Targeting N-cadherin increases vascular permeability and differentially activates AKT in melanoma.

ABSTRACT:

Objective

We investigate the mechanism through which N-cadherin disruption alters the effectiveness of regional chemotherapy for locally advanced melanoma.

Background

N-cadherin antagonism during regional chemotherapy has demonstrated variable treatment effects.

Methods

Isolated limb infusion (ILI) with melphalan (LPAM) or temozolomide (TMZ) was performed on rats bearing melanoma xenografts after systemic administration of the N-cadherin antagonist, ADH-1, or saline. Permeability studies were performed using Evans blue dye as the infusate, and interstitial fluid pressure was measured. Immunohistochemistry of LPAM-DNA adducts and damage was performed as surrogates for LPAM and TMZ delivery. Tumor signaling was studied by Western blotting and reverse-phase protein array

SUBMITTER: Turley RS 

PROVIDER: S-EPMC4431893 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature