Summary
Adjuvant pegylated interferon plus ribavirin treatment (PegIFN/RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma (HCC) patients with chronic hepatitis C ...(CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC‐HCC patients is uncertain. This study aimed to investigate the impact PegIFN/RBV treatment on recurrence‐free interval and survival in patients with HCC receiving transarterial chemoembolization (TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient‐based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching (PSM) (age, gender, AST to Platelet Ratio Index (APRI), tumour size, tumour number and Child‐Turcotte‐Pugh score) with the ratio 1:2 for patients with and without PegIFN/RBV treatment was performed. Statistics were performed with SPSS V.20 (IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response (SVR). The 2‐year cumulative overall survival rate and recurrence‐free survival rate among patients with SVR, non‐SVR, and untreated were 85.2% vs 58.3% vs 69.6% (P=.001) and 73.3% vs 53.8% vs 58.5% (P=.013). By Cox regression analysis, non‐SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by PegIFN/RBV treatment markedly improves survival and reduces tumour recurrence in CHC‐HCC patients receiving TACE treatment after complete response.
Differential expression of the tetracycline-controlled transactivator (tTA)-driven human cytochrome P450 (CYP) 1B1 gene was found in the livers of male mice, at high levels in neonates, but at low ...levels in adults. The goals of this study were to determine whether the differential expression of the tTA-driven human CYP1B1 (hCYP1B1) gene in neonates and adults was testosterone dependent and whether flutamide, a representative potent antiandrogen, led to the induction of hCYP1B1. This was tested by treating castrated transgenic mice with testosterone propionate and musk extracts. It was concluded that: (i) the levels of expression of both tTA and hCYP1B1 gradually declined, with clear changes being apparent between 2 and 4 weeks of age, (ii) castration of adult males resulted in the increased expressions of both tTA and hCYP1B1 to levels similar to those found in adult females, (iii) treatment of castrated male and adult female mice with testosterone propionate and musk extracts led to the restoration of the levels of expression of hCYP1B1 in the adult males, and (iv) treatment of adult males with flutamide caused an increase in the levels of expression of hCYP1B1 in the adult females, as indicated by the antiandrogenic activity. Thus, the differential expression of the tTA-driven hCYP1B1 gene in the transgenic mice was caused by androgen, and it is possible that castrated male and adult female mice expressing the tTA-controlled hCYP1B1 could be used as the basis for a strategy for the detection of androgens and antiandrogens.
Tolerance to the analgesic effect of opioids complicates the management of persistent pain states. We tested whether the intrathecal infusion of small interfering RNA (siRNA) against β-arrestin 2 ...would reduce tolerance to chronic morphine use and the severity of precipitated morphine withdrawal.
Intrathecal β-arrestin 2 (2 μg siRNA per 10 μl per rat) was injected once daily for 3 days. Rats then received a continuous intrathecal infusion of morphine (2 nmol h−1) or saline for 7 days. Daily tail-flick (TF) and intrathecal morphine challenge tests were performed to assess the effect of intrathecal β-arrestin 2 siRNA on antinociception and tolerance to morphine. Naloxone withdrawal (2 mg kg−1) was performed to assess morphine dependence.
In the daily TF test, the antinociception of intrathecal morphine was increased and maintained in rats receiving β-arrestin 2 siRNA compared with the control group (morphine alone). In the probe response test, rats receiving morphine infusion with β-arrestin 2 siRNA treatment showed a significant left shift in their dose–response curve, as measured by per cent maximal possible effect (MPE), such that the AD50 was significantly decreased by a factor of 5.6 when compared with that of morphine-infused rats. In the naloxone-induced withdrawal tests, rats receiving β-arrestin 2 siRNA injection with morphine infusion showed a significant reduction in four of the six signs of withdrawal.
We show here that intrathecal β-arrestin 2 siRNA in rats enhances analgesia and attenuates naloxone-induced withdrawal symptoms. This may warrant further investigation in the context of long-term use of intrathecal opioids for controlling chronic pain.
