Clinical Utility of Cytokeratins for Accurate Diagnosis of Hepatocellular Carcinoma Among Hepatitis C Virus High-Risk Patients.

OBJECTIVES: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Cytokeratins are a marker of hepatic progenitor cells and act as a key player in tumor invasion. Herein, we sought to develop a novel score based on the combination of cytokeratin 18 (CK18) and cytokeratin 19 (CK19) with routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Serum CK18, CK 19, α-fetoprotein, albumin and platelets count were assayed in HCC patients (75), liver cirrhosis patients (55) and healthy control (20). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CK-HCC = CK 19 (ng/ml)×0.001+ CK18 (ng/ml)×0.004 + AFP (U/L)×5.4 - Platelets count (×109)/L×0.003 - Albumin (g/L)×0.27-36 was developed. CK-HCC score produces AUC of 0.919 for differentiating patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.3 (i.e., less than 1.3 the case is considered cirrhotic, whereas above 1.3 it is considered HCC. CONCLUSION: CK-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

Diagnostic Performance of Epithelial Cell Adhesion Molecule for Early Detection of Hepatocellular Carcinoma Among HCV High-Risk Patients.

OBJECTIVE: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Epithelial cell adhesion molecule (EpCAM), α-fetoprotein, albumin, and platelets count were assayed in HCC patients (98), liver cirrhosis patients (77). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. RESULTS: A novel score named EpCAM-HCC = AFP (U/L) × 0.11 - Albumin (g/dl) × 1.5 + EpCAM % × 2.9 - Platelets count (×109)/L× 0.75 - 93. EpCAM-HCC score produce AUC of 1 for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.7 (i.e., less than 1.7 the case is considered cirrhotic, whereas above 1.7 it is considered HCC. CONCLUSION: EpCAM-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

Gypsogenin Battling for a Front Position in the Pentacyclic Triterpenes Game of Thrones on Anti-Cancer Therapy: A Critical Review-Dedicated to the Memory of Professor Hanaa M. Rady.

In the last decade, gypsogenin has attracted widespread attention from medicinal chemists by virtue of its prominent anti-cancer potential. Despite its late identification, gypsogenin has proved itself as a new anti-proliferative player battling for a frontline position among other classic pentacyclic triterpenes such as oleanolic acid, glycyrrhetinic acid, ursolic acid, betulinic acid, and celastrol. Herein, we present the most important reactions of gypsogenin via modification of its four functional groups. Furthermore, we demonstrate insights into the anti-cancer activity of gypsogenin and its semisynthetic derivatives and go further by introducing our perspective to judiciously guide the prospective rational design. The present article opens a new venue for a better exploitation of gypsogenin chemical entity as a lead compound in cancer chemotherapy. To the best of our knowledge, this is the first review article exploring the anti-cancer activity of gypsogenin derivatives.

Circulating Tumor Cells in Breast Cancer: A Step Toward Precision Medicine for Real-Time Monitoring of Metastasis.

BACKGROUND/AIMS: Tumor metastasis involves the dissemination of malignant cells into the basement membrane and vascular system contributes to the circulating pool of these markers. In this context our aim has been focused on development of a non-invasive score based on degradation of glycosaminoglycans in the extracellular matrix for assessment of metastasis in patients with breast cancer. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of Metastases in patients with breast cancer. MATERIAL & METHODS: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19) and CA15.3 were assayed in metastatic breast cancer patients (88), non-metastatic breast cancer patients (129) and healthy control (32). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named CTC-MBS = CA15.3 (U/L) × 0.08 + CK 18 % × 2.9 + CK19 × 3.1. CTC-MBS score produces AUC of 1 for differentiate patients with metastatic breast cancer from those with non-metastatic breast cancer with sensitivity and specificity of a cut-off 0 (i.e., less than 0 the case is considered metastatic, whereas above 0 it is considered non-metastatic. CONCLUSION: CTC-MBS score is a novel, non-invasive and simple can applied to discriminate patients with metastatic breast cancer and could replace CA15.3 during screening and follow-up of breast cancer patients.

