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1.
Artículo en Inglés | MEDLINE | ID: mdl-33416934

RESUMEN

The hepatoprotective activity of heliomycin obtained from the culture broth of actinomycete AB5 against diethylnitrosamine (DEN)-induced hepatic cancer in Wistar rats was estimated. Heliomycin exhibited a significant decrease in the levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) compared to the positive control. For instance, the heliomycin group after 20 weeks showed a significant decline in ALT, AST, and ALP values (70.75 ± 5.12, 140.25 ± 11.75, and 163.25 ± 18.66, respectively) compared to the positive control group (170.00 ± 9.55, 252.75 ± 12.33, and 278.00 ± 21.32, respectively). Additionally, the isolated compound showed a highly significant decrease in serum alpha-fetoprotein (AFP) levels. After 8, 16, and 20 weeks, the mean values of AFP in the heliomycin group revealed a highly significant decrease (33.62 ± 2.46, 30.00 ± 4.05, and 28.50 ± 2.64, respectively) compared to the positive control group (49.45 ± 3.03, 81.90 ± 6.70, and 90.75 ± 5.12, respectively). The histopathological investigation of liver sections supported the results of biochemical analysis. It was demonstrated that heliomycin showed histological improvement of hepatocytes and marked increase of nuclear pyknotic with clear cytoplasm, which is a sign of improving the apoptotic pathway of malignant cells. It also displayed marked fibrosis at most of the malignant cells and the development of some regenerative nodules. Heliomycin showed moderate immunoreactivity with alpha-fetoprotein (AFP), and proliferation cell nuclear antigen (PCNA) compared to the positive control group. To the best of our knowledge, this is the first study to report the anticancer activity of heliomycin against hepatocellular carcinoma in vivo.

2.
J Genet Eng Biotechnol ; 19(1): 17, 2021 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-33492603

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is one of the most frequently diagnosed tumors worldwide with high mortality and morbidity. There is an urgent need for biomarkers to improve the outcomes and early detection of CRC. The sensitivity of traditional CRC tumor markers (carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9)) is not ideal. The levels of leucine-rich-alpha-2-glycoprotein 1 (LRG1) and stem cell factor (SCF) were evaluated, but the combined value of both markers is unclear. This case-control study included four groups: CRC patients before treatments (n = 22), CRC patients after treatments (n = 26), 20 patients with benign tumor, and 20 healthy subjects. Levels of routine biochemical and hematological markers, traditional tumor markers (CA19.9 and CEA), and candidate markers (LRG1 and SCF) were determined. Univariate and multivariate logistic regression analysis and area receiver-operating characteristic analysis (ROC) were used for evaluation the diagnostic performances of single and combined markers. RESULTS: No significance difference in traditional tumor markers CEA, CA 19.9, and neutrophil-lymphocyte ratio (NLR) were found among study groups. SCF, LRG1, and platelet-lymphocyte ratio (PLR) were significantly decreased (p < 0.05) in non-treated CRC patients than after treated CRC. The combination between SCF and LRG1 showed highly significant difference in CRC patients compared with benign, healthy subjects, and among CRC groups (treated and non-treated) (p < 0.0001). The highest areas under curve (AUCs) were observed when LRG1 was used as a single predictor for discriminating CRC from healthy (0.87), benign (0.84), and non-treated CRC vs treated CRC (0.82). AUCs were jumped to 0.90, 0.84, and 0.84 when LRG1 and SCF were combined. CONCLUSION: Our study revealed that LRG1 and SCF were potential diagnostic and follow-up markers for CRC.

3.
Arab J Gastroenterol ; 2020 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-33268243

RESUMEN

BACKGROUND AND STUDY AIMS: MicroRNAs (miRNAs) play key roles in cancer biology; they are used as potential tools in cancer diagnosis. This study investigated the microRNA expression profile of patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Serum microRNA expression profiles (miRNA-29a, miRNA-200, miRNA-335 and miRNA-21) were analysed in 137 patients with HCC and liver cirrhosis and 49 healthy subjects (used as negative controls) using real-time quantitative reverse transcription polymerase chain reaction. Alpha-fetoprotein (AFP), as a routine tumour marker, was also assessed using enzyme-linked immunosorbent assay. RESULTS: The expression levels of miRNA-21, miRNA-335 and miRNA-200 were significantly up-regulated, whereas those of miRNA-29a were remarkably down-regulated in patients with HCC compared with those in healthy subjects. miRNA-200 had the most elevated area under the receiver operating characteristic curve (AUC) among single miRNAs used to predict HCC occurrence (AUC = 0.72). The highest discriminatory power was recorded using a panel based on the combination of four miRNAs, miRNA-200, miRNA-29a, miRNA-21 and miRNA-355, and AFP levels (AUC = 0.92). The four-miRNA panel combined with AFP levels exhibited high accuracy in predicting HCC with small tumour sizes of <2 cm (AUC = 0.90) and ≥2 cm (AUC = 0.93). The combination of the four-miRNA panel and AFP resulted in an AUC value of 0.83 for single lesions, which was lesser than that recorded for ≥2 lesions (AUC = 0.94, 0.95, respectively). CONCLUSION: The combination of the four-miRNA panel and AFP levels can be used as a sensitive and specific biomarker for HCC.

