The potential value of plasma Circ-ITCH in hepatocellular carcinoma patients with current hepatitis C virus infection / El valor potencial de Circ-ITCH en plasma en pacientes con carcinoma hepatocelular con infección actual por el virus de la hepatitis C

Background: There is an obvious need to diagnose hepatocellular carcinoma using novel non-invasive and sensitive biomarkers. Circular RNAs have recently attracted great interest as promising biomarkers and treatment targets. However, their function in hepatocellular carcinoma whose etiology related to hepatitis C has been rarely studied. Aim of work: The current study was conducted to analyze differential expression of circ-ITCH in plasma of Egyptian HCC patients with concomitant HCV infection, compared to normal control subjects, to investigate its correlation with liver function parameters, and to determine the possible diagnostic ability of circ-ITCH in plasma as a non-invasive marker, compared to its linear counterpart. Results: The results showed that the relative expression of circ-ITCH was significantly higher in the plasma of HCC patients (P<0.05). Moreover, when comparing its expression in the metastatic and non-metastatic subgroups, it was significantly higher in the non-metastatic HCC group compared to control group (P<0.05). Circ-ITCH was positively correlated with liver enzymes AST, ALT (P<0.001), also was significantly higher in HCC child C patients. To evaluate the potential diagnostic value of circ-ITCH in plasma, a ROC curve was generated, the AUC was 0.661, (95% CI: 0.5433–0.778) with a sensitivity and specificity 65% and 70% respectively. Conclusion: The results revealed that circ-ITCH is-with no doubt-involved in the pathogenesis of HCC and its high level may be related to HCV infection, further researches in this area will certainly make great contributions in understanding. In conclusion our results suggested that circ-ITCH may be used as a noninvasive diagnostic marker and a promising therapeutic target for HCC.(AU)

Antecedentes: Existe una necesidad obvia de diagnosticar el carcinoma hepatocelular (CHC) utilizando nuevos biomarcadores no invasivos y sensibles. Los ARN circulares han atraído recientemente un gran interés como biomarcadores prometedores y dianas de tratamiento. Sin embargo, su función en el carcinoma hepatocelular, cuya etiología está relacionada con la hepatitis C, apenas ha sido estudiada. Objetivo: Este estudio se realizó para analizar la expresión diferencial de circ-ITCH en el plasma de pacientes egipcios con CHC con infección concomitante por VHC, en comparación con sujetos de control normales, para investigar su correlación con los parámetros de la función hepática y para determinar la posible capacidad diagnóstica de circ-ITCH en plasma como marcador no invasivo, en comparación con su contraparte lineal. Resultados: Los resultados mostraron que la expresión relativa de circ-ITCH fue significativamente mayor en el plasma de pacientes con CHC (p<0,05). Además, al comparar su expresión en los subgrupos metastásico y no metastásico, fue significativamente mayor en el grupo de CHC no metastásico en comparación con el grupo control (p<0,05). Circ-ITCH se correlacionó positivamente con las enzimas hepáticas AST y ALT (p<0,001), y también fue significativamente mayor en pacientes con CHC infantil con VHC. Para evaluar el valor diagnóstico potencial de circ-ITCH en plasma se generó una curva ROC, el AUC fue de 0,661 (IC95%: 0,5433-0,778), con una sensibilidad y una especificidad del 65% y del 70%, respectivamente. Conclusión: Los resultados revelaron que circ-ITCH está, sin duda, involucrado en la patogénesis del CHC, y su alto nivel puede estar relacionado con la infección por VHC, por lo que investigaciones adicionales en esta área ciertamente harán grandes contribuciones para su comprensión. En conclusión, nuestros resultados sugirieron que circ-ITCH puede usarse como un marcador de diagnóstico no invasivo y una diana terapéutica prometedora para el CHC.(AU)