Diagnostic Performance of Circulating Tumor Cells for Predicting of Hepatocellular Carcinoma in Hepatitis C Virus-High Risk Patients: Role of Liquid Biopsy.

PURPOSE: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of HCC. METHODS: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19), albumin, platelets count, and α-fetoprotein were assayed in HCC patients (42), liver cirrhosis patients (83) and healthy control (20). RESULTS: Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named HCC-CTCs = AFP (U/L) × 0.08 - Albumin (g/dl) × 84 + CK 18 % × 2.9 + CK19 × 3.1- Platelets count (×109)/L× 0.75- 510. HCC-CTCs score produce AUC of 1 for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 0. CONCLUSIONS: HCC-CTCs score could replace AFP during screening of HCV patients and early detection of HCC.

In vivo Study of a Newly Synthesized Chromen-4-one Derivative as an Antitumor Agent against HCC.

BACKGROUND: Chromenes are a wide group of natural compounds that can be synthesized chemically. The chromen-4-one nucleus acts as a skeleton for varieties of additional active groups that makes the chromene activity vary between antioxidant and anti-inflammatory agents. In the present study, a newly synthesized chromene compound exhibits different behaviors other than anti-inflammatory and antioxidant activities that it is the first time that a member of chromen-4-one compound can control the cancer progress. Inflammation is the first step in tumor development where the severity grade can potentiate tumor growth and progression. In many tumors, pro-inflammatory genes record high expression level such as tumor necrosis factor (TNF-α) and vascular endothelial growth factors (VEGF). These pro-inflammatory factors act as rate limiting steps in tumor initiation, and controlling its expression acts as an early therapeutic way to control the tumor proliferation. The chromone derivatives have biological activities such as anti-inflammatory and anti-tumor activity. METHODS: In the present study, hepatocellular cancer (HCC) induced by diethylnitrosamine (DEN) in rats and then treated with the new chromene derivative and the parameters TNF-α, VEGF, p53, Cyt C, MMP-9, Bcl2, and Bax were measured. RESULTS: The treatment strategy Ch compound is to downregulate pro-inflammatory gene expression of early genes as TNF-α as well as VEGF and subsequently control other factors such as p53, Cyt C, and MMP-9. Also, retrieve the balance between Bcl2 and Bax proteins in DEN-induced HCC in rats. CONCLUSION: The ability of the new Ch derivative to control the primary initiators of HCC such as TNF-α offers this derivative an anti-tumor activity and encourages further researches to follow and monitor its effect on the molecular level.

MicroRNA-25 Exerts an Oncogenic Function by Regulating the Ubiquitin Ligase Fbxw7 in Hepatocellular Carcinoma.

BACKGROUND: MicroRNA (miRNA) expression abnormalities are implicated in tumor progression. Previous reports have indicated that microRNA-25 (miR-25) acts as a tumor suppressor or oncogene in diverse cancers. However, its molecular mechanisms in hepatocellular carcinoma (HCC) are still unclear. F-box and WD repeat domain 7 (Fbxw7) is a critical tumor suppressor and is one of the most important deregulated proteins of the ubiquitin-proteasome system in cancer. Our objective was to elucidate the role of miR-25 and Fbxw7 in HCC and to clarify the mechanism by which Fbxw7 is regulated. METHODS: Fbxw7 expression was estimated in 210 fixed paraffin-embedded HCC samples by immunohistochemistry, and miR-25 expression was evaluated in 142 frozen HCC tissue samples by quantitative real-time PCR. Oncogenic functions of miR-25 and its role in the regulation of Fbxw7 expression were assayed in vitro. RESULTS: miR-25 was overexpressed in HCC tissue compared with adjacent normal tissue and significantly correlated with a poorer prognosis. Moreover, it was inversely correlated with Fbxw7 expression in HCC tissues. Furthermore, miR-25 inhibition significantly reduced the proliferation, migration, and invasion of HCC cells in vitro. CONCLUSION: miR-25 may promote tumor progression in HCC patients by repression of Fbxw7 and could serve as a promising molecular target for HCC treatment.