4.
Biomed Chromatogr ; 34(1): e4713, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31633807

RESUMEN

Metabolomes are small molecule metabolites (<1000 Da) produced by cellular processes. Metabolomes are close counterparts to the genome, transcriptome and proteome. The aim of this study was to develop a method to detect and quantify candidate nucleoside metabolomes 1-methyl adenosine (1-MA), 1-methylguanosine (1-MG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the urine of patients with breast cancer using gas chromatography-mass spectrometry (GC-MS). The method was applied to urine specimens from patients with breast cancer (n = 56) and benign breast tumors (n = 22), as well as from healthy females (n = 20). The relative standard deviations of precision and repeatability analysis were <10%, and recoveries ranged from 88.5 to 105.6%. Limits of detection were 0.014, 0.012, and 0.018 mg/L for 1-MA, 1-MG and 8-OHdG, respectively. The lower limits of quantitation were 0.056, 0.048 and 0.072 mg/L, respectively. There were significant differences in concentrations of candidate metabolomes between patients with cancer and the healthy individuals, especially for those in the early stages of the disease (p < 0.001). No significant differences were observed between the benign and healthy groups. In conclusion, a reliable GC-MS method for the detection and quantification of 1-MA, 1-MG, and 8-OHdG metabolomes in urine has been developed.


Asunto(s)
Adenosina/análogos & derivados , Neoplasias de la Mama/orina , Cromatografía de Gases y Espectrometría de Masas/métodos , Guanosina , Metabolómica/métodos , Adenosina/química , Adenosina/orina , Adulto , Anciano , Neoplasias de la Mama/metabolismo , Femenino , Guanosina/análogos & derivados , Guanosina/química , Guanosina/orina , Humanos , Límite de Detección , Modelos Lineales , Metaboloma/fisiología , Persona de Mediana Edad , Reproducibilidad de los Resultados
5.
Ann Hepatol ; 19(2): 179-185, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31648804

RESUMEN

INTRODUCTION AND OBJECTIVES: The heterogenous nature of hepatocellular carcinoma (HCC) motivated this attempt at developing and validating a model based on combined biomarkers for improving early HCC detection. PATIENTS/MATERIALS AND METHODS: This study examined 196 patients for an estimation study (104 patients with HCC, 52 with liver cirrhosis and 40 with liver fibrosis) and 122 patients for the validation study (80 patients with HCC, 42 with liver cirrhosis). All patients were positive for hepatitis C virus. Four markers were measured: Midkine and thioredoxin using ELISA, 1-methyladenosine and 1-methylguanosine using a gas chromatography-mass spectrometry (GC-MS). The results were compared with alpha-fetoprotein (AFP). The performance of the model was estimated in BCLC, CLIP and Okuda staging systems of HCC. RESULTS: The model yielded high performance with an area under ROC (AUC) of 0.94 for predicting HCC in patients with liver cirrhosis, compared with AUC of 0.69 for AFP. This model had AUCs of 0.93, 0.94 and 0.94 in patients who had only one single nodule, absent macrovascular invasion and tumor size <2cm, respectively, compared with AUCs of 0.71, 0.6 and 0.59 for AFP. The model produced AUCs of 0.91 for BCLC (0-A), 0.92 for CLIP (0-1) and 0.94 for Okuda (stage I) compared with AUCs of 0.56, 0.58 and 0.64 for AFP. No significant difference was found between AUC in the estimation and the validation groups. CONCLUSION: This model may enhance early-stage HCC detection and help to overcome insufficient sensitivity of AFP.

6.
J Immunoassay Immunochem ; 39(3): 337-347, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29985768

RESUMEN

Myeloperoxidase (MPO) is an inflammatory marker, elevated in acute coronary syndromes (ACSs), especially in acute myocardial infarction (AMI) cases. This study aimed to evaluate the diagnostic power of MPO in AMI patients. MPO, creatine kinase (CK) MB, and Troponin I (cTn I) were performed for all study patients. Area under the curves (AUCs) and 95% confidence intervals (CI); P values of baseline levels of MPO for discriminating AMI patients from noncoronary chest pain (NCCP) patients, stable angina (SA) patients, and unstable angina (UA) patients were 0.91, 95% CI: 0.82-0.99; P < 0.0001, 0.87, 95% CI: 0.77-0.98; P < 0.0001, and 0.72, 95% CI: 0.58-0.85; P = 0.002, respectively. For diagnosing AMI from ACS patients, MPO was the most efficient marker than others markers with efficiency 82.5% within 0-6 hr after the onset time of chest pain. A predictive score that depends on a combination of baseline levels of three markers (MPO, CK-MB, and TnI) was correctly discriminated 91% of the AMI patients with high specificity 76%. In conclusion, the use of baseline levels of three biomarkers in combination could confer the information that is required for best available early diagnosis of AMI.


