-response screening data facilitated the selection of 50 molecules with potential bioactivity in pheochromocytoma cells. These drugs were classified based on molecular/cellular targets and signaling pathways affected, and selected drugs were further validated in a proliferation assay and by flow cytometric cell death analysis. Using meta-analysis information from molecular targets of the top drugs identified by our screening with gene expression data from human and murine microarrays, we identified potential drugs to be used as single drugs or in combination. An example of a combination with a synergistic effect is presented. Our study exemplifies a promising model to identify potential drugs from a group of clinically approved compounds that can more rapidly be implemented into clinical trials in patients with metastatic pheochromocytoma or paraganglioma.