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- Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection. [JOURNAL ARTICLE]
- Hepatology 2014 Mar 6.
All-oral combinations of direct-acting antivirals may improve efficacy and safety outcomes for patients with hepatitis C virus (HCV) infection, particularly those who are poor candidates for current interferon/ribavirin-based regimens. In this open-label, phase 3 study, 135 interferon-ineligible/intolerant and 87 nonresponder patients with chronic HCV genotype 1b infection were enrolled at 24 centers in Japan. Patients received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. The primary end point was sustained virologic response 24 weeks after treatment (SVR24 ). This study is registered with ClinicalTrials.gov (NCT01497834). SVR24 was achieved by 87.4% of interferon-ineligible/intolerant patients and 80.5% of nonresponder (null and partial) patients; rates were similar in cirrhotic (90.9%) and non-cirrhotic (84.0%) patients, and in patients with IL28B CC (84.5%) or non-CC (84.8%) genotypes. Fourteen patients in each group (12.6%) discontinued dual therapy, mainly due to adverse events or lack of efficacy. Nine nonresponder patients received additional treatment with peginterferon/ribavirin per protocol-defined criteria. The rate of serious adverse events was low (5.9%) and varied among patients. The most common adverse events were nasopharyngitis, increased ALT and AST, headache, diarrhea, and pyrexia. Conclusion: Interferon-free, ribavirin-free all oral therapy with daclatasvir and asunaprevir for 24 weeks is well tolerated and can achieve a high rate of SVR in patients with HCV genotype 1b who were ineligible, intolerant, or had not responded to prior interferon-based therapy. (Hepatology 2014;).
- The ileum positively regulates hepatic regeneration in rats. [Journal Article]
- Acta Cir Bras 2014 Feb; 29(2):93-8.
To test the hypothesis that liver regeneration after partial hepatectomy can be influenced by the ileum.Eighteen Wistar rats were distributed into groups of six animals: 1 - ileum resection+ hepatectomy 2/3; 2 - hepatectomy 2/3, and 3 - sham. Anesthesia with ketamine and xylazine i.p., aseptic technique, analgesia with meperidine (10mg/kg s.c.). On day 6, serum ALT, AST, alkaline phosphatase (AP) and albumin were measured. Liver regeneration and hepatocyte mitosis were quantified. Statistical analysis with ANOVA and Tukey tests, with significance p<0.05.In group hepatectomy+ileal resection, ALT, AST and AP were 180.6±24.9, 58.6±3.1 and 254.6±46.6 respectively. They were significantly higher than in the hepatectomy group, whose values were 126.0±16.5, 44.1±3.9 and 163.5±8.6, respectively (p<0.001). Albumin levels were not significantly different among groups. Liver regeneration in hepatectomy group (94.17%) was statistically higher (p<0.001) than in ileal resection+hepatectomy group (55.96%). In the latter group the mitosis of hepatocytes were significantly less frequent than in the hepatectomy group.The data confirm that the ileum positively influence on liver regeneration in rats undergoing hepatectomy.
- Multicenter Phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple negative breast cancer. [JOURNAL ARTICLE]
- Int J Cancer 2014 Mar 6.
Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. Phase I study showed the recommended dose of 750 mg/d with substantial antitumor activity. This phase II study aims to evaluate the optimum dose level for the efficacy and safety of apatinib monotherapy in heavily pretreated patients with metastatic triple negative breast cancer (mTNBC) in China. Phase IIa was first performed among 25 patients previously treated with anthracycline and/or taxane. All patients received apatinib 750 mg/d p.o. in a 4-week cycle. Subsequently, a phase IIb study of 59 patients was activated, with the endpoint progression-free survival (PFS). The dosage of drug for the Phase IIb was determined according to safety, tolerability and efficacy from the phase IIa study. As a result of toxicity associated with the 750 mg dose in phase IIa, the recommended initial dose of apatinib in the phase IIb was 500mg/d. In phase IIb, grade 3/4 hematologic toxicities were thrombocytopenia (13.6%), leukopenia (6.8%), neutropenia (3.4%) and anemia (1.7%). The most frequent grade 3/4 non-hematologic toxicities were hand-foot syndrome, proteinuria, hypertension, and increased ALT. In the 56 evaluable patients, overall response rate and clinical benefit rate (CBR) were 10.7% and 25.0%, respectively. Median PFS and overall survival were 3.3 (95 % CI, 1.7-5.0) and 10.6 (95 % CI, 5.6-15.7) months, respectively. Our results indicate that apatinib dose of 500 mg rather than 750 mg is the recommended starting dose for the heavily pretreated mTNBC patients with measurable rate of PR and PFS. © 2014 Wiley Periodicals, Inc.
- Reversible photoswitching conjugated polymer nanoparticles for cell and ex vivo tumor imaging. [JOURNAL ARTICLE]
- Nanoscale 2014 Mar 7.
