Eman Badr

Role of serum glypican-3 in the diagnosis and differentiation of small hepatocellular carcinoma from hepatitis-C virus cirrhosis

Abstract Background Serum alpha-fetoprotein (AFP) has insufficient sensitivity and specificity for detection of hepatocellular carcinoma (HCC). Recently, glypican-3 (GLP-3) was suggested as a new biomarker for the detection HCC. Objectives To determine the role of serum GLP-3 levels in the early diagnosis and differentiation of small (3 cm or less in diameter) HCC from liver cirrhosis. Also, to correlate GLP-3 levels to clinico-laboratory data. Methods The study included sixty patients; 30 of them with hepatitis C virus (HCV) cirrhosis, and 30 patients with proved HCC. In addition, 20 healthy subjects were included as a control group. Clinical and radiological features (abdominal ultrasonography and/or abdominal triphasic computed tomography) were recorded. Liver function tests, complete blood cell count, and serum AFP were measured. Serum GLP-3 values were determined by an ELISA technique. Results Serum levels of GLP-3 were significantly elevated in patients with HCC compared with HCV cirrhosis group (p < 0.001). Also, these levels were significantly elevated in these two patients’ groups versus controls (p < 0.001). Also, serum GLP-3 levels with cut-off value of ⩾240 ug/L, had a higher sensitivity (100%) and same specificity (93.3%), than AFP with cut-off value of ⩾200 ng/ml, for detection of HCC. Moreover, GLP-3 levels showed a higher sensitivity than AFP (50% vs.41.7%), for detection of small HCC. The combined use of both markers (i.e. when either one of the two markers positive) improved the specificity to 88.9%. Regarding unicentric HCC, GLP-3 at cut-off value of ⩽580 ug/L had better specificity than AFP at cut-off value of ⩽765 ng/ml (57.1% vs. 42.9%). The combined use of both markers improved the sensitivity and specificity to 82.6% and 71.4%, respectively. Conclusion Serum GLP-3 levels are higher in HCC versus HCV cirrhosis, which can differentiate HCC from liver cirrhosis. Also, serum GLP-3 is highly sensitive and specific for detecting HCC. Moreover, GLP-3 is more sensitive than AFP for the detection of small HCC. Furthermore, a combination of both serum markers yielded an improved specificity and both sensitivity and specificity for the diagnosis of small and unicentric HCC, respectively.

Haptoglobin genotypes polymorphism as a risk factor for subclinical atherosclerosis in beta-thalassemia major children; a single center Egyptian study

Abstract Background/Objectives Haptoglobin (Hp) is an antioxidant protein. Its genotypic polymorphism had been proposed to influence vascular complications among diabetics, but no data are available about this association among thalassemia patients so far. We have investigated the assumption of an association between Hp genotypes and subclinical atherosclerosis among beta-thalassemia major (TM) children. Methods One hundred beta-TM children and 70 matched healthy controls were included. Serum ferritin level and fasting lipid profile were assayed. Haptoglobin genotyping was determined by amplification gel electrophoresis. Carotid intima media thickness (cIMT) was measured using high resolution ultrasound. Results The relative distribution of the three Hp genotypes among thalassemia group and the control group were 18 and 14.3% for Hp1-1; 38 and 37.1% for Hp2-1; and 44 and 48.6% for Hp2-2 respectively. There was no significant difference between patients and controls regarding Hp genotypes distribution. Hp2-2 genotype TM children had significantly higher cIMT compared to other genotypes (P < 0.0001). Elevated cIMT was significantly represented in Hp2-2 genotype patients (P < 0.0001) who had higher serum ferritin compared to their counterparts (P < 0.05). Hp2-2 patients were five times more likely to suffer from subclinical atherosclerosis than Hp1-1 and six times than Hp2-1 genotype patients (P = 0.008 and 0.001, respectively); a difference that persisted significant after adjustment for some risk factors compared to Hp2-1 patients (OR 3.96; P = 0.02). Conclusions Hp2-2 genotype is a significant predictor for premature atherosclerosis in TM children and confers them an increased risk for iron overload.

Evaluation of serum and urine fetuin-A levels in children with acute lymphoblastic leukemia during and after high-dose methotrexate therapy: Relation to toxicity.

Background/objectives: Fetuin-A is a multifunctional protein with its urine level was considered as a marker of acute kidney injury. We investigated the serum and urine fetuin-A in acute lymphoblastic leukemia (ALL) children during and after high-dose methotrexate (HDMTX). Methods: Twenty-two ALL children and 20 matched healthy controls were included. Liver transaminases, serum creatinine, estimated glomular filtration rate (eGFR), creatinine clearance (CrCl), serum β2 microglobulin (B2M), and serum and urine fetuin-A levels were assayed pre and 4 months after the consolidation. Among a subgroup of 15 patients, the investigations were performed 42 hours after the start of the second and the fourth HDMTX infusions. Results: HDMTX was well tolerated. During HDMTX, there was significant decline in serum fetuin-A together with significant rise of urine fetuin-A and B2M levels compared to the control and to the pre-consolidation levels, changes that persisted 4 months after the consolidation despite recovery of the significantly altered renal functions. The second HDMTX-related serum fetuin-A level directly correlated with eGFR and CrCl (r = 0.86, P < 0.0001 and r = 0.67, P = 0.016, respectively). Four months after consolidation, urine fetuin-A directly correlated with serum creatinine (r = 0.54, P = 0.004) and inversely correlated with the eGFR (r = −0.66, P < 0.0001). Conclusion: Significant disturbance in serum and urinary fetuin-A levels, which was related to renal functions, had occurred during HDMTX and persisted for at least 4 months after the consolidation. Serum and urine fetuin-A could be sensitive markers for subtle renal dysfunction in ALL children.

