Expression of wild p53, mutated p53 and hypoxia inducible factor-1 alpha in hepatocellular carcinoma

To investigate the expression of wild p53, mutated p53 and hypoxia inducible factor-1 alpha [HIF-1 alpha] genes in hepatocellular carcinoma and correlate their expression with clinicopathological data. Liver biopsy samples of 30 hepatocellular carcinoma [HCC] subjects. 20 chronic hepatitis C [CHC] and 20 liver biopsy samples from non cancerous tissue [i.e control samples] of HCC were assessed by polymerase chain reaction [RT-PCR] and restriction enzyme analysis for the three genes; wild p53 gene, mutations in p53 at codon 249, exon 7 and hypoxia inducible factor-1 alpha gene. Wild p53 gene was detected in 18/30cases of HCC [60%], 16/20 cases of CHC [80%] and 15/20 cases of control samples [75%] with no significant difference between the studied groups. Mutated p53 gene was detected in 12/30 cases of HCC [40%], 4/20 cases of CHC [20%] and 5/20 cases of control samples [25%], also with no statistically significant difference between the studied groups while HIF-lalpha gene was expressed in 20/30 cases of HCC [66.7%] in comparison to 2/20 cases of CHC [10%] and 3/20 of control samples [15%] with a highly statistically significant difference [p<0.001]. The expression of both wild p53 and the mutated p53 correlated with tumor size but did not correlate with grade of malignancy nor serum alpha fetoprotein level, while the expression of HIF-1 alpha correlated with grade of malignancy and alpha fetoprotein level but not with tumor size. No correlation between expression of all genes and capsule infiltration or presence of cirrhosis was found in all groups. HIF-1 alpha is highly expressed in HCC and is related to grade of malignancy and serum alpha fetoprotein level

Cardiac abnormalities in patients with chronic renal failure on haemodialysis: role of parathormone

The study was conducted at Kasr Al-Aini University Hospital between December 2001-December 2003 on 42 patients [19 males and 23 females] with a mean age of 43 +/- 10 years. All patients have established end stage renal disease and on regular haemodialysis at the dialysis unit at Kasr El Aini Teaching Hospital. Patients were divided into three groups according to their serum parathormone [PTH]: Group A includes 11 patients with normal serum PTH ranging between [12-71Pg/dl], group B includes 15 patients with target PTH range [3-4 folds the upper limit of normal 210-280 Pg/dI]. Group C includes 16 patients with high serum PTH [higher than target range >280Pg/dl]. All patients have a target urea reduction ratio [URR] >65% i.e. >1.3 Kt/v indicating efficient dialysis. The mean age of patients in the different groups showed no significant difference. Assessment of the traditional risk factors for atherosclerosis regarding arterial blood pressure, serum lipid profiles showed that the mean arterial blood pressure was significantly higher [p<0.05] in group C when compared to group B and highly significant when compared to group A [p<0.01]. Serum LDL cholesterol was significantly higher in group C patients compared to group A [p<0.01] with no significant difference in relation to group B. Serum HDL was significantly lower in group C compared to group A and B [p<0.01]. Also group B showed highly significant decrease in serum HDL compared to group A [p<0.01]. Serum triglycerides was significantly higher in-group C compared to group B, A with a p value [0.05, 0.01] respectively. The principal serum correlates with parathormone that are calcium and phosphorus were compared between the three groups. Serum calcium was found to be highly significantly lower in group C compared to group B and A and also in group B compared to group A with a p value <0.01]. Also serum phosphorus was highly significant higher in-group C compared to group B and A and also in-group B compared to group A with a p value [<0.01]. Resting ECG ischaemic changes was observed in 6/16 patients in group C compared to 2/15 patients in group B, while no resting ECG changes was observed in group A. Assessment of the systolic functions of the heart by echocardiography showed that the ejection fraction [EF] was significantly higher in group B compared to group A, while in group C the EF was significantly lower compared to group A and B [p<0.01]. As for diastolic functions [E/A] ratio, the only significant difference was found between group C and A [p<0.05]. Structural alteration was studied by assessment of the interventricular system thickness [IVS] and left ventricular mass. Patients with group C showed a highly significant difference compared to group A and B [p<0.01] being higher in group C. Left ventricular mass was also significantly higher in group C compared to group A and B [p<0.01] with no significant difference between group A and B. As regards valvular and soft tissue calcifications patients with group C showed significantly higher calcific valvular lesions compared to group A and B [p<0.01]. Correlation between PTH, calcium and phosphorus and different variables showed that PTH and serum phosphorus was significantly positively correlated with mean arterial blood pressure, triglycerides Total cholesterol, left ventricular mass and interventricular septum thickness while calcium showed significant negative correlation with the same variables [p<0.01]. As for cardiac ejection fraction, serum PTH and phosphorus showed significant negative correlation while serum calcium showed significant positive correlation with the same variables [p<0.01]. In conclusion alteration of serum PTH level with calcium, phosphorus homeostasis in patients with renal failure may play an important role in potentiation of the classic risk factors for cardiovascular morbidity in addition to its direct effect on structural and functional alteration of the myocardium in these patients making control of such metabolic derangement an essential target for the prevention of cardiovascular morbidity in these patients

