Accession Number : AD1006257


Title :   Monoamine Oxidase A: A Novel Target for Progression and Metastasis of Prostate Cancer


Descriptive Note : Technical Report,30 Sep 2012,29 Sep 2015


Corporate Author : University of Southern California Los Angeles United States


Personal Author(s) : Shih,Jean C


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1006257.pdf


Report Date : 01 Dec 2015


Pagination or Media Count : 105


Abstract : The purpose of this project is to investigate the key roles of the monoamine oxidase A (MAO A) enzyme in the progression and metastasis of prostate cancer (PCa). During this funding period, we delineated the functional and mechanistic roles of MAO A in promoting tumor metastasis, determined MAO A functions in PCa by defining its roles in reactive oxygen species production and augmentation of HIF1-mediated signaling, and developed a MHI clorgyline, a novel pharmacological inhibitor of MAO A for targeted therapy and noninvasive imaging of PCa. Throughout the Year 3, we investigated the effect of hypoxia on MAO A and found that hypoxia induces MAO A expression and activity. We assessed the tumor-targeting properties of NIR-clorgyline for PCa in vivo and demonstrated its tumor-specificity in mouse xenograft model through NIR (near infrared) imaging. We generated MAO A/Pten double KO mice and showed that deletion of MAO A delays PCa development and facilitates an immunostimulatory environment in the Pten KO mouse model of prostate adenocarcinoma.


Descriptors :   prostate cancer , therapeutics , Monoamine oxidase , enzymes , metastasis , neoplasms , PHARMACOLOGY , inhibitors , mice


Distribution Statement : APPROVED FOR PUBLIC RELEASE