ABSTRACT
Background: DNA methylation is the commonest known epigenetic change that results in silencing of tumor suppressor genes. Promoter methylation of tumor suppressor genes has the potential for early detection of breast cancer
Aim: Aim is to examine the potential usefulness of blood based methylation specific polymerase chain reaction [MSP] of methylated DKK3 and RASSF1A genes in early detection of breast cancer
Method: Methylation status of DKK3 and RASSF1 was investigated in forty breast cancer patients, twenty fibroadenoma patients and twenty healthy ladies as control group using MSP
Results: Methylation of DKK3 promoter was found in 22.5% of breast cancer patients, while DKK3 methylation was absent in both fibroadenoma patients and control group. Similarly, methylation of RASSF1 promoter was found in 17.5% of breast cancer patients and in none of fibroadenoma and control group
Conclusion: Promoter methylation of DKK3 and RASSF1 was found in breast cancer patients while absent in control group suggesting that tumorspecific methylation of the two genes [DKK3 and RASSF1A] might be a valuable biomarker for the early detection of breast cancer
ABSTRACT
High levels of low-density lipoprotein [LDL] usually found in nephrotic syndrome [NS] may give rise to atherosclerosis. Oxidative modification of LDL has been suggested to be a key step in atherogenesis. Oxidized low-density lipoprotein [oxLRL] can elicit an immune reaction leading to the formation of anti- oxLDL autoantibodies [oxLDL-Ab]. The aim of this work was to study the status of oxLDL and its autoantibodies among children with NS in relation to lipoprotein [a] [Lp[a]] as a proatherogenic factor and the antioxidant reduced glutathione [GSH] that reflects the oxidative stress in such syndrome. The study was conducted on 30 children with NS with a mean age of 8.9 k3.29 years from the Pediatric Nephrology Clinic of Alexandria University Children's Hospital. Twenty-two of them were in protein uric phase [Group I] and eight children were in remission [Group II]. For all patients and 10 healthy control children [Group III], plasma oxLDL and serum oxLDL-Ab by enzyme immunoassay, Lp [a] and blood GSH were quantified. Lipid profile, serum albumin, urea, creatinine and complement 3 [C3] were measured, in addition to quantitative determination of 24 h urine protein. All nephrotic cases in-group I had proteinuria, hypoalbuminemia and hypercholesterolemia. Hypertension was detected in 27% of them. There were statistically significant elevations of oxLDL and oxLDL-Ab in-group I when compared to controls and to those in remission [F0.003 and P=0.008 respectively]. Lp [a] was significantly elevated in group I and group II compared to controls [P=0.006]. Significant reduction of GSH was found in-group I compared to controls [P0.011]. In hypertensive nephrotic children, oxLDL and Lp [a] were significantly higher than normotensives [P 0.02 and P 0.04]. There was a significant positive correlation between oxLDL and oxLDL-Ab [P=0.00l]. Both OXLDL and oxLDL-Ab showed significant positive correlations with urine protein [F0.037 and F0.027 respectively] and significant negative correlations with blood GSH [P=0.046 and P0.001 respectively]. OxLDL-Ab showed positive correlation with plasma Lp [a] [P0.029]
Conclusion: nephrotic syndrome might be a consequence of an imbalance between oxidant and antioxidant activity leading to plasma accumulation of oxLDL that is known to induce atherosclerosis. Childhood NS is associated with an enhanced immune response to oxLDL, mirrored by the increased levels of oxFDL-Ab. These specific autoantibodies among other proatherogenic factors are likely to participate in atherogenesis and glomerular damage. The degree of oxidative damage reflected by the status of GSH, OXLDL and oxLDL-Ab would influence the response of NS to therapy