Fluorescent photoswitchable conjugated polymer nanoparticles (PCPNPs) bearing poly(9,9-dihexylfluorene-alt-2,1,3-benzoxadiazole) (PFBD) as the fluorescent host polymer and the photochromic diarylethene as toggle are synthesized via a modified nano-precipitation method using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG-NH2) as the encapsulation matrix. The PCPNPs are spherical in shape with diameters around 34 nm. The fluorescence switching processes upon UV and white light illumination are successfully demonstrated with high contrast up to 90-fold, recovery efficiency of 95%, and excellent repeatability in solution. The cationic PCPNPs can be easily internalized into cancer cells, and accumulate in tumor tissues, where the fluorescence photoswitching processes can be used to self-validate the imaging results.
- Antioxidant properties of jujube honey and its protective effects against chronic alcohol-induced liver damage in mice. [JOURNAL ARTICLE]
- Food Funct 2014 Mar 7.
The antioxidant potential of jujube honey, one of the most widely consumed honeys in China, has never been determined fully. In this study, jujube honey from six geographical origins in China was analyzed for individual phenolic acid, total phenolic content, and the antioxidant effect in chronic alcohol-related hepatic disease in mice. The results showed that jujube honey from Linxian of Shanxi province contained higher phenol levels, exhibited DPPH antioxidant activity, ferric ion reducing antioxidant power (FRAP) and protective effects against DNA damage. Treatment with jujube honey (Shanxi Linxian) for 12 weeks significantly inhibited serum lipoprotein oxidation, reduced the impact of alcoholism on aspartate aminotransferase (AST) and alanine aminotransferase (ALT). It also inhibited the generation of 8-hydroxy-2-deoxyguanosine (8-OHdG), lowered the levels of malondialdehyde (MDA) and increased the activity of hepatic glutathione peroxidase (GSH-Px). The study indicates that jujube honey exerts potent antioxidant activity and significant protection in hepatic disorders associated with chronic alcoholism. The protective effect is attributed to its antioxidant mechanisms and inhibition of oxidative degradation of lipids.
- Physical activity, sedentary time and liver enzymes in adolescents: The HELENA study. [JOURNAL ARTICLE]
- Pediatr Res 2014 Mar 6.
Background:To examine the association between physical activity (PA) and liver enzyme levels in adolescents from 9 European countries.Methods:The study comprised 718 adolescents (397 girls). PA was measured by accelerometry and expressed as total PA (counts/min), and time (min/d) engaged in moderate to vigorous intensity PA (MVPA). Time spent sedentary was also objectively measured. We measured serum levels of alanine aspartate aminostrasferase (AST), alanine aminostransferase (ALT), and γ-glutamyltrasnferase (GGT), and the AST/ALT ratio was computed.Results:There was an association between MVPA and AST and AST/ALT (age, sex and center adjusted β=0.096, 95% confidence interval (CI): 0.016 to 0.118; and β=0.090, 95% CI: 0.006 to 0.112, respectively). Meeting the PA recommendations (60min/d of MVPA) was significantly associated with higher AST and AST/ALT, which persisted after further adjusting for sedentary time and waist circumference. Sedentary time was not associated with any of the studied liver enzyme levels.Conclusion:Meeting the current PA recommendations of 60min/d of MVPA is associated with higher levels of AST and AST/ALT regardless of time spent sedentary as well as total and central body fat in European adolescents.Pediatric Research (2014); doi:10.1038/pr.2014.26.
- Balanced Duo of Anti-Inflammatory SFRP5 and Pro-Inflammatory WNT5A in Children. [JOURNAL ARTICLE]
- Pediatr Res 2014 Mar 6.
Background:Secreted frizzled-related protein 5 (SFRP5) is an adipokine protecting against obesity-related insulin resistance and diabetes. SFRP5 binds to wingless type MMTV integration site family member 5A (WNT5A) to improve insulin sensitivity. We performed a first study of SFRP5 and WNT5A in children.Methods:Prepubertal children (n=342) were assessed for circulating SFRP5 (all subjects) and circulating WNT5A (210 subjects), and associations were sought with metabolic markers. In conditioned media of adipose tissue explants from 12 additional children, SFRP5 and WNT5A were studied further.Results:The concentrations of SFRP5 and WNT5A correlated positively in serum and in conditioned media (all p<0.001). Lower circulating SFRP5 (lowest quartile) was associated with higher BMI (15% increase, p<0.0001) and lower high molecular weight (HMW) adiponectin (26% decrease, p=0.002). Circulating WNT5A related closely with insulin resistance assessed by the homeostasis model assessment for insulin resistance (HOMA-IR) and hepatic markers (alanine transaminase (ALT) and gamma glutamyl transpeptidase (GGT)), particularly in children with lower circulating SFRP5 (all p<0.004).Conclusion:SFRP5 and WNT5A are a balanced duo that may regulate metabolic homeostasis in prepubertal children.Pediatric Research (2014); doi:10.1038/pr.2014.29.