The formation mechanism of tidal dwarf galaxies means they are expected to contain little or no dark matter. As such, they might be expected to be very sensitive to their environment. We investigate ...the impact of ram pressure on tidal dwarf galaxies in a parameter study, varying dwarf galaxy properties and ram pressures. We submit model tidal dwarf galaxies to wind-tunnel style tests using a toy ram pressure model. The effects of ram pressure are found to be substantial. If tidal dwarf galaxies have their gas stripped, they may be completely destroyed. Ram pressure drag causes acceleration of our dwarf galaxy models, and this further enhances stellar losses. The dragging can also cause stars to lie in a low surface brightness stellar stream that points in the opposite direction to the stripped gas, in a manner distinctive from tidal streams. We investigate the effects of ram pressure on surface density profiles, the dynamics of the stars, and discuss the consequences for dynamical mass measurements.
Skeletal reaction models for n-butane and iso-butane combustion are derived from a detailed chemistry model through directed relation graph (DRG) and DRG-aided sensitivity analysis (DRGASA) methods. ...It is shown that the accuracy of the reduced models can be improved by optimization through the method of uncertainty minimization by polynomial chaos expansion (MUM-PCE). The dependence of model uncertainty on the model size is also investigated by exploring skeletal models containing different number of species. It is shown that the dependence of model uncertainty is subject to the completeness of the model. In principle, for a specific simulation the uncertainty of a complete model, which includes all reactions important to its prediction, is convergent with respect to the model size, while the uncertainty calculated with an incomplete model may display unpredictable correlation with the model size.
Apoptosis is an important process in the variety of different biological system including cell death and embryonic development. Inappropriate apoptosis is implicated in many human diseases such as ...Alzheimer's disease. Central component of the machinery of apoptosis program in neurons of patients with Alzheimer's disease includes proteins of caspases and Bcl-2 families. We examined whether endogenous protein levels of caspases and Bcl-2 families are expressed in a differential manner during the embryonic and postnatal development of BDF1 strain. Here, all four proteins with caspases-3, -9, Bcl-2 and Bax were highly expressed between embryonic day 19 and 1 week age of early postnatal development, but thereafter the expression dramatically declined. These patterns are needed to compare the proteins in the brains of APPsw-transgenic mice that are expected to be expressed highly in the brain of adult mice. Thus, the results are useful to understand fundamentally the mechanisms of the apoptotic changes during the embryonic and postnatal development of Alzheimer's model mice.
To define the clinical, radiologic, and genetic features of periventricular heterotopia (PH) with Ehlers-Danlos syndrome (EDS).
Exonic sequencing and single stranded conformational polymorphism ...(SSCP) analysis was performed on affected individuals. Linkage analysis using microsatellite markers on the X-chromosome was performed on a single pedigree. Western blotting evaluated for loss of filamin A (FLNA) protein and Southern blotting assessed for any potential chromosome rearrangement in this region.
The authors report two familial cases and nine additional sporadic cases of the EDS-variant form of PH, which is characterized by nodular brain heterotopia, joint hypermobility, and development of aortic dilatation in early adulthood. MRI typically demonstrated bilateral nodular PH, indistinguishable from PH due to FLNA mutations. Exonic sequencing or SSCP analyses of FLNA revealed a 2762 delG single base pair deletion in one affected female. Another affected female harbored a C116 single point mutation, resulting in an A39G change. A third affected female had a 4147 delG single base pair deletion. One pedigree with no detectable exonic mutation demonstrated positive linkage to the FLNA locus Xq28, an affected individual in this family also had no detectable FLNA protein, but no chromosomal rearrangement was detected.
These results suggest that the Ehlers-Danlos variant of periventricular heterotopia (PH), in part, represents an overlapping syndrome with X-linked dominant PH due to filamin A mutations.
PDF
