ELIZA

return kwic search for activity out of >500 occurrences
475194 occurrences (No.33 in the rank) during 5 years in the PubMed. [cache]

85) Both hypoxic pancreatic tumors as well as serum from patients with pancreatic cancer accumulated L-2HG as a result of promiscuous activity of LDHA.

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PMID:33990397 DOI:10.1158/0008-5472.CAN-20-2562

2021 Cancer research

* Hypoxia-Driven Oncometabolite L-2HG Maintains Stemness-Differentiation Balance and Facilitates Immune Evasion in Pancreatic Cancer.

- In pancreatic cancer, the robust fibroinflammatory stroma contributes to immune suppression and renders tumors hypoxic, altering intratumoral metabolic pathways and leading to poor survival. One metabolic enzyme activated during hypoxia is lactate dehydrogenase A (LDHA). As a result of its promiscuous activity under hypoxia, LDHA produces L-2 hydroxyglutarate (L-2HG), an epigenetic modifier, that regulates the tumor transcriptome. However, the role of L-2HG in remodeling the pancreatic tumor microenvironment is not known. Here we used mass spectrometry to detect L-2HG in serum samples from patients with pancreatic cancer, comprising tumor cells as well as stromal cells. Both hypoxic pancreatic tumors as well as serum from patients with pancreatic cancer accumulated L-2HG as a result of promiscuous activity of LDHA. This abnormally accumulated L-2HG led to H3 hypermethylation and altered gene expression, which regulated a critical balance between stemness and differentiation in pancreatic tumors. Secreted L-2HG inhibited T-cell proliferation and migration, suppressing antitumor immunity. In a syngeneic orthotopic model of pancreatic cancer, inhibition of LDH with GSK2837808A decreased L-2HG, induced tumor regression, and sensitized tumors to anti-PD1 therapy. In conclusion, hypoxia-mediated promiscuous activity of LDH produces L-2HG in pancreatic tumor cells, regulating the stemness-differentiation balance and contributing to immune evasion. Targeting LDH can be developed as a potential therapy to sensitize pancreatic tumors to checkpoint inhibitor therapy. SIGNIFICANCE: This study shows that promiscuous LDH activity produces L-2HG in pancreatic tumor and stromal cells, modulating tumor stemness and immune cell function and infiltration in the tumor microenvironment.

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[frequency of next (right) word to activity]

(1)69 and	(13)5 are	(25)3 interventions	(37)2 effect;
(2)46 of	(14)5 or	(26)3 limitations	(38)2 for
(3)45 in	(15)5 relationship	(27)3 models	(39)2 has
(4)44 null	(16)5 with	(28)3 opportunities	(40)2 increased
(5)14 was	(17)4 and/or	(29)3 programs	(41)2 levels
(6)13 against	(18)4 at	(30)3 sedentary	(42)2 levels,
(7)12 (PA)	(19)4 may	(31)3 that	(43)2 plays
(8)10 is	(20)3 (PA),	(32)3 through	(44)2 programmes
(9)7 as	(21)3 advice	(33)2 appears	(45)2 using
(10)6 by	(22)3 but	(34)2 assessment
(11)6 during	(23)3 changes	(35)2 counselling
(12)6 on	(24)3 compared	(36)2 differentiation

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--- WordNet output for activity --- =>活動, 活躍, 働き, 動き, 活気 Overview of noun activity The noun activity has 6 senses (first 3 from tagged texts) 1. (43) activity -- (any specific behavior; "they avoided all recreational activity") 2. (36) action, activity, activeness -- (the state of being active; "his sphere of activity"; "he is out of action") 3. (13) bodily process, body process, bodily function, activity -- (an organic process that takes place in the body; "respiratory activity") 4. activity -- ((chemistry) the capacity of a substance to take part in a chemical reaction; "catalytic activity") 5. natural process, natural action, action, activity -- (a process existing in or produced by nature (rather than by the intent of human beings); "the action of natural forces"; "volcanic activity") 6. activeness, activity -- (the trait of being active; moving or acting rapidly and energetically; "the level of activity declines with age") --- WordNet end ---