Circulating apolipoprotein alpha1, haptoglobin and alpha2 macroglobulin as fibrosis markers in chronic hepatitis c patients

Hepatitis C virus [HCV] infection is one of the commonest chronic liver diseases worldwide. Progression to chronic disease occurs in the majority of HCV infected patients. The aim of the present work was to study serum levels of alpha2 macroglobulin [alpha2-MG], Apolipoprotein A1 [Apo-1] and Haptoglobin [HP] as non-invasive index of the presence of cirrhosis in chronic hepatitis C patients in relation to the histopathological findings. The study was carried out on 20 patients with chronic HCV and liver cirrhosis [Group I], 20 patients with chronic HCV without liver cirrhosis [Group II] and 10 healthy subjects of mathing age and sex as controls [Group III]. Quantitative estimation of alpha2-MG, HP and Apo AI in serum was done using turbidimetry. The mean serum level of alpha2-MG was significantly higher in group I than in groups II, III [F=12.8] [p=0.00]. On the other hand, Serum Apo A1 and HP were significantly lower in group I than in groups II, III [F=5.9 and 26.3] [p=0.005 and 0.00]. On the other hand, no significant difference was found between groups II and III. Significant positive correlation was observed between serum alpha2-macroglobulin and Child Pugh score, Grading and staging of liver pathology [P<0.05]. On the other hand, significant negative correlation was noticed between serum Apo-1, HP and Child Pugh score, histopathological grading and staging [P<0.05]. Elevated serum levels of alpha2 macroglobulin in addition to low levels of apolipoprotein A1 and haptoglobin might be considered as valuable non invasive parameters for predicting the occurrence of cirrhosis in chronic hepatitis C patients

Alterations of E-cadherin and MMP-2 in cancer prostate

E-cadherin plays a crucial role in epithelial cell-cell adhesion and maintenance of tissue architecture. Alterations in expression or function of this protein result in loss of intercellular adhesion, with possible consequent increased tumor progression, metastasis, and poor prognosis in different cancer types. Matrix metalloproteinases [MMPs] constitute a multi-gene family of proteolytic enzymes that are capable of degrading connective tissue and almost all extracellular matrix components. Overexpression of MMPs is usually associated with the acquisition of invasiveness by tumor cells, cancer progression, angiogenesis and metastasis. To examine the expression of E-cadherin and MMP-2 in male prostatic lesions using immunohistochemical staining. 30 cases of formalin-fixed, paraffin embedded tissues of male prostatic lesions were examined for the expression of E-cadherin and MMP-2 using immunohistochemistry utilizing rabbit antihuman polyclonal antibodies for E-cadherin and MMP-2. The tissue specimens comprise samples of 25 prostatic adenocarcinoma [PAC] and five benign prostatic hyperplasia [BPH]. H and E histological examination revealed that of the 25 studied malignant cases, six were combined grade CG 10; three were CG9; two were CG8; three were CG7; four were CG6; and seven were CG5, according to combined Gleason's grading system. Immunostaining showed altered expression [cytoplasmic] of E-cadherin in poorly and moderately differentiated foci of carcinoma [CG6-10]. Cell membrane expression of E-cadherin was seen in well differentiated foci as well as in BPH. However for immunostaining of MMP-2, very weak expression of it was seen in BPH as well as in normal glands adjacent to tumor cells. Mild to moderate staining intensity was observed in well differentiated PAC and moderate intensity was seen in moderately differentiated PAC. Overexpression of MMP-2 in the form of positive cytoplasmic aggregates was shown in poorly differentiated PAC. The results suggest the implication of the altered expression of E-cadherin and MMP-2 in increased aggressiveness of the tumor with its subsequent increased invasiveness and progression. Also show that increased expression of collagenase type IV [MMP-2] and decreased expression of E-cadherin are associated with increasing Gleason score and that the expression of MMP-2 and E-cadherin exhibited strongest association with advanced prostate cancer

Study of oncogenic viruses in patients with malignant non Hodgkin's lymphoma

Background: The number of viruses associated with lymphoma has increased in the last 20 years. Several studies from different parts of the world have indicated a potential association between a variety of lymphoproliferative disorders and viruses, as hepatitis C virus [HCV] hepatitis B virus [HBV] and Epstein-Barr Virus [EBV]

