82 research outputs found
Preclinical evaluation of transcriptional targeting strategies for carcinoma of the breast in a tissue slice model system
INTRODUCTION: In view of the limited success of available treatment modalities for metastatic breast cancer, alternative and complementary strategies need to be developed. Adenoviral vector mediated strategies for breast cancer gene therapy and virotherapy are a promising novel therapeutic platform for the treatment of breast cancer. However, the promiscuous tropism of adenoviruses (Ads) is a major concern. Employing tissue specific promoters (TSPs) to restrict transgene expression or viral replication is an effective way to increase specificity towards tumor tissues and to reduce adverse effects in non-target tissues such as the liver. In this regard, candidate breast cancer TSPs include promoters of the genes for the epithelial glycoprotein 2 (EGP-2), cyclooxygenase-2 (Cox-2), α-chemokine SDF-1 receptor (stromal-cell-derived factor, CXCR4), secretory leukoprotease inhibitor (SLPI) and survivin. METHODS: We employed E1-deleted Ads that express the reporter gene luciferase under the control of the promoters of interest. We evaluated this class of vectors in various established breast cancer cell lines, primary breast cancer cells and finally in the most stringent preclinical available substrate system, constituted by precision cut tissue slices of human breast cancer and liver. RESULTS: Overall, the CXCR4 promoter exhibited the highest luciferase activity in breast cancer cell lines, primary breast cancer cells and breast cancer tissue slices. Importantly, the CXCR4 promoter displayed a very low activity in human primary fibroblasts and human liver tissue slices. Interestingly, gene expression profiles correlated with the promoter activities both in breast cancer cell lines and primary breast cancer cells. CONCLUSION: These data suggest that the CXCR4 promoter has an ideal 'breast cancer-on/liver-off' profile, and could, therefore, be a powerful tool in Ad vector based gene therapy or virotherapy of the carcinoma of the breast
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Effect of oral contraceptives on intestinal folate conjugase activity and folate absorption in rats
To study whether oral contraceptive agents (OCA) may interfere with intestinal absorption of folate polyglutamates by inhibiting the activity of intestinal folate conjugase, female rats received either a stock diet and OCA daily for a 6-week period or the stock diet without OCA. The animals receiving the OCA gained 50% less of their original body weight than the controls. There were no significant differences in the in vivo absorption of either folate monoglutamate or folate pentaglutamate between the controls and the OCA-administered animals. The absorption of folate pentaglutamate was lower than that so folate monoglutamate in both groups of rats, but the difference was not statistically significant
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Partial Purification and Some Properties of Pteroylpolyglutamate Hydrolase (Conjugase) from Chicken Pancreas 1
Summary
A simple and rapid procedure for the purification of pteroylpolyglutamate hydrolase (conjugase) from chicken pancreas for the purpose of standardization of microbiological assays of folates has been developed. It yields a stable folate-free preparation in quantity. The purification steps included extraction of conjugase from crude lyophilized chicken pancreas in mer-captoethanol followed by DEAE-cellulose chromatography. The enzyme was further purified by absorption to alumina-C-γ-gel from which it was eluted with phosphate buffer, pH 6.5. The enzyme was concentrated by dialysis against 20 vol of 2 M sucrose, lyophilized, and vacuum-sealed. The purified conjugase exhibited two peaks on Sephadex G-75 chromatography corresponding to molecular weights of 50,000 and 25,000, respectively. The optimu
Phase field model of faceted anatase TiO<sub>2Â </sub>dendrites in low pressure chemical vapor deposition
Anatase TiO2\ua0nanorods with a well-defined\ua0⟨110⟩⟨110⟩\ua0texture have been studied using a model-based characterization technique based on a previous modeling framework. Intricate secondary side facet characteristics of tilt angles of\ua026.5∘26.5\ub0\ua0have been indexed, and a\ua0⟨112⟩⟨112⟩\ua0growth direction of the well-aligned facets is identified. These results have not been accessed experimentally but crucial in understanding the nature of the most abundant facets and their structural properties. We find agreement between our results and indirect experimental measurements. Highly exposed {116} facets are found to be responsible for excellent electrochemical surface properties in nanostructured anatase TiO2\ua0thin films
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