UNASSIGNED: A common hallmark of @entity5 with highly aggressive phenotypes is increased proteolysis in the @entity5 and the surrounding microenvironment. @entity263 has a number of proteases uniquely associated with it that may play various important roles in disease progression. In this report, we utilize the peritumoral proteolytic activity of @entity263 to activate engineered peptide constructs for the treatment and noninvasive imaging of @entity263 . Using a modular "propeptide" approach, a cationic diastereomeric pore-forming peptide domain was linked to an inactivating acidic peptide domain. The inactivating acidic peptide domain was engineered to be a cleavable substrate for the secreted @entity563 protease @entity1486 or the transmembrane metalloprotease @entity27425 ( @entity27425 ). The propeptides were then evaluated in a direct comparison study. Both the @entity1486 and @entity27425 activated propeptides were found to be cytotoxic to @entity263 cells in vitro. In vivo, however, treatment of LNCaP and CWR22Rv1 xenografts with the @entity27425 propeptide resulted in a pronounced cytostatic effect when compared with xenografts treated with the @entity1486 propeptide or the cationic diastereomeric peptide alone. The @entity27425 activated propeptide also proved to be an effective optical imaging probe in vivo when labeled with a near-infrared fluorophore. These data suggest that protease-activated pore-forming peptides could potentially be used for both imaging and treating @entity263 . Mol Cancer Ther; 14(3); 659-68.   2014 AACR.

Protease-Activated Pore-Forming Peptides for the Treatment and Imaging of XXXX .

@entity27425 :: ('2346', 'Gene') :: ['PSMA', 'prostate-specific membrane antigen'] @entity263 :: ('MESH:D011471', 'Disease') :: ['prostate cancer', 'Prostate cancer'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancers'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine'] @entity1486 :: ('354', 'Gene') :: ['prostate-specific antigen (PSA)', 'PSA']
@entity263 :: (MESH:D011471,Disease) :: ['Prostate Cancer']
