Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Assessment of intrahepatic blood flow by Doppler ultrasonography: Relationship between the hepatic vein, portal vein, hepatic artery and portal pressure measured intraoperatively in patients with portal hypertension

<p>Abstract</p> <p>Background</p> <p>Abnormality of hepatic vein (HV) waveforms evaluated by Doppler ultrasonography has been widely studied in patients with chronic liver disease. We investigated the correlation between changes in HV waveforms and portal vein velocity (PVVel), the hepatic artery pulsatility index (HAPI), and also the extent of abnormal Doppler HV waveforms expressed as damping index (DI), severity of portal hypertension expressed as Child-Pugh scores and portal pressure (PP) measured directly from patients with portal hypertension (PHT) to evaluate the indicative value of abnormal HV waveforms and discuss the cause of abnormal HV waveform.</p> <p>Methods</p> <p>Sixty patients who had been diagnosed with PHT and accepted surgical therapy of portosystemic shunts were investigated. PP was measured intraoperatively. Thirty healthy volunteers with no history of chronic liver disease were enrolled as the control group. HV waveforms were categorized as triphasic, biphasic or monophasic. DI was compared as the quantitative indicator of abnormal HV waveforms. Another two Doppler parameters, PVVel and HAPI were also measured. These Doppler features were compared with PP, Child-Pugh scores and histological changes assessed by liver biopsy.</p> <p>Results</p> <p>In the patient group, the Doppler flow waveforms in the middle HV were triphasic in 31.6%, biphasic in 46.7%, and monophasic in 21.6% of subjects. These figures were 86.7%, 10.0%, and 3.3%, respectively, in healthy subjects. With the flattening of HV waveforms, the HAPI increased significantly (<it>r </it>= 00.438, <it>p </it>< 0.0001), whereas PVVel decreased significantly (<it>r </it>= -0.44, <it>p <</it>0.0001). Blood flow parameters, HAPI, PVVel and HV-waveform changes showed no significant correlations with Child-Pugh scores. The latter showed a significant correlation with PP (<it>r </it>= 0.589, <it>p </it>= 0.044). Changes of HV waveform and DI significantly correlated with PP (<it>r </it>= 0.579, <it>r </it>= 0.473, <it>p <</it>0.0001), and significant correlation between DI and Child-Pugh scores was observed (<it>r </it>= 0.411, <it>p = </it>0.001). PP was significantly different with respect to nodule size (<it>p </it>< 0.05), but HV-waveform changes were not significantly correlated with pathological changes.</p> <p>Conclusion</p> <p>In patients with PHT, a monophasic HV waveform indicates higher portal pressure. Furthermore, quantitative indicator DI can reflect both higher portal pressure and more severe liver dysfunction. Flattening of HV waveforms accompanied by an increase in the HAPI and decrease in PVVel support the hypothesis that histological changes reducing HV compliance be the cause of abnormality of Doppler HV waveforms from the hemodynamic angle.</p

Population genomics of post-glacial western Eurasia.

Western Eurasia witnessed several large-scale human migrations during the Holocene &lt;sup&gt;1-5&lt;/sup&gt; . Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations

Transient hepatitis B surface antigenemia after neonatal hepatitis B immunization

Following immunization with hepatitis B vaccine, 39 infants were followed prospectively for hepatitis B surface antigen (HBsAg). A total of 69.2% of the infants tested positive for antigenemia at least once. Antigenemia was identified most often at 2-3 days (43.5%) and 5-6 days (43.5%) after immunization. The longest documented duration of antigenemia was 21 days. In all cases the antigenemia was transient and cleared by the 28th day post-vaccination

Plasma growth arrest-specific 6 levels in term and preterm newborns

Objective: Growth Arrest-Specific 6 (GAS6) is a vitamin K-dependent protein. Despite a similar structure to Protein S, it has no anticoagulant activity. An association between GAS6 and some diseases for adults has been reported. In the absence of prospective clinical studies of GAS6 in neonates, so far, the objective of this study is to obtain, for the first time, plasma GAS6 levels before and after vitamin K1 prophylaxis in full-term and pre-term newborns.Methods: 80 newborns (40 term and 40 preterm) were recruited for this study. Cord blood samples and peripheral blood samples 48h after vitamin K1 injection were collected into EDTA-tubes. GAS6 levels were measured in platelet-poor plasma by ELISA.Results: Cord blood plasma GAS6 levels in preterm and term newborns were 9.075.30ng/mL and 9.75 +/- 4.34ng/mL, respectively. In response to vitamin K1 injection, GAS6 levels increased in preterm newborns (10.50 +/- 5.28ng/mL) (p.05).Conclusion: This pilot study provided, to the best of our knowledge, the first report that GAS6 levels increased significantly after vitamin K1 prophylaxis in preterm newborns but not in term infants. This study may serve as a first step toward more extensive studies in neonates

Early onset Alzheimer's disease

WOS: 000209194000108

Cognitive impairment in general paresis: Alzheimer's disease (AD)-like pattern?

WOS: 000209194000604