Aim of the work: The aim of this work was to study the role of oncogenic viruses in patients with malignant Non Hodgkin's lymphoma [NHL], also, to study the correlation of different subtypes of B cell-NHL and the viruses detected

Patients and methods: Twenty cases of B cell-NHL were investigated for serum HCVAbIgG, HBsAg by Elisa technique. Also HCV-RNA sequences as well as HBV-DNA and EBV-DNA sequences were detected in the tumor tissues by using RT-PCR. HCV is also examined by immunohistochemical method. In addition 10 cases of non neoplastic lymphadenopathy were taken as a control

Results: Out of the 20 B cell-NHL patients 6 [30%] cases showed positive HCV AbIgG, and 8 [40%] cases showed positive HBSAg in their sera. In four cases out of the 6 HCV positive patients, HCV-RNA sequences were detected by PCR, and in 7 patients out of the 8 HBV positive patients, HBV-DNA sequences were present. 5 [25%] out of the 20 cases were negative for both HBV-DNA and HCV-RNA sequences. EBV was positive in all B cell-NHL cases by EBNA gene while it was detected in 9 [45%] out of the 20 NHL cases by LYDMA gene. A coinfection was detected between HCV and EBV in 2 cases out of the 6 HCV positive cases, and between HBV and EBV in 3 out of the 7 HBV positive cases. Two cases were positive for EBV only, and negative for both HCV and HBV sequences. All control cases were positive for polyclonal EBV and negative for HCV-RNA and HBV-DNA sequences, 3 [15%] cases out of the 20 cases of B cell-NHL showed positive staining in the tissues for HCV-Abs by immunohistochemical method. All positive cases of the studied viruses showed no predilection for a particular subtypes of B-cell NHL

Conclusion: A significant association was present between HBV, EBV and B cell-NHL [P= 0.05 and 0.043 respectively] and the association between HCV and B cell-NHL is not significant. This raised the possibility that these viruses may play an etiologic role in the induction of B cell-NHL disease. No relation was found between the different histological subtypes of NHL and the viruses detected

Serum soluble transferrin receptors in patients with chronic hepatitis C

Recently, it has been found that iron is an important element in the natural history of hepatitis C. Serum markers of iron stores are frequently increased in chronic hepatitis C infected patients and therefore, detection of soluble transferrin receptor[sTfR] may allows for quantitative evaluation of intracellular iron. The aim of the present study was to study serum levels of soluble transferrin receptors in patients with chronic HCV. The study was carried out on 40 patients classified into three groups. Group I enrolled 10 chronic HCV with high serum iron and ferritin, Group II included 10 patients with chronic HCV with normal serum iron and ferritin [Both groups I, and II had no cirrhosis], Group III compromised of2O patients with chronic HCV and liver cirrhosis. Also 10 healthy subjects were taken as control. Soluble transferrin receptors were measured in patient sera using humans TJJ? ELISA Kit. The mean serum sTfR was significantly lower in group III than in groups I, II and IV. Also, it was significantly lower in group I than in groups II and IV On the other hand, no significant difference was found between groups II and IV. Correlation study revealed significant negative correlation between serum sTfR and serum iron and ferritin in groups L II and III. Moreover, in group III significant negative correlation was noticed between serum sTfR and staging [r0.83, 0.00]. sTfR can be regarded as a valuable and specific tool for investigating tissue iron that can be used to predict the degree of hepatocellular damage and progression into advanced fibrosis and subsequent cirrhosis

Immunohistochemical study of biomarker "P53" in premalignant lesions

Precancerous lesions of the oral mucosa offer a particularly interesting area of research for understanding the process of cancer formation and its prevention. This study was conducted to investigate P 53 protein expression in cancerous, precancerous conditions and adjacent normal mucosa using an immunohistochemical technique, in an attempt to study its role in the progression of oral premalignant lesions. The immunohistochemical results were further correlated with the clinicopathological parameters of the studied patients. This study included 6 cases of oral squamous cell carcinoma [OSCC], 6 cases of oral lichen planus [OLP] and 6 cases of leukoplakia. The results revealed that P53 accumulation was more strongly observed in OSCC than OLP and leukoplakia. A positive significant correlation was found between the severity of P53 immunoreactivity and smoking, and the frequency of samples showing dysplastic changes. While no significant correlation was found between P53 severity and the age of the patients or lesion duration. It appears that immunohistochemical evaluation of P53 expression may be a practical tool to select cases of oral lichen planus and leukoplakia with a high risk of neoplasia