Asunto(s)
Dolor en el Pecho/diagnóstico , Dolor en el Pecho/enzimología , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/enzimología , Peroxidasa/metabolismo , Enfermedad Aguda , Adulto , Anciano , Biomarcadores/metabolismo , Dolor en el Pecho/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones
7.
Ann Hepatol ; 17(4): 569-576, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29893697

RESUMEN

INTRODUCTION AND AIM: The correlation between interleukin-28B (IL-28B) polymorphisms and chronic hepatitis C (CHC) progression is debatable. Here, we aimed to evaluate the relation between IL-28B C/T genotypes and the development of cirrhotic liver. Extracellular matrix (ECM) proteins, FibroScan and model for end-stage liver disease (MELD) were used to substantiate the severity of liver disease. MATERIAL AND METHODS: IL-28B rs12979860, liver stiffness and ECM proteins were assessed in 272 CHC patients. RESULTS: Cirrhosis percentage increased to 10%, 52% and 96% with the increasing number of T alleles (CC, CT and TT, respectively). Also, elevated ECM proteins levels were correlated with the increasing number of T alleles. Interestingly, among cirrhotic patients, liver stiffness, MELD and ECM proteins were significantly (P < 0.0001) higher in patients with TT more than CT genotype. FibroScan, hyaluronic acid, Laminin, Collagen IV and the N-terminal pro-peptide of collagen type III have high accuracy to differentiate liver status in CC from TT genotype. Area under receiver-operating characteristic curve (95% CI) were 1.0 (1.0-1.0), 0.97 (0.96- 1.0), 0.93 (0.85-1.0), 0.98 (0.97-1.0) and 0.93 (0.91-0.97), respectively. CONCLUSION: This study suggests that IL-28B T allele affects the natural course of CHC type 4 and also suggests that carriage of the IL-28B C allele protects from unfavorable clinical outcomes in CHC as coexistence of C allele with T allele reduced cirrhosis severity.


Asunto(s)
Proteínas de la Matriz Extracelular/análisis , Hepatitis C Crónica/genética , Hepatitis C Crónica/metabolismo , Interleucinas/genética , Hígado/química , Polimorfismo de Nucleótido Simple , Progresión de la Enfermedad , Egipto , Diagnóstico por Imagen de Elasticidad , Predisposición Genética a la Enfermedad , Hepatitis C Crónica/diagnóstico , Hepatitis C Crónica/virología , Humanos , Interferones , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/virología , Fenotipo , Pronóstico , Factores Protectores , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Regulación hacia Arriba
8.
Breast Cancer ; 25(3): 297-302, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29285674

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) has the lymphotropic feature that is supposed to be the reason of related extrahepatic manifestation. HCV viral oncoproteins may participate in the regulation of some gene expression that has been implicated in tumorigenesis. Our aim is to evaluate the HCV-NS4 circulating levels in breast cancer (BC) and to investigate its relation with BC tumor aggressiveness. METHODS: This study was performed among 158 Egyptian women (120 with BC and 38 with benign breast diseases). ELISA was used for detection of anti-HCV antibodies, HCV-NS4, fibronectin, and CA 15-3. RESULTS: No association between HCV detection in this group of BC patients (27.5% in BC vs. 23.7% in breast benign diseases, P = 0.687). Among HCV-infected patients, the mean HCV-NS4 serum level in BC was significantly higher than benign group (61.7 µg/mL vs. 33.9 µg/mL, P = 0.0005). Fibronectin levels were higher (P = 0.014) in patients infected with HCV than noninfected BC patients. Elevated HCV-NS4 levels were associated with tumor severity features like large size, late stages, high grades, and infiltrated lymph nodes. The elevated levels of HCV-NS4 (> 40 µg/mL) yielded an estimated odds ratio (95% confidence intervals) of 2.5 (0.98-6.36), 1.2 (0.44-3.33), 1.9 (0.53-7.00), and 2.5 (0.87-7.33) for developing large size, late stages, high grades, and infiltrated lymph nodes, respectively. Interestingly, HCV-NS4 levels significantly correlated with other BC tumor marker like CA15-3 (r = 0.535; P = 0.0009) and fibronectin (r = 0.432; P < 0.0001). CONCLUSIONS: HCV-NS4 appears to be associated with BC progression features. Oncologists treating such BC patients should consider HCV screening to enable the early identification and to prevent progression of the disease.


