Background:Granulocyte colony-stimulating factor (G-CSF) is a pro-inflammatory cytokine that stimulates myeloid stem cell maturation, proliferation, and migration into circulation. Despite being a known growth factor, the impact of G-CSF on solid tumours has not been well examined. G-CSF receptor (G-CSFR) is expressed by some tumours, and thus the aim of this study was to examine the expression and impact of G-CSF and G-CSFR on gastrointestinal tumours.Methods:In this study, G-CSF expression was examined in human gastric and colon tumours and by tumour-derived stromal myofibroblasts and carcinoma cells. G-CSFR expression was examined on carcinoma cells isolated from human tissues. The effects of G-CSF on gastric and colon carcinoma cell proliferation, migration, and signalling were examined.Results:G-CSFR was highly expressed in 90% of human gastric and colon carcinomas. G-CSF was also found to be highly produced by stromal myofibroblasts and carcinoma cells. Exposure of carcinoma cells to G-CSF led to increased proliferation and migration, and expansion of a sub-population of carcinoma cells expressing stem-like markers. These processes were dependent on ERK1/2 and RSK1 phosphorylation.Conclusions:These data suggest that the G-CSF/R axis promotes gastric and colorectal cancer development and suggest they are potential tumour targets.

Chronic hepatitis C virus (HCV) infection is associated with altered metabolism, including dyslipidemia and insulin resistance. These contribute to disease progression and influences the response to therapy. To investigate the relationships of new direct-acting antiviral drugs, simeprevir/sofosbuvir, with lipid profile and insulin resistance (IR). Eighty chronic hepatitis C genotype 4 patients were included; they were divided into four groups according to the severity of fibrosis as detected by fibroscan. Forty healthy persons volunteered as a control group. Lipid profile changes and IR were analyzed at baseline and after the end of treatment, and any effect of these changes on the response to treatment was studied. Before treatment, the levels of serum triglycerides were significantly higher in patients than in the control, and the levels of fasting insulin showed a progressive increase with advancing stage of fibrosis. At the end of treatment, there were a significant reduction in serum triglycerides, FBS, fasting insulin, and homeostasis model for the assessment of IR (P < 0.001), and a significant elevation of serum cholesterol and low-density lipoprotein (LDL)-c, high-density lipoprotein (HDL)-c, and LDL/HDL ratio (P = 0.001). An end-of-treatment response (week 12) was achieved in (99%) of the treated cases with 99% sustained viral response for 12 weeks post-treatment (week 24). Significant lipid profile changes were detected at the end of treatment. Serum lipid levels and IR are no longer predictors of response to DAAs. Follow-up of the lipid profile is warranted to avoid any possible remote effect of atherosclerotic heart disease.

ObjectiveChemerin was reported to regulate adipogenesis, metabolism, and immunity. But, its relation to cancer remains controversial. In breast cancer, chemerin expression has only been studied in serum, however, its expression in tissue, to our knowledge, has not been studied. The aim of this study was to investigate chemerin expression in breast cancer tissue in comparison to the adjacent normal tissue, and to assess its relationship to disease prognosis.MethodsWe examined chemerin expression in tissue with immunohistochemistry and analyzed the association of chemerin expression with the patients’ clinical and pathological characteristics to determine its role as a predictor of the disease and its relation to disease prognosis.ResultsWe detected a significantly higher expression of chemerin in the malignant vs the non-cancerous tissue specimens in 30/53, (56%) patients, (P=0.001). Moreover, its expression was significantly higher in the metastatic lymph nodes in comparison to the tumor tissues, (P=0.01). Chemerin expression was significantly correlated with weight (r=0.256, P=0.04), body mass index (r=0.233, P=0.03), tumor size (r=0.235, P=0.03), lymph node metastasis (r=0.265, P=0.045), distant metastasis (r=0.267, P=0.02), and tumor grading, (r=0.421, P=0.004), while it was inversely significantly correlated with estrogen receptor and progesterone receptor expression in malignant breast tissues (P=0.038, r=−0.437, and P=0.047, r=–0.316), respectively. The area under the receiver operating characteristic curve for chemerin as a predictor of breast cancer was 0.82, (P<0.001, sensitivity 89%, and specificity 69%). The Kaplan–Meier survival curves revealed that patients with higher chemerin expression had worse overall survival in comparison to those with a lower chemerin expression, (P=0.001).ConclusionOur results revealed higher chemerin expression in malignant vs adjacent normal breast tissue and lend support to a presumable role of chemerin tissue expression as an independent predictor of poor prognosis in breast cancer patients.

BackgroundFibroblast growth factor (FGF) 21 was reported to be induced by different injurious agents, including chronic hepatitis C (CHC) virus, affecting the liver. The aims of this study were to evaluate the FGF21 levels in CHC patients before and after the treatment with direct-acting antiviral agents (DAAs) in comparison to that in control subjects and to correlate these levels with insulin resistance (IR), lipid profile, and fibrosis stages.Patients and methodsWe studied 75 naive CHC patients and 40 age- and gender-matched healthy control subjects. Patients were divided into five groups based on the severity of fibrosis as detected by Fibroscan as follows: F0, n=2; F1, n=13; F2, n=23; F3, n=16; F4, n=21. We estimated the FGF21 levels at the start of the study for all the participants and for the patients only at the end of treatment with simisipivir (SIM) and sofosbuvir (SOF). These levels were compared between the patients and the control subjects and also for the patients before and after the treatment with DAAs. The FGF21 levels were correlated to IR, lipid profile, and stages of liver fibrosis.ResultsThe FGF21, fasting blood sugar (FBS), fasting insulin, and homeostasis model of IR (HOMA-IR) were significantly higher in CHC patients compared to control (5.04±0.75 vs 4.7±0.52, 20.15±5.13 vs 13.15±4.2, 4.49±1.28 vs 2.72±0.87, and 123.7±52.6 vs 21.8±8.8; P≤0.01, P≤0.001, P≤0.001, and P≤0.001, respectively). The posttreatment FGF21 levels were significantly reduced when compared to the pretreatment levels (123.7±52.5 vs 60.5±32.7, P≤0.001). FGF21 levels showed significant negative correlation with FBS and positive correlation with serum albumin (P≤0.05 and P≤0.003, respectively). The multiple linear regression analysis revealed that serum albumin, high-density lipoprotein cholesterol (HDL-c), and the stage of liver fibrosis were independent risk factors for FGF21.ConclusionBesides its metabolic modulator role, FGF21 strongly introduced itself as a novel biomarker of hepatic injury in Egyptian, genotype-4, CHC patients.

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