Amal M. El-Shehaby

Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients

BackgroundColorectal cancer is a common cancer all over the world. Aberrations in the cell cycle checkpoints have been shown to be of prognostic significance in colorectal cancer.MethodsThe expression of cyclin D1, cyclin A, histone H3 and Ki-67 was examined in 60 colorectal cancer cases for co-regulation and impact on overall survival using immunohistochemistry, southern blot and in situ hybridization techniques. Immunoreactivity was evaluated semi quantitatively by determining the staining index of the studied proteins.ResultsThere was a significant correlation between cyclin D1 gene amplification and protein overexpression (concordance = 63.6%) and between Ki-67 and the other studied proteins. The staining index for Ki-67, cyclin A and D1 was higher in large, poorly differentiated tumors. The staining index of cyclin D1 was significantly higher in cases with deeply invasive tumors and nodal metastasis. Overexpression of cyclin A and D1 and amplification of cyclin D1 were associated with reduced overall survival. Multivariate analysis shows that cyclin D1 and A are two independent prognostic factors in colorectal cancer patients.ConclusionsLoss of cell cycle checkpoints control is common in colorectal cancer. Cyclin A and D1 are superior independent indicators of poor prognosis in colorectal cancer patients. Therefore, they may help in predicting the clinical outcome of those patients on an individual basis and could be considered important therapeutic targets.

Correlations of Urinary Biomarkers, TNF-Like Weak Inducer of Apoptosis (TWEAK), Osteoprotegerin (OPG), Monocyte Chemoattractant Protein-1 (MCP-1), and IL-8 with Lupus Nephritis

ObjectiveThis case-controlled study was designed to correlate urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) levels, with renal involvement in a cohort of systemic lupus erythematosus (SLE) patients to examine their diagnostic performance.Patients and MethodsIn 73 SLE patients, and in 23 healthy volunteers, urinary levels of TWEAK, OPG, MCP-1, and IL-8 levels were measured. Disease activity was assessed by total SLE disease activity index, and renal activity by renal activity index (rSLEDAI), and both were correlated with urinary biomarkers. Sensitivity, specificity, and predictive values of individual biomarkers to predict lupus nephritis were also calculated.ResultsSignificantly higher levels of urinary biomarkers were observed in SLE patients with lupus nephritis (LN) compared with those without LN (TWEAK, p < 0.001; MCP-1, p < 0.001; OPG, p < 0.001; IL-8, p < 0.032). Other significantly higher levels were observed in SLE patients with LN compared with control subjects (TWEAK, MCP-1, OPG, and IL-8 p < 0.001). Positive correlations were observed between rSLEDAI and TWEAK (r = 0.612 and p < 0.001), MCP-1 (r = 0.635 and p < 0.001), and OPG (r = 0.505 and p < 0.001).ConclusionsUrinary levels of TWEAK, OPG, and MCP-1 positively correlate with renal involvement as assessed by rSLEDAI with reasonable sensitivity, specificity, and predictive values to detect lupus nephritis while IL-8 was not significantly associated with global or rSLEDAI.

Early Diagnostic Markers for Contrast Nephropathy in Patients Undergoing Coronary Angiography

The present work aimed to prove the usage of neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for kidney injury and to assess the relationship between NGAL and serum creatinine and cystatin C in patients with normal serum creatinine undergoing percutaneous coronary angiography. Thirty patients with normal serum creatinine undergoing coronary angiography were enrolled. Estimation of blood glucose, glycosylated hemoglobin, lipid profile, creatinine, NGAL, and cystatin C were done before coronary angiography for all patients. Serum creatinine, NGAL and cystatin C were evaluated again at 4 and 24 hours after coronary angiography. There was a significant increase in serum NGAL level 4 hours and 24 hours after coronary interventions compared to the baseline value before coronary angiography. Before coronary angiography, serum NGAL was positively correlated with serum creatinine, and cystatin C. Conclusion: Serum NGAL and cystatin C could be valuable in the detection of early renal impairment after coronary angiography.

Human papillomavirus infection in Egyptian esophageal carcinoma: Correlation with p53, p21waf, mdm2, C-erbB2 and impact on survival

The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21waf, c‐erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21wafand c‐erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c‐erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21waf was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c‐erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21waf. Human papillomavirus infection is frequent in Egyptian EC. Both p53‐dependent and p53‐independent pathways seem to be involved in HPV‐associated EC. mdm2 and c‐erbB2 are possible targets for HPV in the p53‐independent pathway. However, only advanced stage and aberrant expression of p53 and p21waf are independent prognostic markers.