Asunto(s)
Neoplasias de la Mama/sangre , Hepacivirus/aislamiento & purificación , Hepatitis C/sangre , Proteínas no Estructurales Virales/sangre , Adulto , Anciano , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Neoplasias de la Mama/virología , Carcinogénesis/inmunología , Progresión de la Enfermedad , Egipto/epidemiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Fibronectinas/sangre , Regulación Neoplásica de la Expresión Génica/inmunología , Hepacivirus/inmunología , Hepacivirus/metabolismo , Hepatitis C/epidemiología , Hepatitis C/inmunología , Anticuerpos contra la Hepatitis C/sangre , Anticuerpos contra la Hepatitis C/inmunología , Humanos , Incidencia , Persona de Mediana Edad , Mucina-1/sangre , Clasificación del Tumor , Estadificación de Neoplasias , Proteínas no Estructurales Virales/inmunología
9.
Br J Biomed Sci ; 74(2): 95-100, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28367737

RESUMEN

BACKGROUND: There is controversial data in the literature about the characteristics and features of dual hepatitis B and hepatitis C infection. This work is concerned with estimating the extent to which HBV could influence circulating levels of hepatitis C viral nonstructural-4 (HCV-NS4) in addition to some direct fibrosis markers in chronic hepatitis C. METHODS: Thirty-eight HCV mono-infected and 87 HCV/HBV co-infected patients constituted this study. Western-blot and ELISA were used for identifying HCV-NS4, hepatitis B surface antigen (HBsAg), collagen III and matrixmetalloproteinase-1 (MMP-1) in patients' sera. RESULTS: Hepatitis B surface antigen (HBsAg) provided area under curve (AUC) of 0.97 for identifying HBV-patients with 89% sensitivity and 94% specificity, while HCV-NS4 antigen provided an AUC of 0.95 for identifying HCV-patients with 89% sensitivity and absolute specificity (100%). In general, patients with significant fibrosis (F2-F4) showed significantly higher concentration of collagen III (P = 0.009) and lower concentrations of MMP-1 (P = 0.007) when compared to patients with minimal fibrosis (F1). However, HCV/HBV co-infected patients with F1 and F2-F4 did not show any significant difference (P > 0.05) from HCV mono-infected patients with respect to HCV-NS4, collagen III and MMP-1. These results indicate that HBV does not influence the rate of HCV-NS4 synthesis and the deposition of extracellular matrix in HCV/HBV co-infected patients and subsequently does not affect the progression rates of hepatic fibrosis. CONCLUSION: HCV/HBV co-infected and HCV- mono-infected patients had similar clinical characteristics and there is no effect of HBV co-infection on the progression rates of liver fibrosis in chronic hepatitis C patients.


Asunto(s)
Coinfección/sangre , Coinfección/virología , Colágeno Tipo III/sangre , Virus de la Hepatitis B/fisiología , Hepatitis B/sangre , Hepatitis C Crónica/sangre , Hepatitis C Crónica/virología , Metaloproteinasa 1 de la Matriz/sangre , Adulto , Biopsia , Femenino , Hepatitis B/virología , Humanos , Hígado/patología , Cirrosis Hepática/patología , Masculino , Proteínas no Estructurales Virales/metabolismo
10.
Int J Clin Oncol ; 22(2): 332-339, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27864623

RESUMEN

BACKGROUND: Small-sized HCC can be effectively cured by surgery with good clinical outcomes. A highly sensitive HCC α-fetoprotein routine test (HCC-ART) for HCC diagnosis as well as a simplied form of the HCC-ART were reported in the British Journal of Cancer. Here, we verified and studied the applicability of the HCC-ART to the detection of early-stage HCC. METHODS: 341 cirrhotic patients and 318 HCC patients were included in this study. For each, the HCC-ART score was calculated, and then the sensitivity, specificity, and results of an ROC curve analysis were compared between the HCC-ART and AFP when these biomarkers were used to detect small-sized HCC. RESULTS: Different HCC-ART cutoffs were set for the detection of different tumor sizes. The HCC-ART (AUC = 0.871, 70% sensitivity, 97% specificity) and the simplified HCC-ART (AUC = 0.934, 82% sensitivity, 100% specificity) were found to have high predictive power when attempting to separate cirrhotic patients from those with small-sized HCC. The simplified HCC-ART score was superior to AFP for determining stages according to the early Okuda (0.950 AUC, 84% sensitivity, 99% specificity), CLIP (0.945 AUC, 84% sensitivity, 99% specificity), and BCLC (1.000 AUC, 100% sensitivity, 99% specificity) staging systems. The simplified HCC-ART score was more strongly correlated than AFP and other staging systems with HCC tumor size (P < 0.0001; r = 0.8). CONCLUSION: The HCC-ART is superior to AFP for diagnosing early-stage HCC. Due to its advantages of minimal variability and a wide continuous scale for assessing HCC severity, the simplified HCC-ART has the potential to be more widely used than the original HCC-ART.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Estadificación de Neoplasias/métodos , alfa-Fetoproteínas/metabolismo , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Detección Precoz del Cáncer , Femenino , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC
11.
Am J Trop Med Hyg ; 95(5): 1044-1050, 2016 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-27527625

