Scientists have shown different outcomes in inflammation, malignancy and apoptosis whether the source of the aforementioned protein is extracellular or intracellular. These findings are offering new insights that anti-inflammatory therapeutic agents and anti-tumorigenic functions of calprotectin can lead to control cancer development.
Calprotectin is a heterodimeric EF-hand Ca2+ binding protein that is typically released by infiltrating polymorphonuclear leukocytes and macrophages. This protein is a key player linking inflammation and cancer. Due to the increased levels of calprotectin in different inflammatory diseases and cancer, it is considered as a marker for diagnostic purposes. In this study, we evaluated the mechanism of cell viability and apoptotic-inducing effects of recombinant human calprotectin (rhS100A8/S100A9) on the gastric adenocarcinoma (AGS), the most common type of gastric cancer cell line. AGS cells were exposed to the different concentrations (5–100 μg/ml) of calprotectin for 24, 48, and 72 h, and cell viability was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic-inducing effects of calprotectin were evaluated by sub-G1 cell cycle assay and Annexin V/propidium iodide double staining. Furthermore, real-time polymerase chain reaction and Western blot analysis were performed to evaluate the mechanism of action of calprotectin. Our findings indicated that calprotectin inhibits growth and viability of AGS cells in a time- and dose-dependent manner. The half-maximal inhibitory concentration values were measured as 85.77, 79.14, and 65.39 μg/ml for 24, 48, and 72 h, respectively. Additionally, we found that calprotectin downregulated the expression of antiapoptotic protein Bcl-2 and upregulated proapoptotic protein Bax in a time- and concentration-dependent fashion. Calprotectin also slightly upregulated the expression of extracellular signal-regulated protein kinase 2 (ERK2), while it significantly decreased the levels of phospho-ERK in a time-dependent manner. Overall, these findings indicated that calprotectin has cytotoxicity and apoptosis-inducing effects on AGS cell lines in high concentration by modulating Bax/Bcl-2 expression ratio accompanied by inhibition of ERK activation.
Background: Primary central nervous system lymphoma (PCNSL) is a malignant tumor, the incidence of which has been increasing in immune compromised patients during the last two decades. Objectives: This study was conducted to determine the most prevalent clinical presenting symptoms of PCNSL patients. Patients and Methods: In this retrospective descriptive study, all PCNSL patients' data over a 25-year period (1990-2014) were assessed. PCNSL was confirmed pathologically after stereotactic biopsy in the Neurosurgery Department of Shohadaye Tajrish Hospital, Tehran, Iran. Results: A total of 176 cases of PCNSL were enrolled. There were 107 (60.8%) male patients, with a 1.5:1 male: female ratio. The patients most commonly presented in the sixth decade of their lives, with a mean age of 47 ± 1.5 years. The most common presenting symptoms were hemiparesis (56.2%) and headache (51.7%). The periventricular white matter (51.1%) and basal ganglion (48.9%) were the most common sites of involvement, and they frequently affected the supratentorial area (84.7%). Conclusions: Based on the data from this study, hemiparesis and headache were the most prevalent clinical presenting symptoms of PCNSL. Cognitive impairment and personality changes were also common in these patients.
The findings provided suggestive evidence of association of the CD14-159C/T gene polymorphism with susceptibility to acute brucellosis in the Iranian population.
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