Effects of Tetrahydrolipstatin on Glioblastoma in Mice: MRI-Based Morphologic and Texture Analysis Correlated with Histopathology and Immunochemistry Findings : A Pilot Study
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Philipps-Universität Marburg
Abstract
Glioblastomas are themost aggressive brain tumors, and affected patients still only
have an extremely poor prognosis with today’s therapeutic options. Further developments are still
necessary, particularly in therapeutic approaches. Orlistat can act as an antitumor agent as it inhibits
fatty acid synthase, decreases tumor cell proliferation, and stimulates tumor cell apoptosis. Investigations
conducted on breast, pancreatic, hepatic, and colorectal tumors showed that FASN—fatty acid
synthase, a protein that catalyzes the de novo synthesis of long-chain fatty acids—is strongly upregulated.
Using an animal model, we tested whether the drug’s effects could be demonstrated visually,
quantitatively, and by texture analysis based on MR studies. Histology and immunochemistry were
used as references. The key results of the present study are as follows: Firstly, a significant difference
was found between orlistat-treated and untreated tumors in MRI studies based on morphology and
texture analyses. Secondly, the expression of FASN was reduced in the orlistat group, which, however,
did not result in a higher apoptosis rate in the treatment group. Our findings suggest that some
effects of orlistat on tumor cell proliferation must have taken place during therapy. Further studies
should investigate the effects of FASN inhibition when combined with targeted therapies.