Imatinib (STI571) br Additionally TNF a regulates lipid meta
Additionally, TNF-a regulates lipid metabolism in adipocytes via increasing lipolysis . Increased lipolysis from adipose tissue is also linked to secretion of fatty acid-binding proteins-4 (FABP-4), which is an important mediator of immunometabolic responses locally at the adipose tissue .
Fatty acid-binding proteins (FABPs) were originally described as intracellular proteins that can affect lipid fluxes, metabolism and signalling within cells. It has become evident that they are critical mediators of metabolism and inflammatory processes. FABP-4 plays a vital role in lipid-mediated biological processes associated with type 2 diabetes, obesity, and metabolic syndrome .
Moreover, Lipid transport and uptake are an important aspect of lipid metabolism in cancer. FABP-4 transports free fatty acids, which helps the regulation of triacylglycerol storage by decreasing
its hydrolysis. In addition, it is becoming clear that lipid droplets are more than just passive storage components and are important in cancer as well, in particular for survival under stressful conditions .
Furthermore, reactive oxygen species (ROS) are regarded as the common denominator in the pathogenesis of hyperglycemic injury . 8-hydroxy- 20-deoxyguanosine (8-OHdG) is a product of DNA damage in the presence of high levels of ROS, with specific enzy-matic cleavage and 8-hydroxylation of guanine bases. It is a biomarker of oxidative DNA damage in the pathogenesis of diabetic complications .
The breast carcinoma DNA contains high concentrations of Imatinib (STI571) modifications. An increased level of 8-OHdG was observed in ma-lignant tissues suggesting that ROS may play an important role in the early phases of carcinogenesis .
Moreover, ROS can promote the angiogenic switch in fibro-blasts by the upregulation of vascular endothelial growth factor (VEGF), VEGF receptors, which are essential for angiogenesis-associated matrix remodeling . ROS might play a role in can-cer angiogenesis not only acting on tumor cells but also on tumor-infiltrated immune cells (i.e., macrophages) . VEGF is involved in pathologic angiogenesis that occurs in tumor growth and metastasis .
Additionally, Selective increase in plasma VEGF may favor aberrant neovascularization and endothelial abnormalities. These abnormalities are closely linked to the pathophysiology of micro-vascular and atherosclerotic vascular complications in type 2 dia-betes .
From another point of view, the antioxidant defense mecha-nism represented by thioredoxin reductase (TrxR), was suggested to modulate glucose and lipid metabolism . Moreover, altered expression of TrxR, which has been described in various malig-nancies and cancer cells, is thought to be closely associated with tumor growth promotion, progression and metastasis .
The aim of the present study is to evaluate the effect of some adipocytokines, inflammatory, epigenetic instability and angio-genesis biomarkers in type 2 diabetic Egyptian women with breast cancer.
3. Subject & methods
The study was performed on eighty female subjects aged from
(50e65 years). The subjects were chosen from patients admitted to the Departments of Internal Medicine, & General surgery of the Tanta University Hospital between February 2016 & February 2017. They were divided into 20 patients with type 2 diabetes mellitus (Group II), 20 patients with breast cancer (Group III), 20 patients with type 2 diabetes mellitus and breast cancer (Group IV) and 20 healthy subjects (Group I) for comparison of assessed data. All patients were of matched menstrual state & socioeconomic status as control group. The breast cancer patients have primary invasive ductal carcinoma of the breast. All of them had mammary gland surgery.
A written consent was obtained from subjects under study in accordance with the principles of Ethical Committee of Faculty of Medicine, Tanta University, Egypt and was in accordance with the principles of the Declaration of Helsinki II.
A complete medical examination was performed for each participant. Based on the American Diabetes Association (2013), the diagnostic criteria of type 2 diabetes mellitus cases where glycemic control was evaluated showing plasma glucose 126 mg/dl or 2 h postprandial 200 mg/dl . Patients with findings suspicious for breast cancer on mammography were confirmed by hitopathological biopsies were diagnosed with invasive ductal carcinoma. Among the cases, classification of malignant tumors (tumor size, nodal-status, and metastasis), grading (G), and hormone receptor status (estrogen receptor [ER] and progesterone receptor [PR]) were confirmed by the pathologists. Clinicopathological features such as age, tumor grade, tumor size, hormone receptor status, lymph node involvement and pathology reports were retrieved from the pa-tients' records after obtaining all the relevant ethical approvals .