Since beneficial effects related to tomato consumption partially overlap with those related to peroxisome proliferator-activated receptor γ (PPARγ) activation, our aim was to test extracts of tomato fruits and tomato components, including polyphenols and isoprenoids, for their capacity to activate PPARγ using the PPARγ2 CALUX reporter cell line. Thirty tomato compounds were tested; seven carotenoids and three polyphenols induced PPARγ2-mediated luciferase expression. Two extracts of tomato, one containing deglycosylated phenolic compounds and one containing isoprenoids, also induced PPARγ2-mediated expression at physiologically relevant concentrations. Furthermore, enzymatically hydrolyzed extracts of seven tomato varieties all induced PPARγ-mediated expression, with a 1.6-fold difference between the least potent and the most potent variety. The two most potent varieties had high flavonoid content, while the two least potent varieties had low flavonoid content. These data indicate that extracts of tomato are able to induce PPARγ-mediated gene expression in vitro and that some tomato varieties are more potent than others.
Clinical trials in malignant glioma have demonstrated excellent safety of recombinant adenovirus type 5 (Ad5) but lack of convincing efficacy. The overall low expression levels of the Coxsackie and Adenovirus receptor and the presence of high anti-Ad5-neutralizing antibody (NAb) titers in the human population are considered detrimental for consistency of clinical results. To identify an adenoviral vector better suited to infect primary glioma cells, we tested a library of fiber-chimeric Ad5-based adenoviral vectors on 12 fresh human glioma cell suspensions. Significantly improved marker gene expression was obtained with several Ad5-chimeric vectors, predominantly vectors carrying fiber molecules derived from B-group viruses (Ad11, Ad16, Ad35 and Ad50). We next tested Ad35 sero prevalence in sera derived from 90 Dutch cancer patients including 30 glioma patients and investigated the transduction efficiency of this vector in glioma cell suspensions. Our results demonstrate that the sero prevalence and the titers of NAb against Ad35 are significantly lower than against Ad5. Also, recombinant Ad35 has significantly increased ability to transfer a gene to primary glioma cells compared to Ad5. We thus conclude that Ad35 represents an interesting candidate vector for gene therapy of malignant glioma.
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