FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3182474600> ?p ?o ?g. }

• W3182474600 abstract "Chemopreventive efficacy of p-XSC is well documented but it failed due to systemic toxicity issues. This toxicity could partially be due to the release of poisonous hydrogen cyanide generated after p-XSC metabolizes to form active bis-selenol (p-XSeH). To address the said concern, we recently designed and developed p-XS-Asp, with the rationale that it would cleave in vivo to release the active p-XSeH and aspirin instead of undesired HCN, thus making the compound less toxic and possibly more potent than p-XSC. Indeed, we have shown previously that p-XS-Asp inhibits NNK-induced lung tumorigenesis in A/J mice more effectively than p-XSC in a complete A/J mouse model, and is better tolerable. The complete model, however, does not reveal at what stage of carcinogenesis does p-XS-Asp acts. In the current study, we evaluated the stage-specificity of chemopreventive efficacy of p-XS-Asp in NNK-induced lung carcinogenesis in A/J mice models. A/J mice were divided into 7 distinct groups (n=30 per group, half male, half female; except group 1 and 2 where n=10). The mice were fed AIN-93M diet (control) or p-XS-Asp diet until they reached termination end point of 26 weeks (adenomas) and 40 weeks (adenocarcinomas). Two weeks after the experiment started, all the groups, except for group 1 and 2, were given a single IP injection of 10 µmol (100 mg/kg) of NNK. Group 3 and 4 were on complete control AIN93M and p-XS-Asp diets, respectively. Group 5 (peri-initiation) was on p-XS-Asp for the first 3 weeks and then on the control diet till the end of the experiment. On the other hand, group 6 (post-initiation) was on control diet for 3 weeks and then was changed to the p-XS-Asp diet. In the progression group 7, mice were on control diet for 14 weeks and subsequently changed to p-XS-Asp diet. The Groups 4 and 5 mice showed a remarkable decrease in the tumor multiplicity (TM) and incidence (TI) as compared to the mice on control diet at both 26 and 40 week time-points. The TM in male mice for groups 1, 2, 3, 4, 5, 6 and 7 at 26 weeks was 0.6, 0, 5.7, 1, 1.54, 4.27, and 6.27, respectively, while at 40 weeks, it was 0.2, 0, 7.7, 1, 1.8, 4.1, and 4.9, respectively. A similar trend was also observed in female mice. These data clearly demonstrated that robust inhibition at peri-initiation stage is mainly responsible for the activity observed in the complete model. The inhibition of both O6-methylguanine and pyridoxobutyl mutagenic DNA adducts by p-XS-Asp further compliments that the compound acts at initial stages of carcinogenesis. Body weights comparison and the blood and tissue analyses showed no systemic toxicity for the p-XS-Asp fed groups. RNA-seq data of the tumor tissues showed numerous signaling pathways to be affected in p-XS-Asp treated mice. The exact mechanism of action is still under investigation. In summary, our results show that p-XS-Asp may be promising candidate for future clinical evaluation as a lung cancer preventive agent.Citation Format: Asif Raza, Amandeep Singh, Cesar Aliaga, Daniel Plano, Shantu Amin, Arun K. Sharma. Stage-specific inhibition of NNK-induced lung carcinogenesis by 1,4-phenylenebis(methylene)seleno-aspirin (p-XS-Asp) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2596." @default.
• W3182474600 created "2021-07-19" @default.
• W3182474600 creator A5001311093 @default.
• W3182474600 creator A5018954418 @default.
• W3182474600 creator A5030453913 @default.
• W3182474600 creator A5036658711 @default.
• W3182474600 creator A5048058203 @default.
• W3182474600 creator A5063979460 @default.
• W3182474600 date "2021-07-01" @default.
• W3182474600 modified "2023-09-27" @default.
• W3182474600 title "Abstract 2596: Stage-specific inhibition of NNK-induced lung carcinogenesis by 1,4-phenylenebis(methylene)seleno-aspirin (p-XS-Asp)" @default.
• W3182474600 doi "https://doi.org/10.1158/1538-7445.am2021-2596" @default.
