Publications by authors named "Penny Costello"

Background: Understanding the prognosis of hepatocellular carcinoma (HCC) informs plans for care. Tumor morphology and molecular markers have been correlated with outcomes. Three-dimensional tissue culture (3DTC) allows for direct in vitro measurement of a tumor's ability to grow and metastasize.

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Introduction: The overexpression of integrin-linked kinase (ILK) has been implicated in the promotion of tumor invasion and metastasis. We studied the anticancer effects of KP-392, a potent selective inhibitor of ILK in the NCI-H460 cell line. In vitro, KP-392 inhibited ILK activity of H460 cells.

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We show that integrin-linked kinase (ILK) stimulates the expression of VEGF by stimulating HIF-1alpha protein expression in a PKB/Akt- and mTOR/FRAP-dependent manner. In human prostate cancer cells, knockdown of ILK expression with siRNA, or inhibition of ILK activity, results in significant inhibition of HIF-1alpha and VEGF expression. In endothelial cells, VEGF stimulates ILK activity, and inhibition of ILK expression or activity results in the inhibition of VEGF-mediated endothelial cell migration, capillary formation in vitro, and angiogenesis in vivo.

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