Matches in SemOpenAlex for { <https://semopenalex.org/work/W1974964199> ?p ?o ?g. }
- W1974964199 endingPage "1332" @default.
- W1974964199 startingPage "1320" @default.
- W1974964199 abstract "Background & AimsNonsteroidal anti-inflammatory drugs (NSAIDs) are effective cancer chemopreventive agents. However, chronic administration of NSAIDs is associated with significant side effects, mainly of the gastrointestinal tract. Given these limitations, we synthesized phospho-sulindac (P-S; OXT-328), a novel sulindac derivative.MethodsHere, we evaluated the safety and efficacy of P-S in preclinical models, including its mechanism of action with human colon cancer cell (HCCC) lines and animal tumor models.Results(1) Compared with sulindac, P-S is much more potent in inhibiting the growth of cultured HCCCs and more efficacious in preventing the growth of HT-29 xenografts in nude mice. P-S also prevents the growth of intestinal tumors in Apc/Min mice. (2) In combination with difluoromethylornithine (DFMO), P-S reduced tumor multiplicity in Apc/Min mice by 90%. (3) P-S is much safer than sulindac as evidenced by its in vitro toxicologic evaluation and animal toxicity studies. Mechanistically, P-S increases the intracellular levels of reactive oxygen and nitrogen species, which are key early mediators of its chemopreventive effect. Moreover, P-S induces spermidine/spermine N1-acetyltransferase enzymatic activity, and together with DFMO it reduces polyamine levels in vitro and in vivo.ConclusionsP-S displays considerable safety and efficacy, two pharmacologic properties that are essential for a potential cancer chemopreventive agent, and thus merits further evaluation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective cancer chemopreventive agents. However, chronic administration of NSAIDs is associated with significant side effects, mainly of the gastrointestinal tract. Given these limitations, we synthesized phospho-sulindac (P-S; OXT-328), a novel sulindac derivative. Here, we evaluated the safety and efficacy of P-S in preclinical models, including its mechanism of action with human colon cancer cell (HCCC) lines and animal tumor models. (1) Compared with sulindac, P-S is much more potent in inhibiting the growth of cultured HCCCs and more efficacious in preventing the growth of HT-29 xenografts in nude mice. P-S also prevents the growth of intestinal tumors in Apc/Min mice. (2) In combination with difluoromethylornithine (DFMO), P-S reduced tumor multiplicity in Apc/Min mice by 90%. (3) P-S is much safer than sulindac as evidenced by its in vitro toxicologic evaluation and animal toxicity studies. Mechanistically, P-S increases the intracellular levels of reactive oxygen and nitrogen species, which are key early mediators of its chemopreventive effect. Moreover, P-S induces spermidine/spermine N1-acetyltransferase enzymatic activity, and together with DFMO it reduces polyamine levels in vitro and in vivo. P-S displays considerable safety and efficacy, two pharmacologic properties that are essential for a potential cancer chemopreventive agent, and thus merits further evaluation." @default.
- W1974964199 created "2016-06-24" @default.
- W1974964199 creator A5033171381 @default.
- W1974964199 creator A5034970510 @default.
- W1974964199 creator A5051957313 @default.
- W1974964199 creator A5052899332 @default.
- W1974964199 creator A5058350630 @default.
- W1974964199 creator A5061750938 @default.
- W1974964199 creator A5074378902 @default.
- W1974964199 creator A5079097444 @default.
- W1974964199 creator A5086259408 @default.
- W1974964199 creator A5086401971 @default.
- W1974964199 date "2010-10-01" @default.
- W1974964199 modified "2023-10-10" @default.
- W1974964199 title "Phospho-Sulindac (OXT-328), a Novel Sulindac Derivative, Is Safe and Effective in Colon Cancer Prevention in Mice" @default.
- W1974964199 cites W1999364273 @default.
- W1974964199 cites W2013165612 @default.
- W1974964199 cites W2025810127 @default.
- W1974964199 cites W2026091191 @default.
- W1974964199 cites W2028953339 @default.
- W1974964199 cites W2046975940 @default.
- W1974964199 cites W2059192510 @default.
- W1974964199 cites W2097235831 @default.
- W1974964199 cites W2111263798 @default.
- W1974964199 cites W2112193780 @default.
- W1974964199 cites W2153037733 @default.
- W1974964199 cites W2166797557 @default.
