Circulating MiRNA-21 and programed cell death [PDCD] 4 gene expression in hepatocellular carcinoma [HCC] in Egyptian patients

Background: Circulating microRNAs [miRNAs] are endogenous, small [17-25 nucleo-tides] non-coding RNAs that are overexpressed in many human cancers including hepatocellular carcinoma [HCC]. Moreover, circulating miRNAs can reflect the level of tissue miRNAs, so could be potential tumor markers. miRNA-21 regulates post-transcriptional expression of tumor suppressor gene; programed cell death 4 [PDCD4] gene which implies that miRNA-21 might be a novel diagnostic and/or prognostic marker for cancer

Objective: To evaluate the diagnostic and prognostic potential of circulating miRNA-21 and study the expression of PDCD4 gene as a target of miRNA-21 in HCC in Egyptian patients

Subjects and methods: This study was conducted on 30 HCC patients, 20 chronic liver disease [CLD] patients due to HCV infection and 20 healthy subjects. Serum alpha fetoprotein [AFP] was measured for all participants. The relative plasma expression of each of miRNA-21 and PDCD4 gene was determined in whole blood samples using real-time polymerase chain reaction

Results: The results revealed over expression of miRNA-21 and under expression of PDCD4 gene in HCC group [p < 0.05] compared to both CLD and healthy subjects, while no significant change was detected between CLD and healthy subjects. miRNA-21 expression was negatively correlated with PDCD4 gene expression. miRNA-21 expression increased significantly with presence of cirrhosis, increased number of focal lesions, larger size of tumor, advanced tumor stage and presence of vascular invasion. Receiver Operator of Characteristics [ROC] curve analysis of plasma miRNA-21 revealed that, at a cut-off value of 3.93 [fold expression], the sensitivity and specificity for differentiation of HCC cases were 93% and 90%, respectively

Conclusion: Circulating miRNA-21 could be a novel early diagnostic and prognostic biomarker for detection of HCC. Approaches interfering with the miRNA-2 l/PDCD4-axis, or releasing PDCD4 expression, may have a strong basis for therapeutic uses in cancer in the future

Serum hepcidin level and disease course of acute leukemia in children

Acute leukemia [AL] is a heterogeneous group of hematopoietic neoplasms and it is the most common childhood malignancy. Many patients with AL develop severe anemia that requires multiple blood transfusions. Hepcidin expression may play a role in anemia which is often seen in these patients. The aim of this study is to evaluate the role of hepcidin in acute lymphoblastic leukemia in children in Egypt. 60 patients with acute lymphoblastic leukemia [ALL] and 20 age and gender matched healthy children, taken as control group, were included in the study. Complete blood count [CBC], Serum ALT and serum AST were measured by colorimetric methods. Serum hepcidin and ferritin were measured by ELISA. The study showed a significant difference between newly diagnosed ALL cases and other groups regarding all CBC parameters. There was a significant difference in serum levels of hepcidin and ferritin between studied groups. A significant negative correlation was found between serum level of hepcidin and ferritin and each of hemoglobin level and reticulocytic count%, while significant positive correlation was found between hepcidin and ferritin serum levels. From this study, it could be concluded that serum hepcidin level is elevated in ALL children patients at time of diagnosis and correlates with the disease extent. Hepcidin may be one of the serum markers that accounting for anemia associated with ALL in children

study of thyroid hormones profile in breast cancer patients

Breast cancer is a hormone dependent neoplasm, estrogen involvement in breast cancer has been established, however the relationship between thyroid disorders and breast cancer is debated. The aim of this work is to study the changes of thyroid hormones profile in women with breast cancer and to find the relationship between thyroid hormones and E2 in the pathogenesis of breast cancer in premenopausal and postmenopausal women. The study was carried out on 60 subjects, 40 breast cancer patients with age range between 28 to 67 years and 20 healthy female subjects served as control with age range between 28 to 65 years. The studied subjects were subjected to full history taking, clinical and radiological examination, measurement of free triiodothyronine [FT3], free thyroxin [FT4], thyroid stimulating hormone [TSH], anti thyroid peroxidase antibodies [anti Tpo] and estradiol [E2]. The results of this study showed a significant decrease as regarding TSH level [p<0.05] and a high significant increase as regarding anti Tpo level [p<0.001] in patient group when compared to control group. Whereas there is no significant differences as regarding FT3, FT4, E2 and FT3/E2 index. High positive prevalence rate of sub-clinical hyperthyroidism and autoimmune thyroid diseases [p<0.01] in breast cancer patients when compared to controls. It could be concluded that there is a high prevalence of subclinical hyperthyroidism in postmenopausal breast cancer patients, while autoimmune thyroid disorders are more in premenopausal breast cancer patients suggesting the relationship between breast cancer and thyroid disorders

role of calcium channel blockers in the treatment of diabetic nephropathy

Diabetic nephropathy [DNP] is a chronic renal disease [CRD] and a major cause of illness and premature death in people with diabetes mellitus [DM]. It is the single most important cause of end-stage renal disease in the Western world and accounts for more than a quarter of all end-stage renal diseases. This article reviews the current development in DNP and the therapeutic challenge with particular reference to the role of calcium channel blockers. Moreover, renal ischaemia hastens the progression of DNP. Diltiazem and amlodipine have a tendency to reverse the changed parameters toward normal values but do not affect the biochemical parameters. Generally speaking, diltiazem is better than amlodipine in reversing biochemical and histopathological changes produced by DNP, and captopril reverses most of the changed parameters with the exception of the histopathological changes. These agents have nephroprotective properties and delay the progression of DNP

mechanism of action of calcium channel blockers in the treatment of diabetic nephropathy

Three types of calcium channels have been identified voltage-sensitive, receptor operated [cardiac muscle and vascular smooth muscle] and stretch operated [in some blood vessels] channels. Using electrophysiological and pharmacological techniques, three different types of voltage-gated calcium channels have been identified, namely, L-type [for long lasting, large channels], T-type [for transient, tiny channels] and N-type [for neuronal, neither L nor T]. Many compounds are known to have a calcium channel inhibitory effect. Calcium antagonists, based on the specificity of inhibition of the slow calcium current, can be classified into three groups: Group A: for 90 to 100 percent inhibition of calcium influx without change in the sodium current [verapamil, diltiazem and the dihydropyridines]; Group B: for 50 to 70 percent inhibition of calcium influx current without change in the sodium current [bepridil, cinnarizine and prenylamine] and Group C: for agents exhibiting some inhibition of calcium influx [phenytoin, indomethacin and propranolol]. There is now increasing evidence that, certain calcium channel blockers especially the dihydropyridines are more strongly associated with vasodilation of afferent arterioles than of efferent arterioles and also with increase intraglomerular pressure and albuminuria. Thus they have a beneficial effect in terms of reducing proteinuria and slowing the progression of diabetic renal failure