Annexin A3 is a therapeutic target for CD133+ liver cancer stem cells

This journal suppl. entitled: Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CAFrequent tumor relapse in hepatocellular carcinoma (HCC) has been commonly attributed to the failure to completely eradicate cancer stem cells (CSCs) in the tumor residues by conventional treatments. We have previously reported that the tumor growth of HCC is fuelled, at least in part, by a small subset of CSCs marked by the CD133 surface phenotype. Our present study aims 1) to delineate the molecular mechanism by which CD133+ liver CSCs mediate HCC tumor formation and progression; and 2) to develop a novel diagnostic / prognostic biomarker and targeted therapy for HCC detection and treatment. RNA-Seq profiling was employed to compare the gene expression profiles between sorted CD133+ and CD133- subsets isolated from HCC cell lines ...postprin

Water Oxidation Catalysed by Iron Complex of N,N′-dimethyl-2,11-diaza[3,3](2,6)pyridinophane. Spectroscopy of Iron–oxo Intermediates and Density Functional Theory Calculations

published_or_final_versio

Boosting the power conversion efficiency of organic solar cells using weakly luminescent gold(III) corrole with long-lived exciton state

Poster Session: P-69Transition metal complexes have been widely used as light-emitting and photon-absorbing materials in optoelectronic devices with diverse applications. While these complexes have been intensively studied in the field of organic light-emitting devices (OLEDs) due to their inherently high phosphorescence quantum yields …postprin

Impact of G 2 checkpoint defect on centromeric instability

Centromeric instability is characterized by dynamic formation of centromeric breaks, deletions, isochromosomes and translocations, which are commonly observed in cancer. So far, however, the mechanisms of centromeric instability in cancer cells are still poorly understood. In this study, we tested the hypothesis that G 2 checkpoint defect promotes centromeric instability. Our observations from multiple approaches consistently support this hypothesis. We found that overexpression of cyclin B1, one of the pivotal genes driving G 2 to M phase transition, impaired G 2 checkpoint and promoted the formation of centromeric aberrations in telomerase-immortalized cell lines. Conversely, centromeric instability in cancer cells was ameliorated through reinforcement of G 2 checkpoint by cyclin B1 knockdown. Remarkably, treatment with KU55933 for only 2.5 h, which abrogated G 2 checkpoint, was sufficient to produce centromeric aberrations. Moreover, centromeric aberrations constituted the major form of structural abnormalities in G 2 checkpoint-defective ataxia telangiectasia cells. Statistical analysis showed that the frequencies of centromeric aberrations in G 2 checkpoint-defective cells were always significantly overrepresented compared with random assumption. As there are multiple pathways leading to G 2 checkpoint defect, our finding offers a broad explanation for the common occurrence of centromeric aberrations in cancer cells. © 2011 Macmillan Publishers Limited All rights reserved.postprin

Luminescent zinc(ii) and copper( i) complexes for high-performance solution-processed monochromic and white organic light-emitting devices

published_or_final_versio

Effectiveness of Myocardial Contrast Echocardiography Quantitative Analysis during Adenosine Stress versus Visual Analysis before Percutaneous Therapy in Acute Coronary Pain: A Coronary Artery TIMI Grading Comparing Study

The study aim was to compare two different stress echocardiography interpretation techniques based on the correlation with thrombosis in myocardial infarction (TIMI) flow grading from acute coronary syndrome (ACS) patients. Forty-one patients with suspected ACS were studied before diagnostic coronary angiography with myocardial contrast echocardiography (MCE) at rest and at stress. The correlation of visual interpretation of MCE and TIMI flow grade was significant. The quantitative analysis (myocardial perfusion parameters: A, beta, and A x beta) and TIMI flow grade were significant. MCE visual interpretation and TIMI flow grade had a high degree of agreement, on diagnosing myocardial perfusion abnormality. If one considers TIMI flow grade <3 as abnormal, MCE visual interpretation at rest had 73.1% accuracy with 58.2% sensitivity and 84.2% specificity and at stress had 80.4% accuracy with 76.6% sensitivity and 83.3% specificity. The MCE quantitative analysis has better accuracy with 100% of agreement with different level of TIMI flow grading. MCE quantitative analysis at stress has showed a direct correlation with TIMI flow grade, more significant than the visual interpretation technique. Further studies could measure the clinical relevance of this more objective approach to managing acute coronary syndrome patient before percutaneous coronary intervention (PCI).Science and Technology Planning Project Grant of Urumqi Municipality of the Xinjiang Uygur Autonomous Region [G06131001]Science and Technology Planning Project Grant of Urumqi Municipality of the Xinjiang Uygur Autonomous Region [G06131001

ANXA3/JNK Signaling Promotes Self-Renewal and Tumor Growth, and Its Blockade Provides a Therapeutic Target for Hepatocellular Carcinoma

