Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313306358> ?p ?o ?g. }
- W4313306358 abstract "Targeting metabolic vulnerabilities has been proposed as a therapeutic strategy in renal cell carcinoma (RCC). Here, we analyzed the metabolism of patient-derived xenografts (tumorgrafts) from diverse subtypes of RCC. Tumorgrafts from VHL -mutant clear cell RCC (ccRCC) retained metabolic features of human ccRCC and engaged in oxidative and reductive glutamine metabolism. Genetic silencing of isocitrate dehydrogenase-1 or isocitrate dehydrogenase-2 impaired reductive labeling of tricarboxylic acid (TCA) cycle intermediates in vivo and suppressed growth of tumors generated from tumorgraft-derived cells. Glutaminase inhibition reduced the contribution of glutamine to the TCA cycle and resulted in modest suppression of tumorgraft growth. Infusions with [amide- 15 N]glutamine revealed persistent amidotransferase activity during glutaminase inhibition, and blocking these activities with the amidotransferase inhibitor JHU-083 also reduced tumor growth in both immunocompromised and immunocompetent mice. We conclude that ccRCC tumorgrafts catabolize glutamine via multiple pathways, perhaps explaining why it has been challenging to achieve therapeutic responses in patients by inhibiting glutaminase." @default.
- W4313306358 created "2023-01-06" @default.
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- W4313306358 date "2022-12-16" @default.
- W4313306358 modified "2023-09-26" @default.
- W4313306358 title "In vivo characterization of glutamine metabolism identifies therapeutic targets in clear cell renal cell carcinoma" @default.
- W4313306358 cites W1503667331 @default.
- W4313306358 cites W1772301402 @default.
- W4313306358 cites W1920051003 @default.
- W4313306358 cites W1932887754 @default.
- W4313306358 cites W1974684460 @default.
- W4313306358 cites W1984882020 @default.
- W4313306358 cites W1985194885 @default.
- W4313306358 cites W1996365670 @default.
- W4313306358 cites W2005703314 @default.
- W4313306358 cites W2010394923 @default.
- W4313306358 cites W2021525020 @default.
- W4313306358 cites W2028743750 @default.
- W4313306358 cites W2031211461 @default.
- W4313306358 cites W2033958147 @default.
- W4313306358 cites W2035983112 @default.
- W4313306358 cites W2036659083 @default.
- W4313306358 cites W2050140657 @default.
- W4313306358 cites W2064115324 @default.
- W4313306358 cites W2069663698 @default.
- W4313306358 cites W2087360892 @default.
- W4313306358 cites W2092152920 @default.
- W4313306358 cites W2114805483 @default.
- W4313306358 cites W2116516144 @default.
- W4313306358 cites W2120553786 @default.
- W4313306358 cites W2130364039 @default.
- W4313306358 cites W2132117833 @default.
- W4313306358 cites W2138033100 @default.
- W4313306358 cites W2151980465 @default.
- W4313306358 cites W2234445408 @default.
- W4313306358 cites W2258066491 @default.
- W4313306358 cites W2264411128 @default.
- W4313306358 cites W2312291090 @default.
- W4313306358 cites W2335012284 @default.
- W4313306358 cites W2513280988 @default.
- W4313306358 cites W2534904302 @default.
- W4313306358 cites W2715137823 @default.
- W4313306358 cites W2739524551 @default.
- W4313306358 cites W2753949998 @default.
- W4313306358 cites W2759230072 @default.
- W4313306358 cites W2764232556 @default.
- W4313306358 cites W2783764907 @default.
- W4313306358 cites W2794427449 @default.
- W4313306358 cites W2796207353 @default.
- W4313306358 cites W2888708599 @default.
- W4313306358 cites W2891318902 @default.
- W4313306358 cites W2903608921 @default.
- W4313306358 cites W2945220204 @default.
- W4313306358 cites W2946454907 @default.
- W4313306358 cites W2962987989 @default.
- W4313306358 cites W2974361058 @default.
- W4313306358 cites W2985764787 @default.
- W4313306358 cites W2995147378 @default.
- W4313306358 cites W3002439510 @default.
- W4313306358 cites W3018515813 @default.
- W4313306358 cites W3020598614 @default.
- W4313306358 cites W3029174966 @default.
- W4313306358 cites W3094719342 @default.
- W4313306358 cites W3146001933 @default.
- W4313306358 cites W3158631244 @default.
- W4313306358 cites W3164259904 @default.
- W4313306358 cites W3168718184 @default.
- W4313306358 cites W3170518524 @default.
- W4313306358 cites W3185688873 @default.
- W4313306358 cites W3203850738 @default.
- W4313306358 cites W3213699945 @default.
- W4313306358 cites W3215948599 @default.