- W1974964199 cites W2170720047 @default.
- W1974964199 cites W2171757752 @default.
- W1974964199 cites W2315613727 @default.
- W1974964199 doi "https://doi.org/10.1053/j.gastro.2010.06.044" @default.
- W1974964199 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2949489" @default.
- W1974964199 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20600034" @default.
- W1974964199 hasPublicationYear "2010" @default.
- W1974964199 type Work @default.
- W1974964199 sameAs 1974964199 @default.
- W1974964199 citedByCount "52" @default.
- W1974964199 countsByYear W19749641992012 @default.
- W1974964199 countsByYear W19749641992013 @default.
- W1974964199 countsByYear W19749641992014 @default.
- W1974964199 countsByYear W19749641992015 @default.
- W1974964199 countsByYear W19749641992016 @default.
- W1974964199 countsByYear W19749641992017 @default.
- W1974964199 countsByYear W19749641992018 @default.
- W1974964199 countsByYear W19749641992019 @default.
- W1974964199 countsByYear W19749641992020 @default.
- W1974964199 countsByYear W19749641992021 @default.
- W1974964199 countsByYear W19749641992022 @default.
- W1974964199 countsByYear W19749641992023 @default.
- W1974964199 crossrefType "journal-article" @default.
- W1974964199 hasAuthorship W1974964199A5033171381 @default.
- W1974964199 hasAuthorship W1974964199A5034970510 @default.
- W1974964199 hasAuthorship W1974964199A5051957313 @default.
- W1974964199 hasAuthorship W1974964199A5052899332 @default.
- W1974964199 hasAuthorship W1974964199A5058350630 @default.
- W1974964199 hasAuthorship W1974964199A5061750938 @default.
- W1974964199 hasAuthorship W1974964199A5074378902 @default.
- W1974964199 hasAuthorship W1974964199A5079097444 @default.
- W1974964199 hasAuthorship W1974964199A5086259408 @default.
- W1974964199 hasAuthorship W1974964199A5086401971 @default.
- W1974964199 hasBestOaLocation W19749641991 @default.
- W1974964199 hasConcept C121608353 @default.
- W1974964199 hasConcept C126322002 @default.
- W1974964199 hasConcept C150903083 @default.
- W1974964199 hasConcept C181199279 @default.
- W1974964199 hasConcept C185592680 @default.
- W1974964199 hasConcept C202751555 @default.
- W1974964199 hasConcept C207001950 @default.
- W1974964199 hasConcept C2776120743 @default.
- W1974964199 hasConcept C2776241388 @default.
- W1974964199 hasConcept C2777497464 @default.
- W1974964199 hasConcept C2778484676 @default.
- W1974964199 hasConcept C2780512811 @default.
- W1974964199 hasConcept C29730261 @default.
- W1974964199 hasConcept C502942594 @default.
- W1974964199 hasConcept C526805850 @default.
- W1974964199 hasConcept C55493867 @default.
- W1974964199 hasConcept C71924100 @default.
- W1974964199 hasConcept C86803240 @default.
- W1974964199 hasConcept C98274493 @default.
- W1974964199 hasConceptScore W1974964199C121608353 @default.
- W1974964199 hasConceptScore W1974964199C126322002 @default.
- W1974964199 hasConceptScore W1974964199C150903083 @default.
- W1974964199 hasConceptScore W1974964199C181199279 @default.
- W1974964199 hasConceptScore W1974964199C185592680 @default.
- W1974964199 hasConceptScore W1974964199C202751555 @default.
- W1974964199 hasConceptScore W1974964199C207001950 @default.
- W1974964199 hasConceptScore W1974964199C2776120743 @default.
- W1974964199 hasConceptScore W1974964199C2776241388 @default.
- W1974964199 hasConceptScore W1974964199C2777497464 @default.
- W1974964199 hasConceptScore W1974964199C2778484676 @default.
- W1974964199 hasConceptScore W1974964199C2780512811 @default.
- W1974964199 hasConceptScore W1974964199C29730261 @default.
- W1974964199 hasConceptScore W1974964199C502942594 @default.
- W1974964199 hasConceptScore W1974964199C526805850 @default.
- W1974964199 hasConceptScore W1974964199C55493867 @default.
- W1974964199 hasConceptScore W1974964199C71924100 @default.
- W1974964199 hasConceptScore W1974964199C86803240 @default.