in vivo protective effects of silymarin on DMN-induced hepatotoxicity in rats

Dimethyl nitrosamine [DMN] is a very potent chemical carcinogen which occurs naturally in the environment and in a wide variety of food stuffs, and can be formed in the body by nitrosation of secondary or tertiary amines in the presence of nitrite, nitrate or nitrogen oxides. Silymarin is a powerful antioxidant and has a potent free radical scavenging activity, said to protect cells of liver, brain and other cells in the body from toxins. To examine the in vivo protective effects of silymarin on the induced oxidative damage in livers of DMN-intoxicated rats histologically and immunohistochemically. The ability of silymarin to protect and detoxify DMN toxicity was examined in rat livers. Dietary pretreatment of rats [body weight 125-135 g] with silymarin [0.9 mg/g body weight] for two weeks prior to the intraperitoneal injection of DMN, reversed the hepatotoxic effects of DMN, as examined histologically. DMN in two doses of 15 micro g/kg or 25 micro g/kg was injected. After DMN treatment, the animals were fed with diet with silymarin or without for 48 hours. Rats were sacrificed 48 hours after DMN injection. The immunoreactivity of cells of rats' livers was examined for antibodies of heat shock protein 70 [HSP70] [HSPs are a family of proteins that are triggered to be induced when a cell undergoes environmental stresses including oxidative stress, pathogenic conditions ...etc]. The histological evaluation revealed prominent changes in groups received DMN in high dose more than low dose. Treatment with silymarin reversed this effect. The immunohistochemical assay for the stress-protective proteins "HSP70" showed that treatment with silymarin triggered more expression of this protein. Silymarin can provide substantial protective effect against DMN-induced hepatic oxidative damage with therapeutic potential to be used in human

Biomonitoring environmental stresses in female endometrial carcinoma versus hyperplasia using HSP70 and HER-2/neu proteins

The intracellular distribution of heat shock or stress-response proteins [HSP], that are triggered to be induced when a cell undergoes environmental stresses, has presumably protective function to enable cells to increase resistance to the harmful effects of pathogens, heavy metal, heat shock, chemical mutagens or carcinogens. HER-2/neu proto-oncogene is a member of epidermal growth factor receptor or erb gene family that plays a key role in the regulation of normal oncogenic cell growth and has been linked to prognosis and response to therapy. To examine the in vivo environmental stresses in female endometrial carcinoma versus hyperplasia using immunohistochemical staining of HSP70 and HER-2/neu proteins. In the present study, 25 cases of formalin-fixed, paraffin embedded human endometrial tissue sections were examined for the expression of HSP70 and HER-2/neu by immunohistochemistry using a rabbit antihuman HSP70 monoclonal antibody and a rabbit anti-human HER-2/neu polyclonal antibody, respectively. The tissue specimens comprise samples of endometrial hyperplasia and cancers, of which five cases were normal control, four cases were simple hyperplasia, five cases were complex hyperplasia with two cases having atypia, five cases were well differentiated endometrial carcinoma [EC], three cases were moderately differentiated EC, and the last three cases were poorly differentiated EC. Positive staining for HSP70, seen as fine dark brown granules mainly confined to the cytoplasm, was observed in all sections examined. There was marked cellular heterogeneity, ranging from cells completely devoid of staining or with faint staining in poorly differentiated endometrial carcinoma to cells with very intense nuclear and cytoplasmic staining [4+] in normal tissue adjacent to the dysplastic epithelium and in cases of simple endometrial hyperplasia, suggesting a possible protective role of HSP70 in the different stages of carcinogenesis. On the other hand, immunoreactivity for HER-2/neu showed different pattern. Positive strong staining was identified cytoplasmic and/or in cell membrane in poorly, moderately and well differentiated endometrial carcinomas. No immunostaining was observed in normal epithelium and in two cases of simple endometrial hyperplasia. The results suggest that HER-2/neu expression may play a role in the pathogenesis and progression of endometrial carcinoma and together with HSP70 could prove useful biomarkers for diagnosis or disease stratification