ABSTRACT
Hepatocellular Carcinoma is a multifactorial, multistep and complex process. Its prognosis is poor and early diagnosis and monitoring of metastasis of HCC is of utmost importance. Circulating alpha-fetoprotien mRNA has been proposed as a marker of HCC cells disseminated into the circulation but the specificity of this molecular marker and its correlation with the main HCC clinico-pathological parameters remain controversial. In recent years; several different multi-marker assays have been developed for the detection of hepatoma cells in the peripheral blood of patients with HCC. In this study 58 patients and 15 matched healthy volunteers were included; the patients were divided into three groups; group A: patients with primary HCC [n = 32], group B: patients with cirrhosis with no evidence of HCC [n = 12], group C: patients with metastatic cancer in liver [n = 14]. Group D: 15 healthy volunteers age and sex matched. The staging of HCC was carried out according to the Tumor/Node/Metastasis [TNM] classification. Peripheral blood samples were obtained from all subjects; MAGE-1 and MAGE-3 and AFP mRNAs were detected by nested RT-PCR. The positive rates of MAGE-1, MAGE-3 and AFP mRNAs were 18/32 [56.3%], 15/32 [46.9%] and 19/32 [59.4%] respectively in the primary HCC patients. In the cirrhotic group only 4/12 [33.3%]patients were positive for AFP mRNA, whereas in the metastatic group 5/14 [35.7%] and 4/14 [28.6%] were positive to MAGE-1 and MAGE-3 mRNAs respectively. MAGE-1 and MAGE-3 mRNAs were correlated with TNM clinical stages; tumor number and tumor size [p < 0.05]. Our results indicate that a multi-marker nested RT-PCR assay with cancer-specific markers such as MAGE-1 and MAGE-3 in combination with a hepatocyte-specific AFP marker may be a promising diagnostic tool for monitoring hepatocellular carcinoma patients. Nested PCR exhibits higher sensitivity, stronger specificity and lower false-positive occurrence as compared to single RT
Subject(s)
Humans , Male , Female , Hepatocytes , /blood , alpha-Fetoproteins/immunology , Polymerase Chain Reaction/methods , Sensitivity and SpecificityABSTRACT
Diabetic Nephropathy is a leading cause of disability in patients with type 1 diabetes mellitus [T1DM]. Recently discovered vasoconstrictors regulators, such as endothelin [ET] have been shown to have possible pathogenic roles in diabetic vascular complications. In type 1 diabetic patients will different stages of nephropathy, we investigated plasma endolhelin-1 [ET-1] levels and urinary albumin excretion to study the relationship between ET-1 and diabetic nephropathy, in addition to the effect of glycemic control on ET-1 urinary albumin excretion. Sixty patients with T1DM [38 males and 22 females] aged [20.0 +/- 4.9 years] with different stages of nephropathy were selected without renal impairment, or edema 17 patients with normal urinary albumin excretion Igp, 1 normal UAE, 21 patients with microalbuminuria [gp. 2 MAU] and 22 patients with proteinurea >lgm/day [gp. 3 PU]. In addition to 15 healthy subjects matched for sex and age acting as a control group. Plasma ET-1 levels, urinary albumin excretion, and glycosilated hemoglobin [HbAlc] were determined in all subjects. There were significant increases of ET-1 in all the diabetic groups as well as urinary albumin excretion, the highest values was found in the pro-leinuric group. Also ET-1 showed positive correlation with the severity of the renal disease as indicated by urinary albumin excretion [r=0.55 p>0.05], such results point to the possibility that ET-1 is involved in diabetic nephropathy. The normoal-buminuric group showed significant increase of ET-1 compared lo controls, this may indicate that ET-1 level may be an earlier marker of diabetic nephropathy than microalbuminuria. Classifying each group according to glycemic control of diabetes [cut point of HbAlc 7%] The subgroups of each group showed non significant change, concerning ET-1 or urinary albumin excretion, this may be due to the fact that the cut point was 7% which is initially lower than other investigators whose ail point was much higher [8.5%], they showed in contrast to that the better the control the better the effect on diabetic nephropathy. Mreviations: Finally it can be concluded that ET-1 appears to be involved in the pathogenesis of diabetic nephropathy. It may be a marker of the early stage of diabetic nephropathy as microalbminruia or may be an earlier marker than microalbuminuria that may appear in the normoproteinuric stage. Also the degree of glycemic control does not affect the ET-1 level or degree of albumin exertion in the same stage of diabetic nephropathy.