Squamous cell carcinoma antigen as a tumor marker in patients with hepatocellular carcinoma

Hepatocellular carcinoma [HCC] is considered the fifth most common cancer in the world. Owing to its increased incidence in the last decade and the expected further increase in the next 2 decades, HCC is arousing great interest. HCC commonly develops on cirrhotic livers and therefore, surveillance programs have been suggested to identify early HCC, at a stage suitable for surgical or interventional therapy and has a better clinical outcome. The only serologic marker used in clinical practice is alpha-fetoprotein [alpha-FP], but its sensitivity is poor. Hence, the investigation of new markers is required. To assess the clinical utility of squamous cell carcinoma antigen [SCCA] as a non invasive marker in the early diagnosis of HCC and whether the association of alpha-FP and SCCA could improves the diagnostic power. This study is conducted on 65 newly diagnosed hepatic focal lesion cases from those attending the Tropical Medicine Department, Cairo University Hospitals [Group I] as well as 20 age and sex matched healthy control subjects [Group II]. Group I was further subdivided into la [49 HCC proved untreated patients] and Ib [16 patients with Cirrhosis only] according to their histopathological findings. All patients were subjected to full history taking, clinical examination, laboratory investigations [including liver function test, hepatitis markers, alpha-FP and SCCA serum levels], triphasic abdominal CT and pathological examination. Group I included 42 males [64.7%] and 23 females [35.3%] with ages ranging between 42-70 years [60.7111.28], of them 16 patients had HBV [24.6%], 37 patients had HCV [56.9%] and 12 patients [18.4%] had mixed HBV and HCV infection. Group I was further subdivided into group la which included 49 HCC proved patients and group Ib which included 16 patients with regeneration nodules [cirrhosis only] according to their histopathologic findings. Group II [control] included 20 age and sex matched healthy subjects. Mean levels of serum alpha-FP and SCCA in group Ia was significantly higher when compared with group Ib [p<0.0005 for both of them]. At a cutoff of serum alpha-FP 200 ng/mL, the sensitivity was 35% and the specificity was 100% while at a cutoff >400ng/mL, the sensitivity decreased to 7.6%. On using the receiver operator curve [ROC], to improve the specificity and sensitivity of alpha-FP and SCCA, the cutoff value of 40ng/ml and 0.55ug/L yielded a sensitivity of 67.2% and 61.2% respectively and specificity of 100% [best cutoff]. When combined sensitivity of them was calculated at the best-chosen cutoff values, sensitivity improved to 87.7% with specificity of 100%.Combined use of alpha-FP and SCCA in the screening of patients with hepatic focal lesions may increase the chance of diagnosis of HCC patients

endothelial nitric oxide synthase gene intron 4 polymorphism in Egyptian patients with end-stage renal disease

Nitric oxide [NO] synthesized by endothelial cell NO synthase [ecNOS] is a potent regulator of intrarenal haemodynamics. A polymorphism in intron 4 of the ecNOS gene is a candidate gene in renal diseases. The aim of this work is to study the gene polymorphism of ecNOS intron 4 in patients with end-stage renal failure and compared it with that of healthy subjects. The study was performed on 40 patients with end stage renal disease [ESRD] patients on regular hemodialysis, and was classified into 2 groups: Group I ESRD patients with diabetic nephropathy [10 patients] and group II includes 30 patients with ESRD due to different etiologies [all causes except diabetic nephropathy], and group III 15 apparently healthy subjects as control group. ecNOS genotypes were determined using polymerase chain reaction. The results showed that two alleles of ecNOS intron 4, labeled a and b could be detected. The frequencies of aa, ba, bb genotypes were 5% [2/40], 12.5% [5/40] 82.5% [33/40] in all the patients, 3.3% [1/30], 13.3% [4/30], 83.3% [25/30] in-group II patients, and 10% [1/10], 10% [1/10] 80% [8/10] in group I patients respectively, and in the control group all were bb100% [15/15]. There is significant difference in the frequencies of ecNOS genotypes between all ESRD patients and the control group [OR 1.423; 95% CI 1.253-1.615, p<0.01]. Compared with controls; the group I patients had much higher frequency of the ecNOS 4a allele than in-group II patients [OR 2.765, 1.556, 95% CI 1.891-4.042, 1.423-1.615, p<0.001, p<0.01] respectively. There was a significantly higher frequency of the ecNOS 4a allele among ESRD patients both diabetic and non-diabetic than in control subjects. This suggests that the ecNOS gene polymorphism in intron 4 appears to be prognostic of renal failure and the ecNOS gene polymorphism in intron 4 is a useful parameter for studying the relationship between NO and the progression of renal failure. This suggests that the ecNOS gene polymorphism might be associated with an increased risk of chronic renal failure