Diagnostic accuracy of hepatocyte growth factor, Fas/CD95 and Endostatin for non-invasive assessment of hepatic fibrosis in biopsy-proven hepatitis C virus patients.

BACKGROUND/AIM: Evaluation of liver fibrosis in chronic hepatitis C patients (CHC) provides a high value, not only for the diagnosis of the disease, but also for the therapeutic decision. The aim of the current study is the construction of simple non-invasive and more accurate score for liver fibrosis staging in CHC patients and estimating its performance against three published non-invasive indexes. MATERIAL AND METHODS: CHC patients were divided into two groups: an estimated group (n = 75) and validated group (n = 50). Liver fibrosis was tested in biopsies by Metavair score system. Fas/CD95, hepatocyte growth factor (HGF) and endostatin were assayed by enzyme linked immunosorbent assay (ELISA). Statistical analysis was performed by stepwise linear discriminate analysis and area under-receiver operating curves (AUCs). RESULTS: The multivariate discriminate analysis (MDA) selects a function based on absolute values of five biochemical markers; FHEPA (Fas/CD95, HGF, Endostatin, Platelets&Albumin)-Test score = 1.2 × Fas/CD95 (ng/mL) + 0.006 × HGF (pg/mL) + 0.03 × Endostatin (ng/mL) - 0.007 × platelets count(109/L)-3.6 × Albumin (g/dL) - 8.6.FHEPA-Test producesAUCs 0.99, 0.877 and 0.847 to discriminate patients with significant fibrosis (F2-F4), advanced fibrosis (F3-F4) and cirrhosis (F4), respectively. CONCLUSION: FHEPA-Test is considered a novel non-invasive test which could be applied in assessment of liver fibrosis in HCV infected patients. Our novel score was more efficient than Immune Fibrosis Index, Fibrosis Index and FibroQ and thus it could be more applicable, feasible & economic for Egyptian HCV patients. Our Novel Scoring system could be globalized to other populations to confirm its advantageous use in early diagnosis of liver fibrosis.

Development of novel score based on Angiogenic panel for accurate diagnosis of hepatocellular carcinoma among hepatitis C virus high-risk patients.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. HCC is identified with hyper-vascularity feature. Herein, we sought to develop a novel score based on the combination of the most significant angiogenic biomarkers with and routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Angiopoietin II, copper, nitric oxide, albumin, platelets count and α-fetoprotein were assayed in HCC patients (75), liver cirrhosis patients (50) and healthy control (20). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named HCC-AngioScore = AFP (U/L) Albumin (g/dl) × 5.4 + Angiopoietin (ng/ml) × 0.001 + Copper (mg/dl) × (-0.004) + Platelets count (×109)/L × 0.003 + Nitric oxide (µ mol/L) × 0.27-36 was developed. HCC-AngioScore produce AUC of 0.919for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 0 (i.e., less than 0 the case is considered cirrhotic, whereas above 0 it is considered HCC. CONCLUSION: HCC-AngioScore could replace AFP during screening of HCV patients and early detection of HCC.

New Biomarkers as Prognostic Factors for Cardiovascular Complications in Type 2 Diabetic Patients.

