Clinical significance of vascular endothelial growth factor [VEGF] in sera of patients with pediatric malignancies

Angiogenesis is essential for solid tumor growth. It is induced by tumor cells through stimulatory angiogenic peptides, one such peptide is vascular endothelial growth factor [VEGF]. The ultimate aim of the work is to investigate the possible role of VEGF as an early biomolecule involved in the progression of pediatric malignant tumors with high metastatic potential. Forty-five pediatric patients were studied. They included four groups with malignant solid tumors suffering from Ewing's sarcoma, osteosarcoma, neuroblastoma and rhabdomyosarcoma. In addition, a healthy control group including fifteen age and sex matched children was included in the study. Serum VEGF levels were determined by ELISA technique. The level of VEGF was significantly higher in all types of solid tumors compared to normal healthy children. The mean values obtained for patients and controls were 429.44 +/- 258.55 pg/ml and 79.36 +/- 63.81 pg/ml, respectively. No significant difference was detected in the level of VEGF among males and females. Also, no statistically significant difference was detected among the different types of malignant tumors. However, a marked significant difference was elucidated between metastatic and non-metastatic cancer patients, the values recorded were 753.33 +/- 173.64 pg/ml and 267.5 +/- 75.54 pg/ml, respectively [p <0.001]. Furthermore, the results showed that 207 pg/ml of serum level of VEGF is the optimal cutoff value [mean +/- 2 SD of control] with sensitivity of 87% and specificity of 100%. Using the receiver operating characteristic [ROC] curve analysis, the area under the curve [0.917] indicated the validity of using serum VEGF level in the diagnosis of all different types of pediatric malignant solid tumors with high potentiality to metastasis. VEGF is an angiogenic stimulatory peptide. Its serum level colud be a reliable marker in assessing pediatric malignancies with high metastatic potentials

Evaluation of serum total bile acids in the diagnosis of hepatocellular carcinoma

Fasting total serum bile acids [FSBA] concentrations were measured in 140 cases of chronic liver diseases including 50 patients with liver cirrhosis, 40 patients with chronic hepatitis and 50 patients with hepatocellular carcinoma [HCC]. FSBA concentrations were significantly higher in patients with HCC than those with chronic hepatitis and cirrhosis and both were significantly higher than the controls [p<0.0001]. FSBA concentrations were not correlated to the size of the tumor, the Child Pugh grades, the histopathologic grades and most of the liver function tests. Using the receiver operative characteristic [ROC] and the differential positive rate [DPR] analysis, 30 pmol/l was the optimal cut-off value that differentiates patients with HCC from those with cirrhosis. At this level, the sensitivity, the specificity and the diagnostic accuracy were 42%, 98% and 70% respectively. AFP was found to be significantly increased in patients with HCC than those with chronic hepatitis and cirrhosis. The best cut-off value of AFP was 100 ng/ml, at which the sensitivity, the speci-ficity and diagnostic accuracy were 52%, 96% and 74% respectively. The simultaneous determination of AFP and total bile acids raised the sensitivity of the test to 76%. The area under the ROC curve for AFP and total bile acids was 0.764 and 0.744 respectively, the difference is non-significant. In conclusion, both AFP and total bile acids are good markers for HCC and their simultaneous determination may improve the detection of HCC in cirrhotic patients negative for AFP

Studies on DNA sequencing of K-ras-2 Gene in patients with liver and pancreas cancer

Point mutations in K-ras-2 gene were detected either in primary liver or pancreas cancer patients using polymerase chain reaction followed by polyacrylamide DNA sequencing determination analysis. The frequencies of point mutations which found liver tumors were mainly due to adenine base insertion, whereas in pancreatic tumors cytosine insertion type was found to be abundant. Both types of tumors showed guanine deletion of K-ras-2 mutations. This work shed light on the possibility of using point mutations in K-ras-2 gene as a useful approach for differential diagnosis of cancers

Gene transfection pattern of hepatoma cell lines with high and low alfa-fetoprotein gene expressions

Depletion of chloramphenicol acetyl transferase [CAT] activity was clearly observed in Hu-h7 [high alpha fetoprotein [AFP]] cultured cells, when the cells were transfected with thymidine Kinase [TK] CAT plasmid. On the contrary, Hu-h1/Cl-2 cells [low AFP] had high CAT activity after transfection with the same plasmid. Hu-h7 and Hu- hl/Cl-2 cells exhibited high and very low CAT positive reaction, respectively, when the cells were transfected with AFP 7300 plasmid. Both cell lines showed negative CAT reaction, when the cells were transfected with albumin-CAT as well as AFP 1000 plasmids [AFP deleted enhancers]. The results revealed some differences between human hepatoma cell lines characterized by high and low AFP gene expression in term of gene transfection patterns indicated by CAT assay. This finding could open new avenues for better differential diagnosis of patients suffering from liver cancer

Studies on molecular mechanisms of natural killer cell functionality in human and rat.1: Protease production

Two types of proteases with molecular weight between 97 and 66 kD were detected in condition media from mixed culture of human or rat natural killer with tumor cells. Meanwhile, human natural killer cells alone showed only 1 protease. Whereas the rat natural killer cells still had the 2 types of the proteases with weaker activity. The protease secreted by the previous natural killer cells were in latent form and required trypsin enzyme to be active. The work suggested the secretion of proteases by natural killer cells as one of the possible biological mechanisms involved in their mode of functions

Effect of retinoic acid and peroxisome proliferate on the transfection of alfa-fetoprotein gene in human hepatoma cell lines

Retinoic acid [t-RNA] at concentration 1 uM led to deplete CAT gene activity induced by AFP 7300 plasmid transfection in Hep3B [B-virus integrated], whereas in Hu-h7 [non-viral type] the effect was just slight down-regulation of the gene activity. However, in the presence of proxisome proliferator [2 uM] complete absence of CAT reaction was clearly observed in this cell line [Hu-h7]. On the other hand, proxisome proliferator [PP] alone did not show any effect at all in the viral type cell line, [Hep3B], whereas in the non-viral type [Hu- h7], down-regulation of CAT gene function was clearly observed. Therefore, the response of the previous mentioned cell lines [viral and non-viral] either to t-RA or PP was absolutely different. The finding sheds a light on new avenues for differential useful therapy for patient suffering from hepatoma with different past-history of the disease