Oxidative stress and antioxidants in hepatitis C virus patients

Malondialdehyde [MDA] is widely used as an index of oxidative injury induced by oxygen free radical on lipid membranes. Vitamin E [Vit.E] has been found to protect the liver against oxidative stress. There are inverse correlations between the increase of peroxide and the decrease of the ceruloplasmin [Cp] in patients with hepatitis C virus [HCV]. To estimate serum levels of malondialdehyde [MDA], of vitamin E [Vit.E] and ceruloplasmin [Cp], and to correlate their serum levels with the presence of cirrhosis and hence their use as non invasive blood markers. This study is a cross sectional study conducted on 40 newly discovered HCV infected cases receiving no treatment for hepatitis C virus [HCV] attending the Tropical Clinic in Cairo University Hospitals. They were 25 females and 15 males [age ranged from 25 to 60 years] as well as 15 age and sex matched healthy control subjects. Diagnosis of HCV was made by hepatitis markers using microparticle enzyme immunoassay [MEIA]. All patients were subjected to full history taking, clinical examination, abdominal ultrasonography, Laboratory tests included serum AST, ALT, total protein and albumin by routine analytical methods. Serum MDA level was estimated by thiobarbituric acid [TBA] chemical method, serum vitamin E by isocratic HPLC/UV method and serum Cp by immuno-nephlometric method. Patients were classified into two groups: Group I [patients with HCV infection] that was further divided into; Group I [a]: Included 26 HCV patients without cirrhosis. Group I [b]: 14 HCV patients with cirrhosis according to their ultrasonographic findings. Group II [control group]: Were HCV-antibody negative. The level of serum Cp did not differ between groups I [a], I [b] and II. The mean values of serum levels of MDA were significantly higher in all HCV positive patients compared to controls [p<0.001] and were higher in group I [a] compared to group I [b] with statistically significant difference [p<0.000]. The mean values of serum levels of Vitamin E were significantly lower in all HCV positive patients compared to controls [p<0.001] and were higher in group I [b] compared to group I [a] with statistically significant difference [p<0.000]. Serum levels of MDA showed a highly significant positive correlation with serum levels of ALT in group I [a] [r=0.633; p=0.001]. Both MDA and vitamin E levels are reliable indicators for the extent of oxidative stress and antioxidant status in HCV patients. MDA can be used as a simple non-invasive blood marker for detection of progression of chronic HCV to fibrosis

Vitamin D receptor [VDR] gene polymorphism and risk of osteoporosis in Egyptian post menopausal women

Identifying people at risk of osteoporosis is very important, as prevention is possible. Because genetic factors were shown to have a great influence on osteoporosis susceptibility, their study may be of great help in targeting high-risk individuals. In this work, we studied the association between VDR gene polymorphism and bone mineral density in postmenopausal Egyptian females. 45 Egyptian postmenopausal women [57 +/- 4.6 years] were studied. Bone mineral density was measured at the lumbar spines, the hip, and the lower radius using dual energy X-ray absorptiometry. Ten of the studied patients [22%] had osteoporosis [T or z scores < -2.5]; 21 [47%] had osteopenia [T or z scores -1 to -2.5]; and 14[31%] were normal [T or z scores > -1]. Restriction fragment length polymorphisms in the VDR gene were assessed by PCR amplification and digestion with restriction enzymes FokI, BsmI, ApaI, and TaqI recognizing polymorphic sites in these four VDR gene loci. The BsmI Bb genotype distribution was significantly higher in the normal postmenopausal women [42.9%] than osteopenic women [4.8%] [p value < 0.002]. The TaqI [T] allele was significantly higher in the normal group [68.0%] than the osteopenic group [45.0%] and TaqI [t] which was significantly higher in the osteopenic group [55.0%] than the normal group [32.0%] [p=0.031 for both], otherwise, there was no significant difference in the distribution of other VDR genotypes in relation to bone density measurement. The higher distribution of the VDR BsmI Bb and TaqI T genotype in the normal postmenopausal than osteopenic women may reflect a protective role, on the other hand, TaqI t allele may be associated with lower bone mineral density in postmenopausal Egyptian females