FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1855250570> ?p ?o ?g. }

• W1855250570 endingPage "744" @default.
• W1855250570 startingPage "734" @default.
• W1855250570 abstract "Clear-cell renal cell carcinoma (ccRCC) exhibits suppressed mitochondrial function and preferential use of glycolysis even in normoxia, promoting proliferation and suppressing apoptosis. ccRCC resistance to therapy is driven by constitutive hypoxia-inducible factor (HIF) expression due to genetic loss of von Hippel-Lindau factor. In addition to promoting angiogenesis, HIF suppresses mitochondrial function by inducing pyruvate dehydrogenase kinase (PDK), a gatekeeping enzyme for mitochondrial glucose oxidation.To reverse mitochondrial suppression of ccRCC using the PDK inhibitor dichloroacetate (DCA).Radical nephrectomy specimens from patients with ccRCC were assessed for PDK expression. The 786-O ccRCC line and two animal models (chicken in ovo and murine xenografts) were used for mechanistic studies.Mitochondrial function, proliferation, apoptosis, HIF transcriptional activity, angiogenesis, and tumor size were measured in vitro and in vivo. Independent-sample t-tests and analysis of variance were used for statistical analyses.PDK was elevated in 786-O cells and in ccRCC compared to normal kidney tissue from the same patient. DCA reactivated mitochondrial function (increased respiration, Krebs cycle metabolites such as α-ketoglutarate [cofactor of factor inhibiting HIF], and mitochondrial reactive oxygen species), increased p53 activity and apoptosis, and decreased proliferation in 786-O cells. DCA reduced HIF transcriptional activity in an FIH-dependent manner, inhibiting angiogenesis in vitro. DCA reduced tumor size and angiogenesis in vivo in both animal models.DCA can reverse the mitochondrial suppression of ccRCC and decrease HIF transcriptional activity, bypassing its constitutive expression. Its previous clinical use in humans makes it an attractive candidate for translation to ccRCC patients.We show that an energy-boosting drug decreases tumor growth and tumor blood vessels in animals carrying human kidney cancer cells. This generic drug has been used in patients for other conditions and thus could be tested in kidney cancer that remains incurable." @default.
• W1855250570 created "2016-06-24" @default.
• W1855250570 creator A5000162397 @default.
• W1855250570 creator A5003441736 @default.
• W1855250570 creator A5004686625 @default.
• W1855250570 creator A5007482612 @default.
• W1855250570 creator A5010164550 @default.
• W1855250570 creator A5020350141 @default.
• W1855250570 creator A5021152638 @default.
• W1855250570 creator A5025958936 @default.
• W1855250570 creator A5026652675 @default.
• W1855250570 creator A5036735906 @default.
• W1855250570 creator A5053151709 @default.
• W1855250570 creator A5064255566 @default.
• W1855250570 creator A5078080787 @default.
• W1855250570 creator A5089836373 @default.
• W1855250570 date "2016-04-01" @default.
• W1855250570 modified "2023-10-10" @default.
• W1855250570 title "Metabolic Modulation of Clear-cell Renal Cell Carcinoma with Dichloroacetate, an Inhibitor of Pyruvate Dehydrogenase Kinase" @default.
• W1855250570 cites W1511590410 @default.
• W1855250570 cites W1973372532 @default.
• W1855250570 cites W1990660527 @default.
• W1855250570 cites W1991510903 @default.
• W1855250570 cites W1994148625 @default.
• W1855250570 cites W1995338702 @default.
• W1855250570 cites W1996715681 @default.
• W1855250570 cites W1998664010 @default.
• W1855250570 cites W2000542942 @default.
• W1855250570 cites W2005833897 @default.
• W1855250570 cites W2011070950 @default.
• W1855250570 cites W2015644147 @default.
• W1855250570 cites W2026252608 @default.
• W1855250570 cites W2027705428 @default.
• W1855250570 cites W2033958147 @default.
• W1855250570 cites W2034427729 @default.
• W1855250570 cites W2039924900 @default.
• W1855250570 cites W2042921832 @default.
• W1855250570 cites W2044137980 @default.
• W1855250570 cites W2046100445 @default.
• W1855250570 cites W2069763554 @default.
• W1855250570 cites W2074171009 @default.
• W1855250570 cites W2083539959 @default.
• W1855250570 cites W2087248411 @default.
• W1855250570 cites W2090168914 @default.
• W1855250570 cites W2091516108 @default.
• W1855250570 cites W2092271538 @default.
• W1855250570 cites W2093378001 @default.
• W1855250570 cites W2097104496 @default.
• W1855250570 cites W2097259163 @default.
• W1855250570 cites W2100723895 @default.
• W1855250570 cites W2101404359 @default.
• W1855250570 cites W2109389570 @default.
• W1855250570 cites W2112167480 @default.
• W1855250570 cites W2119845124 @default.
• W1855250570 cites W2142823303 @default.
• W1855250570 cites W2149755406 @default.
• W1855250570 cites W2151260260 @default.
• W1855250570 cites W2163759582 @default.
• W1855250570 cites W2164524616 @default.
• W1855250570 cites W2164638888 @default.
• W1855250570 cites W2166010840 @default.
• W1855250570 cites W2167845320 @default.
• W1855250570 cites W2171387445 @default.
• W1855250570 doi "https://doi.org/10.1016/j.eururo.2015.09.014" @default.
• W1855250570 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26433571" @default.
• W1855250570 hasPublicationYear "2016" @default.
• W1855250570 type Work @default.
• W1855250570 sameAs 1855250570 @default.
• W1855250570 citedByCount "51" @default.
• W1855250570 countsByYear W18552505702016 @default.
• W1855250570 countsByYear W18552505702017 @default.
• W1855250570 countsByYear W18552505702018 @default.
• W1855250570 countsByYear W18552505702019 @default.
• W1855250570 countsByYear W18552505702020 @default.
• W1855250570 countsByYear W18552505702021 @default.
• W1855250570 countsByYear W18552505702022 @default.
• W1855250570 countsByYear W18552505702023 @default.
• W1855250570 crossrefType "journal-article" @default.
• W1855250570 hasAuthorship W1855250570A5000162397 @default.
• W1855250570 hasAuthorship W1855250570A5003441736 @default.
• W1855250570 hasAuthorship W1855250570A5004686625 @default.
• W1855250570 hasAuthorship W1855250570A5007482612 @default.
• W1855250570 hasAuthorship W1855250570A5010164550 @default.
• W1855250570 hasAuthorship W1855250570A5020350141 @default.
• W1855250570 hasAuthorship W1855250570A5021152638 @default.
• W1855250570 hasAuthorship W1855250570A5025958936 @default.
• W1855250570 hasAuthorship W1855250570A5026652675 @default.
• W1855250570 hasAuthorship W1855250570A5036735906 @default.
• W1855250570 hasAuthorship W1855250570A5053151709 @default.
• W1855250570 hasAuthorship W1855250570A5064255566 @default.
• W1855250570 hasAuthorship W1855250570A5078080787 @default.
• W1855250570 hasAuthorship W1855250570A5089836373 @default.
• W1855250570 hasConcept C104317684 @default.
• W1855250570 hasConcept C126322002 @default.
• W1855250570 hasConcept C134018914 @default.
• W1855250570 hasConcept C160450060 @default.
• W1855250570 hasConcept C169415338 @default.
• W1855250570 hasConcept C181199279 @default.

• next