br Increased ROS activity can result from

Increased ROS activity can result from increased oxidant pro-duction and/or decreased antioxidant function. 8-OHdG levels are increased in diabetes patients and involved in the pathology of diabetes [37]. There was an increased level of 8-OHdG in the DNA of early-stage cancer tissue which suggests that ROS may play an important role in the early phases of carcinogenesis [11].
From another point of view, high glucose in diabetic subjects diminished TrxR activity. Restoration of TrxR activity may be a potentially beneficial therapeutic strategy for the prevention of diabetes-induced vascular complications [38]. Additionally, it was found a novel chemopreventive mechanism in cancer therapy is proposed involving Se catalysis of reversible cysteine/disulfide transformations that occur in a number of redox-regulated pro-teins, including TrxR [39].
Moreover, this study also revealed significant elevation of serum VEGF level in breast cancer subjects with type 2 diabetes compared with breast cancer, diabetic & normal subjects. Moreover, it was significantly elevated in breast cancer subjects compared with diabetic & normal subjects. Additionally, it was significantly elevated in diabetic subjects in comparison with normal subjects. One of the primary factors in the development of diabetic com-plications is pathological release of VEGF [40]. Increased VEGF release results in pathological angiogenesis that is irregularly distributed and features poorly constructed vessels that are prone to leak, leading to increased vascular leakage which is a serious risk factor for diabetic complications [41].
VEGFA may induce the production of matrix metalloproteinases (MMPs), such as MMP-2 and MMP-9, in breast cancer [42]. VEGF has been implicated in breast cancer susceptibility and aggres-siveness. High VEGF 740 Y-P was correlated with the presence of axillary nodal metastasis and lower overall survival rates [43]. 
Furthermore, this study showed positive correlation between FABP-4 & VEGF. It was reported that treatment of endothelial cells with VEGF via VEGF-receptor-2 or basic fibroblast growth factor induced FABP-4 expression. Also, FABP-4 in endothelial cells has also been reported to promote angiogenesis [44]. Consistently, the serum VEGF increments assessed herein may be influenced by expression of other cytokines (as TNF-a) regulating vascular permeability related to angiogenesis and this aligned with Pluda JM et al., 1997 [45]. Thus the current result confirmed positive corre-lation between VEGF & TNF-a.
7. Conclusion
This study confirmed the role of FABP-4 as an adipokine in pathogenesis of type 2 DM, breast cancer & diabetic subjects with breast cancer via enhancing angiogenesis (increased serum VEGF), inflammatory biomarkers (increased serum TNF-a) and oxidative stress (increased serum 8-OHdG & decreased serum ThxR activity). This can gives strong guidelines in management of type 2 DM, breast cancer & diabetic subjects with breast cancer by anti-FABP-4 therapy.
Conflicts of interest
This study confirmed the role of FABP-4 in pathogenesis of type 2 diabetes & breast cancer.
The role of FABP-4 via enhancing angiogenesis, inflammatory and epigenetic instability biomarkers.
This study evaluated the effect of some adipocytokines, in-flammatory, epigenetic instability & angiogenesis biomarkers in type 2 diabetic Egyptian women with breast cancer.
Appendix A. Supplementary data
References
[1] Ertunc M, Hotamisligil G. Lipid signaling and lipotoxicity in metabolic inflammation: indications for metabolic disease pathogenesis and treatment. J Lipid Res 2016;57(12):2099e114. [2] Niu G, Li J, Wang H, et al. Associations of A-FABP with anthropometric and metabolic indices and inflammatory cytokines in obese patients with newly diagnosed type 2 diabetes. BioMed Res Int 2016;2016, 9382092.