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

The role of matrix metalloproteinases in the pathophysiology and progression of human nervous system malignancies: A chance for the development of targeted therapeutic approaches?

Background: Matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases involved in the degradation of extracellular matrix components. MMPs have been implicated in a wide variety of physiological processes, such as angiogenesis, wound healing and tissue remodeling. However, recent studies have revealed a significant role for MMPs in tumorigenesis pathophysiology and prediction of patients' clinical outcome. Alterations in the regulation of MMP expression are thought to play an important role in the development and progression of central nervous system (CNS) malignancies. Objective/methods: This study provides an up-to-date review of the literature on the pathophysiologic involvement of MMPs in the development and progression of human CNS malignancies, as well as the potential use of natural and/or synthetic MMP-inhibitors (MMPIs) as a targeted therapeutic approach to this group of neoplasms. Results/conclusions: The currently available data provide clear evidence for the involvement of MMPs in the pathophysiology of astrocytomas, glioblastomas, meningiomas, medulloblastomas/primitive neuroectodermal tumors and pituitary tumors. The use of MMPIs in the treatment of CNS malignancies has, until now, reached controversial (but mainly disappointing) results that can nevertheless provide the basis for further investigation. The co-administration of other agents, the use of surgery and/or radiation, and elimination of the MMPIs-induced adverse effects, as well as the use of antisense technology, might be the tools by which the natural and synthetic MMPIs could find their place in everyday clinical practice for the management of CNS malignancies. © 2008 Informa UK Ltd

Matrix metalloproteinases in the pathophysiology and progression of gynecological malignancies: Could their inhibition be an effective therapeutic approach?

Background: MMPs are a group of zinc-dependent endopeptidases implicated in the degradation of extracellular matrix components. Angiogenesis, wound healing and tissue remodeling are the main processes in which MMPs have been implicated. MMPs also seem to play a role in the pathophysiological processes during tumorigenesis and are thought to have predictive value for clinical outcome. Alterations in the regulation of MMP expression are considered to be of significant importance in the development and progression of gynecological malignancies. Objectives/methods: This study provides a literature review on the involvement of MMPs in the development and progression of gynecological malignancies, their clinical significance and the potential use of natural and/or synthetic MMP Inhibitors (MMPIs) as a more targeted therapeutic approach to these neoplasms. Results/conclusions: There is mounting evidence that MMPs play an important role in development and progression of gynecological malignancies. Current results provide the basis for further investigation of their role in malignancies, the therapeutic potential of their inhibition and the side-effects that can be expected from the modulation of matrix remodeling during therapeutic intervention. Focused research on the combination of MMPIs with cytotoxic and/or antiangiogenic compounds might provide the key to more successful therapeutic approaches towards gynecological and other malignancies. © 2009 Informa UK Ltd. All rights reserved

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