• W3182474600 hasPublicationYear "2021" @default.
• W3182474600 type Work @default.
• W3182474600 sameAs 3182474600 @default.
• W3182474600 citedByCount "0" @default.
• W3182474600 crossrefType "proceedings-article" @default.
• W3182474600 hasAuthorship W3182474600A5001311093 @default.
• W3182474600 hasAuthorship W3182474600A5018954418 @default.
• W3182474600 hasAuthorship W3182474600A5030453913 @default.
• W3182474600 hasAuthorship W3182474600A5036658711 @default.
• W3182474600 hasAuthorship W3182474600A5048058203 @default.
• W3182474600 hasAuthorship W3182474600A5063979460 @default.
• W3182474600 hasConcept C104317684 @default.
• W3182474600 hasConcept C114246631 @default.
• W3182474600 hasConcept C126322002 @default.
• W3182474600 hasConcept C150903083 @default.
• W3182474600 hasConcept C155647269 @default.
• W3182474600 hasConcept C178790620 @default.
• W3182474600 hasConcept C185592680 @default.
• W3182474600 hasConcept C207001950 @default.
• W3182474600 hasConcept C2777454769 @default.
• W3182474600 hasConcept C2777628954 @default.
• W3182474600 hasConcept C2777714996 @default.
• W3182474600 hasConcept C29730261 @default.
• W3182474600 hasConcept C502942594 @default.
• W3182474600 hasConcept C55493867 @default.
• W3182474600 hasConcept C555283112 @default.
• W3182474600 hasConcept C71240020 @default.
• W3182474600 hasConcept C71924100 @default.
• W3182474600 hasConcept C86803240 @default.
• W3182474600 hasConcept C98274493 @default.
• W3182474600 hasConceptScore W3182474600C104317684 @default.
• W3182474600 hasConceptScore W3182474600C114246631 @default.
• W3182474600 hasConceptScore W3182474600C126322002 @default.
• W3182474600 hasConceptScore W3182474600C150903083 @default.
• W3182474600 hasConceptScore W3182474600C155647269 @default.
• W3182474600 hasConceptScore W3182474600C178790620 @default.
• W3182474600 hasConceptScore W3182474600C185592680 @default.
• W3182474600 hasConceptScore W3182474600C207001950 @default.
• W3182474600 hasConceptScore W3182474600C2777454769 @default.
• W3182474600 hasConceptScore W3182474600C2777628954 @default.
• W3182474600 hasConceptScore W3182474600C2777714996 @default.
• W3182474600 hasConceptScore W3182474600C29730261 @default.
• W3182474600 hasConceptScore W3182474600C502942594 @default.
• W3182474600 hasConceptScore W3182474600C55493867 @default.
• W3182474600 hasConceptScore W3182474600C555283112 @default.
• W3182474600 hasConceptScore W3182474600C71240020 @default.
• W3182474600 hasConceptScore W3182474600C71924100 @default.
• W3182474600 hasConceptScore W3182474600C86803240 @default.
• W3182474600 hasConceptScore W3182474600C98274493 @default.
• W3182474600 hasLocation W31824746001 @default.
• W3182474600 hasOpenAccess W3182474600 @default.
• W3182474600 hasPrimaryLocation W31824746001 @default.
• W3182474600 hasRelatedWork W172564145 @default.
• W3182474600 hasRelatedWork W1984586254 @default.
• W3182474600 hasRelatedWork W1999523634 @default.
• W3182474600 hasRelatedWork W2009786324 @default.
• W3182474600 hasRelatedWork W2046897787 @default.
• W3182474600 hasRelatedWork W2056966621 @default.
• W3182474600 hasRelatedWork W2079763637 @default.
• W3182474600 hasRelatedWork W2271907559 @default.
• W3182474600 hasRelatedWork W2521024263 @default.
• W3182474600 hasRelatedWork W974381337 @default.
• W3182474600 isParatext "false" @default.
• W3182474600 isRetracted "false" @default.
• W3182474600 magId "3182474600" @default.
• W3182474600 workType "article" @default.