onr:"swepub:oai:prod.swepub.kib.ki.se:124821652"
Search: onr:"swepub:oai:prod.swepub.kib.ki.se:124821652" > Tesaglitazar, a dua...
- 1 of 1
- Previous record
- Next record
- To hitlist
Tesaglitazar, a dual PPAR-α/γ agonist, hamster carcinogenicity, investigative animal and clinical studies
- Lindblom, P (author)
- Berg, AL (author)
- Zhang, H (author)
- show more...
- Westerberg, R (author)
- Tugwood, J (author)
- Lundgren, H (author)
- Marcusson-Stahl, M (author)
- Sjogren, N (author)
- Blomgren, B (author)
- Ohman, P (author)
- Skanberg, I (author)
- Evans, J (author)
- show less...
- (creator_code:org_t)
- 2011-11-30
- 2012
- English.
- In: Toxicologic pathology. - : SAGE Publications. - 1533-1601 .- 0192-6233. ; 40:1, s. 18-32
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Tesaglitazar was developed as a dual peroxisome proliferator–activated receptor (PPARα/γ). To support the clinical program, a hamster carcinogenicity study was performed. The only neoplastic findings possibly related to treatment with tesaglitazar were low incidences of hemangioma and hemangiosarcoma in the liver of male animals. A high-power, two-year investigative study with interim necropsies was performed to further elucidate these findings. Treatment with tesaglitazar resulted in changes typical for exaggerated PPARα pharmacology in rodents, such as hepatocellular hypertrophy and hepatocellular carcinoma, but not an increased frequency of hemangiosarcomas. At the highest dose level, there was an increased incidence of sinusoidal dilatation and hemangiomas. No increased endothelial cell (EC) proliferation was detected in vivo, which was confirmed by in vitro administration to ECs. Immunohistochemistry and gene expression analyses indicated increased cellular stress and vascular endothelial growth factor (VEGF) expression in the liver, which may have contributed to the sinusoidal dilatation. A two-fold increase in the level of circulating VEGF was detected in the hamster at all dose levels, whereas no effect on VEGF was observed in patients treated with tesaglitazar. In conclusion, investigations have demonstrated that tesaglitazar does not produce hemangiosarcomas in hamster despite a slight effect on vascular morphology in the liver.
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
- Toxicologic pathology (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Lindblom, P
- Berg, AL
- Zhang, H
- Westerberg, R
- Tugwood, J
- Lundgren, H
- show more...
- Marcusson-Stahl, ...
- Sjogren, N
- Blomgren, B
- Ohman, P
- Skanberg, I
- Evans, J
- Hellmold, H
- show less...
- Articles in the publication
- Toxicologic path ...
- By the university
- Karolinska Institutet
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