Circular RNAs 0064286 and 0000475: Potential Diagnostic Biomarkers in Hepatocellular Carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is considered the highest recorded malignancy in Egypt. The shortage of appropriate biomarkers for early detection often results in the late diagnosis of the HCC. Circular RNAs (CircRNAs) are presented as long stranded non-coding RNA that combine covalently to make a sealed circular form which make them very stable. CircRNAs are known to have interpretative role in cancer development and metastasis. AIM: To examine the dysregulation of two new CircRNAs obtained from Circbase database (hsa_circ_0064286 and hsa_circ_0000475) in the serum of HCC patients as predictable diagnostic biomarkers of HCC and their correlation with some liver biochemical parameters. METHODS: Sixty clinically diagnosed HCC Egyptian patients and 25 healthy volunteers were enrolled in the study. Expression levels of the selected CircRNAs was evaluated in subjects' serum. Moreover, correlation with liver biochemical parameters, sensitivity, and specificity of studied CircRNAs were estimated. RESULTS: Both circular RNAs were significantly down regulated in HCC patients, which was negatively correlated with ALP, ALT, AST, AFP, and bilirubin levels. Circ_0064286 showed more sensitivity and specificity (88.3% and 96%, respectively). CONCLUSION: As far as we know, this is the first study that shed light on the expression levels of both circRNAs in Egyptian HCC patients. They may serve as potential biomarkers for HCC diagnosis. Moreover, those circRNAs draw attention as therapeutic targets for HCC through targeting their sponge miRNAs.

Possible anticancer activity of rosuvastatine, doxazosin, repaglinide and oxcarbazepin.

BACKGROUND: Rosuvastatine, doxazosin, repaglinide and oxcarbazepin are therapeutic drugs available in the market for the treatment of different diseases. Potential to display antitumor activities has also been suggested. The aim of the current study was to evaluate their in vitro effects on some human transformed cell lines. MATERIALS AND METHODS: Cytotoxicity of the four drugs was tested in MCF-7, HeLa and HepG2 cells by the neutral red assay method and also the effect of rosuvastatine and doxazosin against Ehrlich Ascities Carcinoma Cells (EACC) by trypan blue assay. RESULTS: Rosuvastatine exerted the greatest cytotoxic effect against HepG2 cells with an IC50 value of 58.7±69.3; in contrast doxazosin showed least activity with IC50=104.4 ±115.7. Repaglinide inhibited the growth of both HepG2 and HeLa cells with IC50 values of 87.6±117.5 and 89.3±119.5, respectively. Oxcarbazepine showed a potent cytotoxicity against both HeLa (IC50=19.4±43.9) and MCF7 cancer cells ((IC50=22±35.7).On the other hand the growth of EACC was completely inhibited by doxazosine (100% inhibition) while rosuvastatine had weak inhibitory activity (11.6%) . CONCLUSIONS: The four tested drugs may have cytotoxic effects against hepatic, breast and cervical carcinoma cells; also doxazosine may inhibit the growth of endometrial cancer cells. Further investigations in animals are needed to confirm these results.

Consistency of quantitation of HCV genotype 4 from egypt across three HCV-RNA amplification assays.

Different quantitative assays for HCV-RNA are available that report test results in International Units (IU)/ml based on the WHO International Standard. Thus, assays have been calibrated with standard material containing HCV genotype 1, so the consistency of quantitation might differ between assays for other HCV genotypes. Three commercial HCV nucleic acid amplification techniques (HCV-NAT) were compared for quantitation consistency of genotype 4 and 1 specimens from an Egyptian blood donor panel (n = 92). Consistency of quantitation between HCV-NATs was higher for genotype 1 than for genotype 4. Most quantitative results reported by the assays were in the same range, but some genotype 4 samples were missed by two of the assays. The Abbott assay showed higher concentrations for genotype 4 than the two Roche assays. Follow-up investigations of individuals should use the same assay unless another assay has been validated properly. Standardization of HCV-NAT assays remains an issue.