This study was initiated to explore some novel biomarkers like pro-inflammatory markers (chemerin and visfatin) and anti-inflammatory marker (omentin-1) as prognostic factors for cardiovascular complications in type 2 diabetic patients. Forty diabetic patients without cardiovascular disease, 40 diabetic patients with cardiovascular disease and twenty healthy control counterparts were included in this study. Serum chemerin, omentin-1 and visfatin levels were quantified. Receiver operating characteristic curve analysis was done to identify the cut off value for each marker. The mean serum level of chemerin was 57.65 ± 15.69 ng/l in diabetic patients versus 93.97 ± 26.62 ng/l for the cardio-diabetic ones (P < 0.0001). The mean serum level of omentin-1 was 8.77 ± 1.53 ng/ml in diabetic patients versus 1.76 ± 0.96 ng/ml for the cardio-diabetic ones (P < 0.0001). The mean level of visfatin was 1.44 ± 0.71 ug/l in diabetic patients versus 3.92 ± 3.32 ug/l for the cardio-diabetic ones (P < 0.0001). Chemerin and Visfatin levels were significantly enhanced in the cardio-diabetic patients with increasing C-reactive protein (CRP), triglycerides (TG), fasting blood glucose (FBG), micro-albumin and cholesterol. Omentin-1 level was significantly reduced in the cardio-diabetic patients with increasing CRP, TG, FBG, and cholesterol. It was observed that the area under curve for chemerin, omentin-1and visfatin was 0.877, 0.998 and 0.735, respectively. In conclusion, this study evidences that the measuring serum levels of chemerin, omentin-1 and visfatin may help in the prognosis of cardiovascular complications in type 2 diabetic patients.

Diagnostic performance of extrinsic apoptosis pathway in hepatitis C virus patients: apoptosis fibrosis crosstalk.

BACKGROUND/AIM: Liver fibrosis assessment and evaluation of disease severity in hepatitis C virus (HCV) patients provides useful information for therapeutic decisions. Chronic HCV infection is associated with increased levels of peripheral T cell apoptosis. The aim was to study whether peripheral blood T lymphocyte apoptosis markers may contribute to clinical progression, and develop a simple index based on combination of apoptosis and routine biomarkers for accurate evaluation of fibrosis stages in HCV patients. PATIENTS AND METHODS: Peripheral blood T lymphocytes were isolated from 72 patients with hepatitis C virus and 25 healthy control individuals. Serum samples were collected at time of liver biopsy. Liver fibrosis was tested in biopsies using the Metavair score system. Stepwise linear discriminate analysis and area under receiver-operating characteristic curves were utilized to produce a predictive score comprising significant apoptosis biomarkers. RESULTS: A novel score named apoptosis fibrosis index (AFI) was created on the basis of a combination of CD8/Annexin, albumin and platelets. The multivariate discriminate analysis selected a score based on absolute values of the three biochemical markers; score = 5.8 + 0.008×CD8/Annexin-V (%) - 1.4×Albumin (g/dl) - 0.001×Platelet count (10/L), where 5.8 considered numerical constant. AFI produce an area under the curve of one for significant fibrosis, 0.80 for advanced fibrosis, and 0.889 for cirrhosis. CONCLUSION: Apoptosis biomarkers in HCV patients were associated with liver fibrosis. AFI score, a novel noninvasive test, can be used easily for the prediction of liver fibrosis stage and may decrease the need for liver biopsy in hepatitis C virus Egyptian patients.

Effect of co-administration of Bee honey and some chemotherapeutic drugs on dissemination of hepatocellular carcinoma in rats.

Alternative and complimentary usage of the natural compound has raised hopes of finding curative options for liver hepatocarcinogenesis. In the present study, the curative effect of bee honey against diethylnitrosamine (DEN) (50 mg/kg) and carbon tetrachloride (CCl4) (2 mg/Kg)-induced hepatocellular carcinoma (HCC) in male rats in the presence or absence of some chemotherapeutic drugs, Cisplatin (Cis), Cyclophosphamide (CY) and 5- Fluorouracil (5-FU) were investigated. The obtained results demonstrated that treatment with DEN/CCl4 caused oxidative stress as assigned by the increase in malondialdehyde (MDA) and fall in glutathione (GSH) content. Meantime detraction in the antioxidants, including superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and glutathione peroxidase (GPx) was observed. Also, the results showed induction of inflammation as reflected by an increase in the levels of both α- fetoprotein and α- fucosidase in the liver. This was accompanied by changes in the hepatic function biomarkers which characterized by the increased levels of transaminases (AST, ALT), alkaline phosphatase (ALP) and γ-Glutamyl transferase (γ-GT) and decrease in total protein content in the serum. In conclusion, the combination of the selected drugs and bee honey may be an effective chemo- preventive and therapeutic strategy for treating DEN and CCl4-induced HCC.

