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Targeting the IGF-1...
Targeting the IGF-1R using picropodophyllin in the therapeutical 5T2MM mouse model of multiple myeloma : beneficial effects on tumor growth, angiogenesis, bone disease and survival
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Menu, Eline (author)
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- Jernberg-Wiklund, Helena (author)
- Uppsala universitet,Institutionen för genetik och patologi
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De Raeve, Hendrik (author)
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De Leenheer, Evy (author)
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Coulton, Les (author)
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Gallagher, Orla (author)
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Van Valckenborgh, Els (author)
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- Larsson, Olle (author)
- Karolinska Institutet
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- Axelson, Magnus (author)
- Karolinska Institutet
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- Nilsson, Kenneth (author)
- Uppsala universitet,Institutionen för genetik och patologi
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Van Camp, Ben (author)
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Croucher, Peter (author)
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Vanderkerken, Karin (author)
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(creator_code:org_t)
- 2007
- 2007
- English.
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:8, s. 1857-1861
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http://www.ncbi.nlm....
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https://onlinelibrar...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- During the last decade, a central role for insulin-like growth factor 1 (IGF-1) in the pathophysiology of multiple myeloma (MM) has been well established. IGF-I provided by the tumor-microenvironment interaction may directly and indirectly facilitate the migration, survival and expansion of the MM cells in the bone marrow (BM). The inhibition of the IGF-1R-mediated signaling pathway has recently been suggested to be a possible new therapeutic principle in MM. Using the mouse 5T2MM model, we now demonstrate that targeting the IGF-1R using picropodophyllin (PPP) in a therapeutical setting not only has strong antitumor activity on the established MM tumor but also influences the BM microenvironment by inhibiting angiogenesis and bone disease, having a profound effect on the survival of the mice. At therapeutically achievable concentrations of PPP, the average survival was 180 days for the PPP-treated mice as compared to 100 days for vehicle-treated mice. PPP used as single drug treatment in the 5T2MM model resulted in a decrease of tumor burden by 65% while the paraprotein concentrations were reduced by 75%. This decrease was associated with a significant inhibition of tumor-associated angiogenesis and osteolysis. The present studies on the biological effects of PPP in the 5T2MM model constitute an important experimental platform for future therapeutic implementation.
Keyword
- Angiogenesis Inhibitors/*pharmacology
- Animals
- Antineoplastic Agents/*pharmacology
- Bone Neoplasms/*prevention & control
- Disease Models; Animal
- Kaplan-Meiers Estimate
- Mice
- Multiple Myeloma/blood supply/*drug therapy/pathology
- Neovascularization; Pathologic/*prevention & control
- Podophyllotoxin/*analogs & derivatives/pharmacology
- Receptor; IGF Type 1/*drug effects
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Menu, Eline
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Jernberg-Wiklund ...
-
De Raeve, Hendri ...
-
De Leenheer, Evy
-
Coulton, Les
-
Gallagher, Orla
-
show more...
-
Van Valckenborgh ...
-
Larsson, Olle
-
Axelson, Magnus
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Nilsson, Kenneth
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Van Camp, Ben
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Croucher, Peter
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Vanderkerken, Ka ...
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show less...
- Articles in the publication
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International Jo ...
- By the university
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Uppsala University
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Karolinska Institutet