%0 Journal Article
%T Assessing the predictive response of a simple and sensitive blood-based biomarker between estrogen-negative solid tumors.
%A Mohan S
%A Patel S
%A Barlow D
%A Rojas AC
%J Adv Med Sci
%V 65
%N 2
%D Sep 2020
%M 32919119
%F 2.852
%R 10.1016/j.advms.2020.08.004
%X <B>OBJECTIVE: </B>We investigated Nw-hydroxy l-Arginine (NOHA) predictive response in serous ovarian carcinoma based on estrogen-hormone receptor expression status; and assessed the distinctive NOHA response between estrogen-receptor-negative (ER-) tumor subtypes of ovarian and breast cancer.<BR><B>METHODS: </B>Three-dimensional (3D) spheroids models of ER- and estrogen-receptor-positive (ER+) from breast and ovarian tumor, cultured for 9 weeks, were assayed for cellular levels of inducible nitric oxide synthase (NOS2), nitric oxide (as total nitrite) and l-Arginine, and compared to NOHA in culture medium. Statistical difference was set at p < 0.01.<BR><B>RESULTS: </B>Nine-week in vitro studies showed a progressive NOHA reduction in culture medium by at least 0.4-0.8 fold, and 0.65-0.92 fold only in the ER- breast tumor and ER- ovarian tumor 3D spheroids, respectively; with increases in cellular NOS2 and nitric-oxide levels, by at least 1.0-2.45 fold in both ER- tumor subtype 3D spheroids (p < 0.01; n = 6). Within ER- subtypes, medium NOHA decreased by ≥ 38.9% in ovarian cancer over breast cancer 3D-spheroids, with cellular increases in NOS2 (by ≥ 17.4%), and nitric oxide (by ≥ 18.8%). Cellular l-Arginine to medium NOHA ratio was higher, and by at least 6.5-22.5 fold in ER- breast tumor 3D-spheroids, and at least 10-70 fold in ER- ovarian tumor 3D spheroids, than in ER+ and control conditions; and was ≥48% higher in ER- ovarian cancer than in ER- breast cancer 3D-spheroids.<BR><B>CONCLUSIONS: </B>The present study shows NOHA as a sensitive and selective indicator differentiating and distinguishing ER- subtypes based on the tumor grade.