Relationship of BsmI polymorphism of vitamin D receptor gene with left ventricular hypertrophy and atherosclerosis in hemodialysis patients

Abstract Background. Left ventricular hypertrophy (LVH) is a common manifestation of cardiovascular disease and has an important prognostic value in patients with end-stage renal disease (ESRD). Vitamin D receptor (VDR) has been intensively investigated, and one of these (BsmI) already has been associated with survival in the dialysis population. Objective. The aim of this study was to investigate the role of VDR polymorphism (BsmI) on the development of ventricular hypertrophy and atherosclerosis in hemodialysis patients. Subject and methods. The subjects were 80 patients with end-stage renal disease on maintenance hemodialysis, and 40 healthy controls. Clinical and laboratory parameters, including genetic variation in VDR gene (BsmI), were assessed. In addition, echocardiography and intima-media thickness were performed for all subjects. Results. There was no significant difference in the distribution of BsmI genotypes either in patients or in the control group. The frequency of the B allele of BsmI polymorphism (41.6%) in dialysis patients was similar to that of healthy control subjects (39.2%). Patients with BB genotype had significantly lower serum concentrations of 25-hydroxy vitamin D compared to both Bb and bb genotypes. The number of B alleles was positively correlated with left ventricular mass index (LVMI), but not with intima-media thickness. Conclusion. These results suggest that the B alleles of the BsmI polymorphism could be considered as novel markers of altered vitamin D signaling in ESRD patients, and this alteration in BB genotype produces an increase in left ventricle mass.

The Role of PDE5 Inhibitors in Heme Oxygenase–cGMP Relationship in Rat Cavernous Tissues

INTRODUCTION Heme oxygenase (HO) enzyme catalyzes oxidative degradation of heme to biliverdin and carbon monoxide (CO). CO shares many properties with nitric oxide (NO) including the activation of soluble guanyl cyclase. AIM To assess cavernous tissue HO activity and cyclic guanosine monophosphate (cGMP) levels in response to oral phosphodiesterase type 5 (PDE5) inhibitors. METHODS Seven hundred twenty male Sprague-Dawley rats, divided into six groups, were investigated. Group 1, controls; group 2 received sildenafil citrate orally; group 3 received vardenafil hydrochloride; and group 4 received tadalafil. Group 5 was subdivided into three equal subgroups, received the same dose of each drug added to the HO inhibitor, Zn protoporphyrin. Group 6 was subdivided into three equal subgroups, received the same dose of each drug added to the NO inhibitor, L-nitroarginine methylester. Eight rats from each group/subgroup were sacrificed at 0.5, 1, 2, 3, 4, 6, 18, 24, and 36 hours, respectively. MAIN OUTCOME MEASURES HO enzyme activity assay and cGMP tissue levels in dissected rat cavernous tissues. RESULTS Both cavernous tissue HO enzyme activity and cGMP levels were increased significantly in sildenafil-, vardenafil-, and tadalafil-treated rats compared with the controls, with significant decreases after either HO or NO inhibition. Cavernous tissue HO enzyme activity and cGMP showed a positive significant correlation (r = 0.854, P < 0.001). CONCLUSION The effects of PDE5 inhibitors in cavernous tissue are partly mediated through HO enzyme activity.

Bone density, body composition, and markers of bone remodeling in type 1 diabetic patients

Abstract Objective. To assess bone mineral density (BMD), body composition by dual X-ray absorptiometry (DXA), and various biochemical markers of bone growth and resorption in a group of children with type 1 diabetes mellitus (T1DM). Patients and methods. The study included 47 patients with T1DM and 30 age- and sex-matched controls. Anthropometric measurements, biochemical markers for bone formation, bone resorption and DXA were done for all patients and controls. Results. Of our diabetes patients, seven (16.7 %), three (7.3 %), and 17 (41.5%) met diagnostic criteria for osteopenia at the right femur, lumbar spine and total body, respectively. On the other hand, osteoporosis as defined by the WHO criteria was diagnosed in 21 patients (51.2%) at the total body by DXA. Lean body mass and lean fat ratio were lower, while, total fat mass, abdominal fat%, soft tissue fat mass%, and fat/lean ratio were higher in diabetics compared to controls. Also, our patients showed lower serum osteocalcin, osteoprotegerin, procollagen type 1, and higher urinary deoxypyridinoline. Pubertal (diabetics and controls) have higher BMD and BMC than prepubertal. Conclusion. Diabetic patients had a low BMD after adjustment (Z score), low bone formation and high bone resorption markers. Diabetes control and increase in BMI leads to a decrease in the incidence of low bone mineral density. Diabetes causes an increase in body fat especially abdominal fat which leads to an increase in insulin resistance and decrease in lean mass.