- Association between psychosocial distress with cardio metabolic risk factors and liver enzymes in a nationally-representative sample of Iranian children and adolescents: the CASPIAN-III study. [JOURNAL ARTICLE]
- J Diabetes Metab Disord 2014 Mar 6; 13(1):44.
The present study was designed to evaluate association of psychosocial distress with cardio metabolic risk factors and liver enzymes in Iranian children and adolescents.This nationwide study was conducted as the third survey of the school-based surveillance system that was conducted among 5593 school students, 10-18 years in Iran. High triglyceride (TG), high fasting blood sugar (FBS), high total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), hypertension (HTN), generalized obesity and abdominal obesity were considered as cardio metabolic risk factors and alanine transaminase (ALT) and aspartate aminotransferase (AST) were considered as liver enzymes. Data were analyzed using multiple logistic regression (MLR) analysis.Result: Psychosocial distress was detected in2027 (71.2 %) of boys and 1759 (63.3 %) of girls. Among boys, the mean of LDL, AST and DBP were higher and the mean FBS and HDL were lowering those with psychiatric distress than their other counterparts. Girls with psychosocial distress had significantly higher mean of HDL and FBS than those without psychiatric distress. Psychosocial distress significantly increased the odds of high LDL (OR = 2.36, 95%CI 1.53, 3.64), high FBS (OR = 1.23, 95%CI 1.02, 1.49) and low HDL (OR = 1.65, 95%CI 1.41, 1.95).Psychosocial distress in adolescents is associated with increased risk of some cardio metabolic risk factors.
- Stabilization of circulating tumor cells in blood using a collection device with a preservative reagent. [JOURNAL ARTICLE]
- Cancer Cell Int 2014 Mar 7; 14(1):23.
The enumeration and characterization of circulating tumor cells (CTCs) in the blood of cancer patients is useful for cancer prognostic and treatment monitoring purposes. The number of CTCs present in patient blood is very low; thus, robust technologies have been developed to enumerate and characterize CTCs in patient blood samples. One of the challenges to the clinical utility of CTCs is their inherent fragility, which makes these cells very unstable during transportation and storage of blood samples. In this study we investigated Cell-Free DNA BCTTM (BCT), a blood collection device, which stabilizes blood cells in a blood sample at room temperature (RT) for its ability to stabilize CTCs at RT for an extended period of time.Blood was drawn from each donor into K3EDTA tube, CellSave tube and BCT. Samples were then spiked with breast cancer cells (MCF-7), transported and stored at RT. Spiked cancer cells were counted using the Veridex CellSearchTM system on days 1 and 4. The effect of storage on the stability of proteins and nucleic acids in the spiked cells isolated from K3EDTA tube and BCT was determined using fluorescence staining and confocal laser scanning microscopy.MCF-7 cell recovery significantly dropped when transported and stored in K3EDTA tubes. However, in blood collected into CellSave tubes and BCTs, the MCF-7 cell count was stable up to 4 days at RT. Epithelial cell adhesion molecule (EpCAM) and cytokeratin (CK) in MCF-7 cells isolated from BCTs was stable at RT for up to 4 days, whereas in MCF-7 cells isolated from K3EDTA blood showed reduced EpCAM and CK protein expression. Similarly, BCTs stabilized c-fos and cyclin D1 mRNAs as compared to K3EDTA tubes.Cell-Free DNATM BCT blood collection device preserves and stabilizes CTCs in blood samples for at least 4 days at RT. This technology may facilitate the development of new non-invasive diagnostic and prognostic methodologies for CTC enumeration as well as characterization.
- Increased paired box transcription factor 8 has a survival function in Glioma. [JOURNAL ARTICLE]
- BMC Cancer 2014 Mar 6; 14(1):159.
The molecular basis to overcome therapeutic resistance to treat glioblastoma remains unclear. The anti-apoptotic b cell lymphoma 2 (BCL2) gene is associated with treatment resistance, and is transactivated by the paired box transcription factor 8 (PAX8). In earlier studies, we demonstrated that increased PAX8 expression in glioma cell lines was associated with the expression of telomerase. In this current study, we more extensively explored a role for PAX8 in gliomagenesis METHODS: PAX8 expression was measured in 156 gliomas including telomerase-negative tumours, those with the alternative lengthening of telomeres (ALT) mechanism or with a non-defined telomere maintenance mechanism (NDTMM), using immunohistochemistry and quantitative PCR. We also tested the affect of PAX8 knockdown using siRNA in cell lines on cell survival and BCL2 expression RESULTS: Seventy-two percent of glioblastomas were PAX8-positive (80% telomerase, 73% NDTMM, and 44% ALT). The majority of the low-grade gliomas and normal brain cells were PAX8-negative. The suppression of PAX8 was associated with a reduction in both cell growth and BCL2, suggesting that a reduction in PAX8 expression would sensitise tumours to cell death.PAX8 is increased in the majority of glioblastomas and promoted cell survival. Because PAX8 is absent in normal brain tissue, it may be a promising therapeutic target pathway for treating aggressive gliomas.