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309169 occurrences (No.70 in the rank) during 5 years in the PubMed. [cache]

179) Both pharmacologic and genetic inhibition of TrxR impairs the growth of human AML in mouse models.

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PMID:34239044 DOI:10.1038/s41388-021-01924-0

2021 Oncogene

* Thioredoxin reductase is a major regulator of metabolism in leukemia cells.

- Despite the fact that AML is the most common acute leukemia in adults, patient outcomes are poor necessitating the development of novel therapies. We identified that inhibition of Thioredoxin Reductase (TrxR) is a promising strategy for AML and report a highly potent and specific inhibitor of TrxR, S-250. Both pharmacologic and genetic inhibition of TrxR impairs the growth of human AML in mouse models. We found that TrxR inhibition leads to a rapid and marked impairment of metabolism in leukemic cells subsequently leading to cell death. TrxR was found to be a major and direct regulator of metabolism in AML cells through impacts on both glycolysis and the TCA cycle. Studies revealed that TrxR directly regulates GAPDH leading to a disruption of glycolysis and an increase in flux through the pentose phosphate pathway (PPP). The combined inhibition of TrxR and the PPP led to enhanced leukemia growth inhibition. Overall, TrxR abrogation, particularly with S-250, was identified as a promising strategy to disrupt AML metabolism.

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(1)85 and	(12)4 performance	(25)2 as	(36)2 hormone
(2)71 factor	(13)4 phase	(26)2 compared	(37)2 lean
(3)51 of	(14)4 rate	(27)2 conditions	(38)2 on
(4)33 in	(15)4 restriction	(28)2 curve	(39)2 response
(5)26 null	(16)3 factor,	(29)2 curves	(40)2 stage
(6)12 inhibition	(19)3 failure	(30)2 defect	(41)2 the
(7)8 factors	(20)3 is	(31)2 during	(42)2 we
(8)7 plate	(21)3 rates,	(32)2 environmental	(43)2 were
(9)5 by	(22)3 was	(33)2 factor-beta
(10)4 factor-1	(23)3 will	(34)2 for
(11)4 mindset	(24)2 are	(35)2 functions

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--- WordNet output for growth --- =>茂み, 成長, 増加, 発展, 栽培, 腫よう, 成長物 Overview of noun growth The noun growth has 7 senses (first 5 from tagged texts) 1. (37) growth, growing, maturation, development, ontogeny, ontogenesis -- ((biology) the process of an individual organism growing organically; a purely biological unfolding of events involved in an organism changing gradually from a simple to a more complex level; "he proposed an indicator of osseous development in children") 2. (20) growth -- (a progression from simpler to more complex forms; "the growth of culture") 3. (3) increase, increment, growth -- (a process of becoming larger or longer or more numerous or more important; "the increase in unemployment"; "the growth of population") 4. (3) growth -- (vegetation that has grown; "a growth of trees"; "the only growth was some salt grass") 5. (1) emergence, outgrowth, growth -- (the gradual beginning or coming forth; "figurines presage the emergence of sculpture in Greece") 6. growth -- ((pathology) an abnormal proliferation of tissue (as in a tumor)) 7. growth -- (something grown or growing; "a growth of hair") --- WordNet end ---