The clonal assays showed a time dose related response to EGCG. Intravesical instillation of EGCG inhibits the growth of AY-27 rat transitional cells implanted in this model.

To understand the fundamental determinants of urokinase plasminogen activator (uPA) driven angiogenesis in cancer we studied how inhibition of uPA activity could reduce neovascularization and consequently reduce tumor size in experimental animals. Proteolytic enzymes are required to mediate tumor cell invasion to adjacent tissues and initiate the metastatic process. Many different human cancers commonly overexpresses the urokinase plasminogen activator system, one of the proteolytic enzyme systems.Reduction of urokinase (uPA) activity in cancer cells is evidently associated with diminished invasion and metastasis. However, it has been shown recently that inhibitors of uPA could reduce tumor size also. The mechanism of action leading to decline in tumor growth rate is not clear. Proteolysis is responsible for degradation of proteins, for invasion or metastasis, but not for the proliferate properties of the cancer cells. It is difficult to envision that diminishing the size of tumor is due to simply blocking of uPA activity of cancer cells. Instead, inhibitors of uPA may be interacting with the elements of the extracellular matrix, such the neovascular bed surrounding tumors that has been reported to contain high amounts of uPA and its receptor. Overall these data strongly suggest that inhibitors of urokinase limit cancer growth by inhibiting the angiogenesis. However, it is possible also that uPA inhibitors could act on cancer cells directly or prevent angiogenesis by alternative mechanisms that are not related to uPA inhibition. Therefore, we examined if plasminogen activator inhibitor (PAI-1) could limit angiogenesis. If it does, it will provide definitive evidence of uPA/PAI-1 involvement in reduction of cancer growth. Indeed, our study demonstrates that exogenously applied 14-1b PAI-1 is powerful inhibitor of angiogenesis in

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Two 3,5-disubstituted sulfonamide catechol ligands were synthesized. Tris(ligand) iron(III) complexes were prepared and investigated as MRI contrast agents. Longitudinal relaxivity (r1) values were determined for the complexes. The r1 values in water were substantially higher than those of typical six-coordinate iron(III) complexes. The r1 values in plasma under the same conditions increased. The iron(III) complexes were administered to rats, and the kidney and liver signal intensities were measured by T1-weighted MR imaging experiments.