RESUMEN

Hepatitis C virus (HCV)/Schistosoma mansoni coinfection is common in Egypt and other developing countries. This study aimed to investigate the influence of HCV/S. mansoni coinfection on the concentration of HCV-nonstructural protein-4 (NS4) in addition to collagen III and matrix metalloproteinase-1 (MMP-1) in different hepatic fibrosis stages. We found that coinfected patients (N = 186) showed significantly (P < 0.05, Mann-Whitney U test) higher concentrations of HCV-NS4, collagen III, and collagen III/MMP-1 ratio (CMR) than those with HCV monoinfection (N = 104) in different fibrosis stages. Conversely, coinfected patients showed significantly lower concentrations of MMP-1 when compared with HCV monoinfection. The elevated levels of CMR in case of HCV monoinfection yielded an estimated odds ratio of 1.8 and 2.6 for developing significant fibrosis (F2-F4) and cirrhosis (F4), respectively. HCV/S. mansoni coinfection increased the risk for developing F2-F4 and F4 several fold yielding an estimated odds ratio of 11.1 and 5.2, respectively. This means that coinfected patients have a 6-fold and 2-fold increased risk of developing F2-F4 and F4, respectively, over HCV-monoinfected patients. Thus, elevated levels of HCV-NS4 and CMR in HCV/S. mansoni coinfection suggest increased susceptibility of coinfected patients, compared with those with HCV monoinfection, for accelerating hepatic fibrosis progression.


Asunto(s)
Coinfección/parasitología , Coinfección/virología , Proteínas de la Matriz Extracelular/metabolismo , Cirrosis Hepática/parasitología , Cirrosis Hepática/virología , Proteínas no Estructurales Virales/sangre , Adulto , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Aspartato Aminotransferasas/sangre , Estudios de Cohortes , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Progresión de la Enfermedad , Egipto , Proteínas de la Matriz Extracelular/genética , Femenino , Hepacivirus/aislamiento & purificación , Humanos , Modelos Logísticos , Masculino , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 1 de la Matriz/metabolismo , Persona de Mediana Edad , Factores de Riesgo , Schistosoma mansoni/aislamiento & purificación
12.
Tumour Biol ; 37(9): 12571-12577, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27380057

RESUMEN

Conflicting results for circulating glypican-3 (GPC3) were reported in hepatocellular carcinoma (HCC) diagnosis. We aimed to improve the diagnostic power of GPC3 by developing a GPC-HCC model for diagnosing HCC. GPC3 was tested for HCC (138), liver cirrhosis (56), and fibrosis (62) patients by ELISA. Data from patient groups were retrospectively analyzed. A novel score, GPC-HCC, based on combination of GPC3 and routine laboratory tests, was developed for HCC diagnosis. The GPC-HCC model values produced a significant 1.7-fold increase in liver cirrhosis and 3.2-fold increase in HCC, in comparison with liver fibrosis. In contrast to GPC3 and alpha fetoprotein (AFP), the GPC-HCC model showed high HCC diagnostic power with area under the curve (AUC) of 0.939, sensitivity 93 %, specificity 93 %, positive predictive value 89 %, negative predictive value 95 %, and efficiency 93 %. GPC-HCC AUC in HCC with single tumor, absent vascular invasion, and tumor size ≤3 cm were 0.93, 0.92, and 0.92, respectively, compared with 0.63, 0.63, and 0.64, respectively, for GPC3 and 0.69, 0.70, 0.55, respectively, for AFP. In conclusion, owing to these promising findings, the combination of GPC3 with other laboratory simple routine tests (GPC-HCC model) could improve the diagnostic power of GPC3 in HCC screening and follow up of cirrhotic patients.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/diagnóstico , Glipicanos/sangre , Neoplasias Hepáticas/diagnóstico , Adulto , Anciano , Bilirrubina/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Persona de Mediana Edad , alfa-Fetoproteínas/análisis
13.
J Immunoassay Immunochem ; 37(6): 597-610, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27093468

RESUMEN

The relation between interferon-gamma (IFN-γ) levels and the severity of liver diseases through fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) has not been fully clarified. Thus, we aimed to characterize IFN-γ levels in liver-diseased patients. IFN-γ levels were determined by Western-blot and ELISA in sera from 30 healthy individuals, 53 patients with non-significant fibrosis (F0-F1), 47 with moderate/severe fibrosis (F2-F3), 44 cirrhotic patients (F4), and 50 with HCC. Enhanced levels of IFN-γ were associated with the progression of liver disease. The differences were statistically significant (P < 0.0001) when patients with F2-F3, F4, or HCC were compared with F0-F1 or healthy controls. The increase in IFN-γ was associated with HCC (OR = 0.98, 95% CI 0.97-0.99, P = 0.002). There was no statistically significant association between IFN-γ levels and HCV-RNA (IU/ml) (r = 0.1, P = 0.43) or HCV-NS4 (µg/mL) (r = 0.1, P = 0.17). There was significant (P < 0.0001) association between IFN-γ levels and the fibrosis stages and activity, albumin, platelet count, total bilirubin, and international normalized ratio (INR). In conclusion, elevated concentrations of IFN-γ represent a characteristic feature of liver disease severity regardless of underlying disease. Significant correlations with indices of hepatic dysfunction suggest that enhanced IFN-γ levels represent a consequence of liver dysfunction rather than of inflammatory disease.