Evaluation of some tumor markers in diagnosis and prognosis of hepatocellular carcinoma

Early detection of hepatocellular carcinoma [HCC] is critical for successful treatment. However, the differential diagnosis between HCC and benign hepatic lesions is sometimes difficult and new biochemical markers for HCC are required. The aim of the work was to assess the usefulness of serum AFP, PIVKA-II and TGF- beta1 in the diagnosis and prognosis of HCC and to evaluate the role of serum VEGF in the prediction of venous invasion and metastasis in HCC patients. This study was conducted on 50 patients who were divided into 4 groups; Group I: 10 patients with liver cirrhosis, Group II: 20 patients with benign hepatic focal lesion [HFL], Group III: 10 HCC patients without metastasis before and after treatment in the form of per-cutaneous alcohol injection, and Group IV: 10 HCC patients presenting with metastasis. Ten apparently healthy subjects were taken as a control group. Patients as well as the control subjects were submitted to the following: A] Full clinical examination, B] Imaging techniques including abdominal ultrasonography and CT scan. Patients with HCC were subjected to bone scan and MRI brain, chest and abdomen to detect distant metastasis, C] Laboratory investigations including: complete liver function tests, prothrombin time and concentration, serological examination for hydatid disease, cytological examination of fluid aspirated from infectious cyst, serodiagnosis of HCV and HBV infection, serological markers including AFP, PIVKA-II, VEGF and TGF- beta1 Lastly, histopathologic examination of liver biopsies obtained from focal lesions of HCC patients. A statistically significant difference in the median serum level of AFP, PIVKA-II, VEGF and TGF- beta1 was found on comparing the HCC groups [with and without metastasis] with the control, benign focal lesions and cirrhotic groups. The median serum PIVKA-II level was significantly lower in the non-metastatic HCC group [16.2 ng/ml] compared to the metastatic group [33.6 ng/ml] [P=0.001]. On the other hand, the median serum VEGF level was significantly higher in the non-metastatic HCC group [2580 pg/ml] compared to that of the C group with distant metastasis [1840 pg/ml] [P=0.008]. There was a significant lowering of median serum level of all parameters in the non-metastatic HCC patients after ablation therapy. A statistically significant negative correlation was observed between serum VEGF and serum PIVKA-II in the non-metastatic HCC group. Regarding sensitivity and specificity of the four serological markers: at a cut-off level of 28 ng/ml, AFP yielded a sensitivity of 80% and a specificity of 97%, at a cut-off level of 12.5 mAU/ml for PIVKA-II, the sensitivity was 80% and the specificity was 97%, VEGF revealed a sensitivity of 96.7% and a specificity of 85% at a cut-off level of 780 pg/nil, and lastly TGF- beta1 yielded a sensitivity of 76.7% and a specificity of 97% at a cut-off level of 32.4 ng/ml. Combination of these markers improved both sensitivity and specificity, as combination of AFP and PIVKA-II yielded a sensitivity of 93.3% and a specificity of 98.2%, and for AFP with TGF- beta1, the sensitivity was 87.5% and the specificity was 99%. Combined determination of serological markers could be used as a highly valuable tool for screening and diagnosis of HCC. They could also be used as prognostic markers hence decreasing the need for more invasive procedures such as liver biopsy