Coxsackievirus and adenovirus receptor expression in human endometrial adenocarcinoma: possible clinical implications

The coxsackievirus and adenovirus receptor (CAR) is a crucial receptor for the entry of both coxsackie B viruses and adenoviruses into host cells. CAR expression on tumor cells was reported to be associated with their sensitivity to adenoviral infection, while it was considered as a surrogate marker for monitoring and/or predicting the outcome of adenovirus-mediated gene therapy. The aim of the present study was to evaluate the clinical significance of CAR expression in endometrial adenocarcinoma. CAR expression was assessed immunohistochemically in tumoral samples of 41 endometrial adenocarcinoma patients and was statistically analyzed in relation to various clinicopathological parameters, tumor proliferative capacity and patient survival. CAR positivity was noted in 23 out of 41 (56%) endometrial adenocarcinoma cases, while high CAR expression in 8 out of 23 (35%) positive ones. CAR intensity of immunostaining was classified as mild in 11 (48%), moderate in 10 (43%) and intense in 2 (9%) out of the 23 positive cases. CAR positivity was significantly associated with tumor histological grade (p = 0.036), as well differentiated tumors more frequently demonstrating no CAR expression. CAR staining intensity was significantly associated with tumor histological type (p = 0.016), as tumors possessing squamous elements presented more frequently intense CAR immunostaining. High CAR expression showed a trend to be correlated with increased tumor proliferative capacity (p = 0.057). Patients with tumors presenting moderate or intense CAR staining intensity were characterized by longer survival times than those with mild one; however, this difference did not reach statistical significance. These data reveal, for the first time, the expression of CAR in clinical material obtained from patients with endometrial adenocarcinoma in relation to important clinicopathological parameters for their management. As CAR appears to modulate the proliferation and characteristics of cancer cells, its expression could be considered of possible clinical importance for future (gene) therapy applications

Adaptive wavelet Galerkin methods on distorted domains - setup of the algebraic system

We use the algorithm of Bertoluzza, Canuto and Urban for computing integrals of products (of derivatives) of wavelets in order to solve elliptic PDEs on 2D distorted domains. We construct a variant of the original method which turns out to be more efficient. Several numerical results are presented. (orig.)Available from TIB Hannover: RN 8680(178) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Can acetylcholinesterase activity be considered as a reliable biomarker for the assessment of cadmium-induced neurotoxicity?

Gonçalves et al. (2012) recently reported the findings of a long-awaited study on the effects of long-term dietary-induced exposure to cadmium (Cd) on the acetylcholinesterase (AChE) activity of adult rodents' brain regions. Their study can be regarded as a significant contribution to the field, as there is paucity of information on the AChE activity in brain regions following exposure to Cd. However, the Cd-induced modulation of AChE activity is an issue surrounded by controversy. We, herein, discuss and summarize the relative in vivo and in vitro experimental data, and set out to answer the straightforward question: can AChE activity be considered as a reliable biomarker for the assessment of Cd-induced neurotoxicity? At this time, we can not answer in the affirmative because of the variation in techniques used and conclusions reached. We make a plea that authors aiming to explore this potential use of brain AChE activity in the future: (a) are aware of the biases that their experimental approach might exert upon this neurochemical parameter, (b) avoid the use of anaesthesia as a mode of sacrifice and clarify its timing, (c) decide upon the use of previously-studied in vivo experimental schemes (so that they can provide comparable results), and finally, (d) identify pharmacological, biochemical and molecular approaches that are appropriate to clarify the implicated mechanism(s) through which Cd modifies AChE activity. © 2013 Elsevier Ltd

Effects of fulminant hepatic encephalopathy on the adult rat brain antioxidant status and the activities of acetylcholinesterase, (Na +,K+)- and Mg2+-ATPase: Comparison of the enzymes' response to in vitro treatment with ammonia

Hepatic encephalopathy can be a life-threatening complication of fulminant hepatic failure. By understanding the pathophysiology involved in the induction of this neuropsychiatric disorder, future therapeutic and/or preventive attempts could be considered. In this study, an attempt has been made in order to shed more light on the mechanisms involved in the effects of thioacetamide (TAA)-induced fulminant hepatic encephalopathy on: (a) the adult rat brain total antioxidant status (TAS) and (b) the activities of acetylcholinesterase (AChE), (Na+,K+)-ATPase and Mg2+-ATPase. Moreover, in vitro experiments were conducted in order to evaluate the possible role of ammonia (incubated as NH4Cl, in a toxic concentration of 3mM) in the observed effects of TAA-induced fulminant hepatic encephalopathy on the examined adult rat brain enzyme activities. Fulminant hepatic encephalopathy caused a significant decrease in TAS (-22%, p < 0.001) and the activity of Na +,K+-ATPase (-26%, p < 0.001), but had non-significant effects on the whole brain AChE and Mg2+-ATPase activities. The in vitro experiments (conducted through a 3h incubation with ammonia), showed no significant alterations in any of the examined parameters. Our in vitro and in vivo findings suggest that alterations in AChE and Mg2+-ATPase activities are not involved in the pathophysiology of the adult-onset fulminant hepatic encephalopathy, while the observed Na+,K+-ATPase inhibition could be a result of the oxidative stress, neurotransmission deregulation, and/or of the presence of other toxic substances (that appear to act as direct or indirect inhibitors of the enzyme) and not due to the excess accumulation of ammonia in the brain. © 2008 Springer Science+Business Media, LLC

Regulation of gene expression via triple helical formations

Triplex-forming oligonucleotides (TFOs) are a challenging and very promising subject in modern biochemistry and molecular genetics. Over the last decade, several studies have stated that TFOs: a) can bind to DNA in a sequence-specific manner; b) can provoke DNA repair and recombination in mammalian cells, and c) can be a very effective biological tool in embryonic and oncogenic research on gene expression pathways. Herein we review the basic modes in which TFOs exist, their gene-regulation properties, as well as the obstacles that should be overcome before they become useful in clinical practice (chemotherapy and/or gene therapy)