Background Occult hepatitis B virus infection (OBI) frequently occurs in patients with chronic hepatitis C (CHC) infection, but the influence of OBI on CHC outcome is still uncertain. The aim of the present study was to clarify the clinical and pathological characteristics of OBI in CHC-related hepatocellular carcinoma (HCC). Patients and methods DNA was obtained from serum and tumor tissue of patients with hepatitis C virus (HCV)-related HCC with negative HBsAg and from patients with HCV-related liver cirrhosis. HBV-DNA was detected using qPCR. Clinicopathological features were compared between patients with HCC with and without OBI. Results On the basis of positive serum and tissue HBV-DNA typing, the overall frequency of OBI was 50% in patients with HCV-related HCC. HBV genotype D was the most dominant, constituting 35.3% of HCC cases. Almost 80% of patients with OBI had anti-HBc, whereas 20% of patients had no serological markers. Tissue HBV-DNA showed significant association with positive serum HBV-DNA, anti-HBc, and genotype D. There were no clinical differences between patients with HCC with and without OBI; however, patients with OBI tended to be younger. HCC cases with positive OBI were significantly associated with positive anti-HBc antibodies and late histological grades (3–4). Multivariate logistic regression analysis revealed that the presence of OBI was a predictor of more advanced HCC histological grades in patients with HCV infection. Conclusion OBI was detected in 50% of HCV-infected patients with HCC. OBI was strongly associated with the presence of anti-HBc antibodies. Patients with HCC with positive OBI were younger and had more advanced HCC histological grades.
Hepatocellular carcinoma is a major cause of cancer mortality worldwide. The outcome of hepatocellular carcinoma depends mainly on its early diagnosis. To date, the performance of traditional biomarkers is unsatisfactory. Polo-like kinase 1 is a serine/threonine kinase that plays essential roles in cell cycle progression and deoxyribonucleic acid damage. Moreover, polo-like kinase 1 knockdown decreases the survival of hepatocellular carcinoma cells; therefore, polo-like kinase 1 is an attractive target for anticancer treatments. Nobiletin, a natural polymethoxy flavonoid, exhibits a potential antiproliferative effect against a wide variety of cancers. This study targets to identify a reliable diagnostic biomarker for hepatocellular carcinoma and provide a potential therapeutic target for its treatment. Polo-like kinase 1 levels were analyzed in 44 hepatocellular carcinoma patients, 33 non-hepatocellular carcinoma liver cirrhosis patients and 15 healthy controls using the enzyme-linked immunosorbent assay method. Receiver operating characteristics curve analysis was used to establish a predictive model for polo-like kinase 1 relative to α-fetoprotein in hepatocellular carcinoma diagnosis. Furthermore, in the in vitro study, gene expressions were assessed by quantitative polymerase chain reaction in two human hepatocellular carcinoma cell lines after treatment with doxorubicin and polo-like kinase 1 inhibitor volasertib (Vola) either alone or in combination with nobiletin. Cell viability was also determined using the crystal violet assay.: Serum polo-like kinase 1 levels in hepatocellular carcinoma patients were significantly higher than liver cirrhosis and control groups (p < 0.0001). Polo-like kinase 1 showed a reasonable sensitivity, specificity, positive predictive value, and negative predictive value in hepatocellular carcinoma diagnosis. Moreover, nobiletin improved inhibition of cell growth induced by Vola and doxorubicin. Regarding reverse transcription polymerase chain reaction results, nobiletin suppressed expressions of polo-like kinase 1 and proliferating cell nuclear antigen and elevated expressions of P53, poly (ADPribose) polymerase 1, and caspase-3. Nobiletin/doxorubicin and nobiletin/Vola showed a significant increase in caspase-3 activity indicating cell apoptosis. Polo-like kinase 1 may be a potential biomarker for hepatocellular carcinoma diagnosis and follow-up during treatment with chemotherapies. In addition, nobiletin synergistically potentiates the doxorubicin and Vola-mediated anticancer effect that may be attributed partly to suppression of polo-like kinase 1 and proliferating cell nuclear antigen expression and enhancement of chemotherapy-induced apoptosis.
Background Obesity is rapidly emerging as one of the greatest challenges of human health. Many randomized trials and open-label human studies described conflicting results of gastric intra-muscular injections of botulinum toxin type A (BTA). Endoscopic ultrasound (EUS) guidance can assure BTA injection into the subserosal layer and muscularis propria of the gastric wall which may optimize the efficacy of injection. The aim of the study is to assess the efficacy and safety of EUS-guided gastric BTA injections in weight reduction for obese subjects. Results The present study included 25 patients (2 males and 23 females with mean age 35.84 ± 7.776). For nutrient drink tests, median maximum tolerated volumes (MTVs) decreased from 720 cc (range 480–1680) as a baseline value 2 weeks before BTA injection to 360 cc (range 140–820) at 16 weeks after injection. Mean body weight reduction was 11.92 kg (10.8%) after 16 weeks of BTA injection. Mean body weight continued to decrease during the study period from a baseline value of 110 to 98 kg with significant reduction of mean BMI from baseline value of 41.2 to 36.7 at 16 weeks after BTA injection (p > 0.001). The study was completed without major adverse events. Conclusion EUS-guided BTA injection into the antral subserosa and muscularis propria could be an effective technique for weight reduction, or as a bridge for surgery, which can be done safely with minimal complications. Trial registration NCT03901040
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