Asunto(s)
Carcinoma Hepatocelular/sangre , Fibrosis/sangre , Interferón gamma/sangre , Cirrosis Hepática/sangre , Neoplasias Hepáticas/sangre , Adulto , Western Blotting , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad
14.
J Immunoassay Immunochem ; 37(3): 316-30, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26745203

RESUMEN

The goal of this study was to determine the levels of S. mansoni antigen in different liver fibrosis stages with chronic hepatitis C (CHC) Egyptian patients. A total of 174 CHC patients showing HCV-NS4 antigen and HCV- RNA in their sera were included. S. mansoni antigen was detected in serum using Western blot and ELISA. The levels of interferon-γ (IFN- γ) were determined using ELISA. The 50 kDa S. mansoni antigen discriminated patients infected with S. mansoni from healthy individuals with 0.93 area under curve (AUC), 92% sensitivity, and 97% specificity. The level of S. mansoni antigen (µg/ml) was significantly (P < 0.0001) increased with the progression of liver fibrosis stages (26.9 ± 17.5 in F1, 42.1 ± 25.2 in F2, 49.8 ± 30.3 in F3 and 62.2 ± 26.3 µg/mL in F4 liver cirrhosis), 26.9 ± 17.59 in significant fibrosis (F2-F4); 51.2 ± 27.9 in advanced fibrosis (F3-F4). A significant correlation (r = 0.506; P < 0.0001) was shown between the levels of the S. mansoni antigen and the HCV-NS4 antigen. In conclusion, the presence of S. mansoni antigen in different liver fibrosis stages of CHC patients confirming that concomitant schistosome infection aggravates liver disease.


Asunto(s)
Antígenos Helmínticos/sangre , Hepatitis C Crónica/sangre , Cirrosis Hepática/sangre , Cirrosis Hepática/inmunología , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/inmunología , Adulto , Animales , Anticuerpos Monoclonales/inmunología , Reacciones Antígeno-Anticuerpo , Antígenos Helmínticos/inmunología , Western Blotting , Egipto , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepatitis C Crónica/inmunología , Humanos , Cirrosis Hepática/parasitología , Masculino , Persona de Mediana Edad , Schistosoma mansoni/aislamiento & purificación , Esquistosomiasis mansoni/sangre , Esquistosomiasis mansoni/parasitología , Índice de Severidad de la Enfermedad , Adulto Joven
15.
J Immunoassay Immunochem ; 37(3): 273-88, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26685049

RESUMEN

This study aimed to evaluate the diagnostic value of α-1-acid glycoprotein (AGP) and C-reactive protein (CRP) and develop a predictive score to improve the diagnosis of hepatocellular carcinoma (HCC). AGP and CRP were measured in serum of 53 HCC patients and 20 liver cirrhosis (LC) patients, in addition to 15 healthy individuals. Area under receiver-operating characteristic curves (AUCs) was used to create a predictive score comprising AGP, CRP, alpha fetoprotein, and albumin. The diagnostic performances of score was determined and compared with AFP alone for the diagnosis of HCC. The combination of AGP, albumin, CRP, and AFP had AUC 0.92 and sensitivity 85% which was higher than AFP alone. The odds ratio of having HCC was 8.4 for AGP, 5.8 for CRP, 12.5 for AFP and 6.5 for albumin. Our score predicted HCC with an OR of 50.6 for HCC. The AUC of score in HCC with single tumor, absent vascular invasion and CLIP score (0-1) were 0.9, 0.9, 0.82, respectively, compared with 0.71, 0.71, 0.68, respectively, for AFP. In conclusion, a non-invasive and simple score based on AGP, CRP, AFP, and albumin could improve the accuracy of HCC diagnosis.


Asunto(s)
Biomarcadores de Tumor/sangre , Proteína C-Reactiva/análisis , Carcinoma Hepatocelular/diagnóstico , Hepatitis C/diagnóstico , Neoplasias Hepáticas/diagnóstico , Orosomucoide/análisis , Adulto , Anciano , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/etiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepatitis C/sangre , Hepatitis C/complicaciones , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/etiología , Masculino , Persona de Mediana Edad , Adulto Joven
16.
Ann Hepatol ; 14(6): 869-80, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26436359