Frequent tumor relapse in hepatocellular carcinoma (HCC) has been commonly attributed to the presence of residual cancer stem cells (CSCs) after conventional treatments. We have previously identified and characterized CD133 to mark a specific CSC subset in HCC. In the present study, we found endogenous and secretory annexin A3 (ANXA3) to play pivotal roles in promoting cancer and stem cell-like features in CD133+ liver CSCs through a dysregulated JNK pathway. Blockade of ANXA3 with an anti-ANXA3 monoclonal antibody in vitro as well as in human HCC xenograft models resulted in a significant reduction in tumor growth and self-renewal. Clinically, ANXA3 expression in HCC patient sera closely associated with aggressive clinical features. Our results suggest that ANXA3 can serve as a novel diagnostic biomarker and that the inhibition of ANXA3 may be a viable therapeutic option for the treatment of CD133+ liver-CSC-driven HCC. © 2015 The Authors.published_or_final_versio

Clinical and molecular epidemiological features of coronavirus HKU1-associated community-acquired pneumonia

Background. Recently, we described the discovery of a novel group 2 coronavirus, coronavirus HKU1 (CoV-HKU1), from a patient with pneumonia. However, the clinical and molecular epidemiological features of CoV-HKU1-associated pneumonia are unknown. Methods. Prospectively collected (during a 12-month period) nasopharyngeal aspirates (NPAs) from patients with community-acquired pneumonia from 4 hospitals were subjected to reverse-transcription polymerase chain reaction, for detection of CoV-HKU1. The epidemiological, clinical, and laboratory characteristics of patients with CoV-HKU1-associated pneumonia were analyzed. The pol, spike (S), and nucleocapsid (N) genes were also sequenced. Results. NPAs from 10 (2.4%) of 418 patients with community-acquired pneumonia were found to be positive for CoV-HKU1. All 10 cases occurred in spring and winter. Nine of these patients were adults, and 4 had underlying diseases of the respiratory tract. In the 6 patients from whom serum samples were available, all had a 4-fold change in immunoglobulin (Ig) G titer and/or presence of IgM against CoV-HKU1. The 2 patients who died had significantly lower hemoglobin levels, monocyte counts, albumin levels, and oxygen saturation levels on admission and had more-extensive involvement visible on chest radiographs. Sequence analysis of the pol, S, and N genes revealed 2 genotypes of CoV-HKU1. Conclusions. CoV-HKU1 accounts for 2.4% of community-acquired pneumonia, with 2 genotypes in the study population. Without performance of diagnostic tests, the illness was clinically indistinguishable from other community-acquired pneumonia illnesses. © 2005 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Effects of Using Alternative Extreme Pressure (EP) and Anti-Wear (AW) Additives with Oxy-Nitrided Samples

Oxy-nitriding is a widely used industrial process aiming to improve the tribological properties and performance of components. Previous studies have shown the effectiveness of the treatment with friction and wear performance, but very few have focussed on optimising this behaviour. The lubrication properties of several EP and AW additives were examined to investigate their effectiveness in improving the tribological properties of the layers formed after treatment. Previous studies showed the presence of an oxide layer on the sample could improve the effectiveness of the sulphurised olefin (SO) and tricresyl phosphate (TCP) additives. The friction and wear behaviour of oxy-nitrided samples were analysed using a tribometer and surface profiler. Scanning electron microscope, energy-dispersive X-ray spectroscopy and X-ray photoelectron spectroscopy were employed to identify the morphologies and chemical compositions of the treated surface before and after testing. No real effect on friction was observed when using the SO or TCP additives, mostly due to lack of interaction with the less reactive iron nitride layer and their roles as anti-wear additives. However, when the zinc dialkyldithiophosphate-containing lubricant was used, a higher friction coefficient was observed. Greater improvements in anti-wear properties with the presence of additives in comparison with only using base oil were reported, with the TCP additive producing the lowest wear rates. The study effectively demonstrated that the additive package type used could impact the tribological and tribochemical properties of oxy-nitrided surfaces

Promoter Hypermethylation Mediated Downregulation of FBP1 in Human Hepatocellular Carcinoma and Colon Cancer

FBP1, fructose-1,6-bisphosphatase-1, a gluconeogenesis regulatory enzyme, catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate and inorganic phosphate. The mechanism that it functions to antagonize glycolysis and was epigenetically inactivated through NF-kappaB pathway in gastric cancer has been reported. However, its role in the liver carcinogenesis still remains unknown. Here, we investigated the expression and DNA methylation of FBP1 in primary HCC and colon tumor. FBP1 was lowly expressed in 80% (8/10) human hepatocellular carcinoma, 66.7% (6/9) liver cancer cell lines and 100% (6/6) colon cancer cell lines, but was higher in paired adjacent non-tumor tissues and immortalized normal cell lines, which was well correlated with its promoter methylation status. Methylation was further detected in primary HCCs, gastric and colon tumor tissues, but none or occasionally in paired adjacent non-tumor tissues. Detailed methylation analysis of 29 CpG sites at a 327-bp promoter region by bisulfite genomic sequencing confirmed its methylation. FBP1 silencing could be reversed by chemical demethylation treatment with 5-aza-2′-deoxycytidine (Aza), indicating direct epigenetic silencing. Restoring FBP1 expression in low expressed cells significantly inhibited cell growth and colony formation ability through the induction of G2-M phase cell cycle arrest. Moreover, the observed effects coincided with an increase in reactive oxygen species (ROS) generation. In summary, epigenetic inactivation of FBP1 is also common in human liver and colon cancer. FBP1 appears to be a functional tumor suppressor involved in the liver and colon carcinogenesis