A preliminary study of the relation between IL-4 and hypertension in type II diabetes mellitus

Clinical outcome of T2DM can be influenced by a polymorphism of different cytokines. The aim of this study was to evaluate the effect of genetic variation and gene expression of IL-4 in T2DM patients. This study was carried out on type II diabetic patients and healthy people served as controls. All subjects were submitted to estimation of IL-4 gene polymorphism using VNTR PCR method and gene expression by real-time PCR. There was a significant decrease of IL-4 gene expression and serum IL4 levels in subjects with B2B2 genotypes. A significant positive correlation was found between IL-4 gene expression and the HDL-c levels and negative correlation between serum IL4 levels and LDLc. Also, a negative correlation was found between serum IL4 and gene expression with both systolic and diastolic blood pressure levels in patients group. It can be concluded that IL-4 gene expression and serum IL4 reduction in patients with B2B2 genotypes has a relation to dyslipidemia and hypertension in the patient with type 2 diabetes mellitus.

Study of plasma levels of soluble triggering receptor expressed on myeloid cells-1 in rheumatoid arthritis and its correlation with disease activity and tumor necrosis factor-α

Aim of the work The triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell surface receptor expressed mainly on monocytes and neutrophils. It acts as an amplifier of inflammatory response in acute and chronic inflammatory states. The aim of this work was to study the plasma-soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in rheumatoid arthritis (RA) patients and its correlation with disease activity and tumor necrosis factor-α (TNF-α). Patients and methods This study included 80 patients with RA and 20 age-matched and sex-matched controls. All were subjected to demographic, clinical, laboratory, and radiological studies using the 28-joint Disease Activity Score, erythrocyte sedimentation rate, complete blood count, and radiograph of both hands. Plasma levels of sTREM-1 and TNF-α were measured with enzyme-linked immunosorbent assay. Results RA patients had significantly higher sTREM-1 and TNF-a levels compared with controls (206.32±125.75 and 17.83±11.88; P<0.001) and (190.82±69.46 and 54.75±9.46; P<0.001). In RA patients, sTREM-1 levels were found to be positively correlated with 28-joint Disease Activity Score, erythrocyte sedimentation rate, and TNF-a level (r=0.408, P=0.001; r=0.287, P=0.010; r=0.749, P=0.001). sTREM-1 level was significantly increasing as patients had increasing disease activity (F-test=20.62; P=0.001). Conclusion RA patients had higher sTREM-1 and TNF-a level compared with controls, and sTREM-1 level was correlated with disease activity, suggesting that sTREM-1 plays a role in the inflammatory process associated with TNF-a, and it may be a useful disease activity marker in RA. TREM-1 may be a safe therapeutic strategy for RA, as blocking TREM-1 signaling was found to suppress inflammatory responses without affecting the immune system to fight bacterial infection.

The clinical impact of miRNA34a and P53 gene expression in colon cancer

Objective To study the potential role of miRNA34a gene expression and its relationship with P53 gene expression, fate, stage, metastasis and overall survival of colorectal cancer. Patients and methods This study was carried out 30 patients with colon adenocarcinoma, 30 patients with benign colon polyp and 30 apparently healthy persons served as controls. All participants were subjected to full history taking, general clinical examination. Complete blood count, liver and kidney function, determination of serum tumor markers were done. Estimation of microRNA 34a and P53 Gene expression by real-time PCR were done. Results There was a significant negative relationship between serum tumor markers and micro RNA 34a gene expression in cancer patients. Also, there was a statistically significant positive relationship between miRNA34a gene expression and P53 gene expression in both patients groups. The diagnostic accuracy of miRNA34a gene expression was both sensitive and specific for colon cancer. MiRNA34a and P53 gene expression had statistically significant relation with tumor stage and presence of metastases. Conclusion It can be concluded that the level of miRNA34a can be used to differentiate between colon cancers and begin adenomas. MiRNA34a can be used as a prognostic marker in colon cancer.

Cytotoxic T-lymphocyte antigen-4 gene polymorphisms in hepatocellular carcinoma patients in Egypt

Objective Our objective is to examine the genotypes at rs231775 in the cytotoxic T-lymphocyte antigen 4 gene ( CTLA4 ) in an Egyptian population to detect the association between this single-nucleotide polymorphism (SNP) and susceptibility to hepatocellular carcinoma (HCC). Background CTLA-4 is an important negative regulator in immune response. Its polymorphism +49G>A (dbSNP: rs231775) has been linked to an increased risk of T-cell-mediated autoimmune diseases, infectious diseases, and even carcinomas. Methods This study included 30 HCC patients (26 men and four women) and 20 healthy controls (18 men and two women). Laboratory investigations including complete blood picture, liver function tests, serum a-fetoprotein, and hepatitis viral markers (HBsAg, anti-HCV-Ab) were performed for all participants. The CTLA4 polymorphism at rs231775 was genotyped using the TaqMan allelic discrimination Assay technique. Results The data showed a higher frequency of the A/A genotype (40 vs. 10%) and the A allele (55 vs. 27.5%) in patient groups (HCC) compared with the healthy controls. Our results also indicated a statistically significant difference in CTLA4 rs231775 between HCC patients and healthy controls in the AA genotype and the A allele ( P = 0.04, 0.012), respectively. Conclusion Our results suggested that the A/A genotype and the A allele of rs231775 increase the risk of developing HCC in an Egyptian population, whereas the G allele appeared to have a protective effect in developing HCC.