Effects of zinc supplementation on oxidant/antioxidant and lipids status of pesticides sprayers.

Background Excess exposure to pesticides induces oxidative stress and causes alteration in the lipid profile Objectives The study aimed to evaluate the effects of Zinc (Zn) supplementation on the oxidant/antioxidant and lipid status in pesticide sprayers. Methods Forty pesticide sprayers were included in the study. Blood lipids, malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), and Zn were estimated; before and after Zn supplementation. Results Statistical analysis revealed that after Zn supplementation, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and MDA were significantly decreased. However, there was a significant increase in the high density lipoprotein (HDL), SOD, GPx, and Zn levels. After Zn supplementation, significant inverse correlations were detected between the Zn and the levels of MDA, TG, and VLDL, while positive correlation between Zn and the levels of HDL and TC. Conclusions Zn supplementation improves the oxidative/antioxidants and lipid status in pesticide sprayers.

Evaluation of urinary 8-hydroxy-2-deoxyguanosine level in experimental Alzheimer's disease: Impact of carvacrol nanoparticles.

The present study aimed to compare the effect of carvacrol essential oil and carvacrol nanoemulsion against experimental Alzheimer's (AD). Forty male albino rats were used and divided into four groups as follow: control, AlCl3 induced AD, carvacrol oil treated and carvacrol nanoemulsion treated groups. Brain nor-epinephrine, serotonin and dopamine were analyzed by high performance liquid chromatography (HPLC). Levels of brain Thiobarbituric acid-reactive substances (TBARS), Superoxide dismutase (SOD), reduced glutathione (GSH), cholinesterase, and advanced oxidation protein product (AOPP) were evaluated. Urinary 8-hydroxyguanosine (8-OHdG) level was evaluated by HPLC. Brain Cyclooxygenase 1 and 2 (COX 1and 2) were analyzed by immunohistochemistry. AD induced by AlCl3 in rats was depicted by the significant increase in the neurotransmitters levels which is accompanied with high degree of oxidative stress that was revealed in the elevated level of urinary 8-OHdG along with significant elevation in AOPP, TBARS, and cholinesterase levels and a significant decrease in SOD and GSH; these results are confirmed by immunohistochemistry analysis of COX 1 and 2. On the other hand, the treatment with carvacrol oil and carvacrol nanoemulsion were capable of mitigate effects mediated by AlCl3 administration in treated rats. While the treatment with both approached succeeded to retract the negative impact of AlCl3; but the effect of carvacrol nanoemulsion was more notable than the essential oil. Carvacrol oil and carvacrol nanoemulsion were eminent to overturn AlCl3 induced brain AD which could be imputed to antioxidant and anti-inflammatory capabilities of carvacrol to alter oxidative stress effect. In extension; carvacrol nanoemulsion were evident to give more effective and efficient way in carvacrol delivery to pass through blood brain barriers and ameliorate brain changes.

Acetylcholinesterases from entomopathogenic nematode Heterorhabditid bacteriophora: Susceptibility to insecticides and immunological characteristics.

Acetylcholinesterases (AChEs) from the infective juveniles (IJs) of entomopathogenic nematode (EPN) have been investigated with respect to their susceptibility to insecticides and immunological characteristics, aiming at nominating the most compatible insecticide(s) to be used in conjunction with the most insecticide-tolerant EPN strain before incorporation in integrated pest management (IPM) programs. The inhibition kinetics of two purified AChE isoenzymes, AChEAII and AChEBI isolated from Heterorhabditid bacteriophora EM2 strain, by different insecticides revealed that the insensitivity to inhibition by such insecticides could be arranged in a descending order as; methomyl>carbofuran>acetamiprid>oxamyl>malathion. Except for malathion, the insecticides competitively inhibited AChEs with Ki values ranging from 0.1 to 15mM and IC50 values from 1.25 to 23mM. The two AChE isoforms are several folds less sensitive to inhibition by methomyl and carbofuran compared to those previously reported for other insect species. AChEBI was used as an immunogen to raise anti-AChEBI antisera in rabbits. The prepared antisera cross-reacted with AChEs of five different heterorhabditid nematode strains implying the presence of common epitopes shared along all the examined strains. Such studies could aid in the rational selection of the compatible insecticide(s) and the prepared polyclonal anti-AChE antisera would be a valuable immunodiagnostic tool for evaluating the most insecticide-tolerant EPN strain(s) in IPM programs.

