FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387160913> ?p ?o ?g. }

• W4387160913 endingPage "e231" @default.
• W4387160913 startingPage "e231" @default.
• W4387160913 abstract "Selective superoxide dismutase mimetics (DMs), including GC4419 and GC4711, are radiation (RT) modulators which induce opposite effects in tumors and normal tissues and may be ideally suited for locally advanced rectal cancer. However, their tumor radiosensitization effect is limited at RT doses relevant to rectal cancer (2-5 Gy). Over this dose range, they protect normal mucosal tissues, but we and others have shown they do not reliably enhance tumor radiosensitization at doses < 8-15 Gy. We hypothesize that combining DMs and other therapies which also target redox metabolism may effectively sensitize tumors to clinically relevant RT doses for rectal cancer while maintaining their normal tissue sparing effects. Like DMs, pharmacological ascorbate (P-AscH) selectively increases lethal hydrogen peroxide (H2O2) fluxes in tumors, but it does so through distinct mechanisms which are potentially complimentary with DMs (particularly at low RT doses).Human HCT116, SW480, and HT29 colorectal tumor models and non-malignant FHs74 intestinal epithelial cells were used. Clonogenic survival was assessed following single-fraction RT (2-5 Gy) +/- P-AscH (5 pmol/cell) +/- GC4711 (20 µM). Dependency on H202 fluxes was tested by adding bovine catalase with drug and RT treatments. Oxygen consumption in culture media was measured using a Clark electrode. Rectal toxicity was assessed in vivo using IHC in fixed rectal tissues following fractionated, image-guided rectal RT (5-9 Gy x 3). Tumor growth delay was assessed following RT (5 Gy x 3) +/- P-AscH (4 g/kg) +/- GC4419 (10 mg/kg) in animals with unilateral HCT116 flank tumors.Combination therapy with P-AscH and GC4711 potently radiosensitized all tumor lines in vitro whereas neither agent significantly decreased clonogenic survival as a monotherapy. Neither drug nor combination treatment sensitized FHs74 epithelial cells. P-AscH increased oxygen consumption and H2O2 production in culture media and the addition of GC4711 significantly increased both more than P-AscH alone. Co-treatment with exogenous catalase inhibited cancer cell killing with combination therapy +/- RT. In vivo, combination therapy significantly enhanced tumor growth delay and survival. Both agents significantly decreased markers of acute rectal RT injury as monotherapies.Co-treatment with DMs and P-AscH selectively enhanced tumor radiosensitization by increasing oxygen consumption and H202 fluxes even in tumor models which are known to be resistant to oxidative stressors (HT29). In contrast, each agent conferred a radioprotective effect in the rectum. Combination therapy with DMs and P-AscH may represent a novel, potent approach to target dysregulated redox metabolism in colorectal tumors." @default.
• W4387160913 created "2023-09-30" @default.
• W4387160913 creator A5013867222 @default.
• W4387160913 creator A5021536460 @default.
• W4387160913 creator A5021903894 @default.
• W4387160913 creator A5044951080 @default.
• W4387160913 creator A5087974114 @default.
• W4387160913 date "2023-10-01" @default.
• W4387160913 modified "2023-10-17" @default.
• W4387160913 title "Enhanced Peroxide Fluxes and Radiosensitization in Colorectal Tumors but Not Normal Enterocytes from the Combination of Superoxide Dismutase Mimetics and Pharmacological Ascorbate" @default.
• W4387160913 doi "https://doi.org/10.1016/j.ijrobp.2023.06.1145" @default.
• W4387160913 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37784928" @default.
• W4387160913 hasPublicationYear "2023" @default.
• W4387160913 type Work @default.
• W4387160913 citedByCount "0" @default.
• W4387160913 crossrefType "journal-article" @default.
• W4387160913 hasAuthorship W4387160913A5013867222 @default.
• W4387160913 hasAuthorship W4387160913A5021536460 @default.
• W4387160913 hasAuthorship W4387160913A5021903894 @default.
• W4387160913 hasAuthorship W4387160913A5044951080 @default.
• W4387160913 hasAuthorship W4387160913A5087974114 @default.
• W4387160913 hasConcept C117262875 @default.
• W4387160913 hasConcept C121608353 @default.
• W4387160913 hasConcept C126322002 @default.
• W4387160913 hasConcept C142724271 @default.
• W4387160913 hasConcept C150903083 @default.
• W4387160913 hasConcept C207001950 @default.
• W4387160913 hasConcept C2775838275 @default.
• W4387160913 hasConcept C2776151105 @default.
• W4387160913 hasConcept C2778979269 @default.
• W4387160913 hasConcept C2781074409 @default.
• W4387160913 hasConcept C502942594 @default.
• W4387160913 hasConcept C526805850 @default.
• W4387160913 hasConcept C71924100 @default.
• W4387160913 hasConcept C86803240 @default.
• W4387160913 hasConceptScore W4387160913C117262875 @default.
• W4387160913 hasConceptScore W4387160913C121608353 @default.
• W4387160913 hasConceptScore W4387160913C126322002 @default.
• W4387160913 hasConceptScore W4387160913C142724271 @default.
• W4387160913 hasConceptScore W4387160913C150903083 @default.
• W4387160913 hasConceptScore W4387160913C207001950 @default.
• W4387160913 hasConceptScore W4387160913C2775838275 @default.
• W4387160913 hasConceptScore W4387160913C2776151105 @default.
• W4387160913 hasConceptScore W4387160913C2778979269 @default.
• W4387160913 hasConceptScore W4387160913C2781074409 @default.
• W4387160913 hasConceptScore W4387160913C502942594 @default.
• W4387160913 hasConceptScore W4387160913C526805850 @default.
• W4387160913 hasConceptScore W4387160913C71924100 @default.
• W4387160913 hasConceptScore W4387160913C86803240 @default.
• W4387160913 hasIssue "2" @default.
• W4387160913 hasLocation W43871609131 @default.
• W4387160913 hasLocation W43871609132 @default.
• W4387160913 hasOpenAccess W4387160913 @default.
• W4387160913 hasPrimaryLocation W43871609131 @default.
• W4387160913 hasRelatedWork W1511779378 @default.
• W4387160913 hasRelatedWork W1515592398 @default.
• W4387160913 hasRelatedWork W2039129807 @default.
• W4387160913 hasRelatedWork W2054457087 @default.
• W4387160913 hasRelatedWork W2062906738 @default.
• W4387160913 hasRelatedWork W2074324989 @default.
• W4387160913 hasRelatedWork W2081917043 @default.
• W4387160913 hasRelatedWork W2116564275 @default.
• W4387160913 hasRelatedWork W2409285845 @default.
• W4387160913 hasRelatedWork W2414997680 @default.
• W4387160913 hasVolume "117" @default.
• W4387160913 isParatext "false" @default.
• W4387160913 isRetracted "false" @default.
• W4387160913 workType "article" @default.