Association of Low Zinc Finger Antiviral Protein Expression with Progression and Poor Survival of Patients with Hepatocellular Carcinoma.

BACKGROUND/AIMS: Zinc finger antiviral protein (ZAP) has been reported to be expressed in hepatocellular carcinoma (HCC), and ZAP expression is associated with apoptotic signaling in cancer cells. This study aimed at investigating the expression of ZAP in HCC cells and its significance in clinical pathology. METHODS: Real-time quantitative PCR and western blot assays were employed to detect ZAP RNA and protein expression in normal human hepatocytes, HCC cells, and five primary HCC cell lines. Immunohistochemistry was performed to detect ZAP expression in 147 paraffin-embedded HCC tissues and adjacent normal tissues. The clinical significance of ZAP expression was analyzed in tissue samples from patients with or without infection by hepatitis B virus (HBV). RESULTS: ZAP expression in HCC cells and human primary HCC cell lines was significantly lower than that of normal human hepatocytes. Among 147 HCC samples, ZAP expression was lower in HCC tissues than in adjacent normal tissues for 107 (77.0%) samples. In patients with HCC and HBV infection, ZAP expression was related to pathological grade (P < 0.05); in HBV-negative patients with HCC, ZAP expression was associated with tumor size (P < 0.05) and clinical stage (P < 0.05). The overall survival time in patients with low ZAP expression was significantly shorter than survival times of those with high ZAP expression (P < 0.05), especially for patients with moderately to well-differentiated HCC (Grade 1-2) and HCC at stage T1 and T2 (P < 0.05). Cox multivariate analysis showed that ZAP expression was an independent predictor of survival of patients with HCC (P < 0.01). CONCLUSION: Low ZAP expression is closely associated with disease progression and poor prognosis for patients with HCC.

Liver toxicity of chemotherapy and targeted therapy for breast cancer patients with hepatitis virus infection.

BACKGROUND: Chemotherapy has greatly improved the prognosis of breast cancer patients. However, it may also result in undesirable side effects such as hepatitis virus reactivation. Little information is available on the liver toxicity of chemotherapy and targeted therapy for breast cancer patients with hepatitis virus (HBV/HCV) infection. METHODS: We performed a retrospective survey of 835 patients diagnosed with breast cancer between January 2010 and December 2015 at our institution. All patients had been screened for HBV/HCV infection at the time of breast cancer diagnosis. We retrospectively investigated the toxicity of chemotherapy and the changes in HBV/HCV load based on a medical record review. RESULTS: 52 patients with positive anti-HBV antibody test and 21 patients with positive anti-HCV antibody tests received chemotherapy. 762 patients without HBV and HCV infection served as the control group. The morbidity of liver toxicity and disruptions in chemotherapy attributable to liver toxicity were not significantly different among control group, HBV group and HCV groups (27.7% vs 34.6% vs 42.9%, P = 0.189 and 5.0% vs 9.6% vs 9.5%, P = 0.173, respectively). No patients presented with HBV/HCV reactivation. CONCLUSION: Breast cancer patients with HCV can be treated with chemotherapy and targeted therapy with trastuzumab. Breast cancer patients with HBV who accept antiviral therapy can be treated with chemotherapy and targeted therapy with trastuzumab and patients can benefit from prophylactic antiviral therapy before chemotherapy. However, a multidisciplinary cooperation and closely monitoring liver function during the course of chemotherapy may benefit patients.

Genome-Wide Association Study for Pre-harvest Sprouting Resistance in a Large Germplasm Collection of Chinese Wheat Landraces.

Pre-harvest sprouting (PHS) is mainly caused by the breaking of seed dormancy in high rainfall regions, which leads to huge economic losses in wheat. In this study, we evaluated 717 Chinese wheat landraces for PHS resistance and carried out genome-wide association studies (GWAS) using to 9,740 DArT-seq and 178,803 SNP markers. Landraces were grown across six environments in China and germination testing of harvest-ripe grain was used to calculate the germination rate (GR) for each accession at each site. GR was highly correlated across all environments. A large number of landraces (194) displayed high levels of PHS resistance (i.e., mean GR < 0.20), which included nine white-grained accessions. Overall, white-grained accessions displayed a significantly higher mean GR (42.7-79.6%) compared to red-grained accessions (19.1-56.0%) across the six environments. Landraces from mesic growing zones in southern China showed higher levels of PHS resistance than those sourced from xeric areas in northern and north-western China. Three main quantitative trait loci (QTL) were detected by GWAS: one on 5D that appeared to be novel and two co-located with the grain color transcription factor Tamyb10 on 3A and 3D. An additional 32 grain color related QTL (GCR-QTL) were detected when the set of red-grained landraces were analyzed separately. GCR-QTL occurred at high frequencies in the red-grained accessions and a strong correlation was observed between the number of GCR-QTL and GR (R2 = 0.62). These additional factors could be critical for maintaining high levels of PHS resistance and represent targets for introgression into white-grained wheat cultivars. Further, investigation of the origin of haplotypes associated with the three main QTL revealed that favorable haplotypes for PHS resistance were more common in accessions from higher rainfall zones in China. Thus, a combination of natural and artificial selection likely resulted in landraces incorporating PHS resistance in China.