Apelin: a potential link between inflammation and cardiovascular disease in end stage renal disease patients.

Abstract Background and objectives. Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients. Increasing evidence suggests a role for apelin in the pathology of the cardiovascular system. In the present study, the plasma level of apelin was studied in patients with hemodialysis to assess the effect of renal transplantation and dialysis session on plasma apelin and whether circulating apelin levels reflect cardiovascular homeostasis and inflammation in these patients. Patients and methods. Plasma apelin, high sensitive CRP (hsCRP) and IL-6 levels were investigated in 30 end stage renal disease (ESRD) patients on maintenance hemodialysis (HD), a group of 15 HD patients scheduled for renal transplantation and a group of 15 HD patients on maintenance HD, as well as ten healthy volunteer subjects who served as controls. An echocardiography was performed for all subjects. Results. Plasma apelin levels were significantly lower in hemodialyzed patients compared to controls. Plasma apelin was also found to be positively correlated with left ventricular end systolic dimension (LVESD), left ventricular end diastolic dimension (LVEDD), interventricular septum (IVS), right ventricle (RV), left atrium (LA), Aorta (Ao), while, it was negatively correlated with hsCRP and IL-6 in ESRD patients. Regarding the effect of hemodialysis on plasma apelin levels, no significant effect was found after a single hemodialysis session, while levels increased significantly in the early post-transplant period. Conclusions. Apelin is related to echocardiographic features and inflammatory markers in hemodialyzed patients. Apelin may provide a mechanism for systemic inflammatory monitoring and adaptive regulation of cardiovascular function.

Plasma visfatin and retinol binding protein-4 levels in patients with type 2 diabetes mellitus and their relationship to adiposity and fatty liver

OBJECTIVES We investigated whether plasma visfatin and binding protein-4 (RBP-4) levels correlate with obesity and type 2 diabetes mellitus (T2DM). DESIGN AND METHODS Two groups were enrolled: Group 1: 40 patients with T2DM and Group 2: 40 age- and gender-matched healthy controls. Both groups were subdivided according to body mass index (BMI) into non-obese (BMI < 25 kg/m(2)) and obese subjects (BMI ≥ 30 kg/m(2)) (20 each). RESULTS Plasma visfatin and RBP-4 levels were significantly increased in T2DM patients compared with controls with similar BMI values (for both p<0.001). Plasma visfatin and RBP-4 concentrations correlated with BMI, waist/hip ratio, insulin and homeostatic model assessment insulin resistance (HOMA(IR)). Visfatin and RBP-4 correlated with visceral fat and liver fat in diabetic patients (for both p<0.001). CONCLUSION Visfatin level was increased in T2DM, possibly related to hyperglycemia. Plasma RBP-4 correlated positively with liver fat and HOMA(IR) which may reflect its effects on hepatic insulin sensitivity.

Raised serum level of APRIL in patients with systemic lupus erythematosus: correlations with disease activity indices.

The aim of the present study is to assess serum APRIL levels in SLE patients versus rheumatoid arthritis (RA) patients and normal control and to correlate serum APRIL levels in SLE patients with disease activity indices. Serum APRIL levels was measured in 40 SLE patients, 20 patients with RA and 20 healthy volunteers who served as control group. Disease activity in SLE patients was assessed by the British Isles Lupus Assessment Group (BILAG) index and SLE disease activity index (SLEDAI), and results were correlated with serum APRIL levels. Significantly higher serum APRIL levels was observed in SLE patients compared to RA patients and normal controls (p=0.003 and p < or = 0.001, respectively). Positive correlations were found between serum APRIL levels and total BILAG index (r=0.486 and p=0.001), BILAG musculoskeletal score (r=0.848 and p < or = 0.001) and BILAG cardiorespiratory score (r=0.326 and 0.04). Serum APRIL was higher in SLE patients compared to RA patients and normal control subjects and positively correlates with BILAG index and higher levels may be associated with musculoskeletal manifestations of the disease. APRIL antagonism could be a potential therapeutic target in SLE.