Adenovirus-mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastases.

Inhibition of angiogenesis has been shown to be an effective strategy in cancer therapy in mice. However, its widespread application has been hampered by difficulties in the large-scale production of the antiangiogenic proteins. This limitation may be resolved by in vivo delivery and expression of the antiangiogenic genes. We have constructed a recombinant adenovirus that expresses murine endostatin that is biologically active both in vitro, as determined in endothelial cell proliferation assays, and in vivo, by suppression of angiogenesis induced by vascular endothelial growth factor 165. Persistent high serum levels of endostatin (605-1740 ng/ml; mean, 936 ng/ml) were achieved after systemic administration of the vector to nude mice, which resulted in significant reduction of the growth rates and the volumes of JC breast carcinoma and Lewis lung carcinoma (P < 0.001 and P < 0.05, respectively). In addition, the endostatin vector treatment completely prevented the formation of pulmonary micrometastases in Lewis lung carcinoma (P = 0.0001). Immunohistochemical staining of the tumors demonstrated a decreased number of blood vessels in the treatment group versus the controls. In conclusion, the present study clearly demonstrates the potential of vector-mediated antiangiogenic gene therapy as a component in cancer therapy

On a Complete Set of Orthogonal F-Squares of Order 8 with a Mateless Latin Square

9 pages, 1 article*On a Complete Set of Orthogonal F-Squares of Order 8 with a Mateless Latin Square* (Federer, W. T.; Mandeli, J. P.; Schwager, S. J.) 9 page

On Embedding Mateless Latin Squares of Orders 12 and 16 in a Complete Set of Orthogonal F-Squares

17 pages, 1 article*On Embedding Mateless Latin Squares of Orders 12 and 16 in a Complete Set of Orthogonal F-Squares* (Federer, W. T.; Mandeli, J. P.; Schwager, S. J.) 17 page

Embedding Cyclic Latin Squares of Order 2 (n) in a Complete Set of Orthogonal F-Squares

This issue was undated. The date given is an estimate.18 pages, 1 article*Embedding Cyclic Latin Squares of Order 2 (n) in a Complete Set of Orthogonal F-Squares* (Schwager, S. J.; Federer, W. T.; Mandeli, J. P.) 18 page

F-Square Geometries for n = 3, 4, 5, and 6

19 pages, 1 article*F-Square Geometries for n = 3, 4, 5, and 6* (Federer, W. T.; Lee, F. C.; Mandeli, J. P.) 19 page

Pairwise Orthogonal F-Rectangle Designs

This issue was undated. The date given is an estimate.14 pages, 1 article*Pairwise Orthogonal F-Rectangle Designs* (Federer, W. T.; Hedayat, A. S.; Mandeli, J. P.) 14 page