Effects of hepatitis C virus infection on the safety of chemotherapy for breast cancer patients.

PURPOSE: Hepatitis C virus (HCV) is one of the major pathogens of chronic viral hepatitis, and approximately 38 million patients are infected with HCV in China. However, little information is available on the effect of HCV infection during chemotherapy for breast cancer and the impact of HCV infection on the toxicity of chemotherapy and targeted therapy. METHODS: We performed a retrospective survey of 835 patients who were diagnosed with breast cancer between January 2010 and December 2015 at our institution. All patients had been screened for HCV infection at the time of breast cancer diagnosis. We retrospectively investigated the toxicities of chemotherapy and the changes in HCV load based on a review of the medical records. RESULTS: A total of 21 patients with positive anti-HCV antibody tests received chemotherapy. The median patient age was 46.3 ± 11.2 years. Four (19.0%) patients exhibited abnormal liver function at baseline. The morbidity of abnormal liver function at baseline was higher in HCV-infected patients (19.0% vs. 0, P = 0.000). Four patients received trastuzumab therapy. Five (23.8%) patients who received chemotherapy developed hepatitis. No patients presented with HCV reactivation. The morbidity of hepatitis and the rate of disruption of chemotherapy were not significantly different between breast cancer patients without HCV infection and those with HCV infection (23.8 vs. 14.2% P = 0.342, 9.5 vs. 5.0% P = 0.619, respectively). CONCLUSION: HCV infection had no adverse impact on chemotherapy in breast cancer patients. However, consulting a gastroenterologist and closely monitoring liver function during the course of chemotherapy may benefit patients.

Entecavir Combined With Adefovir Ameliorates Patients With Chronic Hepatitis B Who Fail to Respond to Nucleotide (Acid) Analog Monotherapy.

The aim of this study was to evaluate the efficacy and safety of entecavir (ETV) combined treatment with adefovir (ADV) on chronic hepatitic B (CHB) patients who failed to respond to nucleotide (acid) analog (NA) treatment. On this basis, the possible factors in the combined treatment of these patients will be analyzed. The safety, biochemical index, and the possible factors that might affect the ETV and ADV combined treatment at different points in time were retrospectively analyzed. The biochemical index included the following: virological response, hepatitis B virus (HBV) DNA decline, primary nonresponse, biochemical response, and the hepatitis B virus E antigen/hepatitis B virus E antibody seroconversion rate. There were 94 CHB patients and compensated liver cirrhosis patients who received ETV plus ADV treatment for over 12 weeks after failure of treatment with NAs. The authors have also investigated 76 CHB patients (80.9%) and 18 hepatitis B cirrhosis patients (19.1%) in this study. The HBV DNA baseline was 4.4 ± 1.4 log10 IU/mL, and the positive rate of HBeAg before salvage treatment was 78.7% (74/94). The sample sizes were 94, 78, 42, 10, 6, and 1 for follow-up of 24, 48, 96, 144, 192, and 240 weeks, respectively. The virological responses (HBV DNA < 2 log10 IU/mL) and biochemical responses were 52.1%, 74.3%, and 90.4% and 63.1%, 61.6%, and 81.1%, respectively, at 24, 48, and 96 weeks, which showed significant differences (P < 0.001 and P < 0.005, respectively). The HBV DNA decline was presented as mean ± SEM, which were 1.53 ± 1.23, 1.75 ± 1.37, 2.07 ± 1.54, and 2.39 ± 1.77 log10 IU/mL at 12, 24, 48, and 96 weeks, respectively. They showed significant differences compared with the baseline (χ = 8.084, P < 0.05). The rate of primary nonresponse was 30.9% (29/94), and the primary treatment failure rates were 26.6% (25/94), 24.4% (19/78), and 4.8% (2/42) at 24, 48, and 96 weeks, respectively. They all have statistical difference (P = 0.011 < 0.05). There were 23 patients who experienced virological breakthrough after the HBV DNA levels were undetectable, whereas after follow-up for 12-24 weeks, the HBV DNA levels were back to undetectable again. ETV plus ADV treatment is an efficient and safe treatment for CHB and compensated liver cirrhosis patients who experienced NA treatment failure. The high quantity of baseline HBV DNA level is a risk factor for poor efficacy of salvage treatment.