RESUMEN

UNLABELLED: Background and rationale for the study. Continuing search for suitable tumor-markers is of clinical value in managing patients with various malignancies. These markers may be presented as intracellular substances in tissues or may be released into the circulation and appear in serum. Therefore, this work is concerned with identification and quantitative determination of epithelial membrane antigen (EMA) and fibronectin and estimating their performances as surrogate markers for identifying hepatocellular carcinoma (HCC). RESULTS: A total of 627 individuals constituted this study [fibrosis (F1-F3) = 217; cirrhosis = 191; HCC = 219]. Western-blot was used for identifying EMA and fibronectin in sera. As a result, a single immunoreactive band was shown at 130-kDa and 90-kDa corresponding to EMA and fibronectin, respectively. They were quantified using ELISA providing values in HCC higher than fibrosis or cirrhosis with a significant difference (P < 0.0001). For identifying HCC, EMA showed 0.82 area under receiver-operating characteristic curve (AUC) with sensitivity = 70% and specificity = 78% while fibronectin yielded AUC = 0.70 with sensitivity = 67% and specificity = 82%. FEBA-Test comprising fibronectin and EMA together with total-bilirubin and AFP was constructed yielding AUC = 0.92 for identifying HCC from cirrhosis with sensitivity = 89% and specificity = 85%. FEBA-Test was then tested for differentiating HCC from fibrosis showing AUC = 0.97 with sensitivity = 90% and specificity = 89%. FEBA-Test enabled the correct identification of HCC patients with CLIP 0-1 and size ≤ 3 cm with AUC = 0.80 and AUC = 0.84, respectively, indicating its ability in identifying early HCC. CONCLUSIONS: A four-marker index may improve the early detection of HCC with a high degree of accuracy.


Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Detección Precoz del Cáncer , Fibronectinas/sangre , Cirrosis Hepática/sangre , Neoplasias Hepáticas/sangre , Mucina-1/sangre , Adulto , Anciano , Área Bajo la Curva , Bilirrubina/sangre , Western Blotting , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/patología , Detección Precoz del Cáncer/métodos , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , alfa-Fetoproteínas/análisis
17.
Int J Biol Markers ; 30(4): e407-13, 2015 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-26349665

RESUMEN

BACKGROUND: The advent of noninvasive urine-based markers as well as other novel modalities has yielded improved diagnostic accuracy. However, the new markers failed to reach higher sensitivity and specificity. We therefore evaluated the potential role of epithelial membrane antigen (EMA) and nuclear matrix protein 52 (NMP-52) singly and combined as noninvasive biomarkers for the detection of bladder cancer (BC). METHODS: A total of 160 individuals including 66 patients with BC, 54 patients with benign urologic disorders and 40 healthy volunteers were investigated. Urinary EMA at 130 kDa and NMP at 52 kDa were identified, purified and quantified by Western blot, electroelution and enzyme-linked immunosorbent assay (ELISA). The diagnostic performance of each biomarker and their combination were compared using area under receiver operating characteristic curves (AUC). RESULTS: Mean urinary EMA, 2.42 µg/mL, and NMP-52, 17.85 µg/mL, were significantly elevated in patients with BC compared to controls, 1.18 and 3.44 µg/mL, respectively (p<0.0001). The combined use of these markers yielded values which were increased 4.4- and 13.7-fold in the benign and malignant disease groups, respectively, with respect to the normal group. The values of EMA and NMP-52 were significantly higher in patients with higher-grade tumors than those with lower-grade tumors (p<0.0001). Moreover, this combination could predict all BC stages and grades with 0.91 AUC, 94% sensitivity and 80% specificity. CONCLUSIONS: EMA and NMP-52 in combination could be promising noninvasive biomarkers for BC detection.


Asunto(s)
Biomarcadores de Tumor/orina , Carcinoma de Células Transicionales/diagnóstico , Mucina-1/orina , Neoplasias de Células Escamosas/diagnóstico , Proteínas Asociadas a Matriz Nuclear/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/orina , Estudios de Casos y Controles , Detección Precoz del Cáncer , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de Células Escamosas/orina , Estudios Prospectivos , Curva ROC , Neoplasias de la Vejiga Urinaria/orina
18.
Tumour Biol ; 36(10): 7667-74, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25929809

RESUMEN

Currently, the search for suitable hepatocellular carcinoma (HCC) biomarkers is very intensive. Besides, efficacy and cost/effectiveness of screening and surveillance of cirrhotics for the diagnosis of HCC is still debated. So, the present study is concerned with the evaluation of cytokeratin-1 (CK-1) and nuclear matrix protein-52 (NMP-52) for identifying HCC. Two-hundred and eighty individuals categorized into three groups [liver fibrosis (F1-F3), cirrhosis (F4), and HCC] constituted this study. Western blot was used for identifying CK-1 and NMP-52 in serum samples. As a result, a single immunoreactive band was shown at 67 and 52 kDa corresponding to CK-1 and NMP-52, respectively. Both CK-1 and NMP-52 bands were cut and electroeluted separately. These markers were quantified in sera using ELISA. Patients with HCC were associated with higher concentrations of CK-1 and NMP-52 than those without HCC with a significant difference (P < 0.0001). CK-1 showed an area under receiver-operating characteristic curve (AUC) of 0.83 with 75 % sensitivity and 82 % specificity while NMP-52 yielded 0.72 AUC with 62 % sensitivity and 70 % specificity for identifying HCC. HCC-DETECT comprising CK-1 and NMP-52 together with AFP was then constructed yielding 0.90 AUC for identifying HCC with 80 % sensitivity and 92 % specificity. HCC-DETECT was then tested for separating HCC from F1-F3 showing 0.94 AUC with 80 % sensitivity and 93 % specificity. In conclusion, CK-1 in conjunction with NMP-52 and AFP could have a potential role for improving the detection of HCC with a high degree of accuracy.


