FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2495249956> ?p ?o ?g. }

• W2495249956 abstract "When tumor cells home to bone microenvironment they secrete factors that stimulate osteoclast formation, which results in increased bone resorption. This in turn increases the release of factors from bone matrix that stimulate the growth of tumor cells, leading to a vicious cycle characterized by extensive bone loss and enhanced tumor growth in bone. Thus, factors that inhibit osteoclast formation or bone resorption activity of mature osteoclasts may have the potential to inhibit the vicious cycle. The RANKL inhibitor denosumab is approved for treatment of bone metastases from solid tumors, and the cathepsin K inhibitor odanacatib has been shown to suppress bone resorption in breast cancer patients with bone metastases. Human osteoclasts can be generated from bone marrow-derived CD34+ mesenchymal stem cells in the presence of M-CSF and RANKL. In this study we report optimization of separate in vitro culture systems for determining osteoclast differentiation and activity, and validation of denosumab and odanacatib as reference inhibitors of osteoclast differentiation and activity, respectively. CD34+ human osteoclast precursor cells were cultured on bovine bone slices for 7 days. Different concentrations of denosumab (0.01 - 10 μg/ml) were added in the cultures at day 0, and tartrate-resistant acid phosphatase isoform 5b activity (TRACP 5b) was measured from the culture medium collected at day 7 as an index of the number of formed osteoclasts. Osteoclast activity was studied by allowing the formed mature osteoclasts to resorb bone during an additional 3-day culture period. The culture medium was changed and different concentrations of odanacatib (0.001 - 1.0 μM) were added into the cultures at day 7, and the amount of C-terminal cross-linked telopeptides of type I collagen (CTX-I) was measured in the culture medium collected at day 10 to quantitate bone resorption during days 7-10. Denosumab and odanacatib showed strong concentration dependent inhibition of osteoclast differentiation and activity, respectively, with EC50 values of 0.124 μg/ml for denosumab and 0.0433 μM for odanacatib. We conclude that we have validated denosumab as a reference compound of osteoclast differentiation and odanacatib as a reference compound of osteoclast activity in a human in vitro osteoclast culture system. The culture system is a clinically reliable tool for identifying new compounds affecting the vicious cycle of osteolytic bone metastases, and clarifying if these active compounds target directly osteoclast differentiation or activity. Citation Format: Jenni Bernoulli, Jussi M. Halleen, Mari I. Suominen, Johanna Tuomela, Jukka Rissanen, Katja M. Fagerlund. Validation of human osteoclast cultures for studying the mode-of-action and identification of new compounds with the potential of inhibiting the vicious cycle in osteolytic bone metastases. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 364." @default.
• W2495249956 created "2016-08-23" @default.
• W2495249956 creator A5013170089 @default.
• W2495249956 creator A5017479923 @default.
• W2495249956 creator A5027010797 @default.
• W2495249956 creator A5034825484 @default.
• W2495249956 creator A5054563217 @default.
• W2495249956 creator A5061315354 @default.
• W2495249956 date "2016-07-15" @default.
• W2495249956 modified "2023-09-27" @default.
• W2495249956 title "Abstract 364: Validation of human osteoclast cultures for studying the mode-of-action and identification of new compounds with the potential of inhibiting the vicious cycle in osteolytic bone metastases" @default.
• W2495249956 doi "https://doi.org/10.1158/1538-7445.am2016-364" @default.
• W2495249956 hasPublicationYear "2016" @default.
• W2495249956 type Work @default.
• W2495249956 sameAs 2495249956 @default.
• W2495249956 citedByCount "0" @default.
• W2495249956 crossrefType "proceedings-article" @default.
• W2495249956 hasAuthorship W2495249956A5013170089 @default.
• W2495249956 hasAuthorship W2495249956A5017479923 @default.
• W2495249956 hasAuthorship W2495249956A5027010797 @default.
• W2495249956 hasAuthorship W2495249956A5034825484 @default.
• W2495249956 hasAuthorship W2495249956A5054563217 @default.
• W2495249956 hasAuthorship W2495249956A5061315354 @default.
• W2495249956 hasConcept C101990758 @default.
• W2495249956 hasConcept C126322002 @default.
• W2495249956 hasConcept C134018914 @default.
• W2495249956 hasConcept C170493617 @default.
• W2495249956 hasConcept C185592680 @default.
• W2495249956 hasConcept C202751555 @default.
• W2495249956 hasConcept C2776033226 @default.
• W2495249956 hasConcept C2779428903 @default.
• W2495249956 hasConcept C55493867 @default.
• W2495249956 hasConcept C673006 @default.
• W2495249956 hasConcept C71924100 @default.
• W2495249956 hasConcept C88045685 @default.
• W2495249956 hasConceptScore W2495249956C101990758 @default.
• W2495249956 hasConceptScore W2495249956C126322002 @default.
• W2495249956 hasConceptScore W2495249956C134018914 @default.
• W2495249956 hasConceptScore W2495249956C170493617 @default.
• W2495249956 hasConceptScore W2495249956C185592680 @default.
• W2495249956 hasConceptScore W2495249956C202751555 @default.
• W2495249956 hasConceptScore W2495249956C2776033226 @default.
• W2495249956 hasConceptScore W2495249956C2779428903 @default.
• W2495249956 hasConceptScore W2495249956C55493867 @default.
• W2495249956 hasConceptScore W2495249956C673006 @default.
• W2495249956 hasConceptScore W2495249956C71924100 @default.
• W2495249956 hasConceptScore W2495249956C88045685 @default.
• W2495249956 hasLocation W24952499561 @default.
• W2495249956 hasOpenAccess W2495249956 @default.
• W2495249956 hasPrimaryLocation W24952499561 @default.
• W2495249956 hasRelatedWork W1896884837 @default.
• W2495249956 hasRelatedWork W1974742534 @default.
• W2495249956 hasRelatedWork W2006985144 @default.
• W2495249956 hasRelatedWork W2012843603 @default.
• W2495249956 hasRelatedWork W2031442218 @default.
• W2495249956 hasRelatedWork W2051140350 @default.
• W2495249956 hasRelatedWork W2092339321 @default.
• W2495249956 hasRelatedWork W2094539147 @default.
• W2495249956 hasRelatedWork W2106142458 @default.
• W2495249956 hasRelatedWork W2109027220 @default.
• W2495249956 hasRelatedWork W2109288506 @default.
• W2495249956 hasRelatedWork W2114403851 @default.
• W2495249956 hasRelatedWork W2127591055 @default.
• W2495249956 hasRelatedWork W2167056700 @default.
• W2495249956 hasRelatedWork W2215275595 @default.
• W2495249956 hasRelatedWork W2417195887 @default.
• W2495249956 hasRelatedWork W2770277977 @default.
• W2495249956 hasRelatedWork W3094461282 @default.
• W2495249956 hasRelatedWork W3118256783 @default.
• W2495249956 hasRelatedWork W2838280819 @default.
• W2495249956 isParatext "false" @default.
• W2495249956 isRetracted "false" @default.
• W2495249956 magId "2495249956" @default.
• W2495249956 workType "article" @default.