Matches in SemOpenAlex for { <https://semopenalex.org/work/W3196871504> ?p ?o ?g. }
Showing items 1 to 91 of
91
with 100 items per page.
- W3196871504 abstract "Hyperleptinemia is a well-established side-effect of targeting AR signalling in PCa. A concomitant rise in leptin and its receptor (LEPR) are observed in vitro following androgen-deprivation and in patient tissues representing advanced stage disease. As leptin impacts multiple cancer hallmarks, including growth, migration/metastasis, angiogenesis, metabolism and inflammation, targeting leptin is therapeutically appealing. Efficacy of established LEPR antagonist, Allo-aca, was assessed in vitro in PCa cells subjected to 48hr ADT and in vivo, from PSA nadir, in castrated BALB/c nude mice bearing subcutaneous LNCaP tumour xenografts (1mg/kg/d). In ADT-treated LNCaP, leptin increased proliferation, migration and invasion; an effect prevented by Allo-aca. In vivo, Allo-aca reduced tumour weight and volume (P≤0.05) vs control, and in 2 cases fully regressed tumours. Allo-aca conferred a 12d survival advantage, and tended to lower serum PSA, vs control (P=0.07). Body weight was unaffected. Allo-aca altered tumour phenotype, with xenografts paler than the bloody and well-vascularized controls. In concordance, pathway analysis of differentially expressed transcripts (RNAseq) revealed altered hypoxia signalling in Allo-aca vs control tumours. Enrichment was also observed in pathways of mitochondrial dysfunction and sirtuin signalling, glucose metabolism, mTOR signalling and pathways controlling protein synthesis to name a few. In conclusion, Allo-aca combats cancer hallmarks in vitro and is efficacious in preventing PCa progression in vivo. Our data suggest Allo-aca reduces angiogenesis and alters the tumour microenvironment, but this, and other mechanisms of Allo-aca action in PCa, require further investigation. Our data highlight that Allo-aca may be a promising therapeutic in treating advanced PCa. Translational Impact: This translational study is specifically designed to combat an major issue faced by men with advanced prostate cancer (PCa), that disease progression to castrate resistant PCa is currently incurable and that increased therapeutic options are urgently required to delay disease progression. Our preclinical data shows that Allo-aca combats cancer hallmarks in vitro and is efficacious in preventing PCa progression in vivo. Our data highlight that Allo-aca may be a promising therapeutic in treating advanced PCa." @default.
- W3196871504 created "2021-09-13" @default.
- W3196871504 creator A5001444084 @default.
- W3196871504 creator A5028045087 @default.
- W3196871504 creator A5028175913 @default.
- W3196871504 creator A5037704994 @default.
- W3196871504 creator A5051860064 @default.
- W3196871504 creator A5060326270 @default.
- W3196871504 creator A5081577047 @default.
- W3196871504 creator A5086873656 @default.
- W3196871504 creator A5089480920 @default.
- W3196871504 date "2018-01-01" @default.
- W3196871504 modified "2023-09-26" @default.
- W3196871504 title "Targeting Leptin Receptor Signalling Slows the Progression of Advanced Prostate Cancer" @default.
- W3196871504 hasPublicationYear "2018" @default.
- W3196871504 type Work @default.
- W3196871504 sameAs 3196871504 @default.
- W3196871504 citedByCount "0" @default.
- W3196871504 crossrefType "journal-article" @default.
- W3196871504 hasAuthorship W3196871504A5001444084 @default.
- W3196871504 hasAuthorship W3196871504A5028045087 @default.
- W3196871504 hasAuthorship W3196871504A5028175913 @default.
- W3196871504 hasAuthorship W3196871504A5037704994 @default.
- W3196871504 hasAuthorship W3196871504A5051860064 @default.
- W3196871504 hasAuthorship W3196871504A5060326270 @default.
- W3196871504 hasAuthorship W3196871504A5081577047 @default.
- W3196871504 hasAuthorship W3196871504A5086873656 @default.
