Sökning: onr:"swepub:oai:DiVA.org:uu-486976" >
Ra-223 induces clus...
-
Abramenkovs, AndrisUppsala universitet,Institutionen för immunologi, genetik och patologi,Rudbecklaboratoriet
(författare)
Ra-223 induces clustered DNA damage and inhibits cell survival in several prostate cancer cell lines
- Artikel/kapitelEngelska2022
Förlag, utgivningsår, omfång ...
-
Elsevier,2022
-
electronicrdacarrier
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:uu-486976
-
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-486976URI
-
https://doi.org/10.1016/j.tranon.2022.101543DOI
-
http://kipublications.ki.se/Default.aspx?queryparsed=id:150848639URI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
The bone-seeking radiopharmaceutical Xofigo (Radium-223 dichloride) has demonstrated both extended sur-vival and palliative effects in treatment of bone metastases in prostate cancer. The alpha-particle emitter Ra-223, targets regions undergoing active bone remodeling and strongly binds to bone hydroxyapatite (HAp). However, the toxicity mechanism and properties of Ra-223 binding to hydroxyapatite are not fully understood. By exposing 2D and 3D (spheroid) prostate cancer cell models to free and HAp-bound Ra-223 we here studied cell toxicity, apoptosis and formation and repair of DNA double-strand breaks (DSBs). The rapid binding with a high affinity of Ra-223 to bone-like HAp structures was evident (KD= 19.2 x 10-18 M) and almost no dissociation was detected within 24 h. Importantly, there was no significant uptake of Ra-223 in cells. The Ra-223 alpha-particle decay produced track-like distributions of the DNA damage response proteins 53BP1 and gamma H2AX induced high amounts of clustered DSBs in prostate cancer cells and activated DSB repair through non-homologous end-joining (NHEJ). Ra-223 inhibited growth of prostate cancer cells, independent of cell type, and induced high levels of apoptosis. In summary, we suggest the high cell killing efficacy of the Ra-223 was attributed to the clustered DNA damaged sites induced by alpha-particles.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Hariri, MehranUppsala universitet,Institutionen för immunologi, genetik och patologi,Rudbecklaboratoriet(Swepub:uu)mehha904
(författare)
-
Spiegelberg, Diana,1982-Uppsala universitet,Plastikkirurgi,Cancerprecisionsmedicin,Öron-, näs- och halssjukdomar,Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala SE-75185, Sweden,Rudbecklaboratoriet(Swepub:uu)diasp673
(författare)
-
Nilsson, StenKarolinska Institutet
(författare)
-
Stenerlöw, BoUppsala universitet,Cancerprecisionsmedicin,Rudbecklaboratoriet(Swepub:uu)bostener
(författare)
-
Uppsala universitetInstitutionen för immunologi, genetik och patologi
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Translational Oncology: Elsevier261944-71241936-5233
Internetlänk
Hitta via bibliotek
Till lärosätets databas