Open Access. Powered by Scholars. Published by Universities.®
Pharmacology, Toxicology and Environmental Health Commons™
Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 2 of 2
Full-Text Articles in Pharmacology, Toxicology and Environmental Health
Cd44 Containing Complexes As A Therapeutic Target In Multiple Myeloma, Anthony Gebhard
Cd44 Containing Complexes As A Therapeutic Target In Multiple Myeloma, Anthony Gebhard
USF Tampa Graduate Theses and Dissertations
Our laboratory recently reported that treatment with the d-amino acid containing peptide HYD1 induces necrotic cell death in multiple myeloma (MM) cell lines. Due to the intriguing biological activity and promising in vivo activity of HYD1, we pursued strategies for increasing the therapeutic efficacy of the parent linear peptide. These efforts led to the development of a cyclized peptidomimetic, MTI-101, with increased in vitro activity and robust in vivo activity as a single agent using two myeloma models that consider the bone marrow microenvironment. MTI-101 treatment resulted in mechanistically similar hallmarks of HYD1 induced cell death, namely the generation of …
Targeting Α4 Integrin Containing Complexes In Multiple Myeloma Using Peptidomimetics, Michael Foster Emmons
Targeting Α4 Integrin Containing Complexes In Multiple Myeloma Using Peptidomimetics, Michael Foster Emmons
USF Tampa Graduate Theses and Dissertations
In our previous work we demonstrated that the integrin antagonist, HYD1, induced necrotic cell death in myeloma cell lines in vitro and in vivo as a single agent. In order to further delineate biomarkers of response to HYD1 we developed an isogenic drug resistant variant named H929-60. We show that the acquisition of resistance towards HYD1 correlates with reduced expression of the cleaved α4 integrin subunit and beta 1 integrin. Moreover, we demonstrate that HYD1 interacts with α4 integrin in myeloma cells. Consistent with reduced VLA-4 expression, the resistant variant showed ablated functional binding to fibronectin, VCAM-1 and the bone …