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Statements

Subject Item
n2:RIV%2F00216208%3A11130%2F14%3A10293092%21RIV15-MSM-11130___
rdf:type
skos:Concept n19:Vysledek
rdfs:seeAlso
http://dx.doi.org/10.1530/ERC-13-0398
dcterms:description
Warburg's metabolic hypothesis is based on the assumption that a cancer cell's respiration must be under attack, leading to its damage, in order to obtain increased glycolysis. Although this may not apply to all cancers, there is some evidence proving that primarily abnormally functioning mitochondrial complexes are indeed related to cancer development. Thus, mutations in complex II (succinate dehydrogenase (SDH)) lead to the formation of pheochromocytoma (PHEO)/paraganglioma (PGL). Mutations in one of the SDH genes (SDHx mutations) lead to succinate accumulation associated with very low fumarate levels, increased glutaminolysis, the generation of reactive oxygen species, and pseudohypoxia. This results in significant changes in signaling pathways (many of them dependent on the stabilization of hypoxia-inducible factor), including oxidative phosphorylation, glycolysis, specific expression profiles, as well as genomic instability and increased mutability resulting in tumor development. Although there is currently no very effective therapy for SDHx-related metastatic PHEOs/PGLs, targeting their fundamental metabolic abnormalities may provide a unique opportunity for the development of novel and more effective forms of therapy for these tumors. Warburg's metabolic hypothesis is based on the assumption that a cancer cell's respiration must be under attack, leading to its damage, in order to obtain increased glycolysis. Although this may not apply to all cancers, there is some evidence proving that primarily abnormally functioning mitochondrial complexes are indeed related to cancer development. Thus, mutations in complex II (succinate dehydrogenase (SDH)) lead to the formation of pheochromocytoma (PHEO)/paraganglioma (PGL). Mutations in one of the SDH genes (SDHx mutations) lead to succinate accumulation associated with very low fumarate levels, increased glutaminolysis, the generation of reactive oxygen species, and pseudohypoxia. This results in significant changes in signaling pathways (many of them dependent on the stabilization of hypoxia-inducible factor), including oxidative phosphorylation, glycolysis, specific expression profiles, as well as genomic instability and increased mutability resulting in tumor development. Although there is currently no very effective therapy for SDHx-related metastatic PHEOs/PGLs, targeting their fundamental metabolic abnormalities may provide a unique opportunity for the development of novel and more effective forms of therapy for these tumors.
dcterms:title
Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma
skos:prefLabel
Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma
skos:notation
RIV/00216208:11130/14:10293092!RIV15-MSM-11130___
n3:aktivita
n12:I
n3:aktivity
I
n3:cisloPeriodika
3
n3:dodaniDat
n14:2015
n3:domaciTvurceVysledku
n11:2084341
n3:druhVysledku
n10:J
n3:duvernostUdaju
n18:S
n3:entitaPredkladatele
n4:predkladatel
n3:idSjednocenehoVysledku
9456
n3:idVysledku
RIV/00216208:11130/14:10293092
n3:jazykVysledku
n9:eng
n3:klicovaSlova
pseudohypoxia; hypoxia; gastrointestinal stromal tumor; renal cell carcinoma; paraganglioma; pheochromocytoma; succinate dehydrogenase; reactive oxygen species; Warburg effect; glycolysis; SDHx
n3:klicoveSlovo
n5:reactive%20oxygen%20species n5:renal%20cell%20carcinoma n5:glycolysis n5:SDHx n5:paraganglioma n5:Warburg%20effect n5:pheochromocytoma n5:pseudohypoxia n5:succinate%20dehydrogenase n5:hypoxia n5:gastrointestinal%20stromal%20tumor
n3:kodStatuVydavatele
GB - Spojené království Velké Británie a Severního Irska
n3:kontrolniKodProRIV
[374E15E1C427]
n3:nazevZdroje
Endocrine-Related Cancer
n3:obor
n17:FD
n3:pocetDomacichTvurcuVysledku
1
n3:pocetTvurcuVysledku
3
n3:rokUplatneniVysledku
n14:2014
n3:svazekPeriodika
21
n3:tvurceVysledku
Pacak, Karel Vícha, Aleš Taieb, David
n3:wos
000344787700017
s:issn
1351-0088
s:numberOfPages
17
n15:doi
10.1530/ERC-13-0398
n13:organizacniJednotka
11130