ELIZA

return kwic search for higher out of >500 occurrences
487192 occurrences (No.29 in the rank) during 5 years in the PubMed. [cache]

275) Moreover, we attribute the higher selectivity of carbohydrate-conjugated T5 for tumoral cells to its preferential uptake through the overexpressed glucose transporter 1.

--- ABSTRACT ---

PMID:34166611 DOI:10.1016/j.chembiol.2021.05.021

2021 Cell chemical biology

* Targeting ribosomal G-quadruplexes with naphthalene-diimides as RNA polymerase I inhibitors for colorectal cancer treatment.

- Guanine quadruplexes (G4s) are non-canonical nucleic acid structures commonly found in regulatory genomic regions. G4 targeting has emerged as a therapeutic approach in cancer. We have screened naphthalene-diimides (NDIs), a class of G4 ligands, in a cellular model of colorectal cancer (CRC). Here, we identify the leading compound T5 with a potent and selective inhibition of cell growth by high-affinity binding to G4s in ribosomal DNA, impairing RNA polymerase I (Pol I) elongation. Consequently, T5 induces a rapid inhibition of Pol I transcription, nucleolus disruption, proteasome-dependent Pol I catalytic subunit A degradation and autophagy. Moreover, we attribute the higher selectivity of carbohydrate-conjugated T5 for tumoral cells to its preferential uptake through the overexpressed glucose transporter 1. Finally, we succinctly demonstrate that T5 could be explored as a therapeutic agent in a patient cohort with CRC. Therefore, we report a mode of action for these NDIs involving ribosomal G4 targeting.

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(1)37 than	(14)5 mortality	(27)2 activation	(40)2 or
(2)33 in	(15)4 concentrations	(28)2 anti-E	(41)2 percentage
(3)28 levels	(16)4 proportion	(29)2 at	(42)2 performing
(4)27 risk	(17)4 rate	(30)2 auditory-perceptual	(43)2 potency
(5)11 rates	(18)4 regions	(31)2 cognitive	(44)2 risk,
(6)10 among	(19)3 consumption	(32)2 compared	(45)2 scores
(7)8 for	(20)3 frequency	(33)2 disease	(46)2 selectivity
(8)8 prevalence	(21)3 plasma	(34)2 doses	(47)2 social
(9)7 education	(22)3 quality	(35)2 endostatin	(48)2 stimulation
(10)7 level	(23)3 sensitivity	(36)2 extent	(49)2 to
(11)6 expression	(24)3 strength	(37)2 from	(50)2 tumor
(12)5 and	(25)2 F	(38)2 glutamate-cysteine	(51)2 weight
(13)5 incidence	(26)2 NAFLD	(39)2 odds

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--- WordNet output for higher --- =>幹部, おえら方 Overview of adj higher The adj higher has 2 senses (first 2 from tagged texts) 1. (10) higher -- (advanced in complexity or elaboration; "higher finance"; "higher mathematics") 2. (1) higher -- (of education beyond the secondary level; "higher education"; "higher learning") Overview of adj high The adj high has 7 senses (first 5 from tagged texts) 1. (134) high -- (greater than normal in degree or intensity or amount; "a high temperature"; "a high price"; "the high point of his career"; "high risks"; "has high hopes"; "the river is high"; "he has a high opinion of himself") 2. (51) high -- ((literal meaning) being at or having a relatively great or specific elevation or upward extension (sometimes used in combinations like `knee-high'); "a high mountain"; "high ceilings"; "high buildings"; "a high forehead"; "a high incline"; "a foot high") 3. (10) eminent, high -- (standing above others in quality or position; "people in high places"; "the high priest"; "eminent members of the community") 4. (7) high, high-pitched -- (used of sounds and voices; high in pitch or frequency) 5. (2) high, in high spirits -- (happy and excited and energetic) 6. gamey, gamy, high -- ((used of the smell of meat) smelling spoiled or tainted) 7. high, mellow -- (slightly and pleasantly intoxicated from alcohol or a drug (especially marijuana)) --- WordNet end ---