Evaluation of CEP55, SERPINE1 and SMPD3 genes and proteins as diagnostic and prognostic biomarkers in gastric carcinoma in Egyptian patients

Abstract Background Gastric carcinoma (GC) is a fatal disease. Detection of new biomarkers that can be utilized in the early diagnosis of GC is a pressing need. This present study assessed centrosomal protein-55 (CEP55)’ serpin family E member 1 (SERPINE1) and sphingomyelin phosphodiesterase 3 (SMPD3) genes and proteins in gastric adenocarcinoma with different tumor progression features. Thirty surgically resected gastric tissue samples from thirty patients suffered from gastric cancers were obtained. The gastric tissue samples were divided into tumorous (with different stages and grades) and adjacent non-tumorous samples. CEP55, SERPINE1 and SMPD3 genes were assessed by quantitative qRT-PCR, and their proteins were assessed by ELISA in the gastric tissue samples. Results As regards SERPINE1, CEP55 genes and proteins, results revealed significant elevations in the GC samples (p < 0.0001). On the contrary, SMPD3 gene and protein revealed significant decreases as compared to non-tumorous samples. The studied genes and proteins showed highly significant specificity and sensitivity in the early detection of GC. SERPINE1 gene and protein revealed highly significant increases and positive correlations, while SMPD3 gene and protein revealed highly significant decreases and negative correlations as the tumor progresses. Conclusion CEP55, SERPINE1 and SMPD3 genes and proteins could be used as useful biomarkers for the early detection of GC. SERPINE1 and SMPD3 genes and proteins might be used as risk and protective prognostic factors in GC, respectively

Bone-Marrow-Derived Mesenchymal Stem Cells, Their Conditioned Media, and Olive Leaf Extract Protect against Cisplatin-Induced Toxicity by Alleviating Oxidative Stress, Inflammation, and Apoptosis in Rats

Background: Hepatic and renal damage is a cisplatin (Cis)-induced deleterious effect that is a major limiting factor in clinical chemotherapy. Objectives: The current study was designed to investigate the influence of pretreatment with olive leaf extract (OLE), bone-marrow-derived mesenchymal stem cells (BM-MSC), and their conditioned media (CM-MSC) against genotoxicity, nephrotoxicity, hepatotoxicity, and immunotoxicity induced by cisplatin in rats. Methods: The rats were randomly divided into six groups (six rats each) as follows: Control; OLE group, treated with OLE; Cis group, treated with a single intraperitoneal dose of Cis (7 mg/kg bw); Cis + OLE group, treated with OLE and cisplatin; Cis + CM-MSC group, treated with BM-MSC conditioned media and Cis; and Cis + MSC group, treated with BM-MSC in addition to Cis. Results: Cis resulted in a significant deterioration in hepatic and renal functions and histological structures. Furthermore, it increased inflammatory markers (TNF-&alpha;, IL-6, and IL-1&beta;) and malondialdehyde (MDA) levels and decreased glutathione (GSH) content, total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activity in hepatic and renal tissues. Furthermore, apoptosis was evident in rat tissues. A significant increase in serum 8-hydroxy-2-deoxyguanosine (8-OH-dG), nitric oxide (NO) and lactate dehydrogenase (LDH), and a decrease in lysozyme activity were detected in Cis-treated rats. OLE, CM-MSC, and BM-MSC have significantly ameliorated Cis-induced deterioration in hepatic and renal structure and function and improved oxidative stress and inflammatory markers, with preference to BM-MSC. Moreover, apoptosis was significantly inhibited, evident from the decreased expression of Bax and caspase-3 genes and upregulation of Bcl-2 proteins in protective groups as compared to Cis group. Conclusions: These findings indicate that BM-MSC, CM-MSC, and OLE have beneficial effects in ameliorating cisplatin-induced oxidative stress, inflammation, and apoptosis in the hepatotoxicity, nephrotoxicity, immunotoxicity, and genotoxicity in a rat model