Asunto(s)
Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Neoplasias Hepáticas/metabolismo , Adulto , Carcinoma Hepatocelular/diagnóstico , Femenino , Humanos , Queratinas/metabolismo , Cirrosis Hepática/metabolismo , Neoplasias Hepáticas/diagnóstico , Masculino , Persona de Mediana Edad , Proteínas Asociadas a Matriz Nuclear/metabolismo , Curva ROC , Sensibilidad y Especificidad
19.
Infect Dis (Lond) ; 47(8): 568-74, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25922972

RESUMEN

BACKGROUND: Perinatal exposure to hepatitis C virus (HCV) antigens during pregnancy may affect the developing immune system in the fetus. We aimed to study the perinatal transmission of HCV structural and non-structural antigens. METHODS: Sera from 402 pregnant mothers were tested for anti-HCV antibody and HCV RNA. HCV antigens were determined in sera from 101 HCV-infected mothers and their cord blood. RESULTS: In both serum and cord blood samples, HCV NS4 (non-structural 4) at 27 kDa, E1 (envelope 1) at 38 kDa and E2 (envelope 2) at 40 kDa were identified, purified and quantified using western blotting, electroelution and ELISA. Maternal sera and neonate cord blood samples had similar detection rates for NS4 (94.1%), E1 (90.1%) and E2 (90.1%). The mean maternal serum levels (optical density, OD) of HCV NS4 (0.87 ± 0.01), E1 (0.86 ± 0.01) and E2 (0.85 ± 0.01) did not differ significantly (p > 0.05) from those of neonatal cord blood (0.83 ± 0.01, 0.87 ± 0.01 and 0.85 ± 0.01, respectively). Also, strong correlations (p < 0.0001) were shown between sera and cord blood sample levels of HCV NS4, r = 0.77; E1, r = 0.76 and E2, r = 0.80. The vertical transmission of these antigens in vaginal delivery did not differ significantly (p > 0.05) from those in caesarean section. CONCLUSIONS: These findings indicate that vertical transmission of HCV NS4, E1 and E2 antigens was very high. Thus, exposure to these antigens may influence the developing immune responses to natural infection or future vaccination.


Asunto(s)
Hepacivirus/inmunología , Antígenos de la Hepatitis C/sangre , Hepatitis C/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Complicaciones Infecciosas del Embarazo/virología , Proteínas del Envoltorio Viral/sangre , Proteínas no Estructurales Virales/sangre , Adulto , Western Blotting , Femenino , Sangre Fetal/virología , Hepacivirus/genética , Anticuerpos contra la Hepatitis C/sangre , Antígenos de la Hepatitis C/líquido cefalorraquídeo , Humanos , Recién Nacido , Embarazo , Proteínas del Envoltorio Viral/inmunología , Proteínas no Estructurales Virales/inmunología
20.
Ann Hepatol ; 14(2): 225-33, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25671832

RESUMEN

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: The assessment of liver fibrosis provides useful information not only for diagnosis but also for therapeutic decision. This study was concerned with determining the levels of collagen III and its degrading enzyme matrix metalloproteinase-1 (MMP-1) as direct and complementary markers for liver fibrosis staging. RESULTS: A total of 269 chronic hepatitis C patients constituted this study. Western blotting was used for identifying collagen III and MMP-1 in serum samples. As a result, collagen III and MMP-1 were identified, respectively, at 70 and 245 kDa using their respective mono-specific antibodies. These two markers were quantified in sera of patients using ELISA. Next, Fibro-check was constructed combining collagen III and MMP-1 together with other indirect markers which reflect alteration in hepatic functions that proved useful to stage liver fibrosis. Fibro-check produced area under the receiver-operating characteristic curve (AUC) 0.91 and 0.83 for significant (F2-F4) and cirrhosis (F4), respectively. Additionally, we estimated the performance of Fibro-check in comparison with aspartate to platelet ratio index (APRI) and fibrosis index. Fibro-check seems to be more efficient than both of them. Fibro-check was then applied to the validation study to test its accuracy and reproducibility showing AUCs 0.90 for F2-F4 and 0.86 for F4. CONCLUSIONS: Fibro-check combining 'direct' and 'indirect' markers using a mathematical formula may improve the staging of liver fibrosis with a high degree of accuracy and seems more efficient than APRI and Fibrosis index in this group of Egyptian patients.


Asunto(s)
Colágeno Tipo III/sangre , Hepatitis C Crónica/diagnóstico , Cirrosis Hepática/diagnóstico , Pruebas de Función Hepática/métodos , Metaloproteinasa 1 de la Matriz/sangre , Adulto , Área Bajo la Curva , Aspartato Aminotransferasas/sangre , Biomarcadores/sangre , Biopsia , Pruebas Enzimáticas Clínicas , Egipto , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepatitis C Crónica/sangre , Hepatitis C Crónica/complicaciones , Humanos , Cirrosis Hepática/sangre , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad
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