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Melphalan flufenami...
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Byrgazov, KonstantinOncopeptides AB, Stockholm, Sweden.
(author)
Melphalan flufenamide inhibits osteoclastogenesis by suppressing proliferation of monocytes
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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Elsevier,2021
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-457555
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-457555URI
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https://doi.org/10.1016/j.bonr.2021.101098DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Myeloma bone disease is a major complication in multiple myeloma affecting quality of life and survival. It is characterized by increased activity of osteoclasts, bone resorbing cells. Myeloma microenvironment promotes excessive osteoclastogenesis, a process of production of osteoclasts from their precursors, monocytes. The effects of two anti-myeloma drugs, melphalan flufenamide (melflufen) and melphalan, on the activity and proliferation of osteoclasts and their progenitors, monocytes, were assessed in this study. In line with previous research, differentiation of monocytes was associated with increased expression of genes encoding DNA damage repair proteins. Hence monocytes were more sensitive to DNA damage-causing alkylating agents than their differentiated progeny, osteoclasts. In addition, differentiated progeny of monocytes showed increased gene expression of immune checkpoint ligands which may potentially create an immunosuppressive microenvironment. Melflufen was ten-fold more active than melphalan in inhibiting proliferation of osteoclast progenitors. Furthermore, melflufen was also superior to melphalan in inhibition of osteoclastogenesis and bone resorption. These results demonstrate that melflufen may exert beneficial effects in patients with multiple myeloma such as reducing bone resorption and immunosuppressive milieu by inhibiting osteoclastogenesis.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Lind, Thomas,Docent,1965-Uppsala universitet,Klinisk farmakogenomik och osteoporos(Swepub:uu)tli08750
(author)
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Rasmusson, Annica J.Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Klinisk farmakogenomik och osteoporos,Cervenka: Psykiatri(Swepub:uu)annijaco
(author)
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Andersson, ClaesUppsala universitet,Cancerfarmakologi och beräkningsmedicin(Swepub:uu)cland109
(author)
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Slipicevic, AnaOncopeptides AB, Stockholm, Sweden.
(author)
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Lehmann, FredrikOncopeptides AB, Stockholm, Sweden.
(author)
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Gullbo, JoachimUppsala universitet,Cancerfarmakologi och beräkningsmedicin,Experimentell och klinisk onkologi(Swepub:uu)joacgull
(author)
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Melhus, HåkanUppsala universitet,Uppsala kliniska forskningscentrum (UCR),Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab(Swepub:uu)hakamelh
(author)
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Larsson, RolfUppsala universitet,Cancerfarmakologi och beräkningsmedicin,Klinisk immunologi(Swepub:uu)rolflars
(author)
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Fryknäs, MårtenUppsala universitet,Cancerfarmakologi och beräkningsmedicin(Swepub:uu)mafry516
(author)
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Oncopeptides AB, Stockholm, Sweden.Klinisk farmakogenomik och osteoporos
(creator_code:org_t)
Related titles
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In:Bone Reports: Elsevier152352-1872
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Byrgazov, Konsta ...
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Lind, Thomas, Do ...
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Rasmusson, Annic ...
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Andersson, Claes
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Slipicevic, Ana
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Lehmann, Fredrik
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Gullbo, Joachim
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Melhus, Håkan
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Larsson, Rolf
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Fryknäs, Mårten
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Uppsala University