Regression of murine Ehrlich ascites carcinoma using synthesized cobalt complex.

Cisplatin as a chief chemotherapy has nephro-toxicity and so we have tried to develop a novel antitumor drug based on a combination of cobalt metal ion with an organic moiety. The antitumor activity of the complex was tested in vitro and in vivo against murine Ehrlich ascites carcinoma (EAC). Antioxidant capacity and nucleic acids content were determined. Cobalt(ii) diacetyl monoxime-2-hydrazinopyridine complex significantly diminished tumor load. It decreased the tumor proliferation rate and obviously increased the life span of EAC-bearing mice. It reversed the haematological parameters back towards normal, reduced liver enzymes and urea, and increased albumin and total protein. Antioxidant parameters levels were reversed towards normal. An assessment was conducted by comparing these results with those obtained using the standard drug, cisplatin. The results suggest that the cobalt complex can be considered as a potent anticancer agent as it showed appreciable antitumor activity in EAC-bearing mice that was almost analogous to that of the reference standard, cisplatin.

Noninvasive estimation of liver fibrosis in biopsy-proven hepatitis C virus-infected patients: angiogenic fibrogenic link.

BACKGROUND/AIM: The assessment of liver fibrosis provides useful information not only for diagnosis but also for therapeutic decisions. This study aimed to develop and evaluate a predictive score named the angiogenic index (Angio-Index) for liver fibrosis staging and to compare Angio-Index by King, Gotebörg University Cirrhosis Index, Lok, FIB-4, and aspartate aminotranferase/alanine aminotranferase scores in hepatitis C virus-infected patients. PATIENTS AND METHODS: Serum levels of angiopoietin-2, basic fibroblast growth factor, hepatocyte growth factor, and endostatin were assayed using an enzyme-linked immunosorbent assay in 122 HCV patients represented in two sets (estimation group and validation group). Stepwise linear discriminant analysis and area under receiver-operating characteristic curves (AUCs) were utilized to produce a predictive score comprising significant angiogenic biomarkers. RESULTS: A novel score named the Angio-Index score was created on the basis of a combination of angiopoietin-2, basic fibroblast growth factor, hepatocyte growth factor, and endostatin. Angio-Index produces an AUC of 0.90 for significant fibrosis, 0.865 for advanced fibrosis, and 0.857 for cirrhosis. The Angio-Index score correctly classified 71% of the significant fibrosis (F2-F4) with a sensitivity of 93% and a specificity of 91%. The Angio-Index had a similar AUC in the validation study. The above six scores showed lower AUCs than Angio-Index. CONCLUSION: Whereas liver biopsy is invasive, costly, and associated with complications, Angio-Index is simple, noninvasive, and more accurate; it may decrease the need for liver biopsy in Egyptian patients.

Biochemical and molecular evidences for the antitumor potential of Ginkgo biloba leaves extract in rodents.