- W3196871504 hasAuthorship W3196871504A5089480920 @default.
- W3196871504 hasConcept C121608353 @default.
- W3196871504 hasConcept C126322002 @default.
- W3196871504 hasConcept C134018914 @default.
- W3196871504 hasConcept C14372207 @default.
- W3196871504 hasConcept C150903083 @default.
- W3196871504 hasConcept C207001950 @default.
- W3196871504 hasConcept C2779013556 @default.
- W3196871504 hasConcept C2779723316 @default.
- W3196871504 hasConcept C2780192828 @default.
- W3196871504 hasConcept C2780394083 @default.
- W3196871504 hasConcept C2780613262 @default.
- W3196871504 hasConcept C502942594 @default.
- W3196871504 hasConcept C511355011 @default.
- W3196871504 hasConcept C62478195 @default.
- W3196871504 hasConcept C71924100 @default.
- W3196871504 hasConcept C86554907 @default.
- W3196871504 hasConcept C86803240 @default.
- W3196871504 hasConcept C95444343 @default.
- W3196871504 hasConceptScore W3196871504C121608353 @default.
- W3196871504 hasConceptScore W3196871504C126322002 @default.
- W3196871504 hasConceptScore W3196871504C134018914 @default.
- W3196871504 hasConceptScore W3196871504C14372207 @default.
- W3196871504 hasConceptScore W3196871504C150903083 @default.
- W3196871504 hasConceptScore W3196871504C207001950 @default.
- W3196871504 hasConceptScore W3196871504C2779013556 @default.
- W3196871504 hasConceptScore W3196871504C2779723316 @default.
- W3196871504 hasConceptScore W3196871504C2780192828 @default.
- W3196871504 hasConceptScore W3196871504C2780394083 @default.
- W3196871504 hasConceptScore W3196871504C2780613262 @default.
- W3196871504 hasConceptScore W3196871504C502942594 @default.
- W3196871504 hasConceptScore W3196871504C511355011 @default.
- W3196871504 hasConceptScore W3196871504C62478195 @default.
- W3196871504 hasConceptScore W3196871504C71924100 @default.
- W3196871504 hasConceptScore W3196871504C86554907 @default.
- W3196871504 hasConceptScore W3196871504C86803240 @default.
- W3196871504 hasConceptScore W3196871504C95444343 @default.
- W3196871504 hasLocation W31968715041 @default.
- W3196871504 hasOpenAccess W3196871504 @default.
- W3196871504 hasPrimaryLocation W31968715041 @default.
- W3196871504 hasRelatedWork W1496745366 @default.
- W3196871504 hasRelatedWork W1800861137 @default.
- W3196871504 hasRelatedWork W1982624034 @default.
- W3196871504 hasRelatedWork W2007797294 @default.
- W3196871504 hasRelatedWork W2025032168 @default.
- W3196871504 hasRelatedWork W2031925353 @default.
- W3196871504 hasRelatedWork W2057300149 @default.
- W3196871504 hasRelatedWork W227559925 @default.
- W3196871504 hasRelatedWork W231795461 @default.
- W3196871504 hasRelatedWork W2767079966 @default.
- W3196871504 hasRelatedWork W2783262509 @default.
- W3196871504 hasRelatedWork W2789689752 @default.
- W3196871504 hasRelatedWork W2791087798 @default.
- W3196871504 hasRelatedWork W2793155346 @default.
- W3196871504 hasRelatedWork W2992091792 @default.
- W3196871504 hasRelatedWork W3013737061 @default.
- W3196871504 hasRelatedWork W3147573802 @default.
- W3196871504 hasRelatedWork W3200274832 @default.
- W3196871504 hasRelatedWork W2117428432 @default.
- W3196871504 hasRelatedWork W279005318 @default.
- W3196871504 isParatext "false" @default.
- W3196871504 isRetracted "false" @default.
- W3196871504 magId "3196871504" @default.
- W3196871504 workType "article" @default.