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Assessing the predictive response of a simple and sensitive blood-based biomarker between estrogen-negative solid
Srinidi Mohan1, Seema Patel1, David Barlow1
1Department of Pharmaceutical Sciences, College of Pharmacy, University of New England, Portland, ME, USA.
Advances in Medical Sciences
|September 12, 2020
Summary
N-hydroxy-l-arginine (NOHA) effectively distinguishes estrogen-receptor-negative (ER-) ovarian and breast cancer subtypes. This study highlights NOHA
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Estrogen receptor (ER) status is crucial for predicting treatment response in hormone-sensitive cancers.
- Understanding molecular differences between ER- subtypes is essential for targeted therapies.
- Nitric oxide (NO) metabolism, involving l-arginine and its derivatives like NOHA, plays a role in cancer progression.
Purpose of the Study:
- To investigate the predictive response of N-hydroxy-l-arginine (NOHA) in serous ovarian carcinoma based on estrogen receptor (ER) expression.
- To assess the distinctive NOHA response between ER-negative (ER-) ovarian and breast cancer subtypes.
Main Methods:
- Utilized 3D spheroids models of ER-negative (ER-) and ER-positive (ER+) breast and ovarian tumors cultured for 9 weeks.
- Assayed cellular levels of inducible nitric oxide synthase (NOS2), nitric oxide (total nitrite), and l-arginine.
- Compared these levels with NOHA concentrations in the culture medium, setting statistical significance at p < 0.01.
Main Results:
- ER- breast and ovarian tumor spheroids showed significant NOHA reduction in culture medium and increased cellular NOS2 and nitric oxide levels.
- Ovarian cancer ER- spheroids exhibited a greater decrease in medium NOHA (≥38.9%) and increases in cellular NOS2 (≥17.4%) and nitric oxide (≥18.8%) compared to breast cancer ER- spheroids.
- The cellular l-arginine to medium NOHA ratio was substantially higher in ER- tumor spheroids (both breast and ovarian) compared to ER+ and control conditions, with a notably higher ratio in ER- ovarian cancer.
Conclusions:
- N-hydroxy-l-arginine (NOHA) serves as a sensitive and selective indicator for differentiating ER- subtypes.
- The study demonstrates NOHA's potential in distinguishing between ER- ovarian and breast cancer based on tumor grade.
- Findings suggest NOHA's utility in understanding and potentially targeting specific ER- cancer subtypes.