Hepatocellular carcinoma (HCC) is one of the deadliest primary cancers, with a 5-year survival rate of 10% or less. This study was undertaken to elucidate the underlying biochemical and molecular mechanisms in favor of N-nitrosodiethylamine-induced hepatocellular carcinoma. Furthermore, the aim of this work was extended to explore the efficacy of Ginkgo biloba leaves extract in deterioration of HCC in rats. In the current study, HCC group experienced significant downregulation of ING-3 gene expression and upregulation of Foxp-1 gene expression in liver. Treatment of HCC groups with Ginkgo biloba leaves extract resulted in upregulation of ING-3 and downregulation of Foxp-1 gene expression in liver. In addition, there was significant increase in serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and glypican-3 (GPC-3) levels in HCC group versus the negative control group. In contrast, the groups with HCC subjected to either high or low dose of Ginkgo biloba leaves extract elicited significant reduction (P<0.05) of AFP, CEA and GPC-3 in serum compared to the untreated HCC rats. Besides, histological examination of liver tissue sections of rats in HCC group revealed typical anaplasia. Interestingly, treatment with Ginkgo biloba leaves extract elicited marked improvement in the histological feature of liver tissue in HCC groups. In conclusion, this research indicated that the carcinogenic potency of N-nitrosodiethylamine targeted multiple systems on the cellular and molecular levels. In addition, the results of the current study shed light on the promising anticancer activity of Ginkgo biloba leaves extract in treatment of hepatocellular carcinoma induced chemically in the experimental model through its apoptotic and antiproliferative properties.

Chromatographic determination of some biomarkers of liver cirrhosis and hepatocellular carcinoma in Egyptian patients.

Metabolomics has been shown to be an effective tool for disease diagnosis, biomarker screening and characterization of biological pathways. A total of 140 subjects were included in this study; urine metabolomes of patients with liver cirrhosis (LC, n = 40), patients with hepatocellular carcinoma (HCC; n = 55) and healthy male subjects (n = 45) as a control group were studied. Gas chromatography/mass spectrometry-based urine metabolomics profiles were investigated for all participants. Diagnostic models were constructed with a combination of marker metabolites, using principal components analysis and receiver operator characteristic curves. A total of 57 peaks could be auto-identified of which 13 marker metabolites (glycine, serine, threonine, proline, urea, phosphate, pyrimidine, arabinose, xylitol, hippuric acid, citric acid, xylonic acid and glycerol) were responsible for the separation of HCC group from healthy subjects. Also, eight markers metabolites (glycine, serine, threonine, proline, citric acid, urea, xylitol and arabinose) showed significant differences between the LC group and healthy subjects. No significant difference was detected between HCC and LC groups regarding all these metabolites. Metabolomic profile using GC-MS established an optimized diagnostic model to discriminate between HCC patients and healthy subjects; also it could be useful for diagnosis of LC patients. However, it failed to differentiate between HCC and LC patients.

Role of mesenchymal stem cells versus angiotensin converting enzyme inhibitor in kidney repair.

AIM: The current study sought to clarify the role of bone marrow derived mesenchymal stem cells (BM-MSCs) and adipose tissue derived mesenchymal stem cells (AD-MSCs) in repressing nephropathy in the experimental model. Moreover, the aim of this work was extended to compare between stem cells role and angiotensin converting enzyme inhibitor in kidney repair. METHODS: Isolation and preparation of MSCs culture, flow cytometry using CD34, CD44 and CD105 cell surface markers, biochemical analyses for determination of serum creatinine, urea, transforming growth factor ß (TGF-ß), cystatin C (CYS-C) and urinary N-Acetyl-ß-D-Glucosaminidase (UNAG), and histopathological investigation of kidney tissue sections were performed. RESULTS: The results of the present study revealed that single intravenous infusion of MSCs either derived from bone marrow or adipose tissue was able to enhance renal reparative processes through significantly decreased serum creatinine, urea, TGF-ß and CYS-C levels as well as UNAG level and significantly increase glomerular filtration rate. Additionally, the histopathological investigations of kidney tissues showed that MSCs have significant regenerative effects as evidenced by the decrease in focal inflammatory cells infiltration, focal interstitial nephritis and congested glomeruli as well as degenerated tubules. CONCLUSION: The current data provided distinct evidence about the favourable impact of AD-MSCs and BM-MSCs in attenuation of cyclosporine-induced nephropathy in rats through their ability to promote functional and structural kidney repair via transdifferentiation.